First trimester screening of circulating C19MC microRNAs and the evaluation of their potential to predict the onset of preeclampsia and IUGR.

PubMed

Hromadnikova, Ilona; Kotlabova, Katerina; Ivankova, Katarina; Krofta, Ladislav

2017-01-01

A nested case control study of a longitudinal cohort comparing pregnant women enrolled at 10 to 13 gestational weeks was carried out to evaluate risk assessment for preeclampsia and IUGR based on circulating placental specific C19MC microRNAs in early pregnancy. The expression of placental specific C19MC microRNAs (miR-516b-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, and miR-525-5p) was determined in plasma samples from pregnancies that subsequently developed preeclampsia (n = 21), IUGR (n = 18), and 58 normal pregnancies using real-time PCR and comparative Ct method relative to synthetic Caenorhabditis elegans microRNA (cel-miR-39). Circulating C19MC microRNAs were up-regulated (miR-517-5p, p = 0.005; miR-518b, p = 0.013; miR-520h, p = 0.021) or showed a trend toward up-regulation in patients destined to develop preeclampsia (miR-520a-5p, p = 0.067; miR-525-5p, p = 0.073). MiR-517-5p had the best predictive performance for preeclampsia with a sensitivity of 42.9%, a specificity of 86.2%, a PPV of 52.9% and a NPV of 80.6%. The combination of all examined circulating C19MC microRNAs had no advantage over using only the miR-517-5p biomarker to predict the occurrence of preeclampsia (a sensitivity of 20.6%, a specificity of 90.8%, a PPV of 44.8%, and a NPV of 76.0%). Up-regulation of miR-517-5p, miR-518b and miR-520h was associated with a risk of later development of preeclampsia. First trimester screening of extracellular miR-517-5p identified a proportion of women with subsequent preeclampsia. No circulating C19MC microRNA biomarkers were identified that could predict later occurrence of IUGR.

Italian Advisory Board: sFlt-1/PlGF ratio and preeclampsia, state of the art and developments in diagnostic, therapeutic and clinical management.

PubMed

Di Martino, Daniela; Cetin, Irene; Frusca, Tiziana; Ferrazzi, Enrico; Fuse', Federica; Gervasi, Maria Teresa; Plebani, Mario; Todros, Tullia

2016-11-01

Extensive research has been published, showing the usefulness of angiogenic markers in both diagnosis and subsequent prediction and management of preeclampsia and placenta-related disorders. Recent evidence provides a helpful cut off for the Elecsys ratio sFlt-1 to PlGF, that predicts preeclampsia development in women with sign and symptoms, before its clinical onset in the short term. In Europe, no accordance exists for the use of such kind of test in clinical practice; only German guidelines have recently taken it into account, as a diagnostic aid for preeclampsia, in conjunction with other clinical findings. This panel of Italian experts recently met, in order to review the literature and to promote the evaluation of the clinical utility of sFlt-1/PlGF ratio at the Italian country level, as regards: prediction of preeclampsia during the first trimester, prediction or exclusion of new onset or recurrence in patients with risk factors for preeclampsia, triage of patients suffering from gestational hypertension, evaluation of disease severity, prediction of adverse maternal and fetal outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

THE PREDICTIVE VALUE OF SERUM URIC ACID FOR THE OCCURRENCE, SEVERITY AND OUTCOMES OF PRE-ECLAMPSIA AMONG PARTURIENTS AT NNEWI, NIGERIA.

PubMed

Osakwe, Chukwudi Richmond; Ikpeze, Okechukwu C; Ezebialu, Ifeanyi Uzoma; Osakwe, Joy Oluchi; Mbadugha, Norah Nwadiogo

2015-01-01

To determine the predictive value of serum uric acid for preeclampsia, its severity and pregnancy outcome. This is a cohort study that was performed on normal pregnant women attending antenatal clinic at Nnamdi Azikiwe University Teaching Hospital Nnewi Nigeria. Serum uric acid was determined in 200 women attending antenatal clinic between the gestational ages of 14 and 26 weeks. The women were followed up at 2 weekly intervals until 36 weeks and weekly thereafter until delivery. Women who developed pre-eclampsia or eclampsia were identified. Pregnancy outcomes were determined as well as fetal and placental weights. The data was analised with SPSS version 16.0. The chi square was used for test of significance. The positive and negative predictive values were determined. A total of 200 normal pregnant women were recruited for the study. Nine of them were lost to follow up. Subsequently, 10.5% of the women developed preeclampsia. The positive and negative predictive values of serum uric acid for preeclampsia were 78.9% and 97.1%, respectively. Serum uric acid was found to be a useful predictor of the occurrence of preeclampsia and its severity.

[EARLY DETECTION OF PREECLAMPSIA].

PubMed

Todorov, N

2016-01-01

The preeclampsia is one of the most serious complications in the second half of the pregnancy with a high risk of perinatal maternal and neonatal mortality. The study is aiming to determine which pregnant women have a higher risk of developing preeclampsia with a view to the subsequent antenatal care, on the base of the individual factors. From prospectively followed pacients is collected information by a questionnaire and sonographic examination at 11-13 weeks of gestation/w.g./ + 6 days, at the point of biochemical screening implementation. Selected is a group of women with one fetus pregnancy, non-smokers, without chromosomal and structural anomalies of the fetus, excluding those taking prophylactic low-dose of aspirin. The Doppler examination was transabdominaly performed on the ascending branch of the A. Uterina at the level of OICC.Pusatility and resistance index /Pi and Ri/ are bilaterally evaluated and converted to MoM for the relevant age of gestation. The information about the taken values of Pi, Ri, the presence of diastolic incisures and the development of preeclampsia /PE/ or pregnancy indused hypertension /PIH/ is analyzed at 205 pregnant women. Out of them high values of Pi have 9 pregnant women, who subsequently developed PE or PlH. The measurement of Pi at 12-13 weeks of gestation and presence of diastolic incisures have prognostic importance for the development of PE in the later period of pregnancy. The values of Ri, taken at 12-13 weeks of gestation have not essential importance in the forecast of preeclamsia development.

Prepregnancy obesity and complement system activation in early pregnancy and the subsequent development of preeclampsia.

PubMed

Lynch, Anne M; Eckel, Robert H; Murphy, James R; Gibbs, Ronald S; West, Nancy A; Giclas, Patricia C; Salmon, Jane E; Holers, V Michael

2012-05-01

We hypothesized that women who are obese before they become pregnant and also have elevations of complement Bb and C3a in the top quartile in early pregnancy would have the highest risk of preeclampsia compared with a referent group of women who were not obese and had levels of complement less than the top quartile. This was a prospective study of 1013 women recruited at less than 20 weeks' gestation. An EDTA-plasma sample was obtained, and complement fragments were measured using enzyme-linked immunosorbent assays. The data were analyzed using univariable and multivariable logistic regression analysis. Women who were obese with levels of Bb or C3a in the top quartile were 10.0 (95% confidence interval, 3.3-30) and 8.8 (95% confidence interval, 3-24) times, respectively, more likely to develop preeclampsia compared with the referent group. We demonstrate a combined impact of obesity and elevated complement on the development of preeclampsia. Copyright © 2012. Published by Mosby, Inc.

Fetal hemoglobin, α1-microglobulin and hemopexin are potential predictive first trimester biomarkers for preeclampsia.

PubMed

Anderson, Ulrik Dolberg; Gram, Magnus; Ranstam, Jonas; Thilaganathan, Basky; Kerström, Bo; Hansson, Stefan R

2016-04-01

Overproduction of cell-free fetal hemoglobin (HbF) in the preeclamptic placenta has been recently implicated as a new etiological factor of preeclampsia. In this study, maternal serum levels of HbF and the endogenous hemoglobin/heme scavenging systems were evaluated as predictive biomarkers for preeclampsia in combination with uterine artery Doppler ultrasound. Case-control study including 433 women in early pregnancy (mean 13.7weeks of gestation) of which 86 subsequently developed preeclampsia. The serum concentrations of HbF, total cell-free hemoglobin, hemopexin, haptoglobin and α1-microglobulin were measured in maternal serum. All patients were examined with uterine artery Doppler ultrasound. Logistic regression models were developed, which included the biomarkers, ultrasound indices, and maternal risk factors. There were significantly higher serum concentrations of HbF and α1-microglobulin and significantly lower serum concentrations of hemopexin in patients who later developed preeclampsia. The uterine artery Doppler ultrasound results showed significantly higher pulsatility index values in the preeclampsia group. The optimal prediction model was obtained by combining HbF, α1-microglobulin and hemopexin in combination with the maternal characteristics parity, diabetes and pre-pregnancy hypertension. The optimal sensitivity for all preeclampsia was 60% at 95% specificity. Overproduction of placentally derived HbF and depletion of hemoglobin/heme scavenging mechanisms are involved in the pathogenesis of preeclampsia. The combination of HbF and α1-microglobulin and/or hemopexin may serve as a prediction model for preeclampsia in combination with maternal risk factors and/or uterine artery Doppler ultrasound. Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

[Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction].

PubMed

Valdés R, Enrique; Lattes A, Karina; Muñoz S, Hernán; Cumsille, Miguel Angel

2012-05-01

Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselected pregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls. Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively). Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.

Identification of patients at risk for preeclampsia with the use of uterine artery Doppler velocimetry and copeptin.

PubMed

Yeşil, Ali; Kanawati, Ammar; Helvacıoğlu, Çağlar; Kaya, Cihan; Özgün, Çağseli Göksu; Cengiz, Hüseyin

2017-11-01

To investigate the relationship between maternal copeptin levels and uterine artery Doppler examination and progress of preeclampsia. A cross-sectional study was designed with women those were screened at 20 + 0 - 24+  6 weeks' gestation between May 2014 and August 2014. The obstetric records of all normotensive women were examined. Uterine artery Doppler velocimetry results and serum copeptin levels were measured. The patients were divided into two groups according to normal (n = 67) and abnormal uterine artery Doppler (n = 21) findings. Maternal age was significantly lower in group 1 (n = 21, 23.9%) than in group 2 (n= 67, 76.1%) (p < 0.05). We found no differences in maternal characteristics, birth weight, gestational age at delivery and copeptin levels between the two groups. Maternal serum copeptin levels were higher in women who subsequently developed preeclampsia. There was also a significant correlation between copeptin levels and the presence of preeclampsia. (p = 0.002). Copeptin levels are significantly higher in patients who develop preeclampsia.

Hypothesis: Pentoxifylline explores new horizons in treatment of preeclampsia.

PubMed

Azimi, Arsalan; Ziaee, Seyyed Mohyeddin; Farhadi, Pouya; Sagheb, Mohammad Mahdi

2015-10-01

Preeclampsia, the leading cause of maternal morbidity and perinatal mortality, initiates as inappropriate immune response to trophoblastic invasion impairs placentation and placental circulation. A poorly perfused placenta generates superoxide anions as well as anti-angiogenic factors and this series of events result in impairment of endothelial function, followed by maternal morbidities such as hypertension, kidney injury and proteinuria. Renal loss of anti-coagulant proteins and subsequent hyper-coagulable state along with endothelial dysfunction accelerates progression of the disease toward eclampsia. Since Pentoxifylline, a methyl-xanthine derivative known for enhancement of vascular endothelial function, down-regulation of many inflammatory cytokines increased during preeclampsia, improvement of placental circulation, reduction of ischemia-reperfusion injury, enhancement of vasodilatation and endothelial function, ameliorating proteinuria, inhibition of platelet aggregation and decreasing risk of preterm labor, which are all amongst morbidities of preeclampsia, here it is hypothesized that Pentoxifylline prevents development of preeclampsia and/or decelerate progression of the disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

A prospective study of maternal carboxyhemoglobin and preeclampsia risk

PubMed Central

Rudra, Carole B.; Williams, Michelle A.; Schiff, Melissa A.; Koenig, Jane Q.; Dills, Russell; Yu, Jianbo

2009-01-01

Summary We aimed to measure the relation between early-pregnancy maternal carboxyhemoglobin and subsequent preeclampsia risk. We conducted a nested case-control analysis using data from a western Washington State cohort study (1996–2004). We measured maternal whole blood carboxyhemoglobin in 128 women who developed preeclampsia and 419 normotensive controls (mean gestational age at blood draw, 14.8 weeks). After adjustment for confounders, high (≥1%) versus low (<0.7%) carboxyhemoglobin odds ratios [OR] and 95% confidence intervals [CI] were 4.09 [1.30, 12.9] in parous women, 0.53 [0.23, 1.26] in nulliparous women, and 1.11 [0.55, 2.25] in the overall study population (parity interaction p=0.01). The influence of parity on the association was unexpected. The association between high carboxyhemoglobin and preeclampsia risk in parous women implicates hypoxia at the fetal-maternal interface as a pathogenic mechanism. These results also suggest that the etiology of the disease may differ according to parity. PMID:20078828

A prospective study of maternal carboxyhaemoglobin and pre-eclampsia risk.

PubMed

Rudra, Carole B; Williams, Michelle A; Schiff, Melissa A; Koenig, Jane Q; Dills, Russell; Yu, Jianbo

2010-01-01

We aimed to measure the relationship between early-pregnancy maternal carboxyhaemoglobin and subsequent pre-eclampsia risk. A nested case-control analysis was conducted using data from a western Washington State cohort study (1996-2004). We measured maternal whole blood carboxyhaemoglobin in 128 women who developed pre-eclampsia and 419 normotensive controls (mean gestational age at blood draw, 14.8 weeks). After adjustment for confounders, high (>/=1%) vs. low (<0.7%) carboxyhaemoglobin odds ratios [OR] and 95% confidence intervals [CI] were 4.09 [1.30, 12.9] in multiparous women, 0.53 [0.23, 1.26] in primiparae and 1.11 [0.55, 2.25] in the overall study population (parity interaction P = 0.01). The influence of parity on the association was unexpected. The association between high carboxyhaemoglobin and pre-eclampsia risk in multiparae implicates hypoxia at the fetal-maternal interface as a pathogenic mechanism. These results also suggest that the aetiology of the disease may differ according to parity.

The Epidemiology of Liver Diseases Unique to Pregnancy in a US Community: A Population-Based Study.

PubMed

Allen, Alina M; Kim, W Ray; Larson, Joseph J; Rosedahl, Jordan K; Yawn, Barbara P; McKeon, Kimberly; Hay, J Eileen

2016-02-01

Little is known in the United States about the epidemiology of liver diseases that develop only during (are unique to) pregnancy. We investigated the incidence of liver diseases unique to pregnancy in Olmsted County, Minnesota, and long-term maternal and fetal outcomes. We identified 247 women with liver diseases unique to pregnancy from 1996 through 2010 using the Rochester Epidemiology Project database. The crude incidence rate was calculated by the number of liver disease cases divided by 35,101 pregnancies. Of pregnant women with liver diseases, 134 had preeclampsia with liver dysfunction, 72 had hemolysis-associated increased levels of liver enzymes and low-platelet (HELLP) syndrome, 26 had intrahepatic cholestasis of pregnancy, 14 had hyperemesis gravidarum with abnormal liver enzymes, and 1 had acute fatty liver of pregnancy. The crude incidence of liver diseases unique to pregnancy was 0.77%. Outcomes were worse among women with HELLP or preeclampsia than the other disorders--of women with HELLP, 70% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 3% had infant death. Of women with preeclampsia, 56.0% had a premature delivery, 4% had abruptio placentae, 3% had acute kidney injury, and 0.7% had infant death. After 7 median years of follow-up (range, 0-18 years), 14% of the women developed recurrent liver disease unique to pregnancy; the proportions were highest in women with initial hyperemesis gravidarum (36%) or intrahepatic cholestasis of pregnancy (35%). Women with preeclampsia were more likely to develop subsequent hepatobiliary diseases. We found the incidence of liver disease unique to pregnancy in Olmsted County, Minnesota, to be lower than that reported from Europe or US tertiary referral centers. Maternal and fetal outcomes in Olmsted County were better than those reported from other studies, but fetal mortality was still high (0.7%-3.0%). Women with preeclampsia or HELLP are at higher risk for peripartum complications and subsequent development of comorbidities. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Prognostic Value of Cardiovascular Disease Risk Factors Measured in the First-Trimester on the Severity of Preeclampsia

PubMed Central

Cheng, Po-Jen; Huang, Shang-Yu; Su, Sheng-Yuan; Hsiao, Ching-Hwa; Peng, Hsiu-Huei; Duan, Tao

2016-01-01

Abstract Recent studies have suggested that preeclampsia and cardiovascular disease may share common mechanisms. The purpose of this prospective nested case-controlled study was to characterize a variety of cardiovascular disease risk factors measured during the first trimester of pregnancy in predicting subsequent outcomes and the severity of preeclampsia. We ascertained the severity of preeclampsia at the onset of the disease, and the presence of intrauterine growth restriction (IUGR). We compared first trimester maternal serum cardiovascular disease risk factors in preeclampsia subjects versus normal pregnancies, early-onset versus late-onset preeclampsia, and preeclampsia with IUGR versus without IUGR. To identify the prognostic value of independent predictors on the severity of preeclampsia, we calculated the area under the receiver operating characteristics curve (AUC) using logistic regression analysis. There were 134 cases of preeclampsia and 150 uncomplicated pregnancies, and preeclampsia cases were classified as early-onset (53 cases) or late-onset (81 cases), or as with IUGR (44 cases) or without IUGR (90 cases). Among the cardiovascular disease risk factors, maternal serum high-sensitive C-reactive protein (hsCRP) and homocysteine were predictors of both early-onset preeclampsia and preeclampsia with IUGR. For the detection of early onset preeclampsia or preeclampsia with IUGR, the AUC for the combination model (0.943 and 0.952, respectively) was significantly higher than with serum hsCRP or serum homocysteine only. Patients with preeclampsia can be subdivided into different severities according to time of onset and fetal weight. Cardiovascular risk factors distinguish a subgroup of these patients. PMID:26844488

Prognostic Value of Cardiovascular Disease Risk Factors Measured in the First-Trimester on the Severity of Preeclampsia.

PubMed

Cheng, Po-Jen; Huang, Shang-Yu; Su, Sheng-Yuan; Hsiao, Ching-Hwa; Peng, Hsiu-Huei; Duan, Tao

2016-02-01

Recent studies have suggested that preeclampsia and cardiovascular disease may share common mechanisms. The purpose of this prospective nested case-controlled study was to characterize a variety of cardiovascular disease risk factors measured during the first trimester of pregnancy in predicting subsequent outcomes and the severity of preeclampsia.We ascertained the severity of preeclampsia at the onset of the disease, and the presence of intrauterine growth restriction (IUGR). We compared first trimester maternal serum cardiovascular disease risk factors in preeclampsia subjects versus normal pregnancies, early-onset versus late-onset preeclampsia, and preeclampsia with IUGR versus without IUGR. To identify the prognostic value of independent predictors on the severity of preeclampsia, we calculated the area under the receiver operating characteristics curve (AUC) using logistic regression analysis.There were 134 cases of preeclampsia and 150 uncomplicated pregnancies, and preeclampsia cases were classified as early-onset (53 cases) or late-onset (81 cases), or as with IUGR (44 cases) or without IUGR (90 cases). Among the cardiovascular disease risk factors, maternal serum high-sensitive C-reactive protein (hsCRP) and homocysteine were predictors of both early-onset preeclampsia and preeclampsia with IUGR. For the detection of early onset preeclampsia or preeclampsia with IUGR, the AUC for the combination model (0.943 and 0.952, respectively) was significantly higher than with serum hsCRP or serum homocysteine only.Patients with preeclampsia can be subdivided into different severities according to time of onset and fetal weight. Cardiovascular risk factors distinguish a subgroup of these patients.

Placental development and function in women with a history of placenta-related complications: a systematic review.

PubMed

Reijnders, Ignatia F; Mulders, Annemarie G M G J; Koster, Maria P H

2018-03-01

Women with a history of placenta-related pregnancy complications, such as preeclampsia, intrauterine growth restriction or preterm delivery, have an increased risk for recurrence of such complications. This recurrence is likely the result of underlying endothelial dysfunction that leads to abnormal placentation, especially in complications with an early onset. This study provides an overview of biomarkers of placental development and function in pregnancies from women with a history of placenta-related complications. A systematic literature search was conducted limited to human studies and including keywords related to a history of placenta-related complications and markers of placental development and function. Two independent reviewers assessed eligibility and quality of 1553 retrieved unique articles. Five articles reporting on placental development and function in women with an obstetric history of preeclampsia (n = 3), intrauterine growth restriction (n = 1) and preterm delivery (n = 2) were eligible for quality assessment. We identified associations between a history of preeclampsia and abnormal placental histological findings at term in the current pregnancy, but found contradictory results regarding presence of uterine artery notching. In women with a history of very preterm delivery (<32 weeks), one study showed associations with abnormal placental histology. Literature on the association between a history of placenta-related complications and placental development and function in subsequent pregnancies is scarce and studies are heterogeneous. However, literature shows that placenta-related pregnancy complications are associated with subsequent placental histology. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Evidence-Based Revised View of the Pathophysiology of Preeclampsia.

PubMed

Ahmed, Asif; Rezai, Homira; Broadway-Stringer, Sophie

2017-01-01

Preeclampsia is a life-threatening vascular disorder of pregnancy due to a failing stressed placenta. Millions of women risk death to give birth each year and globally each year, almost 300,000 lose their life in this process and over 500,000 babies die as a consequence of preeclampsia. Despite decades of research, we lack pharmacological agents to treat it. Maternal endothelial oxidative stress is a central phenomenon responsible for the preeclampsia phenotype of high maternal blood pressure and proteinuria. In 1997, it was proposed that preeclampsia arises due to the loss of VEGF activity, possibly due to elevation in anti-angiogenic factor, soluble Flt-1 (sFlt-1). Researchers showed that high sFlt-1 and soluble endoglin (sEng) elicit the severe preeclampsia phenotype in pregnant rodents. We demonstrated that heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway prevents placental stress and suppresses sFlt-1 and sEng release. Likewise, hydrogen sulphide (H 2 S)/cystathionine-γ-lyase (Cth) systems limit sFlt-1 and sEng and protect against the preeclampsia phenotype in mice. Importantly, H 2 S restores placental vasculature, and in doing so improves lagging fetal growth. These molecules act as the inhibitor systems in pregnancy and when they fail, preeclampsia is triggered. In this review, we discuss what are the hypotheses and models for the pathophysiology of preeclampsia on the basis of Bradford Hill causation criteria for disease causation and how further in vivo experimentation is needed to establish 'proof of principle'. Hypotheses that fail to meet the Bradford Hill causation criteria include abnormal spiral artery remodelling and inflammation and should be considered associated or consequential to the disorder. In contrast, the protection against cellular stress hypothesis that states that the protective pathways mitigate cellular stress by limiting elevation of anti-angiogenic factors or oxidative stress and the subsequent clinical signs of preeclampsia appear to fulfil most of Bradford Hill causation criteria. Identifying the candidates on the roadmap to this pathway is essential in developing diagnostics and therapeutics to target the pathogenesis of preeclampsia.

Screening for Preeclampsia: US Preventive Services Task Force Recommendation Statement.

PubMed

Bibbins-Domingo, Kirsten; Grossman, David C; Curry, Susan J; Barry, Michael J; Davidson, Karina W; Doubeni, Chyke A; Epling, John W; Kemper, Alex R; Krist, Alex H; Kurth, Ann E; Landefeld, C Seth; Mangione, Carol M; Phillips, William R; Phipps, Maureen G; Silverstein, Michael; Simon, Melissa A; Tseng, Chien-Wen

2017-04-25

Preeclampsia affects approximately 4% of pregnancies in the United States. It is the second leading cause of maternal mortality worldwide and may lead to serious maternal complications, including stroke, eclampsia, and organ failure. Adverse perinatal outcomes for the fetus and newborn include intrauterine growth restriction, low birth weight, and stillbirth. Many of the complications associated with preeclampsia lead to early induction of labor or cesarean delivery and subsequent preterm birth. Preeclampsia is more prevalent among African American women than among white women. Differences in prevalence may be, in part, due to African American women being disproportionally affected by risk factors for preeclampsia. African American women also have case fatality rates related to preeclampsia 3 times higher than rates among white women. Inequalities in access to adequate prenatal care may contribute to poor outcomes associated with preeclampsia in African American women. To update the 1996 US Preventive Services Task Force (USPSTF) recommendation on screening for preeclampsia. The USPSTF reviewed the evidence on the accuracy of screening and diagnostic tests for preeclampsia, the potential benefits and harms of screening for preeclampsia, the effectiveness of risk prediction tools, and the benefits and harms of treatment of screen-detected preeclampsia. Given the evidence that treatment can reduce maternal and perinatal morbidity and mortality, and the well-established accuracy of blood pressure measurements, the USPSTF found adequate evidence that screening for preeclampsia results in a substantial benefit for the mother and infant. In addition, there is adequate evidence to bound the harms of screening for and treatment of preeclampsia as no greater than small. Therefore, the USPSTF concludes with moderate certainty that there is a substantial net benefit of screening for preeclampsia in pregnant women. The USPSTF recommends screening for preeclampsia in pregnant women with blood pressure measurements throughout pregnancy. (B recommendation).

Pre-eclampsia Diagnosis and Treatment Options: A Review of Published Economic Assessments.

PubMed

Zakiyah, Neily; Postma, Maarten J; Baker, Philip N; van Asselt, Antoinette D I

2015-10-01

Pre-eclampsia is a pregnancy complication affecting both mother and fetus. Although there is no proven effective method to prevent pre-eclampsia, early identification of women at risk of pre-eclampsia could enhance appropriate application of antenatal care, management and treatment. Very little is known about the cost effectiveness of these and other tests for pre-eclampsia, mainly because there is no clear treatment path. The aim of this study was to provide a comprehensive overview of the existing evidence on the health economics of screening, diagnosis and treatment options in pre-eclampsia. We searched three electronic databases (PubMed, EMBASE and the Cochrane Library) for studies on screening, diagnosis, treatment or prevention of pre-eclampsia, published between 1994 and 2014. Only full papers written in English containing complete economic assessments in pre-eclampsia were included. From an initial total of 138 references, six papers fulfilled the inclusion criteria. Three studies were on the cost effectiveness of treatment of pre-eclampsia, two of which evaluated magnesium sulphate for prevention of seizures and the third evaluated the cost effectiveness of induction of labour versus expectant monitoring. The other three studies were aimed at screening and diagnosis, in combination with subsequent preventive measures. The two studies on magnesium sulphate were equivocal on the cost effectiveness in non-severe cases, and the other study suggested that induction of labour in term pre-eclampsia was more cost effective than expectant monitoring. The screening studies were quite diverse in their objectives as well as in their conclusions. One study concluded that screening is probably not worthwhile, while two other studies stated that in certain scenarios it may be cost effective to screen all pregnant women and prophylactically treat those who are found to be at high risk of developing pre-eclampsia. This study is the first to provide a comprehensive overview on the economic aspects of pre-eclampsia in its broadest sense, ranging from screening to treatment options. The main limitation of the present study lies in the variety of topics in combination with the limited number of papers that could be included; this restricted the comparisons that could be made. In conclusion, novel biomarkers in screening for and diagnosing pre-eclampsia show promise, but their accuracy is a major driver of cost effectiveness, as is prevalence. Universal screening for pre-eclampsia, using a biomarker, will be feasible only when accuracy is significantly increased.

Cardiovascular risk reduction and weight management at a hospital-based postpartum preeclampsia clinic.

PubMed

Janmohamed, Rahim; Montgomery-Fajic, Erin; Sia, Winnie; Germaine, Debbie; Wilkie, Jodi; Khurana, Rshmi; Nerenberg, Kara A

2015-04-01

Women who develop preeclampsia during pregnancy are at high risk of developing future chronic diseases, including premature cardiovascular disease. We have established an interdisciplinary clinic that aims to prevent cardiovascular disease through educational counselling focused on lifestyle modifications in the early postpartum period. The objective of this study was to evaluate changes in weight and cardiovascular risk factors in participating women after six months of attendance at the clinic. We conducted a retrospective chart review of women who had a pregnancy complicated by preeclampsia, and who subsequently attended the Postpartum Preeclampsia Clinic. Study subjects had baseline assessments of lifestyle, physical, and laboratory parameters. Individualized goals for cardiovascular risk reduction and lifestyle were established, centering on physical activity and dietary modifications. The primary outcome was change in weight. Over the study period, 21 women were seen for a minimum of six months of follow-up. At an average (± SD) of 4.4 ± 1.4 months postpartum, subjects showed a non-significant improvement in weight (mean weight loss of 0.4 ± 4.5 kg) and BMI (mean decrease in BMI 0.1 ± 1.7 kg/m2). Physical activity improved significantly, from 14% of subjects participating in physical activity before pregnancy to 76% at a mean of 4.4 months postpartum. This study has demonstrated the early benefits of a longitudinal interdisciplinary intervention with counselling about lifestyle modifications for prevention of cardiovascular disease in women with recent preeclampsia. A study with a larger sample size and longer duration of follow-up is planned to confirm these findings.

Preeclampsia and subsequent risk of cancer: update from the Jerusalem Perinatal Study

PubMed Central

CALDERON-MARGALIT, R.; FRIEDLANDER, Y.; YANETZ, R.; DEUTSCH, L.; PERRIN, MC; KLEINHAUS, K.; TIRAM, E.; HARLAP, S.; PALTIEL, O.

2009-01-01

Objectives To study the association between preeclampsia and cancer incidence. Study Design The Jerusalem Perinatal Study is a population-based cohort of all births to 41,206 residents of Western Jerusalem in 1964-76. Cancer incidence to 2004 was assessed by linkage of the cohort with the Israel Cancer Registry. Cox’s proportional hazards models were constructed to estimate the hazard ratio (HR) for cancer among women who had had preeclampsia. Results Preeclampsia was associated with a 1.23-fold increased risk of cancer at all sites, a 37% increased risk of breast cancer, and more than a doubling of ovarian cancer risk. Analysis by morphology yielded significantly increased risks for malignancies classed as cystic mucinous and serous (RR:1.96, 95% Confidence interval:1.00-3.83), and for ductal, lobular and medullary carcinomas (1.40, 1.07-1.83). No differential association was observed by sex of offspring. Conclusions Our study suggests that the previously-described protective effect of preeclampsia on cancer is not universal. PMID:18822400

Therapeutically targeting mitochondrial redox signalling alleviates endothelial dysfunction in preeclampsia.

PubMed

McCarthy, Cathal; Kenny, Louise C

2016-09-08

Aberrant placentation generating placental oxidative stress is proposed to play a critical role in the pathophysiology of preeclampsia. Unfortunately, therapeutic trials of antioxidants have been uniformly disappointing. There is provisional evidence implicating mitochondrial dysfunction as a source of oxidative stress in preeclampsia. Here we provide evidence that mitochondrial reactive oxygen species mediates endothelial dysfunction and establish that directly targeting mitochondrial scavenging may provide a protective role. Human umbilical vein endothelial cells exposed to 3% plasma from women with pregnancies complicated by preeclampsia resulted in a significant decrease in mitochondrial function with a subsequent significant increase in mitochondrial superoxide generation compared to cells exposed to plasma from women with uncomplicated pregnancies. Real-time PCR analysis showed increased expression of inflammatory markers TNF-α, TLR-9 and ICAM-1 respectively in endothelial cells treated with preeclampsia plasma. MitoTempo is a mitochondrial-targeted antioxidant, pre-treatment of cells with MitoTempo protected against hydrogen peroxide-induced cell death. Furthermore MitoTempo significantly reduced mitochondrial superoxide production in cells exposed to preeclampsia plasma by normalising mitochondrial metabolism. MitoTempo significantly altered the inflammatory profile of plasma treated cells. These novel data support a functional role for mitochondrial redox signaling in modulating the pathogenesis of preeclampsia and identifies mitochondrial-targeted antioxidants as potential therapeutic candidates.

Hypertension after preeclampsia and relation to the C1114G polymorphism (rs4606) in RGS2: data from the Norwegian HUNT2 study.

PubMed

Kvehaugen, Anne Stine; Melien, Øyvind; Holmen, Oddgeir L; Laivuori, Hannele; Dechend, Ralf; Staff, Anne Cathrine

2014-03-05

Preeclampsia is associated with an increased risk of hypertension later in life. The regulator of G protein signaling 2 negatively regulates several vasoconstrictors. We recently demonstrated an association between preeclampsia and the CG or GG genotype of the C1114G polymorphism (rs4606) of the regulator of G protein signaling 2 gene. Here, we examined the polymorphism with respect to the development of hypertension after pregnancy. We genotyped 934 women on average 15.1 years after preeclampsia and 2011 age matched women with previous normotensive pregnancy. All women in this study were retrospectively recruited from the Nord-Trøndelag Health Study (HUNT2). Information from HUNT2 was linked to the Medical Birth Registry of Norway to identify women with a history of preeclampsia and women without a history of preeclampsia. No significant association was found between hypertension (blood pressure ≥140/90 mmHg and/or taking antihypertensive drugs) and the polymorphism in crude analysis (OR (95% CI): CG genotype: 1.07 (0.90-1.27); GG genotype: 1.23 (0.90-1.67)). However, in a minimally adjusted model (age and BMI adjusted), a significant association between the GG genotype and hypertension was found (OR (95% CI): 1.49 (1.05-2.11)). This association remained significant also after adjustment for a history of preeclampsia (OR (95% CI): 1.46 (1.02-2.09)), but not in a model adjusted for multiple other variables (OR (95% CI): 1.26 (0.82-1.94)). In multivariate, but not in crude, analysis, the GG genotype of rs4606 (OR (95% CI): 1.93 (1.05-3.53)) was significantly and independently associated with severe hypertension later in life, defined as systolic blood pressure ≥160 mmHg (stage 2 hypertension) and/or taking antihypertensive drugs. A significant association was also found for the merged CG and GG genotypes (OR (95% CI): 1.43 (1.02-2.00)). Moreover, an interaction with physical activity was found. A history of preeclampsia was a significant and independent predictor of either definition of hypertension, both in crude and adjusted analyses. Women carrying the rs4606 CG or GG genotype are at elevated risk for developing hypertension after delivery. Physical activity may interact with the association. Preeclampsia remains an independent risk factor for subsequent hypertension after adjusting for this polymorphism and classical CVD risk factors.

Hypertension after preeclampsia and relation to the C1114G polymorphism (rs4606) in RGS2: data from the Norwegian HUNT2 study

PubMed Central

2014-01-01

Background Preeclampsia is associated with an increased risk of hypertension later in life. The regulator of G protein signaling 2 negatively regulates several vasoconstrictors. We recently demonstrated an association between preeclampsia and the CG or GG genotype of the C1114G polymorphism (rs4606) of the regulator of G protein signaling 2 gene. Here, we examined the polymorphism with respect to the development of hypertension after pregnancy. Methods We genotyped 934 women on average 15.1 years after preeclampsia and 2011 age matched women with previous normotensive pregnancy. All women in this study were retrospectively recruited from the Nord-Trøndelag Health Study (HUNT2). Information from HUNT2 was linked to the Medical Birth Registry of Norway to identify women with a history of preeclampsia and women without a history of preeclampsia. Results No significant association was found between hypertension (blood pressure ≥140/90 mmHg and/or taking antihypertensive drugs) and the polymorphism in crude analysis (OR (95% CI): CG genotype: 1.07 (0.90-1.27); GG genotype: 1.23 (0.90-1.67)). However, in a minimally adjusted model (age and BMI adjusted), a significant association between the GG genotype and hypertension was found (OR (95% CI): 1.49 (1.05-2.11)). This association remained significant also after adjustment for a history of preeclampsia (OR (95% CI): 1.46 (1.02-2.09)), but not in a model adjusted for multiple other variables (OR (95% CI): 1.26 (0.82-1.94)). In multivariate, but not in crude, analysis, the GG genotype of rs4606 (OR (95% CI): 1.93 (1.05-3.53)) was significantly and independently associated with severe hypertension later in life, defined as systolic blood pressure ≥160 mmHg (stage 2 hypertension) and/or taking antihypertensive drugs. A significant association was also found for the merged CG and GG genotypes (OR (95% CI): 1.43 (1.02-2.00)). Moreover, an interaction with physical activity was found. A history of preeclampsia was a significant and independent predictor of either definition of hypertension, both in crude and adjusted analyses. Conclusion Women carrying the rs4606 CG or GG genotype are at elevated risk for developing hypertension after delivery. Physical activity may interact with the association. Preeclampsia remains an independent risk factor for subsequent hypertension after adjusting for this polymorphism and classical CVD risk factors. PMID:24593135

The prediction of late-onset preeclampsia: Results from a longitudinal proteomics study.

PubMed

Erez, Offer; Romero, Roberto; Maymon, Eli; Chaemsaithong, Piya; Done, Bogdan; Pacora, Percy; Panaitescu, Bogdan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S; Tarca, Adi L

2017-01-01

Late-onset preeclampsia is the most prevalent phenotype of this syndrome; nevertheless, only a few biomarkers for its early diagnosis have been reported. We sought to correct this deficiency using a high through-put proteomic platform. A case-control longitudinal study was conducted, including 90 patients with normal pregnancies and 76 patients with late-onset preeclampsia (diagnosed at ≥34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2-6 samples per patient, median of 2; late-onset preeclampsia: 2-6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8-16, 16.1-22, 22.1-28, 28.1-32, 32.1-36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap. 1) At 8-16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1-22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor receptor signaling pathway, were perturbed; and 6) from 22.1 weeks of gestation onward, the set of proteins most predictive of severe preeclampsia was different from the set most predictive of the mild form of this syndrome. Elevated MMP-7 early in gestation (8-22 weeks) and low PlGF later in gestation (after 22 weeks) are the strongest predictors for the subsequent development of late-onset preeclampsia, suggesting that the optimal identification of patients at risk may involve a two-step diagnostic process.

The prediction of late-onset preeclampsia: Results from a longitudinal proteomics study

PubMed Central

Erez, Offer; Romero, Roberto; Maymon, Eli; Chaemsaithong, Piya; Done, Bogdan; Pacora, Percy; Panaitescu, Bogdan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

2017-01-01

Background Late-onset preeclampsia is the most prevalent phenotype of this syndrome; nevertheless, only a few biomarkers for its early diagnosis have been reported. We sought to correct this deficiency using a high through-put proteomic platform. Methods A case-control longitudinal study was conducted, including 90 patients with normal pregnancies and 76 patients with late-onset preeclampsia (diagnosed at ≥34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2–6 samples per patient, median of 2; late-onset preeclampsia: 2–6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8–16, 16.1–22, 22.1–28, 28.1–32, 32.1–36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap. Results 1) At 8–16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1–22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor receptor signaling pathway, were perturbed; and 6) from 22.1 weeks of gestation onward, the set of proteins most predictive of severe preeclampsia was different from the set most predictive of the mild form of this syndrome. Conclusions Elevated MMP-7 early in gestation (8–22 weeks) and low PlGF later in gestation (after 22 weeks) are the strongest predictors for the subsequent development of late-onset preeclampsia, suggesting that the optimal identification of patients at risk may involve a two-step diagnostic process. PMID:28738067

Genetic Aspects of Preeclampsia and the HELLP Syndrome

PubMed Central

Mortensen, Jan Helge; Nagy, Bálint

2014-01-01

Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. The STOX1 gene, the ERAP1 and 2 genes, the syncytin envelope gene, and the −670 Fas receptor polymorphisms are involved in the development of preeclampsia. The ACVR2A gene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of the MTHFR C677T polymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. The ACE I/D polymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases. PMID:24991435

3D power Doppler ultrasound in early diagnosis of preeclampsia.

PubMed

Neto, R Moreira; Ramos, J G L

2016-01-01

Preeclampsia is a known cause of maternal, fetal and neonatal morbidity and mortality. Thus, evaluation of the predicting value of comparing 3D power Doppler indices (3DPD) of uteroplacental circulation (UPC) in the first and second trimester in patients who developed preeclampsia (PE) and those who did not and testing the hypothesis that the parameters of vascularization and placenta flow intensity, as determined by three-dimensional ultrasound (3D), are different in normal pregnancies compared with preeclampsia, could be a suitable screening method. A prospective observational study using 3D power Doppler were performed to evaluate the placental perfusion in 96 pregnant women who came to do the ultrasound routine between 11 and 14 weeks. The placental vascular index (VI), flow index (FI), blood vessels and blood flow index (VFI) by three-dimensional Doppler histogram were calculated. All patients repeated the exam between 16 and 20 weeks. The outcome was scored as normal or preeclamptic. Placental vascular indices including VI, FI and VFI were significantly lower in preeclamptic placentas compared with controls in the study performed in the second trimester (p<0.001). There was not any statistical difference in the patients examined in the first trimester. Our findings suggest that 3D-power Doppler assessment of placental vascular indices in the second trimester has the potential to detect women at risk for subsequent development of PE. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Physical Activity During Pregnancy and Subsequent Risk of Preeclampsia and Gestational Hypertension: A Case Control Study.

PubMed

Spracklen, Cassandra N; Ryckman, Kelli K; Triche, Elizabeth W; Saftlas, Audrey F

2016-06-01

Physical activity (PA) is hypothesized to reduce the risk of preeclampsia, but few epidemiologic studies have simultaneously evaluated leisure time PA (LTPA), sedentary activity, occupational activity, and non-occupational, non-leisure time PA. Thus, we assessed the independent and combined effects of these different types of PA during pregnancy on preeclampsia and gestational hypertension risk. Preeclamptic (n = 258), gestational hypertensive (n = 233), and normotensive (n = 182) women identified from Iowa live birth records (2002-2005) were participants in Study of Pregnancy Hypertension in Iowa. Disease status was verified by medical chart review. All PA exposures were self-reported. Multinomial logistic regression was used to test for associations between various PA types and risk for preeclampsia or gestational hypertension. After adjusting for prepregnancy BMI, increasing levels of LTPA were associated with a reduced risk of preeclampsia (trend, p = 0.02). Additionally, increasing amount of time spent active each day was associated with decreasing risks for preeclampsia (adjusted, trend; p = 0.03). Increasing amount of time spent sitting per day was associated with an increasing risk of preeclampsia (adjusted, trend; p = 0.10). Women whose activity averaged >8.25 h per day were at a significantly reduced risk of preeclampsia relative to women active <4.2 h per day (adjusted OR 0.58, 95 % CI 0.36, 0.95). Most analyses evaluating the risk of gestational hypertension yielded null results or results that trended in the direction opposite of the preeclampsia results. Consistent with previous studies, these data suggest increasing PA during pregnancy may reduce preeclampsia risk while increasing levels of sedentary activity may increase disease risk.

Incident Coronary Heart Disease After Preeclampsia: Role of Reduced Fetal Growth, Preterm Delivery, and Parity.

PubMed

Riise, Hilde Kristin Refvik; Sulo, Gerhard; Tell, Grethe S; Igland, Jannicke; Nygård, Ottar; Vollset, Stein Emil; Iversen, Ann-Charlotte; Austgulen, Rigmor; Daltveit, Anne Kjersti

2017-03-06

Preeclampsia is a severe pregnancy disorder often complicated by reduced fetal growth or preterm delivery and is associated with long-term maternal morbidity and mortality. We aimed to assess the association between preeclampsia phenotypes and risk of subsequent coronary heart disease and maternal cardiovascular mortality. Women aged 16 to 49 years who gave birth during 1980-2002 and registered in the Medical Birth Registry of Norway were followed prospectively (1-29 years) for an incident major coronary event and mortality through linkage with the Cardiovascular Disease in Norway 1994-2009 (CVDNOR) project and the Norwegian Cause of Death Registry. Preeclampsia was subdivided based on the presence of a child born small for gestational age or preterm delivery. Among 506 350 women with 1 to 5 singleton births, there were 1275 (0.3%) occurrences of major coronary event, 468 (0.1%) cardiovascular deaths, and 5411 (1.1%) deaths overall. Compared with women without preeclampsia, the hazard ratio (95% CI) for major coronary event was 2.1 (1.73-2.65) after preeclampsia alone, 3.3 (2.37-4.57) after preeclampsia in combination with small for gestational age, and 5.4 (3.74-7.74) after preeclampsia in combination with preterm delivery. Analyses distinguishing women with 1 (n=61 352) or >1 (n=281 069) lifetime pregnancy and analyses with cardiovascular mortality as outcome followed the same pattern. The occurrence of major coronary events was increased among women with preeclampsia and highest for preeclampsia combined with a child born small for gestational age and/or preterm delivery. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Is ethnicity a risk factor for developing preeclampsia? An analysis of the prevalence of preeclampsia in China.

PubMed

Xiao, J; Shen, F; Xue, Q; Chen, G; Zeng, K; Stone, P; Zhao, M; Chen, Q

2014-11-01

Preeclampsia is a major complication of pregnancy. Risk factors for preeclampsia include population and regional ethnicity. Chinese women living outside the Chinese mainland have a lower prevalence of preeclampsia than resident Caucasians. We performed a retrospective study to identify potential factors that may be associated with developing preeclampsia in China. A total of 67,746 pregnant women were included in this study from 2002 to 2011. Data included maternal age, maternal body mass index (BMI), age at marriage, parity, gestation and blood pressure at diagnosis, proteinuria, and birth weight. In the study period, 1301 (1.92%) nulliparous women developed preeclampsia. The prevalence of mild or severe preeclampsia was 1.42% or 0.49%, respectively. The average BMI was 21.61 kg m(-2). On the basis of the WHO BMI classification, 78.8% of women were of normal BMI, 18.3% were overweight and 2.9% were obese. A total of 37.8% of preeclamptic women had lived with the same partner for less than 1 year, which was significantly higher than those healthy pregnant women who did not develop preeclampsia (24.2%). The prevalence of preeclampsia in China is low compared with Caucasians, and the contribution to this lower prevalence may be dependent on BMI or lifestyle including period of cohabitation with the partner. Our data suggest that Chinese ethnicity may be a factor responsible for the low risk of developing preeclampsia in the populations studied.

The interrelationship of complement-activation fragments and angiogenesis-related factors in early pregnancy and their association with pre-eclampsia

PubMed Central

Lynch, AM; Murphy, JR; Gibbs, RS; Levine, RJ; Giclas, PC; Salmon, JE; Holers, VM

2016-01-01

Objective To determine the interrelationships during early pregnancy of complement-activation fragments Bb, C3a and sC5b-9, and angiogenesis-related factors placental growth factor (PiGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and their associations with pre-eclampsia. Design Prospective cohort study. Setting Denver complement study (June 2005–June 2008). Population A total of 668 pregnant women with singleton gestations, recruited between 10 and 15 weeks of gestation. Methods Using univariable and multivariable logistic regression analysis, concentrations of complement-activation fragments and angiogenesis-related factors were compared between 10 and 15 weeks of gestation in women who subsequently did or did not develop pre-eclampsia. Interrelationships between these variables were tested using the non-parametric Spearman rank correlation coefficient. Main outcome measure Pre-eclampsia. The association of complement-activation fragments and angiogenesis-related factors with obesity was also examined. Results The mean (±SD) levels of complement Bb in early pregnancy among women who did and did not develop pre-eclampsia were 0.84 (±0.26) µg/ml and 0.69 (±0.2) µg/ml, respectively (P = 0.001). Concentrations of PiGF were significantly (P = 0.01) lower (31 ± 12 pg/ml) in early pregnancy in the pre-eclamptic group of women, as compared with the normotensive group (39 ± 32 pg/ml). The adjusted odds ratio (AOR) of Bb and PiGF were 2.1 (CI = 1.4–3.1, P < 0.0003) and 0.2 (CI = 0.07–0.7, P = 0.01), respectively. There was no significant difference in the levels of C3a, sC5b-9, sFlt-1 and sEng in early pregnancy among women who developed pre-eclampsia, compared with women who remained normotensive during pregnancy. Higher levels of Bb (P = 0.0001) and C3a (P = 0.03), and lower levels of sFlt-1 (P = 0.0002) and sEng (P = 0.0001) were found among women with obesity, compared with non-obese controls. No meaningful relationships were found between the complement-activation fragments and the angiogenesis-related factors. Conclusions In this cohort during early pregnancy, increased concentrations of complement-activation factor Bb and lower concentrations of PiGF were associated with the development of pre-eclampsia later in pregnancy. PMID:20074261

Invited Commentary: Induced Abortion and the Risk of Preeclampsia in a Subsequent Pregnancy.

PubMed

Basso, Olga

2015-10-15

Although it is well established that a having a pregnancy that ends in a birth protects against subsequent preeclampsia, it is unclear whether a pregnancy ending in miscarriage or induced abortion confers any protection. In this issue of the Journal, Parker et al. (Am J Epidemiol. 2015;182(8):663-669) examine whether, in nulliparous women, a history of induced abortion is associated with a lower risk of preeclampsia in a later pregnancy, focusing on the hypothesis that endometrial injury facilitates later implantation. The authors take advantage of data obtained by linking several Finnish population-based registries that include detailed data on induced abortions, although information on miscarriages was of lower quality. Parker et al. found a modest reduction in risk among women with a history of induced abortion. However, there was little evidence that risk differed between women who had medical abortions and those who had surgical abortions (the latter of which is presumably associated with a higher degree of injury). History of miscarriage was not associated with preeclampsia risk. Although the study by Parker et al. adds to the evidence that suggests that women with a history of induced abortion have a lower risk of preeclampsia, it is difficult to evaluate whether the observed association is due to having had a previous pregnancy (however short) versus none, to confounding, or to an actual effect of induced abortion. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Competing risks model in screening for preeclampsia by maternal characteristics and medical history.

PubMed

Wright, David; Syngelaki, Argyro; Akolekar, Ranjit; Poon, Leona C; Nicolaides, Kypros H

2015-07-01

The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history. This was a screening study of 120,492 singleton pregnancies at 11-13 weeks' gestation, including 2704 pregnancies (2.2%) that experienced preeclampsia. A survival-time model for the gestational age at delivery with preeclampsia was developed from variables of maternal characteristics and history. This approach assumes that, if the pregnancy was to continue indefinitely, all women would experience preeclampsia and that whether they do so or not before a specified gestational age depends on competition between delivery before or after development of preeclampsia. A 5-fold cross validation study was conducted to compare the performance of the new model with the National Institute for Health and Clinical Excellence (NICE) guidelines. In the new model, increased risk for preeclampsia, with a consequent shift in the Gaussian distribution of the gestational age at delivery with preeclampsia to the left, is provided by advancing maternal age, increasing weight, Afro-Caribbean and South Asian racial origin, medical history of chronic hypertension, diabetes mellitus and systemic lupus erythematosus or antiphospholipid syndrome, family history and personal history of preeclampsia, and conception by in vitro fertilization. The risk for preeclampsia decreases with increasing maternal height and in parous women with no previous preeclampsia; in the latter, the protective effect, which is related inversely to the interpregnancy interval, persists beyond 15 years. At a screen-positive rate of 11%, as defined by NICE, the new model predicted 40%, 48%, and 54% of cases of total preeclampsia and preeclampsia requiring delivery at <37 and <34 weeks' gestation, respectively, which were significantly higher than the respective values of 35%, 40%, and 44% achieved by application of NICE guidelines. A new model that is based on maternal characteristics and medical history has been developed for the estimation of patient-specific risks for preeclampsia. Such estimation of the a priori risk for preeclampsia is an essential first step in the use of Bayes theorem to combine maternal factors with biomarkers for the continuing development of more effective methods of screening for the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Mid-trimester maternal ADAM12 levels differ according to fetal gender in pregnancies complicated by preeclampsia.

PubMed

Myers, Jenny E; Thomas, Grégoire; Tuytten, Robin; Van Herrewege, Yven; Djiokep, Raoul O; Roberts, Claire T; Kenny, Louise C; Simpson, Nigel A B; North, Robyn A; Baker, Philip N

2015-02-01

An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n = 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver-operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia. © The Author(s) 2014.

Maternal serum fatty acid binding protein 4 (FABP4) and the development of preeclampsia.

PubMed

Scifres, Christina M; Catov, Janet M; Simhan, Hyagriv

2012-03-01

Serum fatty acid binding protein 4 (FABP4) is associated with components of the metabolic syndrome in nonpregnant individuals, including dyslipidemia and insulin resistance. Preeclampsia shares many features with the metabolic syndrome, but the relationship between early pregnancy serum FABP4 levels and the development of preeclampsia is unknown. The aim of the study was to test the hypothesis that FABP4 is elevated in women who develop preeclampsia before the onset of disease. This was a nested case-control study within a larger prospective cohort of healthy women with singleton gestations. Cases included 22 women who developed preeclampsia, and a random sample of 72 unmatched controls delivered without preeclampsia was identified. Maternal serum FABP4 was measured at less than 13 wk gestation and 24-28 wk gestation, which was before the onset of preeclampsia in all patients. The main outcome measure was preeclampsia (new-onset gestational hypertension and proteinuria for the first time after 20 wk gestation). Maternal serum FABP4 concentrations were higher in women who ultimately developed preeclampsia both at 8-13 wk (20.4±12.3 vs. 10.1±4.7 ng/ml; P<0.01) and at 24-28 wk (20.7±11.7 vs. 9.9±4.5 ng/ml; P<0.01). After controlling for first trimester body mass index, systolic blood pressure, and nulliparity, FABP4 was associated with the development of preeclampsia (adjusted odds ratio, 1.2; 95% confidence interval, 1.1-1.3; P<0.01). Maternal serum FABP4 levels are elevated before the clinical onset of preeclampsia, and this increase occurs independently of maternal body mass index.

Circulating Angiogenic Factors and the Risk of Preeclampsia in Systemic Lupus Erythematosus Pregnancies.

PubMed

Leaños-Miranda, Alfredo; Campos-Galicia, Inova; Berumen-Lechuga, María Guadalupe; Molina-Pérez, Carlos José; García-Paleta, Yolanda; Isordia-Salas, Irma; Ramírez-Valenzuela, Karla Leticia

2015-07-01

To investigate whether angiogenic factors are associated with risk of developing preeclampsia in pregnant women with systemic lupus erythematosus (SLE). We performed a nested case-control study within a cohort of SLE women with singleton pregnancies. The study included 42 patients with SLE who eventually developed preeclampsia and 75 normal SLE pregnancies. Serum samples were collected at 4-week intervals (from weeks 12 to 36). Serum samples were analyzed for soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng). Women destined to develop preeclampsia had lower PlGF levels and higher sFlt-1 and sEng levels, and a higher sFlt-1/PlGF ratio than normal pregnancies. These changes became significant at 12 weeks in patients destined to develop either early onset (< 34 weeks, p ≤ 0.003) or late-onset preeclampsia (≥ 34 weeks, p ≤ 0.02). The risk to develop preeclampsia was higher among patients with PlGF concentration values in the lowest quartile or with sFlt-1 and sEng levels, and sFlt-1/PlGF ratio, in the highest quartile of the normal SLE pregnancies distribution. The OR were higher and appeared earlier in patients destined to develop early onset preeclampsia (OR ≥ 16.2, from Week 12 onward) than in patients who presented preeclampsia later (OR ≥ 8.9, from Week 24 onward). Changes in circulating concentrations of sFlt-1, PlGF, sEng, and the sFlt-1/PlGF ratio precede the onset of preeclampsia in SLE pregnancies. The risk profile of circulating angiogenic factors for developing preeclampsia distinctly evolves depending on whether this condition is manifested earlier or later.

Women Born Preterm or with Inappropriate Weight for Gestational Age Are at Risk of Subsequent Gestational Diabetes and Pre-Eclampsia

PubMed Central

á Rogvi, Rasmus; Forman, Julie Lyng; Damm, Peter; Greisen, Gorm

2012-01-01

Introduction Low birthweight, which can be caused by inappropriate intrauterine growth or prematurity, is associated with development of gestational diabetes mellitus (GDM) as well as pre-eclampsia later in life, but the relative effects of prematurity and inappropriate intrauterine growth remain uncertain. Methods Through nation-wide registries we identified all Danish mothers in the years 1989–2007. Two separate cohorts consisting mothers born 1974–1977 (n = 84219) and 1978–1981 (n = 32376) were studied, due to different methods of registering birthweight and gestational age in the two periods. Data was linked with information on GDM, pre-eclampsia and education. Results In a multivariate logistic regression model the odds of developing GDM was increased by 5–7% for each week the mother was born before term (p = 0.018 for 1974–1977, p = 0.048 for 1978–1981), while the odds were increased by 13–17% for each standard deviation (SD) reduction in birthweight for gestational age for those who were small or normal for gestational age (p<0.0001 and p = 0.035) and increased by 118–122% for each SD increase above the normal range (p<0.0001 and p = 0.024). The odds of pre-eclampsia was increased by 3–5% for each week the mother was born before term (p = 0.064 and p = 0.04), while the odds were increased 11–12% for each SD reduction in birthweight for gestational age (p<0.0001 and p = 0.0002). Conclusion In this cohort of young Danish mothers, being born premature or with increasingly low birthweight for gestational age was associated with an increased risk of GDM and pre-eclampsia in adulthood, while increasingly high birthweight for gestational age was associated with an increased risk of GDM and a decreased risk of pre-eclampsia. Inappropriate weight for gestational age was a more important risk factor than prematurity. PMID:22479500

Massive vulvar edema in a woman with preeclampsia: a case report.

PubMed

Daponte, Alexandros; Skentou, Hara; Dimopoulos, Konstantinos D; Kallitsaris, Athanasios; Messinis, Ioannis E

2007-11-01

Massive vulvar edema in a woman with preeclampsia preceded the development of massive ascites and impending eclampsia. A 17-year-old preeclamptic, primiparous woman was admitted with preeclampsia and massive vulvar edema. Other causes were excluded. The vulvar edema increased as the blood pressure and ascites increased, and a severe headache developed. Cesarean section for increasing preclampsia was performed. In the puerperium, the blood pressure improved and vulvar edema resolved. The clinical picture of the vulvar edema correlated with the severity of the preeclampsia. The presence of vulvar edema in women with preeclampsia should indicate immediate admission to the hospital. These patients must be considered as at high risk, and close monitoring must be instituted. In our case, vulvar edema preceded massive ascites development. We assume a common development mechanism for these signs in preeclampsia, due mainly to increased capillary permeability and hypoalbuminemia. The attending physician must be prepared for immediate delivery and possible preeclampsia complications in these patients.

Pre-eclampsia in American Indians/Alaska Natives and Whites: The Significance of Body Mass Index.

PubMed

Zamora-Kapoor, Anna; Nelson, Lonnie A; Buchwald, Dedra S; Walker, Leslie R; Mueller, Beth A

2016-11-01

Introduction The prevalence of pre-eclampsia, a major cause of maternal morbidity, varies by race, being greater in African Americans, and lower in Asians and Hispanics than in White women. Little is known about its prevalence in American Indians/Alaska Natives (AI/ANs). We estimated pre-eclampsia risk in AI/ANs compared to Whites, with consideration of the potential effect of obesity, a major risk factor for pre-eclampsia, and a condition disproportionately affecting AI/AN women. Methods This retrospective cohort study of linked birth-hospital discharge data from Washington State (2003-2013) included all AI/AN women and a sample of White first-time mothers with singleton deliveries. Logistic regression was used to estimate odds ratio (OR) and 95 % confidence intervals (CI) for pre-eclampsia risk in AI/ANs compared to Whites, first controlling for several important risk factors, and subsequently with additional adjustment for pre-pregnancy body mass index (BMI). Results AI/ANs had an increased risk of pre-eclampsia compared to Whites after controlling for all covariates except BMI (OR 1.17, 95 % CI 1.06-1.29). After further adjustment for BMI, the racial disparity in pre-eclampsia risk was greatly attenuated (OR 1.05, 95 % CI 0.95-1.16). Discussion This population-based study suggests that any increased risk in AI/ANs relative to Whites may be at least partly due to differences in BMI.

Pre-eclampsia in American Indians/Alaska Natives and Whites: The Significance of Body Mass Index

PubMed Central

Nelson, Lonnie A.; Buchwald, Dedra S.; Walker, Leslie R.; Mueller, Beth A.

2016-01-01

Introduction The prevalence of pre-eclampsia, a major cause of maternal morbidity, varies by race, being greater in African Americans, and lower in Asians and Hispanics than in White women. Little is known about its prevalence in American Indians/Alaska Natives (AI/ANs). We estimated pre-eclampsia risk in AI/ANs compared to Whites, with consideration of the potential effect of obesity, a major risk factor for pre-eclampsia, and a condition disproportionately affecting AI/AN women. Methods This retrospective cohort study of linked birth-hospital discharge data from Washington State (2003–2013) included all AI/AN women and a sample of White first-time mothers with singleton deliveries. Logistic regression was used to estimate odds ratio (OR) and 95 % confidence intervals (CI) for pre-eclampsia risk in AI/ANs compared to Whites, first controlling for several important risk factors, and subsequently with additional adjustment for pre-pregnancy body mass index (BMI). Results AI/ANs had an increased risk of pre-eclampsia compared to Whites after controlling for all covariates except BMI (OR 1.17, 95 % CI 1.06–1.29). After further adjustment for BMI, the racial disparity in pre-eclampsia risk was greatly attenuated (OR 1.05, 95 % CI 0.95–1.16). Discussion This population-based study suggests that any increased risk in AI/ANs relative to Whites may be at least partly due to differences in BMI. PMID:27461024

sFlt-1/PlGF ratio test for pre-eclampsia: an economic assessment for the UK.

PubMed

Vatish, M; Strunz-McKendry, T; Hund, M; Allegranza, D; Wolf, C; Smare, C

2016-12-01

To assess the economic impact of introducing into clinical practice in the UK the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test for guiding the management of pre-eclampsia. We used an economic model estimating the incremental value of information, from a UK National Health Service payer's perspective, generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. The economic model estimated costs associated with the diagnosis and management of pre-eclampsia in pregnant women between 24 + 0 and 36 + 6 weeks' gestation, managed in either a 'test' scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a 'no-test' scenario in which clinical decisions are based on current diagnostic procedures alone. Test characteristics and resource use were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of pre-eclampsia. The main outcome measure from the economic model was the cost per patient per episode of care, from first suspicion of pre-eclampsia to birth. Introduction of the sFlt-1/PlGF ratio test into clinical practice is expected to result in cost savings of £344 per patient compared with a no-test scenario. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalization. Introducing the sFlt-1/PlGF ratio test into clinical practice in the UK was shown to be cost-saving by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia. In addition, the test ensures that those women at higher risk are identified and managed appropriately. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

The reduction in circulating levels of melatonin may be associated with the development of preeclampsia.

PubMed

Zeng, K; Gao, Y; Wan, J; Tong, M; Lee, A C; Zhao, M; Chen, Q

2016-11-01

Placental dysfunction and oxidative stress contribute to the pathogenesis of preeclampsia, which is a pregnancy-specific disorder. It has been suggested that the incidence of preeclampsia has a seasonal variation. Melatonin, as a seasonal factor, has been suggested to be involved in a successful pregnancy. In this study, we investigated the association of circulating levels of melatonin with preeclampsia. Serum was collected from women with preeclampsia (n=113) and gestation-matched healthy pregnant women, and the levels of melatonin were measured. In addition, the expression of melatonin receptors was examined in preeclamptic placentae (n=27). The association of the incidence of preeclampsia and seasonal variation was also analysed from 1491 women with preeclampsia within 77 745 healthy pregnancies. The serum levels of melatonin were significantly reduced in women with preeclampsia at presentation and these reduced serum levels of melatonin were not associated with the severity or time onset of preeclampsia nor with seasonal variation. The expression of melatonin receptor, MT1 was reduced in preeclamptic placentae. The incidence of preeclampsia was did exhibit seasonal variation, but this was largely due to the increase in the incidence of mild or late-onset preeclampsia. Our results demonstrate that reduced melatonin levels are associated with the development of preeclampsia but that the circulating levels of melatonin do not appear to be subject to seasonal variation during pregnancy.

Exposure to experimental preeclampsia in mice enhances the vascular response to future injury.

PubMed

Pruthi, Dafina; Khankin, Eliyahu V; Blanton, Robert M; Aronovitz, Mark; Burke, Suzanne D; McCurley, Amy; Karumanchi, S Ananth; Jaffe, Iris Z

2015-04-01

Cardiovascular disease (CVD) remains the leading killer of women in developed nations. One sex-specific risk factor is preeclampsia, a syndrome of hypertension and proteinuria that complicates 5% of pregnancies. Although preeclampsia resolves after delivery, exposed women are at increased long-term risk of premature CVD and mortality. Pre-existing CVD risk factors are associated with increased risk of developing preeclampsia but whether preeclampsia merely uncovers risk or contributes directly to future CVD remains a critical unanswered question. A mouse preeclampsia model was used to test the hypothesis that preeclampsia causes an enhanced vascular response to future vessel injury. A preeclampsia-like state was induced in pregnant CD1 mice by overexpressing soluble fms-like tyrosine kinase-1, a circulating antiangiogenic protein that induces hypertension and glomerular disease resembling human preeclampsia. Two months postpartum, soluble fms-like tyrosine kinase-1 levels and blood pressure normalized and cardiac size and function by echocardiography and renal histology were indistinguishable in preeclampsia-exposed compared with control mice. Mice were then challenged with unilateral carotid injury. Preeclampsia-exposed mice had significantly enhanced vascular remodeling with increased vascular smooth muscle cell proliferation (180% increase; P<0.01) and vessel fibrosis (216% increase; P<0.001) compared with control pregnancy. In the contralateral uninjured vessel, there was no difference in remodeling after exposure to preeclampsia. These data support a new model in which vessels exposed to preeclampsia retain a persistently enhanced vascular response to injury despite resolution of preeclampsia after delivery. This new paradigm may contribute to the substantially increased risk of CVD in woman exposed to preeclampsia. © 2015 American Heart Association, Inc.

Relationship between Fas and Fas Ligand gene polymorphisms and pre-eclampsia.

PubMed

Masoumi, Elham; Tavakkol-Afshari, Jalil; Nikpoor, Amin Reza; Ghaffari-Nazari, Haniyeh; Tahaghoghi-Hajghorbani, Sahar; Jalali, Seyed Amir

2016-10-01

In normal pregnancy, the Th1 subtype, responsible for the production of inflammatory cytokines, is reduced, and the Th2 subtype is increased to prohibit inflammation. In pre-eclampsia, the Th1 cell population is increased; thus, subsequent inflammation and trophoblast destruction occur. Polymorphisms in the Fas and Fas Ligand (FasL) promoter regions can influence Fas and FasL expression and accused to increase of Th1 subtype. DNA samples from 153 pregnant women with pre-eclampsia and 140 controls were genotyped through polymerase chain reaction-restriction fragment length polymorphism. A Fisher's exact test was used to compare the distribution of individual polymorphisms. Fas-1377 AA, AG and GG genotypes were observed in 2.61%, 18.30% and 79.08% in the pre-eclampsia group opposed to 0%, 27.14% and 72.85% in the control group (P = 0.037), respectively. Fas-670 AA, AG and GG genotypes were observed in 37.9%, 41.8% and 20.3% of pre-eclampsia patients compared with 33.6%, 50.7% and 15.7% in healthy pregnant women (P = 0.291), respectively. No statically significant differences in the FasL-844 genotype were observed between the groups (P = 0.69). The Fas-1377G > A polymorphism is associated with a higher risk of pre-eclampsia. © 2016 Japan Society of Obstetrics and Gynecology.

Higher prepregnancy body mass index is a risk factor for developing preeclampsia in Maya-Mestizo women: a cohort study.

PubMed

Canto-Cetina, Thelma; Coral-Vázquez, Ramón Mauricio; Rojano-Mejía, David; Pérez Godoy, Sergio; Coronel, Agustín; Canto, Patricia

2018-08-01

Preeclampsia and obesity are two closely related syndromes. The high maternal prepregnancy body mass index (BMI) is a risk factor for present preeclampsia, independently of the ethnic background of the studied population. The aim of this study was to analyse in a prospective cohort study the relation between prepregnancy BMI and development of preeclampsia in Maya-Mestizo women. This is a prospective cohort study of 642 pregnant women that were included in the first trimester of the pregnancy (gestational age ≤12 weeks at the first antenatal visit) and all of them were of Maya-Mestizo ethnic origin from the state of Yucatán, México. We assessed the potential risk factors for preeclampsia and documented the prepregnancy BMI (kg/m 2 ) that was based on measured height and maternal self-report of prepregnancy weight at the initial visit. Besides, in the antenatal visit we documented if the pregnant women developed preeclampsia. Of the 642 pregnant Maya-Mestizo women, 49 developed preeclampsia, with an incidence of 7.6% (44.9% had severe and 55% mild). The prepregnancy BMI was higher in women with developed preeclampsia than in those with normal pregnancies. Women with overweight or obesity in comparison with normal weight presented a RR = 2.82 (95% CI: 1.32-6.03; P = 0.008) and RR= 4.22 (95% CI: 2.07-8.61; P = 0.001), respectively. Our findings expand the previous studies to show that the higher prepregnancy BMI is a strong, independent risk factor for preeclampsia.

Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

PubMed

Nevalainen, Jaana; Skarp, Sini; Savolainen, Eeva-Riitta; Ryynänen, Markku; Järvenpää, Jouko

2017-10-26

To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

Role of fetal DNA in preeclampsia (review).

PubMed

Konečná, Barbora; Vlková, Barbora; Celec, Peter

2015-02-01

Preeclampsia is an autoimmune disorder characterized by hypertension. It begins with abnormal cytotrophoblast apoptosis, which leads to inflammation and an increase in the levels of anti-angiogenic factors followed by the disruption of the angiogenic status. Increased levels of fetal DNA and RNA coming from the placenta, one of the most commonly affected organs in pregnancies complicated by preeclampsia, have been found in pregnant women with the condition. However, it remains unknown as to whether this is a cause or a consequence of preeclampsia. Few studies have been carried out on preeclampsia in which an animal model of preeclampsia was induced by an injection of different types of DNA that are mimic fetal DNA and provoke inflammation through Toll-like receptor 9 (TLR9) or cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). The specific mechanisms involved in the development of preeclampsia are not yet fully understood. It is hypothesized that the presence of different fragments of fetal DNA in maternal plasma may cause for the development of preeclampsia. The function of DNase during preeclampsia also remains unresolved. Studies have suggested that its activity is decreased or the DNA is protected against its effects. Further research is required to uncover the pathogenesis of preeclampsia and focus more on the condition of patients with the condition.

HtrA3 as an Early Marker for Preeclampsia: Specific Monoclonal Antibodies and Sensitive High-Throughput Assays for Serum Screening

PubMed Central

Dynon, Kemperly; Heng, Sophea; Puryer, Michelle; Li, Ying; Walton, Kelly; Endo, Yaeta; Nie, Guiying

2012-01-01

Mammalian HtrA3 (high temperature requirement A3) is a serine protease of the HtrA family. It has two isoforms [long (HtrA3-L) and short (HtrA3-S)] and is important for placental development and cancer progression. Recently, HtrA3 was identified as a potential diagnostic marker for early detection of preeclampsia, a life-threatening pregnancy-specific disorder. Currently there are no high-throughput assays available to detect HtrA3 in human serum. In this study we generated and fully tested a panel of five HtrA3 mouse monoclonal antibodies (mAbs). Three mAbs recognised both HtrA3-L and HtrA3-S and the other two detected HtrA3-L only. All five mAbs were highly specific to HtrA3 and applicable in western blotting and immunohistochemical analysis of endogenous HtrA3 proteins in the mouse and human tissues. Amplified luminescent proximity homogeneous assays-linked immunosorbent assays (AlphaLISAs), were developed to detect HtrA3 isoforms in picomolar levels in serum. The HtrA3 AlphaLISA detected significantly higher serum levels of HtrA3 in women at 13–14 weeks of gestation who subsequently developed preeclampsia compared to gestational-age matched controls. These HtrA3 mAbs are valuable for the development of immunoassays and characterisation of HtrA3 isoform-specific biology. The newly developed HtrA3 AlphaLISA assays are suitable for large scale screening of human serum. PMID:23049902

Adenosine and preeclampsia.

PubMed

Salsoso, Rocío; Farías, Marcelo; Gutiérrez, Jaime; Pardo, Fabián; Chiarello, Delia I; Toledo, Fernando; Leiva, Andrea; Mate, Alfonso; Vázquez, Carmen M; Sobrevia, Luis

2017-06-01

Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3-5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia. Preeclampsia associates with increased adenosine concentration in the maternal blood and placental tissue, likely due to local hypoxia and ischemia (although not directly demonstrated), microthrombosis, increased catecholamine release, and platelet activation. In addition, abnormal expression and function of equilibrative nucleoside transporters is described in foetoplacental tissues from preeclampsia; however, the role of adenosine receptors in the aetiology of this disease is not well understood. Adenosine receptors activation may be related to abnormal trophoblast invasion, angiogenesis, and ischemia/reperfusion mechanisms in the placenta from preeclampsia. These mechanisms may explain only a low fraction of the associated abnormal transformation of spiral arteries in preeclampsia, triggering cellular stress and inflammatory mediators release from the placenta to the maternal circulation. Although increased adenosine concentration in preeclampsia may be a compensatory or adaptive mechanism favouring placental angiogenesis, a poor angiogenic state is found in preeclampsia. Thus, preeclampsia-associated complications might affect the cell response to adenosine due to altered expression and activity of adenosine receptors, membrane transporters, or cell signalling mechanisms. This review summarizes the evidence available on the potential involvement of the adenosine in the clinical, pathophysiology, and therapeutic features of preeclampsia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Follistatin-like 3 across gestation in preeclampsia and uncomplicated pregnancies among lean and obese women.

PubMed

Founds, Sandra A; Ren, Dianxu; Roberts, James M; Jeyabalan, Arun; Powers, Robert W

2015-04-01

The purpose of this study was to examine circulating maternal follistatin-like 3 (FSTL-3) by gestational age and obesity in pregnancy and preeclampsia. FSTL-3 was quantified in maternal plasma collected in each trimester from prepregnancy body mass index-determined groups: 15 lean and 24 obese controls and 20 obese women who developed preeclampsia. Repeated measures mixed models and logistic regression were conducted (P ≤ .05). FSTL-3 was not related to maternal adiposity. FSTL-3 changed across pregnancy in lean controls and obese preeclampsia but not in obese controls. FSTL-3 was higher in preeclampsia in the second trimester compared to lean controls and in the third trimester compared to both control groups. Elevated FSTL-3 at mid-gestation was associated with an increased odds of preeclampsia (odds ratio 3.15; 95% confidence interval 1.19-8.36; P = .02). Elevated FSTL-3 concentrations were attributable to preeclampsia and were associated with increased likelihood of later developing preeclampsia, suggesting further study as a biomarker prior to clinically evident disease. © The Author(s) 2014.

Prediction of early and late preeclampsia by flow-mediated dilation of the brachial artery*

PubMed Central

Brandão, Augusto Henriques Fulgêncio; Evangelista, Aline Aarão; Martins, Raphaela Menin Franco; Leite, Henrique Vítor; Cabral, Antônio Carlos Vieira

2014-01-01

Objective To assess the accuracy in the prediction of both early and late preeclampsia by flow-mediated dilation of the brachial artery (FMD), a biophysical marker for endothelial dysfunction. Materials and Methods A total of 91 patients, considered at high risk for development of preeclampsia were submitted to brachial artery FMD between 24 and 28 weeks of gestation. Results Nineteen out of the selected patients developed preeclampsia, 8 in its early form and 11 in the late form. With a cut-off value of 6.5%, the FMD sensitivity for early preeclampsia prediction was 75.0%, with specificity of 73.3%, positive predictive value (PPV) of 32.4% and negative predictive value (NPV) of 91.9%. For the prediction of late preeclampsia, sensitivity = 83.3%, specificity = 73.2%, PPV = 34.4% and NPV = 96.2% were observed. And for the prediction of all associated forms of preeclampsia, sensitivity = 84.2%, specificity = 73.6%, PPV = 45.7% and NPV = 94.6% were observed. Conclusion FMD of the brachial artery is a test with good accuracy in the prediction of both early and late preeclampsia, which may represent a positive impact on the follow-up of pregnant women at high risk for developing this syndrome. PMID:25741086

Soluble fms-Like Tyrosine Kinase 1 (sFlt1), Endoglin and Placental Growth Factor (PlGF) in Preeclampsia among High Risk Pregnancies

PubMed Central

Powers, Robert W.; Jeyabalan, Arun; Clifton, Rebecca G.; Van Dorsten, Peter; Hauth, John C.; Klebanoff, Mark A.; Lindheimer, Marshall D.; Sibai, Baha; Landon, Mark; Miodovnik, Menachem

2010-01-01

Background Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. Methods This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. Results The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. Conclusions The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women. PMID:20948996

High normal blood pressure in early pregnancy also contribute to early onset preeclampsia and severe preeclampsia.

PubMed

He, Dian; Wu, Shaowen; Zhao, Haiping; Zheng, Zihe; Zhang, Weiyuan

2017-11-27

This study was to evaluate effects of high normal blood pressure (HNBP) in early pregnancy on total preeclampsia, early preeclampsia, and severe preeclampsia. We conducted a multicenter, national representative retrospective cohort study. HNBP was defined as systolic blood pressure between 130 and 140 mmHg or diastolic blood pressure between 85 and 90 mmHg. We used multivariable logistic regression to examine the associations of HNBP and the risks of above three types of preeclampsia. We included 58 054 women who were normotensive and nulliparous in early pregnancy. 4 809 (8.3%) fulfilled the definition of having HNBP, 16 682 (28.7%) were in normal blood pressure group, and 36 563 (63.0%) were in optimal blood pressure group. The incidence rates of total preeclampsia, early preeclampsia, and severe preeclampsia were 2.1% (1 217), 0.8% (491), and 1.4% (814), respectively. Compared to having optimal blood pressure, women with HNBP had significantly higher odds of total preeclampsia (odds ratio (OR) = 4.028, 95% confidence interval (CI) 3.377, 4.804), severe preeclampsia (OR = 3.542, 95% CI 2.851, 4.400), and early preeclampsia (OR = 8.163, 95% CI 6.219, 10.715). Our restricted cubic spline results supported the dose-response relationship between continuous blood pressure and the odds ratio of three types of preeclampsia. The fraction of early preeclampsia associated with prehypertension was 58.6%, which was higher than those of total preeclampsia (42.2%) or severe preeclampsia (40.5%). Women in early pregnancy with HNBP more likely develop total preeclampsia, early preeclampsia and severe preeclampsia, compared to those with optimal blood pressure. HNBP contribute more to early preeclampsia than severe preeclampsia. Our study provided robust epidemiological evidences for monitoring HNBP in early pregnancy to reduce the risks of preeclampsia.

Metabolic syndrome in the non-pregnant state is associated with the development of preeclampsia.

PubMed

Cho, Geum Joon; Park, Jong Heon; Shin, Soon-Ae; Oh, Min-Jeong; Seo, Hong Seog

2016-01-15

The aim of this study was to investigate the association between metabolic syndrome in the non-pregnant state and the development of preeclampsia. We enrolled 212,463 Korean women who had their first delivery between January, 2011 and December, 2012 and had undergone a national health screening examination through the National Health Insurance during the 1-2 years before their first delivery. Women who had hypertension in the non-pregnant state were excluded. The presence of metabolic syndrome was defined using the modified criteria published in National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence of metabolic syndrome in non-pregnant state was 1.2%. Preeclampsia developed in 3.1% and its prevalence among women with and without metabolic syndrome was 7.3% and 3.0%, respectively. The pre-pregnancy prevalence of metabolic syndrome was higher in women who developed preeclampsia compared to that in those who had a normal pregnancy (1.1% vs. 2.8%; p<0.001). On multivariate regression analysis, women with metabolic syndrome had an increased risk of developing preeclampsia (odds ratio: 1.48; 95% CI: 1.26 to 1.74) compared to that in those without metabolic syndrome, after adjusting for age, family history of hypertension, smoking status, and pre-pregnancy body mass index. The risk of preeclampsia increased with a rise in the number of components of metabolic syndrome. Metabolic syndrome in the non-pregnant state was associated with the development of preeclampsia. Further studies are needed to evaluate whether early intervention for metabolic syndrome before pregnancy can decrease the risk of developing preeclampsia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Biomarkers of glomerular dysfunction in pre-eclampsia - A systematic review.

PubMed

Kerley, Robert N; McCarthy, Cathal

2018-03-10

Early detection of pre-eclampsia remains one of the major focuses of antenatal obstetric care. There is often a delay in the diagnosis, mainly due to the non-specific nature of the condition. Podocytes which play a pivotal role in glomerular function become injured in pre-eclampsia leading to subsequent proteinuria. Our aim was to review available studies to determine the clinical utility of biomarkers of podocyte injury in pre-eclampsia. We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature to determine the clinical utility of podocyte injury biomarkers in predicting pre-eclampsia. This study identified five potential renal biomarkers including podocytes, nephrin, synaptopodin, podocin and podocalyxin. The pooled sensitivity of all biomarkers was 0.78 (95% CI 0.74-0.82) with a specificity of 0.82 (95% CI 0.79-0.85). The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.926 (SE 0.30). Urinary nephrin achieved the highest diagnostic values with a sensitivity of 0.81 (95% CI 0.72-0.88) and specificity of 0.84 (95% CI 0.79-0.84). Biomarkers of glomerular injury show promise as diagnostic aids in pre-eclampsia. A large-scale prospective cohort study is warranted before these biomarkers can be recommended for routine clinical care. Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Differences in clinical presentation and pregnancy outcomes in antepartum preeclampsia and new-onset postpartum preeclampsia: Are these the same disorder?

PubMed

Vilchez, Gustavo; Hoyos, Luis R; Leon-Peters, Jocelyn; Lagos, Moraima; Argoti, Pedro

2016-11-01

New-onset postpartum preeclampsia is a poorly defined condition that accounts for a significant percentage of eclampsia cases. It is unclear whether new-onset postpartum preeclampsia is a different disorder from or belongs to the same spectrum of classic antepartum preeclampsia. The objective of this study was to compare the clinical presentation and pregnancy outcomes of antepartum preeclampsia and new-onset postpartum preeclampsia. A retrospective study including 92 patients with antepartum preeclampsia and 92 patients with new-onset postpartum preeclampsia was performed. Clinical presentation and pregnancy outcomes were compared. Chi-square test was used to analyze categorical variables, and independent t -test and Mann-Whitney U -test for numerical variables. P -values of <0.05 were used to indicate statistical signifi cance. Patients with antepartum preeclampsia and new-onset postpartum preeclampsia differ significantly in profile, symptoms at presentation, laboratory markers and pregnancy outcomes. New-onset postpartum preeclampsia has a distinct patient profile and clinical presentation than antepartum preeclampsia, suggesting they may represent different disorders. Characterization of a patient profile with increased risk of developing this condition will help clinicians to identify patients at risk and provide early and targeted interventions to decrease the morbidity associated with this condition.

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

PubMed Central

Phipps, Elizabeth; Prasanna, Devika; Brima, Wunnie

2016-01-01

Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after. PMID:27094609

Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

PubMed

Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

2015-02-24

Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

Intake of antioxidant nutrients and coefficients of variation in pregnant women with preeclampsia.

PubMed

Menezes de Oliveira, Alane Cabral; Albuquerque Santos, Arianne; Rodrigues Bezerra, Alexandra; Machado Tavares, Myrian Cicyanne; Rocha de Barros, Amanda Maria; Costa Ferreira, Raphaela

2016-09-01

Oxidative stress appears to play a critical role in the pathogenesis of preeclampsia. Evidence suggests that adequate intake of antioxidants can modulate this condition. The objective of this study was to assess the intake of antioxidant nutrients and coefficients of variation in pregnant women with preeclampsia. In a cross-sectional study in the public health network of the city of Maceió, Brazil, a dietary survey was performed consisting of 24-hour food recalls, with subsequent adjustment of nutrients using the estimated average requirement as the cutoff point, and a questionnaire on frequency of consumption of antioxidants. We studied 90 pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia (PWoP) with mean ages of 25.8±6.7 years and 24.1±6.2 years (p=0.519), respectively. A low mean intake of antioxidants (vitamin A, selenium, zinc and copper) was observed in both PWP and PWoP, although intakes of vitamin A (p=0.045) and selenium (p=0.008) were higher in PWoP. In addition, we observed high coefficients of variation in nutrient intakes in both groups, which were higher for vitamin C (p<0.001), vitamin A (p=0.006) and copper (p=0.005) in PWP. Consumption of antioxidant nutrients by pregnant women with preeclampsia is inadequate, with considerable daily variations in intake, which points to a need for nutrition education strategies aimed at improving intakes, because diet is without doubt a key factor in the modulation of oxidative stress caused by preeclampsia. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Dietary fiber intake in early pregnancy and risk of subsequent preeclampsia.

PubMed

Qiu, Chunfang; Coughlin, Kara B; Frederick, Ihunnaya O; Sorensen, Tanya K; Williams, Michelle A

2008-08-01

Substantial epidemiological evidence documents diverse health benefits, including reduced risks of hypertension, associated with diets high in fiber. Few studies, however, have investigated the extent to which dietary fiber intake in early pregnancy is associated with reductions in preeclampsia risk. We assessed the relationship between maternal dietary fiber intake in early pregnancy and risk of preeclampsia. We also evaluated cross-sectional associations of maternal early pregnancy plasma lipid and lipoprotein concentrations with fiber intake. The study population comprised 1,538 pregnant Washington State residents. A 121-item food frequency questionnaire (FFQ) was used to assess maternal dietary intake, 3 months before and during early pregnancy; and generalized linear regression procedures were used to derive relative risk (RR) and 95% confidence intervals (CIs). Dietary total fiber intake was associated with reduced preeclampsia risk. After adjusting for confounders, the RR of preeclampsia for women in the highest (> or =21.2 g/day) vs. the lowest quartile (<11.9 g/day) was 0.28 (95% CI = 0.11-0.75). We observed associations of similar magnitude when the highest vs. the lowest quartiles of water-soluble fiber (RR = 0.30; 95% CI = 0.11-0.86) and insoluble fiber (RR = 0.35; 95% CI = 0.14-0.87) were evaluated. Mean triglyceride concentrations were lower (-11.9 mg/dl, P = 0.02) and high-density lipoprotein cholesterol concentrations were higher (+2.63 mg/dl, P = 0.09) for women in the highest quartile vs. those in the lowest quartile. These findings of reduced preeclampsia risk with higher total fiber intake corroborate an earlier report; and expand the literature by providing evidence, which suggests that dietary fiber may attenuate pregnancy-associated dyslipidemia, an important clinical characteristic of preeclampsia.

Preeclampsia - self-care

MedlinePlus

... preeclampsia is mild, you may be able to stay at home on bed rest. You will need to have ... and your baby if you develop preeclampsia: The mother can have kidney ... to detach from the uterus (abruption) and for stillbirth.

Pre-eclampsia: contribution of maternal constitutional factors and the consequences for cardiovascular health.

PubMed

Barden, Anne

2006-09-01

1. Pre-eclampsia is a serious complication of pregnancy that is potentially life threatening for both the mother and baby. It encompasses a number of abnormalities that may be present in other clinical conditions. 2. A placenta is essential for the development of pre-eclampsia and can be important in the pathogenesis of pre-eclampsia. Normal pregnancy is associated with remodelling of the maternal spiral arteries, which deliver blood to the placental villous space. Remodelling involves invasion by placental cytotrophoblasts that cause the maternal spiral arteries to lose their smooth muscle and become capacitance vessels; this process, known as placentation, is complete by 20 weeks of pregnancy. Poor placentation is associated with small-for-gestational-age fetuses and some cases of pre-eclampsia. It is thought that poor placentation can result in a hypoxic placenta that releases 'toxic substances' into the maternal circulation, contributing to the maternal syndrome. A number of candidate 'toxic substances' have been proposed, but none is universally raised in pre-eclampsia. 3. Although the placenta is necessary for the development of pre-eclampsia, the extent to which placental abnormalities contribute to the condition varies. It is becoming apparent that maternal constitutional factors may also be important in this syndrome. Underlying hypertension, diabetes and obesity strongly predispose to pre-eclampsia. However, a continuum of risk may exist for blood pressure, bodyweight, glucose and lipids, which, in combination with each other and some degree of placental abnormalities, may lead to the development of pre-eclampsia. 4. The present review will focus on the maternal constitutional factors that define the metabolic syndrome and examine their contribution to pre-eclampsia and the long-term consequences for cardiovascular health.

Morphological Characteristics of Placental Complex in Pregnant Women without Complications in Pregnancy and in the Presence of Severe Preeclampsia

ERIC Educational Resources Information Center

Umbetov, Turakbai Zh.; Berdalinova, Akzhenis K.; Tusupkalieyv, Akylbek B.; Koishybayev, Arip K.; Zharilkasynov, Karaman Ye.

2016-01-01

According to the WHO data, preeclampsia develops during late pregnancy in 2-8% of women. Preeclampsia is a major cause of maternal and perinatal morbidity and mortality, therefore, the study of the morphological features of placental complex, taking into account gestational complications in postpartum women with severe preeclampsia is an important…

Placental weight in the first pregnancy and risk for preeclampsia in the second pregnancy: A population-based study of 186 859 women.

PubMed

Dypvik, Johanne; Larsen, Sandra; Haavaldsen, Camilla; Jukic, Anne M; Vatten, Lars J; Eskild, Anne

2017-07-01

To study whether placental weight in the first pregnancy is associated with preeclampsia in the second pregnancy. In this population-based study, we included all women with two consecutive singleton pregnancies reported to the Medical Birth Registry of Norway during 1999-2012 (n=186 859). Placental weight in the first pregnancy was calculated as z-scores, and the distribution was divided into five groups of equal size (quintiles). We estimated crude and adjusted odds ratios with 95% confidence intervals for preeclampsia in the second pregnancy according to quintiles of placental weight z-scores in the first pregnancy. The 3rd quintile was used as the reference group. Among women without preeclampsia in the first pregnancy, 1.4% (2507/177 149) developed preeclampsia in the second pregnancy. In these women, the risk for preeclampsia in the second pregnancy was associated with placental weight in the first pregnancy in both lowest (crude odds ratio (cOR) 1.30, 95% confidence interval (CI); 1.14-1.47) and highest quintile (cOR 1.20, 95% CI; 1.06-1.36). The risk associated with the highest quintile of placental weight was confined to term preeclampsia. Among women with preeclampsia in the first pregnancy, 15.7% (1522/9710) developed recurrent preeclampsia, and the risk for recurrent preeclampsia was associated with placental weight in lowest quintile in the first pregnancy (cOR 1.30, 95% CI; 1.10-1.55). Adjustment for interval between pregnancies, maternal diabetes, age, and smoking in the first pregnancy did not alter these estimates notably. Placental weight in the first pregnancy might help to identify women who could be at risk for developing preeclampsia in a second pregnancy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Preeclampsia is associated with increased maternal body weight in a northeastern Brazilian population

PubMed Central

2013-01-01

Background Preeclampsia is a disease with great variability in incidence across the world. The mortality is higher in lower income countries, where it is the leading cause of maternal mortality. This study aimed to determine the frequency of and risk factors for preeclampsia in a low income population from an urban area of Brazil. Methods A prospective case control study of 242 women of which 30 developed preeclampsia, 4 had gestational hypertension, 2 had superimposed hypertension, 11 had spontaneous abortion, 13 were lost to follow up and 192 had normal pregnancy. This latter group was considered the normotensive controls. The rate of preeclampsia and the risk of cardiovascular disease, after onset of preeclampsia, were determined. Results Of the 218 women who completed the study, the frequency of hypertensive disorder of pregnancy was 16.5% (36 of 218) and of preeclampsia was 13.8% (30 of 218). Women with preeclampsia had a higher body mass index (BMI), mean of 25.3 ± 4.8 compared to 23.5 ± 3.7 for the normotensive controls, p = 0.02. The risk of preeclampsia increased with BMI [Odds ratio (OR) 1.12, 95% Confidence Interval (CI = 1.02;1.24, p-value = 0.023)]. Women with preeclampsia developed chronic hypertension more often than normotensive controls (p = 0.043) and their systolic and ambulatory blood pressure monitoring was elevated (p = 0.034). Women with preeclampsia had higher BMI even 5 years post-pregnancy (p = 0.008). Conclusions Women who are overweight or older have an increased risk of preeclampsia. Previous history of preeclampsia increases the risk of early onset of chronic hypertension. Therefore, effective preventive measures are needed, particularly women at lower social economic stratum who have less access to proper medical care and adequate nutrition. PMID:23927768

Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia

PubMed Central

Lynch, Anne M.; Murphy, James R.; Byers, Tim; Gibbs, Ronald S.; Neville, Margaret C.; Giclas, Patricia C.; Salmon, Jane E.; Holers, V. Michael

2008-01-01

OBJECTIVE Preeclampsia is a multisystem disease classically defined on the basis of hypertension and proteinuria. As shown in animal studies, complement activation is associated with inflammation in the placenta and adverse pregnancy outcomes. The association between complement activation in humans and adverse pregnancy outcomes is unclear. The purpose of this study was to determine whether elevated levels of the activation fragment Bb in early pregnancy are predictive of preeclampsia. STUDY DESIGN This prospective study of 701 women was conducted in Denver, CO. A single plasma sample was obtained from each woman before 20 weeks’ gestation. The cohort was followed up throughout pregnancy for the development of preeclampsia. Analysis included multivariate logistic regression to adjust for established risk factors for preeclampsia. RESULTS Preeclampsia developed in 4.6% of the cohort. Women with elevated Bb (90th or greater percentile) were substantially more likely to develop preeclampsia than women who had levels less than the 90th percentile (unadjusted relative risk [RR], 3.3, 95% confidence interval [CI] 1.6 to 7, P = .0009). Other significant risk factors for preeclampsia included nulliparity (RR, 2.1, 95% CI, 1–4), a high body mass index (P = .006 for trend), and maternal medical (preexisting maternal hypertension, type 1 diabetes, systemic lupus erythematosus) disease (RR, 4.4, 95% CI, 2–10). Significant risk factors among multiparous women included a history of hypertension in a previous pregnancy (RR, 5, 95% CI, 1.6 to 16) and a change of paternity (RR, 5.1, 95% CI, 1.6 to 15). Adjustment for risk factors did not attenuate the association between an elevated Bb and preeclampsia (adjusted odds ratio [OR], 3.8, 95% CI, 1.6 to 9, P = .002) in the cohort. After removing women with plasma obtained before 10 weeks, the adjusted OR of Bb in the top decile for preeclampsia was 6.1 (95% CI 2.2, 17, P = .0005). CONCLUSION The complement activation product Bb in early pregnancy is a biomarker for elevated risk of preeclampsia. This observation suggests that events linked to activation of complement in early pregnancy are associated with the pathogenesis of preeclampsia. PMID:18221926

Vasoactive agents for the prediction of early- and late-onset preeclampsia in a high-risk cohort

PubMed Central

2013-01-01

Background To evaluate the soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio for the prediction of early- and late-onset preeclampsia in a high-risk cohort. Methods We studied serial serum samples collected prospectively at 12 + 0 - 14 + 0, 18 + 0 - 20 + 0, and 26 + 0 - 28 + 0 weeks + days of gestation in 6 women who developed early-onset preeclampsia (before 34 weeks of gestation) and in 21 women who developed late-onset preeclampsia (after 34 weeks of gestation) with automated ElecSys 2010 immunoanalyzer (Roche Diagnostics, Germany). Twenty-six high-risk women and 53 women without risk factors with normal pregnancies served as controls. Results Serum PlGF concentrations were lower at 18 + 0 to 20 + 0, and 26 + 0 to 28 + 0 weeks of gestation in women who developed early-onset preeclampsia compared to women who developed late-onset preeclampsia and to controls (p < 0.05 for all comparisons). At 18 + 0 to 20 + 0 weeks of gestation area under the receiver-operating characteristic curve (AUC) for serum PlGF was 99.8% (p = 0.0007, 95% CI 99.0-100.0). At 26 + 0 to 28 + 0 weeks of gestation serum sFlt-1/PlGF ratio explicitly detects those women who developed early-onset preeclampsia (AUC 100.0%, p = 0.0007, 95% CI 100–100). Amongst women with late-onset preeclampsia, those who developed severe form of the disease (N = 8) had significantly higher serum sFlt-1 concentrations at all three timepoints (p = 0.004, p = 0.006, and p = 0.003, respectively) compared to women with non-severe form (N = 13). Conclusions Low serum PlGF concentration predicts early-onset preeclampsia from the second trimester and elevated serum sFlt-1/PlGF ratio from 26 to 28 weeks of gestation. Elevated serum sFlt-1 concentration in the first trimester in women who later develop late-onset, severe preeclampsia may suggest different etiology compared to the late-onset non-severe form of the disease. PMID:23663420

Severe preeclampsia and maternal self-report of oral health, hygiene, and dental care.

PubMed

Boggess, Kim A; Berggren, Erica K; Koskenoja, Viktoria; Urlaub, Diana; Lorenz, Carol

2013-02-01

Maternal periodontal disease diagnosed by a detailed oral health examination is associated with preeclampsia. Our objective was to measure the association between maternal self-report of oral symptoms/problems, oral hygiene practices, and/or dental service use before or during pregnancy and severe preeclampsia. A written questionnaire was administered to pregnant females at the time of prenatal ultrasound and outcomes were ascertained by chart abstraction. The χ(2) test compared maternal oral symptoms/problems, hygiene practices, and dental service use between females with severe preeclampsia versus normotensive females. Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for severe preeclampsia. A total of 48 (10%) of 470 females reported ≥2 oral symptoms/problems in the 6 months before pregnancy and 77 (16%) since pregnancy. Fifty-one (11%) reported previous periodontal treatment. Twenty-eight (6%) of 470 developed severe preeclampsia. Females with a history of periodontal treatment were more likely to develop severe preeclampsia (aOR = 3.71; 95% CI = 1.40 to 9.83) than females without a history of periodontal treatment. Self-reported oral health symptoms/problems, oral hygiene practices, or dental service use before or during pregnancy were not associated with severe preeclampsia when considered in the context of other maternal risk factors. Maternal self-report of previous periodontal treatment before pregnancy is associated with severe preeclampsia.

Early pregnancy vitamin D status and risk of preeclampsia.

PubMed

Mirzakhani, Hooman; Litonjua, Augusto A; McElrath, Thomas F; O'Connor, George; Lee-Parritz, Aviva; Iverson, Ronald; Macones, George; Strunk, Robert C; Bacharier, Leonard B; Zeiger, Robert; Hollis, Bruce W; Handy, Diane E; Sharma, Amitabh; Laranjo, Nancy; Carey, Vincent; Qiu, Weilliang; Santolini, Marc; Liu, Shikang; Chhabra, Divya; Enquobahrie, Daniel A; Williams, Michelle A; Loscalzo, Joseph; Weiss, Scott T

2016-12-01

Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia. We assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (10-18 weeks), on the development of preeclampsia. The effects of serum vitamin D (25-hydroxyvitamin D [25OHD]) levels on preeclampsia incidence at trial entry and in the third trimester (32-38 weeks) were studied. We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin D-associated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia. Of 881 women randomized, outcome data were available for 816, with 67 (8.2%) developing preeclampsia. There was no significant difference between treatment (N = 408) or control (N = 408) groups in the incidence of preeclampsia (8.08% vs. 8.33%, respectively; relative risk: 0.97; 95% CI, 0.61-1.53). However, in a cohort analysis and after adjustment for confounders, a significant effect of sufficient vitamin D status (25OHD ≥30 ng/ml) was observed in both early and late pregnancy compared with insufficient levels (25OHD <30 ng/ml) (adjusted odds ratio, 0.28; 95% CI, 0.10-0.96). Differential expression of 348 vitamin D-associated genes (158 upregulated) was found in peripheral blood of women who developed preeclampsia (FDR <0.05 in the Vitamin D Antenatal Asthma Reduction Trial [VDAART]; P < 0.05 in a replication cohort). Functional enrichment and network analyses of this vitamin D-associated gene set suggests several highly functional modules related to systematic inflammatory and immune responses, including some nodes with a high degree of connectivity. Vitamin D supplementation initiated in weeks 10-18 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm. However, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia. Differentially expressed vitamin D-associated transcriptomes implicated the emergence of an early pregnancy, distinctive immune response in women who went on to develop preeclampsia. ClinicalTrials.gov NCT00920621. Quebec Breast Cancer Foundation and Genome Canada Innovation Network. This trial was funded by the National Heart, Lung, and Blood Institute. For details see Acknowledgments.

Elevation of urinary adipsin in preeclampsia: correlation with urine protein concentration and the potential use for a rapid diagnostic test.

PubMed

Wang, Tao; Zhou, Rong; Gao, Linbo; Wang, Yanyun; Song, Changping; Gong, Yunhui; Jia, Jin; Xiong, Wei; Dai, Li; Zhang, Lin; Hu, Huaizhong

2014-10-01

Early diagnosis and treatment of preeclampsia are essential for prevention of seizure development and fetus maturation. Although various methods have been developed for predicting or monitoring the onset of preeclampsia, a simple assay that can be used as a home or point of care test remains unavailable. We attempted to find a urinary protein that could be used as a biomarker for developing such a test. Urinary samples were collected from 124 preeclampsia and 135 healthy pregnant women for screening using a protein array technology and quantification by ELISA. A urinary protein, adipsin, was found significantly increased, and the adipsin creatinine ratio was closely correlated with the urinary 24-hour protein in patients with preeclampsia. When combined with the increased diastolic blood pressure (≥90 mm Hg), the sensitivity was 90.3% and the specificity reached 100.0% for preeclampsia diagnosis. We then developed a laminar flow immunoassay for rapid diagnosis, and the sensitivity and specificity were 89.04% and 100%, respectively, when combined with increased diastolic blood pressure. Because of the easiness of sample collection, assay conduction, and result interpretation, this urine test can be potentially used as a home test for monitoring preeclampsia onset for high-risk pregnant women and as a rapid test for a preliminary diagnosis for emergency patients at hospitals. © 2014 American Heart Association, Inc.

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines.

PubMed

Phipps, Elizabeth; Prasanna, Devika; Brima, Wunnie; Jim, Belinda

2016-06-06

Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after. Copyright © 2016 by the American Society of Nephrology.

Pregnancy Complications: Preeclampsia

MedlinePlus

... have preeclampsia after you’ve given birth. It most often happens within 48 hours (2 days) of having a baby, but it can develop up to 6 weeks after a baby’s birth. It’s just as dangerous as preeclampsia during pregnancy and needs immediate treatment. ...

Preeclampsia Research

MedlinePlus

... did not develop recurrent preeclampsia served as a control group. CRP levels were measured in the serum samples ... 20 years after pregnancy. Blood samples from a group of women who did not have preeclampsia served as the controls. Similar to the earlier findings that TSH was ...

Upregulation of cathepsin C expression contributes to endothelial chymase activation in preeclampsia.

PubMed

Gu, Yang; Lewis, David F; Alexander, J Steven; Wang, Yuping

2017-12-01

Chymase is an ACE (angiotensin-converting enzyme)-independent angiotensin II-forming enzyme whose expression is increased in the maternal vascular endothelium in preeclampsia. However, mechanisms underlying chymase activation in preeclampsia remain unclear. Cathepsin C is a key enzyme in the activation of several serine proteases including chymase. In this study, we determined whether increased cathepsin C expression/activity might be responsible for the upregulation of chymase expression in preeclampsia. Maternal vascular cathepsin C, chymase and ACE expression were examined through immunohistochemical staining of subcutaneous fat tissue sections of normal and preeclamptic pregnant women. The role of cathepsin C in endothelial chymase and ACE expression was determined in cells treated with cathepsin C. Consequences of chymase activation were then determined by measurement of angiotensin II production in cells treated with the ACE inhibitor captopril and the chymase inhibitor chymostatin, separately and in combination. Expression of both cathepsin C and chymase, but not ACE expression, was markedly increased in the maternal vascular endothelium in subjects with preeclampsia compared with normal pregnant controls. Exogenous cathepsin C induced a dose-dependent increase in expression of mature cathepsin C and chymase, but not ACE, in endothelial cells. Moreover, angiotensin II production was significantly inhibited in cells treated with captopril or chymostatin alone and was further inhibited in cells treated with both inhibitors. These results suggest that cathepsin C upregulation induces chymase activation and subsequently promotes angiotensin II generation in endothelial cells. These data also provide evidence of upregulation of the cathepsin C-chymase-angiotensin signaling axis in maternal vasculature in preeclampsia.

Combined Screening for Early Detection of Pre-Eclampsia

PubMed Central

Park, Hee Jin; Shim, Sung Shin; Cha, Dong Hyun

2015-01-01

Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers. PMID:26247944

Evaluation of glycosaminoglycans and heparanase in placentas of women with preeclampsia.

PubMed

Famá, Eduardo Augusto Brosco; Souza, Renan Salvioni; Melo, Carina Mucciolo; Melo Pompei, Luciano; Pinhal, Maria Aparecida Silva

2014-11-01

Preeclampsia is a multisystem disorder whose etiology remains unclear. It is already known that circulation of soluble fms-like tyrosine kinase-1 (sFlt-1) is directly involved in pre-eclampsia development. However, the molecular mechanisms involved with sFlt-1 shedding are still unidentified. We identified, quantified glycosaminoglycans and determined the enzymatic activity of heparanase in placentas of women with preeclampsia, in order to possibly explain if these compounds could be related to cellular processes involved with preeclampsia. A total of 45 samples collected from placentas, 15 samples from placentas of preeclampsia women and 30 samples from non-affected women. Heparan sulfate and dermatan sulfate were identified and quantified by agarose gel electrophoresis, whilst hyaluronic acid was quantified by an ELISA like assay. Heparanase activity was determined using biotynilated heparan sulfate as substrate. The results showed that dermatan sulfate (P=0.019), heparan sulfate levels (P=0.015) and heparanase activity (P=0.006) in preeclampsia were significantly higher than in the control group. There was no significant difference between the groups for hyaluronic acid expression in placentas (P=0.110). The present study is the first to demonstrate directly the increase of heparan sulfate in human placentas from patients with preeclampsia, suggesting that endogenous heparan sulfate could be involved in the release of sFlt-1 from placenta, increasing the level of circulating sFlt-1. Alterations of extracellular matrix components in placentas with preeclampsia raise the possibility that heparan sulfate released by heparanase is involved in mechanisms of preeclampsia development. Published by Elsevier B.V.

Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes.

PubMed

Nomura, Yoko; John, Rosalind M; Janssen, Anna Bugge; Davey, Charles; Finik, Jackie; Buthmann, Jessica; Glover, Vivette; Lambertini, Luca

2017-06-01

Preeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3-8% of all pregnancies in the US are complicated by preeclampsia and another 5-7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring. Pub Med and Web of Science databases were searched using the terms "preeclampsia," "gestational hypertension," "imprinting genes," "imprinting dysregulation," and "epigenetic modification," in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism. The high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development. Furthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants.

A Common Profile of Disordered Angiogenic Factor Production and the Exacerbation of Inflammation in Early Preeclampsia, Late Preeclampsia, and Intrauterine Growth Restriction.

PubMed

Kwiatkowski, Sebastian; Dołęgowska, Barbara; Kwiatkowska, Ewa; Rzepka, Rafał; Torbè, Andrzej; Bednarek-Jędrzejek, Magdalena

2016-01-01

Preeclampsia and intrauterine growth restriction are two separate disease entities that, according to numerous reports, share the same pathogenesis. In both, angiogenesis disorders and generalized inflammation are the dominant symptoms. In this study, we hypothesized that both diseases demonstrate the same profile in early preeclampsia, late preeclampsia, and intrauterine growth restriction patients, with the only difference being the degree of exacerbation of lesions. One hundred sixty-seven patients were enrolled in the study and divided into four groups: early preeclampsia, late preeclampsia, and intrauterine growth restriction groups, and one control group. Concentrations of the angiogenesis and inflammatory markers soluble fms-like tyrosine kinase receptor 1, placental growth factor, high-sensitivity C-reactive protein, and interleukin-6 were determined, and the behavior of these markers and correlations among them were studied. Higher concentrations of soluble fms-like tyrosine kinase receptor 1, high-sensitivity C-reactive protein, and interleukin-6 and a lower concentration of placental growth factor were observed in the study groups compared with the control group. No differences in concentrations of the studied markers were found among the study groups but significant correlations were observed. The higher values for the angiogenesis and inflammatory markers both in preeclampsia patients and patients with intrauterine growth restriction of placental origin compared with the control group suggest the existence of the same underlying disorders in the development of these pathologies. The observed mutual correlations for disordered angiogenesis and inflammatory markers are suggestive of a mutual relationship between these processes in the development of pathologies evolving secondary to placental ischemia. The same lesion profile was observed for both preeclampsia and 'placental' intrauterine growth restriction patients, which could be used in developing common diagnostic criteria for pregnant patients.

Biomarker identification and pathway analysis of preeclampsia based on serum metabolomics.

PubMed

Chen, Tingting; He, Ping; Tan, Yong; Xu, Dongying

2017-03-25

Preeclampsia presents serious risk of both maternal and fetal morbidity and mortality. Biomarkers for the detection of preeclampsia are critical for risk assessment and targeted intervention. The goal of this study is to screen potential biomarkers for the diagnosis of preeclampsia and to illuminate the pathogenesis of preeclampsia development based on the differential expression network. Two groups of subjects, including healthy pregnant women, subjects with preeclampsia, were recruited for this study. The metabolic profiles of all of the subjects' serum were obtained by liquid chromatography quadruple time-of-flight mass spectrometry. Correlation between metabolites was analyzed by bioinformatics technique. Results showed that the PC(14:0/00), proline betaine and proline were potential sensitive and specific biomarkers for preeclampsia diagnosis and prognosis. Perturbation of corresponding biological pathways, such as iNOS signaling, nitric oxide signaling in the cardiovascular system, mitochondrial dysfunction were responsible for the pathogenesis of preeclampsia. This study indicated that the metabolic profiling had a good clinical significance in the diagnosis of preeclampsia as well as in the study of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Vitamin D and the risk of preeclampsia--a nested case-control study.

PubMed

Gidlöf, Sebastian; Silva, Aldo T; Gustafsson, Sven; Lindqvist, Pelle G

2015-08-01

We aimed to determine the relation between vitamin D deficiency in early pregnancy and preeclampsia. In a nested case-control study of 2496 pregnant women, we identified 39 women who developed preeclampsia and 120 non-preeclamptic controls. Blood was sampled in 12th gestational week and analyzed for serum vitamin D. Vitamin D levels were similar in women who developed preeclampsia, 52.2 ± 20.5 nmol/L, and controls, 48.6 ± 20.5 nmol/L, p = 0.3. In addition, vitamin D deficiency (<50 nmol/L) was found in a similar proportion of control group (51.7%) as those with severe preeclampsia (41.2%). Women with vitamin D deficiency were 3 cm shorter than those with normal vitamin D levels (p = 0.002). Our data do not support the hypothesis that vitamin D deficiency in early pregnancy is associated with preeclampsia, but we cannot rule out a relation later in gestation. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin.

PubMed

Balani, Jyoti; Hyer, Steve; Syngelaki, Argyro; Akolekar, Ranjit; Nicolaides, Kypros H; Johnson, Antoinette; Shehata, Hassan

2017-12-01

To examine whether the reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is mediated by changes in insulin resistance. This was a secondary analysis of obese pregnant women in a randomised trial (MOP trial). Fasting plasma glucose and insulin were measured in 384 of the 400 women who participated in the MOP trial. Homeostasis model assessment of insulin resistance (HOMA-IR) was compared in the metformin and placebo groups and in those that developed preeclampsia versus those that did not develop preeclampsia. At 28 weeks, median HOMA-IR was significantly lower in the metformin group. Logistic regression analysis demonstrated that there was a significant contribution in the prediction of preeclampsia from maternal history of chronic hypertension and gestational weight gain, but not HOMA-IR either at randomisation ( p  = 0.514) or at 28 weeks ( p  = 0.643). Reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is unlikely to be due to changes in insulin resistance.

First Trimester Maternal Serum PP13 in the Risk Assessment for Preeclampsia

PubMed Central

ROMERO, Roberto; KUSANOVIC, Juan Pedro; THAN, Nandor Gabor; EREZ, Offer; GOTSCH, Francesca; ESPINOZA, Jimmy; EDWIN, Samuel; CHEFETZ, Ilana; GOMEZ, Ricardo; NIEN, Jyh Kae; SAMMAR, Marei; PINELES, Beth; HASSAN, Sonia S.; MEIRI, Hamutal; TAL, Yossi; KUHNREICH, Ido; PAPP, Zoltan; CUCKLE, Howard S.

2008-01-01

Objective To determine whether first trimester maternal serum Placental Protein 13 (PP13) concentrations can be used in the risk assessment for preeclampsia. Study Design This case-control study included 50 patients with preeclampsia and 250 patients with normal pregnancies. Samples were collected between 8-13 weeks of gestation. Serum PP13 concentrations were measured by ELISA and expressed as medians and multiples of the median (MoM) for gestational age. Sensitivity and specificity were derived from receiver operating characteristic curve analysis. Results 1) Serum PP13 concentration in the first trimester was significantly lower in patients who developed preterm and early-onset preeclampsia than in those with normal pregnancies; and 2) At 80% specificity, a cutoff of 0.39 MoM had a sensitivity of 100% for early-onset preeclampsia and 85% for preterm preeclampsia. Conclusion Maternal serum first trimester PP13 appears to be a reasonable marker for risk assessment, but a weak marker for severe preeclampsia at term, and ineffective for identifying mild preeclampsia at term. PMID:18539259

Correlations between serum assays of human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) and pre-eclampsia or intrauterine growth restriction (IUGR) among nulliparas younger than 38 years.

PubMed

Merviel, P; Müller, F; Guibourdenche, J; Berkane, N; Gaudet, R; Bréart, G; Uzan, S

2001-03-01

To study the relation between serum human chorionic gonadotrophin (hCG) levels measured at 15-18 weeks and gestational disorders, assess their correlation with the artery uteroplacental Doppler (AUD) at 24 weeks among nulliparas, and assess the predictivity of the hCG/hPL (human placental lactogen) ratio for pre-eclampsia. Retrospective study of two groups of women younger than 38 years old: one with an elevated serum hCG level (2 MoM (multiples of the median) or more) and a normal fetal karyotype (group A), and the other with a lower hCG level (group B). Within each group, we studied the nulliparas separately (respectively groups AO and BO). We analyzed the double screening, elevated hCG levels with abnormal AUD, for the predicting of hypertensive disorders. Elevated hCG levels were significantly (p<0.05) more prevalent among women who developed gestational diabetes (groups A and AO) and among nulliparas with pregnancy-induced hypertension and pre-eclampsia (AO). Among nulliparas, the combination of the hCG assay and a subsequent Doppler increased the positive predictive value (PPV) of the assay from 19 to 75%, without reducing its negative predictive value (NPV) for gestational vascular disorders. The hCG/hPL ratio did not improve the predictivity of the hCG assay alone for pre-eclampsia. An hCG level of 2 MoM or more at 15-18 weeks identifies a group of women at risk of gestational vascular disorders; it therefore ought to lead to an AUD at 24 weeks. This double screening should be able to define a population of women at risk of developing a hypertensive disorder, who could thus benefit from a preventive treatment, as aspirin.

Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes

PubMed Central

Yu, Y; Hanssen, KF; Kalyanaraman, V; Chirindel, A; Jenkins, AJ; Nankervis, AJ; Torjesen, PA; Scholz, H; Henriksen, T; Lorentzen, B; Garg, SK; Menard, MK; Hammad, SM; Scardo, JA; Stanley, JR; Wu, M; Basu, A; Aston, CE; Lyons, TJ

2014-01-01

Objective Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. Design Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. Setting Antenatal clinics. Population Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). Methods Maternal serum levels of sRAGE (total circulating pool), Nε-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. Main outcome measures Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE–). Results In DM PE+ versus DM PE–, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE : hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE : AGE and sRAGE : CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. Conclusions In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM. PMID:22900949

Risk of future cardiovascular disease in women with prior preeclampsia: a focus group study.

PubMed

Seely, Ellen W; Rich-Edwards, Janet; Lui, Janet; Nicklas, Jacinda M; Saxena, Aditi; Tsigas, Eleni; Levkoff, Sue E

2013-12-21

A history of preeclampsia is a risk factor for the future development of hypertension and cardiovascular disease (CVD). The objective of this study was to assess, in women with prior preeclampsia, the level of knowledge regarding the link between preeclampsia and CVD, motivators for and barriers to lifestyle change and interest in a lifestyle modification program to decrease CVD risk following a pregnancy complicated by preeclampsia. Twenty women with a history of preeclampsia participated in 5 phone-based focus groups. Focus groups were recorded, transcribed, and analyzed. Qualitative content analysis was used to identify common themes across focus groups. Consensus was reached on a representative set of themes describing the data. Women with prior preeclampsia were in general unaware of the link between preeclampsia and future CVD but eager to learn about this link and motivated to achieve a healthy lifestyle. Major perceived barriers to lifestyle change were lack of time, cost of healthy foods and family responsibilities. Perceived facilitators included knowledge of the link between preeclampsia and CVD, a desire to stay healthy, and creating a healthy home for their children. Women with prior preeclampsia were interested in the idea of a web-based program focused on lifestyle strategies to decrease CVD risk in women. Women with prior preeclampsia were eager to learn about the link between preeclampsia and CVD and to take steps to reduce CVD risk. A web-based program to help women with prior preeclampsia adopt a healthy lifestyle may be an appropriate strategy for this population.

Pregnant women with the sickle cell trait are not at increased risk for developing preeclampsia.

PubMed

Stamilio, David M; Sehdev, Harish M; Macones, George A

2003-01-01

The primary objective of this study was to determine whether having the sickle cell trait is independently associated with preeclampsia. We performed a retrospective cohort study of 1998 pregnant patients who either did or did not have the sickle cell trait. All patients were screened for the sickle trait using the "Sickledex" test. Data on neonatal and maternal outcome, including preeclampsia, and potential confounding variables were abstracted from medical records. Unadjusted, stratified, and multiple logistic regression analyses were used to identify interactions, and confounding between multiple variables and the association between sickle cell trait and preeclampsia. With an anticipated 6.5% rate of preeclampsia, and alpha = 0.05, this cohort study has 80% power to detect a relative risk (RR) of 2.3 for preeclampsia. Univariate analysis revealed that the two cohorts were similar with regard to primiparity, maternal age, chronic diseases, birth weight, and gestational age at delivery, but the sickle cell trait cohort was more likely to have gestational diabetes and had a higher mean body mass index (BMI). In the univariate analysis, the sickle cell trait cohort was not at increased risk for preeclampsia [unadjusted RR = 0.5, 95% CI (0.2-1.6)]. After controlling for potential confounding variables with logistic regression analysis, sickle trait was not independently associated with preeclampsia [adjusted RR = 0.5, 95% CI (0.2- 1.6)]. In contrast to prior work, these data suggest that the sickle cell trait is not an independent risk factor for preeclampsia or postpartum complications. In fact, the data are more consistent with the sickle trait being protective for developing preeclampsia.

Pre-eclampsia part 2: prediction, prevention and management

PubMed Central

Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Korzeniewski, Steven J.; Yeo, Lami; Romero, Roberto

2018-01-01

An antiangiogenic state might constitute a terminal pathway for the multiple aetiologies of pre-eclampsia, especially those resulting from placental abnormalities. The levels of angiogenic and antiangiogenic proteins in maternal blood change prior to a diagnosis of pre-eclampsia, correlate with disease severity and have prognostic value in identifying women who will develop maternal and/or perinatal complications. Potential interventions exist to ameliorate the imbalance of angiogenesis and, hence, might provide opportunities to improve maternal and/or perinatal outcomes in pre-eclampsia. Current strategies for managing pre-eclampsia consist of controlling hypertension, preventing seizures and timely delivery of the fetus. Prediction of pre-eclampsia in the first trimester is of great interest, as early administration of aspirin might reduce the risk of pre-eclampsia, albeit modestly. Combinations of biomarkers typically predict pre-eclampsia better than single biomarkers; however, the encouraging initial results of biomarker studies require external validation in other populations before they can be used to facilitate intervention in patients identified as at increased risk. Angiogenic and antiangiogenic factors might also be useful in triage of symptomatic patients with suspected pre-eclampsia, differentiating pre-eclampsia from exacerbations of pre-existing medical conditions and performing risk assessment in asymptomatic women. This Review article discusses the performance of predictive and prognostic biomarkers for pre-eclampsia, current strategies for preventing and managing the condition and its long-term consequences. PMID:25003612

Blood-based cerebral biomarkers in preeclampsia: Plasma concentrations of NfL, tau, S100B and NSE during pregnancy in women who later develop preeclampsia - A nested case control study.

PubMed

Bergman, Lina; Zetterberg, Henrik; Kaihola, Helena; Hagberg, Henrik; Blennow, Kaj; Åkerud, Helena

2018-01-01

To evaluate if concentrations of the neuronal proteins neurofilament light chain and tau are changed in women developing preeclampsia and to evaluate the ability of a combination of neurofilament light chain, tau, S100B and neuron specific enolase in identifying neurologic impairment before diagnosis of preeclampsia. A nested case-control study within a longitudinal study cohort was performed. 469 healthy pregnant women were enrolled between 2004-2007 and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Plasma concentrations of tau and neurofilament light chain were analyzed in 16 women who eventually developed preeclampsia and 36 controls throughout pregnancy with single molecule array (Simoa) method and compared within and between groups. S100B and NSE had been analyzed previously in the same study population. A statistical model with receiving characteristic operation curve was constructed with the four biomarkers combined. Plasma concentrations of neurofilament light chain were significantly increased in women who developed preeclampsia in gestational week 33 (11.85 ng/L, IQR 7.48-39.93 vs 6.80 ng/L, IQR 5.65-11.40) and 37 (22.15 ng/L, IQR 10.93-35.30 vs 8.40 ng/L, IQR 6.40-14.30) and for tau in gestational week 37 (4.33 ng/L, IQR 3.97-12.83 vs 3.77 ng/L, IQR 1.91-5.25) in contrast to healthy controls. A combined model for preeclampsia with tau, neurofilament light chain, S100B and neuron specific enolase in gestational week 25 displayed an area under the curve of 0.77, in week 28 it was 0.75, in week 33 it was 0.89 and in week 37 it was 0.83. Median week for diagnosis of preeclampsia was at 38 weeks of gestation. Concentrations of both tau and neurofilament light chain are increased in the end of pregnancy in women developing preeclampsia in contrast to healthy pregnancies. Cerebral biomarkers might reflect cerebral involvement before onset of disease.

First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study.

PubMed

Austdal, Marie; Tangerås, Line H; Skråstad, Ragnhild B; Salvesen, Kjell; Austgulen, Rigmor; Iversen, Ann-Charlotte; Bathen, Tone F

2015-09-08

Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension). Preeclampsia developed in 26 (4.3%) and gestational hypertension in 21 (3.5%) women. Multivariate analyses of the metabolic profiles were performed to establish prediction models for the hypertensive disorders individually and combined. Urinary metabolomic profiles predicted preeclampsia and gestational hypertension at 51.3% and 40% sensitivity, respectively, at 10% false positive rate, with hippurate as the most important metabolite for the prediction. Serum metabolomic profiles predicted preeclampsia and gestational hypertension at 15% and 33% sensitivity, respectively, with increased lipid levels and an atherogenic lipid profile as most important for the prediction. Combining maternal characteristics with the urinary hippurate/creatinine level improved the prediction rates of preeclampsia in a logistic regression model. The study indicates a potential future role of clinical importance for metabolomic analysis of urine in prediction of preeclampsia.

An RGS2 3'UTR polymorphism is associated with preeclampsia in overweight women.

PubMed

Karppanen, Tiina; Kaartokallio, Tea; Klemetti, Miira M; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Staff, Anne Cathrine; Laivuori, Hannele

2016-08-24

Preeclampsia is a common and heterogeneous vascular syndrome of pregnancy. Its genetic risk profile is yet unknown and may vary between individuals and populations. The rs4606 3' UTR polymorphism of the Regulator of G-protein signaling 2 gene (RGS2) in the mother has been implicated in preeclampsia as well as in the development of chronic hypertension after preeclampsia. The RGS2 protein acts as an inhibitor of physiological vasoconstrictive pathways, and a low RGS2 level is associated with hypertension and obesity, two conditions that predispose to preeclampsia. We genotyped the rs4606 polymorphism in 1339 preeclamptic patients and in 697 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort to study the association of the variant with preeclampsia. No association between rs4606 and preeclampsia was detected in the analysis including all women. However, the polymorphism was associated with preeclampsia in a subgroup of overweight women (body mass index ≥ 25 kg/m(2), and < 30 kg/m(2)) (dominant model; odds ratio, 1.64; 95 % confidence interval, 1.10-2.42). Our results suggest that RGS2 might be involved in the pathogenesis of preeclampsia particularly in overweight women and contribute to their increased risk for hypertension and other types of cardiovascular disease later in life.

A prospective cohort study on the clinical utility of second trimester mean arterial blood pressure in the prediction of late-onset preeclampsia among Nigerian women.

PubMed

Udenze, I C; Arikawe, A P; Makwe, C C; Olowoselu, O F

2017-06-01

Early detection of preeclampsia will help reduce the morbidities and mortalities associated with the disorder. Late-onset preeclampsia was the predominant presentation in this cohort. The search for biomarkers for predicting preeclampsia is still ongoing. Mean arterial blood pressure (MABP), which has the advantage of presenting a single cutoff value compared with the use of systolic and diastolic blood pressure measurements, merits evaluation. The study aims to evaluate the clinical utility of second trimester MABP in the prediction of preeclampsia. This was a prospective cohort study of 155 normotensive, nonproteinuric pregnant women without prior history of gestational hypertension. The women were booked patients attending the antenatal clinic at the Lagos University Teaching Hospital and were all in their second trimesters of pregnancy. The outcome measures were systolic blood pressure, diastolic blood pressure, and MABP. The end point of the study was the development of preeclampsia. The diagnosis of preeclampsia was made by the attending obstetrician. The data were analyzed using the IBM SPSS statistical software. Statistical significance was set at P < 0.05. One hundred and fifty-five pregnant women participated in the study. Eleven (7.1%) of the women developed preeclampsia after 34 weeks gestation and 144 (92.9%) had normal pregnancy. The mean gestational age at the time of assessment was 18.88 ± 3.15 weeks with a range of 14 weeks to 27 completed weeks. There was a statistically significant increase in the systolic blood pressure, diastolic blood pressure, and MABP values in the group of women who later developed preeclampsia, P = 0.005, 0.001, and <0.001, respectively. At a false-positive rate of 10%, MABP value of 88.33 mmHg predicted preeclampsia with a specificity of 90% and a sensitivity of 45.5%, P <0.05. The area under the receiver-operative characteristics curve (AUC) was 0.732 (95% confidence interval, 0.544-0.919, P = 0.011). The negative predictive value (NPV) was 88.88% and the positive predictive value (PPV) was 45.45%, P < 0.05. At an MABP cutoff of 88.33 mmHg, preeclampsia was predicted with a relative risk of 4.44 and a positive likelihood ratio of 6.46, P < 0.05. With an AUC of 0.732, MABP performed moderately (considering that excellent performance has an AUC of 1.0) in the prediction of late-onset preeclampsia in Nigerian women. Its high NPV suggests a strong ability to rule out preeclampsia and help to appropriate management.

Low-Dose Aspirin for the Prevention of Preeclampsia.

PubMed

Fantasia, Heidi Collins

2018-02-01

Preeclampsia is a hypertensive disorder specific to pregnancy that remains a significant cause of maternal and neonatal morbidity and mortality. Identification of women who are most at risk for preeclampsia is imprecise. Because of the potential negative health consequences of preeclampsia for women and newborns and the lack of effective screening mechanisms preventing preeclampsia is an important component of prenatal care. Researchers have documented that low-dose aspirin, taken daily after the first trimester, can decrease the development of preeclampsia and reduce the incidence of preterm birth and birth of small-for-gestational-age infants. This column includes an overview of low-dose aspirin in pregnancy and a review of current recommendations from leading national organizations. © 2018 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

VEGF-A and VEGFR1 SNPs associate with preeclampsia in a Philippine population.

PubMed

Amosco, Melissa D; Villar, Van Anthony M; Naniong, Justin Michael A; David-Bustamante, Lara Marie G; Jose, Pedro A; Palmes-Saloma, Cynthia P

The vascular endothelial growth factor (VEGF) family is important for establishing normal pregnancy, and related single nucleotide polymorphisms (SNPs) are implicated in abnormal placentation and preeclampsia. We evaluated the association between preeclampsia and several VEGF SNPs among Filipinos, an ethnically distinct group with high prevalence of preeclampsia. The genotypes and allelic variants were determined in a case-control study (191 controls and 165 preeclampsia patients) through SNP analysis of VEGF-A (rs2010963, rs3025039) and VEGF-C (rs7664413) and their corresponding receptors VEGFR1 (rs722503, rs12584067, rs7335588) and VEGFR3 (rs307826) from venous blood DNA. VEGF-A rs3025039 C allele has been shown to associate with preeclampsia (odds ratio of 1.648 (1.03-2.62)), while the T allele bestowed an additive effect for the maintenance of normal, uncomplicated pregnancy and against the development of preeclampsia (odds ratio of 0.62 (0.39-0.98)). VEGFR1 rs722503 is associated with preeclampsia occurring at or after the age of 40 years. The results showed that genetic variability of VEGF-A and VEGFR1 are important in the etiology of preeclampsia among Filipinos.

Perinatal epidemiological risk factors for preeclampsia.

PubMed

Bobić, Mirna Vuković; Habek, Dubravko; Habek, Jasna Čerkez

2015-03-01

In the present study, the impact of the potential perinatal epidemiological factors on preeclampsia development was assessed. This clinical study included 55 pregnant women with preeclampsia and control group of 50 healthy pregnant women. Positive family history of cardiovascular disease, diabetes mellitus or thromboembolic disease was recorded in 50% of women with preeclampsia versus 28% of control group women. Positive personal history of this disease was recorded in 15% of women with preeclampsia, whereas all control group women had negative personal history of preeclampsia. Dietary habits, i.e. the intake of meat and meat products, fruit and vegetables, coffee and alcohol drinks were similar in the two groups, without statistically significant differences. The women with preeclampsia and control women reported comparable habits; there was no difference in the consumption of meat, fruit, vegetables, coffee and alcohol, smoking, use of folate and oral hormonal contraception before pregnancy, or in physical activity as the potential risk factors for preeclampsia in current pregnancy. However, personal and family history of vascular disease proved to be significant risk factors for the occurrence of preeclampsia, emphasizing the need of lifestyle and dietary modifications with healthy dietary habits, while avoiding adverse habits in pregnancy.

First-trimester screening for early and late preeclampsia using maternal characteristics, biomarkers, and estimated placental volume.

PubMed

Sonek, Jiri; Krantz, David; Carmichael, Jon; Downing, Cathy; Jessup, Karen; Haidar, Ziad; Ho, Shannon; Hallahan, Terrence; Kliman, Harvey J; McKenna, David

2018-01-01

Preeclampsia is a major cause of perinatal morbidity and mortality. First-trimester screening has been shown to be effective in selecting patients at an increased risk for preeclampsia in some studies. We sought to evaluate the feasibility of screening for preeclampsia in the first trimester based on maternal characteristics, medical history, biomarkers, and placental volume. This is a prospective observational nonintervention cohort study in an unselected US population. Patients who presented for an ultrasound examination between 11-13+6 weeks' gestation were included. The following parameters were assessed and were used to calculate the risk of preeclampsia: maternal characteristics (demographic, anthropometric, and medical history), maternal biomarkers (mean arterial pressure, uterine artery pulsatility index, placental growth factor, pregnancy-associated plasma protein A, and maternal serum alpha-fetoprotein), and estimated placental volume. After delivery, medical records were searched for the diagnosis of preeclampsia. Detection rates for early-onset preeclampsia (<34 weeks' gestation) and later-onset preeclampsia (≥34 weeks' gestation) for 5% and 10% false-positive rates using various combinations of markers were calculated. We screened 1288 patients of whom 1068 (82.99%) were available for analysis. In all, 46 (4.3%) developed preeclampsia, with 13 (1.22%) having early-onset preeclampsia and 33 (3.09%) having late-onset preeclampsia. Using maternal characteristics, serum biomarkers, and uterine artery pulsatility index, the detection rate of early-onset preeclampsia for either 5% or 10% false-positive rate was 85%. With the same protocol, the detection rates for preeclampsia with delivery <37 weeks were 52% and 60% for 5% and 10% false-positive rates, respectively. Based on maternal characteristics, the detection rates for late-onset preeclampsia were 15% and 48% for 5% and 10%, while for preeclampsia at ≥37 weeks' gestation the detection rates were 24% and 43%, respectively. The detection rates for late-onset preeclampsia and preeclampsia with delivery at >37 weeks' gestation were not improved by the addition of biomarkers. Screening for preeclampsia at 11-13+6 weeks' gestation using maternal characteristics and biomarkers is associated with a high detection rate for a low false-positive rate. Screening for late-onset preeclampsia yields a much poorer performance. In this study the utility of estimated placental volume and mean arterial pressure was limited but larger studies are needed to ultimately determine the effectiveness of these markers. Copyright © 2017 Elsevier Inc. All rights reserved.

[Pre-eclampsia prevention in 2018 in general population and in lupic women: At the dawn of a personalized medicine?

PubMed

de Moreuil, C; Fauchais, A-L; Merviel, P; Tremouilhac, C; Le Moigne, E; Pasquier, E; Pan-Petesch, B; Lacut, K

2018-06-19

Pre-eclampsia prevention represents a major public health issue, as this vasculo-placental disorder generates a great burden of foeto-maternal morbi-mortality. Aspirin has proved its efficacy in primary and secondary pre-eclampsia prevention, especially when it is given at 150mg per day bedtime before 15 weeks of gestation to high-risk women. In the English trial ASPRE, high-risk women were identified by an algorithm taking into account angiogenic biomarkers ascertained at the end of first trimester of pregnancy. This article focuses on physiopathological mechanisms and risk factors of pre-eclampsia and on the interest of early angiogenic biomarkers dosing during pregnancy, for the assessment of pre-eclampsia risk. Unlike Great Britain or Israel, cost-effectiveness of this algorithm in general population has not been assessed in France. Finally, systemic lupus erythematous is at high risk of vasculo-placental disorders. Although few studies of angiogenic biomarkers dosing during lupus pregnancies identified a correlation between high sFlt1 levels at the end of first trimester and subsequent onset of severe vasculo-placental disorders, with a very good negative predictive value of sFtl1. Angiogenic biomarkers ascertainment for screening of vasculo-placental disorders in pregnant women with systemic lupus erythematous could allow targeting at best women needing an aspirin treatment and a closer monitoring. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

Impact of Preeclampsia on Clinical and Functional Outcomes in Women With Peripartum Cardiomyopathy.

PubMed

Lindley, Kathryn J; Conner, Shayna N; Cahill, Alison G; Novak, Eric; Mann, Douglas L

2017-06-01

Preeclampsia is a risk factor for the development of peripartum cardiomyopathy (PPCM), but it is unknown whether preeclampsia impacts clinical or left ventricular (LV) functional outcomes. This study sought to assess clinical and functional outcomes in women with PPCM complicated by preeclampsia. This retrospective cohort study included women diagnosed with PPCM delivering at Barnes-Jewish Hospital between 2004 to 2014. The primary outcome was one-year event-free survival rate for the combined end point of death and hospital readmission. The secondary outcome was recovery of LV ejection fraction. Seventeen of 39 women (44%) with PPCM had preeclampsia. The groups had similar mean LV ejection fraction at diagnosis (29.6 with versus 27.3 without preeclampsia; P =0.5). Women with preeclampsia had smaller mean LV end-diastolic diameters (5.2 versus 6.0 cm; P =0.001), greater relative wall thickness (0.41 versus 0.35 mm Hg; P =0.009), and lower incidence of eccentric remodeling (12% versus 48%; P =0.03). Clinical follow-up was available for 32 women; 5 died of cardiovascular complications within 1 year of diagnosis (4/15 with versus 1/17 without preeclampsia; P =0.16). In time to event analysis, patients with preeclampsia had worse event-free survival during 1-year follow-up ( P =0.047). Echocardiographic follow-up was available in 10 survivors with and 16 without preeclampsia. LV ejection fraction recovered in 80% of survivors with versus 25% without preeclampsia ( P =0.014). PPCM with concomitant preeclampsia is associated with increased morbidity and mortality and different patterns of LV remodeling and recovery of LV function when compared with patients with PPCM that is not complicated by preeclampsia. © 2017 American Heart Association, Inc.

Indicators of Moderate and Severe Preeclampsia in Correlation with Maternal IL10

PubMed Central

Markova, Ana Daneva; Hadži-Lega, Marija; Mijakoski, Dragan

2016-01-01

AIM: The purpose of the actual study was to evaluate the relationship between the formation of anti-inflammatory cytokine IL10 and several indicators of moderate and severe preeclampsia in the third trimester of pregnancy. MATERIAL AND METHODS: Examination of the indicators of preeclampsia and maternal IL10 levels was conducted in 50 women with pregnancies complicated by varying degrees of preeclampsia in the third trimester of gestation as well as in 50 normotensive patients, hospitalized at the University Clinic of Gynecology and Obstetrics, Skopje, Republic of Macedonia. The levels of IL10 were determined with a commercial test developed by Orgenium Laboratories (Finland), using reagents from AviBion ELISA research kits. Patients with preeclampsia were categorized into moderate and severe preeclampsia group according to the degree of preeclampsia. Logistic regression analysis was used to determine the predictive value of different parameters for the occurrence of severe preeclampsia. Odds ratios and 95% Confidence Intervals were calculated in order to quantify independent associations. RESULTS: The regression analysis detected systolic blood pressure (160 mmHg or higher), diastolic blood pressure (100 mmHg or higher), persistent proteinuria in pregnancy, serum LDH concentration (450 U/L or higher) and reduced serum concentrations of IL10 as significant predictors of severe preeclampsia in pregnant women after adjusting for age. CONCLUSION: The findings of significantly lower serum IL10 concentrations in patients with severe preeclampsia in comparison with respective concentrations in patients with moderate preeclampsia can be considered as major pathognomonic laboratory sign of severe preeclampsia. PMID:27335593

Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia.

PubMed

Huang, Aji; Wu, Hongyu; Iriyama, Takayuki; Zhang, Yujin; Sun, Kaiqi; Song, Anren; Liu, Hong; Peng, Zhangzhe; Tang, Lili; Lee, Minjung; Huang, Yun; Ni, Xin; Kellems, Rodney E; Xia, Yang

2017-07-01

Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA hypomethylation. Immunohistochemical studies revealed that elevated placental adenosine-mediated DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine trophoblasts and that this effect is independent of A2B adenosine receptor activation in both preeclampsia models. Extending our mouse findings to humans, we used cultured human trophoblasts to demonstrate that adenosine functions intracellularly and induces DNA hypomethylation without A2B adenosine receptor activation. Altogether, both mouse and human studies reveal novel mechanisms underlying placental DNA hypomethylation and potential therapeutic approaches for preeclampsia. © 2017 American Heart Association, Inc.

Early pregnancy waist-to-hip ratio and risk of preeclampsia: a prospective cohort study.

PubMed

Taebi, Mahboubeh; Sadat, Zohreh; Saberi, Farzaneh; Kalahroudi, Masoumeh Abedzadeh

2015-01-01

Preeclampsia is a major cause of maternal death and morbidity. Body mass index (BMI) predicts an increased risk of developing hypertensive disorders and preeclampsia. However, waist-to-hip ratio (WHR), as a central obesity index, has not been assessed in predicting this disorder in pregnancy. We assumed that WHR might be more sensitive in predicting the risk of preeclampsia, compared with BMI. The aim of this cohort study was to investigate the relationships of BMI and WHR with preeclampsia. This was a prospective cohort study of 1200 pregnant women with singleton pregnancies. Anthropometric indices included WHR and BMI, which were measured at the first antenatal visit (⩽ 12 weeks of gestational age). The incidence of preeclampsia was assessed after 20 weeks of gestation. Maternal demographic data and obstetric outcomes were also recorded for each subject. All of the statistical tests were performed using SPSS software, version 16. The overall incidence of preeclampsia in the study population was 4.2%. The maternal WHR and BMI at the beginning of pregnancy were significantly associated with the occurrence of preeclampsia (P = 0.006 and P = 0.001, respectively). WHR ⩾ 0.85 and BMI ⩾ 25 kg m(-2) in the first 12 weeks of pregnancy had relative risks of 2.317 (confidence interval (CI): 1.26-4.27) and 3.317 (CI: 1.6-6.86) for preeclampsia. BMI and WHR were anthropometric indicators that presented correlations with preeclampsia. Of these anthropometric indices, BMI had greater predictive value in preeclampsia.

Preeclampsia and Long-term Renal Function in Women Who Underwent Kidney Transplantation.

PubMed

Vannevel, Valerie; Claes, Kathleen; Baud, David; Vial, Yvan; Golshayan, Delaviz; Yoon, Eugene W; Hodges, Ryan; Le Nepveu, Anne; Kerr, Peter G; Kennedy, Claire; Higgins, Mary; Resch, Elisabeth; Klaritsch, Philipp; Van Mieghem, Tim

2018-01-01

Preeclampsia often complicates pregnancies after maternal kidney transplantation. We aimed to assess whether preeclampsia is associated with kidney function decline either during the pregnancy or in the long term. We performed an international multicenter retrospective cohort study. Renal function at conception, pregnancy outcomes, and short- and long-term graft outcomes were collected for women who were pregnant after renal transplantation and had transplant and obstetric care at the participating centers. In women who had multiple pregnancies during the study period, only the last pregnancy was included. Univariate and multivariable analyses were performed. We retrieved pregnancy outcomes and long-term renal outcomes for 52 women. Chronic hypertension was present at baseline in 27%. Mean estimated glomerular filtration rate (GFR) at start of pregnancy was 52.4±17.5 mL/min/1.73 m. Mean estimated GFR at delivery was 47.6±21.6 mL/min/1.73 m, which was significantly lower than at conception (P=.03). Twenty women (38%) developed preeclampsia. In multivariable analysis, women who developed preeclampsia had a 10.7-mL/min/1.73 m higher drop in estimated GFR between conception and delivery than women who did not develop preeclampsia (P=.02). Long-term estimated GFR follow-up was obtained at a median of 5.8 years (range 1.3-27.5 years). Mean estimated GFR at last follow-up was 38±23 mL/kg/1.73 m. Seventeen women (33%) experienced graft loss over the follow-up period. Incidence of graft loss was similar in women with and without preeclampsia in their last pregnancy (30% and 34%, respectively; P=.99). In multivariable analysis, the decrease in estimated GFR between conception and last follow-up was similar in women who experienced preeclampsia during pregnancy and those who did not (difference -2.69 mL/min/1.73 m, P=.65). Preeclampsia commonly complicates pregnancies after renal transplantation but is not associated with long-term renal dysfunction or graft loss.

D2-Thr92Ala, thyroid hormone levels and biochemical hypothyroidism in preeclampsia.

PubMed

Procopciuc, Lucia Maria; Caracostea, Gabriela; Hazi, Georgeta; Nemeti, Georgiana; Stamatian, Florin

2017-02-01

To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia. We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA. Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia. The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism - as a result of deiodination effects due to D2 genotypes.

The Role of Interleukin-10 in the Pathophysiology of Preeclampsia.

PubMed

Cubro, Hajrunisa; Kashyap, Sonu; Nath, Meryl C; Ackerman, Allan W; Garovic, Vesna D

2018-04-30

The pathophysiology of preeclampsia is complex and not entirely understood. A key feature in preeclampsia development is an immunological imbalance that shifts the maternal immune response from one of tolerance towards one promoting chronic inflammation and endothelial dysfunction. As a key regulator of immunity, IL-10 not only has immunomodulatory activity, but also directly benefits vasculature and promotes successful cellular interactions at the maternal-fetal interface. Here we focus on the mechanisms by which the dysregulation of IL-10 may contribute to the pathophysiology of preeclampsia. Dysregulation of IL-10 has been demonstrated in various animal models of preeclampsia. Decreased IL-10 production in both placenta and peripheral blood mononuclear cells has been reported in human studies, but with inconsistent results. The significance of IL-10 in preeclampsia has shifted from a key biomarker to one with therapeutic potential. As such, a better understanding of the role of this cytokine in the pathophysiology of preeclampsia is of paramount importance.

Low expression of soluble human leukocyte antigen G in early gestation and subsequent placenta-mediated complications of pregnancy.

PubMed

Marozio, Luca; Garofalo, Anna; Berchialla, Paola; Tavella, Anna Maria; Salton, Loredana; Cavallo, Franco; Benedetto, Chiara

2017-09-01

Abnormal placentation is a common pathogenic mechanism of many placenta-mediated complications of late pregnancy, including pre-eclampsia, fetal growth restriction, stillbirth, and placental abruption. During successful placentation, the trophoblast (which is a semi-allograft) is not rejected by decidual immune cells because of maternal immune tolerance, mainly induced by human leukocyte antigen G (HLA-G). Deficient HLA-G expression seems to be associated with the development of complications of pregnancy. The aim of this study was to determine whether low soluble HLA-G (sHLA-G) levels in maternal blood at the beginning of pregnancy may be associated with subsequent placenta-mediated complications. For this retrospective case-control study, 117 cases of placenta-mediated complications of pregnancy and 234 controls with uneventful pregnancy were selected. Plasma sHLA-G levels were measured at 11-13 weeks' gestation by the enzyme-linked immunosorbent assay method in blood samples previously obtained at first-trimester prenatal screening for chromosomal fetal abnormalities. Women who subsequently developed placenta-mediated complications had significantly lower sHLA-G levels at the beginning of pregnancy (median, 43.08 IU/mL) than controls (median, 49.10 IU/mL; P = 0.008). An sHLA-G level lower than 43.50 IU/mL at the end of the first trimester was associated with a twofold increased risk of developing a pregnancy complication (odds ratio, 1.82; 95% confidence interval, 1.22-2.73). The strongest association, although only moderately strong, was observed with severe pre-eclampsia (odds ratio, 2.66; 95% confidence interval, 1.08-6.56). Placenta-mediated complications of pregnancy may be associated with low sHLA-G levels in the first trimester, suggesting a potential role of sHLA-G in the early stages of placentation. © 2017 Japan Society of Obstetrics and Gynecology.

Atypical preeclampsia – Gestational proteinuria

PubMed Central

Stevens, Amy B.; Brasuell, Diane M.; Higdon, Rebecca N.

2017-01-01

There are many rural areas where obstetric care is predominately performed by family medicine physicians. As such, it is important for family medicine physicians to stay up to date with the latest obstetric guidelines. Preeclampsia is a well-established disorder and the guidelines for screening and treatment are well known. However, atypical presentations of preeclampsia have been less studied. Notably, what constitutes atypical preeclampsia and when to be concerned for increased morbidity and mortality in the mother and neonate. This report describes a unique case in which a woman with proteinuria of pregnancy developed atypical preeclampsia with severe features. This report discusses the care that was given by a practicing family medicine physician and the reasoning behind it. PMID:29417031

Clinical risk factors for preeclampsia in the 21st century.

PubMed

Paré, Emmanuelle; Parry, Samuel; McElrath, Thomas F; Pucci, Dominick; Newton, Amy; Lim, Kee-Hak

2014-10-01

We sought to validate several clinical risk factors previously described for preeclampsia in a large contemporary multicenter prospective cohort. We enrolled women from three sites before 15 weeks of gestation. Demographic and clinical risk factors were collected through standardized chart review. The main outcome of preeclampsia was diagnosed using the American College of Obstetricians and Gynecologists definitions from 2002. Multivariable logistic regression was used to control for confounders. Two thousand six hundred thirty-seven women are included in this analysis; 237 (9.0%) developed preeclampsia. In adjusted analysis, chronic hypertension (adjusted odds ratio [OR] 2.72; 95% confidence interval 1.78-4.13), pregestational diabetes (adjusted OR 3.88; 2.08-7.26), multiple gestation (adjusted OR 2.96; 1.74-5.03), African American race (adjusted OR 1.91; 1.35-2.71), prior preeclampsia (adjusted OR 3.63; 2.29-5.73), nulliparity (adjusted OR 1.73; 1.26-2.38), assisted reproductive techniques (adjusted OR: 1.72; 1.10-2.68), and being overweight (adjusted OR for body mass index [BMI, kg/m] greater than 25-30: 1.65; 1.13-2.41) or obese (adjusted OR for BMI greater than 30-35: 2.34, 1.51-3.61; adjusted OR for BMI greater than 35-40: 3.59, 2.13-6.03; adjusted OR for BMI greater than 40: 6.04, 3.56-10.24) were associated with preeclampsia, but advanced maternal age was not. Similar associations were found for severe preeclampsia. A dose-response effect was observed in the relationship between BMI and both preeclampsia and severe preeclampsia. Being overweight or obese was the most important risk factor for both preeclampsia and severe preeclampsia with an attributable risk percent of 64.9% and 64.4%, respectively. In this contemporary cohort, increasingly prevalent and potentially modifiable factors were confirmed as significant risk factors for preeclampsia and severe preeclampsia, the most important being overweight or obese. This information is important to guide public health efforts in preeclampsia prevention. : II.

Baseline placental growth factor levels for the prediction of benefit from early aspirin prophylaxis for preeclampsia prevention.

PubMed

Moore, Gaea S; Allshouse, Amanda A; Winn, Virginia D; Galan, Henry L; Heyborne, Kent D

2015-10-01

Placental growth factor (PlGF) levels early in pregnancy are lower in women who ultimately develop preeclampsia. Early initiation of low-dose aspirin reduces preeclampsia risk in some high risk women. We hypothesized that low PlGF levels may identify women at increased risk for preeclampsia who would benefit from aspirin. Secondary analysis of the MFMU High-Risk Aspirin study including singleton pregnancies randomized to aspirin 60mg/d (n=102) or placebo (n=72), with PlGF collected at 13w 0d-16w 6d. Within the placebo group, we estimated the probability of preeclampsia by PlGF level using logistic regression analysis, then determined a potential PlGF threshold for preeclampsia prediction using ROC analysis. We performed logistic regression modeling for potential confounders. ROC analysis indicated 87.71pg/ml as the threshold between high and low PlGF for preeclampsia-prediction. Within the placebo group high PlGF weakly predicted preeclampsia (AUC 0.653, sensitivity/specificity 63%/66%). We noted a 2.6-fold reduction in preeclampsia with aspirin in the high-PlGF group (12.15% aspirin vs 32.14% placebo, p=0.057), but no significant differences in preeclampsia in the low PlGF group (21.74% vs 15.91%, p=0.445). Unlike other studies, we found that high rather than low PlGF levels were associated with an increased preeclampsia risk. Low PlGF neither identified women at increased risk of preeclampsia nor women who benefitted from aspirin. Further research is needed to determine whether aspirin is beneficial in women with high PlGF, and whether the paradigm linking low PlGF and preeclampsia needs to be reevaluated. High-risk women with low baseline PlGF, a risk factor for preeclampsia, did not benefit from early initiation of low-dose aspirin. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Altered Global Gene Expression in First Trimester Placentas of Women Destined to Develop Preeclampsia

PubMed Central

Founds, Sandra A.; Conley, Yvette P.; Lyons-Weiler, James F.; Jeyabalan, Arun; Hogge, W. Allen; Conrad, Kirk P.

2009-01-01

Background Preeclampsia is a pregnancy-specific disorder that remains a leading cause of maternal, fetal and neonatal morbidity and mortality, and is associated with risk for future cardiovascular disease. There are no reliable predictors, specific preventative measures or treatments other than delivery. A widely-held view is that the antecedents of preeclampsia lie with impaired placentation in early pregnancy. Accordingly, we hypothesized dysregulation of global gene expression in first trimester placentas of women who later manifested preeclampsia. Methods Surplus chorionic villus sampling (CVS) tissues were collected at 10–12 weeks gestation in 160 patients with singleton fetuses. Four patients developed preeclampsia, and their banked CVS specimens were matched to 8 control samples from patients with unaffected pregnancies. Affymetrix HG-U133 Plus 2.0 GeneChips were utilized for microarray analysis. Naïve Bayes prediction modeling and pathway analysis were conducted. qRT-PCR examined three of the dysregulated genes. Results Thirty-six differentially expressed genes were identified in the preeclampsia placentas. qRT-PCR verified the microarray analysis. Thirty-one genes were down-regulated. Many were related to inflammation/immunoregulation and cell motility. Decidual gene dysregulation was prominent. No evidence was found for alterations in hypoxia and oxidative stress regulated genes. Conclusions To our knowledge, this is the first study to show dysregulation of gene expression in the early placentas of women ~6 months before developing preeclampsia, thereby reinforcing a placental origin of the disorder. We hypothesize that placentation in preeclampsia is compromised in the first trimester by maternal and fetal immune dysregulation, abnormal decidualization, or both, thereby impairing trophoblast invasion. Several of the genes provide potential targets for the development of clinical biomarkers in maternal blood during the first trimester. Supplementary materials are available for this article via the publisher’s online edition. PMID:19027158

Intake of Probiotic Food and Risk of Preeclampsia in Primiparous Women

PubMed Central

Brantsæter, Anne Lise; Myhre, Ronny; Haugen, Margaretha; Myking, Solveig; Sengpiel, Verena; Magnus, Per; Jacobsson, Bo; Meltzer, Helle Margrete

2011-01-01

Probiotics have been suggested to modify placental trophoblast inflammation, systemic inflammation, and blood pressure, all potentially interesting aspects of preeclampsia. The authors examined the association between consumption of milk-based probiotic products in pregnancy and development of preeclampsia and its subtypes. The study was performed in the Norwegian Mother and Child Cohort Study by using a prospective design in 33,399 primiparous women in the years 2002–2008. The intake of milk-based products containing probiotic lactobacilli was estimated from a self-reported food frequency questionnaire. Preeclampsia diagnoses were obtained from the Norwegian Medical Birth Registry. Intake of probiotic milk products was associated with reduced risk of preeclampsia. The association was most prominent in severe preeclampsia (adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI): 0.66, 0.96). With probiotic intakes divided into categories representing no, monthly, weekly, or daily intake, a lower risk for preeclampsia (all subtypes) was observed for daily probiotic intake (OR = 0.80, 95% CI: 0.66, 0.96). Lower risks for severe preeclampsia were observed for weekly (OR = 0.75, 95% CI: 0.57, 0.98) and daily (OR = 0.61, 95% CI: 0.43, 0.89) intakes. These results suggest that regular consumption of milk-based probiotics could be associated with lower risk of preeclampsia in primiparous women. PMID:21821542

Possible Common Aetiology behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in Norway Project Study.

PubMed

Brodwall, Kristoffer; Leirgul, Elisabeth; Greve, Gottfried; Vollset, Stein Emil; Holmstrøm, Henrik; Tell, Grethe S; Øyen, Nina

2016-01-01

The aetiology of congenital heart defects (CHD) is mostly unknown, but maternal factors may modify the infant risk of CHD. We investigated the association between maternal preeclampsia and offspring risk of severe CHD in a nation-wide cohort study. Information on all births registered in the Medical Birth Registry of Norway, 1994-2009, was completed with information on CHD diagnoses from national health registries and the Cardiovascular Diseases in Norway Project (CVDNOR). Among 914 703 singleton births without chromosomal abnormalities, 32 864 (3.6%) were born after a pregnancy with preeclampsia. The preeclampsia was diagnosed before the 34th week of pregnancy (early-onset preeclampsia) in 2618 (8.0% of preeclamptic pregnancies). CHDs were diagnosed in 10 691 infants; of these, 2473 had severe CHD. The risk of severe CHD was compared between births with and without maternal preeclampsia and estimated with binomial log-linear regression. When adjusting for year of birth, maternal age, parity, and pregestational diabetes, the risk ratio (RR) for severe CHD in offspring of mothers with any preeclampsia was 1.3 [95% confidence interval (CI) 1.1, 1.5], and in pregnancies with early-onset preeclampsia, the RR was 2.8 (95% CI 1.8, 4.4). The association between early-onset preeclampsia and specific types of severe CHD was stronger for atrioventricular septal defects (AVSD), with adjusted RR 13.5 (95% CI 6.8, 26.8). Early-onset preeclampsia was strongly associated with infant risk of severe CHD, specifically; the risk of AVSD was 15-fold higher if the mother was diagnosed with early-onset preeclampsia, suggesting common aetiological factors for early-onset preeclampsia and erroneous fetal heart development. © 2015 John Wiley & Sons Ltd.

Embryo cryopreservation and preeclampsia risk.

PubMed

Sites, Cynthia K; Wilson, Donna; Barsky, Maya; Bernson, Dana; Bernstein, Ira M; Boulet, Sheree; Zhang, Yujia

2017-11-01

To determine whether assisted reproductive technology (ART) cycles involving cryopreserved-warmed embryos are associated with the development of preeclampsia. Retrospective cohort study. IVF clinics and hospitals. A total of 15,937 births from ART: 9,417 singleton and 6,520 twin. We used linked ART surveillance, birth certificate, and maternal hospitalization discharge data, considering resident singleton and twin births from autologous or donor eggs from 2005-2010. We compared the frequency of preeclampsia diagnosis for cryopreserved-warmed versus fresh ET and used multivariable logistic regression to adjust for confounders. Among pregnancies conceived with autologous eggs resulting in singletons, preeclampsia was greater after cryopreserved-warmed versus fresh ET (7.51% vs. 4.29%, adjusted odds ratio = 2.17 [95% CI 1.67-2.82]). Preeclampsia without and with severe features, preeclampsia with preterm delivery, and chronic hypertension with superimposed preeclampsia were more frequent after cryopreserved-warmed versus fresh ET (3.99% vs. 2.55%; 2.95% vs. 1.41%; 2.76 vs. 1.48%; and 0.95% vs. 0.43%, respectively). Among pregnancies from autologous eggs resulting in twins, the frequency of preeclampsia with severe features (9.26% vs. 5.70%) and preeclampsia with preterm delivery (14.81% vs. 11.74%) was higher after cryopreserved versus fresh transfers. Among donor egg pregnancies, rates of preeclampsia did not differ significantly between cryopreserved-warmed and fresh ET (10.78% vs. 12.13% for singletons and 28.0% vs. 25.15% for twins). Among ART pregnancies conceived using autologous eggs resulting in live births, those involving transfer of cryopreserved-warmed embryos, as compared with fresh ETs, had increased risk for preeclampsia with severe features and preeclampsia with preterm delivery. Copyright © 2017 American Society for Reproductive Medicine. All rights reserved.

Relationship of Liver X Receptors α and Endoglin Levels in Serum and Placenta with Preeclampsia.

PubMed

Wang, Jing; Dong, Xing; Wu, Hong-Yan; Wu, Nan; Zhang, Xue-Jun; Wang, Xin; Shang, Li-Xin

2016-01-01

Liver X receptor alpha (LXRα) and endoglin have been postulated to play roles in trophoblast invasion and lipid metabolic disturbances. However, the relationship between LXRα and endoglin levels in serum and placenta of patients with preeclampsia remains poorly understood. The objective of this study was to identify correlations between LXRα, endoglin and preeclampsia and provide new feasible methods of clinical prediction and treatment for preeclampsia. We enrolled 45 patients with preeclampsia (24 with moderate preeclampsia and 21 with severe preeclampsia) and 15 normal pregnant women (control group) who were admitted to the Department of Obstetrics of the General Hospital of Beijing Command between October 2012 and July 2013 in this study. Serum and placental LXRα and endoglin levels were analyzed by enzyme-linked immunosorbent assay, real-time quantitative PCR, tissue microarray and immunohistochemistry. Serum and placental LXRα and endoglin levels were significantly higher in patients with preeclampsia than those in control group (P<0.05, each). Moreover, patients with severe preeclampsia displayed significantly higher LXRα and endoglin levels than those with moderate preeclampsia (P<0.05, each). The LXRα sensitivity, specificity and positive and negative predictive values were 66.00%, 80.00%, 89.19% and 48.48%, respectively, while those of endoglin levels were 62.00%, 85.00%, 91.18% and 47.22%, respectively. LXRα and endoglin levels in serum and placenta from patients with preeclampsia were positively correlated (serum: r = 0.486, P<0.01; placenta: r = 0.569, P<0.01). Elevated LXRα and endoglin levels may be associated with preeclampsia pathogenesis and development and could be used as potential predictors for this disorder.

Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction in women with a history: a randomized trial.

PubMed

Groom, Katie M; McCowan, Lesley M; Mackay, Laura K; Lee, Arier C; Said, Joanne M; Kane, Stefan C; Walker, Susan P; van Mens, Thijs E; Hannan, Natalie J; Tong, Stephen; Chamley, Larry W; Stone, Peter R; McLintock, Claire

2017-03-01

Preeclampsia and small-for-gestational-age pregnancy are major causes of maternal and perinatal morbidity and mortality. Women with a previous pregnancy affected by these conditions are at an increased risk of recurrence in a future pregnancy. Past trials evaluating the effect of low-molecular-weight heparin for the prevention of recurrence of preeclampsia and small-for-gestational-age pregnancy have shown conflicting results with high levels of heterogeneity displayed when trials were compared. We sought to assess the effectiveness of enoxaparin in addition to high-risk care for the prevention of preeclampsia and small-for-gestational-age pregnancy in women with a history of these conditions. This was an open-label randomized controlled trial in 5 tertiary care centers in 3 countries. Women with a viable singleton pregnancy were invited to participate between >6 +0 and <16 +0 weeks if deemed to be at high risk of preeclampsia and/or small for gestational age based on their obstetric history. Eligible participants were randomly assigned in a 1-to-1 ratio to standard high-risk care or standard high-risk care plus enoxaparin 40 mg (4000 IU) by subcutaneous injection daily from recruitment until 36 +0 weeks or delivery, whichever occurred sooner. Standard high-risk care was defined as care coordinated by a high-risk antenatal clinic service, aspirin 100 mg daily until 36 +0 weeks, and-for women with prior preeclampsia-calcium 1000-1500 mg daily until 36 +0 weeks. In a subgroup of participants serum samples were taken at recruitment and at 20 and 30 weeks' gestation and later analyzed for soluble fms-like tyrosine kinase-1, soluble endoglin, endothelin-1, placental growth factor, and soluble vascular cell adhesion molecule 1. The primary outcome was a composite of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile. All data were analyzed on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12609000699268). Between July 26, 2010, and Oct. 28, 2015, a total of 156 participants were enrolled and included in the analysis. In all, 149 participants were included in the outcome analysis (72 receiving standard high-risk care plus enoxaparin and 77 receiving standard high-risk care only). Seven women who miscarried <16 weeks' gestation were excluded. The majority of participants (151/156, 97%) received aspirin. The addition of enoxaparin had no effect on the rate of preeclampsia and/or small-for-gestational-age <5th customized birthweight percentile: enoxaparin 18/72 (25%) vs no enoxaparin 17/77 (22.1%) (odds ratio, 1.19; 95% confidence interval, 0.53-2.64). There was also no difference in any of the secondary outcome measures. Levels of soluble fms-like tyrosine kinase-1 and soluble endoglin increased among those who developed preeclampsia, but there was no difference in levels of these antiangiogenic factors (nor any of the other serum analytes measured) among those treated with enoxaparin compared to those receiving standard high-risk care only. The use of enoxaparin in addition to standard high-risk care does not reduce the risk of recurrence of preeclampsia and small-for-gestational-age infants in a subsequent pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

Cluster analysis to estimate the risk of preeclampsia in the high-risk Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study.

PubMed

Villa, Pia M; Marttinen, Pekka; Gillberg, Jussi; Lokki, A Inkeri; Majander, Kerttu; Ordén, Maija-Riitta; Taipale, Pekka; Pesonen, Anukatriina; Räikkönen, Katri; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele

2017-01-01

Preeclampsia is divided into early-onset (delivery before 34 weeks of gestation) and late-onset (delivery at or after 34 weeks) subtypes, which may rise from different etiopathogenic backgrounds. Early-onset disease is associated with placental dysfunction. Late-onset disease develops predominantly due to metabolic disturbances, obesity, diabetes, lipid dysfunction, and inflammation, which affect endothelial function. Our aim was to use cluster analysis to investigate clinical factors predicting the onset and severity of preeclampsia in a cohort of women with known clinical risk factors. We recruited 903 pregnant women with risk factors for preeclampsia at gestational weeks 12+0-13+6. Each individual outcome diagnosis was independently verified from medical records. We applied a Bayesian clustering algorithm to classify the study participants to clusters based on their particular risk factor combination. For each cluster, we computed the risk ratio of each disease outcome, relative to the risk in the general population. The risk of preeclampsia increased exponentially with respect to the number of risk factors. Our analysis revealed 25 number of clusters. Preeclampsia in a previous pregnancy (n = 138) increased the risk of preeclampsia 8.1 fold (95% confidence interval (CI) 5.7-11.2) compared to a general population of pregnant women. Having a small for gestational age infant (n = 57) in a previous pregnancy increased the risk of early-onset preeclampsia 17.5 fold (95%CI 2.1-60.5). Cluster of those two risk factors together (n = 21) increased the risk of severe preeclampsia to 23.8-fold (95%CI 5.1-60.6), intermediate onset (delivery between 34+0-36+6 weeks of gestation) to 25.1-fold (95%CI 3.1-79.9) and preterm preeclampsia (delivery before 37+0 weeks of gestation) to 16.4-fold (95%CI 2.0-52.4). Body mass index over 30 kg/m2 (n = 228) as a sole risk factor increased the risk of preeclampsia to 2.1-fold (95%CI 1.1-3.6). Together with preeclampsia in an earlier pregnancy the risk increased to 11.4 (95%CI 4.5-20.9). Chronic hypertension (n = 60) increased the risk of preeclampsia 5.3-fold (95%CI 2.4-9.8), of severe preeclampsia 22.2-fold (95%CI 9.9-41.0), and risk of early-onset preeclampsia 16.7-fold (95%CI 2.0-57.6). If a woman had chronic hypertension combined with obesity, gestational diabetes and earlier preeclampsia, the risk of term preeclampsia increased 4.8-fold (95%CI 0.1-21.7). Women with type 1 diabetes mellitus had a high risk of all subgroups of preeclampsia. The risk of preeclampsia increases exponentially with respect to the number of risk factors. Early-onset preeclampsia and severe preeclampsia have different risk profile from term preeclampsia.

Superimposed Preeclampsia.

PubMed

Guedes-Martins, Luís

2017-01-01

Superimposed preeclampsia refers to women with chronic arterial hypertension (primary or secondary) who develop preeclampsia (PE). Because hypertension affects 5-15 % of pregnancies, it is itself a matter of concern. However, this concern should be permanent, given the increased risk of the hypertension worsening and, particularly, the appearance of superimposed PE. The search for factors that underlie or promote the development of this disorder has been the subject of intense research. However, despite the wealth of knowledge, the cause or causes remain to be determined.

The Efficiency of First-Trimester Uterine Artery Doppler, ADAM12, PAPP-A and Maternal Characteristics in the Prediction of Pre-Eclampsia

PubMed Central

GOETZINGER, Katherine R.; ZHONG, Yan; CAHILL, Alison G.; ODIBO, Linda; MACONES, George A.; ODIBO, Anthony O.

2014-01-01

Objective To estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A) and maternal characteristics in the prediction of pre-eclampsia. Methods This is a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11-14 weeks’ gestation. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices (PI) were calculated. Outcomes of interest included pre-eclampsia, early pre-eclampsia, defined as requiring delivery at <34 weeks’ gestation, and gestational hypertension. Logistic regression analysis was used to model the prediction of pre-eclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler PI MoM, either individually or in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves (AUC) were used to compare the screening efficiency of the models using non-parametric U-statistics. Results Of 578 patients with complete outcome data, there were 54 (9.3%) cases of preeclampsia and 13 (2.2%) cases of early pre-eclampsia. Median ADAM12 levels were significantly lower in patients who developed pre-eclampsia compared to those who did not. (0.81 v. 1.01 MoMs; p<0.04) For a fixed false positive rate (FPR) of 10%, ADAM12, PAPP-A, and uterine artery Doppler in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed pre-eclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. Conclusion First-trimester ADAM12, PAPP-A, and uterine artery Doppler are not sufficiently predictive of pre-eclampsia. Combinations of these parameters do not further improve their screening efficiency. PMID:23980220

Identifying mild and severe preeclampsia in asymptomatic pregnant women by levels of cell-free fetal DNA.

PubMed

Jakobsen, Tanja Roien; Clausen, Frederik Banch; Rode, Line; Dziegiel, Morten Hanefeld; Tabor, Ann

2013-09-01

The objective was to investigate whether women who develop preeclampsia can be identified in a routine analysis when determining fetal RHD status at 25 weeks' gestation in combination with PAPP-A levels at the first-trimester combined risk assessment for Trisomy 21. D- women participating in the routine antenatal RHD screening program in the capital region of Denmark were retrospectively studied. We used a standard dilution curve to quantify the amounts of cell-free fetal DNA (cffDNA) and divided women into groups according to cffDNA levels. PAPP-A was measured at 11 to 14 weeks. Information about pregnancy outcome and complications was obtained from the National Fetal Medicine Database, medical charts, and discharge letters. The odds ratio (OR) of developing severe preeclampsia given a cffDNA level above the 90th percentile compared to cffDNA below the 90th percentile was 8.1 (95% confidence interval [CI], 2.6-25.5). The OR of developing mild preeclampsia given a cffDNA level below the 5th percentile compared to cffDNA levels above the 5th percentile was 3.6 (95% CI, 1.1-11.7). PAPP-A levels below the 5th percentile were associated with mild preeclampsia, but adding it to the analysis did not increase the detection rate (DR). Women with cffDNA levels below the 5th percentile and above the 90th percentile quantified at 25 weeks' gestation are at increased risk of developing preeclampsia. Adding PAPP-A levels to the analysis did not increase the DR of preeclampsia. © 2013 American Association of Blood Banks.

Maternal bradycardia occurring prior to onset of HELLP syndrome in a woman with pre-eclampsia.

PubMed

Hosokawa, Ami; Umazume, Takeshi; Yamada, Takahiro; Minakami, Hisanori

2017-05-13

A 36-year-old nulliparous woman developed pre-eclampsia at gestational week (GW) 28 -6/7 Cardiac status was checked regularly. Heart rate of 93 beats per minute (bpm) with left atrial diameter (LAD) of 35 mm, left ventricular hypertrophy and inferior vena cava diameter (IVCD) of 8 mm at GW 32 -0/7 decreased to 48 bpm with an expanded IVCD to 25 mm, dilated left atrium (LAD to 39 mm), increased pulmonary arterial pressure, increased systemic vascular resistance (approximate 3000  dyn s/cm 5 ) and biphasic intrarenal venous flow pattern 3.5 hours prior to childbirth at GW 32 -3/7 Epigastralgia, tachycardia (160 bpm) and marked hypertension (201/111 mm Hg) occurring 2 hours after echocardiography necessitated caesarean section, with subsequent development of HELLP syndrome. Acute fluid shift from the splanchnic vasculature to central vasculature may have occurred causing HELLP syndrome as a result from vasospasm associated with sympathetic hyperactivity. The cause of bradycardia prior to tachycardia remains unclear. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Microvascular remodelling in preeclampsia: quantifying capillary rarefaction accurately and independently predicts preeclampsia.

PubMed

Antonios, Tarek F T; Nama, Vivek; Wang, Duolao; Manyonda, Isaac T

2013-09-01

Preeclampsia is a major cause of maternal and neonatal mortality and morbidity. The incidence of preeclampsia seems to be rising because of increased prevalence of predisposing disorders, such as essential hypertension, diabetes, and obesity, and there is increasing evidence to suggest widespread microcirculatory abnormalities before the onset of preeclampsia. We hypothesized that quantifying capillary rarefaction could be helpful in the clinical prediction of preeclampsia. We measured skin capillary density according to a well-validated protocol at 5 consecutive predetermined visits in 322 consecutive white women, of whom 16 subjects developed preeclampsia. We found that structural capillary rarefaction at 20-24 weeks of gestation yielded a sensitivity of 0.87 with a specificity of 0.50 at the cutoff of 2 capillaries/field with the area under the curve of the receiver operating characteristic value of 0.70, whereas capillary rarefaction at 27-32 weeks of gestation yielded a sensitivity of 0.75 and a higher specificity of 0.77 at the cutoff of 8 capillaries/field with area under the curve of the receiver operating characteristic value of 0.82. Combining capillary rarefaction with uterine artery Doppler pulsatility index increased the sensitivity and specificity of the prediction. Multivariable analysis shows that the odds of preeclampsia are increased in women with previous history of preeclampsia or chronic hypertension and in those with increased uterine artery Doppler pulsatility index, but the most powerful and independent predictor of preeclampsia was capillary rarefaction at 27-32 weeks. Quantifying structural rarefaction of skin capillaries in pregnancy is a potentially useful clinical marker for the prediction of preeclampsia.

Impaired Flow-Mediated Dilation Before, During and After Preeclampsia: A Systematic Review and Meta-analysis

PubMed Central

Weissgerber, Tracey L.; Milic, Natasa M.; Milin-Lazovic, Jelena S.; Garovic, Vesna D.

2015-01-01

Endothelial dysfunction is believed to play a critical role in preeclampsia, however it is unclear whether this dysfunction precedes the pregnancy or is caused by early pathophysiological events. It is also unclear for how long vascular dysfunction may persist post-partum, and whether it represents a mechanism linking preeclampsia with future cardiovascular disease. Our objective was to determine whether women with preeclampsia have worse vascular function compared to women who did not have preeclampsia by performing systematic review and meta-analysis of studies that examined endothelial dysfunction using flow-mediated dilation (FMD). We included studies published before May 29, 2015 that examined FMD before, during and after preeclampsia. Differences in FMD between study groups were evaluated by standardized mean differences. Out of 610 abstracts identified through PubMED, EMBASE and Web of Science, 37 studies were eligible for the meta-analysis. When compared to women who did not have preeclampsia, women who had preeclampsia had lower FMD prior to the development of preeclampsia (~20–29 weeks gestation), at the time of preeclampsia, and for three years post-partum, with the estimated magnitude of the effect ranging between 0.5 and 3 standard deviations. Similar effects were observed when the analysis was limited to studies that excluded women with chronic hypertension, smokers, or both. Vascular dysfunction predates preeclampsia and may contribute to its pathogenesis. Future studies should address whether vascular changes that persist after preeclamptic pregnancies may represent a mechanistic link with the increased risk for future cardiovascular disease. PMID:26711737

Potential Value of Coagulation Parameters for Suggesting Preeclampsia During the Third Trimester of Pregnancy.

PubMed

Chen, Ying; Lin, Li

2017-07-01

Preeclampsia is a relatively common complication of pregnancy and considered to be associated with different degrees of coagulation dysfunction. This study was developed to evaluate the potential value of coagulation parameters for suggesting preeclampsia during the third trimester of pregnancy. Data from 188 healthy pregnant women, 125 patients with preeclampsia in the third trimester and 120 age-matched nonpregnant women were analyzed. Prothrombin time, prothrombin activity, activated partial thromboplastin time, fibrinogen (Fg), antithrombin, platelet count, mean platelet volume, platelet distribution width and plateletcrit were tested. All parameters, excluding prothrombin time, platelet distribution width and plateletcrit, differed significantly between healthy pregnant women and those with preeclampsia. Platelet count, antithrombin and Fg were significantly lower and mean platelet volume and prothrombin activity were significantly higher in patients with preeclampsia (P < 0.001). Among these parameters, the largest area under the receiver operating characteristic curve for preeclampsia was 0.872 for Fg with an optimal cutoff value of ≤2.87g/L (sensitivity = 0.68 and specificity = 0.98). For severe preeclampsia, the area under the curve for Fg reached up to 0.922 with the same optimal cutoff value (sensitivity = 0.84, specificity = 0.98, positive predictive value = 0.96 and negative predictive value = 0.93). Fg is a biomarker suggestive of preeclampsia in the third trimester of pregnancy, and our data provide a potential cutoff value of Fg ≤ 2.87g/L for screening preeclampsia, especially severe preeclampsia. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Decreased maternal plasma apelin concentrations in preeclampsia.

PubMed

Bortoff, Katherine D; Qiu, Chunfang; Runyon, Scott; Williams, Michelle A; Maitra, Rangan

2012-01-01

Preeclampsia is a hypertensive disorder that complicates 3-7% of pregnancies. The development of preeclampsia has not been completely elucidated and current therapies are not broadly efficacious. The apelinergic system appears to be involved in hypertensive disorders and experimental studies indicate a role of this system in preeclampsia. Thus, an epidemiological evaluation of apelin protein concentration in plasma was conducted in case-control study of pregnant women. Data and maternal plasma samples were collected from pregnant women with confirmed preeclampsia (n = 76) or normotensive controls (n = 79). Concentrations of apelin peptides were blindly measured using enzyme-linked immunosorbent assay. Data were subjected to statistical analyses. Plasma apelin concentrations, measured at delivery, were lower in preeclampsia cases compared with controls (mean ± standard deviation: 0.66 ± 0.29 vs. 0.78 ± 0.31 ng/mL, p = 0.02). After controlling for confounding by maternal age, smoking status, and pre-pregnancy body mass index, odds of preeclampsia were 48% lower for women with high versus low plasma apelin (≥0.73 vs. <0.73 ng/mL) concentrations. Reduced circulating apelin peptides may be associated with preeclampsia. The apelinergic system should be further investigated to elucidate its role in preclampsia and other hypertensive maternal disorders.

Vasopressin: the missing link for preeclampsia?

PubMed

Sandgren, Jeremy A; Scroggins, Sabrina M; Santillan, Donna A; Devor, Eric J; Gibson-Corley, Katherine N; Pierce, Gary L; Sigmund, Curt D; Santillan, Mark K; Grobe, Justin L

2015-11-01

Preeclampsia is a devastating cardiovascular disorder of late pregnancy, affecting 5-7% of all pregnancies and claiming the lives of 76,000 mothers and 500,000 children each year. Various lines of evidence support a "tissue rejection" type reaction toward the placenta as the primary initiating event in the development of preeclampsia, followed by a complex interplay among immune, vascular, renal, and angiogenic mechanisms that have been implicated in the pathogenesis of preeclampsia beginning around the end of the first trimester. Critically, it remains unclear what mechanism links the initiating event and these pathogenic mechanisms. We and others have now demonstrated an early and sustained increase in maternal plasma concentrations of copeptin, a protein by-product of arginine vasopressin (AVP) synthesis and release, during preeclampsia. Furthermore, chronic infusion of AVP during pregnancy is sufficient to phenocopy essentially all maternal and fetal symptoms of preeclampsia in mice. As various groups have demonstrated interactions between AVP and immune, renal, and vascular systems in the nonpregnant state, elevations of this hormone are therefore positioned both in time (early pregnancy) and function to contribute to preeclampsia. We therefore posit that AVP represents a missing mechanistic link between initiating events and established midpregnancy dysfunctions that cause preeclampsia. Copyright © 2015 the American Physiological Society.

DECREASED LEVEL OF CORD BLOOD CIRCULATING ENDOTHELIAL COLONY-FORMING CELLS IN PREECLAMPSIA

PubMed Central

Muñoz-Hernandez, Rocio; Miranda, Maria L.; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M.; Dominguez-Simeon, Maria J.; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M.

2014-01-01

Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation and migration towards VEGF-A and FGF-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P = .04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events. PMID:24752434

PP087. Multicenter external validation and recalibration of a model for preconceptional prediction of recurrent early-onset preeclampsia.

PubMed

van Kuijk, Sander; Delahaije, Denise; Dirksen, Carmen; Scheepers, Hubertina C J; Spaanderman, Marc; Ganzevoort, W; Duvekot, Hans; Oudijk, M A; van Pampus, M G; Dadelszen, Peter von; Peeters, Louis L; Smiths, Luc

2013-04-01

In an earlier paper we reported on the development of a model aimed at the prediction of preeclampsia recurrence, based on variables obtained before the next pregnancy (fasting glucose, BMI, previous birth of a small-for-gestational-age infant, duration of the previous pregnancy, and the presence of hypertension). To externally validate and recalibrate the prediction model for the risk of recurrence of early-onset preeclampsia. We collected data about course and outcome of the next ongoing pregnancy in 229 women with a history of early-onset preeclampsia. Recurrence was defined as preeclampsia requiring delivery before 34 weeks. We computed risk of recurrence and assessed model performance. In addition, we constructed a table comparing sensitivity, specificity, and predictive values for different suggested risk-thresholds. Early-onset preeclampsia recurred in 6.6% of women. The model systematically underestimated recurrence risk. The model's discriminative ability was modest, the area under the receiver operating characteristic curve was 58.9% (95% CI: 45.1 - 72.7). Using relevant risk-thresholds, the model created groups that were only moderately different in terms of their average risk of recurrent preeclampsia (Table 1). Compared to an AUC of 65% in the development cohort, the discriminate ability of the model was diminished. It had inadequate performance to classify women into clinically relevant risk groups. Copyright © 2013. Published by Elsevier B.V.

The role of genetics in pre-eclampsia and potential pharmacogenomic interventions

PubMed Central

Williams, Paula Juliet; Morgan, Linda

2012-01-01

The pregnancy-specific condition pre-eclampsia not only affects the health of mother and baby during pregnancy but also has long-term consequences, increasing the chances of cardiovascular disease in later life. It is accepted that pre-eclampsia has a placental origin, but the pathogenic mechanisms leading to the systemic endothelial dysfunction characteristic of the disorder remain to be determined. In this review we discuss some key factors regarded as important in the development of pre-eclampsia, including immune maladaptation, inadequate placentation, oxidative stress, and thrombosis. Genetic factors influence all of these proposed pathophysiological mechanisms. The inherited nature of pre-eclampsia has been known for many years, and extensive genetic studies have been undertaken in this area. Genetic research offers an attractive strategy for studying the pathogenesis of pre-eclampsia as it avoids the ethical and practical difficulties of conducting basic science research during the preclinical phase of pre-eclampsia when the underlying pathological changes occur. Although pharmacogenomic studies have not yet been conducted in pre-eclampsia, a number of studies investigating treatment for essential hypertension are of relevance to therapies used in pre-eclampsia. The pharmacogenomics of antiplatelet agents, alpha and beta blockers, calcium channel blockers, and magnesium sulfate are discussed in relation to the treatment and prevention of pre-eclampsia. Pharmacogenomics offers the prospect of individualized patient treatment, ensuring swift introduction of optimal treatment whilst minimizing the use of inappropriate or ineffective drugs, thereby reducing the risk of harmful effects to both mother and baby. PMID:23226061

Exploring knowledge of pre-eclampsia and views on a potential screening test in women with type 1 diabetes.

PubMed

Wotherspoon, Amy C; Young, Ian S; McCance, David R; Holmes, Valerie A

2017-07-01

to explore knowledge of pre-eclampsia and opinions on potential screening tests for pre-eclampsia in women with type 1 diabetes. a qualitative study using semi-structured interviews of women planning a pregnancy, currently pregnant or post-partum with experience of pre-eclampsia. SETTING, PARTICIPANTS AND METHODS: eleven women with type 1 diabetes were recruited from a pre-pregnancy planning clinic or antenatal clinic. Semi-structured interviews were conducted with the women, asking a series of open-ended questions about their current knowledge of pre-eclampsia and their views on screening for pre-eclampsia. Data analysis was conducted using inductive thematic analysis. four main themes were identified: Information, sources of stress, awareness and acceptability of screening. Generally, women's knowledge of pre-eclampsia was limited. Most did not appear to be aware of their increased risk of developing the disease. Similarly, the majority of women were unaware as to why their blood pressure and urine were checked regularly. The introduction of a screening test for pre-eclampsia was favoured, with only a small number of women raising concerns related to the screening tests. health care professionals need to raise awareness of pre-eclampsia in this high risk group. The introduction of a screening test for pre-eclampsia appears to be acceptable in this population, however, further research is required to validate these findings and also to explore the views of women in other high risk groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is inflammation the cause of pre-eclampsia?

PubMed Central

Ramma, Wenda; Ahmed, Asif

2011-01-01

It has been proposed that either excessive inflammation or an imbalance in angiogenic factors cause pre-eclampsia. In the present review, the arguments for and against the role of inflammation and/or angiogenic imbalance as the cause of pre-eclampsia are discussed on the basis of the Bradford–Hill criteria for disease causation. Although both angiogenic imbalance and systemic inflammation are implicated in pre-eclampsia, the absence of temporality of inflammatory markers with pre-eclampsia challenges the concept that excessive inflammation is the cause of pre-eclampsia. In contrast, the elevation of anti-angiogenic factors that precede the clinical signs of pre-eclampsia fulfils the criterion of temporality. The second most important criterion is the dose–response relationship. Although such a relationship has not been proven between pro-inflammatory cytokines and pre-eclampsia, high levels of anti-angiogenic factors have been shown to correlate with increased incidence and disease severity, hence satisfying this condition. Finally, as the removal of circulating sFlt-1 (soluble Fms-like tyrosine kinase receptor-1) from pre-eclamptic patients significantly improves the clinical outcome, it fulfils the Hill's experiment principle, which states that removal of the cause by an appropriate experimental regimen should ameliorate the condition. In contrast, treatment with high doses of corticosteroid fails to improve maternal outcome in pre-eclampsia, despite suppressing inflammation. Inflammation may enhance the pathology induced by the imbalance in the angiogenic factors, but does not by itself cause pre-eclampsia. Development of therapies based on the angiogenic and cytoprotective mechanisms seems more promising. PMID:22103497

A new mouse model to explore therapies for preeclampsia.

PubMed

Ahmed, Abdulwahab; Singh, Jameel; Khan, Ysodra; Seshan, Surya V; Girardi, Guillermina

2010-10-27

Pre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. This syndrome has been known to medical science since ancient times. However, despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment. Here we show that the CBA/J x DBA/2 mouse model of recurrent miscarriage is also a model of immunologically-mediated preeclampsia (PE). DBA/J mated CBA/J females spontaneously develop many features of human PE (primigravidity, albuminuria, endotheliosis, increased sensitivity to angiotensin II and increased plasma leptin levels) that correlates with bad pregnancy outcomes. We previously reported that antagonism of vascular endothelial growth factor (VEGF) signaling by soluble VEGF receptor 1 (sFlt-1) is involved in placental and fetal injury in CBA/J x DBA/2 mice. Using this animal model that recapitulates many of the features of preeclampsia in women, we found that pravastatin restores angiogenic balance, ameliorates glomerular injury, diminishes hypersensitivity to angiotensin II and protects pregnancies. We described a new mouse model of PE, were the relevant key features of human preeclampsia develop spontaneously. The CBA/J x DBA/2 model, that recapitulates this complex disorder, helped us identify pravastatin as a candidate therapy to prevent preeclampsia and its related complications. We recognize that these studies were conducted in mice and that clinical trials are needed to confirm its application to humans.

Monocytes and Macrophages in Pregnancy and Pre-Eclampsia

PubMed Central

Faas, Marijke M.; Spaans, Floor; De Vos, Paul

2014-01-01

Preeclampsia is an important complication in pregnancy, characterized by hypertension and proteinuria in the second half of pregnancy. Generalized activation of the inflammatory response is thought to play a role in the pathogenesis of pre-eclampsia. Monocytes may play a central role in this inflammatory response. Monocytes are short lived cells that mature in the circulation and invade into tissues upon an inflammatory stimulus and develop into macrophages. Macrophages are abundantly present in the endometrium and play a role in implantation and placentation in normal pregnancy. In pre-eclampsia, these macrophages appear to be present in larger numbers and are also activated. In the present review, we focused on the role of monocytes and macrophages in the pathophysiology of pre-eclampsia. PMID:25071761

Maternal serum theobromine and the development of preeclampsia.

PubMed

Klebanoff, Mark A; Zhang, Jun; Zhang, Cuilin; Levine, Richard J

2009-09-01

Preeclampsia, a disorder with prominent cardiovascular manifestations, is a cause of maternal, fetal, and infant morbidity and mortality. Chocolate contains compounds that may promote cardiovascular health. A recent study found chocolate consumption during pregnancy, and, particularly, increasing cord serum concentration of theobromine (the primary methylxanthine alkaloid in chocolate), to be associated with reduced occurrence of preeclampsia. We studied 2769 women who comprised the control group from a case-control study of caffeine metabolites and spontaneous abortion nested within the Collaborative Perinatal Project. These women were pregnant between 1959 and 1966, with liveborn infants of at least 28 weeks' gestation. Serum was drawn at <20 weeks and >26 weeks' gestation, and assayed for theobromine by high-performance liquid chromatography. Odds ratios (ORs) for preeclampsia were estimated using logistic regression, and adjusted for age, education, prepregnant weight, race, parity, smoking, and gestation at blood draw. Preeclampsia occurred in 68 (2.9%) of 2105 eligible women. Adjusted ORs for preeclampsia were near unity across most third-trimester theobromine concentrations. Adjusted ORs for preeclampsia according to theobromine concentration in serum at <20 weeks' gestation increased with increases in concentration, although estimates were imprecise. This study does not support the previous finding that chocolate consumption is associated with a reduced occurrence of preeclampsia. Unmeasured confounding or reverse causation may account for the positive association between early-pregnancy theobromine and preeclampsia.

First trimester uterine artery Doppler, sFlt-1 and PlGF to predict preeclampsia in a high-risk population.

PubMed

Diguisto, Caroline; Piver, Eric; Gouge, Amélie Le; Eboue, Florence; Vaillant, Claudine Le; Maréchaud, Martine; Goua, Valérie; Giraudeau, Bruno; Perrotin, Franck

2017-07-01

The study aims to evaluate the accuracy of combining uterine artery Doppler (UAD), PlGF and sFlt-1 in the first trimester for preeclampsia screening. Prospectively enrolled women at high risk of preeclampsia were included. Transabdominal UAD measurements and serum biomarkers were collected between 11 and 13 weeks of gestation in three university hospitals and in one general hospital. The main outcome was preeclampsia. UAD parameters and biomarker levels among women with preeclampsia were compared with those of women in the unaffected group in univariate and multivariate analyses. Out of 226 women included from May 2007 to January 2011, 27 (11.9%) women developed preeclampsia. Among women affected by preeclampsia, the lowest pulsatility index was higher (p = 0.02), bilateral notching was more frequent (p = 0.01), and PlGF was lower (p < 0.001). No significant differences were observed for other indicators. The multivariate model, adjusted for laboratory and sonographic indicators, had an area under the curve (AUC) estimated at 0.76, which was not significantly different from the AUC of the univariate model adjusted only for PlGF (p = 0.7). In a high-risk population, PlGF in the first trimester is useful for predicting preeclampsia, but neither sFlt-1 nor any UAD indices improved the prediction of preeclampsia.

Intake of probiotic food and risk of preeclampsia in primiparous women: the Norwegian Mother and Child Cohort Study.

PubMed

Brantsaeter, Anne Lise; Myhre, Ronny; Haugen, Margaretha; Myking, Solveig; Sengpiel, Verena; Magnus, Per; Jacobsson, Bo; Meltzer, Helle Margrete

2011-10-01

Probiotics have been suggested to modify placental trophoblast inflammation, systemic inflammation, and blood pressure, all potentially interesting aspects of preeclampsia. The authors examined the association between consumption of milk-based probiotic products in pregnancy and development of preeclampsia and its subtypes. The study was performed in the Norwegian Mother and Child Cohort Study by using a prospective design in 33,399 primiparous women in the years 2002-2008. The intake of milk-based products containing probiotic lactobacilli was estimated from a self-reported food frequency questionnaire. Preeclampsia diagnoses were obtained from the Norwegian Medical Birth Registry. Intake of probiotic milk products was associated with reduced risk of preeclampsia. The association was most prominent in severe preeclampsia (adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI): 0.66, 0.96). With probiotic intakes divided into categories representing no, monthly, weekly, or daily intake, a lower risk for preeclampsia (all subtypes) was observed for daily probiotic intake (OR = 0.80, 95% CI: 0.66, 0.96). Lower risks for severe preeclampsia were observed for weekly (OR = 0.75, 95% CI: 0.57, 0.98) and daily (OR = 0.61, 95% CI: 0.43, 0.89) intakes. These results suggest that regular consumption of milk-based probiotics could be associated with lower risk of preeclampsia in primiparous women.

Cluster analysis to estimate the risk of preeclampsia in the high-risk Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study

PubMed Central

Marttinen, Pekka; Gillberg, Jussi; Lokki, A. Inkeri; Majander, Kerttu; Ordén, Maija-Riitta; Taipale, Pekka; Pesonen, Anukatriina; Räikkönen, Katri; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele

2017-01-01

Objectives Preeclampsia is divided into early-onset (delivery before 34 weeks of gestation) and late-onset (delivery at or after 34 weeks) subtypes, which may rise from different etiopathogenic backgrounds. Early-onset disease is associated with placental dysfunction. Late-onset disease develops predominantly due to metabolic disturbances, obesity, diabetes, lipid dysfunction, and inflammation, which affect endothelial function. Our aim was to use cluster analysis to investigate clinical factors predicting the onset and severity of preeclampsia in a cohort of women with known clinical risk factors. Methods We recruited 903 pregnant women with risk factors for preeclampsia at gestational weeks 12+0–13+6. Each individual outcome diagnosis was independently verified from medical records. We applied a Bayesian clustering algorithm to classify the study participants to clusters based on their particular risk factor combination. For each cluster, we computed the risk ratio of each disease outcome, relative to the risk in the general population. Results The risk of preeclampsia increased exponentially with respect to the number of risk factors. Our analysis revealed 25 number of clusters. Preeclampsia in a previous pregnancy (n = 138) increased the risk of preeclampsia 8.1 fold (95% confidence interval (CI) 5.7–11.2) compared to a general population of pregnant women. Having a small for gestational age infant (n = 57) in a previous pregnancy increased the risk of early-onset preeclampsia 17.5 fold (95%CI 2.1–60.5). Cluster of those two risk factors together (n = 21) increased the risk of severe preeclampsia to 23.8-fold (95%CI 5.1–60.6), intermediate onset (delivery between 34+0–36+6 weeks of gestation) to 25.1-fold (95%CI 3.1–79.9) and preterm preeclampsia (delivery before 37+0 weeks of gestation) to 16.4-fold (95%CI 2.0–52.4). Body mass index over 30 kg/m2 (n = 228) as a sole risk factor increased the risk of preeclampsia to 2.1-fold (95%CI 1.1–3.6). Together with preeclampsia in an earlier pregnancy the risk increased to 11.4 (95%CI 4.5–20.9). Chronic hypertension (n = 60) increased the risk of preeclampsia 5.3-fold (95%CI 2.4–9.8), of severe preeclampsia 22.2-fold (95%CI 9.9–41.0), and risk of early-onset preeclampsia 16.7-fold (95%CI 2.0–57.6). If a woman had chronic hypertension combined with obesity, gestational diabetes and earlier preeclampsia, the risk of term preeclampsia increased 4.8-fold (95%CI 0.1–21.7). Women with type 1 diabetes mellitus had a high risk of all subgroups of preeclampsia. Conclusion The risk of preeclampsia increases exponentially with respect to the number of risk factors. Early-onset preeclampsia and severe preeclampsia have different risk profile from term preeclampsia. PMID:28350823

Estimating the Cost of Preeclampsia in the Healthcare System: Cross-Sectional Study Using Data From SCOPE Study (Screening for Pregnancy End Points).

PubMed

Fox, Aimée; McHugh, Sheena; Browne, John; Kenny, Louise C; Fitzgerald, Anthony; Khashan, Ali S; Dempsey, Eugene; Fahy, Ciara; O'Neill, Ciaran; Kearney, Patricia M

2017-12-01

To estimate the cost of preeclampsia from the national health payer's perspective using secondary data from the SCOPE study (Screening for Pregnancy End Points). SCOPE is an international observational prospective study of healthy nulliparous women with singleton pregnancies. Using data from the Irish cohort recruited between November 2008 and February 2011, all women with preeclampsia and a 10% random sample of women without preeclampsia were selected. Additional health service use data were extracted from the consenting participants' medical records for maternity services which were not included in SCOPE. Unit costs were based on estimates from 3 existing Irish studies. Costs were extrapolated to a national level using a prevalence rate of 5% to 7% among nulliparous pregnancies. Within the cohort of 1774 women, 68 developed preeclampsia (3.8%) and 171 women were randomly selected as controls. Women with preeclampsia used higher levels of maternity services. The average cost of a pregnancy complicated by preeclampsia was €5243 per case compared with €2452 per case for an uncomplicated pregnancy. The national cost of preeclampsia is between €6.5 and €9.1 million per annum based on the 5% to 7% prevalence rate. Postpartum care was the largest contributor to these costs (€4.9-€6.9 million), followed by antepartum care (€0.9-€1.3 million) and peripartum care (€0.6-€0.7 million). Women with preeclampsia generate significantly higher maternity costs than women without preeclampsia. These cost estimates will allow policy-makers to efficiently allocate resources for this pregnancy-specific condition. Moreover, these estimates are useful for future research assessing the cost-effectiveness of preeclampsia screening and treatment. © 2017 American Heart Association, Inc.

Molecular Mechanisms of Preeclampsia

PubMed Central

Hod, Tammy; Cerdeira, Ana Sofia; Karumanchi, S. Ananth

2015-01-01

Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension and proteinuria after 20 wk of gestation. It is a leading cause of maternal and fetal morbidity and mortality worldwide. Exciting discoveries in the last decade have contributed to a better understanding of the molecular basis of this disease. Epidemiological, experimental, and therapeutic studies from several laboratories have provided compelling evidence that an antiangiogenic state owing to alterations in circulating angiogenic factors leads to preeclampsia. In this review, we highlight the role of key circulating antiangiogenic factors as pathogenic biomarkers and in the development of novel therapies for preeclampsia. PMID:26292986

HELLP syndrome

MedlinePlus

... It is considered to be a variant of preeclampsia. Sometimes the presence of HELLP syndrome is due ... out of 1,000 pregnancies. In women with preeclampsia or eclampsia , the condition develops in 10% to ...

Uterine artery velocity waveforms as predictors of pregnancy outcome in patients with antiphospholipid syndrome: a review.

PubMed

De Carolis, Sara; Botta, Angela; Garofalo, Serafina; Ferrazzani, Sergio; Martino, Carmelinda; Fatigante, Gabriella; Caforio, Leonardo; Caruso, Alessandro

2007-06-01

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk for preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, as the likely consequence of the physiologic change of spiral arteries into low-resistance vessels. The presence of antiphospholipid antibodies can impair this vascular adaptation, resulting in a reduced placental perfusion. Doppler investigation provides a noninvasive method for the study of uteroplacental blood flow. Several studies were performed to detect the predictive role of uterine artery Doppler velocimetry in relation to pregnancy outcome in APS patients. In some studies, a high resistance index in the uterine arteries strongly predicted the subsequent development of obstetric complications. In other studies, persistent bilateral uterine artery notches identified the risk of preeclampsia and fetal intrauterine growth restriction. To date, the uterine artery Doppler velocimetry resulted to be a useful tool for identifying APS pregnancies at risk for adverse pregnancy outcome. These findings might have important implications for the management of these patients.

PP172. Indian scenario of preeclampsia and its consequences and early prophylaxis.

PubMed

Jariwala, M C

2012-07-01

Preeclampsia remains one of the major obstetrical problems in less-developed countries. The causes of this condition are still unknown, we have designed a prevention protocol with new concept to describe the etiology and cause of preeclampsia. To study the effectiveness of the Jariwala's therapy and etiological causes of preeclapsia. we want to establish the new version of efficient prophylactic management to prevent the concequences of preeclampsia. We have selected 800 cases who have developed preeclampsia during any phase of pregnancy and tried to prevent the developing preeclampsia (predicted with roll over test, color doppler and weight gain and or edema) by Jariwala's protocol. our aim is to reduce the severity of disease process by early prediction and treatment. we have not included the cases who may have completely treated after the inclusion criteria to predict the preclampsia and treated. the inclusion criteris is strictly followed by a protocol designed. Jariwala's therapy is effective in mild to moderate cases of preeclampsia. Till date we have successfully treated 800 cases of mild to moderate preeclapsia with 98% neonates delivered with birth weight of 2kg and more, 92% neonates sent directly to home without any complication; and developed well at home. If we try to treat the blood pressure (during pregnancy) by anti hypertensive we have noticedà IUGR and rebound increase of blood pressure, means decrease maternal blood pressure à decrease placental supplyà deficient nutrientà rebound increase in toxin secretion (by fetus and placenta) à increase in blood pressure to supply more nutrient). So that it is my suggestion that the antihypertensive should be avoided if possible 2: increase permeability of placental membranes due to toxins secreted by fetus to supply more nutrient leads to increase permeability of placental membranes means increase protein loss from kidneys (due to toxins secreted from the fetus and placenta) increase third space leakage of fluid as nutrient leads to serum protein deficiency and increase permeability of endovascularities of all organs multi system disorder. so instead of treating the developing preeclampsia with routine treatment either terminate the pregnancy if it is severe and developing intensely or treat with the Jariwala's protocol. Copyright © 2012. Published by Elsevier B.V.

The impact of preeclampsia in pregnancy

PubMed Central

Manaj, Aferdita; Rrugia, Arben; Manoku, Nikita

2011-01-01

Objective. To observe the influence of preeclampsia during pregnancy. Materials and methods. 5711 patient’s records of the year 2008 and 6188 patient’s records of the year 2009 of Obstetric/Gynecologic hospital ‘Queen Geraldina’ have been consulted. The age of women that we studied in 2008 was between 23-35 and in 2009 was be-tween 25-34 years old. We have made a careful diagnose of inducted hypertension of pregnancy and preeclampsia. Results. The incidence of preeclampsia in the population was 4.1% (n =238) in 2008 and 3.1% (n=192) in 2009.The incidence of the cases that developed from preeclampsia to eclampsia were respectively 1.6% (n=4) and 1.5% (n=3) on 2009. Babies which have preeclamptic mothers were preterm in 13% (n=31) of cases, and 14.5% (n=28) of which have severe hypotrophia vs. 10% (n=24) and 11% (n=21) severe hypotrophia in 2009. Babies mortality on the preeclamptic population were respectively 8% (n=19) and 7.8% (n=15). Conclusions. From the survey resulted that patients diagnosed with preeclampsia manifested on a high rate hypertension and proteinuria. Prematurity, severe hypotrophy and baby’s mortality were the major complications of preeclampsia. Women with preeclampsia were especially the youngest. PMID:22439070

Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case-control study.

PubMed

Ye, Yunzhen; Zhou, Qiongjie; Feng, Liping; Wu, Jiangnan; Xiong, Yu; Li, Xiaotian

2017-12-01

Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. We conducted a nested case-control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16-20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (<2.24 µg/l), medium (2.24-4.44 µg/l), and high (>4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42-49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association.

Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case–control study

PubMed Central

Ye, Yunzhen; Zhou, Qiongjie; Feng, Liping; Wu, Jiangnan; Xiong, Yu; Li, Xiaotian

2017-01-01

Abstract Background Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. Methods We conducted a nested case–control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16–20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. Results BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (<2.24 µg/l), medium (2.24-4.44 µg/l), and high (>4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42–49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). Conclusions These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia. PMID:29186464

Effects of lactation on postpartum blood pressure among women with gestational hypertension and preeclampsia.

PubMed

Countouris, Malamo E; Schwarz, Eleanor B; Rossiter, Brianna C; Althouse, Andrew D; Berlacher, Kathryn L; Jeyabalan, Arun; Catov, Janet M

2016-08-01

Women with a history of hypertensive disorders of pregnancy are at an increased risk of hypertension and cardiovascular disease in later life. Lactation has been associated with a reduced risk of maternal hypertension, both in the postpartum period and later life. However, little is known about whether lactation is also cardioprotective in women with hypertensive disorders of pregnancy such as preeclampsia or gestational hypertension. This study aimed to characterize the relationship between lactation and postpartum blood pressure among women with preeclampsia and gestational hypertension. Data were obtained from women who participated in the Prenatal Exposures and Preeclampsia Prevention study (n = 379; 66% African American; 85% overweight or obese). Women enrolled during pregnancy and attended a postpartum visit (on average, 9.1 months after delivery) during which data on lactation duration and blood pressure were collected. The significance of the associations between postpartum blood pressure and lactation among women who remained normotensive during pregnancy, developed gestational hypertension, or developed preeclampsia were assessed with an analysis of variance. Linear regression models were used to adjust for maternal age, race, education, prepregnancy weight, and time since delivery. Gestational hypertension affected 42 subjects (11%) and preeclampsia affected 33 (9%). Lactation was reported by 217 (57%) with 78 (21%) reporting ≥ 6 months of lactation. Women who lactated were somewhat older, more educated, and had higher socioeconomic status. Among women who had gestational hypertension, lactation was associated with lower systolic blood pressure (P = .02) and diastolic blood pressure (P = .02). This association persisted after adjustment for age, race, education, prepregnancy weight, and time since delivery. However, for women who had preeclampsia and women who remained normotensive during pregnancy, lactation was not associated with postpartum blood pressure in either bivariate or multivariate analyses. This study found that lactation is associated with lower postpartum blood pressure among overweight women who develop gestational hypertension but not among women who develop preeclampsia. Future studies are needed to explore the association of lactation and blood pressure in later life for women with hypertensive disorders of pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes mellitus: A systematic review.

PubMed

Wotherspoon, Amy C; Young, Ian S; McCance, David R; Holmes, Valerie A

2016-07-01

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes. To undertake a systematic review to identify potential biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes. We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL SELECTION CRITERIA: Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta-analysis could not be performed, due to high study heterogeneity. A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful. Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

Decreased level of cord blood circulating endothelial colony-forming cells in preeclampsia.

PubMed

Muñoz-Hernandez, Rocio; Miranda, Maria L; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M; Dominguez-Simeon, Maria J; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M

2014-07-01

Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation, and migration toward vascular endothelial growth factor-A and fibroblast growth factor-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P=0.04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events. © 2014 American Heart Association, Inc.

Placental glucose transporter (GLUT)-1 is down-regulated in preeclampsia.

PubMed

Lüscher, Benjamin P; Marini, Camilla; Joerger-Messerli, Marianne S; Huang, Xiao; Hediger, Matthias A; Albrecht, Christiane; Baumann, Marc U; Surbek, Daniel V

2017-07-01

Transplacental fetal glucose supply is predominantly regulated by glucose transporter-1 (GLUT1). Altered expression and/or function of GLUT1 may affect the intrauterine environment, which could compromise fetal development and may contribute to fetal programming. To date it is unknown whether placental GLUT1 is affected by preeclampsia, which is often associated with intrauterine growth restriction (IUGR). We addressed the hypothesis that preeclampsia leads to decreased expression and function of placental GLUT1. Placentae were obtained following normal pregnancy and from pregnancies affected by preeclampsia. Washed villous tissue fragments were used to prepare syncytial microvillous (MVM) and basal plasma membranes (BM) microvesicles. GLUT1 protein and mRNA expression was assessed by western blot analysis and qPCR using Fast SYBR Green. A radio-labeled glucose up-take assay using placenta-derived syncytial microvesicles was used to analyze GLUT1 function. GLUT1 protein expression was significantly down-regulated in (apical) MVM of the syncytiotrophoblast in preeclampsia (n = 6) compared to controls (n = 6) (0.40 ± 0.04 versus 1.00 ± 0.06, arbitrary units, P < 0.001, Student's t-test), while GLUT1 mRNA expression did not show a significant difference. In addition, the functional assay in syncytial microvesicles showed a significantly decreased glucose transport activity in preeclampsia (61.78 ± 6.48%, P < 0.05) compared to controls. BM GLUT1 protein expression was unchanged and glucose up-take into BM microvesicles showed no differences between the preeclampsia and control groups. Our study shows for the first time that in preeclampsia placental GLUT1 expression and function are down-regulated at the apical plasma membrane of the syncytiotrophoblast. Further studies are needed to assess whether these changes occur also in vivo and contribute to the development of IUGR in preeclampsia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vascular dysfunction in women with a history of preeclampsia and intrauterine growth restriction: insights into future vascular risk.

PubMed

Yinon, Yoav; Kingdom, John C P; Odutayo, Ayodele; Moineddin, Rahim; Drewlo, Sascha; Lai, Vesta; Cherney, David Z I; Hladunewich, Michelle A

2010-11-02

Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate-induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; P<0.0001). Flow-independent vasodilatation was similar among all groups. Similarly, the radial augmentation index was significantly increased among women with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects (P=0.0105). Circulating angiogenic factors were similar in all groups. Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher risk of future vascular disease.

Elucidating the Pathogenesis of Pre-eclampsia Using In Vitro Models of Spiral Uterine Artery Remodelling.

PubMed

McNally, Ross; Alqudah, Abdelrahim; Obradovic, Danilo; McClements, Lana

2017-10-23

The aim of the study is to perform a critical assessment of in vitro models of pre-eclampsia using complementary human and cell line-based studies. Molecular mechanisms involved in spiral uterine artery (SUA) remodelling and trophoblast functionality will also be discussed. A number of proteins and microRNAs have been implicated as key in SUA remodelling, which could be explored as early biomarkers or therapeutic targets for prevention of pre-eclampsia. Various 2D and 3D in vitro models involving trophoblast cells, endothelial cells, immune cells and placental tissue were discussed to elucidate the pathogenesis of pre-eclampsia. Nevertheless, pre-eclampsia is a multifactorial disease, and the mechanisms involved in its pathogenesis are complex and still largely unknown. Further studies are required to provide better understanding of the key processes leading to inappropriate placental development which is the root cause of pre-eclampsia. This new knowledge could identify novel biomarkers and treatment strategies.

Preeclampsia in low and middle income countries-health services lessons learned from the PRE-EMPT (PRE-Eclampsia-Eclampsia Monitoring, Prevention and Treatment) project.

PubMed

von Dadelszen, Peter; Firoz, Tabassum; Donnay, France; Gordon, Rebecca; Justus Hofmeyr, G; Lalani, Shifana; Payne, Beth A; Roberts, James M; Teela, Katherine C; Vidler, Marianne; Sawchuck, Diane; Magee, Laura A

2012-10-01

The hypertensive disorders of pregnancy, in particular preeclampsia, matter because adverse events occur in women with preeclampsia and, to a lesser extent, in women with the other hypertensive disorders. These adverse events are maternal, perinatal, and neonatal and can alter the life trajectory of each individual, should that life not be ended by complications. In this review we discuss a number of priorities and dilemmas that we perceive to be facing health services in low and middle income countries as they try to prioritize interventions to reduce the health burden related to preeclampsia. These priorities and dilemmas relate to calcium for preeclampsia prevention, risk stratification, antihypertensive and magnesium sulphate therapy, and mobile health. Significant progress has been and is being made to reduce the impact of preeclampsia in low and middle income countries, but it remains a priority focus as we attempt to achieve Millennium Development Goal 5.

A novel marker in pregnant with preeclampsia: renalase.

PubMed

Yılmaz, Zehra Vural; Akkaş, Elif; Yıldırım, Tolga; Yılmaz, Rahmi; Erdem, Yunus

2017-04-01

Preeclampsia is characterized by an increase in high blood pressure and decrease in GFR and proteinuria, however, the underlying mechanisms are still unclear. Renalase is a recently discovered protein implicated in regulation of blood pressure in humans. Plasma concentrations of serum renalase were measured in healthy controls, healthy pregnant and pregnant with preeclampsia matched for age, gestational age, in the third trimester of pregnancy. Serum renalase levels were compared in pregnant with and without preeclampsia and non-pregnant controls. Factors associated with serum renalase levels in pregnancies were also evaluated. In healthy pregnant serum renalase levels were significantly higher than in controls. However, pregnant with preeclampsia had lower renalase levels than healthy controls. Serum renalase levels were inversely associated with blood pressure levels and positively correlated with glomerular filtration rate. The results indicated that the development of preeclampsia in pregnant is accompanied by altered serum renalase levels. High blood pressure and kidney damage that characterize this disorder are mediated at least in part by low renalase levels.

Folic acid supplement use and the risk of gestational hypertension and preeclampsia.

PubMed

De Ocampo, Maria P G; Araneta, Maria Rosario G; Macera, Caroline A; Alcaraz, John E; Moore, Thomas R; Chambers, Christina D

2018-04-01

Hypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality. Studies suggest that the use of folic acid may lower the risk of hypertensive disorders in pregnant women. The aim of this study was to assess the effects of timing and duration of folic acid-containing supplement use on the risk for gestational hypertension and preeclampsia. Exposures and outcomes data were obtained through interviews and review of participant's medical records from the MotherToBaby cohort studies across the United States and Canada. Demographics, medical history, lifestyle factors, substance use, and fetal sex were assessed as potential confounders. Unadjusted and adjusted risks for gestational hypertension and preeclampsia were examined using odds ratios and 95% confidence intervals. 3247 women were included in the study. Compared to non-supplement use, early and late supplement use were not significantly associated with the development of gestational hypertension or preeclampsia. The odds of developing gestational hypertension and preeclampsia were significantly reduced as the duration of folic acid-containing supplement use increased. Findings from this study suggest that the use of folic acid-containing supplements may mitigate the risk for gestational hypertension and preeclampsia. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Spot urine protein measurements in normotensive pregnancies, pregnancies with isolated proteinuria and preeclampsia.

PubMed

Kattah, Andrea; Milic, Natasa; White, Wendy; Garovic, Vesna

2017-10-01

We performed a prospective, longitudinal study of pregnant women presenting to their first obstetrics visits to characterize the changes in spot urine protein-to-creatinine (UPCR) and albumin-to-creatinine ratios (UACR) in normotensive pregnancies, as well as identify clinical characteristics associated with isolated proteinuria and preeclampsia. We measured spot urinary albumin, protein, and creatinine at the first prenatal visit, end of the second trimester, and at delivery. In the normotensive pregnancies ( n = 142), we found that from the beginning of pregnancy to delivery, UACR increased by a median [interquartile range (IQR)] of 14.7 mg/g Cr (3.74-51.8) and UPCR by 60 mg/g Cr (30-130) ( P < 0.001 for both changes). Isolated proteinuria (defined as UPCR > 300 mg/g Cr in the absence of hypertension) was identified in 19/142 (13.4%) normotensive pregnancies. Increases in systolic and diastolic blood pressure from early pregnancy to delivery and increases in UACR from early to midpregnancy were associated with isolated proteinuria at delivery. Twelve women developed preeclampsia. Nulliparity, early, and midpregnancy diastolic blood pressures were strongly associated with the development of preeclampsia, but early changes in UACR were not. In conclusion, women who develop isolated proteinuria at delivery have a larger increase in blood pressure than women without proteinuria and have a "microalbuminuric" phase earlier in gestation, unlike women who develop preeclampsia. These findings suggest a different mechanism of urine protein excretion in women with isolated proteinuria as compared with women with preeclampsia, where proteinuria has a more abrupt onset. Copyright © 2017 the American Physiological Society.

Combination of serum angiopoietin-2 and uterine artery Doppler for prediction of preeclampsia.

PubMed

Puttapitakpong, Ploynin; Phupong, Vorapong

2016-02-01

The aim of this study was to determine the predictive value of the combination of serum angiopoietin-2 (Ang-2) levels and uterine artery Doppler for the detection of preeclampsia in women at 16-18 weeks of gestation and to identify other pregnancy complications that could be predicted with these combined tests. Maternal serum Ang-2 levels were measured, and uterine artery Doppler was performed in 400 pregnant women. The main outcome was preeclampsia. The predictive values of this combination were calculated. Twenty-five women (6.3%) developed preeclampsia. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of uterine artery Doppler combined with serum Ang-2 levels for the prediction of preeclampsia were 24.0%, 94.4%, 22.2% and 94.9%, respectively. For the prediction of early-onset preeclampsia, the sensitivity, specificity, PPV and NPV were 57.1%, 94.1%, 14.8% and 99.2%, respectively. Patients with abnormal uterine artery Doppler and abnormal serum Ang-2 levels (above 19.5 ng ml(-1)) were at higher risk for preterm delivery (relative risk=2.7, 95% confidence interval 1.2-5.8). Our findings revealed that the combination of uterine artery Doppler and serum Ang-2 levels at 16-18 weeks of gestation can be used to predict early-onset preeclampsia but not overall preeclampsia. Thus, this combination may be a useful early second trimester screening test for the prediction of early-onset preeclampsia.

Selenium and Preeclampsia: a Systematic Review and Meta-analysis.

PubMed

Xu, Min; Guo, Dan; Gu, Hao; Zhang, Li; Lv, Shuyan

2016-06-01

Conflicting results exist between selenium concentration and preeclampsia. The role of selenium in the development of preeclampsia is unclear. We conducted a meta-analysis to compare the blood selenium level in patients with preeclampsia and healthy pregnant women, and to determine the effectiveness of selenium supplementation in preventing preeclampsia. We searched PubMed, ScienceDirect, the Cochrane Library, and relevant references for English language literature up to November 25, 2014. Mean difference from observational studies and relative risk from randomized controlled trials were meta-analyzed by a random-effect model. Thirteen observational studies with 1515 participants and 3 randomized controlled trials with 439 participants were included in the meta-analysis. Using a random-effect model, a statistically significant difference in blood selenium concentration of -6.47 μg/l (95 % confidence interval (CI) -11.24 to -1.7, p = 0.008) was seen after comparing the mean difference of observational studies. In randomized controlled trials, using a random-effect model, the relative risk for preeclampsia was 0.28 (0.09 to 0.84) for selenium supplementation (p = 0.02). Evidence from observational studies indicates an inverse association of blood selenium level and the risk of preeclampsia. Supplementation with selenium significantly reduces the incidence of preeclampsia. However, more prospective clinical trials are required to assess the association between selenium supplementation and preeclampsia and to determine the dose, beginning time, and duration of selenium supplementation.

Original Article: Preeclampsia, Placental Insufficiency and Autism Spectrum Disorder or Developmental Delay

PubMed Central

Walker, Cheryl K.; Krakowiak, Paula; Baker, Alice; Hansen, Robin L.; Ozonoff, Sally; Hertz-Picciotto, Irva

2014-01-01

Importance Increasing evidence suggests that autism spectrum disorder (ASD) and many forms of developmental delay (DD) originate during fetal development. Preeclampsia may trigger aberrant neurodevelopment through placental, maternal and fetal physiologic mechanisms. Objective To determine whether preeclampsia is associated with ASD and/or DD. Design, Setting and Participants The CHildhhood Autism Risks from Genetics and the Environment (CHARGE) Study is a population-based case-control investigation of ASD and/or DD origins. Children from 20 California counties aged 24-60 months at the time of recruitment, and living in catchment areas with a biologic parent fluent in English or Spanish were enrolled from January 29, 2003 through April 7, 2011. Children with ASD (n=517) and DD (n=194) were recruited through the California Department of Developmental Services, the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute and referrals. Controls with typical development (TD) controls (n=350) were randomly selected from birth records and frequency-matched on age, sex, and broad geographic region. Physicians diagnosing preeclampsia were masked to neurodevelopmental outcome, and those assessing neurodevelopmental function were masked to preeclampsia status. Exposure Preeclampsia and placental insufficiency were self-reported and abstracted from medical records. Main Outcome Measure The Autism Diagnostic Observation Schedule and Autism Diagnostic Interview–Revised were used to confirm ASD, whereas children with DD and TD were confirmed by Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales and were free of autistic symptoms. Hypotheses were formulated before data collection. Results Children with ASD were twice as likely to have been exposed in utero to preeclampsia as controls with TD after adjustment for maternal educational level, parity, and prepregnancy obesity (adjusted odds ratio, 2.36; 95% CI, 1.18-4.68); risk increased with greater preeclampsia severity (test for trend p=0.02). Placental insufficiency appeared responsible for the increase in DD risk associated with severe preeclampsia (adjusted odds ratio, 5.49; 95% CI, 2.06-14.64). Conclusions and Relevance Preeclampsia, particularly severe disease, is associated with ASD and DD. Faulty placentation manifests in the mother as preeclampsia with vascular damage, enhanced systemic inflammation and insulin resistance; in the placenta as oxygen and nutrient transfer restriction and oxidative stress; and in the fetus as growth restriction and progressive hypoxemia. All are potential mechanisms for neurodevelopmental compromise. PMID:25485869

The genetics of pre-eclampsia and other hypertensive disorders of pregnancy

PubMed Central

Williams, Paula J.; Broughton Pipkin, Fiona

2011-01-01

Hypertension is the most frequent medical complication occurring during pregnancy. In this chapter, we aim to address the genetic contribution to these disorders, with specific focus on pre-eclampsia. The pathogenic mechanisms underlying pre-eclampsia remain to be elucidated; however, immune maladaptation, inadequate placental development and trophoblast invasion, placental ischaemia, oxidative stress and thrombosis are all thought to represent key factors in the development of disease. Furthermore, all of these components have genetic factors that may be involved in the pathogenic changes occurring. The familial nature of pre-eclampsia has been known for many years and, as such, extensive genetic research has been carried out in this area using strategies that include candidate gene studies and linkage analysis. Interactions between fetal and maternal genotypes, the effect of environmental factors, and epistasis will also be considered. PMID:21429808

Molecular Mechanisms of Preeclampsia.

PubMed

Hod, Tammy; Cerdeira, Ana Sofia; Karumanchi, S Ananth

2015-08-20

Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension and proteinuria after 20 wk of gestation. It is a leading cause of maternal and fetal morbidity and mortality worldwide. Exciting discoveries in the last decade have contributed to a better understanding of the molecular basis of this disease. Epidemiological, experimental, and therapeutic studies from several laboratories have provided compelling evidence that an antiangiogenic state owing to alterations in circulating angiogenic factors leads to preeclampsia. In this review, we highlight the role of key circulating antiangiogenic factors as pathogenic biomarkers and in the development of novel therapies for preeclampsia. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Pre-Eclampsia and Eclampsia: An Update on the Pharmacological Treatment Applied in Portugal †

PubMed Central

Peres, Gonçalo Miguel; Mariana, Melissa

2018-01-01

Pre-eclampsia and eclampsia are two hypertensive disorders of pregnancy, considered major causes of maternal and perinatal death worldwide. Pre-eclampsia is a multisystemic disease characterized by the development of hypertension after 20 weeks of gestation, with the presence of proteinuria or, in its absence, of signs or symptoms indicative of target organ injury. Eclampsia represents the consequence of brain injuries caused by pre-eclampsia. The correct diagnosis and classification of the disease are essential, since the therapies for the mild and severe forms of pre-eclampsia are different. Thus, this review aims to describe the most advisable antepartum pharmacotherapy for pre-eclampsia and eclampsia applied in Portugal and based on several national and international available guidelines. Slow-release nifedipine is the most recommended drug for mild pre-eclampsia, and labetalol is the drug of choice for the severe form of the disease. Magnesium sulfate is used to prevent seizures caused by eclampsia. Corticosteroids are used for fetal lung maturation. Overall, the pharmacological prevention of these diseases is limited to low-dose aspirin, so it is important to establish the safest and most effective available treatment. PMID:29367581

Pathogenesis of preeclampsia.

PubMed

Sircar, Monica; Thadhani, Ravi; Karumanchi, S Ananth

2015-03-01

Preeclampsia is a gestational kidney disease characterized by glomerular endothelial injury, leading to maternal hypertension and proteinuria. If not addressed promptly, there is significant maternal and fetal morbidity and mortality. When severe, this disorder can cause hepatic and neurologic dysfunction. Understandably, this placental disease enters the focus of the obstetrician first; however, with progression, the nephrologist can also be enlisted. Typical complications include acute kidney injury, refractory hypertension, and acute pulmonary edema. This review summarizes recent literature on the pathogenesis of this condition and will highlight new diagnostic and therapeutic options for preeclampsia. Over the past decade, the role of soluble vascular factors in preeclampsia has shed light on the mechanism underlying this disease. During the last 2 years, several new therapeutics have been developed that target implicated circulating angiogenic factors, including soluble fms-like tyrosine kinase 1, an endogenous vascular endothelial growth factor inhibitor. Serum levels of angiogenic factors have been correlated with a constellation of hemodynamic and pathophysiologic changes. Thus, circulating levels of these factors may serve both diagnostic and prognostic purposes. Overall, our understanding of preeclampsia has developed significantly and the future holds promise for mechanism-based novel diagnostics and therapeutics.

Preeclampsia: is it because of the asymptomatic, unrecognized renal scars caused by urinary tract infections in childhood that become symptomatic with pregnancy?

PubMed

Ozlü, Tülay; Alçelik, Aytekin; Calişkan, Billur; Dönmez, Melahat Emine

2012-11-01

Preeclampsia is an important disease of pregnancy whose exact etiology is still unknown despite continuing developments in medicine. Although most commonly it is believed to be caused by a defective placentation, in this paper, we hypothesize that the primary underlying problem in the development of preeclampsia can be in kidneys in a greater proportion of cases than it is believed today. The increased intravascular volume and the increased work load of kidneys together with the resulting glomerular hypertrophy may precipitate nephrotic syndrome, which in this case is called "preeclampsia" in a previously affected kidney. Urinary tract infections in childhood leaving silent, unrecognized small scars in the kidneys may be the underlying renal cause which disrupts its silence with an increased work load of kidneys prominently occurring after the midtrimester. The histopathologic finding in kidneys with renal scars after childhood urinary tract infections and in preeclampsia is focal segmental glomerulosclerosis in the majority of cases and this similarity strengthens our hypothesis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Maternal vitamin D status and the risk of mild and severe preeclampsia

PubMed Central

Bodnar, Lisa M.; Simhan, Hyagriv N.; Catov, Janet M.; Roberts, James M.; Platt, Robert W.; Diesel, Jill C.; Klebanoff, Mark A.

2014-01-01

Background We sought to determine the association between maternal vitamin D status at ≤26 weeks gestation and the risk of preeclampsia separately by clinical subtype. Methods We conducted a case-cohort study among women enrolled at 12 U.S. sites from 1959 to 1966 in the Collaborative Perinatal Project. In 717 women who later developed preeclampsia (560 mild and 157 severe cases) and in 2986 mothers without preeclampsia, we measured serum 25-hydroxyvitamin D at ≤26 weeks gestation (median 20.9 weeks) over 40 years later using liquid-chromatography-tandem mass spectrometry. Results Half of women in the subcohort had 25(OH)D <50 nmol/L. Maternal 25(OH)D 50–<75 nmol/L was associated with a reduction in the absolute and relative risk of preeclampsia and mild preeclampsia compared with 25(OH)D <30 nmol/L, but the effects were no longer present after adjustment for confounders including race, prepregnancy body mass index, and parity. For severe preeclampsia, 25(OH)D ≥50 nmol/L was associated with a reduction of 3 cases per 1,000 pregnancies (adjusted RD −.003, 95% CI: −.005, .0002) and a 40% reduction in risk (adjusted RR .65, 95% CI .43, .98) compared with 25(OH)D <50 nmol/L. The conclusions were the same after restricting to women with 25(OH)D measured at <22 weeks gestation and after formal sensitivity analyses for unmeasured confounding. Conclusions Maternal vitamin D deficiency may be a risk factor for severe preeclampsia, but it is not associated with preeclampsia overall or its mild subtypes. Contemporary cohorts with large numbers of severe preeclampsia cases are needed to confirm or refute these findings. PMID:24457526

Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

PubMed

Penning, Marlies; Chua, Jamie S; van Kooten, Cees; Zandbergen, Malu; Buurma, Aletta; Schutte, Joke; Bruijn, Jan Anthonie; Khankin, Eliyahu V; Bloemenkamp, Kitty; Karumanchi, S Ananth; Baelde, Hans

2015-07-01

A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia. © 2015 American Heart Association, Inc.

Increased incidence of preeclampsia in mothers of advanced age conceiving by oocyte donation.

PubMed

Dior, Uri P; Laufer, Neri; Chill, Henry H; Granovsky-Grisaru, Sorina; Yagel, Simcha; Yaffe, Haim; Gielchinsky, Yuval

2018-05-01

The aim of this study was to evaluate the risk of preeclampsia in women of advanced age who conceived through donated oocytes as compared with natural conceptions. A historical prospective study of singleton live births of parturients ≥ 45 years of age at four university hospitals was conducted. For the purpose of the study, the population was divided by the mode of conception into two groups: oocyte donation and natural conception. The main outcome variable in this study was preeclampsia. Secondary outcomes included pregnancy-induced hypertension and Small for Gestational Age. Two hundred and seventy pregnancies were achieved naturally and 135 women conceived by oocyte donation. Mean age at delivery for the natural conception and oocyte donation groups was 45.7 and 47.8, respectively. Preeclampsia complicated 3 out of 270 (1.1%) natural conception pregnancies and 17 out of 135 (12.6%) oocyte donation conceptions. After adjusting for confounders, oocyte donation pregnancies were found to be associated with a 12-fold increased risk for preeclampsia (P = 0.001). Among oocyte donation pregnancies, the risk of preeclampsia was not affected by parity or age. A substantially increased risk for preeclampsia was found in oocyte donation pregnancies, suggesting that the foreign oocyte may play a specific biologic role in the development of preeclampsia after the age of 45.

Low socioeconomic status is a risk factor for preeclampsia: the Generation R Study.

PubMed

Silva, Lindsay M; Coolman, Marianne; Steegers, Eric Ap; Jaddoe, Vincent Wv; Moll, Henriëtte A; Hofman, Albert; Mackenbach, Johan P; Raat, Hein

2008-06-01

To examine whether maternal socioeconomic status, as indicated by maternal educational level, is associated with preeclampsia, and if so, to what extent known risk factors for preeclampsia mediate the effect of educational level. In the Generation R Study, a population-based cohort study, we examined data of 3547 pregnant women. Odds ratios of preeclampsia for low, mid-low and mid-high educational level compared with high educational level were calculated after adjustment for confounders and additional adjustment for a selection of potential mediators (family history, material factors, psychosocial factors, substance use, working conditions, preexisting medical conditions, maternal anthropometrics and blood pressure at enrollment) that individually caused more than 10% change in the odds ratio for low education. Adjusted for the confounding effects of age, gravidity and multiple pregnancy, women with low educational level were more likely to develop preeclampsia (odds ratio 5.12; 95% confidence interval: 2.20, 11.93) than women with high educational level. After additional adjustment for financial difficulties, smoking in pregnancy, working conditions, body mass index and blood pressure at enrollment, the odds ratio was 4.91 (95% confidence interval: 1.93, 12.52). Low maternal socioeconomic status is a strong risk factor for preeclampsia. Only a small part of this association can be explained by the mediating effects of established risk factors for preeclampsia. Further research is needed to disentangle the pathway from low socioeconomic status to preeclampsia.

Markers of insulin resistance and sedentary lifestyle are predictors of preeclampsia in women with adverse obstetric results.

PubMed

Hoirisch-Clapauch, S; Benchimol-Barbosa, P R

2011-12-01

Some thrombophilias and severe preeclampsia may increase the risk for preterm deliveries and fetal death due to placental insufficiency. Our objective was to evaluate clinical and laboratory data as predictors of preeclampsia in a population of mothers with 3rd trimester fetal losses or preterm deliveries. In a longitudinal retrospective study, 54 consecutive women (age range: 16 to 39 years) with normotensive pregnancies were compared to 79 consecutive women with preeclampsia (age range: 16 to 43 years). Weight accrual rate (WAR) was arbitrarily defined as weight gain from age 18 years to the beginning of pregnancy divided by elapsed years. Independent predictors of preeclampsia were past history of oligomenorrhea, WAR >0.8 kg/years, pre-pregnancy or 1st trimester triglyceridemia >150 mg/dL, and elevated acanthosis nigricans in the neck. In a multivariate logistic regression model, two or more predictors conferred an odds ratio of 15 (95%CI [5.9-37]; P < 0.001) to develop preeclampsia (85% specificity, 73% sensitivity, c-statistic of 81 ± 4%; P < 0.0001). Clinical markers related to insulin resistance and sedentary lifestyles are strong independent predictors of preeclampsia in mothers with 3rd trimester fetal losses or preterm deliveries due to placental insufficiency. Women at risk for preeclampsia in this particular population might benefit from measures focused on overcoming insulin resistance.

Chocolate Consumption in Pregnancy and Reduced Likelihood of Preeclampsia

PubMed Central

Triche, Elizabeth W.; Grosso, Laura M.; Belanger, Kathleen; Darefsky, Amy S.; Benowitz, Neal L.; Bracken, Michael B.

2009-01-01

Background Preeclampsia is a major pregnancy complication with cardiovascular manifestations. Recent studies suggest that chocolate consumption may benefit cardiovascular health. Methods We studied the association of chocolate consumption with risk of preeclampsia in a prospective cohort study of 2291 pregnant women who delivered a singleton livebirth between September 1996 and January 2000. Chocolate consumption was measured by self report in the first and third trimesters, and by umbilical cord serum concentrations of theobromine, the major methylxanthine component of chocolate. Preeclampsia was assessed by detailed medical record review for 1943 of the women. We derived adjusted odds ratios (aOR) and 95% confidence intervals (CIs) from logistic regression models controlling for potential confounders. Results Preeclampsia developed in 3.7% (n = 63) of 1681 women. Cord serum theobromine concentrations were negatively associated with preeclampsia (aOR = 0.31; CI = 0.11–0.87 for highest compared with lowest quartile). Self-reported chocolate consumption estimates also were inversely associated with preeclampsia. Compared with women consuming under 1 serving of chocolate weekly, women consuming 5+ servings per week had decreased risk: aOR = 0.81 with consumption in the first 3 months of pregnancy (CI = 0.37–1.79) and 0.60 in the last 3 months (0.30–1.24). Conclusions Our results suggest that chocolate consumption during pregnancy may lower risk of preeclampsia. However, reverse causality may also contribute to these findings. PMID:18379424

Chocolate consumption in pregnancy and reduced likelihood of preeclampsia.

PubMed

Triche, Elizabeth W; Grosso, Laura M; Belanger, Kathleen; Darefsky, Amy S; Benowitz, Neal L; Bracken, Michael B

2008-05-01

Preeclampsia is a major pregnancy complication with cardiovascular manifestations. Recent studies suggest that chocolate consumption may benefit cardiovascular health. We studied the association of chocolate consumption with risk of preeclampsia in a prospective cohort study of 2291 pregnant women who delivered a singleton livebirth between September 1996 and January 2000. Chocolate consumption was measured by self report in the first and third trimesters, and by umbilical cord serum concentrations of theobromine, the major methylxanthine component of chocolate. Preeclampsia was assessed by detailed medical record review for 1943 of the women. We derived adjusted odds ratios (aOR) and 95% confidence intervals (CIs) from logistic regression models controlling for potential confounders. Preeclampsia developed in 3.7% (n = 63) of 1681 women. Cord serum theobromine concentrations were negatively associated with preeclampsia (aOR = 0.31; CI = 0.11-0.87 for highest compared with lowest quartile). Self-reported chocolate consumption estimates also were inversely associated with preeclampsia. Compared with women consuming under 1 serving of chocolate weekly, women consuming 5+ servings per week had decreased risk: aOR = 0.81 with consumption in the first 3 months of pregnancy (CI = 0.37-1.79) and 0.60 in the last 3 months (0.30-1.24). Our results suggest that chocolate consumption during pregnancy may lower risk of preeclampsia. However, reverse causality may also contribute to these findings.

Strategy for standardization of preeclampsia research study design.

PubMed

Myatt, Leslie; Redman, Christopher W; Staff, Anne Cathrine; Hansson, Stefan; Wilson, Melissa L; Laivuori, Hannele; Poston, Lucilla; Roberts, James M

2014-06-01

Preeclampsia remains a major problem worldwide for mothers and babies. Despite intensive study, we have not been able to improve the management or early recognition of preeclampsia. At least part of this is because of failure to standardize the approach to studying this complex syndrome. It is possible that within the syndrome there may be different phenotypes with pathogenic pathways that differ between the subtypes. The capacity to recognize and to exploit different subtypes is of obvious importance for prediction, prevention, and treatment. We present a strategy for research to study preeclampsia, which will allow discrimination of such possible subtypes and also allow comparison and perhaps combinations of findings in different studies by standardized data and biosample collection. To make studies relevant to current clinical practice, the definition of preeclampsia can be that currently used and accepted. However, more importantly, sufficient data should be collected to allow other diagnostic criteria to be used and applied retrospectively. To that end, we present what we consider to be the minimum requirements for a data set in a study of preeclampsia that will facilitate comparisons. We also present a comprehensive or optimal data set for in-depth investigation of pathophysiology. As we approach the definition of phenotypes of preeclampsia by clinical and biochemical criteria, adherence to standardized protocols will hasten our understanding of the causes of preeclampsia and development of targeted treatment strategies.

The association between angiogenic markers and fetal sex: Implications for preeclampsia research.

PubMed

Andersen, L B; Jørgensen, J S; Herse, F; Andersen, M S; Christesen, H T; Dechend, R

2016-09-01

Current research suggests sexual dimorphism between the male and female fetoplacental units, but with unknown relevance for preeclampsia. We investigated the association between fetal sex and concentrations of the angiogenic markers soluble Fms-like kinase 1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in first and second-third trimester in women with/without preeclampsia, and the impact of fetal sex on the prognostic value of angiogenic markers for preeclampsia. Observational study in a prospective, population-based cohort of 2110 singleton pregnancies with 150 preeclampsia cases. Higher sFlt-1 concentrations were observed for women carrying female fetuses in first trimester (all, 1107.65 vs. 992.27pg/ml; preeclampsia cases, 1118.79 vs. 934.49pg/ml, p<0.05) and in second-third trimester (all, 1130.03 vs. 1043.15pg/ml; preeclampsia, 1480.30 vs. 1152.86pg/ml, p<0.05), with similar findings for the sFlt-1/PlGF ratio concentrations in first (29.67 vs. 27.39 p<0.05) and second-third trimester (3.56 vs. 3.22, p<0.05). In first trimester, log transformed concentrations of PlGF, sFlt-1 and sFlt-1/PlGF (all participants) and sFlt-1 (preeclampsia cases) associated with fetal sex in adjusted analyses (p<0.05). In second-third trimester, only log(sFlt-1) associated with fetal sex (all, p=0.028; preeclampsia, p=0.067) In receiver operating curve analysis, prediction of early-onset preeclampsia by sFlt-1/PlGF tended to be superior in pregnancies with female vs. male fetuses (p=0.06). Sexual dimorphism was observed for concentrations of angiogenic markers. Female fetal sex was associated to higher sFlt-1 and sFlt-1/PlGF ratio concentrations in both healthy pregnancies and women developing preeclampsia. Fetal sex should be considered in research and clinical use of angiogenic markers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cardiac diastolic function after recovery from pre-eclampsia.

PubMed

Soma-Pillay, P; Louw, M C; Adeyemo, A O; Makin, J; Pattinson, R C

Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks' gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11-10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

Translating research into maternal health care policy: a qualitative case study of the use of evidence in policies for the treatment of eclampsia and pre-eclampsia in South Africa

PubMed Central

Daniels, Karen; Lewin, Simon

2008-01-01

Background Few empirical studies of research utilisation have been conducted in low and middle income countries. This paper explores how research information, in particular findings from randomised controlled trials and systematic reviews, informed policy making and clinical guideline development for the use of magnesium sulphate in the treatment of eclampsia and pre-eclampsia in South Africa. Methods A qualitative case-study approach was used to examine the policy process. This included a literature review, a policy document review, a timeline of key events and the collection and analysis of 15 interviews with policy makers and academic clinicians involved in these policy processes and sampled using a purposive approach. The data was analysed thematically and explored theoretically through the literature on agenda setting and the policy making process. Results Prior to 1994 there was no national maternal care policy in South Africa. Consequently each tertiary level institution developed its own care guidelines and these recommended a range of approaches to the management of pre-eclampsia and eclampsia. The subsequent emergence of new national policies for maternal care, including for the treatment of pre-eclampsia and eclampsia, was informed by evidence from randomised controlled trials and systematic reviews. This outcome was influenced by a number of factors. The change to a democratic government in the mid 1990s, and the health reforms that followed, created opportunities for maternal health care policy development. The new government was open to academic involvement in policy making and recruited academics from local networks into key policy making positions in the National Department of Health. The local academic obstetric network, which placed high value on evidence-based practice, brought these values into the policy process and was also linked strongly to international evidence based medicine networks. Within this context of openness to policy development, local researchers acted as policy entrepreneurs, bringing attention to priority health issues, and to the use of research evidence in addressing these. This resulted in the new national maternity care guidelines being informed by evidence from randomised controlled trials and recommending explicitly the use of magnesium sulphate for the management of eclampsia. Conclusion Networks of researchers were important not only in using research information to shape policy but also in placing issues on the policy agenda. A policy context which created a window of opportunity for new research-informed policy development was also crucial. PMID:19091083

DNA Methylation as a Biomarker for Preeclampsia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.

Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-widemore » DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.« less

Interleukin-1 alpha variation is associated with the risk of developing preeclampsia.

PubMed

Ghasemi, Masoumeh; Kashani, Elham; Fayyaz, Azadeh; Attar, Marzieh; Shahbazi, Majid

2015-10-01

Preeclampsia is a syndrome that affects 5% of all pregnancies, producing substantial maternal and prenatal morbidity and mortality. Several studies have reported that cytokine genes are associated with the persistence of preeclampsia or the severity of the disease. The aim of this study is to investigate the relationships between the polymorphisms of interleukin-1 alpha-889 (IL-1A) gene and preeclampsia. Genomic DNA was extracted from the peripheral blood of 305 patients with preeclampsia and 325 normal controls from Sayyad Shirazi Hospital of Golestan University. Then subjected to SSP-PCR amplification. STATA software and the chi square test were used for statistic calculations. The frequencies of IL-1A -889 genotypes C/C, T/T and C/T in preeclampsia cases were 34.8%, 8.2%, 57% and in controls were 20.9%, 7.6% and 71.3% respectively. There was a significant 1.5 fold excess frequency in genotype C/C in cases (CI=1.44-3.07, OR=2.1, P=0.0001). There was a significant difference in the frequencies of alleles or genotypes in IL-1A promoter regions between patients with preeclampsia and the control group. Turkomans showed the highest frequency of the C allele and Sistanies had the lowest frequency of the C allele in preeclampsia compared to control groups (CI=1.5-3.9, OR=2.48, P=0.0001). Our findings suggest that the IL-1A-899C/C genotype and C allele are associated with susceptibility to preeclampsia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Morphological characteristics of kidneys connective tissue of mature fetuses and newborns from mothers, whose pregnancy was complicated by preeclampsia of varying degrees of severity].

PubMed

Sorokina, Iryna V; Myroshnychenko, Mykhailo S; Kapustnyk, Nataliia V; Khramova, Tetyana O; Dehtiarova, Oksana V; Danylchenko, Svitlana I

2018-01-01

Introduction: The kidneys connective tissue condition in the antenatal period affects the formation of tissues and it changes with the development of various general pathological processes in this organ. The aim of the study was to identify the morphological features of kidneys connective tissue of fetuses and newborns from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity. Materials and methods: The material of the study was the tissue of kidneys of mature fetuses and newborns from mothers with physiological pregnancy (28 cases), as well as from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity (78 cases). Immunohistochemical study was performed by an indirect Coons method according to M. Brosman's technique using monoclonal antibodies to collagen type I, III and IV. Results: The kidneys connective tissue of fetuses and newborns developing under the maternal preeclampsia conditions is characterized by the qualitative and quantitative changes that indicate the development of sclerotic processes in this organ, the severity of which increase with the age and with the increase of the maternal preeclampsia severity. Qualitative changes are characterized by an increase of the fibrous component, thickening of the bundles of connective tissue fibers, and a decrease in the distance between them. Quantitative changes are characterized by a pronounced predominance of collagen fibers over elastic fibers, almost total absence in some field of view elastic fibers and the violation of the content of collagen type I, III and IV. Conclusion: Maternal preeclampsia underlies the development of qualitative and quantitative changes in kidneys connective tissue of fetuses and newborns, which as a result will lead to disruption of the functions of these organs in such children.

Nanomedicine as a potential approach to empower the new strategies for the treatment of preeclampsia.

PubMed

Valero, Lucie; Alhareth, Khair; Gil, Sophie; Lecarpentier, Edouard; Tsatsaris, Vassilis; Mignet, Nathalie; Fournier, Thierry; Andrieux, Karine

2018-01-31

Preeclampsia is a serious pregnancy disorder characterized by the onset of high blood pressure and proteinuria. Although the understanding of the disease is increasing, it remains without treatment, other than the delivery of the baby and the placenta. This review sets out to discuss some new developments and strategies in the treatment of preeclampsia. We briefly review the current knowledge on the preeclamptic pathophysiology. We then examine the recent trends in preeclampsia treatment and, in particular, the tracks of potential therapeutic targets. Finally, we focus on the possibilities nanocarriers could offer in the management of preeclampsia. Indeed, nanocarriers could help to prevent transplacental passage and promote placental-specific drug delivery, thereby enhancing efficacy and improving safety. Tendencies are then drawn from the available studies on the optimal characteristics of a nanocarrier to deliver drugs to the placenta. Copyright © 2018 Elsevier Ltd. All rights reserved.

G protein-coupled receptor 30 regulates trophoblast invasion and its deficiency is associated with preeclampsia.

PubMed

Tong, Chao; Feng, Xiang; Chen, Jun; Qi, Xingchen; Zhou, Liyuan; Shi, Shuming; Kc, Kamana; Stanley, Joanna L; Baker, Philip N; Zhang, Hua

2016-04-01

Preeclampsia is known to be associated with reduced circulating levels of estrogen. The effects of estrogen in preeclampsia are normally mediated by the classical estrogen receptors. Intriguingly, a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), has been recently found to play an important role in several estrogenic effects. However, the mechanisms by which GPR30 may mediate the development of preeclampsia remain unknown. We observed that the expression of GPR30 in placental trophoblast cells is lower in preeclamptic placentas compared with normotensive controls. We then investigated the role of GPR30 in trophoblast cell invasion by utilizing placental explants and the immortalized human trophoblast cell line (HTR8/SVneo). The selective GPR30 agonist G1 and a general estrogen receptors agonist 17-β-estradiol (E2) both improved trophoblast cells invasion by upregulating MMP9 expression and the PI3K-Akt signaling pathway. This effect was abolished by a selective GPR30 inhibitor G15, implying that GPR30 may be involved in regulating trophoblast invasion, and that down-regulation of this receptor may result in the development of preeclampsia. The present study suggests that GPR30 is a critical regulator of trophoblast cell invasion, and as such may be a potential therapeutic interventional target for preeclampsia and other pregnancy complications resulting from impaired trophoblast invasion.

Human infectious diseases and risk of preeclampsia: an updated review of the literature.

PubMed

Nourollahpour Shiadeh, Malihe; Behboodi Moghadam, Zahra; Adam, Ishag; Saber, Vafa; Bagheri, Maryam; Rostami, Ali

2017-10-01

Preeclampsia (PE) is one of the major causes of maternal and perinatal morbidity and mortality, especially in low- and middle-income countries. In recent years, a growing body of literatures suggests that infections by bacteria, viruses, and parasites and their related inflammations play an important role in the pathogenesis of PE. We searched PubMed, Google scholar, and Cochrane databases using the following search words: "infection and preeclampsia," "bacterial infection and preeclampsia," "viral infection and preeclampsia" and "parasitic infection and preeclampsia." The literature review revealed that many bacteria including Helicobacter pylori, Chlamydia pneumonia, and those are involved in periodontal disease or urinary tract infections (UTIs) and some viral agents such as Cytomegalovirus, herpes simplex virus type-2, human immunodeficiency virus, and some parasites especially Plasmodium spp. and Toxoplasma gondii can be effective in development of PE. Inflammation responses against infections has major role in the inducement of PE. The shift of immunological cytokine profile of Th2 toward Th1 and high levels of pro-inflammatory cytokines (TNF-ɑ, IL-12, IFN-γ, etc.), increase of oxidative stress, increase of anti-angiogenic proteins, increase of vascular endothelial growth factor receptor 1 (sVEGFR1), and complement C5a are the main potential mechanisms related to infections and enhanced development of PE. Thus, early diagnosis and treatment of bacterial, viral, and parasitic infections could be an effective strategy to reduce the incidence of PE.

Alpha-1 Antitrypsin Prevents the Development of Preeclampsia Through Suppression of Oxidative Stress.

PubMed

Feng, Yaling; Xu, Jianjuan; Zhou, Qin; Wang, Rong; Liu, Nin; Wu, Yanqun; Yuan, Hua; Che, Haisha

2016-01-01

Preeclampsia (PE) and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT) played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS, and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

Late onset postpartum preeclampsia 3 months after delivery.

PubMed

Giwa, Al; Nguyen, Melissa

2017-10-01

Preeclampsia is defined by the American College of Obstetrics and Gynecology (ACOG) as "the occurrence of new onset hypertension plus new-onset proteinuria" [1]. Up-to-Date elaborates a little further on this by defining preeclampsia as "the new onset of hypertension and proteinuria, or hypertension and end-organ dysfunction with or without proteinuria, after 20 weeks of gestation in a previously normotensive woman. It may also develop postpartum. Severe hypertension or signs/symptoms of end-organ injury represent the severe end of the disease spectrum" [2] In 2013, the American College of Obstetricians and Gynecologists removed proteinuria as a key component in the diagnosis of preeclampsia. They also removed massive proteinuria (previously, 5 g/24 hours) and fetal growth restriction as possible features of severe disease. They found that were was a poor correlation in many outcomes between massive proteinuria and fetal growth restriction when managed similarly, with or without preeclampsia as a diagnosis. Oliguria was also removed as a characteristic of severe disease. [3] There have been several cases reported in the literature as well as by Obstetricians citing the incidence of preeclampsia occurring upwards of 6 to even 12 weeks postpartum. We hope to demonstrate what we believe to be a case of postpartum preeclampsia at 89 days postpartum. Published by Elsevier Inc.

Pre-eclampsia part 1: current understanding of its pathophysiology

PubMed Central

Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Yeo, Lami; Romero, Roberto

2018-01-01

Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation. In the absence of proteinuria, hypertension together with evidence of systemic disease (such as thrombocytopenia or elevated levels of liver transaminases) is required for diagnosis. This multisystemic disorder targets several organs, including the kidneys, liver and brain, and is a leading cause of maternal and perinatal morbidity and mortality. Glomeruloendotheliosis is considered to be a characteristic lesion of pre-eclampsia, but can also occur in healthy pregnant women. The placenta has an essential role in development of this disorder. Pathogenetic mechanisms implicated in pre-eclampsia include defective deep placentation, oxidative and endoplasmic reticulum stress, autoantibodies to type-1 angiotensin II receptor, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and the presence of an antiangiogenic state, among which an imbalance of angiogenesis has emerged as one of the most important factors. However, this imbalance is not specific to pre-eclampsia, as it also occurs in intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction (massive perivillous fibrin deposition). The severity and timing of the angiogenic imbalance, together with maternal susceptibility, might determine the clinical presentation of pre-eclampsia. This Review discusses the diagnosis, classification, clinical manifestations and putative pathogenetic mechanisms of pre-eclampsia. PMID:25003615

Variability and epistemic uncertainty in water ingestion rates and pharmacokinetic parameters, and impact on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population.

PubMed

Avanasi, Raghavendhran; Shin, Hyeong-Moo; Vieira, Veronica M; Bartell, Scott M

2016-04-01

We recently utilized a suite of environmental fate and transport models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations, and also assessed the association of those concentrations with preeclampsia for participants in the C8 Health Project (a cross-sectional study of over 69,000 people who were environmentally exposed to PFOA near a major U.S. fluoropolymer production facility located in West Virginia). However, the exposure estimates from this integrated model relied on default values for key independent exposure parameters including water ingestion rates, the serum PFOA half-life, and the volume of distribution for PFOA. The aim of the present study is to assess the impact of inter-individual variability and epistemic uncertainty in these parameters on the exposure estimates and subsequently, the epidemiological association between PFOA exposure and preeclampsia. We used Monte Carlo simulation to propagate inter-individual variability/epistemic uncertainty in the exposure assessment and reanalyzed the epidemiological association. Inter-individual variability in these parameters mildly impacted the serum PFOA concentration predictions (the lowest mean rank correlation between the estimated serum concentrations in our study and the original predicted serum concentrations was 0.95) and there was a negligible impact on the epidemiological association with preeclampsia (no change in the mean adjusted odds ratio (AOR) and the contribution of exposure uncertainty to the total uncertainty including sampling variability was 7%). However, when epistemic uncertainty was added along with the inter-individual variability, serum PFOA concentration predictions and their association with preeclampsia were moderately impacted (the mean AOR of preeclampsia occurrence was reduced from 1.12 to 1.09, and the contribution of exposure uncertainty to the total uncertainty was increased up to 33%). In conclusion, our study shows that the change of the rank exposure among the study participants due to variability and epistemic uncertainty in the independent exposure parameters was large enough to cause a 25% bias towards the null. This suggests that the true AOR of the association between PFOA and preeclampsia in this population might be higher than the originally reported AOR and has more uncertainty than indicated by the originally reported confidence interval. Copyright © 2016 Elsevier Inc. All rights reserved.

Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies.

PubMed

Davis, Esther F; Newton, Laura; Lewandowski, Adam J; Lazdam, Merzaka; Kelly, Brenda A; Kyriakou, Theodosios; Leeson, Paul

2012-07-01

Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2-5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu.

Effect of indoor air pollution from biomass and solid fuel combustion on symptoms of preeclampsia/eclampsia in Indian women.

PubMed

Agrawal, S; Yamamoto, S

2015-06-01

Available evidence concerning the association between indoor air pollution (IAP) from biomass and solid fuel combustion and preeclampsia/eclampsia is not available in developing countries. We investigated the association between exposure to IAP from biomass and solid fuel combustion and symptoms of preeclampsia/eclampsia in Indian women by analyzing cross-sectional data from India's third National Family Health Survey (NFHS-3, 2005-2006). Self-reported symptoms of preeclampsia/eclampsia during pregnancy such as convulsions (not from fever), swelling of legs, body or face, excessive fatigue or vision difficulty during daylight, were obtained from 39,657 women aged 15-49 years who had a live birth in the previous 5 years. Effects of exposure to cooking smoke, ascertained by type of fuel used for cooking on preeclampsia/eclampsia risk, were estimated using logistic regression after adjusting for various confounders. Results indicate that women living in households using biomass and solid fuels have two times higher likelihood of reporting preeclampsia/eclampsia symptoms than do those living in households using cleaner fuels (OR = 2.21; 95%: 1.26-3.87; P = 0.006), even after controlling for the effects of a number of potentially confounding factors. This study is the first to empirically estimate the associations of IAP from biomass and solid fuel combustion and reported symptoms suggestive of preeclampsia/eclampsia in a large nationally representative sample of Indian women and we observed increased risk. These findings have important program and policy implications for countries such as India, where large proportions of the population rely on polluting biomass fuels for cooking and space heating. More epidemiological research with detailed exposure assessments and clinical measures of preeclampsia/eclampsia is needed in a developing country setting to validate these findings. © 2014 The Authors. Indoor Air published by John Wiley & Sons Ltd.

Effect of Indoor air pollution from biomass and solid fuel combustion on symptoms of preeclampsia/eclampsia in Indian women

PubMed Central

Agrawal, S; Yamamoto, S

2015-01-01

Available evidence concerning the association between indoor air pollution (IAP) from biomass and solid fuel combustion and preeclampsia/eclampsia is not available in developing countries. We investigated the association between exposure to IAP from biomass and solid fuel combustion and symptoms of preeclampsia/eclampsia in Indian women by analyzing cross-sectional data from India's third National Family Health Survey (NFHS-3, 2005–2006). Self-reported symptoms of preeclampsia/eclampsia during pregnancy such as convulsions (not from fever), swelling of legs, body or face, excessive fatigue or vision difficulty during daylight, were obtained from 39 657 women aged 15–49 years who had a live birth in the previous 5 years. Effects of exposure to cooking smoke, ascertained by type of fuel used for cooking on preeclampsia/eclampsia risk, were estimated using logistic regression after adjusting for various confounders. Results indicate that women living in households using biomass and solid fuels have two times higher likelihood of reporting preeclampsia/eclampsia symptoms than do those living in households using cleaner fuels (OR = 2.21; 95%: 1.26–3.87; P = 0.006), even after controlling for the effects of a number of potentially confounding factors. This study is the first to empirically estimate the associations of IAP from biomass and solid fuel combustion and reported symptoms suggestive of preeclampsia/eclampsia in a large nationally representative sample of Indian women and we observed increased risk. These findings have important program and policy implications for countries such as India, where large proportions of the population rely on polluting biomass fuels for cooking and space heating. More epidemiological research with detailed exposure assessments and clinical measures of preeclampsia/eclampsia is needed in a developing country setting to validate these findings. PMID:25039812

The Norwegian preeclampsia family cohort study: a new resource for investigating genetic aspects and heritability of preeclampsia and related phenotypes.

PubMed

Roten, Linda Tømmerdal; Thomsen, Liv Cecilie Vestrheim; Gundersen, Astrid Solberg; Fenstad, Mona Høysæter; Odland, Maria Lisa; Strand, Kristin Melheim; Solberg, Per; Tappert, Christian; Araya, Elisabeth; Bærheim, Gunhild; Lyslo, Ingvill; Tollaksen, Kjersti; Bjørge, Line; Austgulen, Rigmor

2015-12-01

Preeclampsia is a major pregnancy complication without curative treatment available. A Norwegian Preeclampsia Family Cohort was established to provide a new resource for genetic and molecular studies aiming to improve the understanding of the complex pathophysiology of preeclampsia. Participants were recruited from five Norwegian hospitals after diagnoses of preeclampsia registered in the Medical birth registry of Norway were verified according to the study's inclusion criteria. Detailed obstetric information and information on personal and family disease history focusing on cardiovascular health was collected. At attendance anthropometric measurements were registered and blood samples were drawn. The software package SPSS 19.0 for Windows was used to compute descriptive statistics such as mean and SD. P-values were computed based on t-test statistics for normally distributed variables. Nonparametrical methods (chi square) were used for categorical variables. A cohort consisting of 496 participants (355 females and 141 males) representing 137 families with increased occurrence of preeclampsia has been established, and blood samples are available for 477 participants. Descriptive analyses showed that about 60% of the index women's pregnancies with birth data registered were preeclamptic according to modern diagnosis criteria. We also found that about 41% of the index women experienced more than one preeclamptic pregnancy. In addition, the descriptive analyses confirmed that preeclamptic pregnancies are more often accompanied with delivery complications. The data and biological samples collected in this Norwegian Preeclampsia Family Cohort will provide an important basis for future research. Identification of preeclampsia susceptibility genes and new biomarkers may contribute to more efficient strategies to identify mothers "at risk" and contribute to development of novel preventative therapies.

MMP-8 C-799T and MMP-8 C+17G polymorphisms in mild and severe preeclampsia: Association between MMP-8 C-799T with susceptibility to severe preeclampsia.

PubMed

Rahimi, Ziba; Zangeneh, Maryam; Rezaeyan, Arezoo; Shakiba, Ebrahim; Rahimi, Zohreh

2018-01-01

The aim of present study was to determine the role of matrix metalloproteinase-8 (MMP-8) C-799T (rs11225395) and C+17 (rs2155052) polymorphisms in susceptibility to preeclampsia. In a case-control study, 256 pregnant women including 152 women with preeclampsia (86 women with mild preeclampsia and 66 women with severe preeclampsia) and 104 women with normal pregnancy from Western Iran with Kurdish ethnic background were investigated for MMP-8 C-799T and C + 17G polymorphisms using polymerase chain reaction-restriction fragment length polymorphism method. Comparing the MMP-8 TT genotype with the combined genotype of CC+CT (recessive model) indicated a significantly higher frequency of the MMP-8 TT genotype (47%) in severe preeclamptic patients than that in healthy pregnant women (30.8%) that was associated with 1.99-fold increased risk of severe preeclampsia (95% CI = 1.05-3.77, p = 0.034). The frequency of MMP-8 G allele was 27.3% in all preeclamptic patients compared to 30.2% in controls (p = 0.56). Also, no significant difference was detected comparing the frequency of G allele in mild (26.6%, p = 0.46) and severe preeclamptic patients (28.4%, p = 0.75) with controls (30.2%). Our study demonstrated that the MMP-8 C-799T is associated with the risk of developing severe preeclampsia during pregnancy. However, the MMP-8 C + 17G polymorphism might not be a risk factor for susceptibility to preeclampsia.

The Risk of Preeclampsia According to High Thyroid Function in Pregnancy Differs by hCG Concentration.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

2016-12-01

During pregnancy, there is an increased demand for thyroid hormone. The pregnancy hormone human chorionic gonadotropin (hCG) is an important physiological stimulator of thyroid function. Already high-normal maternal free T 4 concentrations are associated with a higher risk of preeclampsia. The objective of the investigation was to study our hypothesis that hCG concentrations can distinguish a physiological form of high thyroid function from a more pathological form of high thyroid function and that the risk of preeclampsia would differ accordingly. TSH, free T 4 , hCG, or thyroperoxidase antibody concentrations were determined in pregnant women participating in a population-based prospective cohort study. The study was conducted in the general community. A nonselected sample of 5146 pregnant women participated in the study. There were no interventions. Preeclampsia was measured. Women with high hCG-associated high thyroid function did not have a higher risk of preeclampsia than women with normal thyroid function. In contrast, women with low hCG and high thyroid function had a 3.4- to 11.1-fold higher risk of preeclampsia. These risk estimates were amplified in women with a high body mass index. Women with a low hCG and suppressed TSH (<0.10 mU/L) had a 3.2- to 8.9-fold higher risk of preeclampsia. hCG was not associated with preeclampsia, and results remained similar after exclusion of thyroperoxidase antibody-positive women. This study suggests that, in contrast to women with a high hCG associated high thyroid function, women with low hCG and high thyroid function during pregnancy are at a higher risk of developing preeclampsia. The additional measurement of hCG may therefore help to distinguish a more pathological form of high thyroid function and women at a high risk of preeclampsia.

Preeclampsia is associated with increased ambulatory arterial stiffness index in type 1 diabetes mellitus.

PubMed

Al-Far, Hanine F M; Tjessem, Ingvild H; Fuglsang, Jens; Lauszus, Finn F

2017-09-01

Treatment of mild to moderate hypertension might not benefit maternal or fetal outcome. This pessimistic point of view may have come about by using non-validated methods for measuring blood pressure in pregnancy combined with inadequate methodology for diagnosis, treatment, and monitoring effects. To determine the association between AASI in women with type 1 diabetes mellitus (T1DM) and preeclampsia, and to assess the ability of AASI to diagnose preeclampsia. Repeated 24-h ambulatory blood pressure recordings were performed three times during pregnancy and once three months postpartum in 151 women with T1DM and 50 control women without diabetes. Circadian rhythm was evaluated as the night day ratio, night blood pressure divided by day blood pressure. Of the T1DM women, 33 developed preeclampsia, which was associated with AASI in the 3rd trimester (p<0.05). The best predictor of preeclampsia in T1DM was an AASI of 0.35. The diurnal blood pressure was significantly higher in all trimesters in women who later had preeclampsia. A flattened circadian rhythm was present in T1DM women with preeclampsia compared to women without preeclampsia (night-day ratio: systole 2nd trimester: 0.94±0.07 vs. 0.91±0.05, women with and without preeclampsia, respectively, p=0.015; diastole 2nd trimester: 0.89±0.07 vs. 0.85±0.07, p=0.003). AASI was higher during pregnancy compared to postpartum in women with T1DM (0.31±0.16, 0.31±0.16 and 0.33±0.18 vs. 0.25±0.17; 1st, 2nd and 3rd trimester vs. postpartum). Women with T1DM and preeclampsia demonstrate increased arterial stiffness and had early manifestations in the non-dipping of blood pressure. Copyright © 2017 Elsevier B.V. All rights reserved.

First trimester serum afamin concentrations are associated with the development of pre-eclampsia and gestational diabetes mellitus in pregnant women.

PubMed

Tramontana, Allessandra; Dieplinger, Benjamin; Stangl, Gerhard; Hafner, Erich; Dieplinger, Hans

2018-01-01

Aim of this study was to assess the prognostic capability of afamin to predict pregnancy complications. First-trimester screening was consecutively performed in 4948 pregnant women, of whom 474 women developed pregnancy complications [gestational hypertension (n=84), pre-eclampsia (n=30), intrauterine growth restriction (n=107), preterm birth (n=44), and gestational diabetes mellitus (n=209)]. To each woman with pregnancy complications an uncomplicated pregnancy was matched for body mass index. Afamin serum concentrations were measured in 948 pregnant women at the first-trimester screening. Median afamin concentrations were significantly higher in women developing pre-eclampsia or gestational diabetes mellitus when compared to women with uncomplicated pregnancies (76mg/L vs. 65mg/L, p=0.001 and 80mg/L vs. 69mg/L, p<0.001). There was no difference in median afamin values between all other pregnancy complications and their matched controls. Increased afamin (i.e. >65mg/L) was a strong and independent predictor for the development of pre-eclampsia (risk ratio, 24.58; 95%CI, 2.82-214.12; p=0.004) as well as gestational diabetes mellitus (risk ratio, 2.07; 95%CI, 1.33-3.22; p=0.001). In this large nested case-control study increased afamin concentrations were a strong and independent predictor for pre-eclampsia and gestational diabetes mellitus, suggesting a potential role of afamin as predictive marker for pregnancy-related metabolic disorders. Copyright © 2017. Published by Elsevier B.V.

First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia.

PubMed

Saxena, Aditi R; Seely, Ellen W; Rich-Edwards, Janet W; Wilkins-Haug, Louise E; Karumanchi, S Ananth; McElrath, Thomas F

2013-04-04

First trimester Pregnancy Associated Plasma Protein A (PAPP-A) levels, routinely measured for aneuploidy screening, may predict development of preeclampsia. This study tests the hypothesis that first trimester PAPP-A levels correlate with soluble fms-like tyrosine kinase-1 (sFlt-1) levels, an angiogenic marker associated with preeclampsia, throughout pregnancy. sFlt-1 levels were measured longitudinally in 427 women with singleton pregnancies in all three trimesters. First trimester PAPP-A and PAPP-A Multiples of Median (MOM) were measured. Student's T and Wilcoxon tests compared preeclamptic and normal pregnancies. A linear mixed model assessed the relationship between log PAPP-A and serial log sFlt-1 levels. PAPP-A and PAPP-A MOM levels were significantly lower in preeclamptic (n = 19), versus normal pregnancies (p = 0.02). Although mean third trimester sFlt-1 levels were significantly higher in preeclampsia (p = 0.002), first trimester sFlt-1 levels were lower in women who developed preeclampsia, compared with normal pregnancies (p = 0.03). PAPP-A levels correlated significantly with serial sFlt-1 levels. Importantly, low first trimester PAPP-A MOM predicted decreased odds of normal pregnancy (OR 0.2, p = 0.002). Low first trimester PAPP-A levels suggests increased future risk of preeclampsia and correlate with serial sFlt-1 levels throughout pregnancy. Furthermore, low first trimester PAPP-A status significantly predicted decreased odds of normal pregnancy.

Gestational diabetes, preeclampsia and cytokine release: similarities and differences in endothelial cell function.

PubMed

Rao, Rashmi; Sen, Suvajit; Han, Bing; Ramadoss, Sivakumar; Chaudhuri, Gautam

2014-01-01

Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy affects the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. Similarly, some but not all studies have suggested that infection of the mother under certain circumstances can also lead to preeclampsia as women with either a bacterial or viral infection were at a higher risk of developing preeclampsia, compared to women without infection and infection also leads to a release in TNFα. Endothelial cells exposed to either high glucose or TNFα leads to an increase in the production of H2O2 and to a decrease in endothelial cell proliferation. The cellular and molecular mechanisms involved in this phenomenon are discussed.Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy has profound effects on the fetus and long term effects on the neonate. All three conditions affect the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. It has also been suggested although not universally accepted that under certain circumstances maternal infection may also predispose to pre-eclampsia. Pre-eclampsia is also associated with the release of TNFα and endothelial dysfunction. However, the cellular and molecular mechanism(s) leading to the endothelial dysfunction by either hyperglycemia or by the cytokine TNFα appear to be different. In this chapter, we explore some of the similarities and differences leading to endothelial dysfunction by both hyperglycemia and by the inflammatory cytokine TNFα and the cellular and molecular mechanism(s) involved.

[Relations between hypertensive disorders in pregnancy and subsequent risk of early-term birth: a birth cohort study].

PubMed

Li, F Y; Yan, S Q; Huang, K; Mao, L J; Pan, W J; Ge, X; Han, Y; Hao, J H; Tao, F B

2017-12-10

Objective: To evaluate the relations between hypertensive disorders (HDP) in pregnancy and early-term birth. Methods: A total of 3 474 pregnant women were consecutively recruited. Demographic information was collected in early pregnancy. HDP was diagnosed in the first, second and third trimesters, respectively. On the basis of precise evaluation on gestation age, early-term birth was defined as gestational age of 37-38 weeks+6 days. Logistic regression models were conducted to examine the associations between HDP and early-term birth. Results: The current study included 3 260 pregnant women, with the rates of HDP, pregnancy-induced hypertension syndrome and pre-eclampsia as 6.0% ( n =194), 4.2% ( n =137) and 1.8% ( n =57), respectively. After controlling for potential confounders, no significant differences between pregnancy-induced hypertension syndrome and earlyterm birth ( OR =1.49, 95% CI : 0.94-2.36) were found. Pre-eclampsia appeared to have increased the risk of early-term birth ( OR =4.46, 95% CI : 2.09-9.54). Conclusion: Pre-eclampsia could significantly increase the risk of early-term birth. This finding suggested that early detection and intervention programs were helpful in reducing the risk of early-term birth.

Hypertensive disorders during pregnancy and risk of type 2 diabetes in later life: a systematic review and meta-analysis.

PubMed

Wang, Zengfang; Wang, Zengyan; Wang, Luang; Qiu, Mingyue; Wang, Yangang; Hou, Xu; Guo, Zhong; Wang, Bin

2017-03-01

Many studies assessed the association between hypertensive disorders during pregnancy and risk of type 2 diabetes mellitus in later life, but contradictory findings were reported. A systemic review and meta-analysis was carried out to elucidate type 2 diabetes mellitus risk in women with hypertensive disorders during pregnancy. Pubmed, Embase, and Web of Science were searched for cohort or case-control studies on the association between hypertensive disorders during pregnancy and subsequent type 2 diabetes mellitus. Random-effect model was used to pool risk estimates. Bayesian meta-analysis was carried out to further estimate the type 2 diabetes mellitus risk associated with hypertensive disorders during pregnancy. Seventeen cohort or prospective matched case-control studies were finally included. Those 17 studies involved 2,984,634 women and 46,732 type 2 diabetes mellitus cases. Overall, hypertensive disorders during pregnancy were significantly correlated with type 2 diabetes mellitus risk (relative risk = 1.56, 95 % confidence interval 1.21-2.01, P = 0.001). Preeclampsia was significantly and independently correlated with type 2 diabetes mellitus risk (relative risk = 2.25, 95 % confidence interval 1.73-2.90, P < 0.001). In addition, gestational hypertension was also significantly and independently correlated with subsequent type 2 diabetes mellitus risk (relative risk = 2.06, 95 % confidence interval 1.57-2.69, P < 0.001). The pooled estimates were not significantly altered in the subgroup analyses of studies on preeclampsia or gestational hypertension. Bayesian meta-analysis showed the relative risks of type 2 diabetes mellitus risk for individuals with hypertensive disorders during pregnancy, preeclampsia, and gestational hypertension were 1.59 (95 % credibility interval: 1.11-2.32), 2.27 (95 % credibility interval: 1.67-2.97), and 2.06 (95 % credibility interval: 1.41-2.84), respectively. Publication bias was not evident in the meta-analysis. Preeclampsia and gestational hypertension are independently associated with substantially elevated risk of type 2 diabetes mellitus in later life.

Associations of personal and family preeclampsia history with the risk of early-, intermediate- and late-onset preeclampsia.

PubMed

Boyd, Heather A; Tahir, Hassaan; Wohlfahrt, Jan; Melbye, Mads

2013-12-01

Preeclampsia encompasses multiple conditions of varying severity. We examined the recurrence and familial aggregation of preeclampsia by timing of onset, which is a marker for severity. We ascertained personal and family histories of preeclampsia for women who delivered live singletons in Denmark in 1978-2008 (almost 1.4 million pregnancies). Using log-linear binomial regression, we estimated risk ratios for the associations between personal and family histories of preeclampsia and the risk of early-onset (before 34 weeks of gestation, which is typically the most severe), intermediate-onset (at 34-36 weeks of gestation), and late-onset (after 36 weeks of gestation) preeclampsia. Previous early-, intermediate-, or late-onset preeclampsia increased the risk of recurrent preeclampsia with the same timing of onset 25.2 times (95% confidence interval (CI): 21.8, 29.1), 19.7 times (95% CI: 17.0, 22.8), and 10.3 times (95% CI: 9.85, 10.9), respectively, compared with having no such history. Preeclampsia in a woman's family was associated with a 24%-163% increase in preeclampsia risk, with the strongest associations for early- and intermediate-onset preeclampsia in female relatives. Preeclampsia in the man's family did not affect a woman's risk of early-onset preeclampsia and was only weakly associated with her risks of intermediate- and late-onset preeclampsia. Early-onset preeclampsia appears to have the largest genetic component, whereas environmental factors likely contribute most to late-onset preeclampsia. The role of paternal genes in the etiology of preeclampsia appears to be limited.

Serum Fatty Acid Binding Protein 4 (FABP4) Predicts Pre-eclampsia in Women With Type 1 Diabetes.

PubMed

Wotherspoon, Amy C; Young, Ian S; McCance, David R; Patterson, Chris C; Maresh, Michael J A; Pearson, Donald W M; Walker, James D; Holmes, Valerie A

2016-10-01

To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes. Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeks' gestation, respectively). FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6-21.4] vs. 12.7 ng/mL [interquartile range 9.6-17]; P < 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6-25.8] vs. 14.6 ng/mL [interquartile range 10.8-19.7]; P < 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24-6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester. Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes. © 2016 by the American Diabetes Association.

Inventory of Novel Animal Models Addressing Etiology of Preeclampsia in the Development of New Therapeutic/Intervention Opportunities.

PubMed

Erlandsson, Lena; Nääv, Åsa; Hennessy, Annemarie; Vaiman, Daniel; Gram, Magnus; Åkerström, Bo; Hansson, Stefan R

2016-03-01

Preeclampsia is a pregnancy-related disease afflicting 3-7% of pregnancies worldwide and leads to maternal and infant morbidity and mortality. The disease is of placental origin and is commonly described as a disease of two stages. A variety of preeclampsia animal models have been proposed, but all of them have limitations in fully recapitulating the human disease. Based on the research question at hand, different or multiple models might be suitable. Multiple animal models in combination with in vitro or ex vivo studies on human placenta together offer a synergistic platform to further our understanding of the etiology of preeclampsia and potential therapeutic interventions. The described animal models of preeclampsia divide into four categories (i) spontaneous, (ii) surgically induced, (iii) pharmacologically/substance induced, and (iv) transgenic. This review aims at providing an inventory of novel models addressing etiology of the disease and or therapeutic/intervention opportunities. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Global Methylation in the Placenta and Umbilical Cord Blood From Pregnancies With Maternal Gestational Diabetes, Preeclampsia, and Obesity

PubMed Central

Lambertini, Luca; Rialdi, Alexander; Lee, MenJean; Mystal, Elana Ying; Grabie, Mordy; Manaster, Isaac; Huynh, Nancy; Finik, Jackie; Davey, Mia; Davey, Kei; Ly, Jenny; Stone, Joanne; Loudon, Holly; Eglinton, Gary; Hurd, Yasmin; Newcorn, Jeffrey H.; Chen, Jia

2014-01-01

Emerging evidence indicates that maternal medical risk during pregnancy, such as gestational diabetes mellitus (GDM), preeclampsia, and obesity, predisposes the offspring to suboptimal development. However, the underlying biological/epigenetic mechanism in utero is still unknown. The current pilot study (N = 50) compared the levels of global methylation in the placenta and umbilical cord blood among women with and without each risk condition (GDM, preeclampsia, and obesity) and explored whether the levels of global methylation were associated with fetal/infant growth. Results show that global methylation levels in the placenta were lower in patients with gestational diabetes (P = .003) and preeclampsia (P = .05) but higher with obesity (P = .01). Suggestive negative associations were found between global methylation level in the placenta and infant body length and head circumference. While preliminary, it is possible that the placenta tissue, but not umbilical cord blood, may be epigenetically programmed by maternal GDM, preeclampsia, and obesity to carry out its own specific functions that influence fetal growth. PMID:23765376

Association study between GSTT1 and GSTM1 polymorphisms and risk of preeclampsia in Chinese population.

PubMed

Guan, Linbo; Fan, Ping; Liu, Xinghui; Liu, Rui; Chen, Yihong; Ye, Liyan; Chen, Jinxin; Zhu, Yue; Liu, Yu; Bai, Huai

2016-09-01

Preeclampsia is a pregnancy-specific disorder associated with oxidative stress. The glutathione S-transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1) have previously been reported. The aim of this study was to investigate the association of GST gene polymorphisms with the risk of preeclampsia in Chinese subjects. The case-control population consists of 525 subjects. The genotyping of the GSTT1 and GSTM1 polymorphisms was carried out on genomic DNA using the multiplex polymerase chain reaction (PCR). We calculated odds ratios (ORs), adjusted for the confounding variables, to estimate the association between gene polymorphisms and preeclampsia. The GSTT1 null genotype was found to be protective from the development of preeclampsia (odds ratios 0.645, 95% confidence interval 0.421-0.989; P=0.044). Further analysis showed that a combination of deletion genotypes of the GSTT1 and GSTM1 genes conferred an even lower risk of preeclampsia (OR=0.470, 95%CI=0.255-0.866; P=0.015). There is no relationship between the GSTT1 and GSTM1 gene polymorphisms and blood pressure levels in pregnant women with and without preeclampsia. Our data suggest that a GSTT1 null polymorphism might be associated with decreased risk for preeclampsia in the Chinese population, and that this risk decreases with the combination of both GSTT1 and GSTM1 null polymorphisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Estimating rate of insulin resistance in patients with preeclampsia using HOMA-IR index and comparison with nonpreeclampsia pregnant women.

PubMed

Abhari, Farideh Rezaei; Ghanbari Andarieh, Maryam; Farokhfar, Asadollah; Ahmady, Soleiman

2014-01-01

Women with preeclampsia, independent of obesity and glucose intolerance, exhibit insulin resistance during pregnancy. The purpose of the present study is to determine whether early diagnosis of insulin resistance during pregnancy can predict preeclampsia. Through a case-control study, 675 pregnant women were selected and their first trimester blood was taken. Their fasting blood glucose and insulin were also measured after diagnosis of preeclampsia by 20 weeks of pregnancy. Based on the experiments conducted on 675 women who were 20 weeks past their pregnancy, 375 cases with preeclampsia were selected and assigned to the case group. 35 other pregnant women were put in the control group. Diagnosis criteria for the participants included blood pressure above 140/90 and proteinuria above 300 mg or above +1. Both groups were matched according to age, parity, gestational age, and BMI. Homa-Irand rate of insulin resistance was calculated by HOMA-IR and patients were followed up. Homeostatic model assessments (HOMA-IR) revealed that the average insulin resistance increased during pregnancy among both the case and control groups. There was a significant difference between insulin resistance of these two groups in both first trimester and third trimester and after developing preeclampsia (P < 0.001, P = 0.021). Insulin-resistance of the group with preeclampsia was higher in first trimester prior to diagnosis as well as the third trimester after diagnosis compared to natural pregnancy under similar conditions. Measurement of insulin resistance in first trimester may be useful in predicting the risk of preeclampsia.

Novel cardiovascular biomarkers in women with a history of early preeclampsia.

PubMed

Drost, José T; Maas, Angela H E M; Holewijn, Suzanne; Joosten, Leo A B; van Eyck, Jim; van der Schouw, Yvonne T; de Graaf, Jacqueline

2014-11-01

Women with a history of preeclampsia are at increased risk for future cardiovascular disease. Determination of cardiovascular biomarkers may be useful to understand the pathophysiological mechanism of cardiovascular disease development in these women. We performed an analysis in the Preeclampsia Risk EValuation in FEMales study, a retrospective cohort consisting of 339 women with a history of early preeclampsia and 332 women after normotensive pregnancy. Women attended a follow-up visit ten years after the index pregnancy. A subset of 8 different cardiovascular biomarkers was investigated, reflecting inflammatory, metabolic, thrombotic and endothelial function markers. Associations between PE and these novel biomarkers were analyzed by linear regression analysis and adjusted for traditional cardiovascular risk factors. Mean age of 671 women of the PREVFEM cohort was 39 years and women were on average 10 years post index pregnancy. Women post preeclampsia had significantly higher levels of SE-selectin (adjusted difference 4.55, 99%CI 0.37; 8.74) and PAPPA (adjusted difference 19.08; 99%CI 13.18; 24.99), whereas ApoB (adjusted difference -0.23 99%CI -0.32; -0.14) was inversely associated with preeclampsia, compared to women with a previous normotensive pregnancy. Adiponectin, leptin, sICAM-1, sVCAM-1 and PAI-1 were not different between both groups. We demonstrated an independent association of preeclampsia with SE-selectin and PAPPA (markers of vascular dysfunction), which may contribute to future cardiovascular events in women post preeclampsia. However, ApoB (an apolipoprotein) was significantly lower and could point at a protective mechanism in our PE study women. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe and Early-Onset Preeclampsia.

PubMed

Kaartokallio, Tea; Utge, Siddheshwar; Klemetti, Miira M; Paananen, Jussi; Pulkki, Kari; Romppanen, Jarkko; Tikkanen, Ilkka; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Lakkisto, Päivi; Laivuori, Hannele

2018-01-01

Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1 ) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine-thymine (GT n ) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother's preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GT n repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GT n repeat may increase mother's risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes. © 2017 American Heart Association, Inc.

Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies

PubMed Central

Davis, Esther F.; Newton, Laura; Lewandowski, Adam J.; Lazdam, Merzaka; Kelly, Brenda A.; Kyriakou, Theodosios; Leeson, Paul

2012-01-01

Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2–5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu. PMID:22455350

Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation.

PubMed

O'Gorman, Neil; Wright, David; Syngelaki, Argyro; Akolekar, Ranjit; Wright, Alan; Poon, Leona C; Nicolaides, Kypros H

2016-01-01

Preeclampsia affects approximately 3% of all pregnancies and is a major cause of maternal and perinatal morbidity and death. In the last decade, extensive research has been devoted to early screening for preeclampsia with the aim of reducing the prevalence of the disease through pharmacologic intervention in the high-risk group starting from the first trimester of pregnancy. The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history (maternal factors) and biomarkers. The data for this study were derived from prospective screening for adverse obstetric outcomes in women who attended for their routine first hospital visit at 11-13 weeks gestation in 2 maternity hospitals in England. We screened 35,948 singleton pregnancies that included 1058 pregnancies (2.9%) that experienced preeclampsia. Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A, and placental growth factor multiple of the median values. Five-fold cross validation was used to assess the performance of screening for preeclampsia that delivered at <37 weeks gestation (preterm-preeclampsia) and ≥37 weeks gestation (term-preeclampsia) by models that combined maternal factors with individual biomarkers and their combination with screening by maternal factors alone. In pregnancies that experienced preeclampsia, the values of uterine artery pulsatility index and mean arterial pressure were increased, and the values of serum pregnancy-associated plasma protein-A and placental growth factor were decreased. For all biomarkers, the deviation from normal was greater for early than late preeclampsia; therefore, the performance of screening was related inversely to the gestational age at which delivery became necessary for maternal and/or fetal indications. Combined screening by maternal factors, uterine artery pulsatility index, mean arterial pressure, and placental growth factor predicted 75% (95% confidence interval, 70-80%) of preterm-preeclampsia and 47% (95% confidence interval, 44-51%) of term-preeclampsia, at a false-positive rate of 10%; inclusion of pregnancy-associated plasma protein-A did not improve the performance of screening. Such detection rates are superior to the respective values of 49% (95% confidence interval, 43-55%) and 38% (34-41%) that were achieved by screening with maternal factors alone. Combination of maternal factors and biomarkers provides effective first-trimester screening for preterm-preeclampsia. Copyright © 2016. Published by Elsevier Inc.

Diet and Pre-eclampsia: A Prospective Multicentre Case-Control Study in Ethiopia.

PubMed

Endeshaw, Mulualem; Abebe, Fantu; Bedimo, Melkamu; Asart, Anemaw

2015-06-01

Pre-eclampsia is one of the most commonly encountered hypertensive disorders of pregnancy that accounts for 20-80% of maternal mortality in developing countries, including Ethiopia. For many years, diet has been suggested to play a role in pre-eclampsia. However, the hypotheses have been diverse with inconsistent results across studies, and this has not been studied in Ethiopia. The objective of this study was to determine the effect of dietary habits on the incidence of pre-eclampsia in Bahir Dar, Ethiopia A prospective multicentre unmatched case-control study was conducted among 453 (151 cases and 302 controls) pregnant women attending antepartum or intrapartum care in public health facilities of Bahir Dar City from June to September 2014. The interviewer conducted a face-to-face interview, measured the mid-upper arm circumference (MUAC) and collected the mid-pregnancy haemoglobin level from clinical notes using a standardized and pretested questionnaire. Epi Info 3.5.3 was used for data entry and cleaning, while IBM SPSS Statistics 20 was used for data analysis. Backward stepwise unconditional logistic regression analysis was employed to determine the strength of association of predictive variables with the outcome variable and to control for the effect of confounding variables. A P-value ≤0.05 was considered statistically significant. For every 1-cm increase of MUAC, there was an increase in the incidence rate of pre-eclampsia by a factor of 1.35 (adjusted odds ratio (AOR)=1.35, 95% confidence interval (CI): 1.21, 1.51). A higher incidence of pre-eclampsia was found in women who reported to have consumed coffee daily during pregnancy (AOR=1.78, 95% CI: 1.20, 3.05). Similarly, for women who had anaemia during the first trimester, the incidence of pre-eclampsia was 2.5 times higher than their counterparts (AOR=2.47, 95% CI: 1.12, 7.61). This study also revealed consumption of fruit or vegetables at least three times a week during pregnancy to be protective against pre-eclampsia (AOR=0.51, 95% CI: 0.29, 0.91; AOR=0.46, 95% CI: 0.24, 0.90, respectively). In addition, compliance with folate intake during pregnancy has shown a significant independent effect on the prevention of pre-eclampsia in this study (AOR=0.16, 95% CI: 0.08, 0.29). Adequate vegetable and fruit consumption and compliance with folate intake during pregnancy are independent protective factors against pre-eclampsia. On the other hand, higher MUAC, anaemia and daily coffee intake during pregnancy are risk factors for the development of pre-eclampsia. Audience-specific education and promotion of the use of the protective factors identified in this study should be prioritized. The risk factors identified can be used for prediction and early diagnoses of pre-eclampsia allowing timely interventions to be performed to minimize deaths associated with severe pre-eclampsia/eclampsia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Finding NEMO in preeclampsia.

PubMed

Sakowicz, Agata; Hejduk, Paulina; Pietrucha, Tadeusz; Nowakowska, Magdalena; Płuciennik, Elżbieta; Pospiech, Karolina; Gach, Agnieszka; Rybak-Krzyszkowska, Magda; Sakowicz, Bartosz; Kaminski, Marek; Krasomski, Grzegorz; Biesiada, Lidia

2016-04-01

The mechanism of preeclampsia and its way of inheritance are still a mystery. Biochemical and immunochemical studies reveal a substantial increase in tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 concentrations in the blood of women with preeclampsia. The level of these factors is regulated by nuclear facxtor-kappa B, whose activation in a classical pathway requires inhibitory kappa B kinase gamma (known as NEMO or IKBKG). Moreover, NEMO can schedule between cytoplasma and the nucleus. In the nucleus, IKBKG interacts with other proteins, and thus, it is implicated in the regulation of different gene expressions, which are related to cell cycle progression, proliferation, differentiation, and apoptosis. This is the first study investigating the association between the level of NEMO gene expression and the presence of preeclampsia. We tested the hypothesis that the simultaneous increase in NEMO gene expression both in the mother and her fetus may be responsible for the preeclampsia development. Moreover, the relationships between clinical risk factors of preeclampsia and the levels of NEMO gene expression in blood, umbilical cord blood, and placentas were investigated. A total of 91 women (43 preeclamptic women and 48 controls) and their children were examined. Real-time reverse transcription-polymerase chain reaction was used to assess the amount total NEMO messenger ribonucleic acid (mRNA) content and the mRNA level of each NEMO transcript from exons 1A, 1B, and 1C in maternal blood, umbilical cord blood, and placentas. Univariate analyses and correlation tests were performed to examine the association between NEMO gene expression and preeclampsia. Newborn weight and height, maternal platelet number, and gestational age (week of delivery) were lower in the group of women with preeclampsia than controls. NEMO gene expression level was found to be almost 7 times higher in the group of women with preeclampsia than healthy controls. The correlation analysis found that a simultaneous increase in the expression level of total NEMO mRNA in maternal blood and the mRNA for total NEMO (Rs = 0.311, P < .05), transcripts 1A (Rs = 0.463, P < .01), 1B (Rs = 0.454, P < .01), and 1C (Rs = 0.563, P < .001) in fetal blood was observed in preeclamptic pregnancies. In addition, the mRNA levels for total NEMO and transcripts 1A, 1B, and 1C were lower in placentas derived from pregnancies complicated by preeclampsia. Simultaneous increase of NEMO gene expression in maternal and fetal blood seems to be relevant for preeclampsia development. The results of our study also suggest that a decreased NEMO gene expression level in preeclamptic placentas may be the main reason for their intensified apoptosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Association of Maternal Preeclampsia With Infant Risk of Premature Birth and Retinopathy of Prematurity.

PubMed

Shulman, Julia P; Weng, Cindy; Wilkes, Jacob; Greene, Tom; Hartnett, M Elizabeth

2017-09-01

Studies report conflicting associations between preeclampsia and retinopathy of prematurity (ROP). This study provides explanations for the discrepancies to clarify the relationship between preeclampsia and ROP. To evaluate the association of maternal preeclampsia and risk of ROP among infants in an unrestricted birth cohort and a restricted subcohort of preterm, very low birth weight (P-VLBW) infants. A retrospective review of 290 992 live births within the Intermountain Healthcare System in Utah from January 1, 2001, through December 31, 2010, was performed. Generalized estimating equations for logistic regressions with covariate adjustment were applied to relate ROP to preeclampsia among the full cohort and in a subcohort of P-VLBW infants born at younger than 31 weeks' gestation and weighing less than 1500 g. The occurrence of ROP was related to maternal preeclampsia in the full cohort and in a subcohort of P-VLBW infants. In the full cohort, 51% of the infants were male and the mean (SD) gestational age was 38.38 (1.87) weeks. In the P-VLBW cohort, 55% were male and the mean (SD) gestational age was 26.87 (2.40) weeks. In the full cohort, preeclampsia was associated with an increased risk of all ROP (adjusted odds ratio [aOR], 2.46; 95% CI, 2.17-2.79; P < .001), severe ROP (aOR, 5.21; 95% CI, 3.44-7.91; P < .001), infant death (aOR, 1.66; 95% CI, 1.16-2.38; P = .006), and giving birth to a P-VLBW infant (aOR, 7.74; 95% CI, 6.92-8.67; P < .001). In the P-VLBW subcohort, preeclampsia was inversely associated with the development of all ROP (aOR, 0.79; 95% CI, 0.68-0.92; P = .003), severe ROP (aOR, 0.62; 95% CI, 0.36-1.06; P = .08), and infant death (aOR, 0.19; 95% CI, 0.11-0.32; P < .001). Preeclampsia was associated with an increased risk of developing ROP among an unrestricted cohort but with a reduced risk of ROP among a restricted subcohort of P-VLBW infants. Although the conflicting associations in the full and P-VLBW cohorts may reflect true differences, the association of a reduced risk of ROP among the P-VLBW subcohort also may reflect biases from restricting the cohort to prematurity, because prematurity is an outcome of preeclampsia.

Cardiac angiogenic imbalance leads to peripartum cardiomyopathy.

PubMed

Patten, Ian S; Rana, Sarosh; Shahul, Sajid; Rowe, Glenn C; Jang, Cholsoon; Liu, Laura; Hacker, Michele R; Rhee, Julie S; Mitchell, John; Mahmood, Feroze; Hess, Philip; Farrell, Caitlin; Koulisis, Nicole; Khankin, Eliyahu V; Burke, Suzanne D; Tudorache, Igor; Bauersachs, Johann; del Monte, Federica; Hilfiker-Kleiner, Denise; Karumanchi, S Ananth; Arany, Zoltan

2012-05-09

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.

Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy

PubMed Central

Patten, Ian S.; Rana, Sarosh; Shahul, Sajid; Rowe, Glenn C; Jang, Cholsoon; Liu, Laura; Hacker, Michele R.; Rhee, Julie S.; Mitchell, John; Mahmood, Feroze; Hess, Phil; Farrell, Caitlin; Koulisis, Nicole; Khankin, Eliyahu V; Burke, Suzanne D.; Tudorache, Igor; Bauersachs, Johann; del Monte, Federica; Hilfiker-Kleiner, Denise; Karumanchi, S. Ananth; Arany, Zoltan

2012-01-01

Peri-partum cardiomyopathy (PPCM) is a frequently fatal disease that affects women near delivery, and occurs more frequently in women with pre-eclampsia and/or multiple gestation. The etiology of PPCM, or why it associates with pre-eclampsia, remains unknown. We show here that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble Flt1 (sFlt1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by sub-clinical cardiac dysfunction, the extent of which correlates with circulating levels of sFlt1. Exogenous sFlt1 alone caused diastolic dysfunction in wildtype mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFlt1. These data strongly suggest that PPCM is in large part a vascular disease, caused by excess anti-angiogenic signaling in the peri-partum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM. PMID:22596155

Cost-effectiveness analysis of cardiovascular risk factor screening in women who experienced hypertensive pregnancy disorders at term.

PubMed

van Baaren, Gert-Jan; Hermes, Wietske; Franx, Arie; van Pampus, Maria G; Bloemenkamp, Kitty W M; van der Post, Joris A; Porath, Martina; Ponjee, Gabrielle A E; Tamsma, Jouke T; Mol, Ben Willem J; Opmeer, Brent C; de Groot, Christianne J M

2014-10-01

To assess the cost-effectiveness of post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term. Two separate Markov models evaluated the cost-effectiveness analysis of hypertension (HT) screening and screening on metabolic syndrome (MetS), respectively, as compared to current practice in women with a history of term hypertensive pregnancy disorders. Analyses were performed from the Dutch health care perspective, using a lifetime horizon. One-way sensitivity analyses and Monte Carlo simulation evaluated the robustness of the results. Both screening on HT and MetS in women with a history of gestational hypertension or pre-eclampsia resulted in increase in life expectancy (HT screening 0.23year (95% CI -0.06 to 0.54); MetS screening 0.14years (95% CI -0.16 to 0.45)). The gain in QALYs was limited, with HT screening and MetS screening generating 0.04 QALYs (95% CI -0.12 to 0.20) and 0.03 QALYs (95% CI -0.14 to 0.19), resulting in costs to gain one QALY of €4228 and €28,148, respectively. Analyses for uncertainty showed a chance of 74% and 75%, respectively, that post-partum screening is cost-effective at a threshold of €60,000/QALY. According to the available knowledge post-partum screening on cardiovascular risk factors and subsequent treatment in women with a history of gestational hypertension or pre-eclampsia at term is likely to be cost-effective. Copyright © 2014 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study.

PubMed

Myers, J E; Kenny, L C; McCowan, L M E; Chan, E H Y; Dekker, G A; Poston, L; Simpson, N A B; North, R A

2013-09-01

To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women. Predictive test accuracy study. Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE). Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression. Preterm pre-eclampsia (delivered before 37(+0)  weeks of gestation). Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement. Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

Incidence of posterior reversible encephalopathy syndrome in eclamptic and patients with preeclampsia with neurologic symptoms.

PubMed

Mayama, Michinori; Uno, Kaname; Tano, Sho; Yoshihara, Masato; Ukai, Mayu; Kishigami, Yasuyuki; Ito, Yasuhiro; Oguchi, Hidenori

2016-08-01

Posterior reversible encephalopathy syndrome is observed frequently in patients with eclampsia; however, it has also been reported in some patients with preeclampsia. The aim of this study was to determine the incidence of posterior reversible encephalopathy syndrome in patients with preeclampsia and eclampsia and to assess whether these 2 patient groups share similar pathophysiologic backgrounds by comparing clinical and radiologic characteristics. This was a retrospective cohort study of 4849 pregnant patients. A total of 49 patients with eclampsia and preeclampsia and with neurologic symptoms underwent magnetic resonance imaging and magnetic resonance angiography; 10 patients were excluded from further analysis because of a history of epilepsy or dissociative disorder. The age, parity, blood pressure, and routine laboratory data at the onset of symptoms were also recorded. Among 39 patients with neurologic symptoms, 12 of 13 patients with eclampsia (92.3%) and 5 of 26 patients with preeclampsia (19.2%) experienced the development of posterior reversible encephalopathy syndrome. Whereas age and blood pressure at onset were not significantly different between patients with and without encephalopathy, hematocrit, serum creatinine, aspartate transaminase, alanine transaminase, and lactate dehydrogenase values were significantly higher in patients with posterior reversible encephalopathy syndrome than in those without magnetic resonance imaging abnormalities. In contrast, patients with eclampsia with posterior reversible encephalopathy syndrome did not show any significant differences in clinical and laboratory data compared with patients with preeclampsia with posterior reversible encephalopathy syndrome. In addition to the parietooccipital regions, atypical regions (such as the frontal and temporal lobes), and basal ganglia were also involved in patients with eclampsia and patients with preeclampsia with posterior reversible encephalopathy syndrome. Finally, intraparenchymal hemorrhage was detected in 1 patient with eclampsia, and subarachnoid hemorrhage was observed in 1 patient with preeclampsia. Although the incidence of posterior reversible encephalopathy syndrome was high in patients with eclampsia, nearly 20% of the patients with preeclampsia with neurologic symptoms also experienced posterior reversible encephalopathy syndrome. The similarities in clinical and radiologic findings of posterior reversible encephalopathy syndrome between the 2 groups support the hypothesis that these 2 patient groups have a shared pathophysiologic background. Thus, magnetic resonance imaging studies should be considered for patients with the recent onset of neurologic symptoms, regardless of the development of eclampsia. Copyright © 2016 Elsevier Inc. All rights reserved.

Elevated venous thromboembolism risk in preeclampsia: molecular mechanisms and clinical impact.

PubMed

Egan, Karl; Kevane, Barry; Ní Áinle, Fionnuala

2015-08-01

Venous thromboembolism (VTE) remains a leading cause of maternal death and morbidity in the developed world. Strategies for prevention of VTE in pregnancy have been the subject of recent guidelines and consensus statements. These guidelines recommend thrombosis prevention in women who have risk factors associated with an elevated VTE risk. Preeclampsia is characterized by maternal hypertension and proteinuria developing after 20 weeks gestation, complicating up to 7% of pregnancies and is associated with a massive annual morbidity and mortality burden. Women with preeclampsia have been shown to be at increased risk of VTE with studies to date suggesting that this risk may be up to 5-fold greater than the risk of pregnancy-associated VTE in the general population. Despite the fact that preeclampsia is so common and potentially devastating, our understanding of its pathogenesis and potential therapeutic strategies remain poor. In addition, the mechanisms underlying the prothrombotic phenotype in preeclampsia are also poorly characterized although a number of potential mechanisms have been postulated. Derangements of platelet and endothelial activation and impairment of endogenous anti-coagulant pathways have been reported and may contribute to the observed VTE risk. Recently, evidence for the role of neutrophil extracellular traps (NETs) and cell-free DNA in the pathogenesis of VTE has emerged and some evidence exists to suggest that this may be of relevance in preeclampsia. Future studies aimed at understanding the diagnostic and potential therapeutic relevance of this procoagulant state are likely to be of enormous clinical benefit for pregnant women affected with this potentially devastating condition. © 2015 Authors; published by Portland Press Limited.

IL-17 producing innate lymphoid cells 3 (ILC3) but not Th17 cells might be the potential danger factor for preeclampsia and other pregnancy associated diseases.

PubMed

Barnie, Prince A; Lin, Xin; Liu, Yueqin; Xu, Huaxi; Su, Zhaoliang

2015-01-01

In pregnancy, the immunologic system plays an important role that ensures normal pregnancy development and can as well promote the development of complications. Pregnancy success appears to rely on a discrete balance between the Th cytokines, which are involved in fetal growth and development. Preeclampsia and gestational diabetes are known complications associated with pregnancy. However, the source of the increased IL-17 cytokine in preeclampsia and other pregnancy associated diseases still remains unclear amidst numerous inconsistencies. The recent identification of innate lymphoid cells (ILC) has raised more doubts about the sources of most of the Th associated cytokines. We investigated the source of peripheral IL-17 levels in preeclamptic, gestational diabetics and chronic diabetics compared to healthy pregnancy subjects. To evaluate the source of the increased IL-17 cytokine among preeclampsia, chronic diabetic and gestational diabetic patients we investigated the proportion of Th17 cell populations in peripheral blood mononuclear cells using flow cytometry as well as analyzing levels of IFN-γ, IL-17, IL-1β and HMGB1. This study found that the Th17 cell populations in peripheral blood of preeclamptic, gestational nor chronic diabetes during pregnancy did not correlate with the increased IL-17. We report that the increased IL-17 levels observed in patients with preeclampsia, gestational diabetes and chronic diabetes are associated with innate lymphoid cells 3 (ILC3) and may pose threats to the fetus if disregulated.

Role of cytokines in development of pre-eclampsia associated with periodontal disease - Cohort Study.

PubMed

Kumar, Ashok; Begum, Nargis; Prasad, Sudha; Lamba, Arundeep K; Verma, Mahesh; Agarwal, Sarita; Sharma, Shashi

2014-04-01

The present study was designed to find any association of cytokines in women with periodontal disease and development of pre-eclampsia in North Indian population. A total of 504 consecutively registered primigravida with a single live pregnancy were recruited at 14-18 weeks of gestation from antenatal clinic of Maulana Azad Medical College & associated Lok Nayak Hospital and Maulana Azad Institute of Dental Sciences, New Delhi. One periodontist performed oral health examination of all patients at inclusion into study. Blood samples were collected to measure the level of cytokines IL-4, IL-10, TNF-α and IFN-γ. The profile of blood levels of cytokines from women with periodontal disease was observed. The log serum levels of TNF-α & IL-4 at 16-18 weeks of gestation were significantly higher in women with periodontal disease (4.13 ± 2.06; 0.47 ± 1.56 pg/ml respectively) than in women with healthy gums (2.16 ± 1.51; 0.02 ± 1.84 pg/ml respectively, p < 0.001). Periodontal disease is associated with log serum TNF-α levels at cut-off ≥14.43 pg/ml at sensitivity 71.2% and specificity 62% (OR = 4.04; 95%CI = 2.77-5.87). Woman with periodontal disease who later developed pre-eclampsia had lower levels of TNF-α (3.72 ± 1.33 pg/ml) than those with periodontal disease who did not develop pre-eclampsia (4.20 ± 2.15 pg/ml, p ≥ 0.05). Reduced TNF-α level secretion in the early second trimester in women with periodontal disease appears to be associated with the development of pre-eclampsia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The incidence of preeclampsia in ICSI pregnancies

PubMed Central

Ulkumen, BurcuArtunc; Silfeler, DilekBenk; Sofuoglu, Kenan; Silfeler, Ibrahim; Dayicioglu, Vedat

2014-01-01

Objective: We aimed to evaluate the association between infertility etiology in ICSI pregnancies and preeclampsia; besides, we aimed to discuss the effect of the paternal factor in the pathogenesis of preeclampsia. Hypothesis:We hypothesized that preeclampsia is more common in ICSI pregnancies with male factor. It is known that maternal exposure to paternal sperm cells over a time period has a protective effect against preeclampsia. Male partners with azospermia have no sperm cells in their seminal fluid, whose female partners will not be able to develop some protective immunity against preeclampsia. We hypothesized that the infertile couples with male factor (partner with azoospermia and also oligospermia) would be an ideal model to test the partner-specific protective immunity against preeclampsia, as the women had no chance to develop adequate protective immunity via the partner’s sperm exposure. Methods: This Single-center, retrospective study included 508 infertile couples admitted to our IVF center between January 2001 and March 2008. The data regarding the maternal age, etiology of the infertility, the pregnancy rates, abortus ratio and viable pregnancy rates was collected from the case files. Antenatal complications such as preeclampsia, placenta previa, abruptio placenta, premature rupture of membranes, premature labor, oligohydramnios, gestational diabetes, postmaturity, postpartum complications and neonatal outcomes were evaluated via the file records and phone interviewing. The study population was divided into two main groups according to the etiology of infertility. 301 of the study population (group 1) was infertile due to male factor and 207 of the study population (group 2) was female factor and unexplained infertility cases.Group 1 patients were divided further into two subgroups: group 1a included 56 cases in which TESE (testicular sperm extraction) was used to obtain the sperm cells as the male factor was severe and as there was no sperm cells in seminal fluid. Group 1 b consists of 245oligospermic cases who obtained sperm cells via conventional methods. Results: The mean ages of women in Group one and two were 30.22±5.06 and 31.58±4.36 years respectively (p=0.001). 129 cases (42,8%) from group one and 106 cases (51,2%) from Group two ended in first trimester and early second trimester (<24 gestational weeks) pregnancy loss. In group one, only 172 cases of 301 pregnancies passed over 24 weeks of gestational age, whereas in group two, 101 cases of 207 patients passed over 24 gestational weeks. There was no significant difference between two groups regarding chemical pregnancies and early pregnancy loss (p=0.314). There was no significant difference between the groups regarding placenta previa, gestational diabetes, oligo hydramnios and intrauterine growth retardation. One one pregnancy was 1.5 times more vulnerable for preeclampsia. Conclusion: Pregnancies with azoospermic and oligospermic partners had an increased risk for developing preeclampsia. PMID:24639840

Maternal/newborn VEGF-C936T interaction and its influence on the risk, severity and prognosis of preeclampsia, as well as on the maternal angiogenic profile.

PubMed

Procopciuc, Lucia Maria; Caracostea, Gabriela; Zaharie, Gabriela; Stamatian, Florin

2014-11-01

To analyze the influence of maternal/newborn vascular endothelial growth factor (VEGF)-CT936 interaction as a modulating factor in preeclampsia as well as its influence on the maternal angiogenic balance. Seventy pairs of preeclamptic women/newborns and 94 pairs of normal pregnant mothers/newborns were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum VEGF and soluble VEGF receptor-1 (sVEGFR-1) levels were measured using ELISA. The risk to develop mild (odds ratio; OR: 3.79, p = 0.008) and severe (OR: 2.94, p = 0.037) preeclampsia being increased in association with the CT936-VEGF genotype and increased in severe preeclampsia to 6.07 (p = 0.03) if the women were carriers of the homozygous TT936-VEGF genotype. The presence of the VEGF-T936 allele in both the mother and the newborn significantly increases the risk of pregnancy-induced hypertension (PIH), mild and severe preeclampsia. If both the mothers and newborns were carriers of the VEGF-T936 allele, significantly lower VEGF and higher sVEGFR-1 levels were observed for all types of preeclampsia. Pregnant women with PIH and severe preeclampsia delivered at a significantly earlier gestational age neonates with a significantly lower birth weight if both the preeclamptic mothers and their newborns were carriers of the VEGF-T936 allele. Our study suggests the role of maternal/fetal VEGF-CT936 polymorphism as a modulating factor in preeclampsia, which affects the angiogenic balance in preeclamptic mothers, as well as their pregnancy outcome.

Association study between GAS6 gene polymorphisms and risk of preeclampsia in Chinese population.

PubMed

Ye, Liyan; Guan, Linbo; Fan, Ping; Liu, Xinghui; Liu, Rui; Chen, Jinxin; Zhu, Yue; Wei, Xing; Liu, Yu; Bai, Huai

2017-04-01

Preeclampsia is a pregnancy-specific disorder associated with pro-inflammatory and pro-thrombotic events. The growth arrest-specific 6 (GAS6) has been implicated in systemic inflammation and coagulation. Common genetic polymorphisms of GAS6 gene have previously been reported. The aim of this study was to investigate the association of GAS6 gene polymorphisms with the risk of preeclampsia in Chinese subjects. The case-control population consists of 551 subjects. The genotyping of the single-nucleotide polymorphisms of GAS6 gene, GAS6 834 +7G/A(rs8191974) and +1332C/T (rs1803628), was carried out on genomic DNA using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) analysis. There were significant differences in the +1332C/T genotype and allele frequencies between the patients with preeclampsia and the controls (P=0.03 and 0.02, respectively). The +1332 TT genotype was found to be protective from the development of preeclampsia (odds ratios 0.271, 95% confidence interval 0.077-0.953; P=0.03). Further analysis showed that the TT genotype of the GAS6 +1332C/T conferred a risk of severe preeclampsia (OR=0.597, 95% confidence interval 0.416-0.855; P=0.01). However, there were no differences in the 834+7G/A genotype and allele frequencies between the patients with preeclampsia and the controls. Our data suggest that a TT genotype at +1332C/T polymorphism might be associated with decreased risk for preeclampsia, but the 834+7G/A polymorphism is not associated with the disorder, in the Chinese population. Copyright © 2017. Published by Elsevier B.V.

Cardiovascular risk factor assessment after pre-eclampsia in primary care

PubMed Central

2009-01-01

Background Pre-eclampsia is associated with an increased risk of development of cardiovascular disease later in life. It is not known how general practitioners in the Netherlands care for these women after delivery with respect to cardiovascular risk factor management. Methods Review of medical records of 1196 women in four primary health care centres, who were registered from January 2000 until July 2007 with an International Classification of Primary Care (ICPC) code indicating pregnancy. Records were searched for indicators of pre-eclampsia. Of those who experienced pre-eclampsia and of a random sample of 150 women who did not, the following information on cardiovascular risk factor management after pregnancy was extracted from the records: frequency and timing of blood pressure, cholesterol and glucose measurements - and vascular diagnoses. Additionally the sensitivity and specificity of ICPC coding for pre-eclampsia were determined. Results 35 women experienced pre-eclampsia. Blood pressure was more often checked after pregnancy in these women than in controls (57.1% vs. 12.0%, p < 0.001). In 50% of the cases blood pressure was measured within 3 months after delivery with no further follow-up visit. A check for glucose and cholesterol levels was rare, and equally frequent in PE and control women. 20% of the previously normotensive women in the PE group had hypertension at one or more occasions after three months post partum versus none in the control group. The ICPC coding for pre-eclampsia showed a sensitivity of 51.4% and a specificity of 100.0%. Conclusion Despite the evidence of increased risk of future cardiovascular disease in women with a history of pre-eclampsia, follow-up of these women is insufficient and undeveloped in primary care in the Netherlands. PMID:19995418

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial

PubMed Central

Souza, E.V.; Torloni, M.R.; Atallah, A.N.; dos Santos, G.M.S.; Kulay, L.; Sass, N.

2014-01-01

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler. PMID:24728212

Preeclampsia and toxic metals: a case-control study in Kinshasa, DR Congo.

PubMed

Elongi Moyene, Jean-Pierre; Scheers, Hans; Tandu-Umba, Barthélémy; Haufroid, Vincent; Buassa-Bu-Tsumbu, Baudouin; Verdonck, Fons; Spitz, Bernard; Nemery, Benoit

2016-04-05

Preeclampsia is frequent in Kinshasa (Democratic Republic of Congo), especially during the dry season. We tested whether preeclampsia was associated with exposure to environmental metals. Using a case-control design, 88 women hospitalized with preeclampsia (cases) and 88 healthy pregnant women from the antenatal clinic (controls) were included in the study; 67 and 109 women were enrolled during the rainy and dry season, respectively. The concentrations of 24 elements were quantified by inductively coupled plasma mass spectrometry (ICP-MS) in 24-h urine collections. Differences in the urinary excretion of metals were investigated between cases and controls, and the interaction with season was assessed. Cases and controls were well matched regarding age, parity and duration of pregnancy. In controls, the urinary concentrations of most elements were substantially higher than reference values for adults from industrially developed countries, e.g. for lead: geometric mean (GM) 8.0 μg/L [25(th)-75(th) percentile 3.1-13.8]. The daily urinary excretions of 14 metals were significantly higher in women with preeclampsia than in control women, e.g. for lead: GM 61 μg/day (25(th)-75(th) percentile 8-345) in women with preeclampsia vs 9 μg/day (25(th)-75(th) percentile 3-21) in controls (p < 0.001). A significant interaction was found between season and preeclampsia for several elements, with higher urinary excretions in preeclamptic women than controls during the dry season, but not during the rainy season. This study revealed not only that women with preeclampsia excrete higher amounts of several toxic metals, especially lead, than control women, but also that this excretion exhibits seasonal variation, thus possibly explaining the high incidence and seasonal variation of preeclampsia in Kinshasa. Although the exact sources of this exposure are unknown, these findings underscore the need for preventing environmental exposures to lead and other toxic metals.

Maternal Antioxidant Levels in Pregnancy and Risk of Preeclampsia and Small for Gestational Age Birth: A Systematic Review and Meta-Analysis.

PubMed

Cohen, Jacqueline M; Beddaoui, Margaret; Kramer, Michael S; Platt, Robert W; Basso, Olga; Kahn, Susan R

2015-01-01

Oxidative stress in preeclampsia and small for gestational age (SGA) birth suggests antioxidant supplementation could prevent these conditions. However, it remains unclear whether maternal antioxidant levels are systematically lower in these pregnancies. To conduct a systematic review of the association between maternal antioxidant levels during pregnancy and preeclampsia or SGA. We searched PubMed, Embase, and several other databases from 1970-2013 for observational studies that measured maternal blood levels of non-enzymatic antioxidants (vitamins A, C, E, and carotenoids) during pregnancy or within 72 hours of delivery. The entire review process was done in duplicate. Study quality was assessed using the Newcastle-Ottawa Scale and additional questions. We pooled the standardized mean difference (SMD) across studies, stratified by outcome and pregnancy trimester, and investigated heterogeneity using meta-regression. We reviewed 1,882 unique citations and 64 studies were included. Most studies were small with important risk of bias. Among studies that addressed preeclampsia (n = 58) and SGA (n = 9), 16% and 66%, respectively, measured levels prior to diagnosis. The SMDs for vitamins A, C, and E were significantly negative for overall preeclampsia, but not for mild or severe preeclampsia subtypes. Significant heterogeneity was observed in all meta-analyses and most could not be explained. Evidence for lower carotenoid antioxidants in preeclampsia and SGA was limited and inconclusive. Publication bias appears likely. Small, low-quality studies limit conclusions that can be drawn from the available literature. Observational studies inconsistently show that vitamins C and E or other antioxidants are lower in women who develop preeclampsia or SGA. Reverse causality remains a possible explanation for associations observed. New clinical trials are not warranted in light of this evidence; however, additional rigorous observational studies measuring antioxidant levels before clinical detection of preeclampsia and SGA may clarify whether levels are altered at a causally-relevant time of pregnancy.

Maternal Antioxidant Levels in Pregnancy and Risk of Preeclampsia and Small for Gestational Age Birth: A Systematic Review and Meta-Analysis

PubMed Central

Cohen, Jacqueline M.; Beddaoui, Margaret; Kramer, Michael S.; Platt, Robert W.; Basso, Olga; Kahn, Susan R.

2015-01-01

Background Oxidative stress in preeclampsia and small for gestational age (SGA) birth suggests antioxidant supplementation could prevent these conditions. However, it remains unclear whether maternal antioxidant levels are systematically lower in these pregnancies. Objective To conduct a systematic review of the association between maternal antioxidant levels during pregnancy and preeclampsia or SGA. Methods We searched PubMed, Embase, and several other databases from 1970–2013 for observational studies that measured maternal blood levels of non-enzymatic antioxidants (vitamins A, C, E, and carotenoids) during pregnancy or within 72 hours of delivery. The entire review process was done in duplicate. Study quality was assessed using the Newcastle-Ottawa Scale and additional questions. We pooled the standardized mean difference (SMD) across studies, stratified by outcome and pregnancy trimester, and investigated heterogeneity using meta-regression. Results We reviewed 1,882 unique citations and 64 studies were included. Most studies were small with important risk of bias. Among studies that addressed preeclampsia (n = 58) and SGA (n = 9), 16% and 66%, respectively, measured levels prior to diagnosis. The SMDs for vitamins A, C, and E were significantly negative for overall preeclampsia, but not for mild or severe preeclampsia subtypes. Significant heterogeneity was observed in all meta-analyses and most could not be explained. Evidence for lower carotenoid antioxidants in preeclampsia and SGA was limited and inconclusive. Publication bias appears likely. Conclusions Small, low-quality studies limit conclusions that can be drawn from the available literature. Observational studies inconsistently show that vitamins C and E or other antioxidants are lower in women who develop preeclampsia or SGA. Reverse causality remains a possible explanation for associations observed. New clinical trials are not warranted in light of this evidence; however, additional rigorous observational studies measuring antioxidant levels before clinical detection of preeclampsia and SGA may clarify whether levels are altered at a causally-relevant time of pregnancy. PMID:26247870

Ferulic acid alleviates symptoms of preeclampsia in rats by upregulating vascular endothelial growth factor.

PubMed

Gong, Weiyan; Wan, Jipeng; Yuan, Qing; Man, Quanzhan; Zhang, Xiaojing

2017-10-01

Preeclampsia is a complication affecting pregnant women worldwide, which leads to maternal and fetal morbidity and mortality. In this study, we evaluated the efficacy of ferulic acid (FA) on an N ω -nitro-L-arginine methyl ester hydrochloride (L-NAME) induced rat model of preeclampsia. L-NAME was administered to pregnant rats to induce preeclampsia. 48 rats were divided into three experimental groups (n=16 each): control group, preeclampsia group and preeclampsia with FA treatment (preeclampsia+FA). Physiological characteristics such as urine volume, total urine protein and blood pressure were assessed. Expressions levels of urinary nephrin and podocin mRNAs were analyzed by RT-PCR. Levels of renal vascular endothelial growth factor (VEGF), renal soluble fms-like tyrosine kinase-1 (sFlt-1) and serum placenta growth factor (PlGF) were also examined. Urine volume, total urine protein and blood pressure were markedly increased in preeclampsia group rats compared to control (P<.05), which were then significantly reduced in preeclampsia+FA group (P<.05). Expressions of urinary nephrin and podocin mRNAs, levels of VEGF, sFlt-1 and PlGF were also reversed in preeclampsia+FA group compared to preeclampsia rats (P<.05). We hereby report for the first time, FA alleviates preeclampsia symptoms in a rat preeclampsia model, supporting its potential value in treating preeclampsia. © 2017 John Wiley & Sons Australia, Ltd.

Angiogenic factors for prediction of preeclampsia and intrauterine growth restriction onset in high-risk women: AngioPred study.

PubMed

Raia-Barjat, Tiphaine; Prieux, Carole; Gris, Jean-Christophe; Chapelle, Céline; Laporte, Silvy; Chauleur, Céline

2017-09-22

The study aimed to compare the level of two angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng), for the prediction of preeclampsia and intrauterine growth restriction in high-risk pregnant women. A prospective multicenter cohort study of 200 pregnant patients was conducted between June 2008 and October 2010. sFlt1 and sEng were measured by enzyme-linked immunosorbent assay. Forty-five patients developed a placenta-mediated adverse pregnancy outcome. Plasma levels of sFlt1 and sEng were higher in patients who will experience a preeclampsia at 28, 32, and 36 weeks compared with patients with no complication. The same results were observed for intrauterine growth restriction. Plasma levels of sFlt1 and sEng were not significantly different for patients with preeclampsia compare to patients with intrauterine growth restriction. Patients with early pre-eclampsia (PE) had very high rates of angiogenic factors at 20, 24, and 28 weeks. Patients with late PE and early and late intrauterine growth retardation (IUGR) had high rates at 32 and 36 weeks. In high-risk women, angiogenic factors are disturbed before the onset of preeclampsia and this is true for intrauterine growth restriction.

Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice.

PubMed

Szalai, Gabor; Romero, Roberto; Chaiworapongsa, Tinnakorn; Xu, Yi; Wang, Bing; Ahn, Hyunyoung; Xu, Zhonghui; Chiang, Po Jen; Sundell, Birgitta; Wang, Rona; Jiang, Yang; Plazyo, Olesya; Olive, Mary; Tarca, Adi L; Dong, Zhong; Qureshi, Faisal; Papp, Zoltan; Hassan, Sonia S; Hernandez-Andrade, Edgar; Than, Nandor Gabor

2015-01-01

Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3 ± 51.7 μg/mg vs. 19.3 ± 5.6 μg/mg, p = 4.4 x 10(-2); GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2 x 10(-2)). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR). A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.

Full-Length Human Placental sFlt-1-e15a Isoform Induces Distinct Maternal Phenotypes of Preeclampsia in Mice

PubMed Central

Szalai, Gabor; Romero, Roberto; Chaiworapongsa, Tinnakorn; Xu, Yi; Wang, Bing; Ahn, Hyunyoung; Xu, Zhonghui; Chiang, Po Jen; Sundell, Birgitta; Wang, Rona; Jiang, Yang; Plazyo, Olesya; Olive, Mary; Tarca, Adi L.; Dong, Zhong; Qureshi, Faisal; Papp, Zoltan; Hassan, Sonia S.; Hernandez-Andrade, Edgar; Than, Nandor Gabor

2015-01-01

Objective Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring. Methods Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia. Results Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10-2). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR). Conclusions A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the in vivo pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome. PMID:25860260

Geographic Distribution of Healthy Resources and Adverse Pregnancy Outcomes.

PubMed

Young, Christopher; Laurent, Olivier; Chung, Judith H; Wu, Jun

2016-08-01

Objective To determine the risk of gestational diabetes (GDM) and preeclampsia associated with various community resources. Methods An ecological study was performed in Los Angeles and Orange counties in California. Fast food restaurants, supermarkets, grocery stores, gyms, health clubs and green space were identified using Google © Maps Extractor and through the Southern California Association of Government. California Birth Certificate data was used to identify cases of GDM and preeclampsia. Unadjusted and adjusted risk ratios were calculated using negative binomial regression. Results There were 9692 cases of GDM and 6288 cases of preeclampsia corresponding to incidences of 2.5 and 1.4 % respectively. The adjusted risk of GDM was reduced in zip codes with greater concentration of grocery stores [relative risk (RR) 0.95, 95 % confidence interval (CI) 0.92-0.99] and supermarkets (RR 0.94, 95 % CI 0.90-0.98). There were no significant relationships between preeclampsia and the concentration of fast food restaurants, grocery store, supermarkets or the amount of green space. Conclusion The distribution of community resources has a significant association with the risk of developing GDM but not preeclampsia.

SUPPLEMENTATION WITH VITAMINS C AND E DURING PREGNANCY FOR THE PREVENTION OF PREECLAMPSIA AND OTHER ADVERSE MATERNAL AND PERINATAL OUTCOMES: A SYSTEMATIC REVIEW AND METAANALYSIS

PubMed Central

CONDE-AGUDELO, Agustín; ROMERO, Roberto; KUSANOVIC, Juan Pedro; HASSAN, Sonia

2011-01-01

OBJECTIVE To determine whether supplementation with vitamins C and E during pregnancy reduces the risk of preeclampsia and other adverse maternal and perinatal outcomes. STUDY DESIGN Systematic review and metaanalysis of randomized controlled trials. RESULTS Nine trials involving a total of 19,810 women were included. Overall, there were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (9.6% versus 9.6%; relative risk 1.00, 95% confidence interval 0.92–1.09). Similar results were obtained when subgroup analyses were restricted to women at high risk or low/moderate risk for preeclampsia. Women supplemented with vitamins C and E were at increased risk of developing gestational hypertension and premature rupture of membranes, and a decreased risk of abruptio placentae. There were no significant differences between the vitamin and placebo groups in the risk of other adverse maternal or fetal/perinatal outcomes. CONCLUSION Supplementation with vitamins C and E during pregnancy does not prevent preeclampsia. PMID:21529757

MicroRNA-210 contributes to preeclampsia by downregulating potassium channel modulatory factor 1.

PubMed

Luo, Rongcan; Shao, Xuan; Xu, Peng; Liu, Yanlei; Wang, Yongqing; Zhao, Yangyu; Liu, Ming; Ji, Lei; Li, Yu-Xia; Chang, Cheng; Qiao, Jie; Peng, Chun; Wang, Yan-Ling

2014-10-01

Preeclampsia is a pregnancy-specific syndrome manifested by the onset of hypertension and proteinuria after the 20th week of gestation. Abnormal placenta development has been generally accepted as the initial cause of the disorder. Recently, microRNA-210 (miR-210) has been found to be upregulated in preeclamptic placentas compared with normal placentas, indicating a possible association of this small molecule with the placental pathology of preeclampsia. However, the function of miR-210 in the development of the placenta remains elusive. The aim of this study was to characterize the molecular mechanism of preeclampsia development by examining the role of miR-210. In this study, miR-210 and potassium channel modulatory factor 1 (KCMF1) expressions were compared in placentas from healthy pregnant individuals and patients with preeclampsia, and the role of miR-210 in trophoblast cell invasion via the downregulation of KCMF1 was investigated in the immortal trophoblast cell line HTR8/SVneo. The levels of KCMF1 were significantly lower in preeclamptic placenta tissues than in gestational week-matched normal placentas, which was inversely correlated with the level of miR-210. KCMF1 was validated as the direct target of miR-210 using real-time polymerase chain reaction, Western blotting, and dual luciferase assay in HTR8/SVneo cells. miR-210 inhibited the invasion of trophoblast cells, and this inhibition was abrogated by the overexpression of KCMF1. The inflammatory factor tumor necrosis factor-α could upregulate miR-210 while suppressing KCMF1 expression in HTR8/SVneo cells. This is the first report on the function of KCMF1 in human placental trophoblast cells, and the data indicate that aberrant miR-210 expression may contribute to the occurrence of preeclampsia by interfering with KCMF1-mediated signaling in the human placenta. © 2014 American Heart Association, Inc.

Tissue transglutaminase contributes to the pathogenesis of preeclampsia and stabilizes placental angiotensin receptor AT1 by ubiquitination-preventing isopeptide modification

PubMed Central

Liu, Chen; Wang, Wei; Parchim, Nicholas; Irani, Roxanna A.; Blackwell, Sean; Sibai, Baha; Jin, Jianping; Kellems, Rodney E.; Xia, Yang

2014-01-01

Preeclampsia is a life-threatening pregnancy disorder that is widely believed to be triggered by impaired placental development. However, the placenta-related pathogenic factors are not fully identified and their underlying mechanisms in disease development remain unclear. Here we report that the protein level and enzyme activity of tissue transglutaminase (TG2 or tTG), the most ubiquitous member of a family of enzymes that conducts posttranslational modification of proteins by forming ε-(γ-glutamyl)-lysine isopeptide bonds, are significantly elevated in placentas of preeclamptic women. TG2 is localized in the placental syncytiotrophoblasts of preeclamptic patients where it catalyzes the isopeptide modification of the angiotensin receptor AT1. To determine the role of elevated TG2 in preeclampsia, we employed a mouse model of preeclampsia based on injection of angiotensin receptor type 1 agonistic autoantibody (AT1-AA). A pathogenic role for TG2 in preeclampsia is suggested by in vivo experiments in which cystamine, a potent transglutaminase inhibitor, or siRNA-mediated TG2 knockdown, significantly attenuated autoantibody-induced hypertension and proteinuria in pregnant mice. Cystamine treatment also prevented isopeptide modification of placental AT1 receptors in preeclamptic mice. Mechanistically, we revealed that AT1-AA stimulation enhances the interaction between AT1 receptor and TG2, and results in increased AT1 receptor stabilization via transglutaminase-mediated isopeptide modification in trophoblasts. Mutagenesis studies further demonstrated that TG2-mediated isopeptide modification of AT1 receptors prevents the ubiquitination-dependent receptor degradation. Taken together, our studies not only identify a novel pathogenic involvement of TG2 in preeclampsia but also suggest a previously unrecognized role of TG2 in the regulation of GPCR stabilization by inhibiting ubiquitination-dependent degradation. PMID:24191290

The impact of fetal growth restriction on latency in the setting of expectant management of preeclampsia.

PubMed

McKinney, David; Boyd, Heather; Langager, Amanda; Oswald, Michael; Pfister, Abbey; Warshak, Carri R

2016-03-01

Fetal growth restriction is a common complication of preeclampsia. Expectant management for qualifying patients has been found to have acceptable maternal safety while improving neonatal outcomes. Whether fetal growth restriction influences the duration of latency during expectant management of preeclampsia is unknown. The objective of the study was to determine whether fetal growth restriction is associated with a reduced interval to delivery in women with preeclampsia being expectantly managed prior to 34 weeks. We performed a retrospective cohort of singleton, live-born, nonanomalous deliveries at the University of Cincinnati Medical Center between 2008 and 2013. Patients were included in our analysis if they were diagnosed with preeclampsia prior to 34 completed weeks and if the initial management plan was to pursue expectant management beyond administration of steroids for fetal lung maturity. Two study groups were determined based on the presence or absence of fetal growth restriction. Patients were delivered when they developed persistent neurological symptoms, severe hypertension refractory to medical therapy, renal insufficiency, nonreassuring fetal status, pulmonary edema, or hemolysis elevated liver low platelet syndrome or when they reached 37 weeks if they remained stable without any other indication for delivery. Our primary outcome was the interval from diagnosis of preeclampsia to delivery, measured in days. Secondary outcomes included indications for delivery, rates of induction and cesarean delivery, development of severe morbidities of preeclampsia, and select neonatal outcomes. We performed a multivariate logistic regression analysis comparing those with fetal growth restriction with those with normally grown fetuses to determine whether there is an association between fetal growth restriction and a shortened interval to delivery, neonatal intensive care unit admission, prolonged neonatal stay, and neonatal mortality. A total of 851 patients met the criteria for preeclampsia, of which 199 met inclusion criteria, 139 (69%) with normal growth, and 60 (31%) with fetal growth restriction. Interval to delivery was significantly shorter in women with fetal growth restriction, median (interquartile range) of 3 (1.6) days vs normal growth, 5 (2.12) days, P < .001. The association between fetal growth restriction and latency less than 7 days remained significant, even after post hoc analysis controlling for confounding variables (adjusted odds ratio, 1.66 [95% confidence interval, 1.12-2.47]). There were no differences in the development of severe disease (85.9 vs 91.7%, P = .26), need for intravenous antihypertensive medications (47.1 vs 46.7%, P = .96), and the development of severe complications of preeclampsia (51.1 vs 42.9%, P = .30) in normally grown and growth-restricted fetuses, respectively. Fewer women with fetal growth restriction attained their scheduled delivery date, 3 of 60 (5.0%), compared with normally grown fetuses,12 of 139 (15.7%), P = .03. Admission to the neonatal intensive care unit, neonatal length of stay, and neonatal mortality were higher when there was fetal growth restriction; however, after a logistic regression analysis, these associations were no longer significant. Fetal growth restriction is associated with a shortened interval to delivery in women undergoing expectant management of preeclampsia when disease is diagnosed prior to 34 weeks. These data may be helpful in counseling patients regarding the expected duration of pregnancy, guiding decision making regarding administration of steroids and determining the need for maternal transport. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of current and new biomarkers in severe preeclampsia: a microarray approach reveals the VSIG4 gene as a potential blood biomarker.

PubMed

Textoris, Julien; Ivorra, Delphine; Ben Amara, Amira; Sabatier, Florence; Ménard, Jean-Pierre; Heckenroth, Hélène; Bretelle, Florence; Mege, Jean-Louis

2013-01-01

Preeclampsia is a placental disease characterized by hypertension and proteinuria in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia) and 19 gestational age-matched women with normal pregnancies as controls. We measured circulating factors that are associated with the coagulation pathway (including fibrinogen, fibronectin, factor VIII, antithrombin, protein S and protein C), endothelial activation (such as soluble endoglin and CD146), and the release of total and platelet-derived microparticles. These markers enabled us to discriminate the preeclampsia condition from a normal pregnancy but were not sufficient to distinguish severe from non-severe preeclampsia. We then used a microarray to study the transcriptional signature of blood samples. Preeclampsia patients exhibited a specific transcriptional program distinct from that of the control group of women. Interestingly, we also identified a severity-related transcriptional signature. Functional annotation of the upmodulated signature in severe preeclampsia highlighted two main functions related to "ribosome" and "complement". Finally, we identified 8 genes that were specifically upmodulated in severe preeclampsia compared with non-severe preeclampsia and the normotensive controls. Among these genes, we identified VSIG4 as a potential diagnostic marker of severe preeclampsia. The determination of this gene may improve the prognostic assessment of severe preeclampsia.

Reduced Expression of the Epidermal Growth Factor Signaling System in Preeclampsia

PubMed Central

Armant, D. Randall; FRITZ, Rani; KILBURN, Brian A.; KIM, Yeon Mee; NIEN, Jyh Kae; MAIHLE, Nita J.; ROMERO, Roberto; LEACH, Richard E.

2014-01-01

Introduction The epidermal growth factor (EGF) signaling system regulates trophoblast differentiation, and its disruption could contribute to perinatal disease. We hypothesized that this pathway is altered in preeclampsia, a disorder associated with trophoblast apoptosis and failure to invade and remodel the uterine spiral arteries. Methods Six EGF family peptides and a truncated EGF receptor splice variant (p110/EGFR) were examined using immunocytochemistry in the trophoblast of placentas (N=76) from women with preeclampsia, and compared to placentas from women of similar gestational age (GA) with preterm labor (PTL) or small for gestational age (SGA) fetuses, as well as normal term placentas. EGF, transforming growth factor-α (TGFA), and heparin-binding EGF-like growth factor (HBEGF) were evaluated using ELISA in maternal plasma from another 20 pregnancies with or without preeclampsia. Cell death was evaluated in the HTR-8/SVneo human cytotrophoblast cell line using TUNEL to evaluate the protective effects of EGF peptides. Results Trophoblast HBEGF, TGFA, and EGF were significantly reduced in preeclampsia compared to PTL and SGA, while p110/EGFR accumulated significantly on the surface of the chorionic villi (p<0.05). Plasma EGF levels were significantly decreased in preeclamptic patients, compared to non-preeclamptic patients (p<0.05). HBEGF, EGF, TGFA, epiregulin, and betacellulin each blocked cytotrophoblast cell death in vitro (p< 0.05). Discussion Three members of the EGF family are dysregulated in placentas with preeclampsia, whereas p110/EGFR, a potential EGF receptor antagonist, is overexpressed. These findings are consistent with the concept that disruption of the EGF signaling system contributes to aberrant trophoblast development associated with preeclampsia. PMID:25589361

Down-regulated long non-coding RNA-ATB in preeclampsia and its effect on suppressing migration, proliferation, and tube formation of trophoblast cells.

PubMed

Liu, Xijing; Chen, Hongqin; Kong, Weiqi; Zhang, Yanping; Cao, Liyuan; Gao, Linbo; Zhou, Rong

2017-01-01

Preeclampsia is a pregnancy-specific syndrome and is one of the main causes of maternal, fetal, and neonatal morbidity and mortality. Inadequate trophoblast invasion and failure of uterine spiral artery remodeling exert a major role in the development of preeclampsia, especially the early-onset one. LncRNA-ATB is verified to be aberrantly expressed in many cancers and promote the invasion-metastasis and proliferation cascades. But little is known of lncRNA-ATB's role in preeclampsia. The aim of current study is to identify the changes of lncRNA-ATB in preeclampsia and its effects on trophoblast. The lncRNA-ATB levels were decreased in placental samples collected from preeclampsia women (n = 51) compared to those of healthy pregnant women (n = 40) by qRT-PCR analysis. Besides, it is demonstrated that lncRNA-ATB was intense stained in the trophoblast of the placenta by performing in-situ hybridization. By designing RNA interference species to suppress lncRNA-ATB and specific plasmids designed to overexpress lncRNA-ATB, we identify the role of lncRNA-ATB on the functions of trophoblast cell-line, HTR-8/SVneo. Inhibition of endogenous lncRNA-ATB decreased migration, proliferation, tube-formation of HTR-8/SVneo cells. In addition, overexpression of lncRNA-ATB promoted migration, proliferation, and tube-formation of HTR-8/SVneo cells. Therefore, lncRNA-ATB might be involved in the pathogenesis of preeclampsia by regulating the process of trophoblast invasion and endovascular formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

LMWH in the prevention of preeclampsia and fetal growth restriction in women without thrombophilia. A systematic review and meta-analysis.

PubMed

Mastrolia, Salvatore Andrea; Novack, Lena; Thachil, Jecko; Rabinovich, Anat; Pikovsky, Oleg; Klaitman, Vered; Loverro, Giuseppe; Erez, Offer

2016-10-28

Placental mediated pregnancy complications such as preeclampsia and fetal growth restriction (FGR) are common, serious, and associated with increased morbidity and mortality. We conducted a systematic review and meta-analysis to determine the effect of treatment with low-molecular-weight heparins (LMWHs) for secondary prevention of these complications in non thrombophilic women. We searched the electronic databases PubMed, Scopus, and Cochrane Library for randomised controlled trials addressing this question. Five studies including 403 patients met the inclusion criteria, 68 developed preeclampsia and 118 FGR. The studies were very heterogeneous in terms of inclusion criteria, LMWH preparation, and dosage. Meta-analyses were performed using random-effect models. The overall use of LMWHs was associated with a risk reduction for preeclampsia (Relative risk (RR) 0.366; 95 % confidence interval (CI), 0.219-0.614) and FGR (RR 0.409; 95 % CI, 0.195-0.932) vs. no treatment. From the data available for analysis it appears that the use of Dalteparin is associated with a risk reduction for preeclampsia (p=0.002) and FGR (p<0.001); while Enoxaparin is associated with risk reduction for preeclampsia (p=0.013) but not for FGR (p=0.3). In spite of the small number of studies addressing the research question, and the high variability among them, our meta-analysis found a modest beneficial effect of LMWH for secondary prevention of preeclampsia and FGR. Further studies are needed to address these questions before a definite conclusion can be reached.

The kidney in pregnancy: A journey of three decades.

PubMed

Prakash, J

2012-05-01

The spectrum of kidney disease occurring during pregnancy includes preeclampsia, hypertensive disorders of pregnancy, urinary tract infection, acute kidney injury, and renal cortical necrosis (RCN). Preeclampsia affects approximately 3-5% of pregnancies. We observed preeclampsia in 5.8% of pregnancies, and 2.38% of our preeclamptic women developed eclampsia. Severe preeclampsia and the eclampsia or hemolysis, elevated liver enzymes levels, and low platelets count (HELLP) syndrome accounted for about 40% of cases of acute kidney injury (AKI) in pregnancy. Preeclampsia/eclampsia was the cause of acute renal failure (ARF) in 38.3% of the cases. Preeclampsia was the most common (91.7%) cause of hypertension during pregnancy, and chronic hypertension was present in 8.3% of patients. We observed urinary tract infection (UTI) in 9% of pregnancies. Sepsis resulting from pyelonephritis can progress to endotoxic shock, disseminated intravascular coagulation, and AKI. The incidence of premature delivery and low birth weight is higher in women with UTI. The incidence of AKI in pregnancy with respect to total ARF cases has decreased over the last 30 years from 25% in 1980s to 5% in 2000s. Septic abortion-related ARF decreased from 9% to 3%. Prevention of unwanted pregnancy and avoidance of septic abortion are key to eliminate abortion-associated ARF in early pregnancy. The two most common causes of ARF in third trimester and postpartum periods were puerperal sepsis and preeclampsia/HELLP syndrome. Pregnancy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and acute fatty liver of pregnancy were rare causes of ARF. Despite decreasing incidence, AKI remains a serious complication during pregnancy.

The kidney in pregnancy: A journey of three decades

PubMed Central

Prakash, J.

2012-01-01

The spectrum of kidney disease occurring during pregnancy includes preeclampsia, hypertensive disorders of pregnancy, urinary tract infection, acute kidney injury, and renal cortical necrosis (RCN). Preeclampsia affects approximately 3–5% of pregnancies. We observed preeclampsia in 5.8% of pregnancies, and 2.38% of our preeclamptic women developed eclampsia. Severe preeclampsia and the eclampsia or hemolysis, elevated liver enzymes levels, and low platelets count (HELLP) syndrome accounted for about 40% of cases of acute kidney injury (AKI) in pregnancy. Preeclampsia/eclampsia was the cause of acute renal failure (ARF) in 38.3% of the cases. Preeclampsia was the most common (91.7%) cause of hypertension during pregnancy, and chronic hypertension was present in 8.3% of patients. We observed urinary tract infection (UTI) in 9% of pregnancies. Sepsis resulting from pyelonephritis can progress to endotoxic shock, disseminated intravascular coagulation, and AKI. The incidence of premature delivery and low birth weight is higher in women with UTI. The incidence of AKI in pregnancy with respect to total ARF cases has decreased over the last 30 years from 25% in 1980s to 5% in 2000s. Septic abortion-related ARF decreased from 9% to 3%. Prevention of unwanted pregnancy and avoidance of septic abortion are key to eliminate abortion-associated ARF in early pregnancy. The two most common causes of ARF in third trimester and postpartum periods were puerperal sepsis and preeclampsia/HELLP syndrome. Pregnancy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and acute fatty liver of pregnancy were rare causes of ARF. Despite decreasing incidence, AKI remains a serious complication during pregnancy. PMID:23087548

Mid-pregnancy circulating immune biomarkers in women with preeclampsia and normotensive controls.

PubMed

Taylor, Brandie D; Tang, Gong; Ness, Roberta B; Olsen, Jørn; Hougaard, David M; Skogstrand, Kristin; Roberts, James M; Haggerty, Catherine L

2016-01-01

To determine if mid-pregnancy circulating immune biomarkers are associated with preeclampsia. Nested case-control study of 410 preeclamptic women and 297 normotensive controls with primiparous singleton pregnancies enrolled in the Danish National Birth Cohort. The mean gestational age in our cohort is 16 weeks (range 9-26). Preeclampsia was defined by blood pressure ⩾140/90 mmHg and proteinuria ⩾3 g/24 h. Serum immune biomarkers included interleukin (IL)-6, IL-6 receptor, IL-4, IL-4 receptor, IL-5, IL-12, IL-2, TNF-α, TNF-β, TNF-receptor, IL-1β, IL-1α, IL-8, IL-10, IFN-γ, IL-18, macrophage migration inhibitory factor, macrophage inflammatory protein, transforming growth factor-beta (TGF-β), and RANTES. Associations with preeclampsia, term preeclampsia and preterm preeclampsia were determined using two logistic regression models; (1) biomarkers were dichotomized by the limit of detection (LOD); (2) on the continuous scale, non-detectable values were imputed by LOD/2 and transformed (base 2). All models were adjusted for body mass index and smoking. IL1β was significantly associated with a decrease in the log odds of preeclampsia (p=0.0065), term preeclampsia (p=0.0230) and preterm preeclampsia (p=0.0068). Results were similar for IL4r and preeclampsia (p=0.0383). In the dichotomized models, detectable TNF-β was significantly associated with preeclampsia (ORadj 1.6, 95% CI 1.1-2.3) and term preeclampsia (OR 1.7, 95% CI 1.1-2.5) but not preterm preeclampsia. Detectable IL6 was significantly with term preeclampsia only (OR 1.5, 95% CI 1.1-2.2). Mid-pregnancy circulating IL1β, IL4r, IL6, and TNFβ were associated with preeclampsia. However, results were not consistent across statistical models. As the relationship is complex, future studies should explore cytokine clusters in preeclampsia risk. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia.

PubMed

Leavey, Katherine; Bainbridge, Shannon A; Cox, Brian J

2015-01-01

Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3-5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify "PE-specific" genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a "canonical" PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder.

Reduction of cardiovascular risk after preeclampsia: the role of framing and perceived probability in modifying behavior.

PubMed

Bokslag, Anouk; Hermes, Wietske; de Groot, Christianne J M; Teunissen, Pim W

2016-11-01

To reduce cardiovascular risk after preeclampsia, we investigated the effect of framing, the perceived probability and its interaction, on the willingness to modify behavior. Participants scored their willingness to modify behavior on two cases with different probabilities of developing cardiovascular disease. Both cases were either presented as "chance of health" or "risk of disease". 165 questionnaires were analyzed. ANOVA revealed a significant effect of probability, non-significant effect of framing and a non-significant interaction between probability and framing. Perceived probability influences willingness to modify behavior to reduce cardiovascular risk after preeclampsia; framing and the interaction was not of influence.

Action on Pre-eclampsia: Crisis and recovery.

PubMed

Milne, Fiona

2011-01-01

This is a review of the antenatal guidelines developed under the auspices of the charity Action on Preeclampsia since 2001. They are evidence-based and cover the screening and diagnosis of preeclampsia. They include a risk assessment early in pregnancy, referral for specialist input, a two tier schedule of assessment based on risk, signs and symptoms, referral for step-up care and confirmation of diagnosis, including blood tests. They describe methods for improving reliability of proteinuria testing, and reducing errors in the measurement of blood pressure. Management flowcharts are provided. Copyright © 2010 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Is preeclampsia an independent predictor of diastolic dysfunction? A retrospective cohort study.

PubMed

Guirguis, George F; Aziz, Michael M; Boccia Liang, Claire; Williams, Shauna F; Apuzzio, Joseph J; Bilinski, Robyn; Mornan, Adenieki J D; Shah, Leena P

2015-10-01

To determine if preeclampsia is an independent predictor of diastolic dysfunction and what factors among patients with preeclampsia are associated with diastolic dysfunction. This is a retrospective cohort study of patients who delivered between 2008 and 2013 at a single institution who had a maternal echocardiogram during their pregnancy or within 5months of delivery. Patients with structural heart disease, ejection fraction less than 45%, pulmonary embolus, or age over 45years were excluded. Medical records were reviewed for medical and obstetric complications and echocardiogram findings. Demographic characteristics and rate of diastolic dysfunction were compared between patients with preeclampsia and without preeclampsia. Multivariate logistic regression was performed controlling for age, ethnicity, gestational age at delivery, diabetes, preeclampsia, intrauterine growth restriction (IUGR), antihypertensive use and magnesium sulfate administration. Sixty-six patients were identified, of which 39 (59%) had preeclampsia. Past history of preeclampsia, IUGR in the current pregnancy, antihypertensive use and magnesium sulfate use were higher in the preeclampsia group. Fifteen patients (39%) in the preeclampsia group were African-American compared to 2 (3%) in the control group (p<0.01). Seventeen (44%) of the patients with preeclampsia were found to have diastolic dysfunction compared to 3 (11%) controls (OR=6.18, 95% CI 1.59,24.02; p=0.006). Logistic regression analysis did not reveal other independent predictors of diastolic dysfunction. In the patients with preeclampsia, history of preeclampsia with severe features and IUGR were not associated with diastolic dysfunction. Our study supports previous findings that preeclampsia is associated with diastolic dysfunction. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Magnesium sulfate versus esomeprazole impact on the neonates of preeclamptic rats.

PubMed

Shafik, Amani N; Khattab, Mahmoud A; Osman, Ahmed H

2018-06-01

Preeclampsia represents a major complication of pregnancy, associated with greater maternal and fetal complications. We compared the effects of esomeprazole (a proton pump inhibitor) and magnesium sulfate (MgSO4) on the deleterious effects observed on the mother and neonates in experimentally induced preeclampsia in rats. Preeclampsia was induced in pregnant rats with NG-nitro-l-arginine methyl ester (L-NAME) starting from day 10-till end of pregnancy. Pregnant rats were divided into four groups: control pregnant; untreated preeclampsia; preeclamptic rats treated with MgSO4 and preeclamptic treated with esomeprazole. Treatment was started on day 14 and continued until end of pregnancy. Systolic blood pressure, gestation duration, the total number of pups/fetal resorption, pups birth weight, and histopathology examination of the pup's organs were recorded. In comparison with the L-NAME group, the MgSO4 and esomeprazole treatment reduced the values of systolic blood pressure; MgSO4 normalized gestational duration while esomeprazole prolonged it (post-term pregnancy); both restored number of delivered pups; with no statistical differences between the numbers of died pups between the four groups studied while with esomeprazole, out of 10 pregnant females, 2 of them had complete intrauterine fetal resorption; esomeprazole normalized birth weight and histological structure of fetal liver, kidney, and brain. On the other side, MgSO4 treatment gave rise to lower than normal birth weight and minimal tissue damage. Esomeprazole and MgSO4 improved systolic blood pressure, prevented preterm labor and restored numbers of pups delivered and fetal weight. Esomeprazole prolonged gestational period post-term with subsequent improving reproductive outcome. Copyright © 2018 Elsevier B.V. All rights reserved.

Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations.

PubMed

Gormley, Matthew; Ona, Katherine; Kapidzic, Mirhan; Garrido-Gomez, Tamara; Zdravkovic, Tamara; Fisher, Susan J

2017-08-01

The maternal signs of preeclampsia, which include the new onset of high blood pressure, can occur because of faulty placentation. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would lend new insights into the role of these cells in preeclampsia pathogenesis. Our goal was to enrich syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts from the placentas of severe preeclampsia cases. Total RNA was subjected to global transcriptional profiling to identify RNAs that were misexpressed compared with controls. This was a cross-sectional analysis of placentas from women who had been diagnosed with severe preeclampsia. Gestational age-matched controls were placentas from women who had a preterm birth with no signs of infection. Laser microdissection enabled enrichment of syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts. After RNA isolation, a microarray approach was used for global transcriptional profiling. Immunolocalization identified changes in messenger RNA expression that carried over to the protein level. Differential expression of non-protein-coding RNAs was confirmed by in situ hybridization. A 2-way analysis of variance of non-coding RNA expression identified particular classes that distinguished trophoblasts in cases vs controls. Cajal body foci were visualized by coilin immunolocalization. Comparison of the trophoblast subtype data within each group (severe preeclampsia or noninfected preterm birth) identified many highly differentially expressed genes. They included molecules that are known to be expressed by each subpopulation, which is evidence that the method worked. Genes that were expressed differentially between the 2 groups, in a cell-type-specific manner, encoded a combination of molecules that previous studies associated with severe preeclampsia and those that were not known to be dysregulated in this pregnancy complication. Gene ontology analysis of the syncytiotrophoblast data highlighted the dysregulation of immune functions, morphogenesis, transport, and responses to vascular endothelial growth factor and progesterone. The invasive cytotrophoblast data provided evidence of alterations in cellular movement, which is consistent with the shallow invasion often associated with severe preeclampsia. Other dysregulated pathways included immune, lipid, oxygen, and transforming growth factor-beta responses. The data for endovascular cytotrophoblasts showed disordered metabolism, signaling, and vascular development. Additionally, the transcriptional data revealed the differential expression in severe preeclampsia of 2 classes of non-coding RNAs: long non-coding RNAs and small nucleolar RNAs. The long non-coding RNA, urothelial cancer associated 1, was the most highly up-regulated in this class. In situ hybridization confirmed severe preeclampsia-associated expression in syncytiotrophoblasts. The small nucleolar RNAs, which chemically modify RNA structure, also correlated with severe preeclampsia. Thus, we enumerated Cajal body foci, sites of small nucleolar RNA activity, in primary cytotrophoblasts that were isolated from control and severe preeclampsia placentas. In severe preeclampsia, cytotrophoblasts had approximately double the number of these foci as the control samples. A laser microdissection approach enabled the identification of novel messenger RNAs and non-coding RNAs that were misexpressed by various trophoblast subpopulations in severe preeclampsia. The results suggested new avenues of investigation, in particular, the roles of PRG2, Kell blood group determinants, and urothelial cancer associated 1 in syncytiotrophoblast diseases. Additionally, many of the newly identified dysregulated molecules might have clinical utility as biomarkers of severe preeclampsia. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Cardiovascular mortality after pre-eclampsia in one child mothers: prospective, population based cohort study.

PubMed

Skjaerven, Rolv; Wilcox, Allen J; Klungsøyr, Kari; Irgens, Lorentz M; Vikse, Bjørn Egil; Vatten, Lars J; Lie, Rolv Terje

2012-11-27

To assess the association of pre-eclampsia with later cardiovascular death in mothers according to their lifetime number of pregnancies, and particularly after only one child. Prospective, population based cohort study. Medical Birth Registry of Norway. We followed 836,147 Norwegian women with a first singleton birth between 1967 and 2002 for cardiovascular mortality through linkage to the national Cause of Death Registry. About 23,000 women died by 2009, of whom 3891 died from cardiovascular causes. Associations between pre-eclampsia and cardiovascular death were assessed by hazard ratios, estimated by Cox regression analyses. Hazard ratios were adjusted for maternal education (three categories), maternal age at first birth, and year of first birth The rate of cardiovascular mortality among women with preterm pre-eclampsia was 9.2% after having only one child, falling to 1.1% for those with two or more children. With term pre-eclampsia, the rates were 2.8% and 1.1%, respectively. Women with pre-eclampsia in their first pregnancy had higher rates of cardiovascular death than those who did not have the condition at first birth (adjusted hazard ratio 1.6 (95% confidence interval 1.4 to 2.0) after term pre-eclampsia; 3.7 (2.7 to 4.8) after preterm pre-eclampsia). Among women with only one lifetime pregnancy, the increase in risk of cardiovascular death was higher than for those with two or more children (3.4 (2.6 to 4.6) after term pre-eclampsia; 9.4 (6.5 to 13.7) after preterm pre-eclampsia). The risk of cardiovascular death was only moderately elevated among women with pre-eclamptic first pregnancies who went on to have additional children (1.5 (1.2 to 2.0) after term pre-eclampsia; 2.4 (1.5 to 3.9) after preterm pre-eclampsia). There was little evidence of additional risk after recurrent pre-eclampsia. All cause mortality for women with two or more lifetime births, who had pre-eclampsia in first pregnancy, was not elevated, even with preterm pre-eclampsia in first pregnancy (1.1 (0.87 to 1.14)). Cardiovascular death in women with pre-eclampsia in their first pregnancy is concentrated mainly in women with no additional births. This association might be due to health problems that discourage or prevent further pregnancies rather than to pre-eclampsia itself. As a screening criterion for cardiovascular disease risk, pre-eclampsia is a strong predictor primarily among women with only one child-particularly with preterm pre-eclampsia.

An analysis of the differences between early and late preeclampsia with severe hypertension.

PubMed

Li, X L; Guo, P L; Xue, Y; Gou, W L; Tong, M; Chen, Q

2016-01-01

Preeclampsia is clinically divided into early onset and late onset preeclampsia based on the gestational age at delivery. Although the diagnostic criteria are the same in each subgroup of preeclampsia, it has been suggested that the maternal and perinatal mortalities of early onset and late onset preeclampsia are different. However, studies that compare clinical parameters or laboratory biomarkers between early onset and late onset preeclampsia are limited. Data on 177 women with early or late preeclampsia with severe hypertension were collected from a University Teaching Hospital from January 2010 to January 2011 and analysed. Data included all the clinical parameters and laboratory biomarkers of liver and renal function. 63 women and 114 women were diagnosed with early and late preeclampsia with severe hypertension, respectively. There was no difference in the maternal age and the incidence of clinical symptoms including edema, vision disturbance, severe headache and stillbirth between two groups. There was a decrease in alkaline phosphatase levels in early preeclampsia with severe hypertension but other markers of liver function were not altered. However, renal function including blood urea nitrogen, creatinine and uric acid were significantly higher in early preeclampsia with severe hypertension. Umbilical artery systolic velocity/diastolic velocity ratio was significantly higher in early preeclampsia with severe hypertension. Our data demonstrates that the laboratory biomarkers of renal function differ between early and late preeclampsia with severe hypertension. The severity of renal dysfunction correlated with the time of delivery in preeclampsia with severe hypertension. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Prediction of Preeclampsia Using the Soluble fms-Like Tyrosine Kinase 1 to Placental Growth Factor Ratio

PubMed Central

Gaccioli, Francesca; Cook, Emma; Hund, Martin; Charnock-Jones, D. Stephen; Smith, Gordon C.S.

2017-01-01

We sought to assess the ratio of sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) in maternal serum as a screening test for preeclampsia in unselected nulliparous women with a singleton pregnancy. We studied 4099 women recruited to the POP study (Pregnancy Outcome Prediction) (Cambridge, United Kingdom). The sFlt-1:PlGF ratio was measured using the Roche Cobas e411 platform at ≈20, ≈28, and ≈36 weeks of gestational age (wkGA). Screen positive was defined as an sFlt-1:PlGF ratio >38, but higher thresholds were also studied. At 28 wkGA, an sFlt-1:PlGF ratio >38 had a positive predictive value (PPV) of 32% for preeclampsia and preterm birth, and the PPV was similar comparing women with low and high prior risk of disease. At 36 wkGA, an sFlt-1:PlGF ratio >38 had a PPV for severe preeclampsia of 20% in high-risk women and 6.4% in low-risk women. At 36 wkGA, an sFlt-1:PlGF ratio >110 had a PPV of 30% for severe preeclampsia, and the PPV was similar comparing low- and high-risk women. Overall, at 36 wkGA, 195 (5.2%) women either had an sFlt-1:PlGF ratio of >110 or an sFlt-1:PlGF ratio >38 plus maternal risk factors: 43% of these women developed preeclampsia, about half with severe features. Among low-risk women at 36 wkGA, an sFlt-1:PlGF ratio ≤38 had a negative predictive value for severe preeclampsia of 99.2%. The sFlt-1:PlGF ratio provided clinically useful prediction of the risk of the most important manifestations of preeclampsia in a cohort of unselected nulliparous women. PMID:28167687

Distribution of HLA-G extended haplotypes and one HLA-E polymorphism in a large-scale study of mother-child dyads with and without severe preeclampsia and eclampsia.

PubMed

Nilsson, L L; Djurisic, S; Andersen, A-M N; Melbye, M; Bjerre, D; Ferrero-Miliani, L; Hackmon, R; Geraghty, D E; Hviid, T V F

2016-10-01

The etiological pathways and pathogenesis of preeclampsia have rendered difficult to disentangle. Accumulating evidence points toward a maladapted maternal immune system, which may involve aberrant placental expression of immunomodulatory human leukocyte antigen (HLA) class Ib molecules during pregnancy. Several studies have shown aberrant or reduced expression of HLA-G in the placenta and in maternal blood in cases of preeclampsia compared with controls. Unlike classical HLA class Ia loci, the nonclassical HLA-G has limited polymorphic variants. Most nucleotide variations are clustered in the 5'-upstream regulatory region (5'URR) and 3'-untranslated regulatory region (3'UTR) of HLA-G and reflect a stringent expressional control. Based on genotyping and full gene sequencing of HLA-G in a large number of cases and controls (n > 900), the present study, which to our knowledge is the largest and most comprehensive performed, investigated the association between the HLA-G 14-bp ins/del (rs66554220) and HLA-E polymorphisms in mother and newborn dyads from pregnancies complicated by severe preeclampsia/eclampsia and from uncomplicated pregnancies. Furthermore, results from extended HLA-G haplotyping in the newborns are presented in order to assess whether a combined contribution of nucleotide variations spanning the 5'URR, coding region, and 3'UTR of HLA-G describes the genetic association with severe preeclampsia more closely. In contrast to earlier findings, the HLA-G 14-bp ins/del polymorphism was not associated with severe preeclampsia. Furthermore, the polymorphism (rs1264457) defining the two nonsynonymous HLA-E alleles, HLA-E*01:01:xx:xx and HLA-E*01:03:xx:xx, were not associated with severe preeclampsia. Finally, no specific HLA-G haplotypes were significantly associated with increased risk of developing severe preeclampsia/eclampsia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Community health workers' knowledge and practice in relation to pre-eclampsia in Ogun State, Nigeria: an essential bridge to maternal survival.

PubMed

Sotunsa, J O; Vidler, M; Akeju, D O; Osiberu, M O; Orenuga, E O; Oladapo, O T; Qureshi, R; Sawchuck, D; Adetoro, O O; von Dadelszen, P; Dada, O A

2016-09-30

Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality worldwide. Early detection and treatment have been instrumental in reducing case fatality in high-income countries. To achieve this in a low-income country, like Nigeria, community health workers who man primary health centres must have adequate knowledge and skills to identify and provide emergency care for women with pre-eclampsia. This study aimed to determine community health workers' knowledge and practice in the identification and treatment of pre-eclampsia, as they are essential providers of maternal care services in Nigeria. This study was part of a multi-country evaluation of community treatment of pre-eclampsia. Qualitative data were obtained from four Local Government Areas of Ogun State, in south western Nigeria by focus group discussions (N = 15) and in-depth interviews (N = 19). Participants included a variety of community-based health care providers - traditional birth attendants, community health extension workers, nurses and midwives, chief nursing officers, medical officers - and health administrators. Data were transcribed and validated with field notes and analysed with NVivo 10.0. Community-based health care providers proved to be aware that pre-eclampsia was due to the development of hypertension and proteinuria in pregnant women. They had a good understanding of the features of the condition and were capable of identifying women at risk, initiating care, and referring women with this condition. However, some were not comfortable managing the condition because of the limitation in their 'Standing Order'; these guidelines do not explicitly authorize community health extension workers to treat pre-eclampsia in the community. Community-based health care providers were capable of identifying and initiating appropriate care for women with pre-eclampsia. These competencies combined with training and equipment availability could improve maternal health in the rural areas. There is a need for regular training and retraining to enable successful task-sharing with these cadres. NCT01911494 .

Variable effects of maternal and paternal-fetal contribution to the risk for preeclampsia combining GSTP1, eNOS, and LPL gene polymorphisms.

PubMed

Pappa, Kalliopi I; Roubelakis, Maria; Vlachos, George; Marinopoulos, Spyros; Zissou, Antonia; Anagnou, Nicholas P; Antsaklis, Aris

2011-04-01

To evaluate the maternal, paternal, and fetal genotype contribution to preeclampsia. STUDY DESIGN, MATERIALS, AND METHODS: We combined the analysis of polymorphisms of the GSTP1, eNOS, and LPL genes - affecting biotransformation enzymes and endothelial function - in a cohort of 167 preeclamptic and normal control trios (mother, father, and child) comprising a total of 501 samples in the Greek population, never analyzed before by this approach. For the frequency of the GSTP1 Ile(105)/Val(105), the eNOS Glu298Asp and the LPL-93 polymorphisms, statistically significant differences were found between the two groups. However, the transmission rates of the parental alleles to neonates studied by the transmission disequilibrium test, disclosed no increased rate of transmission to preeclampsia children for the variant alleles of Val(105) GSTP1, 298Asp eNOS, and -93G LPL. These novel data, suggest that interaction of all three types of genotypes (mother, father and neonate), reveals no effects on the development of preeclampsia, but provide the impetus for further studies to decipher the individual contribution of each genetic parameter of preeclampsia.

Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura

PubMed Central

Jiang, Yang; McIntosh, Jennifer J.; Reese, Jessica A.; Deford, Cassandra C.; Kremer Hovinga, Johanna A.; Lämmle, Bernhard; Terrell, Deirdra R.; Vesely, Sara K.; Knudtson, Eric J.

2014-01-01

Pregnancy may precipitate acute episodes of thrombotic thrombocytopenic purpura (TTP), but pregnancy outcomes in women who have recovered from acquired TTP are not well documented. We analyzed pregnancy outcomes following recovery from TTP associated with acquired, severe ADAMTS13 deficiency (ADAMTS13 activity <10%) in women enrolled in the Oklahoma TTP-HUS Registry from 1995 to 2012. We also systematically searched for published reports on outcomes of pregnancies following recovery from TTP associated with acquired, severe ADAMTS13 deficiency. Ten women in the Oklahoma Registry had 16 subsequent pregnancies from 1999 to 2013. Two women had recurrent TTP, which occurred 9 and 29 days postpartum. Five of 16 pregnancies (31%, 95% confidence interval, 11%-59%) in 3 women were complicated by preeclampsia, a frequency greater than US population estimates (2.1%-3.2%). Thirteen (81%) pregnancies resulted in normal children. The literature search identified 382 articles. Only 6 articles reported pregnancies in women who had recovered from TTP associated with acquired, severe ADAMTS13 deficiency, describing 10 pregnancies in 8 women. TTP recurred in 6 pregnancies. Conclusions: With prospective complete follow-up, recurrent TTP complicating subsequent pregnancies in Oklahoma patients is uncommon, but the occurrence of preeclampsia may be increased. Most pregnancies following recovery from TTP in Oklahoma patients result in normal children. PMID:24398329

The Two Stage Model of Preeclampsia: Variations on the Theme

PubMed Central

Roberts, James M; Hubel, Carl A.

2009-01-01

The Two Stage Model of preeclampsia proposes that a poorly perfused placenta (Stage 1) produces factor(s) leading to the clinical manifestations of preeclampsia (Stage2). Stage 1 is not sufficient to cause the maternal syndrome but interacts with maternal constitutional factors (genetic, behavioral or environmental) to result in Stage 2. Recent information indicates the necessity for modifications of this model. It is apparent that changes relevant to preeclampsia and other implantation disorders can be detected in the first trimester, long before the failed vascular remodeling necessary to reduce placental perfusion. In addition, although the factor(s) released from the placenta has usually been considered a toxin, we suggest that what is released may also be an appropriate signal from the fetal/placental unit to overcome reduced nutrient availability that cannot by tolerated by some women who develop preeclampsia. Further, it is evident that linkage is not likely to be by one factor but several, different for different women. Also although the initial model limited the role of maternal constitutional factors to the genesis of Stage 2, this does not appear to be the case. It is evident that the factors increasing risk for preeclampsia are also associated with abnormal implantation. These several modifications have important implications. An earlier origin for Stage 1, which appears to be recognizable by altered concentrations of placental products, could allow earlier intervention. The possibility of a fetal placental factor increasing nutrient availability could provide novel therapeutic options. Different linkages and preeclampsia subtypes could direct specific preventive treatments for different women while the role of maternal constitutional factors to affect placentation provides targets for prepregnancy therapy. The modified Two Stage Model provides a useful guide towards investigating pathophysiology and guiding therapy. PMID:19070896

Reduced expression of the epidermal growth factor signaling system in preeclampsia.

PubMed

Armant, D R; Fritz, R; Kilburn, B A; Kim, Y M; Nien, J K; Maihle, N J; Romero, R; Leach, R E

2015-03-01

The epidermal growth factor (EGF) signaling system regulates trophoblast differentiation, and its disruption could contribute to perinatal disease. We hypothesized that this pathway is altered in preeclampsia, a disorder associated with trophoblast apoptosis and failure to invade and remodel the uterine spiral arteries. Six EGF family peptides and a truncated EGF receptor splice variant (p110/EGFR) were examined using immunohistochemistry in the trophoblast of placentas (N = 76) from women with preeclampsia, and compared to placentas from women of similar gestational age (GA) with preterm labor (PTL) or small for gestational age (SGA) fetuses, as well as normal term placentas. EGF, transforming growth factor-α (TGFA), and heparin-binding EGF-like growth factor (HBEGF) were evaluated using ELISA in maternal plasma from another 20 pregnancies with or without preeclampsia. Cell death was evaluated in the HTR-8/SVneo human cytotrophoblast cell line using TUNEL to evaluate the protective effects of EGF peptides. Trophoblast HBEGF, TGFA, and EGF were significantly reduced in preeclampsia compared to PTL and SGA, while p110/EGFR accumulated significantly on the surface of the chorionic villi (p < 0.05). Plasma EGF levels were significantly decreased in preeclamptic patients, compared to non-preeclamptic patients (p < 0.05). HBEGF, EGF, TGFA, epiregulin, and betacellulin each blocked cytotrophoblast cell death in vitro (p < 0.05). Three members of the EGF family are dysregulated in placentas with preeclampsia, whereas p110/EGFR, a potential EGF receptor antagonist, is overexpressed. These findings are consistent with the concept that disruption of the EGF signaling system contributes to aberrant trophoblast development associated with preeclampsia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

PubMed

van Uitert, Miranda; Moerland, Perry D; Enquobahrie, Daniel A; Laivuori, Hannele; van der Post, Joris A M; Ris-Stalpers, Carrie; Afink, Gijs B

2015-01-01

Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia.

Seasonal variation in the incidence of preeclampsia and eclampsia in tropical climatic conditions.

PubMed

Subramaniam, Vidya

2007-10-15

Observational studies have demonstrated various correlations between hypertensive disorders of pregnancy and different weather parameters. We aim to study if a correlation exists between the incidence of eclampsia and pre-eclampsia and various weather parameters in the tropical coastal city of Mumbai which has the distinction of having relatively uniform meteorological variables all throughout the year, except for the monsoon season. We retrospectively analysed data from a large maternity centre in Mumbai, India over a period of 36 months from March 1993 to February 1996, recording the incidence of preeclampsia and eclampsia. Meteorological data was acquired from the regional meteorological centre recording the monthly average temperature, humidity, barometric pressure and rainfall during the study period. Study period was then divided into two climate conditions: monsoon season (June to August) and dry season September to May. The incidence of preeclampsia and eclampsia and the meteorological differences between the two seasons were compared. Over a 36-month period, a total of 29562 deliveries were recorded, of which 1238 patients developed preeclampsia (4.18%) and 34 developed eclampsia (0.11%). The incidence of preeclampsia did not differ between the monsoon and the dry season (4.3% vs. 4.15%, p = 0.5). The incidence of eclampsia was significantly higher in the monsoon (0.2% vs. 0.08%, p = 0.01). The monsoon was significantly cooler (median maximum temperature 30.7 degrees C vs. 32.3 degrees C, p = 0.01), more humid (median relative humidity 85% vs. 70%, p = 0.0008), and received higher rainfall (median 504.9 mm vs. 0.3 mm, p = 0.0002) than the rest of the year. The median barometric pressure (1005 mb) during the monsoon season was significantly lower than the rest of the year (1012 mb, p < 0.0001). In the tropical climate of Mumbai, the incidence of eclampsia is significantly higher in monsoon, when the weather is cooler and humid with a lower barometric pressure than the rest of the year. This effect is not seen with preeclampsia. This strengthens the association of low temperature and high humidity with triggering of eclampsia.

Protein profiling of preeclampsia placental tissues.

PubMed

Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y; He, Jin; Ye, Fei

2014-01-01

Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia.

Nutritional approach to preeclampsia prevention.

PubMed

Achamrah, Najate; Ditisheim, Agnès

2018-05-01

Although not fully understood, the physiopathology of preeclampsia is thought to involve an abnormal placentation, diffuse endothelial cell dysfunction and increased systemic inflammation. As micronutrients play a key role in placental endothelial function, oxidative stress and expression of angiogenic factors, periconceptional micronutrient supplementation has been proposed to reduce the risk of preeclampsia. However, recent studies reported conflicting results. Calcium intake (>1 g/day) may reduce the risk of preeclampsia in women with low-calcium diet. Data from recently updated Cochrane reviews did not support routine supplementation of vitamins C, E or D for either the prevention or treatment of preeclampsia. Evidences are also poor to support zinc or folic acid supplementation for preeclampsia prevention. Dark chocolate, flavonoid-rich food, and long-chain polyunsaturated fatty acids might also be candidates for prevention of preeclampsia. Through antioxidant, anti-inflammatory or vasoactive proprieties, micronutrients are good candidates for preeclampsia prevention. Calcium supplementation is recommended to prevent preeclampsia in women with low-calcium intake. Despite positive clinical and in-vitro data, strong evidence to support periconceptional supplementation of other micronutrients for preeclampsia risk-reduction is still lacking. Further studies are also needed to evaluate the benefit of nutritional supplementation such as chocolate and long-chain polyunsaturated fatty acids.

Protein Profiling of Preeclampsia Placental Tissues

PubMed Central

Shu, Chang; Liu, Zitao; Cui, Lifeng; Wei, Chengguo; Wang, Shuwen; Tang, Jian Jenny; Cui, Miao; Lian, Guodong; Li, Wei; Liu, Xiufen; Xu, Hongmei; Jiang, Jing; Lee, Peng; Zhang, David Y.

2014-01-01

Preeclampsia is a multi-system disorder involved in pregnancy without an effective treatment except delivery. The precise pathogenesis of this complicated disorder is still not completely understood. The objective of this study is to evaluate the alterations of protein expression and phosphorylations that are important in regulating placental cell function in preterm and term preeclampsia. Using the Protein Pathway Array, 38 proteins in placental tissues were found to be differentially expressed between preterm preeclampsia and gestational age matched control, while 25 proteins were found to be expressed differentially between term preeclampsia and matched controls. Among these proteins, 16 proteins and their associated signaling pathways overlapped between preterm and term preeclampsia, suggesting the common pathogenesis of two subsets of disease. On the other hand, many proteins are uniquely altered in either preterm or term preeclampsia and correlated with severity of clinical symptoms and outcomes, therefore, providing molecular basis for these two subsets of preeclampsia. Furthermore, the expression levels of some of these proteins correlated with neonatal small for gestational age (PAI-1 and PAPP-A) and adverse outcomes (Flt-1) in women with preterm preeclampsia. These proteins could potentially be used as candidate biomarkers for predicting outcomes of preeclampsia. PMID:25392996

PP165. Treatment approaches for preeclampsia: A sample from a big city of a developing country.

PubMed

De Oliveira, L; Rocha, R M; Da Silva, L L; Rosas, C F; Korkes, H; Sass, N

2012-07-01

Preeclampsia is a major cause of maternal morbidity and mortality worldwide, mainly in developing countries. Here we show an example of how is the clinical condition of these patients when they are referred from first care units to a tertiary care teaching maternity in the city of São Paulo, Brazil. To evaluate how has been the approach for preeclamptic women in a big city of Brazil, an example of developing country. This is a retrospective study that evaluated 41 patients that were referred to our hospital from August 2010 to December 2011. In most of the cases patients were referred due to elevations in blood pressure. The diagnosis of preeclampsia was based on the ISSHP recommendations. The diagnosis of severe preeclampsia was based either on clinical symptoms and/or laboratory parameters. Fetal distress was defined when Doppler velocimetry assessment demonstrated abnormal parameters (centralization with abnormal diastolic blood flow at umbilical arteries). Severe preeclampsia was diagnosed in 26 cases (63.4%) and 34 patients were treated with magnesium sulfate (82.9%). One case of eclampsia (2.4%) and five cases of "Abruptio Placentae" (12.1%) were registered. Fetal distress was diagnosed at the moment of admission in 13 cases (31.7%) and two of these fetuses ended in stillbirth (4.8%). Neonatal death occurred in three cases (7.3%), mainly due to extreme preterm delivery. Other outcomes are reported in the following table. ICU: Intensive Care Unit. This is a good example of how has been the approach of preeclamptic women in a big city of Brazil. Our results suggest that a special concern about the moment of referring these patients to tertiary care units should be taken by doctors at first care units. Copyright © 2012. Published by Elsevier B.V.

Adverse maternal and neonatal outcomes in women with preeclampsia in Iran.

PubMed

Omani-Samani, Reza; Ranjbaran, Mehdi; Amini, Payam; Esmailzadeh, Arezoo; Sepidarkish, Mahdi; Almasi-Hashiani, Amir

2017-09-18

Preeclampsia is relatively a common complication in pregnancy and is characterized by high blood pressure and protein in urine during pregnancy. Consistent with the adverse outcomes followed by preeclampsia, this study designed to investigate the how preeclampsia is associated with preterm, low birth weight (LBW), cesarean section, and weigh gain during pregnancy. In this population-based cross-sectional study, 5166 deliveries from 103 hospitals in Tehran (Capital of Iran) were included in the analysis in 2015. The independent variable was preeclampsia during pregnancy and weight gain during pregnancy, preterm birth, cesarean section, and LBW were considered as interested outcomes. The data were analyzed by statistical Stata software (version 13, Stata Inc., College Station, TX). Adjusted results showed that the mean of weight gain in women with preeclampsia was significantly higher than women without preeclampsia (mean difference: 1.77 kg, 95%CI: 0.76-12.78, p = .001). The adjusted odds ratio for preterm birth, cesarean section, and LBW were 4.19 (95%CI: 2.71-6.48, p = .001), 1.92 (95%CI: 1.24-2.98, p = .003), and 1.19 (95%CI: 0.61-2.31, p = .599), respectively. Weight gain in women with preeclampsia was higher than women without preeclampsia and also the odds of preterm birth, cesarean section and LBW in women with preeclampsia was higher than women without preeclampsia.

Venous and autonomic function in formerly pre-eclamptic women and BMI-matched controls.

PubMed

Heidema, Wieteke M; van Drongelen, Joris; Spaanderman, Marc E A; Scholten, Ralph R

2018-03-25

Pre-pregnancy reduced plasma volume increases the risk on subsequent pre-eclamptic pregnancy. Reduced plasma volume is thought to reflect venous reserve capacity, especially when venous vasculature is constricted and sympathetic tone is elevated. As obesity might affect these variables and also relates to pre-eclampsia, increased body weight may underlie these observations. We hypothesized that the relationship between reduced venous reserve and preeclampsia is independent of body mass index (BMI). We compared the non-pregnant venous reserve capacity in 30 formerly pre-eclamptic women, equally divided in 3 BMI-classes (BMI 19.5-24.9, BMI 25-29.9, BMI ≥30) to 30 controls. Cases and controls were matched for BMI, age and parity. The venous reserve capacity was quantified by assessing plasma volume and venous compliance. The autonomic nervous system regulating the venous capacitance was evaluated with heart rate variability analysis in resting supine position and during positive head-up tilt (HUT). Formerly pre-eclamptic women had in supine position lower plasma volume than controls (1339 ± 79 vs 1547 ± 139 ml/m 2 (p<0.001)), lower venous compliance (0.04 ± 0.02 vs 0.07 ± 0.02 ml/dl/mmHg (p<0.001)), higher sympathetic tone (1.9 ± 0.1 vs 1.2 ± 0.7 mmHg 2 (p=0.002)) and lower baroreceptor sensitivity (8.7 ± 3.8 vs 19.0 ± 1.7 ms/mmHg (p<0.001)). During HUT, women with a history of preeclampsia have less modulatory capacity over venous compliance and baroreceptor sensitivity, while heart rate and sympathetic tone remain consistently higher. Women with a history of pre-eclampsia have, compared to BMI-matched controls, reduced venous reserve capacity. This is reflected by lower plasma volume and venous compliance, the autonomic balance is shifted towards sympathetic dominance and lower baroreceptor sensitivity. This suggests that not BMI, but underlying reduced venous reserve relates to pre-eclampsia. This article is protected by copyright. All rights reserved.

Meta analysis of angiotensin-converting enzyme I/D polymorphism as a risk factor for preeclampsia in Chinese women.

PubMed

Zhong, W G; Wang, Y; Zhu, H; Zhao, X

2012-08-13

Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. Inappropriate activation of the renin-angiotensin system may play a role in the development of preeclampsia. An insertion/deletion polymorphism in the angiotensin-converting enzyme gene (ACE-I/D) has been associated with differences in ACE activity. However, there are controversies in reports on the association of ACE-I/D with preeclampsia. Data were analyzed using Review Manager Version 5.0 and a random effects model was applied irrespective of between studies heterogeneity, which was evaluated via sensitivity and subgroup analyses. Publication bias was evaluated using the fail-safe number. A systematic search was performed based on published case control studies up to October 1, 2011, and 11 studies were included, involving 800 patients and 949 controls. Significant association of the ACE D allele with increase risk of preeclampsia was found (odds ratio = 1.93, 95% confidence interval = 1.19-3.12; P = 0.008). Sensitivity analysis showed that no individual study had an undue influence on the summary odds ratios for all contrasts. An analysis stratified by study size showed an attenuated odds ratio towards a null effect as study size increased. Based on our meta-analysis, we suggest that the D allele of the ACE gene is related with increased risk for preeclampsia in the Chinese population. Considering the potential existence of small study bias, further research should be performed with a larger dataset.

Hyperuricaemia and preeclampsia: is there a pathogenic link?

PubMed

Schackis, R C

2004-01-01

A hypothesis, based on animal studies and human observational studies, was developed proposing a direct pathogenic link between hyperuricemia and preeclampsia. Epidemiological characteristics of preeclampsia such as its uniqueness to humans and an increased incidence of preeclampsia in multiple pregnancies, increased body mass index, renal and hypertensive disease all have uric acid as their common denominator. Animal studies have linked hyperuricaemia to hypertensive, cardiovascular and renal disease. The aim of the study was to determine whether lowering the serum uric acid levels in preeclampsia would affect biochemical parameters and hypertensive control. A randomized, double-blind, placebo controlled study. A tertiary referral center. Forty women with preeclampsia between 26 and 32 weeks gestation. Probenecid 250 mg twice daily for seven days. Renal function and haematological parameters, hypertensive control. In the Probenecid group, there was a significant drop in the serum uric acid levels. Lower uric acid levels in the Probenecid group had no significant effect on blood pressure. Patients in the Probenecid group had a significantly lower serum creatinine value at the end of the study when compared to patients in the placebo group. Other renal function parameters (creatinine clearance, urea, 24 h urinary protein excretion) did not show any significant difference between the two groups. Platelet count differed between the two groups with the platelet count being significantly higher in the Probenecid group at the end of the study. The significant improvement in the platelet count in the Probenecid group warrants further study.

Congenital Perisylvian Syndrome presenting as Post-partum Seizures with Preeclampsia.

PubMed

Agarwal, Arun; Goyal, Manju; Jain, Jainendra; Agarwal, Aakanksha

2017-06-01

Whether preceded by preeclampsia, or occuring without antecedent warning symptoms, eclamptic seizures usually occur in the antepartum period between 20 and 40 weeks of gestation or within a few hours to 2 days postpartum. We report the case of a patient with pre-eclampsia who developed seizures after more than 2 days of delivery. In view of late onset postpartum seizures and non-responsiveness to magnesium sulphate, she was further evaluated and diagnosed to have congenital perisylvian syndrome(CPS). In CPS, polymicrogyric cortex is distributed in variable extensions around the sylvian fissure i.e. a structural malformation of the brain with underlying anomaly of polymicrogyria. © Journal of the Association of Physicians of India 2011.

Spatial Memory in the Progeny of Rats Subjected to Different Types of Experimental Preeclampsia.

PubMed

Perfilova, V N; Zhakupova, G A; Lashchenova, L I; Lebedeva, S A; Tyurenkov, I N

2016-09-01

Spatial memory was studied in 2-month-old offspring of rats subjected to different types of experimental preeclampsia (replacement of drinking water with 1.8% NaCl from day 1 to 21 of gestation or intraperitoneal administration of non-selective NO-synthase inhibitor L-NAME to pregnant rats in a daily dose of 25 mg/kg for 7 days on gestation days 14-20). Spatial memory was evaluated in an elevated 8-arm radial maze. Both types of experimental preeclampsia impaired spatial (long-term and short-term) memory and can be used in the development of drugs correcting negative effects of this pregnancy complication on memory.

Elevated Ratio of Maternal Plasma ApoCIII to ApoCII in Preeclampsia

DTIC Science & Technology

2011-05-01

presentation of preeclampsia varies significantly between individuals.3 Although both dyslipidemia and endothelial dysfunction are characteristic of...preeclampsia,3,4 a mechanism unifying the 2 phenomena remains to be estab- lished. Dyslipidemia becomes apparent in most patients with preeclampsia before... dyslipidemia components, leading to atherogenesis.8,9 We hypothesize that a similar mechanism may be applicable to the atherosis of preeclampsia. Apolipoprotein

Development and validation of Prediction models for Risks of complications in Early-onset Pre-eclampsia (PREP): a prospective cohort study.

PubMed

Thangaratinam, Shakila; Allotey, John; Marlin, Nadine; Mol, Ben W; Von Dadelszen, Peter; Ganzevoort, Wessel; Akkermans, Joost; Ahmed, Asif; Daniels, Jane; Deeks, Jon; Ismail, Khaled; Barnard, Ann Marie; Dodds, Julie; Kerry, Sally; Moons, Carl; Riley, Richard D; Khan, Khalid S

2017-04-01

The prognosis of early-onset pre-eclampsia (before 34 weeks' gestation) is variable. Accurate prediction of complications is required to plan appropriate management in high-risk women. To develop and validate prediction models for outcomes in early-onset pre-eclampsia. Prospective cohort for model development, with validation in two external data sets. Model development: 53 obstetric units in the UK. Model transportability: PIERS (Pre-eclampsia Integrated Estimate of RiSk for mothers) and PETRA (Pre-Eclampsia TRial Amsterdam) studies. Pregnant women with early-onset pre-eclampsia. Nine hundred and forty-six women in the model development data set and 850 women (634 in PIERS, 216 in PETRA) in the transportability (external validation) data sets. The predictors were identified from systematic reviews of tests to predict complications in pre-eclampsia and were prioritised by Delphi survey. The primary outcome was the composite of adverse maternal outcomes established using Delphi surveys. The secondary outcome was the composite of fetal and neonatal complications. We developed two prediction models: a logistic regression model (PREP-L) to assess the overall risk of any maternal outcome until postnatal discharge and a survival analysis model (PREP-S) to obtain individual risk estimates at daily intervals from diagnosis until 34 weeks. Shrinkage was used to adjust for overoptimism of predictor effects. For internal validation (of the full models in the development data) and external validation (of the reduced models in the transportability data), we computed the ability of the models to discriminate between those with and without poor outcomes ( c -statistic), and the agreement between predicted and observed risk (calibration slope). The PREP-L model included maternal age, gestational age at diagnosis, medical history, systolic blood pressure, urine protein-to-creatinine ratio, platelet count, serum urea concentration, oxygen saturation, baseline treatment with antihypertensive drugs and administration of magnesium sulphate. The PREP-S model additionally included exaggerated tendon reflexes and serum alanine aminotransaminase and creatinine concentration. Both models showed good discrimination for maternal complications, with anoptimism-adjusted c -statistic of 0.82 [95% confidence interval (CI) 0.80 to 0.84] for PREP-L and 0.75 (95% CI 0.73 to 0.78) for the PREP-S model in the internal validation. External validation of the reduced PREP-L model showed good performance with a c -statistic of 0.81 (95% CI 0.77 to 0.85) in PIERS and 0.75 (95% CI 0.64 to 0.86) in PETRA cohorts for maternal complications, and calibrated well with slopes of 0.93 (95% CI 0.72 to 1.10) and 0.90 (95% CI 0.48 to 1.32), respectively. In the PIERS data set, the reduced PREP-S model had a c -statistic of 0.71 (95% CI 0.67 to 0.75) and a calibration slope of 0.67 (95% CI 0.56 to 0.79). Low gestational age at diagnosis, high urine protein-to-creatinine ratio, increased serum urea concentration, treatment with antihypertensive drugs, magnesium sulphate, abnormal uterine artery Doppler scan findings and estimated fetal weight below the 10th centile were associated with fetal complications. The PREP-L model provided individualised risk estimates in early-onset pre-eclampsia to plan management of high- or low-risk individuals. The PREP-S model has the potential to be used as a triage tool for risk assessment. The impacts of the model use on outcomes need further evaluation. Current Controlled Trials ISRCTN40384046. The National Institute for Health Research Health Technology Assessment programme.

[Use of sFlt-1/PlGF ratio in preeclampsia : a monocentric retrospective analysis].

PubMed

Verbeurgt, L; Chantraine, F; De Marchin, J; Minon, J-M; Nisolle, M

2017-09-01

Soluble Fms-like tyrosine kinase 1 (sFlt-1) is an anti-angiogenic factor released in higher amounts in preeclampsia and implicated in endothelial dysfunction. sFlt-1/PlGF ratio is used in the prediction of preeclampsia. An sFlt-1/PlGF ratio inferior to 38 predicts the short-term absence of preeclampsia. A ratio ? 85 (early-onset PE) or ? 110 (late-onset of PE) could diagnose preeclampsia. In this study, sFlt-1/PlGF ratio has been measured in 183 patients. Sixty-seven preeclampsia have been diagnosed preeclamptic at delivery. The median sFlt-1/PlGF ratio was 100.3. The median ratio among women with preeclampsia (N=67) versus no preeclampsia (N=116) was 212.7 versus 35.4. In accordance with this analysis, an sFlt-1/PlGF ratio ? 38 has a sensibility of 95,5 % and a specificity of 73.3 %. The positive predictive value and the negative predictive value were 67.4 % and 96.6 %, respectively. These results suggest that sFlt-1/PlGF ratio is helpful in the diagnosis of preeclampsia.

Ethical issues related to screening for preeclampsia.

PubMed

Jørgensen, Jennifer M; Hedley, Paula L; Gjerris, Mickey; Christiansen, Michael

2014-09-01

The implementation of new methods of treating and preventing disease raises many question of both technical and moral character. Currently, many studies focus on developing a screening test for preeclampsia (PE), a disease complicating 2-8% of pregnancies, potentially causing severe consequences for pregnant women and their fetuses. The purpose is to develop a test that can identify pregnancies at high risk for developing PE sufficiently early in pregnancy to allow for prophylaxis. However, the question of implementing a screening test for PE does not only involve an evaluation of technical feasibility and clinical efficacy, it also requires an analysis of how the test influences the conditions and choices for those tested. This study evaluates state-of-the-art techniques for preeclampsia screening in an ethical framework, pointing out the central areas of moral relevance within the context of such screening activity. Furthermore, we propose ethical guidelines that a screening programme for PE should meet in order to become an uncontroversial addition to prenatal health care. © 2012 John Wiley & Sons Ltd.

EG-VEGF Maintenance Over Early Gestation to Develop a Pregnancy-Induced Hypertensive Animal Model.

PubMed

Reynaud, Déborah; Sergent, Frédéric; Abi Nahed, Roland; Brouillet, Sophie; Benharouga, Mohamed; Alfaidy, Nadia

2018-01-01

During the last decade, multiple animal models have been developed to mimic hallmarks of pregnancy-induced hypertension (PIH) diseases, which include gestational hypertension, preeclampsia (PE), or eclampsia. Converging in vitro, ex vivo, and clinical studies from our group strongly suggested the potential involvement of the new angiogenic factor EG-VEGF (endocrine gland-derived-VEGF) in the development of PIH. Here, we described the protocol that served to demonstrate that maintenance of EG-VEGF production over 11.5 days post coitus (dpc) in the gravid mice caused the development of PIH. The developed model exhibited most hallmarks of preeclampsia.

Blood pressure self-monitoring in pregnancy (BuMP) feasibility study; a qualitative analysis of women's experiences of self-monitoring.

PubMed

Hinton, Lisa; Tucker, Katherine L; Greenfield, Sheila M; Hodgkinson, James A; Mackillop, Lucy; McCourt, Christine; Carver, Trisha; Crawford, Carole; Glogowska, Margaret; Locock, Louise; Selwood, Mary; Taylor, Kathryn S; McManus, Richard J

2017-12-19

Hypertensive disorders in pregnancy are a leading cause of maternal and fetal morbidity worldwide. Raised blood pressure (BP) affects 10% of pregnancies worldwide, of which almost half develop pre-eclampsia. The proportion of pregnant women who have risk factors for pre-eclampsia (such as pre-existing hypertension, obesity and advanced maternal age) is increasing. Pre-eclampsia can manifest itself before women experience symptoms and can develop between antenatal visits. Incentives to improve early detection of gestational hypertensive disorders are therefore strong and self-monitoring of blood pressure (SMBP) in pregnancy might be one means to achieve this, whilst improving women's involvement in antenatal care. The Blood Pressure Self-Monitoring in Pregnancy (BuMP) study aimed to evaluate the feasibility and acceptability of SMBP in pregnancy. To understand women's experiences of SMBP during pregnancy, we undertook a qualitative study embedded within the BuMP observational feasibility study. Women who were at higher risk of developing hypertension and/or pre-eclampsia were invited to take part in a study using SMBP and also invited to take part in an interview. Semi-structured interviews were conducted at the women's homes in Oxfordshire and Birmingham with women who were self-monitoring their BP as part of the BuMP feasibility study in 2014. Interviews were conducted by a qualitative researcher and transcribed verbatim. A framework approach was used for analysis. Fifteen women agreed to be interviewed. Respondents reported general willingness to engage with monitoring their own BP, feeling that it could reduce anxiety around their health during pregnancy, particularly if they had previous experience of raised BP or pre-eclampsia. They felt able to incorporate self-monitoring into their weekly routines, although this was harder post-partum. Self-monitoring of BP made them more aware of the risks of hypertension and pre-eclampsia in pregnancy. Feelings of reassurance and empowerment were commonly reported by the women in our sample. SMBP in pregnancy was both acceptable and feasible to women in this small pilot study.

First versus second trimester mean platelet volume and uric acid for prediction of preeclampsia in women at moderate and low risk.

PubMed

Rezk, Mohamed; Gaber, Wael; Shaheen, Abdelhamid; Nofal, Ahmed; Emara, Mahmoud; Gamal, Awni; Badr, Hassan

2018-06-12

To determine if second trimester mean platelet volume (MPV) and serum uric acid are reasonable predictors of preeclampsia (PE) or not, in patients at moderate and low risk. This prospective study was conducted on 9522 women at low or moderate risk for developing PE who underwent dual measurements of MPV and serum uric acid at late first trimester (10-12 weeks) and at second trimester (18-20 weeks) and subsequently divided into two groups; PE group (n = 286) who later developed PE and non-PE group (n = 9236). Test validity of MPV and serum uric acid was the primary outcome measure. Data were collected and analyzed. Second trimester MPV is a good predictor for development of PE at a cutoff value of 9.55 fL with area under the curve (AUC) of 0.86, sensitivity of 95.2%, specificity of 66.7%, positive predictive value (PPV) of 87%, negative predictive value (NPV) of 85.7%, and accuracy of 86.7%. Second trimester serum uric acid is a good predictor for development of PE at a cutoff value of 7.35 mg/dL, with AUC of 0.85, sensitivity of 95.2%, specificity of 55.6%, PPV of 83.3%, NPV of 83.3%, and accuracy of 83.3%. Combination of both tests has a sensitivity of 100%, specificity of 22.2%, PPV of 75%, NPV of 100%, and accuracy of 76.7%. Second trimester MPV and serum uric acid alone or in combination could be used as a useful biochemical markers for prediction of PE based on their validity, simplicity, and availability.

[Diagnostic value of radom spot albuminuria to creatinine ratio in women with preeclampsia].

PubMed

Gao, Yun-fei; Huang, Qi-tao; Zhong, Mei; Wang, Yan; Wang, Wei; Wang, Zhi-jian; Leng, Ling-zhi; Yu, Yan-hong

2012-03-01

To investigate the correlation between spot albuminuria to creatinine ratio (ACR) and 24 h urinary protein excretion in women with preeclampsia and determine the optimal cut-off values of spot ACR in mild preeclampsia and severe preeclampsia. Twenty-eight women with mild preeclampsia and 22 with severe preeclampsia at Nanfang Hospital, Southern Medical University between October 2010 and June 2011 were recruited. Maternal serum cystatin, uric acid, urea nitrogen, creatinine and albumin levels were collected and analyzed. Twenty-four hours urinary protein excretion was measured with immunoturbidimetric assay and ACR with automatic analyzer DCA2000. The correlation between ACR and 24 hours urinary protein excretion was explored. And the optimal cut-off values of the spot ACR for mild and severe preeclampsia were determined with receiver operating characteristic curve. (1) Maternal serum biochemical parameters: uric acid levels in mild and severe preeclampsia were (359 ± 114) µmol/L and (450 ± 132) µmol/L, while cystatin levels were (1.3 ± 0.3) mg/L and (1.6 ± 0.5) mg/L respectively. The differences were statistically significant (P < 0.05). Serum urea nitrogen, creatinine and albumin in mild preeclampsia were (3.6 ± 1.6) mmol/L, (52 ± 38) µmol/L and (33 ± 3) g/L, while in severe preeclampsia were (6.2 ± 3.1) mmol/L, (78 ± 59) µmol/L and (29 ± 6) g/L respectively. There were no statistical significant differences (P > 0.05). (2) Twenty-four hours urinary protein excretion and ACR: 24 hours urinary protein levels in mild and severe preeclampsia was (700 ± 160) mg and (4800 ± 2200) mg (P < 0.05). ACR in mild and severe preeclampsia was (72.7 ± 12.4) mg/mmol and (401 ± 245) mg/mmol respectively (P < 0.05). (3) There was a strong correlation between the spot ACR and 24 hours urine protein excretion (r = 0.938; P < 0.05). (4) The optimal spot ACR cut-off point for the diagnosis of preeclampsia: the optimal spot ACR cut-off point was 22.8 mg/mmol for 300 mg/24 hours of protein excretion in mild preeclampsia, the area under curve was 0.956, with a sensitivity, specificity of 82.4%, 99.4% respectively. And the optimal spot ACR cut-off point was 155.6 mol for 2000 mg/24 hours of protein excretion in severe preeclampsia, the area under curve was 0.956, with a sensitivity, specificity of 88.6%, 91.3% respectively. Compared with 24 hours urinary protein excretion, the spot ACR may be a simple, convenient and accurate indicator of early diagnosis of preeclampsia. Spot ACR may be used as a replacement for 24 hours urine protein excretion in assessment of preeclampsia. The optimal spot ACR cut off points were 22.8 mg/mmol for mild preeclampsia and 155.6 mg/mmol for severe preeclampsia.

Diastolic blood pressure is a potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes.

PubMed

Nørgaard, Sidse Kjærhus; Vestgaard, Marianne Jenlev; Jørgensen, Isabella Lindegaard; Ásbjörnsdóttir, Björg; Ringholm, Lene; McIntyre, Harold David; Damm, Peter; Mathiesen, Elisabeth Reinhardt

2018-04-01

To identify early clinical, modifiable risk factors for preeclampsia present at first antenatal visit and assess the prevalence of pregnancy-related hypertensive disorders in women with pre-existing diabetes treated with tight glycemic and blood pressure (BP) control. A population-based cohort study of 494 women with pre-existing diabetes (307 and 187 women with type 1 and type 2 diabetes, respectively), included at their first antenatal visit from 2012 to 2016. The prevalence of chronic hypertension (without diabetic nephropathy or microalbuminuria), gestational hypertension and preeclampsia was recorded. Diabetic microangiopathy included presence of nephropathy, microalbuminuria and/or retinopathy. Treatment target was BP <135/85 mmHg. HbA1c was 6.9 ± 2.4% (50 ± 12 mmol/mol) at first antenatal visit and 6.0 ± 0.6% (43 ± 6 mmol/mol) before delivery with no differences between women with type 1 and type 2 diabetes. At the first antenatal visit, the prevalence of microalbuminuria was 6% (6% vs. 6%), nephropathy 2% (1% vs. 2%) and chronic hypertension 6% (3% vs. 10%, p = 0.03). Gestational hypertension developed in 8% (9% vs. 6%) and preeclampsia developed in 8% (9% vs. 7%). Presence of diabetic microangiopathy (adjusted odds ratio (OR) 4.35 (confidence interval 2.12-8.93)) and diastolic BP (adjusted OR 1.72 per 10 mmHg (1.05-2.82)) at the first antenatal visit were independent risk factors for preeclampsia. At the first antenatal visit, diastolic BP was the only independent, potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes in the context of tight glycemic and BP control. One out of four women had hypertensive disorders during pregnancy. Copyright © 2018 Elsevier B.V. All rights reserved.

Triggers for Preeclampsia Onset: a Case-Crossover Study.

PubMed

Ford, Jane B; Schemann, Kathrin; Patterson, Jillian A; Morris, Jonathan; Herbert, Robert D; Roberts, Christine L

2016-11-01

Risk factors for preeclampsia are well established, whereas, the triggers associated with timing of preeclampsia onset are not. The aim of this study was to establish whether recent infection or other triggers were associated with timing of preeclampsia onset. We used a case-crossover design with preeclampsia cases serving as their own controls. Women with singleton pregnancies of ≥20 weeks gestation presenting at three hospitals were eligible for inclusion. Exposures to potential triggers were identified via guided questionnaire. Infective episodes included symptoms lasting >24 h. Preeclampsia was defined as hypertension (BP ≥140 mmHg and/or ≥90 mmHg) and proteinuria (protein/creatinine ratio ≥30 mg/mmol). Conditional logistic regression was used to compare the odds of exposure to potential triggers in the case windows (1-7 days preceding diagnosis of preeclampsia) and control windows (8-14 days prior to diagnosis); unadjusted odds ratios (ORs) are reported. Among 286 recruited women, 25 (8.7%) reported a new infection in the 7 days prior to preeclampsia onset and 21 (7.3%) in the 8-14 days prior. There was no significant association between onset of infection in the 7 days prior and preeclampsia diagnosis (OR 1.24, 95% CI 0.65, 2.34). Consumption of caffeine (OR 0.51, 95% CI 0.33, 0.77), spicy food (OR 0.49, 95% CI 0.30, 0.81), and alcohol (OR 0.26, 95% CI 0.10, 0.71) were strongly inversely associated with preeclampsia onset. Recent infection does not appear to trigger preeclampsia. Decreased consumption of caffeine, spicy food, and alcohol may be prodromal markers. Such behaviours may be early markers of imminent preeclampsia. © 2016 John Wiley & Sons Ltd.

Calcium supplementation prevents endothelial cell activation: possible relevance to preeclampsia.

PubMed

Chen, Qi; Tong, Mancy; Wu, Man; Stone, Peter R; Snowise, Saul; Chamley, Lawrence W

2013-09-01

Preeclampsia is a leading cause of maternal and fetal mortality and morbidity. A hallmark of preeclampsia is endothelial cell dysfunction/activation in response to 'toxins' from the placenta. Necrotic trophoblastic debris (NTD) is one possible placental toxin and other activators of endothelial cells include inflammatory cytokines. Calcium supplementation appears to protect 'at-risk' women from developing preeclampsia but how is unclear. Placental explants were cultured with interleukin-6 (IL-6) in varied concentrations of calcium. The resultant trophoblastic debris was exposed to endothelial cells. Endothelial cells were exposed to activators including NTD, IL-6, and preeclamptic sera in the presence of varied concentrations of calcium and activation monitored by quantifying cell surface markers by ELISA. Raising the levels of calcium did not prevent the IL-6-induced shedding of NTD from placental explants but did prevent the activation of endothelial cells in response to IL-6, preeclamptic sera, or NTD. Reducing the level of calcium directly induced the activation of endothelial cells. Inhibiting nitric oxide synthetase ablated the ability of high calcium levels to protect endothelial cell activation. The activity of endothelial cell nitric oxide synthetase was blocked with L-N-nitroarginine methyl ester. Our results demonstrate calcium levels do not affect the shedding of trophoblastic debris but are important to endothelial cell activation and supplemental calcium may reverse the activation of the endothelium in preeclamptic women. These results may in part explain the benefits of calcium supplementation in the reduction of risk for developing preeclampsia and provide in-vitro mechanistic support for the use of calcium supplementation in at-risk women.

Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.

PubMed

Duffy, Jmn; Hirsch, M; Pealing, L; Showell, M; Khan, K S; Ziebland, S; McManus, R J

2018-06-01

Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. To assess safety reporting in pre-eclampsia trials. Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC. © 2017 Royal College of Obstetricians and Gynaecologists.

Preeclampsia – Will Orphan Drug Status Facilitate Innovative Biological Therapies?

PubMed Central

Hahn, Sinuhe

2015-01-01

It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia. PMID:25767802

Preeclampsia - will orphan drug status facilitate innovative biological therapies?

PubMed

Hahn, Sinuhe

2015-01-01

It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia.

Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies

PubMed Central

Barrera, David; Díaz, Lorenza; Noyola-Martínez, Nancy; Halhali, Ali

2015-01-01

Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease. PMID:26247971

Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies.

PubMed

Barrera, David; Díaz, Lorenza; Noyola-Martínez, Nancy; Halhali, Ali

2015-08-04

Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

Maternal one carbon metabolism through increased oxidative stress and disturbed angiogenesis can influence placental apoptosis in preeclampsia.

PubMed

Kasture, Vaishali V; Sundrani, Deepali P; Joshi, Sadhana R

2018-05-14

Adequate maternal nutrition is critical for a healthy pregnancy outcome and poor maternal nutrition is known to be associated with pregnancy complications like preeclampsia. We have earlier demonstrated that there is an imbalance in the levels of micronutrients (folate and vitamin B 12 ) along with low levels of long chain polyunsaturated fatty acids (LCPUFA) and high homocysteine levels in women with preeclampsia. Homocysteine is known to be involved in the formation of free radicals leading to increased oxidative stress. Higher oxidative stress has been shown to be associated with increased apoptotic markers in the placenta. Preeclampsia is of placental origin and is associated with increased oxidative stress, disturbed angiogenesis and placental apoptosis. The process of angiogenesis is important for placental and fetal development and various angiogenic growth factors inhibit apoptosis by inactivation of proapoptotic proteins through a series of cellular signalling pathways. We propose that an altered one carbon cycle resulting in increased oxidative stress and impaired angiogenesis will contribute to increased placental apoptosis leading to preeclampsia. Understanding the association of one carbon cycle components and the possible mechanisms through which they regulate apoptosis will provide clues for reducing risk of pregnancy complications. Copyright © 2017. Published by Elsevier Inc.

Morphological changes of placental syncytium and their implications for the pathogenesis of preeclampsia.

PubMed

Roland, Cynthia S; Hu, Jian; Ren, Chun-E; Chen, Haibin; Li, Jinping; Varvoutis, Megan S; Leaphart, Lynn W; Byck, David B; Zhu, Xueqiong; Jiang, Shi-Wen

2016-01-01

Preeclampsia is a hypertensive disease that complicates many pregnancies, typically presenting with new-onset or worsening hypertension and proteinuria. It is well recognized that the placental syncytium plays a key role in the pathogenesis of preeclampsia. This review summarizes the findings pertaining to the structural alterations in the syncytium of preeclamptic placentas and analyzes their pathological implications for the development of preeclampsia. Changes in the trophoblastic lineage, including those in the proliferation of cytotrophoblasts, the formation of syncytiotrophoblast through cell fusion, cell apoptosis and syncytial deportation, are discussed in the context of preeclampsia. Extensive correlations are made between functional deficiencies and the alterations on the levels of gross anatomy, tissue histology, cellular events, ultrastructure, molecular pathways, and gene expression. Attention is given to the significance of dynamic changes in the syncytial turnover in preeclamptic placentas. Specifically, experimental evidences for the complex and obligatory role of syncytin-1 in cell fusion, cell-cycle regulation at the G1/S transition, and apoptosis through AIF-mediated pathway, are discussed in detail in the context of syncytium homeostasis. Finally, the recent observations on the aberrant fibrin deposition in the trophoblastic layer and the trophoblast immature phenotype in preeclamptic placentas and their potential pathogenic impact are also reviewed.

Should we recommend universal aspirin for all pregnant women?

PubMed

Mone, Fionnuala; Mulcahy, Cecilia; McParland, Peter; McAuliffe, Fionnuala M

2017-02-01

Low-dose aspirin has been demonstrated to reduce the incidence of preeclampsia and fetal growth restriction in at-risk populations. Its role in low-risk populations is as yet unknown. Novel preeclampsia screening tests are emerging that can predict the risk of the development of preeclampsia from as early as 11 weeks of gestation. It may be more efficacious, acceptable, and cost-effective to prescribe low-dose aspirin to all pregnant women from the first trimester as opposed to performing a screening test in the first instance. There is variation in opinion: the American College of Obstetricians and Gynecologists suggests the use of aspirin only in women who are at risk of preeclampsia, based on patient history; the National Institute for Health and Clinical Excellence, UK, and the US Preventative Services Task Force recommend the use of low-dose aspirin if there is 1 major or 2 moderate risk factors. This point-counterpoint discussion shall address (1) controversies regarding the real impact of low-dose aspirin; (2) controversies in the actual guidelines among the different national societies; (3) controversies regarding emerging preeclampsia screening tests in terms of cost-effectiveness and efficacy, and (4) points in favor of the provision of universal vs screened-positive women. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetics of preeclampsia: what are the challenges?

PubMed

Bernard, Nathalie; Giguère, Yves

2003-07-01

Despite recent efforts to identify susceptibility genes of preeclampsia, the genetic determinants of the condition remain ill-defined, as is the situation for most disorders of complex inheritance patterns. The angiotensinogen, factor V, and methylenetetrahydrofolate reductase genes have been investigated in different populations, as have other genes involved in blood pressure, vascular volume control, thrombophilia, lipid metabolism, oxidative stress, and endothelial dysfunction. The study of the genetics of complex traits is faced with both methodological and genetic issues; these include adequate sample size to allow for the identification of modest genetic effects, of gene-gene and gene-environment interactions, the study of adequate quantitative traits and extreme phenotypes, haplotype analyses, statistical genetics, genome-wide (hypothesis-free) versus candidate-gene (hypothesis-driven) approaches, and the validation of positive associations. The use of genetically well-characterized populations showing a founder effect, such as the French-Canadian population of Quebec, in genetic association studies, may help to unravel the susceptibility genes of disorders showing complex inheritance, such as preeclampsia. It is necessary to better evaluate the role of the fetal genome in the resulting predisposition to preeclampsia and its complications. Eventually, we may be able to integrate genetic information to better identify the women at risk of developing preeclampsia, and to improve the management of those suffering from this condition.

[Pregnancy in patients with renal transplantation: maternal and fetal morbidity].

PubMed

Romero Arauz, Juan Fernando; Ayala Méndez, José Antonio; Jiménez Solís, Guillermo

2008-11-01

Preeclampsia is a multisystemic syndrome with unknown etiology and characterized by abnormal vascular placentation response. Patients with renal transplantation restore them fertility 10 months after the intervention. To evaluate incidence of preeclampsia and maternal-perinatal outcome in patients with renal transplantation. Comparative, observational and retrospective study performed in pregnant patients with renal transplantation, from December 1999 to April 2008 at Perinatology of Hypertensive Diseases Department of the Unidad Medica de Alta Especialidad de Ginecoobstetricia Luis Castelazo Ayala, IMSS. Davison' guide, descriptive statistic, and Fischer exact test were used. Thirty patients were analyzed, 27 cases satisfy Davison's recommended guidelines, and the rest did not achieve these criteria (p = 0.001). Preeclampsia occurred in 15 cases (50%), preterm delivery in 15 (50%), and fetal growth restriction in 6 (20%). Among the 11 patients with previous chronic hypertension, 8 developed superimposed preeclampsia (72%), and 9 had delivery before 37 weeks of gestation (82%). Malfunction of renal transplantation, before pregnancy, was associated with maternal and perinatal poor outcome (p = 0.006). There were no maternal deaths, but one perinatal (3%) Successful pregnancy is possible in patients with renal transplantation, however there is a high risk of preeclampsia, infection, and fetal growth restriction. Patients with renal transplantation must fulfill Davison's pre-pregnancy guidelines.

Molecular association of pathogenetic contributors to pre-eclampsia (pre-eclampsia associome)

PubMed Central

2015-01-01

Background Pre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point. Results The use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA or INS]-[NOS3]-[pre-eclampsia]; [INS]-[HSPA4 or CLU]-[pre-eclampsia]; [ACE]-[MTHFR]-[pre-eclampsia]. Conclusions For pre-eclampsia, diabetes mellitus, gestational diabetes and obesity, we showed that the size and connectivity of the associative molecular genetic networks, which describe interactions between comorbid diseases, statistically exceeded the size and connectivity of those built for randomly chosen pairs of diseases. Recently, we have shown a similar result for inversely comorbid diseases. This suggests that comorbid and inversely comorbid diseases have common features concerning structural organization of associative molecular genetic networks. PMID:25879409

First-trimester smoking cessation in pregnancy did not increase the risk of preeclampsia/eclampsia: A Murmansk County Birth Registry study

PubMed Central

Grjibovski, Andrej M.; Krettek, Alexandra; Nieboer, Evert; Odland, Jon Ø.

2017-01-01

Background Although prior studies have shown that smoking reduces preeclampsia/eclampsia risk, the consequence of giving up this habit during pregnancy should be assessed. The aims of the current study were threefold: (i) describe maternal characteristics of women with preeclampsia/eclampsia; (ii) examine a possible association between the number of cigarettes smoked daily during pregnancy and the development of this affliction; and (iii) determine if first-trimester discontinuation of smoking during pregnancy influences the risk. Methods A registry-based study was conducted using data from the Murmansk County Birth Registry (MCBR). It included women without pre-existing hypertension, who delivered a singleton infant during 2006–2011 and had attended the first antenatal visit before 12 week of gestation. We adjusted for potential confounders using logistic regression. Results The prevalence of preeclampsia/eclampsia was 8.3% (95%CI: 8.0–8.6). Preeclampsia/eclampsia associated with maternal age, education, marital status, parity, excessive weight gain and body mass index at the first antenatal visit. There was a dose-response relationship between the number of smoked cigarettes per day during pregnancy and the risk of preeclampsia/eclampsia (adjusted OR1-5 cig/day = 0.69 with 95%CI: 0.56–0.87; OR6-10 cig/day = 0.65 with 95%CI: 0.51–0.82; and OR≥11 cig/day = 0.49 with 95%CI: 0.30–0.81). There was no difference in this risk among women who smoked before and during pregnancy and those who did so before but not during pregnancy (adjusted OR = 1.10 with 95%CI: 0.91–1.32). Conclusions Preeclampsia/eclampsia was associated with maternal age, education, marital status, parity, excessive weight gain, and body mass index at the first antenatal visit. There was a negative dose-response relationship between the number of smoked cigarettes per day during pregnancy and the odds of preeclampsia/eclampsia. However, women who gave up smoking during the first trimester of gestation had the same risk of preeclampsia/eclampsia as those who smoked while pregnant. Consequently, antenatal clinic specialists are advised to take these various observations into account when counselling women on smoking cessation during pregnancy. PMID:28797036

Gestational weight gain as a risk factor for hypertensive disorders of pregnancy.

PubMed

Macdonald-Wallis, Corrie; Tilling, Kate; Fraser, Abigail; Nelson, Scott M; Lawlor, Debbie A

2013-10-01

Pregnancy interventions to limit gestational weight gain (GWG) have been proposed as a means of preventing hypertensive disorders of pregnancy (HDP); however, it is currently unclear whether GWG has a causal influence on the development of HDP. Thus, we aimed to determine whether GWG in early pregnancy is a risk factor for preeclampsia and gestational hypertension and whether GWG precedes the increases in blood pressure in normotensive women across pregnancy. We examined repeat antenatal clinic measurements of weight and blood pressure (median of 12 and 14 per woman, respectively) of 12,522 women in the Avon Longitudinal Study of Parents and Children. Greater prepregnancy weight was associated with an increased risk of gestational hypertension and preeclampsia per 10 kg of prepregnancy weight: odds ratio (OR), 1.80; 95% confidence interval (CI), 1.70-1.91 and OR, 1.71; 95% CI, 1.49-1.95, respectively, for women weighing 90 kg or less before pregnancy; OR, 1.24; 95% CI, 1.03-1.49 and OR, 1.61; 95% CI, 1.18-2.19 for women weighing more than 90 kg. Fully adjusted odds ratios for gestational hypertension and preeclampsia per 200 g per week GWG up to 18 weeks were OR, 1.26; 95% CI, 1.16-1.38 and OR, 1.31; 95% CI, 1.07-1.62. In normotensive women, GWG in early pregnancy was associated positively with blood pressure change in midpregnancy and negatively with blood pressure change in late pregnancy. In all gestational periods, GWG was positively associated with concurrent blood pressure change. However, there was no evidence that blood pressure changes in any period were associated with subsequent GWG. These findings suggest that GWG in early pregnancy may be a potential target for interventions aimed at reducing the risk of HDP. Copyright © 2013 Mosby, Inc. All rights reserved.

Preeclampsia; short and long-term consequences for mother and neonate.

PubMed

Bokslag, Anouk; van Weissenbruch, Mirjam; Mol, Ben Willem; de Groot, Christianne J M

2016-11-01

Preeclampsia is a common pregnancy specific disease, that presents with hypertension and a variety of organ failures, including malfunction of kidneys, liver and lungs. At present, the only definitive treatment of preeclampsia is end the pregnancy and deliver the neonate and placenta. For women with mild preeclampsia in the preterm phase of pregnancy, expectant management is generally indicated to improve fetal maturity, often requiring maternal medical treatment. Last decades, more evidence is available that the underlying mechanism of preeclampsia, endothelial disease, is not limited to pregnancy but increases cardiovascular risk in later life. In this review, we present the most recent insight in preeclampsia with focus on impact on the fetus, short and long-term outcome of offspring's, and long-term outcome of women with a history of preeclampsia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Angiotensin-Converting Enzyme I/D Polymorphism and Preeclampsia Risk: Evidence of Small-Study Bias

PubMed Central

Serrano, Norma C; Díaz, Luis A; Páez, Maria C; Mesa, Clara M; Cifuentes, Rodrigo; Monterrosa, Alvaro; González, Adriana; Smeeth, Liam; Hingorani, Aroon D; Casas, Juan P

2006-01-01

Background Inappropriate activation of the renin–angiotensin system may play a part in the development of preeclampsia. An insertion/deletion polymorphism within the angiotensin-I converting enzyme gene (ACE-I/D) has shown to be reliably associated with differences in angiotensin-converting enzyme (ACE) activity. However, previous studies of the ACE-I/D variant and preeclampsia have been individually underpowered to detect plausible genotypic risks. Methods and Findings A prospective case-control study was conducted in 1,711 unrelated young pregnant women (665 preeclamptic and 1,046 healthy pregnant controls) recruited from five Colombian cities. Maternal blood was obtained to genotype for the ACE-I/D polymorphism. Crude and adjusted odds ratio (OR) and 95% confidence interval (CI) using logistic regression models were obtained to evaluate the strength of the association between ACE-I/D variant and preeclampsia risk. A meta-analysis was then undertaken of all published studies to February 2006 evaluating the ACE-I/D variant in preeclampsia. An additive model (per-D-allele) revealed a null association between the ACE-I/D variant and preeclampsia risk (crude OR = 0.95 [95% CI, 0.81–1.10]) in the new case-control study. Similar results were obtained after adjusting for confounders (adjusted per-allele OR = 0.90 [95% CI, 0.77–1.06]) and using other genetic models of inheritance. A meta-analysis (2,596 cases and 3,828 controls from 22 studies) showed a per-allele OR of 1.26 (95% CI, 1.07–1.49). An analysis stratified by study size showed an attenuated OR toward the null as study size increased. Conclusions It is highly likely that the observed small nominal increase in risk of preeclampsia associated with the ACE D-allele is due to small-study bias, similar to that observed in cardiovascular disease. Reliable assessment of the origins of preeclampsia using a genetic approach may require the establishment of a collaborating consortium to generate a dataset of adequate size. PMID:17194198

A1M Ameliorates Preeclampsia-Like Symptoms in Placenta and Kidney Induced by Cell-Free Fetal Hemoglobin in Rabbit

PubMed Central

Axelsson, Josefin; Larsson, Irene; Johansson, Martin; Wester-Rosenlöf, Lena; Mörgelin, Matthias; Casslén, Vera; Gram, Magnus; Åkerström, Bo; Hansson, Stefan R.

2015-01-01

Preeclampsia is one of the most serious pregnancy-related diseases and clinically manifests as hypertension and proteinuria after 20 gestational weeks. The worldwide prevalence is 3-8% of pregnancies, making it the most common cause of maternal and fetal morbidity and mortality. Preeclampsia lacks an effective therapy, and the only “cure” is delivery. We have previously shown that increased synthesis and accumulation of cell-free fetal hemoglobin (HbF) in the placenta is important in the pathophysiology of preeclampsia. Extracellular hemoglobin (Hb) and its metabolites induce oxidative stress, which may lead to acute renal failure and vascular dysfunction seen in preeclampsia. The human endogenous protein, α1-microglobulin (A1M), removes cell-free heme-groups and induces natural tissue repair mechanisms. Exogenously administered A1M has been shown to alleviate the effects of Hb-induced oxidative stress in rat kidneys. Here we attempted to establish an animal model mimicking the human symptoms at stage two of preeclampsia by administering species-specific cell-free HbF starting mid-gestation until term, and evaluated the therapeutic effect of A1M on the induced symptoms. Female pregnant rabbits received HbF infusions i.v. with or without A1M every second day from gestational day 20. The HbF-infused animals developed proteinuria and a significantly increased glomerular sieving coefficient in kidney that was ameliorated by co-administration of A1M. Transmission electron microscopy analysis of kidney and placenta showed both intracellular and extracellular tissue damages after HbF-treatment, while A1M co-administration resulted in a significant reduction of the structural and cellular changes. Neither of the HbF-treated animals displayed any changes in blood pressure during pregnancy. In conclusion, infusion of cell-free HbF in the pregnant rabbits induced tissue damage and organ failure similar to those seen in preeclampsia, and was restored by co-administration of A1M. This study provides preclinical evidence supporting further examination of A1M as a potential new therapy for preeclampsia. PMID:25955715

Trisomy 13 and Massive Fetomaternal Hemorrhage

PubMed Central

Matsui, Ryoko; Suzuki, Shunji; Ito, Marie; Terada, Yusuke; Kumasaka, Sakae

2015-01-01

This is the first case report of trisomy 13 complicated by massive fetomaternal hemorrhage (FMH). A pale male infant weighing 2,950 g was delivered with low Apgar scores by emergency cesarean section due to non-reassuring fetal status. The umbilical arterial pH and hemoglobin level were 6.815 and 6.9 g/dL (normal: 13 - 22 g/dL), respectively. The maternal hemoglobin-F and serum alpha-fetoprotein levels were 6.0% (normal: < 1.0%) and 1,150 ng/mL (4.1 multiple of median), respectively. The neonate was diagnosed as having trisomy 13 by a subsequent chromosome examination. In the placenta, massive intervillous thrombosis was observed microscopically. This placental finding has been reported to be associated with both preeclampsia and massive FMH. In addition, the incidence of preeclampsia in pregnancies complicated by trisomy 13 has been reported to be significantly higher than normal karyotype populations. Therefore, the current finding may support the association between trisomy 13 and the incidence of massive FMH. PMID:26015824

A novel mechanism of angiotensin II-regulated placental vascular tone in the development of hypertension in preeclampsia.

PubMed

Gao, Qinqin; Tang, Jiaqi; Li, Na; Zhou, Xiuwen; Li, Yongmei; Liu, Yanping; Wu, Jue; Yang, Yuxian; Shi, Ruixiu; He, Axin; Li, Xiang; Zhang, Yingying; Chen, Jie; Zhang, Lubo; Sun, Miao; Xu, Zhice

2017-05-09

The present study tested the hypothesis that angiotensin II plays a role in the regulation of placental vascular tone, which contributes to hypertension in preeclampsia. Functional and molecular assays were performed in large and micro placental and non-placental vessels from humans and animals. In human placental vessels, angiotensin II induced vasoconstrictions in 78.7% vessels in 155 tests, as referenced to KCl-induced contractions. In contrast, phenylephrine only produced contractions in 3.0% of 133 tests. In non-placental vessels, phenylephrine induced contractions in 76.0% of 67 tests, whereas angiotensin II failed to produce contractions in 75 tests. Similar results were obtained in animal placental and non-placental vessels. Compared with non-placental vessels, angiotensin II receptors and β-adrenoceptors were significantly increased in placental vessels. Compared to the vessels from normal pregnancy, angiotensin II-induced vasoconstrictions were significantly reduced in preeclamptic placentas, which was associated with a decrease in angiotensin II receptors. In addition, angiotensin II and angiotensin converting enzyme in the maternal-placenta circulation in preeclampsia were increased, whereas angiotensin I and angiotensin1-7 concentrations were unchanged. The study demonstrates a selective effect of angiotensin II in maintaining placental vessel tension, which may play an important role in development of hypertension in preeclampsia.

Vitamin D, secondary hyperparathyroidism, and preeclampsia123

PubMed Central

Scholl, Theresa O; Chen, Xinhua; Stein, T Peter

2013-01-01

Background: Secondary hyperparathyroidism, which is defined by a high concentration of intact parathyroid hormone when circulating 25-hydroxyvitamin D [25(OH)D] is low, is a functional indicator of vitamin D insufficiency and a sign of impaired calcium metabolism. Two large randomized controlled trials examined effects of calcium supplementation on preeclampsia but did not consider the vitamin D status of mothers. Objective: We examined the association of secondary hyperparathyroidism with risk of preeclampsia. Design: Circulating maternal 25-hydroxyvitamin D [25(OH)D] and intact parathyroid hormone were measured at entry to care (mean ± SD: 13.7 ± 5.7 wk) using prospective data from a cohort of 1141 low-income and minority gravidae. Results: Secondary hyperparathyroidism occurred in 6.3% of the cohort and 18.4% of women whose 25(OH)D concentrations were <20 ng/mL. Risk of preeclampsia was increased 2.86-fold (95% CI: 1.28-, 6.41-fold) early in gestation in these women. Gravidae with 25(OH)D concentrations <20 ng/mL who did not also have high parathyroid hormone and women with high parathyroid hormone whose 25(OH)D concentrations were >20 ng/mL were not at increased risk. Intact parathyroid hormone was related to higher systolic and diastolic blood pressures and arterial pressure at week 20 before clinical recognition of preeclampsia. Energy-adjusted intakes of total calcium and lactose and circulating 25(OH)D were correlated inversely with systolic blood pressure or arterial pressure and with parathyroid hormone. Conclusion: Some women who are vitamin D insufficient develop secondary hyperparathyroidism, which is associated with increased risk of preeclampsia. PMID:23885046

Historical evolution of ideas on eclampsia/preeclampsia: A proposed optimistic view of preeclampsia.

PubMed

Robillard, Pierre-Yves; Dekker, Gustaaf; Chaouat, Gérard; Scioscia, Marco; Iacobelli, Silvia; Hulsey, Thomas C

2017-09-01

Eclampsia (together with epilepsy) being the first disease ever written down since the beginning of writings in mankind 5000 years ago, we will make a brief presentation of the different major steps in comprehension of Pre-eclampsia. 1) 1840. Rayer, description of proteinuria in eclampsia, 2) 1897 Vaquez, discovery of gestational hypertension in eclamptic women, 3) In the 1970's, description of the "double" trophoblastic invasion existing only in humans (Brosens & Pijnenborg,), 4) between the 1970's and the 1990's, description of preeclampsia being a couple disease. The "paternity problem" (and therefore irruption of immunology), 5) at the end of the 1980's, a major step forward: Preeclampsia being a global endothelial cell disease (glomeruloendotheliosis, hepatic or cerebral endotheliosis, HELLP, eclampsia), inflammation (J.Roberts.C Redman, R Taylor), 6) End of the 1990's: Consensus for a distinction between early onset preeclampsia EOP and late onset LOP (34 weeks gestation), EOP being rather a problem of implantation of the trophoblast (and the placenta), LOP being rather a pre-existing maternal problem (obesity, diabetes, coagulopathies etc…). LOP is predominant everywhere on this planet, but enormously predominant in developed countries: 90% of cases. This feature is very different in countries where women have their first child very young (88% of world births), where the fatal EOP (early onset) occurs in more than 30% of cases. 7) What could be the common factor which could explain the maternal global endotheliosis in EOP and LOP? Discussion about the inositol phospho glycans P type. Copyright © 2017. Published by Elsevier B.V.

The Impact of Magnesium Sulfate Therapy on Angiogenic Factors in Preeclampsia

PubMed Central

VADNAIS, Mary A.; RANA, Sarosh; QUANT, Hayley S.; SALAHUDDIN, Saira; DODGE, Laura E.; LIM, Kee-Hak; KARUMANCHI, S. Ananth; HACKER, Michele R.

2011-01-01

Objective The objective was to evaluate whether intravenous magnesium sulfate (magnesium) alters levels of angiogenic factors in women with preeclampsia. Study Design This was a prospective cohort study comparing women with preeclampsia treated with magnesium for seizure prophylaxis to those who were not. Serum levels of angiogenic factors, soluble fms-like tyrosine kinase 1, soluble endoglin and placental growth factor, were measured at the time of diagnosis and approximately 24 hours later. Secondary analysis compared women receiving magnesium for preeclampsia to women receiving magnesium for preterm labor. Analysis of covariance was used to compare levels at 24 hours, adjusting for levels at enrollment and potential confounders. Results Angiogenic factor levels did not differ between preeclampsia groups with and without magnesium or between preeclampsia and preterm labor groups treated with magnesium (all P > 0.05). Conclusion Magnesium likely decreases seizure risk in preeclampsia by a mechanism other than altering angiogenic factor levels. PMID:22247820

The Impact of Magnesium Sulfate Therapy on Angiogenic Factors in Preeclampsia.

PubMed

Vadnais, Mary A; Rana, Sarosh; Quant, Hayley S; Salahuddin, Saira; Dodge, Laura E; Lim, Kee-Hak; Karumanchi, S Ananth; Hacker, Michele R

2012-01-01

OBJECTIVE: The objective was to evaluate whether intravenous magnesium sulfate (magnesium) alters levels of angiogenic factors in women with preeclampsia. STUDY DESIGN: This was a prospective cohort study comparing women with preeclampsia treated with magnesium for seizure prophylaxis to those who were not. Serum levels of angiogenic factors, soluble fms-like tyrosine kinase 1, soluble endoglin and placental growth factor, were measured at the time of diagnosis and approximately 24 hours later. Secondary analysis compared women receiving magnesium for preeclampsia to women receiving magnesium for preterm labor. Analysis of covariance was used to compare levels at 24 hours, adjusting for levels at enrollment and potential confounders. RESULTS: Angiogenic factor levels did not differ between preeclampsia groups with and without magnesium or between preeclampsia and preterm labor groups treated with magnesium (all P > 0.05). CONCLUSION: Magnesium likely decreases seizure risk in preeclampsia by a mechanism other than altering angiogenic factor levels.

Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial

PubMed Central

Perichart-Perera, Otilia; Espino, Salvador; Avila-Vergara, Marco Antonio; Ibarra, Isabel; Ahued, Roberto; Godines, Myrna; Parry, Samuel; Macones, George; Strauss, Jerome F

2011-01-01

Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. Design Randomised, blinded, placebo controlled clinical trial. Setting Tertiary public hospital in Mexico City. Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy. Main outcome measure Development of pre-eclampsia/eclampsia. Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14). Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846. PMID:21596735

Resolution of hypertension and proteinuria after preeclampsia.

PubMed

Berks, Durk; Steegers, Eric A P; Molas, Marek; Visser, Willy

2009-12-01

To estimate the time required for hypertension and proteinuria to resolve after preeclampsia, and to estimate how this time to resolution correlates with the levels of blood pressure and proteinuria during preeclampsia and prolonging pregnancy after the development of preeclampsia. This is a historic prospective cohort study of 205 preeclamptic women who were admitted between 1990 and 1992 at the Erasmus MC Medical Centre, Rotterdam, The Netherlands. Data were collected at 1.5, 3, 6, 12, 18, and 24 months after delivery. Hypertension was defined as a blood pressure 140/90 mm Hg or higher or use of antihypertensive drugs. Proteinuria was defined as 0.3 g/d or more. Resolution of hypertension and proteinuria were analyzed with the Turnbull extension to the Kaplan-Meier procedure. Correlations were calculated with an accelerated failure time model. At 3 months postpartum, 39% of women still had hypertension, which decreased to 18% at 2 years postpartum. Resolution time increased by 60% (P<.001) for every 10-mm Hg increase in maximal systolic blood pressure, 40% (P=.044) for every 10-mm Hg increase in maximal diastolic blood pressure, and 3.6% (P=.001) for every 1-day increase in the diagnosis-to-delivery interval. At 3 months postpartum, 14% still had proteinuria, which decreased to 2% at 2 years postpartum. Resolution time increased by 16% (P=.001) for every 1-g/d increase in maximal proteinuria. Gestational age at onset of preeclampsia was not correlated with resolution time of hypertension and proteinuria. The severity of preeclampsia and the time interval between diagnosis and delivery are associated with postpartum time to resolution of hypertension and proteinuria. After preeclampsia, it can take up to 2 years for hypertension and proteinuria to resolve. Therefore, the authors suggest that further invasive diagnostic tests for underlying renal disease may be postponed until 2 years postpartum. III.

Smoking in preeclamptic women is associated with higher birthweight for gestational age and lower soluble fms-like tyrosine kinase-1 levels: a nested case control study

PubMed Central

2011-01-01

Background Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U-shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers. Methods From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit. Results In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (β = -0.29; p = 0.008, and β = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (β = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054). Conclusions Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti-angiogenic protein sFlt-1. PMID:22074109

Deconstructing the smoking-preeclampsia paradox through a counterfactual framework.

PubMed

Luque-Fernandez, Miguel Angel; Zoega, Helga; Valdimarsdottir, Unnur; Williams, Michelle A

2016-06-01

Although smoking during pregnancy may lead to many adverse outcomes, numerous studies have reported a paradoxical inverse association between maternal cigarette smoking during pregnancy and preeclampsia. Using a counterfactual framework we aimed to explore the structure of this paradox as being a consequence of selection bias. Using a case-control study nested in the Icelandic Birth Registry (1309 women), we show how this selection bias can be explored and corrected for. Cases were defined as any case of pregnancy induced hypertension or preeclampsia occurring after 20 weeks' gestation and controls as normotensive mothers who gave birth in the same year. First, we used directed acyclic graphs to illustrate the common bias structure. Second, we used classical logistic regression and mediation analytic methods for dichotomous outcomes to explore the structure of the bias. Lastly, we performed both deterministic and probabilistic sensitivity analysis to estimate the amount of bias due to an uncontrolled confounder and corrected for it. The biased effect of smoking was estimated to reduce the odds of preeclampsia by 28 % (OR 0.72, 95 %CI 0.52, 0.99) and after stratification by gestational age at delivery (<37 vs. ≥37 gestation weeks) by 75 % (OR 0.25, 95 %CI 0.10, 0.68). In a mediation analysis, the natural indirect effect showed and OR > 1, revealing the structure of the paradox. The bias-adjusted estimation of the smoking effect on preeclampsia showed an OR of 1.22 (95 %CI 0.41, 6.53). The smoking-preeclampsia paradox appears to be an example of (1) selection bias most likely caused by studying cases prevalent at birth rather than all incident cases from conception in a pregnancy cohort, (2) omitting important confounders associated with both smoking and preeclampsia (preventing the outcome to develop) and (3) controlling for a collider (gestation weeks at delivery). Future studies need to consider these aspects when studying and interpreting the association between smoking and pregnancy outcomes.

Existence of compensatory defense mechanisms against oxidative stress and hypertension in preeclampsia.

PubMed

Roland, L; Gagné, A; Bélanger, M-C; Boutet, M; Berthiaume, L; Fraser, W D; Julien, P; Bilodeau, J-F

2010-01-01

Preeclampsia is a complex obstetrical syndrome characterized by hypertension and proteinuria. This syndrome is associated with oxidative stress, antioxidant imbalance and impaired production of vasoactive eicosanoids such as thromboxane A(2) (TXA(2)), a potent vasoconstrictor, and prostacyclin (PGI(2)), a well-known vasodilator. We hypothesized that there was a relationship between antioxidant vitamins, such as vitamin E and coenzyme Q(10) (CoQ(10)), and the production of vasoactive eicosanoids- PGI(2) and TXA(2)-potentially regulated by pro-oxidants and antioxidants in preeclampsia. Therefore, the plasma levels of vitamin E, CoQ(10), TXA(2) and PGI(2) in normotensive (n = 30) and preeclamptic (n = 29) pregnancies were evaluated. Reduced and oxidized forms of vitamin E and CoQ(10) in blood were measured using a HPLC coupled to electrochemical detection. The levels of TXB(2) and 6-keto-PGF(1alpha), stable metabolites of TXA(2) and PGI(2) respectively, were measured by ELISA. The CoQ(10) oxidized/reduced ratio was significantly higher in preeclamptic compared to normotensive pregnancies (p = 0.04). A strong correlation between plasma levels of reduced vitamin E and CoQ(10), corrected for apolipoprotein B, was observed only in preeclampsia (r = 0.69, p < 0.0001). The 6-keto-PGF(1alpha)/TXB(2) ratio was higher in preeclampsia than in controls (p = 0.02), and this ratio was correlated to the oxidized/reduced ratio of both, vitamin E and CoQ(10) in all pregnancies (p <0.023). The data indicated that CoQ(10) is a sensitive marker of oxidative stress in preeclampsia. The correlation between vitamin E and CoQ(10) suggested a coordinated defense mechanism against oxidation. Furthermore, the higher 6-keto-PGF(1alpha)/TXB(2) ratio that strongly correlated with oxidative stress markers, suggests a mechanism developed by the maternal cardiovascular system to counteract hypertension during preeclampsia.

Placental-Specific sFLT-1 e15a Protein Is Increased in Preeclampsia, Antagonizes Vascular Endothelial Growth Factor Signaling, and Has Antiangiogenic Activity.

PubMed

Palmer, Kirsten R; Kaitu'u-Lino, Tu'uhevaha J; Hastie, Roxanne; Hannan, Natalie J; Ye, Louie; Binder, Natalie; Cannon, Ping; Tuohey, Laura; Johns, Terrance G; Shub, Alexis; Tong, Stephen

2015-12-01

In preeclampsia, the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) is released from placenta into the maternal circulation, causing endothelial dysfunction and organ injury. A recently described splice variant, sFLT-1 e15a, is primate specific and the most abundant placentally derived sFLT-1. Therefore, it may be the major sFLT-1 isoform contributing to the pathophysiology of preeclampsia. sFLT-1 e15a protein remains poorly characterized: its bioactivity has not been comprehensively examined, and serum levels in normal and preeclamptic pregnancy have not been reported. We generated and validated an sFLT-1 e15a-specific ELISA to further characterize serum levels during pregnancy, and in the presence of preeclampsia. Furthermore, we performed assays to examine the bioactivity and antiangiogenic properties of sFLT-1 e15a protein. sFLT-1 e15a was expressed in the syncytiotrophoblast, and serum levels rose across pregnancy. Strikingly, serum levels were increased 10-fold in preterm preeclampsia compared with normotensive controls. We confirmed sFLT-1 e15a is bioactive and is able to inhibit vascular endothelial growth factor signaling of vascular endothelial growth factor receptor 2 and block downstream Akt phosphorylation. Furthermore, sFLT-1 e15a has antiangiogenic properties. sFLT-1 e15a decreased endothelial cell migration, invasion, and inhibited endothelial cell tube formation. Administering sFLT-1 e15a blocked vascular endothelial growth factor induced sprouts from mouse aortic rings ex vivo. We have demonstrated that sFLT-1 e15a is increased in preeclampsia, antagonizes vascular endothelial growth factor signaling, and has antiangiogenic activity. Future development of diagnostics and therapeutics for preeclampsia should consider targeting placentally derived sFLT-1 e15a. © 2015 American Heart Association, Inc.

Maternal and Paternal Height and the Risk of Preeclampsia.

PubMed

Lee, Yunsung; Magnus, Per

2018-04-01

The etiology of preeclampsia is unknown. Tall women have been found to have lower incidence of preeclampsia. This points to a possible biological causal effect but may be because of socioeconomic confounding. We used paternal height as an unexposed control to examine confounding. The MoBa (Norwegian Mother and Child Cohort Study) was used to extract data on parental heights, maternal prepregnancy weight, other background factors, and pregnancy outcomes for 99 968 singleton births. Multiple logistic regression was used to estimate odds ratios for preeclampsia according to parental height. The adjusted odds ratio for preeclampsia was 0.74 (95% CI, 0.66-0.82) for women >172 cm as compared with women <164 cm. The adjusted odds ratio for preeclampsia for men >186 cm was 1.03 (95% CI, 0.93-1.15) compared with men <178 cm. The association between maternal height and preeclampsia is unlikely to be because of confounding by familial, socioeconomic factors or by fetal genes related to height. The observed association between maternal height and preeclampsia merits further investigation. © 2018 American Heart Association, Inc.

The common single-nucleotide polymorphism rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.

PubMed

Wan, Ji-Peng; Wang, Hong; Li, Chang-Zhong; Zhao, Han; You, Li; Shi, Dong-Hong; Sun, Xiu-Hua; Lv, Hong; Wang, Fei; Wen, Ze-Qing; Wang, Xie-Tong; Chen, Zi-Jiang

2014-11-01

Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women. © The Author(s) 2014.

Prevalence of Preeclampsia and Eclampsia in Iran.

PubMed

Kharaghani, Roghieh; Cheraghi, Zahra; Okhovat Esfahani, Batool; Mohammadian, Zahra; Nooreldinc, Reyhaneh Sadat

2016-01-01

Several studies have been conducted to investigate the prevalence of preeclampsia and eclampsia in Iran. These studies have yielded different results. This meta-analysis was aimed to estimate the prevalence of preeclampsia and eclampsia in Iran. International and national electronic databases were searched up to August 2014 including PubMed, Science Direct, Scopus, Science Information Database, MagIran, and IranMedex as well as conference databases. All studies, in which the prevalence or cumulative incidence of preeclampsia in Iran was reported, were included in this meta-analysis. Thirty-six separate studies were assessed involving overall 132,737 participants, of which 4360 had preeclampsia and 49 had eclampsia. Overall prevalence of preeclampsia and eclampsia was 0.05 (95% CI: 0.05, 0.06) and 0.23% (95% CI: 0.12%, 0.33%) respectively. The prevalence of preeclampsia, increased from 0.04 (95% CI: 0.03, 0.05) during 1996 to 2005 to 0.07 (95% CI: 0.04, 0.09) during 2010 to 2013, while the prevalence of eclampsia decreased from 0.30% (95% CI: 0.15%, 0.45%) to 0.01% (95% CI: 0.01%, 0.01%), during the same period. The preeclampsia prevalence had an increasing growth and the eclampsia prevalence had declining growth in recent years. In addition, despite many studies aimed the prevalence of preeclampsia and eclampsia in Iran, there is a significant variation between the results. So, it is difficult to give an exact estimation of the preeclampsia and eclampsia prevalence in Iran.

Electronegativity and intrinsic disorder of preeclampsia-related proteins.

PubMed

Polanco, Carlos; Castañón-González, Jorge Alberto; Uversky, Vladimir N; Buhse, Thomas; Samaniego Mendoza, José Lino; Calva, Juan J

2017-01-01

Preeclampsia, hemorrhage, and infection are the leading causes of maternal death in underdeveloped countries. Since several proteins associated with preeclampsia are known, we conducted a computational study which evaluated the commonness and potential functionality of intrinsic disorder of these proteins and also made an attempt to characterize their origin. The origin of the preeclampsia-related proteins was assessed with a supervised technique, a Polarity Index Method (PIM), which evaluates the electronegativity of proteins based solely on their sequence. The commonness of intrinsic disorder was evaluated using several disorder predictors from the PONDR family, the charge-hydropathy plot (CH-plot) and cumulative distribution function (CDF) analyses, and using the MobiDB web-based tool, whereas potential functionality of intrinsic disorder was studied with the D2P2 resource and ANCHOR predictor of disorder-based binding sites, and the STRING tool was used to build the interactivity networks of the preeclampsia-related proteins. Peculiarities of the PIM-derived polar profile of the group of preeclampsia-related proteins were then compared with profiles of a group of lipoproteins, antimicrobial peptides, angiogenesis-related proteins, and the intrinsically disordered proteins. Our results showed a high graphical correlation between preeclampsia proteins, lipoproteins, and the angiogenesis proteins. We also showed that many preeclampsia-related proteins contain numerous functional disordered regions. Therefore, these bioinformatics results led us to assume that the preeclampsia proteins are highly associated with the lipoproteins group, and that some preeclampsia-related proteins contain significant amounts of functional disorders.

Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia.

PubMed

Spracklen, Cassandra N; Saftlas, Audrey F; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

2015-07-01

Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia. Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04). Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Validity of preeclampsia registration in the Medical Birth Registry of Norway for women participating in the Norwegian Mother and Child Cohort Study, 1999-2010

PubMed Central

Harmon, Quaker E.; Skard, Linn Beate; Simonsen, Ingeborg; Austvoll, Elise; Alsaker, Elin Hilde Roti; Starling, Anne; Trogstad, Lill; Magnus, Per; Engel, Stephanie

2014-01-01

Background The Norwegian Mother and Child Cohort study (MoBa), a prospective population-based pregnancy cohort, is a valuable database for studying causes of preeclampsia. Preeclampsia data in MoBa comes from the Medical Birth Registry of Norway (MBRN), thus, we wanted to study the validity of MBRN preeclampsia registration for MoBa women. Methods We selected all MoBa pregnancies with preeclampsia registered in the MBRN (n=4081) and a random control group (n=2000) without preeclampsia registrations. After excluding two delivery units not participating in MoBa and one no longer operating, units were asked to provide copies of antenatal charts with blood pressure and urinary measurements from all antenatal visits during pregnancy, and hospital discharge codes from the delivery stay. We received data for 5340 pregnancies delivered 1999-2010 (87% of all eligible). We calculated positive predictive value (PPV), sensitivity and specificity of MBRN registration, using hypertension and proteinuria on the antenatal charts and/or hospital discharge codes indicating preeclampsia as gold standard. Results Overall PPV was 83.9% (95% confidence interval 82.7, 85.1), and was higher when women were primiparous, or delivered preterm or low birth weight infants. Severe preeclampsia in the MBRN was found to be a true severe preeclampsia in 70% of cases. Extrapolating to the total MoBa population, the estimated sensitivity was low: 43.0% (38.7, 48.2), while specificity was high: 99.2% (99.2, 99.3). False negative cases seemed to have mild forms of preeclampsia. Conclusions PPV and specificity of preeclampsia registration in the MBRN during 1999-2010 was satisfactory, while sensitivity was low. PMID:25040774

Thrombophilic mutations and susceptibility to preeclampsia in Western Iran.

PubMed

Malek-Khosravi, Shohreh; Rahimi, Zohreh; Rahimi, Ziba; Jalilvand, Faranak; Parsian, Abbas

2012-01-01

The aim of the present study was to investigate the frequency and the possible association between thrombophilic mutations of factor V Leiden (FVL) and prothrombin G20210A with preeclampsia among Kurdish population of Western Iran. We studied 198 women with preeclampsia including 128 women with mild and 70 women with severe forms and 101 healthy pregnant women with uncomplicated pregnancy. Among cases there were 23 women with early onset preeclampsia and 175 cases with late-onset preeclampsia. The sample was genotyped by polymerase chain reaction-restriction fragment-length polymorphism using Mnl I and Hind III for FVL and prothrombin G20210A, respectively. The frequency of heterozygous FVL mutation was 7.6% among all preeclamptic women (8.6% in mild and 5.7% in severe preeclamptic women) and 7.9% in controls (P > 0.05). However, the prevalence of heterozygous FVL were 10.5 and 3.9% among severe preeclamptic women with early onset and late-onset preeclampsia, respectively (P > 0.05). The prevalence of prothrombin G20210A were 1.6, 2.9, and 3% among women with mild preeclamsia, severe preeclampsia and controls, respectively (P > 0.05). The level of serum triglycerides (TG) was significantly higher among women with preeclampsia compared to healthy pregnant women that was not associated with the two thrombophilic mutations. Our results indicate that neither FVL nor prothrombin G20210A could be a risk factor for preeclampsia in our population. However, high prevalence of FVL in preeclamptic women with early onset compared to those with late-onset preeclampsia may suggest a role for this mutation in predisposition to early onset preeclampsia that need to be confirmed with larger sample size.

Associations between phenotypes of preeclampsia and thrombophilia.

PubMed

Berks, Durk; Duvekot, Johannes J; Basalan, Hillal; De Maat, Moniek P M; Steegers, Eric A P; Visser, Willy

2015-11-01

Preeclampsia complicates 2-8% of all pregnancies. Studies on the association of preeclampsia with thrombophilia are conflicting. Clinical heterogeneity of the disease may be one of the explanations. The present study addresses the question whether different phenotypes of preeclampsia are associated with thrombophilia factors. Study design We planned a retrospective cohort study. From 1985 until 2010 women with preeclampsia were offered postpartum screening for the following thrombophilia factors: anti-phospholipid antibodies, APC-resistance, protein C deficiency and protein S deficiency, hyperhomocysteineamia, factor V Leiden and Prothrombin gene mutation. Hospital records were used to obtain information on phenotypes of the preeclampsia and placental histology. We identified 844 women with singleton pregnancies who were screened for thrombophilia factors. HELLP complicated 49% of pregnancies; Fetal growth restriction complicated 61% of pregnancies. Early delivery (<34th week) occurred in 71% of pregnancies. Any thrombophilia factor was present in 29% of the women. Severe preeclampsia was associated with protein S deficiency (p=0.01). Fetal growth restriction was associated with anti-phospholipid antibodies (p<0.01). Early onset preeclampsia was associated with anti-phospholipid antibodies (p=0.01). Extensive placental infarction (>10%) was associated with anti-phospholipid antibodies (p<0.01). Low placental weight (<5th percentile) was associated with hyperhomocysteineamia (p=0.03). No other associations were observed. Early onset preeclampsia, especially if complicated by fetal growth restriction, are associated with anti-phospholipid antibodies. Other phenotypes of preeclampsia, especially HELLP syndrome, were not associated with thrombophilia. We advise only to test for anti-phospholipid antibodies after early onset preeclampsia, especially if complicated by fetal growth restriction. We suggest enough evidence is presented to justify no further studies are needed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Proteinuria in preeclampsia: Not essential to diagnosis but related to disease severity and fetal outcomes.

PubMed

Dong, Xin; Gou, Wenli; Li, Chunfang; Wu, Min; Han, Zhen; Li, Xuelan; Chen, Qi

2017-04-01

Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality globally and proteinuria can be one of the cardinal features of this disease. However, studies about the association of the amount of proteinuria and the severity of preeclampsia, and perinatal outcomes are limited. Data on 239 women with preeclampsia were retrospectively collected from a university teaching hospital from September 2011 to June 2013 and analysed. Data included all clinical parameters and proteinuria in a 24h urine collection. In cases of severe preeclampsia, significantly fewer patients had proteinuria levels <0.3g/L in comparison to any of the other groups with proteinuria >0.3g/L, but there was no difference in cases of severe preeclampsia when proteinuria levels were >0.3g/L. Furthermore, when proteinuria levels were >0.3g/L, the frequency of severe preeclampsia in each group was significantly higher than the frequency of mild pre-eclampsia cases. Time of onset was significantly earlier in patients with proteinuria >3g/L in a 24h urine collection, but time between the onset of preeclampsia and delivery was not correlated with the amount of proteinuria. The birth weight was significantly lower in patients with proteinuria >3g/L. The incidence of fetal growth restriction or stillbirth was significantly higher in patients with proteinuria >5g/L. Our data demonstrate that the amount of proteinuria is not associated with the severe of preeclampsia, once proteinuria is detected, but is related to the severity of preeclampsia. The adverse fetal outcomes appear to be the function of prematurity rather than proteinuria itself. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia.

PubMed

Turner, Rosanne J; Bloemenkamp, Kitty W M; Bruijn, Jan A; Baelde, Hans J

2016-04-01

Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are increased. We aimed to investigate placental thrombomodulin dysregulation and consequent downstream effects in the pathogenesis of preeclampsia. Placentas from 28 preeclampsia pregnancies, 30 uncomplicated pregnancies, and 21 pregnancies complicated by growth restriction as extra controls were included. Immunohistochemical staining of thrombomodulin, caspase-3, and fibrin was performed. Placental mRNA expression of thrombomodulin, inflammatory markers, matrix metalloproteinases 2 and 9, and soluble Flt-1 were measured with quantitative polymerase chain reaction. Thrombomodulin mRNA expression was determined in vascular endothelial growth factor-transfected trophoblast cell lines. Thrombomodulin protein and mRNA expression were decreased in preeclampsia as compared with both control groups (P=0.001). Thrombomodulin mRNA expression correlated with maternal body mass index (P<0.01) and diastolic blood pressure (P<0.05) in preeclampsia. An increase in placental apoptotic cells was associated with preeclampsia (P<0.001). Thrombomodulin expression correlated positively with matrix metalloproteinase expression (P<0.01) in preeclampsia, but not with fibrin deposits or inflammatory markers. Placental soluble Flt-1 expression correlated with decreased thrombomodulin expression. Vascular endothelial growth factor induced upregulation of thrombomodulin expression in trophoblast cells. Decreased thrombomodulin expression in preeclampsia may play a role in placental dysfunction in preeclampsia and is possibly caused by an angiogenic imbalance. Hypertension and obesity are associated with thrombomodulin downregulation. These results set the stage for further basic and clinical research on thrombomodulin in the pathogenesis of preeclampsia and other syndromes characterized by endothelial dysfunction. © 2016 American Heart Association, Inc.

Platelet count and platelet indices in women with preeclampsia.

PubMed

AlSheeha, Muneera A; Alaboudi, Rafi S; Alghasham, Mohammad A; Iqbal, Javed; Adam, Ishag

2016-01-01

Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia. To compare platelet indices, namely platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and PC to MPV ratio in women with preeclampsia compared with healthy controls. Qassim Hospital, Kingdom of Saudi Arabia. A case-control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls. There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC) curves, the PC cutoff was 248.0×10 3 /µL for diagnosis of pre-eclampsia ( P =0.019; the area under the ROC curve was 62.4%). Binary regression suggests that women with PC <248.010×10 3 /µL were at higher risk of preeclampsia (odds ratio =2.2, 95% confidence interval =1.08-4.6, P =0.03). The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia ( P =0.035, the area under the ROC curve was 62.2%). PC <248.010×10 3 /µL and PC to MPV ratio 31.2 are valid predictors of preeclampsia.

Ambient Air Pollution and Preeclampsia: A Spatiotemporal Analysis

PubMed Central

Figueras, Francesc; Basagaña, Xavier; Beelen, Rob; Martinez, David; Cirach, Marta; Schembari, Anna; Hoek, Gerard; Brunekreef, Bert; Nieuwenhuijsen, Mark J

2013-01-01

Background: Available evidence concerning the association between air pollution and preeclampsia is limited, and specific associations with early- and late-onset preeclampsia have not been assessed. Objectives: We investigated the association, if any, between preeclampsia (all, early-, and late-onset) and exposure to nitrogen dioxide, nitrogen oxides, particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5; fine particles), ≤ 10 μm, and 2.5–10 μm, and PM2.5 light absorption (a proxy for elemental carbon) during the entire pregnancy and during the first, second, and third trimesters. Methods: This study was based on 8,398 pregnancies (including 103 cases of preeclampsia) among women residing in Barcelona, Spain (2000–2005). We applied a spatiotemporal exposure assessment framework using land use regression models to predict ambient pollutant levels during each week of pregnancy at the geocoded residence address of each woman at the time of birth. Logistic and conditional logistic regression models were used to estimate unadjusted and adjusted associations. Results: We found positive associations for most of our evaluated outcome–exposure pairs, with the strongest associations observed for preeclampsia and late-onset preeclampsia in relation to the third-trimester exposure to fine particulate pollutants, and for early-onset preeclampsia in relation to the first-trimester exposure to fine particulate pollutants. Among our investigated associations, those of first- and third-trimester exposures to PM2.5 and third-trimester exposure to PM2.5 absorbance and all preeclampsia, and third-trimester PM2.5 exposure and late-onset preeclampsia attained statistical significance. Conclusion: We observed increased risk of preeclampsia associated with exposure to fine particulate air pollution. Our findings, in combination with previous evidence suggesting distinct pathogenic mechanisms for early- and late-onset preeclampsia, support additional research on this topic. Citation: Dadvand P, Figueras F, Basagaña X, Beelen R, Martinez D, Cirach M, Schembari A, Hoek G, Brunekreef B, Nieuwenhuijsen MJ. 2013. Ambient air pollution and preeclampsia: a spatiotemporal analysis. Environ Health Perspect 121:1365–1371; http://dx.doi.org/10.1289/ehp.1206430 PMID:24021707

Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker

PubMed Central

Zadora, Julianna; Singh, Manvendra; Herse, Florian; Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Yung, Hong Wa; Huppertz, Berthold; Cartwright, Judith E.; Whitley, Guy; Johnsen, Guro M.; Levi, Giovanni; Isbruch, Annette; Schulz, Herbert; Luft, Friedrich C.; Müller, Dominik N.; Staff, Anne Cathrine

2017-01-01

Background: Preeclampsia is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in preeclampsia. Our study aims to investigate whether disturbed imprinting contributes to preeclampsia. Methods: We first aimed to confirm that preeclampsia is a disease of the placenta by generating and analyzing genome-wide molecular data on well-characterized patient material. We performed high-throughput transcriptome analyses of multiple placenta samples from healthy controls and patients with preeclampsia. Next, we identified differentially expressed genes in preeclamptic placentas and intersected them with the list of human imprinted genes. We used bioinformatics/statistical analyses to confirm association between imprinting and preeclampsia and to predict biological processes affected in preeclampsia. Validation included epigenetic and cellular assays. In terms of human specificity, we established an in vitro invasion-differentiation trophoblast model. Our comparative phylogenetic analysis involved single-cell transcriptome data of human, macaque, and mouse preimplantation embryogenesis. Results: We found disturbed placental imprinting in preeclampsia and revealed potential candidates, including GATA3 and DLX5, with poorly explored imprinted status and no prior association with preeclampsia. As a result of loss of imprinting, DLX5 was upregulated in 69% of preeclamptic placentas. Levels of DLX5 correlated with classic preeclampsia markers. DLX5 is expressed in human but not in murine trophoblast. The DLX5high phenotype resulted in reduced proliferation, increased metabolism, and endoplasmic reticulum stress-response activation in trophoblasts in vitro. The transcriptional profile of such cells mimics the transcriptome of preeclamptic placentas. Pan-mammalian comparative analysis identified DLX5 as part of the human-specific regulatory network of trophoblast differentiation. Conclusions: Our analysis provides evidence of a true association among disturbed imprinting, gene expression, and preeclampsia. As a result of disturbed imprinting, the upregulated DLX5 affects trophoblast proliferation. Our in vitro model might fill a vital niche in preeclampsia research. Human-specific regulatory circuitry of DLX5 might help explain certain aspects of preeclampsia. PMID:28904069

Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker.

PubMed

Zadora, Julianna; Singh, Manvendra; Herse, Florian; Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Yung, Hong Wa; Huppertz, Berthold; Cartwright, Judith E; Whitley, Guy; Johnsen, Guro M; Levi, Giovanni; Isbruch, Annette; Schulz, Herbert; Luft, Friedrich C; Müller, Dominik N; Staff, Anne Cathrine; Hurst, Laurence D; Dechend, Ralf; Izsvák, Zsuzsanna

2017-11-07

Preeclampsia is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in preeclampsia. Our study aims to investigate whether disturbed imprinting contributes to preeclampsia. We first aimed to confirm that preeclampsia is a disease of the placenta by generating and analyzing genome-wide molecular data on well-characterized patient material. We performed high-throughput transcriptome analyses of multiple placenta samples from healthy controls and patients with preeclampsia. Next, we identified differentially expressed genes in preeclamptic placentas and intersected them with the list of human imprinted genes. We used bioinformatics/statistical analyses to confirm association between imprinting and preeclampsia and to predict biological processes affected in preeclampsia. Validation included epigenetic and cellular assays. In terms of human specificity, we established an in vitro invasion-differentiation trophoblast model. Our comparative phylogenetic analysis involved single-cell transcriptome data of human, macaque, and mouse preimplantation embryogenesis. We found disturbed placental imprinting in preeclampsia and revealed potential candidates, including GATA3 and DLX5 , with poorly explored imprinted status and no prior association with preeclampsia. As a result of loss of imprinting, DLX5 was upregulated in 69% of preeclamptic placentas. Levels of DLX5 correlated with classic preeclampsia markers. DLX5 is expressed in human but not in murine trophoblast. The DLX5 high phenotype resulted in reduced proliferation, increased metabolism, and endoplasmic reticulum stress-response activation in trophoblasts in vitro. The transcriptional profile of such cells mimics the transcriptome of preeclamptic placentas. Pan-mammalian comparative analysis identified DLX5 as part of the human-specific regulatory network of trophoblast differentiation. Our analysis provides evidence of a true association among disturbed imprinting, gene expression, and preeclampsia. As a result of disturbed imprinting, the upregulated DLX5 affects trophoblast proliferation. Our in vitro model might fill a vital niche in preeclampsia research. Human-specific regulatory circuitry of DLX5 might help explain certain aspects of preeclampsia. © 2017 The Authors.

Myeloperoxidase in the plasma and placenta of normal pregnant women and women with pregnancies complicated by preeclampsia and intrauterine growth restriction.

PubMed

Hung, T-H; Chen, S-F; Lo, L-M; Li, M-J; Yeh, Y-L; Hsieh, T-T

2012-04-01

Myeloperoxidase (MPO) is a heme protein produced and released by activated neutrophils and monocytes, and increased MPO is considered important in the pathophysiology of cardiovascular diseases (CVD). Accumulating evidence suggests that preeclampsia (PE), idiopathic intrauterine growth restriction (IUGR), and CVD share many similar metabolic disturbances, including an enhanced systemic inflammatory response and endothelial dysfunction. We hypothesized that MPO plays an important role in the development of PE and IUGR. Plasma samples were collected mid-gestation and at delivery from women with normal pregnancies (n = 40) and those who subsequently developed PE (n = 20), IUGR (n = 11) or both (PE + IUGR, n = 8). Placental samples were obtained immediately after delivery from 22 women with normal pregnancies, 19 women with PE, 14 women with IUGR, and 14 women with PE + IUGR. The MPO concentrations were measured using ELISA. Women with PE + IUGR had significantly higher plasma MPO before delivery than normal pregnant women. There was no difference in plasma levels at mid-gestation or the placental concentrations between women with normal pregnancies and those who developed PE, IUGR, or PE + IUGR. Using explants prepared from the placentas of 8 women with normal pregnancies and 8 women with PE, we found no difference in the levels of MPO in the tissue homogenates and culture media between these two groups of women. Together, these results indicate that increased maternal circulating MPO in women with PE + IUGR is likely a result of enhanced systemic inflammation caused by the established disease rather than a primary pathophysiological factor. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hypertensive disorders in pregnancy among pregnant women in a Nigerian Teaching Hospital

PubMed Central

Singh, Swati; Ahmed, Ekele Bissallah; Egondu, Shehu Constance; Ikechukwu, Nwobodo Emmanuel

2014-01-01

Background: Hypertensive disorders in pregnancy (HDP) represent a group of conditions associated with high blood pressure during pregnancy. It is an important cause of feto-maternal morbidity and mortality, particularly in developing countries. The aims of the study were to find the prevalence of hypertensive disorders and its associated risk factors among women attending the antenatal clinic of Usmanu Danfodiyo University Teaching Hospital,(UDUTH) Sokoto. Materials and Methods: A longitudinal study of 216 consecutively recruited women that were less than 20 weeks pregnant at booking was carried out. Blood pressure was measured for each woman at booking and at subsequent visits. Urinalysis was done at booking and whenever blood pressure was elevated. Patients were followed-up to delivery and 6 weeks postpartum. Data entry and analysis was done using Statistical Analysis System (SAS) statistical package. Results: The prevalence of HDP in the study was 17% while preeclampsia was 6%. Previous history of preeclampsia (P < 0.001; Relative risk (RR) 4.2; conficence interval (CI) 2.144-6.812), multiple gestation (P < 0.03; RR 3.8; CI 1.037-6.235), gestational diabetes (P < 0.02; RR 4.8; CI 1.910-6.751) and obesity (P < 0.002; RR 2.7; CI 1.373-5.511) were the significant risk factors in the development of HDP among the study population. Conclusion: The prevalence of HDP in the study group is high. Therefore, paying attention to the risk factors will ensure early detection and prevention of the progression of the disease and its sequelae. PMID:25298602

Maternal factors associated with offspring polycystic ovarian syndrome.

PubMed

Steiner, Anne Z

2018-04-19

In this Swedish national registry-based cohort study Valgeirsdottir et al. sought to determine the association between 1) in-utero exposures and 2) birth indices and the subsequent development of polycystic ovarian syndrome (PCOS) after age 15. To do this, they selected 681,123 girls, whose birth was recorded in the Swedish birth registry between 1982 and 1995. They followed the girls in the Swedish Patient Registry until 2010 for a diagnosis of PCOS using International Classification of Diseases (ICD) codes. The authors found that in-utero exposure to maternal obesity and smoking, but not maternal pre-eclampsia or gestational diabetes, increased the risk of PCOS as an adolescent or young adult. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

miR-125b-1-3p inhibits trophoblast cell invasion by targeting sphingosine-1-phosphate receptor 1 in preeclampsia.

PubMed

Li, Qinghua; Pan, Zhifang; Wang, Xuejian; Gao, Zhiqin; Ren, Chune; Yang, Weiwei

2014-10-10

Preeclampsia (PE) is the leading cause of maternal and perinatal mortality and morbidity. Understanding the molecular mechanisms underlying placentation facilitates the development of better intervention of this disease. MicroRNAs are strongly implicated in the pathogenesis of this syndrome. In current study, we found that miR-125b-1-3p was elevated in placentas derived from preeclampsia patients. Transfection of miR-125b-1-3p mimics significantly inhibited the invasiveness of human trophoblast cells, whereas miR-125b-1-3p inhibitor enhanced trophoblast cell invasion. Luciferase assays identified that S1PR1 was a novel direct target of miR-125b-1-3p in the placenta. Overexpression of S1PR1 could reverse the inhibitory effect of miR-125b-1-3p on the invasion of trophoblast cells. These findings suggested that abnormal expression of miR-125b-1-3p might contribute to the pathogenesis of preeclampsia. Copyright © 2014 Elsevier Inc. All rights reserved.

Biochemistry of HELLP syndrome.

PubMed

Benedetto, Chiara; Marozio, Luca; Tancredi, Annalisa; Picardo, Elisa; Nardolillo, Paola; Tavella, Anna Maria; Salton, Loredana

2011-01-01

The HELLP syndrome is a serious complication of pregnancy characterized by hemolysis (H), elevated liver (EL) enzymes, and low platelet (LP) count that occurs in 0.2-0.6% of all pregnancies and in 10-20% of cases with severe preeclampsia and frequently leads to adverse maternal and perinatal outcome. The exact pathobiology of HELLP syndrome has not been clearly defined. As it is considered a form or a complication of severe preeclampsia, it likely has its origin in aberrant placental development and function resulting in ischemia-producing oxidative stress. However, there is still a debate on whether HELLP must be considered a severe form of preeclampsia or a separate disease entity. It can be described as a placenta-induced disease, as is preeclampsia itself, but with a more acute and predominant inflammatory process typically targeting the liver and with a greater activation of the coagulation system. This occurs during a disordered immunologic process and may be due to a genetic predisposition. In this review, we discuss the main biochemical characteristics of HELLP syndrome, particularly focusing on molecular aspects of placental involvement and maternal systemic responses.

Alteration of serum adropin level in preeclampsia.

PubMed

Wang, Huihua; Gao, Bo; Wu, Zaigui; Wang, Hanzhi; Dong, Minyue

2017-04-01

To clarify the alterations in serum adropin and preptin concentrations in preeclampsia, we determined serum adropin and preptin levels in 29 women with normal pregnancy and 32 women with preeclampsia. We found that maternal age, body mass index and fetal gender were not significantly different between two groups; however, blood pressure, gestational age and neonatal birth weight were significantly different. Serum adropin levels were significantly increased in women with preeclampsia compared with those with normal pregnancy but there were no significant differences in preptin levels. An increase in maternal serum adropin level was found in preeclampsia, and this may be a compensation for pregnancy complicated with preeclampsia. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics.

PubMed

Austdal, Marie; Thomsen, Liv Cecilie Vestrheim; Tangerås, Line Haugstad; Skei, Bente; Mathew, Seema; Bjørge, Line; Austgulen, Rigmor; Bathen, Tone Frost; Iversen, Ann-Charlotte

2015-12-01

Preeclampsia is a heterogeneous gestational disease characterized by maternal hypertension and proteinuria, affecting 2-7% of pregnancies. The disorder is initiated by insufficient placental development, but studies characterizing the placental disease components are lacking. Our aim was to phenotype the preeclamptic placenta using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS MRS). Placental samples collected after delivery from women with preeclampsia (n = 19) and normotensive pregnancies (n = 15) were analyzed for metabolic biomarkers including amino acids, osmolytes, and components of the energy and phospholipid metabolism. The metabolic biomarkers were correlated to clinical characteristics and inflammatory biomarkers in the maternal sera. Principal component analysis showed inherent differences in placental metabolic profiles between preeclamptic and normotensive pregnancies. Significant differences in metabolic profiles were found between placentas from severe and non-severe preeclampsia, but not between preeclamptic pregnancies with fetal growth restricted versus normal weight neonates. The placental metabolites correlated with the placental stress marker sFlt-1 and triglycerides in maternal serum, suggesting variation in placental stress signaling between different placental phenotypes. HR-MAS MRS is a sensitive method for defining the placental disease component of preeclampsia, identifying several altered metabolic pathways. Placental HR-MAS MRS analysis may improve insight into processes affected in the preeclamptic placenta, and represents a novel long-required tool for a sensitive placental phenotyping of this heterogeneous disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessment of quality of care among in-patients with postpartum haemorrhage and severe pre-eclampsia at st. Francis hospital nsambya: a criteria-based audit.

PubMed

Lumala, Alfred; Sekweyama, Peter; Abaasa, Andrew; Lwanga, Humphrey; Byaruhanga, Romano

2017-01-13

The maternal mortality ratio of Uganda is still high and the leading causes of maternal mortality are postpartum haemorrhage (PPH), severe pre-eclampsia and eclampsia. Criteria-based audit (CBA) is a way of improving quality of care that has not been commonly used in low income countries. This study aimed at finding out the quality of care provided to patients with these conditions and to find out if the implementation of recommendations from the audit cycle resulted in improvement in quality of care. This study was a CBA following a time series study design. It was done in St. Francis Hospital Nsambya and it involved assessment of adherence to standards of care for PPH, severe pre-eclampsia and eclampsia. An initial audit was done for 3 consecutive months, then findings were presented to health workers and recommendations made; we implemented the recommendations in a subsequent month and this comprised three interventions namely continuing medical education (CME), drills and displaying guidelines; a re-audit was done in the proceeding 3 consecutive months and analysis compared adherence rates of the initial audit with those of the re-audit. Pearson Chi-Square test revealed that the adherence rates of 7 out of 10 standards of care for severe pre-eclampsia/eclampsia were statistically significantly higher in the re-audit than in the initial audit; also, the adherence rates of 3 out of 4 standards of care for PPH were statistically significantly higher in the re-audit than in the initial audit. The giving of feedback on quality of care and the implementation of recommendations made during the CBA including CME, drills and displaying guidelines was associated with improvements in the quality of care for patients with PPH, severe pre-eclampsia and eclampsia.

miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia.

PubMed

Anton, Lauren; Olarerin-George, Anthony O; Schwartz, Nadav; Srinivas, Sindhu; Bastek, Jamie; Hogenesch, John B; Elovitz, Michal A

2013-11-01

Preeclampsia is characterized by hypertension and proteinuria in pregnant women. Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal morbidity and mortality. Although delivery, often premature, is the only known cure, early targeted interventions may improve maternal and fetal outcomes. Successful intervention requires a better understanding of the molecular etiology of preeclampsia and the development of accurate methods to predict women at risk. To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression reduced trophoblast invasion, a process necessary for uteroplacental perfusion, in an extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore, given that the placenta secretes miRNAs into the maternal circulation, we tested if serum expression of miR-210 was associated with the disease. We measured miR-210 expression in two clinical studies: a case-control study and a prospective cohort study. Serum miR-210 expression was significantly associated with a diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves = 0.81) and was predictive of the disease, even months before clinical diagnosis (P < 0.0001, area under the receiver operator curve = 0.89). Hence, we conclude that aberrant expression of miR-210 may contribute to trophoblast function and that miR-210 is a novel predictive serum biomarker for preeclampsia that can help in identifying at-risk women for monitoring and treatment. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Microvascular function in pre-eclampsia is influenced by insulin resistance and an imbalance of angiogenic mediators.

PubMed

Ghosh, Anshuman; Freestone, Nicholas S; Anim-Nyame, Nicholas; Arrigoni, Francesca I F

2017-04-01

In preeclampsia, maternal microvascular function is disrupted and angiogenesis is dysfunctional. Insulin resistance that occurs in some pregnancies also pathologically affects microvascular function. We wished to examine the relationship of angiogenic mediators and insulin resistance on microvascular health in pregnancy. We performed a nested, case-control study of 16 women who developed preeclampsia with 17 normal pregnant controls. We hypothesized that the impaired microvascular blood flow in preeclamptic women associated with an increased ratio of the antiangiogenic factors; (s-endoglin [sEng] and soluble fms-like tyrosine kinase-1 [sFlt-1]) and proangiogenic molecule (placental growth factor [PlGF]) could be influenced by insulin resistance. Serum samples taken after 28 weeks of gestation were measured for the angiogenic factors, insulin, and glucose alongside the inflammatory marker; tumor necrosis factor-α and endothelial activation, namely; soluble vascular cell adhesion molecule 1, intercellular adhesion molecule-1, and e-selectin. Maternal microvascular blood flow, measured by strain gauge plethysmography, correlated with ratios of pro- and antiangiogenic mediators independently of preeclampsia. Decreased microvascular function measured in preeclampsia strongly correlated with both the antiangiogenic factor (sFlt-1 + sEng): PlGF ratio and high levels of insulin resistance, and combining insulin resistance with antiangiogenic factor ratios further strengthened this relationship. In pregnancy, microvascular blood flow is strongly associated with perturbations in pro- and antiangiogenic mediators. In preeclampsia, the relationship of maternal microvascular dysfunction with antiangiogenic mediators is strengthened when combined with insulin resistance. © 2017 Kingston University. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Association of Plasminogen Activator Inhibitor-Type 1 (-675 4G/5G) Polymorphism with Pre-Eclampsia: Systematic Review

PubMed Central

Morgan, Jessie A.; Bombell, Sarah; McGuire, William

2013-01-01

Background and Aims Excessive generation of plasminogen activator inhibitor-type 1 (PAI-1) is implicated in the pathogenesis of pre-eclampsia and related conditions. The PAI-1 (−675 4G/5G) promoter polymorphism (rs1799889) affects transcriptional activity and is a putative genetic risk factor for pre-eclampsia. The aim of this study was identify, appraise and synthesise the available evidence for the association of the PAI-1 (−675 4G/5G) polymorphism with pre-eclampsia. Methods Systematic review and random effects meta-analysis of genetic association studies. Results We found 12 eligible genetic association studies in which a total of 1511 women with pre-eclampsia, eclampsia or HELLP syndrome and 3492 controls participated. The studies were generally small (median number of cases 102, range 24 to 403) and underpowered to detect plausible association sizes. Meta-analysis of all of the studies detected statistically significant gene-disease associations in the recessive [pooled odds ratio 1.28 (95% confidence interval 1.09, 1.50); population attributable risk 7.7%] and dominant [pooled odds ratio 1.21 (95% confidence interval 1.01, 1.44); population attributable risk 13.7%] models. We did not find evidence of statistical heterogeneity, funnel plot asymmetry or small study bias. Conclusions These data suggest that the fibrinolytic pathway regulated by the PAI-1 gene may contribute to the pathogenesis of pre-eclampsia and related conditions. This association, if confirmed in larger genetic association studies, may inform research efforts to develop novel interventions or help to prioritise therapeutic targets that merit evaluation in randomised clinical trials. PMID:23457639

Protein misfolding, congophilia, oligomerization, and defective amyloid processing in preeclampsia.

PubMed

Buhimschi, Irina A; Nayeri, Unzila A; Zhao, Guomao; Shook, Lydia L; Pensalfini, Anna; Funai, Edmund F; Bernstein, Ira M; Glabe, Charles G; Buhimschi, Catalin S

2014-07-16

Preeclampsia is a pregnancy-specific disorder of unknown etiology and a leading contributor to maternal and perinatal morbidity and mortality worldwide. Because there is no cure other than delivery, preeclampsia is the leading cause of iatrogenic preterm birth. We show that preeclampsia shares pathophysiologic features with recognized protein misfolding disorders. These features include urine congophilia (affinity for the amyloidophilic dye Congo red), affinity for conformational state-dependent antibodies, and dysregulation of prototype proteolytic enzymes involved in amyloid precursor protein (APP) processing. Assessment of global protein misfolding load in pregnancy based on urine congophilia (Congo red dot test) carries diagnostic and prognostic potential for preeclampsia. We used conformational state-dependent antibodies to demonstrate the presence of generic supramolecular assemblies (prefibrillar oligomers and annular protofibrils), which vary in quantitative and qualitative representation with preeclampsia severity. In the first attempt to characterize the preeclampsia misfoldome, we report that the urine congophilic material includes proteoforms of ceruloplasmin, immunoglobulin free light chains, SERPINA1, albumin, interferon-inducible protein 6-16, and Alzheimer's β-amyloid. The human placenta abundantly expresses APP along with prototype APP-processing enzymes, of which the α-secretase ADAM10, the β-secretases BACE1 and BACE2, and the γ-secretase presenilin-1 were all up-regulated in preeclampsia. The presence of β-amyloid aggregates in placentas of women with preeclampsia and fetal growth restriction further supports the notion that this condition should join the growing list of protein conformational disorders. If these aggregates play a pathophysiologic role, our findings may lead to treatment for preeclampsia. Copyright © 2014, American Association for the Advancement of Science.

Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia.

PubMed

Smith, Caitlin J; Saftlas, Audrey F; Spracklen, Cassandra N; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

2016-01-01

Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia. Subjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry. GRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations. GRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Preeclampsia does not share common risk alleles in 9p21 with coronary artery disease and type 2 diabetes.

PubMed

Kaartokallio, Tea; Lokki, A Inkeri; Peterson, Hanna; Kivinen, Katja; Hiltunen, Leena; Salmela, Elina; Lappalainen, Tuuli; Maanselkä, Paula; Heino, Sanna; Knuutila, Sakari; Sayed, Ayat; Poston, Lucilla; Brennecke, Shaun P; Johnson, Matthew P; Morgan, Linda; Moses, Eric K; Kere, Juha; Laivuori, Hannele

2016-08-01

Preeclampsia is a common and partially genetic pregnancy complication characterized by hypertension and proteinuria. Association with cardiovascular disease and type 2 diabetes has been reported in 9p21 by several genome-wide association studies. It has been hypothesized that cardiometabolic diseases may share common etiology with preeclampsia. We tested association with the 9p21 region to preeclampsia in the Finnish population by genotyping 23 tagging single nucleotide polymorphisms (SNPs) in 15 extended preeclampsia families and in a nationwide cohort consisting of 281 cases and 349 matched controls. Replication was conducted in additional datasets. Four SNPs (rs7044859, rs496892, rs564398 and rs7865618) showed nominal association (p ≤ 0.024 uncorrected) with preeclampsia in the case-control cohort. To increase power, we genotyped two SNPs in additional 388 cases and 341 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort. Partial replication was also attempted in a UK cohort (237 cases and 199 controls) and in 74 preeclamptic families from Australia/New Zealand. We were unable to replicate the initial association in the extended Finnish dataset or in the two international cohorts. Our study did not find evidence for the involvement of the 9p21 region in the risk of preeclampsia. Key Message Chromosome 9p21 is not associated with preeclampsia.

[THE ROLE OF ANGIOGENIC FACTORS IN THE DIAGNOSTICS OF PREGNANCY COMPLICATED WITH PREECLAMPSIA].

PubMed

Tagiyeva, I; Aliyeva, S; Bagirova, S; Shamsadinskaya, N; Agaeva, K

2017-01-01

The pathophysiology of preeclampsia remains largely unknown. It has been hypothesized that placental ischemia is an early event, leading to placental production of a soluble factor or factors that cause maternal endothelial dysfunction, resulting in the clinical findings of hypertension, proteinuria, and edema. Here, we confirm that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of vascular growth factor (VEGF) and placental growth factor (PIGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt1. Our research demonstrate that increased circulating sFlt1 in III trimester in patients with preeclampsia is associated with decreased circulating levels of free VEGF and PIGF, resulting in endothelial dysfunction, comparing with control group. These observations suggest that excess circulating sFlt1 contributes to the pathogenesis of preeclampsia. 45 pregnant women with preeclampsia of different severity degrees were under observation. Control group included 20 healthy pregnant. Pregnant women with preeclampsia were subdivided into 2 groups. There were 11 (24,4%) pregnant with severe degree of preeclamsia (I group), the II group included 34 pregnant with mild degree of preeclampsia. Increased expression of soluble tyrosine kinase-1 (sFlt-1), together with decreased PIGF and VEGF signaling, were first abnormalities described. Thus, determination of levels angiogenic factors: PIGF, VEGF and sFlt-1 is very important for prediction severity of preeclampsia.

Using clinical symptoms to predict adverse maternal and perinatal outcomes in women with preeclampsia: data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study.

PubMed

Yen, Tin-Wing; Payne, Beth; Qu, Ziguang; Hutcheon, Jennifer A; Lee, Tang; Magee, Laura A; Walters, Barry N; von Dadelszen, Peter

2011-08-01

Preeclampsia is a leading cause of maternal morbidity. The clinical challenge lies in predicting which women with preeclampsia will suffer adverse outcomes and would benefit from treatment, while minimizing potentially harmful interventions. Our aim was to determine the ability of maternal symptoms (i.e., severe nausea or vomiting, headache, visual disturbance, right upper quadrant pain or epigastric pain, abdominal pain or vaginal bleeding, and chest pain or dyspnea) to predict adverse maternal or perinatal outcomes. We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a multicentre, prospective cohort study designed to investigate the maternal risks associated with preeclampsia. Relative risks and receiver operating characteristic (ROC) curves were assessed for each preeclampsia symptom and outcome pair. Of 2023 women who underwent assessment, 52% experienced at least one preeclampsia symptom, with 5.2% and 5.3% respectively experiencing an adverse maternal or perinatal outcome. No symptom and outcome pair, in either of the maternal or perinatal groups, achieved an area under the ROC curve value > 0.7, which would be necessary to demonstrate a discriminatory predictive value. Maternal symptoms of preeclampsia are not independently valid predictors of maternal adverse outcome. Caution should be used when making clinical decisions on the basis of symptoms alone in the preeclamptic patient.

Preeclampsia with and without intrauterine growth restriction-Two pathogenetically different entities?

PubMed

Milosevic-Stevanovic, Jelena; Krstic, Miljan; Radovic-Janosevic, Dragana; Stefanovic, Milan; Antic, Vladimir; Djordjevic, Ivana

2016-11-01

The objective of this study is to determine the differences in histopathological features of basal decidua and placenta in cases of preeclampsia with or without fetal intrauterine growth restriction (IUGR). A prospective case-control study included a study group consisting of 30 pregnant women with preeclampsia completed by cesarean section (CS), in 19 of whom preeclampsia was associated with IUGR, and in 11 it was not. The control group consisted of 20 healthy pregnant women delivered by elective CS. Placentas and samples of placental bed obtained during CS were histopathologically (HP) analyzed after hematoxylin-eosin staining and immunohistochemical labeling of Cytokeratin 7 (CK7) trophoblastic cells in decidua. Regarding the HP changes in the spiral arteries in preeclampsia, the most frequent features were inadequate transformation of spiral arteries with poor trophoblastic invasion (70.0%) and fibrinoid necrosis of the media (66.7%), and rarely acute atherosis (33.3%) and thrombosis (30.0%). Villous hypermaturity was more frequently found in placentas of patients with preeclampsia with IUGR (p < 0.05), while there were no differences between subgroups of preeclampsia with and without IUGR regarding some of HP alterations of placental bed. Alterations of the placental bed in terms of decidual vasculopathy are more the characteristics of the preeclampsia itself than IUGR, while changes in placental villi primarily follow the presence of IUGR, which could indicate that preeclampsia with and without IUGR are two pathogenetically different entities.

Role of agonistic autoantibodies against type-1 angiotensin II receptor in the pathogenesis of retinopathy in preeclampsia.

PubMed

Liu, Fang; Wang, Yuxian; Wang, Xiaofang; Zheng, Yanqian; Jin, Zhu; Zhi, Jianming

2016-07-06

To investigate the mechanism underlying AT1-AA-induced retinopathy in severe preeclampsia by measuring the positive rate and titer of AT1-AA in plasma from women with severe preeclampsia and normal pregnant women to see whether AT1-AA titer was correlated with the grade of retinopathy. A preeclampsia rat model was also established by intravenous injection of AT1-AA extracted from the plasma of patient suffering from severe preeclampsia. The results showed that the plasma titer and positive rate of AT1-AA were significantly higher in women with severe preeclampsia than normal pregnant women. The antibody titer in cases of severe preeclampsia was associated with the grade of retinopathy, and positively correlated with the level of TNF-α and VEGF. The animal experiment results showed that the modeled rats presented symptoms very similar to symptoms of human preeclampsia, including retinopathy. Ocular fundus examination showed retinal microvascular abnormalities, hemorrhaging and leakage in the severe preeclampsia. Morphological changes included edema, thickening of the INL and ONL, and pigment atrophy. TNF-α and VEGF levels were increased in the vitreous humor and retina of the model rats. Our studies results suggest that abnormal expression of AT1-AA could induce damage to retinal capillary endothelial cells and increase vascular permeability, resulting in retinopathy.

A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

PubMed

Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

Assessment of the diagnostic value of a urinary adipsin rapid strip test for pre-eclampsia: A prospective multicenter study.

PubMed

Peng, Bing; Zhang, Li; Yan, Jianying; Qi, Hongbo; Zhang, Weiyuan; Fan, Ling; Hu, Yayi; Lin, Li; Li, Xiaotian; Hu, Rong; Xie, Lan; Zhang, Jianping; Wu, Yanqiao; Li, Li; Zhou, Rong

2017-01-01

The purpose of the present study was to evaluate the clinical value of the rapid strip test of urinary adipsin for the quick diagnosis of pre-eclampsia. In a multicenter diagnostic test study, we studied the diagnostic accuracy of the rapid strip test of urinary adipsin in women presenting with pre-eclampsia. A total of 204 pre-eclampsia patients and 254 healthy pregnant women were recruited for this study, respectively. The rapid strip test of urinary adipsin was used to detect the adipsin in the urine of each patient. The diagnostic value of the rapid strip test of urinary adipsin for pre-eclampsia was demonstrated by its high sensitivity and specificity (95.10% and 97.64%, respectively). The diagnostic accuracy was 96.51%. The consistency analysis showed that the kappa value was 0.93 compared with the gold standard diagnosis of pre-eclampsia. The rapid strip test of urinary adipsin is a non-invasive test for the diagnosis of pre-eclampsia with high sensitivity and specificity. It could help the quick diagnosis of pre-eclampsia in clinical practice greatly. © 2016 Japan Society of Obstetrics and Gynecology.

The relationship between urinary tract infection during pregnancy and preeclampsia: causal, confounded or spurious?

PubMed

Karmon, Anatte; Sheiner, Eyal

2008-06-01

Preeclampsia is a major cause of maternal morbidity, although its precise etiology remains elusive. A number of studies suggest that urinary tract infection (UTI) during the course of gestation is associated with elevated risk for preeclampsia, while others have failed to prove such an association. In our medical center, pregnant women who were exposed to at least one UTI episode during pregnancy were 1.3 times more likely to have mild preeclampsia and 1.8 times more likely to have severe preeclampsia as compared to unexposed women. Our results are based on univariate analyses and are not adjusted for potential confounders. This editorial aims to discuss the relationship between urinary tract infection and preeclampsia, as well as examine the current problems regarding the interpretation of this association. Although the relationship between UTI and preeclampsia has been demonstrated in studies with various designs, carried-out in a variety of settings, the nature of this association is unclear. By taking into account timeline, dose-response effects, treatment influences, and potential confounders, as well as by neutralizing potential biases, future studies may be able to clarify the relationship between UTI and preeclampsia by determining if it is causal, confounded, or spurious.

Advances in the pathophysiology of pre-eclampsia and related podocyte injury

PubMed Central

Craici, Iasmina M.; Wagner, Steven J.; Weissgerber, Tracey L.; Grande, Joseph P.; Garovic, Vesna D.

2014-01-01

Pre-eclampsia is a pregnancy-specific hypertensive disorder that may lead to serious maternal and fetal complications. It is a multisystem disease that is commonly, but not always, accompanied by proteinuria. Its cause(s) remain unknown, and delivery remains the only definitive treatment. It is increasingly recognized that many pathophysiological processes contribute to this syndrome, with different signaling pathways converging at the point of systemic endothelial dysfunction, hypertension, and proteinuria. Different animal models of pre-eclampsia have proven utility for specific aspects of pre-eclampsia research, and offer insights into pathophysiology and treatment possibilities. Therapeutic interventions that specifically target these pathways may optimize pre-eclampsia management and may improve fetal and maternal outcomes. In addition, recent findings regarding placental, endothelial, and podocyte pathophysiology in pre-eclampsia provide unique and exciting possibilities for improved diagnostic accuracy. Emerging evidence suggests that testing for urinary podocytes or their markers may facilitate the prediction and diagnosis of pre-eclampsia. In this review, we explore recent research regarding placental, endothelial, and podocyte pathophysiology. We further discuss new signaling and genetic pathways that may contribute to pre-eclampsia pathophysiology, emerging screening and diagnostic strategies, and potential targeted interventions. PMID:24573315

Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

PubMed

Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

2005-08-01

Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (<34 weeks gestation) with 14 matched normotensive controls, as well as 15 cases late-onset preeclampsia (>34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

Pre-eclampsia: pathophysiology, diagnosis, and management

PubMed Central

Uzan, Jennifer; Carbonnel, Marie; Piconne, Olivier; Asmar, Roland; Ayoubi, Jean-Marc

2011-01-01

The incidence of pre-eclampsia ranges from 3% to 7% for nulliparas and 1% to 3% for multiparas. Pre-eclampsia is a major cause of maternal mortality and morbidity, preterm birth, perinatal death, and intrauterine growth restriction. Unfortunately, the pathophysiology of this multisystem disorder, characterized by abnormal vascular response to placentation, is still unclear. Despite great polymorphism of the disease, the criteria for pre-eclampsia have not changed over the past decade (systolic blood pressure >140 mmHg or diastolic blood pressure ≥90 mmHg and 24-hour proteinuria ≥0.3 g). Clinical features and laboratory abnormalities define and determine the severity of pre-eclampsia. Delivery is the only curative treatment for pre-eclampsia. Multidisciplinary management, involving an obstetrician, anesthetist, and pediatrician, is carried out with consideration of the maternal risks due to continued pregnancy and the fetal risks associated with induced preterm delivery. Screening women at high risk and preventing recurrences are key issues in the management of pre-eclampsia. PMID:21822394

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

PubMed Central

Conrad, Kirk P.

2016-01-01

BACKGROUND Important roles for G-protein-coupled receptors (GPCRs) have been identified in the maternal physiological adaptations to pregnancy and in the pathogenesis of preeclampsia. On this basis, GPCRs are potential therapeutic targets for preeclampsia. OBJECTIVES AND RATIONALE In this review, vasopressin and apelin are initially considered in this context before the focus on the hormone relaxin and its cognate receptor, the relaxin/insulin-like family peptide receptor 1 (RXFP1). Based on both compelling scientific rationale and a promising safety profile, the relaxin ligand–receptor system is comprehensively evaluated as a potential therapeutic endpoint in preeclampsia. SEARCH METHODS The published literature relating to the topic was searched through January 2016 using PubMed. OUTCOMES Relaxin is a peptide hormone secreted by the corpus luteum; it circulates in the luteal phase and during pregnancy. Activation of RXFP1 is vasodilatory; thus, relaxin supplementation is expected to at least partly restore the fundamental vasodilatory changes of normal pregnancy, thereby alleviating maternal organ hypoperfusion, which is a major pathogenic manifestation of severe preeclampsia. Specifically, by exploiting its pleiotropic hemodynamic attributes in preeclampsia, relaxin administration is predicted to (i) reverse robust arterial myogenic constriction; (ii) blunt systemic and renal vasoconstriction in response to activation of the angiotensin II receptor, type 1; (iii) mollify the action of endogenous vasoconstrictors on uterine spiral arteries with failed remodeling and retained smooth muscle; (iv) increase arterial compliance; (v) enhance insulin-mediated glucose disposal by promoting skeletal muscle vasodilation and (vi) mobilize and activate bone marrow-derived angiogenic progenitor cells, thereby repairing injured endothelium and improving maternal vascularity in organs such as breast, uterus, pancreas, skin and fat. By exploiting its pleiotropic molecular attributes in preeclampsia, relaxin supplementation is expected to (i) enhance endothelial nitric oxide synthesis and bioactivity, as well as directly reduce vascular smooth muscle cytosolic calcium, thus promoting vasodilation; (ii) improve the local angiogenic balance by augmenting arterial vascular endothelial and placental growth factor (VEGF and PLGF) activities; (iii) ameliorate vascular inflammation; (iv) enhance placental peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PCG1α) expression, and hence, peroxisome proliferator-activated receptor gamma (PPAR-γ) activity and (v) confer cytotrophoblast and endothelial cytoprotection. Insofar as impaired endometrial maturation (decidualization) predisposes to the development of preeclampsia, relaxin administration in the late secretory phase and during early pregnancy would be anticipated to improve decidualization, and hence trophoblast invasion and spiral artery remodeling, thereby reducing the risk of preeclampsia. Relaxin has a favorable safety profile both in the non-pregnant condition and during pregnancy. WIDER IMPLICATIONS There is a strong scientific rationale for RXFP1 activation in severe preeclampsia by administration of relaxin, relaxin analogs or small molecule mimetics, in order to mollify the disease pathogenesis for safe prolongation of pregnancy, thus allowing time for more complete fetal maturation, which is a primary therapeutic endpoint in treating the disease. In light of recent data implicating deficient or defective decidualization as a potential etiological factor in preeclampsia and the capacity of relaxin to promote endometrial maturation, the prophylactic application of relaxin to reduce the risk of preeclampsia is a plausible therapeutic approach to consider. Finally, given its pleiotropic and beneficial attributes particularly in the cardiovascular system, relaxin, although traditionally considered as a ‘pregnancy’ hormone, is likely to prove salutary for several disease indications in the non-pregnant population. PMID:27385360

PREECLAMPSIA AND SMALL FOR GESTATIONAL AGE ARE ASSOCIATED WITH DECREASED CONCENTRATIONS OF A FACTOR INVOLVED IN ANGIOGENESIS: SOLUBLE TIE-2

PubMed Central

Gotsch, Francesca; Romero, Roberto; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Dombrowski, Michael; Erez, Offer; Than, Nandor Gabor; Mazaki-Tovi, Shali; Mittal, Pooja; Espinoza, Jimmy; Hassan, Sonia S

2009-01-01

OBJECTIVE An anti-angiogenic state has been described in patients with preeclampsia, small for gestational age (SGA) fetuses and fetal death, and changes in the concentration of circulating angiogenic and anti-angiogenic factors can precede the clinical recognition of preeclampsia and small for gestational age by several weeks. Gene deletion studies demonstrate that a selective group of endothelial growth factors are required for vascular development, including members of the vascular endothelial growth factor (VEGF) family, as well as Angiopoietin-1 and Angiopoietin-2, both ligands for the tyrosine kinase endothelial cell receptor Tie-2. These angiogenic factors have been proposed to promote angiogenesis in a coordinated and complementary fashion. Soluble Tie-2 (sTie-2) is the soluble form of the Tie-2 receptor which is detectable in biological fluids. The purpose of this study was to determine whether patients with preeclampsia and mothers who deliver a small for gestational age neonate have changes in the plasma concentrations of sTie-2. STUDY DESIGN This cross-sectional study included patients in the following groups: 1) non-pregnant women (n=40); 2) women with normal pregnancies (n=135); 3) patients with preeclampsia (n=112); and 4) patients who delivered a small for gestational age (SGA) neonate (n=53). Maternal plasma concentrations of sTie-2 were measured by a sensitive immunoassay. Parametric statistics were used for analysis. RESULTS 1) The median maternal plasma concentration of sTie-2 was lower in normal pregnant women than in non-pregnant women [median 16.0 ng/ml (range 5.0–71.6) vs. median 20.7 ng/ml (range 10.8–52.4), respectively; p=0.01)]; 2) Plasma sTie-2 concentrations in normal pregnancy changed significantly as a function of gestational age; 3) Patients with preeclampsia and those who delivered SGA neonates had a lower median maternal plasma concentration of sTie-2 than those with a normal pregnancy [Preeclampsia: median 14.9 ng/ml (range 4.9–67.3); SGA: median 10.9 ng/ml (range 5.1–29.1); Normal pregnancy: median 16.0 ng/ml (range 5.0–71.6); p=0.048 and p<0.001, respectively]; 4) Patients with SGA neonates had a lower median plasma concentration of sTie-2 than that of those with preeclampsia [median 10.9 ng/ml (range 5.1–29.1) vs. median 14.9 ng/ml (range 4.9–67.3), respectively; p<0.001)]; and 5) Patients with early-onset preeclampsia (≤34 weeks) had lower concentrations of sTie-2 than women with late-onset preeclampsia (>34 weeks) [median of delta values: −0.13 ng/ml (range −0.47–0.58) vs. median of delta values: −0.09 ng/ml (range: −0.60–0.58), respectively; p=0.043]. In contrast, there were no significant differences in the maternal plasma sTie-2 concentration between women with severe and mild preeclampsia (p=0.6). CONCLUSION Patients with preeclampsia and those with SGA fetuses have lower median plasma concentrations of soluble Tie-2 than women with normal pregnancies. PMID:18570117

Epidemiology of preeclampsia: Impact of obesity

PubMed Central

Jeyabalan, Arun

2013-01-01

Preeclampsia is a pregnancy-specific disorder that affects 2 to 8% of all pregnancies and remains a leading cause of maternal and perinatal morbidity and mortality worldwide. Diagnosis is based on new onset of hypertension and proteinuria. Multiple organ systems can be affected with severe disease. The wide range of risk factors reflects the heterogeneity of preeclampsia. Obesity, which is increasing at an alarming rate, is also a risk factor for preeclampsia as well as for later life cardiovascular disease. Exploring common features may provide insight into the pathophysiologic mechanisms underlying preeclampsia among obese and overweight women. PMID:24147919

Vascular Dysfunction in Mother and Offspring During Preeclampsia: Contributions from Latin-American Countries.

PubMed

Giachini, Fernanda Regina; Galaviz-Hernandez, Carlos; Damiano, Alicia E; Viana, Marta; Cadavid, Angela; Asturizaga, Patricia; Teran, Enrique; Clapes, Sonia; Alcala, Martin; Bueno, Julio; Calderón-Domínguez, María; Ramos, María P; Lima, Victor Vitorino; Sosa-Macias, Martha; Martinez, Nora; Roberts, James M; Escudero, Carlos

2017-10-06

Pregnancy is a physiologically stressful condition that generates a series of functional adaptations by the cardiovascular system. The impact of pregnancy on this system persists from conception beyond birth. Recent evidence suggests that vascular changes associated with pregnancy complications, such as preeclampsia, affect the function of the maternal and offspring vascular systems, after delivery and into adult life. Since the vascular system contributes to systemic homeostasis, defective development or function of blood vessels predisposes both mother and infant to future risk for chronic disease. These alterations in later life range from fertility problems to alterations in the central nervous system or immune system, among others. It is important to note that rates of morbi-mortality due to pregnancy complications including preeclampsia, as well as cardiovascular diseases, have a higher incidence in Latin-American countries than in more developed countries. Nonetheless, there is a lack both in the amount and impact of research conducted in Latin America. An impact, although smaller, can be seen when research in vascular disorders related to problems during pregnancy is analyzed. Therefore, in this review, information about preeclampsia and endothelial dysfunction generated from research groups based in Latin-American countries will be highlighted. We relate the need, as present in many other countries in the world, for increased effective regional and international collaboration to generate new data specific to our region on this topic.

A systematic review of first trimester biochemical and molecular predictive tests for preeclampsia.

PubMed

Abdi, Fatemeh; Aghaie, Zohreh; Rahnemaie, Fatemeh Sadat; Alimoradi, Zainab

2018-04-16

Preeclampsia is a multisystem disorder affecting 5%-8% of pregnant women. Considering the ongoing debate over the predicting value of some commercial first trimester tests, the aim of this study was to compare the existing first trimester screening tests for preeclampsia. In this systematic review, relevant articles published during 2000-2017 were extracted from PubMed, Science Direct, Scopus, Cochrane Library, ISI Web of Science, and ProQuest databases. After thorough evaluation of the 412 potentially eligible papers, only 26 papers were selected based on the inclusion criteria. From a total of 412 retrieved studies, 28 papers were found eligible. Most studies had case-control or nested case-control designs. A total of 15164 pregnant women were evaluated in the reviewed studies. Various tests were applied in the first trimester of pregnancy to predict the development of preeclampsia. The most commonly used biomarkers were uterine artery pulsatility index, pregnancy-associated plasma protein A (PAPP-A), adiponectin, human chorionic gonadotropin (hCG) hormone and inhibin-A. Other tests were used in only one or two studies. Based on this review, a combination of markers should be evaluated for the identification of high risk women. Novel methods measuring multiple markers will hopefully facilitate the development of clinically effective screening programs in the future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

External validation of preexisting first trimester preeclampsia prediction models.

PubMed

Allen, Rebecca E; Zamora, Javier; Arroyo-Manzano, David; Velauthar, Luxmilar; Allotey, John; Thangaratinam, Shakila; Aquilina, Joseph

2017-10-01

To validate the increasing number of prognostic models being developed for preeclampsia using our own prospective study. A systematic review of literature that assessed biomarkers, uterine artery Doppler and maternal characteristics in the first trimester for the prediction of preeclampsia was performed and models selected based on predefined criteria. Validation was performed by applying the regression coefficients that were published in the different derivation studies to our cohort. We assessed the models discrimination ability and calibration. Twenty models were identified for validation. The discrimination ability observed in derivation studies (Area Under the Curves) ranged from 0.70 to 0.96 when these models were validated against the validation cohort, these AUC varied importantly, ranging from 0.504 to 0.833. Comparing Area Under the Curves obtained in the derivation study to those in the validation cohort we found statistically significant differences in several studies. There currently isn't a definitive prediction model with adequate ability to discriminate for preeclampsia, which performs as well when applied to a different population and can differentiate well between the highest and lowest risk groups within the tested population. The pre-existing large number of models limits the value of further model development and future research should be focussed on further attempts to validate existing models and assessing whether implementation of these improves patient care. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Impact of USPSTF recommendations for aspirin for prevention of recurrent preeclampsia.

PubMed

Tolcher, Mary Catherine; Chu, Derrick M; Hollier, Lisa M; Mastrobattista, Joan M; Racusin, Diana A; Ramin, Susan M; Sangi-Haghpeykar, Haleh; Aagaard, Kjersti M

2017-09-01

The US Preventive Services Task Force recommends low-dose aspirin for the prevention of preeclampsia among women at high risk for primary occurrence or recurrence of disease. Recommendations for the use of aspirin for preeclampsia prevention were issued by the US Preventive Services Task Force in September 2014. The objective of the study was to evaluate the incidence of recurrent preeclampsia in our cohort before and after the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. This was a retrospective cohort study designed to evaluate the rates of recurrent preeclampsia among women with a history of preeclampsia. We utilized a 2-hospital, single academic institution database from August 2011 through June 2016. We excluded multiple gestations and included only the first delivery for women with multiple deliveries during the study period. The cohort of women with a history of preeclampsia were divided into 2 groups, before and after the release of the US Preventive Services Task Force 2014 recommendations. Potential confounders were accounted for in multivariate analyses, and relative risk and adjusted relative risk were calculated. A total of 17,256 deliveries occurred during the study period. A total of 417 women had a documented history of prior preeclampsia: 284 women before and 133 women after the US Preventive Services Task Force recommendation. Comparing the before and after groups, the proportion of Hispanic women in the after group was lower and the method of payment differed between the groups (P <.0001). The prevalence of type 1 diabetes was increased in the after period, but overall rates of pregestational diabetes were similar (6.3% before vs 5.3% after [P > .05]). Risk factors for recurrent preeclampsia included maternal age >35 years (relative risk, 1.83; 95% confidence interval, 1.34-2.48), Medicaid insurance (relative risk, 2.08; 95% confidence interval, 1.15-3.78), type 2 diabetes (relative risk, 2.13; 95% confidence interval, 1.37-3.33), and chronic hypertension (relative risk, 1.96; 95% confidence interval, 1.44-2.66). The risk of recurrent preeclampsia was decreased by 30% in the after group (adjusted relative risk, 0.70; 95% confidence interval, 0.52-0.95). Rates of recurrent preeclampsia among women with a history of preeclampsia decreased by 30% after release of the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. Future prospective studies should include direct measures of aspirin compliance, gestational age at initiation, and explore the influence of race and ethnicity on the efficacy of this primary prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

A Study on Atherogenic Indices of Pregnancy Induced Hypertension Patients as Compared to Normal Pregnant Women

PubMed Central

Pathak, Mauchumi Saikia; Paul, Anindita

2015-01-01

Introduction Pregnancy induced hypertension (PIH) includes Gestational hypertension, Pre-eclampsia and Eclampsia and is one of the most common obstetric complication. Worldwide about 76,000 pregnant women die each year from pre-eclampsia and related hypertensive disorders. The aetiology of Pre-eclampsia is unknown but it is thought to be related to abnormal development of placenta. Several studies have shown the presence of reduced endothelial function in pre-eclamptic pregnancy. Endothelial dysfunction is also a feature of atherosclerosis. Aim To assess fasting lipid profile and atherogenic indices in women diagnosed with pre-eclampsia as well as in women with normal pregnancy and to correlate the findings of pre-eclamptic women with that of normal pregnant women, in an attempt to utilize the data for the development of a new clinical approach for early recognition and prevention of risk of future cardiovascular diseases in women with PIH. Materials and Methods This case-control study was conducted on 50 pre-eclampsia patients who were in third trimester of pregnancy (Case group). A control group of 50 age and gestational age matched normal pregnant women was taken. Strict inclusion and exclusion criteria were followed. Fasting Lipid profile parameters were assessed and used to calculate the atherogenic indices namely Atherogenic index of plasma (AIP), Cardiac risk ratio (CRR) and Atherogenic coefficient (AC). Statistical Analysis was done by using student’s t-test. Mann-Whitney U-test was used wherever applicable and correlations between the variables were estimated by Pearson’s correlation coefficients. Results There was an extremely significant (p<0.0001) increase in Atherogenic indices (AIP, CRR and AC) in case group as compared to the control group. A positive and significant correlation of systolic blood pressure with AIP (r=0.3583), CRR (r=0.3137), AC (r=0.3193) was found in cases. There was a positive and significant correlation between gestational age and atherogenic indices in the case group. Conclusion Women with pre-eclampsia present abnormalities in lipid profile and these lipids turn out to be a risk factor for cardiovascular complications. Evaluation of the atherogenic indices during pregnancy may help prevent this risk. PMID:26393117

The association between maternal antioxidant levels in midpregnancy and preeclampsia.

PubMed

Cohen, Jacqueline M; Kramer, Michael S; Platt, Robert W; Basso, Olga; Evans, Rhobert W; Kahn, Susan R

2015-11-01

We sought to determine whether midpregnancy antioxidant levels are associated with preeclampsia, overall and by timing of onset. We carried out a case-control study, nested within a cohort of 5337 pregnant women in Montreal, Quebec, Canada. Blood samples obtained at 24-26 weeks were assayed for nonenzymatic antioxidant levels among cases of preeclampsia (n = 111) and unaffected controls (n = 441). We excluded women diagnosed with gestational hypertension only. We used logistic regression with the z-score of each antioxidant level as the main predictor variable for preeclampsia risk. We further stratified early-onset (<34 weeks) and late-onset preeclampsia and carried out multinomial logistic regression. Finally, we assessed associations between antioxidant biomarkers and timing of onset (in weeks) by Cox regression, with appropriate selection weights. We summed levels of correlated biomarkers (r(2) > 0.3) and log-transformed positively skewed distributions. We adjusted for body mass index, nulliparity, preexisting diabetes, hypertension, smoking, and proxies for ethnicity and socioeconomic status. The odds ratios for α-tocopherol, α-tocopherol:cholesterol, lycopene, lutein, and carotenoids (sum of α-carotene, β-carotene, anhydrolutein, α-cryptoxanthin, and β-cryptoxanthin) suggested an inverse association between antioxidant levels and overall preeclampsia risk; however, only lutein was significantly associated with overall preeclampsia in adjusted models (odds ratio, 0.60; 95% confidence interval, 0.46-0.77) per SD. In multinomial logistic models, the relative risk ratio (RRR) estimates for the early-onset subgroup were farther from the null than those for the late-onset subgroup. The ratio of α-tocopherol to cholesterol and retinol were significantly associated with early- but not late-onset preeclampsia: RRRs (95% confidence intervals) for early-onset preeclampsia 0.67 (0.46-0.99) and 1.61 (1.12-2.33), respectively. Lutein was significantly associated with both early- and late-onset subtypes in adjusted models; RRRs 0.53 (0.35-0.80) and 0.62 (0.47-0.82), respectively. Survival analyses confirmed these trends. Most antioxidants were more strongly associated with early-onset preeclampsia, suggesting that oxidative stress may play a greater role in the pathophysiology of early-onset preeclampsia. Alternatively, reverse causality may explain this pattern. Lutein was associated with both early- and late-onset preeclampsia and may be a promising nutrient to consider in preeclampsia prevention trials, if this finding is corroborated. Copyright © 2015 Elsevier Inc. All rights reserved.

Environmental noise pollution and risk of preeclampsia.

PubMed

Auger, Nathalie; Duplaix, Mathilde; Bilodeau-Bertrand, Marianne; Lo, Ernest; Smargiassi, Audrey

2018-08-01

Environmental noise exposure is associated with a greater risk of hypertension, but the link with preeclampsia, a hypertensive disorder of pregnancy, is unclear. We sought to determine the relationship between environmental noise pollution and risk of preeclampsia during pregnancy. We analyzed a population-based cohort comprising 269,263 deliveries on the island of Montreal, Canada between 2000 and 2013. We obtained total environmental noise pollution measurements (LA eq24 , L den , L night ) from land use regression models, and assigned noise levels to each woman based on the residential postal code. We computed odds ratios (OR) and 95% confidence intervals (CI) for the association of noise with preeclampsia in mixed logistic regression models with participants as a random effect, and adjusted for air pollution, neighbourhood walkability, maternal age, parity, multiple pregnancy, comorbidity, socioeconomic deprivation, and year of delivery. We assessed whether noise exposure was more strongly associated with severe or early onset preeclampsia than mild or late onset preeclampsia. Prevalence of preeclampsia was higher for women exposed to elevated environmental noise pollution levels (LA eq24h  ≥ 65 dB(A) = 37.9 per 1000 vs. <50 dB(A) = 27.9 per 1000). Compared with 50 dB(A), an LA eq24h of 65.0 dB(A) was not significantly associated the risk of preeclampsia (OR 1.09, 95% CI 0.99-1.20). Associations were however present with severe (OR 1.29, 95% CI 1.09-1.54) and early onset (OR 1.71, 95% CI 1.20-2.43) preeclampsia, with results consistent across all noise indicators. The associations were much weaker or absent for mild and late preeclampsia. Environmental noise pollution may be a novel risk factor for pregnancy-related hypertension, particularly more severe variants of preeclampsia. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preeclampsia Associates with Asthma, Allergy, and Eczema in Childhood.

PubMed

Stokholm, Jakob; Sevelsted, Astrid; Anderson, Ulrik D; Bisgaard, Hans

2017-03-01

Preeclampsia reflects an unusual increase in systemic inflammation during pregnancy. We studied associations between preeclampsia and asthma, allergy, and eczema in Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC 2000 ) and in national registries. COPSAC 2000 is a high-risk birth cohort of 411 Danish children. Asthma, allergy, and eczema were diagnosed prospectively, and lung function measured at age 1 month and 7 years. Sensitization was evaluated at age 6 months, 18 months, 4 years, and 6 years by skin prick tests and IgE measurements. The register-based cohort included 1.7 million children from Danish national registries in the 35-year period 1977-2012. Children born to mothers with preeclampsia were analyzed regarding risk of asthma, allergy, and eczema. In the COPSAC 2000 cohort, 5.6% (n = 23) were diagnosed with preeclampsia. Preeclampsia was associated with increased risk of treatment with inhaled corticosteroids at age 7 years (adjusted odds ratio, 4.01 [95% confidence interval (CI), 1.11-14.43]; P = 0.0337), increased bronchial responsiveness to methacholine (adjusted β-coefficient log-μmol, -0.80 [95% CI, -1.55 to -0.06]; P = 0.0348), and allergic rhinitis (adjusted odds ratio, 4.83 [95% CI, 1.58-14.78]; P = 0.0057) in the 7-year-old children. Furthermore, the children had an increased risk of sensitization to both aeroallergens and food allergens, and increased amount of total IgE during childhood. In the registry-based cohort, 3.7% (n = 62,728) were born to mothers with preeclampsia. Preeclampsia was associated with increased risk of asthma, eczema, and aeroallergen and food allergy, especially pronounced after a duration of preeclampsia of 14 days or more. Maternal asthma increased the risk of preeclampsia. Preeclampsia is a shared prenatal risk factor for asthma, eczema, and allergy in childhood pointing toward in utero immune programming of the child.

Low-dose aspirin at ≤16 weeks of gestation for preventing preeclampsia and its maternal and neonatal adverse outcomes: A systematic review and meta-analysis

PubMed Central

Cui, Yuechong; Zhu, Bin; Zheng, Fei

2018-01-01

The aim of the present meta-analysis study was to evaluate the efficacy of low-dose aspirin, commenced at ≤16 weeks of gestation, in preventing preterm and term preeclampsia, as well as associated maternal and neonatal adverse events in women at risk of preeclampsia. The Embase, PubMed, Cochrane Central Register of Controlled Trials and the Web of Science databases were searched for relevant random controlled trials (RCTs) published between January 1979 and October 2017. After quality assessment and data extraction, a meta-analysis was performed using RevMan 5.3 software. Outcomes of interest were preeclampsia with subgroups of preterm preeclampsia (delivery at <37 weeks) and term preeclampsia, as well as maternal adverse outcomes, including gestational hypertension, postpartum hemorrhage and preterm birth, and neonatal adverse outcomes, including intrauterine growth retardation (IUGR) or small for gestation age infant (SGA), stillbirth or death, and newborn weight. A total of 10 RCTs involving 3,168 participants were included. The meta-analysis demonstrated that, compared with placebo or no treatment, low-dose aspirin was associated with a significant reduction in the overall risk ratio (RR) of preeclampsia regardless of the time to delivery [RR=0.67; 95% confidence interval (CI)=0.57–0.80]. This was apparent for preterm preeclampsia (RR=0.35; 95% CI=0.13–0.94) but not for term preeclampsia (RR=1.01; 95% CI=0.60–1.70). Except for postpartum hemorrhage, low-dose aspirin also significantly reduced the risk of maternal and neonatal adverse outcomes. In conclusion, low-dose aspirin in women at risk of preeclampsia, commenced at ≤16 weeks of gestation, was associated with a reduced risk of preterm preeclampsia, and of adverse maternal and neonatal outcomes. PMID:29725376

Delta-aminolevulinate dehydratase activity and oxidative stress markers in preeclampsia.

PubMed

de Lucca, Leidiane; Rodrigues, Fabiane; Jantsch, Letícia B; Kober, Helena; Neme, Walter S; Gallarreta, Francisco M P; Gonçalves, Thissiane L

2016-12-01

Preeclampsia is an important pregnancy-specific multisystem disorder characterized by the onset of hypertension and proteinuria. It is of unknown etiology and involves serious risks for the pregnant women and fetus. One of the main factors involved in the pathophysiology of preeclampsia is oxidative stress, where excess free radicals produce harmful effects, including damage to macromolecules such as lipids, proteins and DNA. In addition, the sulfhydryl delta-aminolevulinate dehydratase enzyme (δ-ALA-D) that is part of the heme biosynthetic pathway in pro-oxidant conditions can be inhibited, which may result in the accumulation of 5-aminolevulinic acid (ALA), associated with the overproduction of free radicals, suggesting it to be an indirect marker of oxidative stress. As hypertensive pregnancy complications are a major cause of morbidity and mortality maternal and fetal where oxidative stress appears to be an important factor involved in preeclampsia, the aim of this study was to evaluate the activity of δ-ALA-D and classic oxidative stress markers in the blood of pregnant women with mild and severe preeclampsia. The analysis and quantification of the following oxidative stress markers were performed: thiobarbituric acid-reactive species (TBARS); presence of protein and non-protein thiol group; quantification of vitamin C; Catalase and δ-ALA--D activities in samples of blood of pregnant women with mild preeclampsia (n=25), with severe preeclampsia (n=30) and in a control group of healthy pregnant women (n=30). TBARS was significantly higher in women with preeclampsia, while the presence of thiol groups, levels of vitamin C, catalase and δ-ALA-D activity were significantly lower in groups of pregnant women with preeclampsia compared with healthy women. In addition, the results showed no significant difference between groups of pregnant women with mild and severe preeclampsia. The data suggest a state of increased oxidative stress in pregnant women with preeclampsia compared to healthy pregnant women, which may be related to the complications of this disease. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Retinol-Binding Protein 4 and Lipids Prospectively Measured During Early to Mid-Pregnancy in Relation to Preeclampsia and Preterm Birth Risk.

PubMed

Mendola, Pauline; Ghassabian, Akhgar; Mills, James L; Zhang, Cuilin; Tsai, Michael Y; Liu, Aiyi; Yeung, Edwina H

2017-06-01

Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk. Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors. RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation. Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women. © Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2017. This work is written by (a) US Government employees(s) and is in the public domain in the US.

Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction

PubMed Central

2011-01-01

Background It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR. Methods We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8) and normotensive pregnancies with or (n = 8) without FGR (n = 8) using a microarray method. Results A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels. Conclusions Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia. PMID:21810232

Treatment of Sleep Disordered Breathing Reverses Low Fetal Activity Levels in Preeclampsia

PubMed Central

Blyton, Diane M.; Skilton, Michael R.; Edwards, Natalie; Hennessy, Annemarie; Celermajer, David S.; Sullivan, Colin E.

2013-01-01

Study Objectives: Preeclampsia affects 5% to 7% of pregnancies, is strongly associated with low birth weight and fetal death, and is accompanied by sleep disordered breathing. We hypothesized that sleep disordered breathing may link preeclampsia with reduced fetal movements (a marker of fetal health), and that treatment of sleep disordered breathing might improve fetal activity during sleep. Design, Setting, and Participants: First, a method of fetal movement recording was validated against ultrasound in 20 normal third trimester pregnancies. Second, fetal movement was measured overnight with concurrent polysomnography in 20 patients with preeclampsia and 20 control subjects during third trimester. Third, simultaneous polysomnography and fetal monitoring was done in 10 additional patients with preeclampsia during a control night and during a night of nasal CPAP. Intervention: Overnight continuous positive airway pressure. Measurements and Results: Women with preeclampsia had inspiratory flow limitation and an increased number of oxygen desaturations during sleep (P = 0.008), particularly during REM sleep. Preeclampsia was associated with reduced total fetal movements overnight (319 [SD 32]) versus controls (689 [SD 160], P < 0.0001) and a change in fetal movement patterns. The number of fetal hiccups was also substantially reduced in preeclampsia subjects (P < 0.0001). Continuous positive airway pressure treatment increased the number of fetal movements and hiccups (P < 0.0001 and P = 0.0002, respectively). Conclusions: The effectiveness of continuous positive airway pressure in improving fetal movements suggests a pathogenetic role for sleep disordered breathing in the reduced fetal activity and possibly in the poorer fetal outcomes associated with preeclampsia. Citation: Blyton DM; Skilton MR; Edwards N; Hennessy A; Celermajer DS; Sullivan CE. Treatment of sleep disordered breathing reverses low fetal activity levels in preeclampsia. SLEEP 2013;36(1):15–21. PMID:23288967

Maternal serum uric acid level and maternal and neonatal complications in preeclamptic women: A cross-sectional study.

PubMed

Asgharnia, Maryam; Mirblouk, Fariba; Kazemi, Soudabeh; Pourmarzi, Davood; Mahdipour Keivani, Mina; Dalil Heirati, Seyedeh Fatemeh

2017-09-01

Preeclampsia is associated with maternal and neonatal complications. It has been indicated that increased uric acid might have a predictive role on preeclampsia. We aimed to investigate the relationship between the level of uric acid with maternal and neonatal complications in women with preeclampsia. In this cross-sectional study, 160 singleton preeclamptic women at more than 28 wk gestational age were included. Hemoglobin, hematocrit, platelet count, liver and uric acid tests, and maternal and neonatal complications were assessed. The severity of preeclampsia, placental abruption, preterm labor, thrombocytopenia, elevated alanine aminotransferase and aspartate aminotransferase (ALT and AST), HELLP syndrome, eclampsia and required hospitalization in the ICU was considered as the maternal complication. Fetal complications were: small for gestational age (SGA), intrauterine fetal death, hospitalization in the neonatal intensive care unit, and Apgar score <7 at five minutes. Of our participants, 38 women had severe preeclampsia (23.8%). The mean level of uric acid in women with severe preeclampsia was significantly higher than non-severe preeclampsia (p=0.031), also in those with an abnormal liver test (p=0.009). The mean level of uric acid in women with preterm delivery was significantly higher than women with term delivery (p=0.0001). Also, the level of uric acid had no effect on neonatal hospitalization in neonate invasive care unit. Based on logistic regression, the incidence of severe preeclampsia not affected by decreased or increased serum levels of uric acid. With higher level of uric acid in server preeclampsia we can expected more complications such as hepatic dysfunction and preterm delivery. Thus serum uric acid measurement can be helpful marker for severe preeclampsia.

Differences in preeclampsia rates between African American and Caucasian women: trends from the National Hospital Discharge Survey.

PubMed

Breathett, Khadijah; Muhlestein, David; Foraker, Randi; Gulati, Martha

2014-11-01

African Americans are at higher risk for preeclampsia compared with Caucasians, but longitudinal changes are unknown. We hypothesized that preeclampsia rates among African Americans would be higher than that of Caucasians and over time would maintain a consistent divergence. We analyzed the annual prevalence rates and calculated prevalence odds ratios (POR) with 95% confidence intervals (95% CI) for preeclampsia comparing 4,644 African American (weighted 608,109) with 12,131 Caucasian (weighted 1,844,391) women from the National Hospital Discharge Survey (1979-2006), including all women for whom a delivery was associated with preeclampsia. We estimated the race-specific prevalence of preeclampsia while adjusting for age, geographic region, diabetes, essential hypertension, prior myocardial infarction, heart failure, benign essential hypertension complicating a pregnancy, transient hypertension, and gestational diabetes. There was an increasing trend in preeclampsia rates per year from 1979 to 2006 for African Americans [POR 0.76 (95% CI 0.49, 1.03)] and Caucasians [0.29 (95% CI 0.17, 0.41)]. However, there was an initial decrease in prevalence from 1979-1988 among African-Americans [-0.96 (95% CI -1.78, -0.14)] that was not seen in Caucasians [0.12 (95% CI -0.33, 0.57)]. Across all study years, preeclampsia rates remained higher for African Americans compared to Caucasians, from a POR of 0.98 (95% CI 0.96, 1.0) to POR of 1.75 (95% CI 1.73, 1.78). There was an increase in the prevalence of preeclampsia in African Americans compared to Caucasians in the most recent decade under study. This may be explained by healthcare system changes and disparities in obesity. Action is needed to reduce the trajectory of future cardiovascular disease caused by preeclampsia.

Maternal Factors and Adverse Perinatal Outcomes in Women with Preeclampsia in Maceió, Alagoas

PubMed Central

de Oliveira, Alane Cabral Menezes; Santos, Arianne Albuquerque; Bezerra, Alexandra Rodrigues; de Barros, Amanda Maria Rocha; Tavares, Myrian Cicyanne Machado

2016-01-01

Background Preeclampsia has been associated with several risk factors and events. However, it still deserves further investigation, considering the multitude of related factors that affect different populations. Objective To evaluate the maternal factors and adverse perinatal outcomes in a cohort of pregnant women with preeclampsia receiving care in the public health network of the city of Maceió. Methods Prospective cohort study carried out in 2014 in the public health network of the city with a sample of pregnant women calculated based on a prevalence of preeclampsia of 17%, confidence level of 90%, power of 80%, and ratio of 1:1. We applied a questionnaire to collect socioeconomic, personal, and anthropometric data, and retrieved perinatal variables from medical records and certificates of live birth. The analysis was performed with Poisson regression and chi-square test considering p values < 0.05 as significant. Results We evaluated 90 pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia (PWoP). A previous history of preeclampsia (prevalence ratio [PR] = 1.57, 95% confidence interval [95% CI] 1.47 - 1.67, p = 0.000) and black skin color (PR = 1.15, 95% CI 1.00 - 1.33, p = 0.040) were associated with the occurrence of preeclampsia. Among the newborns of PWP and PWoP, respectively, 12.5% and 13.1% (p = 0.907) were small for gestational age and 25.0% and 23.2% (p = 0.994) were large for gestational age. There was a predominance of cesarean delivery. Conclusion Personal history of preeclampsia and black skin color were associated with the occurrence of preeclampsia. There was a high frequency of birth weight deviations and cesarean deliveries. PMID:26761076

Maternal Factors and Adverse Perinatal Outcomes in Women with Preeclampsia in Maceió, Alagoas.

PubMed

de Oliveira, Alane Cabral Menezes; Santos, Arianne Albuquerque; Bezerra, Alexandra Rodrigues; de Barros, Amanda Maria Rocha; Tavares, Myrian Cicyanne Machado

2016-02-01

Preeclampsia has been associated with several risk factors and events. However, it still deserves further investigation, considering the multitude of related factors that affect different populations. To evaluate the maternal factors and adverse perinatal outcomes in a cohort of pregnant women with preeclampsia receiving care in the public health network of the city of Maceió. Prospective cohort study carried out in 2014 in the public health network of the city with a sample of pregnant women calculated based on a prevalence of preeclampsia of 17%, confidence level of 90%, power of 80%, and ratio of 1:1. We applied a questionnaire to collect socioeconomic, personal, and anthropometric data, and retrieved perinatal variables from medical records and certificates of live birth. The analysis was performed with Poisson regression and chi-square test considering p values < 0.05 as significant. We evaluated 90 pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia (PWoP). A previous history of preeclampsia (prevalence ratio [PR] = 1.57, 95% confidence interval [95% CI] 1.47 - 1.67, p = 0.000) and black skin color (PR = 1.15, 95% CI 1.00 - 1.33, p = 0.040) were associated with the occurrence of preeclampsia. Among the newborns of PWP and PWoP, respectively, 12.5% and 13.1% (p = 0.907) were small for gestational age and 25.0% and 23.2% (p = 0.994) were large for gestational age. There was a predominance of cesarean delivery. Personal history of preeclampsia and black skin color were associated with the occurrence of preeclampsia. There was a high frequency of birth weight deviations and cesarean deliveries.

Inherited predisposition to preeclampsia: Analysis of the Aberdeen intergenerational cohort.

PubMed

Ayorinde, Abimbola A; Bhattacharya, Sohinee

2017-04-01

To assess the magnitude of familial risk of preeclampsia and gestational hypertension in women born of a preeclamptic pregnancy and those born of pregnancy complicated by gestational hypertension while accounting for other risk factors. An intergenerational dataset was extracted from the Aberdeen Maternity and Neonatal Databank (AMND) which records all pregnancy and delivery details occurring in Aberdeen, Scotland since 1950. The analysis included all nulliparous women whose mothers' records at their births are also recorded in the AMND. Multinomial logistic regression was used to assess the risk of having preeclampsia or gestational hypertension based on maternal history of preeclampsia or gestational hypertension. There were 17302 nulliparous women included, of whom 1057(6.1%) had preeclampsia while 4098(23.7%) had gestational hypertension. Furthermore, 424(2.5%) and 2940(17.0%) had maternal history of preeclampsia and gestational hypertension respectively. The risk of preeclampsia was higher in women who were born of pregnancies complicated by preeclampsia (adjusted RRR 2.55 95% CI 1.87-3.47). This was higher than the risk observed in women whose mothers had gestational hypertension (adjusted RRR 1.44 95% CI 1.23-1.69). Conversely, the risk of gestational hypertension was similar in those who were born of preeclamptic pregnancies (adjusted RRR 1.37 95% CI 1.09-1.71) and those whose mothers had gestational hypertension (adjusted RRR 1.36 95% CI 1.24-1.49). There was a dose response effect in the inheritance pattern of preeclampsia with the highest risk in women born of preeclamptic pregnancies. Gestational hypertension showed similar increased risk with maternal gestational hypertension and preeclampsia. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Novel SNPs of WNK1 and AKR1C3 are associated with preeclampsia.

PubMed

Sun, Cheng-Juan; Li, Lin; Li, Xueyan; Zhang, Wei-Yuan; Liu, Xiao-Wei

2018-08-20

Preeclampsia is a hypertensive disorder of pregnancy and is one of the most common causes of poor perinatal outcomes. Preeclampsia increases the risk of hypertension in the future. Variants of WNK1 (lysine deficient protein kinase 1), ADRB2 (β2 adrenergic receptor), NEDD4L (ubiquitin-protein ligase NEDD4-like), KLK1 (kallikrein 1) contribute to hypertension, and AKR1C3 (aldo-keto reductase family1 member C3), is associated with preeclampsia. The association of single nucleotide polymorphisms (SNPs) in these five candidate preeclampsia susceptibility genes and the related traits in Chinese individuals were investigated. In this study, 13 SNPs of the five genes were genotyped in 276 preeclampsia patients and 229 age- and area-matched normal pregnancies in women of Chinese Northern Han origin. The 95% confidence interval (CI) and odds ratio (OR) were estimated by binary logistic regression. No obvious linkage disequilibrium or haplotypes were observed among these SNPs. Those with GG genotype and allele G of AKR1C3 (rs10508293) had a decreased risk of preeclampsia (adjusted OR = 3.011, 95% CI = 1.758-5.159, and adjusted OR = 1.745, 95% CI = 1.349-2.257, respectively). The AA genotype and allele A of WNK1 (rs1468326) were significantly associated with an increased risk in preeclampsia (adjusted OR = 2.307, 95% CI = 1.206-3.443, and adjusted OR = 1.663, 95% CI = 1.283-2.157, respectively). The findings indicate that the GG genotype of AKR1C3 rs10508293 is associated with decreased risk for preeclampsia and the AA genotype of WNK1 rs1468326 are related with an increased risk for preeclampsia. Copyright © 2018 Elsevier B.V. All rights reserved.

Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia

PubMed Central

Southcombe, J H; Redman, C W G; Sargent, I L; Granne, I

2015-01-01

Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/β/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother. PMID:25693732

Peripartum Cardiomyopathy Treatment with Dopamine Agonist and Subsequent Pregnancy with a Satisfactory Outcome.

PubMed

Melo, Maria Adélia Medeiros E; Carvalho, Jordão Sousa; Feitosa, Francisco Edson de Lucena; Araujo Júnior, Edward; Peixoto, Alberto Borges; Costa Carvalho, Francisco Herlânio; Carvalho, Regina Coeli Marques

2016-06-01

Pathophysiological mechanisms of peripartum cardiomyopathy are not yet completely defined, although there is a strong association with various factors that are already known, including pre-eclampsia. Peripartum cardiomyopathy treatment follows the same recommendations as heart failure with systolic dysfunction. Clinical and experimental studies suggest that products of prolactin degradation can induce this cardiomyopathy. The pharmacological suppression of prolactin production by D2 dopamine receptor agonists bromocriptine and cabergoline has demonstrated satisfactory results in the therapeutic response to the treatment. Here we present a case of an adolescent patient in her first gestation with peripartum cardiomyopathy that evolved to the normalized left ventricular function after cabergoline administration, which was used as an adjuvant in cardiac dysfunction treatment. Subsequently, despite a short interval between pregnancies, the patient exhibited satisfactory progress throughout the entire gestation or puerperium in a new pregnancy without any cardiac alterations. Dopamine agonists that are orally used and are affordable in most tertiary centers, particularly in developing countries, should be considered when treating peripartum cardiomyopathy cases. Thieme Publicações Ltda Rio de Janeiro, Brazil.

Cell-free fetal DNA concentration in plasma of patients with abnormal uterine artery Doppler waveform and intrauterine growth restriction--a pilot study.

PubMed

Caramelli, Elisabetta; Rizzo, Nicola; Concu, Manuela; Simonazzi, Giuliana; Carinci, Paolo; Bondavalli, Corrado; Bovicelli, Luciano; Farina, Antonio

2003-05-01

To evaluate if an increased amount of fetal DNA concentration can be found in women screened positive for intrauterine growth restriction because of abnormal uterine artery Doppler waveforms. We enrolled eight pregnant women (each bearing a male fetus), with the evidence of abnormal uterine artery Doppler waveforms, and 16 control patients for a case-control study matched for gestational age (1 : 2). Uterine artery Doppler was carried out at 20 to 35 weeks' gestation (median 29). The mean uterine artery resistance index (RI) was subsequently calculated, and a value >0.6 was considered positive for the clinical features of pre-eclampsia. The SRY locus was used to determine the amount of male fetal DNA in the maternal plasma at the time of Doppler analysis. Two controls (normal Doppler) were excluded from the final analysis because they had a pre-term delivery. One case (abnormal Doppler) had evidence of intrauterine growth restriction at the time of enrolment. In four out of eight cases (abnormal Doppler), intrauterine growth restriction was subsequently observed. Multiples of median (MoM) conversion of the fetal DNA values showed an increase of 1.81 times in the cases when compared to the controls. An increase of 2.16 times was instead observed for the cases with a growth-restricted fetus (5 cases out of 8) in comparison with the controls (14 cases). In subjects positive to uterine artery Doppler velocimetry analysis (Doppler analysis for pre-eclampsia screening), the fetal DNA concentration is higher than expected, in the absence of any other clinical feature. Since the increase in fetal DNA seems to be related to the presence or to the future development of intrauterine growth restriction, this paper suggests a possible integration between ultrasound and molecular markers for predicting the disease in some cases. Copyright 2003 John Wiley & Sons, Ltd.

Meta-Analysis and Systematic Review to Assess the Role of Soluble FMS-Like Tyrosine Kinase-1 and Placenta Growth Factor Ratio in Prediction of Preeclampsia: The SaPPPhirE Study.

PubMed

Agrawal, Swati; Cerdeira, Ana Sofia; Redman, Christopher; Vatish, Manu

2018-02-01

Preeclampsia is a major cause of morbidity and mortality worldwide. Numerous candidate biomarkers have been proposed for diagnosis and prediction of preeclampsia. Measurement of maternal circulating angiogenesis biomarker as the ratio of sFlt-1 (soluble FMS-like tyrosine kinase-1; an antiangiogenic factor)/PlGF (placental growth factor; an angiogenic factor) reflects the antiangiogenic balance that characterizes incipient or overt preeclampsia. The ratio increases before the onset of the disease and thus may help in predicting preeclampsia. We conducted a meta-analysis to explore the predictive accuracy of sFlt-1/PlGF ratio in preeclampsia. We included 15 studies with 534 cases with preeclampsia and 19 587 controls. The ratio has a pooled sensitivity of 80% (95% confidence interval, 0.68-0.88), specificity of 92% (95% confidence interval, 0.87-0.96), positive likelihood ratio of 10.5 (95% confidence interval, 6.2-18.0), and a negative likelihood ratio of 0.22 (95% confidence interval, 0.13-0.35) in predicting preeclampsia in both high- and low-risk patients. Most of the studies have not made a distinction between early- and late-onset disease, and therefore, the analysis for it could not be done. It can prove to be a valuable screening tool for preeclampsia and may also help in decision-making, treatment stratification, and better resource allocation. © 2017 American Heart Association, Inc.

Characteristics and severity of preeclampsia in young and elderly gravidas with hypertensive disease.

PubMed

Rymer-Haskel, Noa; Schushan-Eisen, Irit; Hass, Yigal; Rahav, Roni; Maayan-Metzger, Ayala; Hendler, Israel

2018-06-01

Advanced maternal age (AMA) is associated with increased risk for preeclampsia, however, a paucity of data exists regarding the characteristics of the disease in this age group. Our aim was to compare the characteristics and severity of preeclampsia in older and younger gravidas. A retrospective, small case control study of women diagnosed with preeclampsia in a single tertiary care center. Nulliparous women ≥40 years old with singleton pregnancies ≥ 24 0/7 weeks' gestation were matched (1:2 ratio) with young (20-34 years old) nulliparous women. The rate of severe preeclampsia (60.9 vs 69.6% respectively), HELLP, eclampsia or the need for magnesium treatment did not differ between the groups. However, the AMA group had an increased rate of postpartum presentation or exacerbation of preeclampsia compared to the control group (50.0 vs. 28.3% respectively, p = 0.01). In the AMA group, 93.5% of births were by cesarean section (CS) compared to 52.2% in the control group (p < 0.0001). There was no difference in birthweight, rate of small for gestational age or composite neonatal morbidity between the groups. Preeclampsia at an advanced maternal age carries a similar rate of severe preeclampsia and complications as in young women. However, women over 40 years old have an increased risk for presentation or exacerbation of preeclampsia in the postpartum period and an increased rate of CS compared to younger gravidas. Copyright © 2018 Elsevier B.V. All rights reserved.

Protective Low-Frequency Variants for Preeclampsia in the Fms Related Tyrosine Kinase 1 Gene in the Finnish Population.

PubMed

Lokki, A Inkeri; Daly, Emma; Triebwasser, Michael; Kurki, Mitja I; Roberson, Elisha D O; Häppölä, Paavo; Auro, Kirsi; Perola, Markus; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Salmon, Jane E; Meri, Seppo; Daly, Mark; Atkinson, John P; Laivuori, Hannele

2017-08-01

Preeclampsia is a common pregnancy-specific vascular disorder characterized by new-onset hypertension and proteinuria during the second half of pregnancy. Predisposition to preeclampsia is in part heritable. It is associated with an increased risk of cardiovascular disease later in life. We have sequenced 124 candidate genes implicated in preeclampsia to pinpoint genetic variants contributing to predisposition to or protection from preeclampsia. First, targeted exomic sequencing was performed in 500 preeclamptic women and 190 controls from the FINNPEC cohort (Finnish Genetics of Preeclampsia Consortium). Then 122 women with a history of preeclampsia and 1905 parous women with no such history from the National FINRISK Study (a large Finnish population survey on risk factors of chronic, noncommunicable diseases) were included in the analyses. We tested 146 rare and low-frequency variants and found an excess (observed 13 versus expected 7.3) nominally associated with preeclampsia ( P <0.05). The most significantly associated sequence variants were protective variants rs35832528 (E982A; P =2.49E-4; odds ratio=0.387) and rs141440705 (R54S; P =0.003; odds ratio=0.442) in Fms related tyrosine kinase 1. These variants are enriched in the Finnish population with minor allele frequencies 0.026 and 0.017, respectively. They may also be associated with a lower risk of heart failure in 11 257 FINRISK women. This study provides the first evidence of maternal protective genetic variants in preeclampsia. © 2017 American Heart Association, Inc.

Counselling and management of cardiovascular risk factors after preeclampsia.

PubMed

van Kesteren, Floortje; Visser, Sanne; Hermes, Wietske; Teunissen, Pim W; Franx, Arie; van Pampus, Maria G; Mol, Ben W; de Groot, Christianne J M

2016-01-01

Women with a history of preeclampsia have an increased risk of cardiovascular disease. Gynaecologists have an important role in the counselling and management of cardiovascular risk factors after preeclampsia. We aimed to assess the role of gynaecologists in informing women on interventions and risk factor follow-up after early and late preeclampsia. In 2011 and 2014, all gynaecologists in the Netherlands were invited for a questionnaire. Results were analysed and compared over time. In 2011, the questionnaire was answered by 244 and in 2014 by 167 gynaecologists. After early preeclampsia, in 2011, 53% advised yearly blood pressure measurements; this increased to 65% in 2014. Over the years there was an increase in respondents advising an increased physical activity of 35% in 2011 to 56% in 2014. After late preeclampsia, in 2011, 36% advised yearly blood pressure measurements; this increased to 46% in 2014. There was an increase in gynaecologists advising increased activity (32% in 2011 to 56% in 2014). In both early and late preeclampsia, smoking cessation and weigh loss were advised often (70-80%); glucose and lipid screening were advised rarely (6-20%). Although there is still a considerable scope for improvement, an increasing number of gynaecologists advise women after preeclampsia on preventive interventions to decrease risks of cardiovascular disease.

Is maternal colonization with group B streptococci a risk factor for preeclampsia?

PubMed

Mulla, Zuber D; Carrillo, Thelma; Kalamegham, Ramaswami; Hernandez, Loretta L; Portugal, Elizabeth; Nuwayhid, Bahij S

2015-01-01

To explore the association between maternal rectovaginal colonization with group B Streptococcus (GBS) and the outcome of preeclampsia, and to identify other factors such as maternal chocolate consumption that may be associated with preeclampsia on the Texas-Mexico border. A case-control study was conducted among 330 women who delivered at a teaching hospital in El Paso, Texas, during the time period April 2010 to April 2012. Preeclamptic cases (n = 165) and controls free of preeclampsia (n = 165) were matched by gestational age and date of delivery. Conditional logistic regression (with multiple imputation for missing data) was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) that were adjusted for maternal age and other factors. Cases (94.6%) and controls (97.0%) were predominantly Hispanic. GBS colonization was not associated with preeclampsia: adjusted OR = 1.73 (95% CI 0.63-4.74, p = 0.29). Maternal consumption of chocolate desserts once daily or more frequently as compared to < 7 times weekly was associated with a 76% reduction in the odds of preeclampsia: adjusted OR = 0.24 (95% CI 0.09-0.63, p = 0.004). Our study did not confirm the protective association between GBS and preeclampsia that was found in 2 existing state hospital datasets. Chocolate consumption during pregnancy was inversely associated with preeclampsia.

Fractional excretion of urea in pre-eclampsia: a clinical observation.

PubMed

Zar, Tausif; Kohn, Orly F; Kaplan, Andre A

2011-11-01

Pre-eclampsia is one of the leading causes of maternal and fetal mortality and morbidity. It occurs in 7% of all the pregnancies and accounts for 80% of the cases of pregnancy-induced hypertension. Diagnosis of pre-eclampsia in patients with pre-existing chronic kidney disease, proteinuria, and hypertension is a dilemma. The fractional excretion of urea has been described as a marker for renal perfusion. Since pre-eclampsia is associated with a marked decline in renal perfusion, we explored the utility of the fractional excretion of urea as a marker for pre-eclampsia. Urine and serum chemistries were evaluated in 6 pregnant women with pre-eclampsia on their first visit, immediately prior to delivery, and postpartum. For each of these three measurements, the fractional excretion of urea was calculated and proteinuria was assessed by random urine protein-creatinine ratio or 24-hour urine protein studies. In patients diagnosed with pre-eclampsia, the fractional excretion of urea decreased substantially from higher values obtained during the 3rd trimester to values consistent with renal hypoperfusion (< 35%) just prior to delivery, and it rapidly normalized immediately after delivery. Alterations in fractional excretion of urea, which suggest a decreased renal perfusion, may be a useful tool in supporting the diagnosis of preeclampsia.

The effect of serum from women with preeclampsia on JAR (trophoblast-like) cell line.

PubMed

Mahameed, Safa; Goldman, Shlomit; Gabarin, Diane; Weiss, Amir; Shalev, Eliezer

2005-09-01

Pathologic placentation has been implicated in the pathogenesis of preeclamsia. We sought to assess the effect serum obtained from women with preeclampsia would have on JAR human choriocarcinoma cells regarding growth, invasiveness, and matrix metalloproteinase (MMP) secretion as compared to normotensive pregnant woman. Blood was collected from 11 healthy pregnant women and from10 patients with preeclampsia at 28-33 weeks of gestation. The JAR human choriocarcinoma cell line was cultured in the presence of 10% serum obtained from each group. Cell proliferation, invasiveness, and MMP secretion was measured using a cell proliferation kit, the Matrigel (BD Biosciences, Beit-Ha'Emek, Israel) invasion assay, and gel zymography, respectively. Cell growth increased by 6% when exposed to serum from patients with preeclampsia compared to 30% from controls (P <.01). Trophoblast invasion was significantly (P <.01) reduced in the preeclampsia group (21 +/- 1.9%) compared to controls (27 +/- 2.5%). Valid MMP-2 secretion was reduced by 51% in the preeclampsia group compared to controls (P <.05). Serum obtained from women with preeclampsia contains a factor or factors that exhibit an inhibitory effect on JAR trophoblast cell proliferation, invasiveness, and MMP-2 secretion. These factors may be involved in the pathologic placentation associated with the pathogenesis of preeclampsia.

Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for pre-eclampsia?

PubMed

Rousseau, Aurélie; Favier, Rémi; Van Dreden, Patrick

2009-09-01

One of the most frequently proposed mechanisms for pre-eclampsia refers to uteroplacental thrombosis. However, the contribution of classical thrombotic risk factors remains questionable. The aims of this study were to investigate the activities of thrombomodulin, tissue factor and procoagulant phospholipids to assess endothelial cell injury in pregnant women with pre-eclampsia and to compare them with other classical markers of vascular injury and thrombotic risk. Using three new functional assays we studied the plasma levels of these new markers in 35 healthy women, 30 healthy pregnant women, and 35 women with pre-eclampsia. We found that plasma levels of thrombomodulin activity, tissue factor activity and procoagulant phospholipids were significantly elevated in women with pre-eclampsia versus normal pregnant and non-pregnant women. It is thus suggested that elevated levels of these parameters in pre-eclampsia may reflect vascular endothelium damage, and may be a more valuable biomarker than antigen for the assessment of endothelial damage in pre-eclampsia. The high increased levels of procoagulant phospholipids and tissue factor activities in pre-eclampsia could suggest that the procoagulant potential may be implicated in this complication and makes these markers very promising for the understanding, follow-up and therapeutic handling of complicated pregnancy.

Risk factors for and perinatal mortality of abruptio placentae in patients hospitalised for early onset severe pre-eclampsia - a case controlled study.

PubMed

Odendaal, H J; Hall, D R; Grové, D

2000-07-01

We set out to determine which patients admitted for expectant management of early onset severe pre-eclampsia develop abruptio placentae and to compare the perinatal mortality rate of patients who developed abruptio placentae with those who did not have this complication. This was a case controlled study, using gestational age at delivery to select a control group for 69 patients who developed abruptio placentae. The only significant difference on admission was the higher uric acid levels in patients who developed abruptio placentae. Mean admission to delivery intervals were 11.9 and 8.8 days for the control and abruption groups respectively (P = 0.0083). Fifty-eight per cent of the babies in the abruptio placentae group developed late decelerations, as determined by fetal heart rate monitoring compared with 32% in the control group. Lactate dehydrogenase levels before delivery were significantly higher in the abruption group, but it only became elevated shortly before delivery and in the minority of cases. There were two intrauterine and four neonatal deaths in the abruption group and two neonatal deaths in the control group. Late decelerations detected by frequent fetal heart rate monitoring in patients with early onset severe pre-eclampsia is the only early warning of abruptio placentae.

Preeclampsia: A review of the pathogenesis and possible management strategies based on its pathophysiological derangements.

PubMed

El-Sayed, Amel A F

2017-10-01

This review is divided into three parts. The first part briefly describes the pathogenesis of preeclampsia. This is followed by reviewing previously reported management strategies of the disease based on its pathophysiological derangements. Finally, the author defines the safe and acceptable methods/medications that may be used to 'prevent' preeclampsia (in high risk patients) and those that may be used to 'treat' preeclampsia (meant to prolong the pregnancy in patients with established preeclampsia). The review concludes that multi-center trials are required to include multiple drugs in the same management protocol. Copyright © 2017. Published by Elsevier B.V.

Does aggressive and expectant management of severe preeclampsia affect the neurologic development of the infant?

PubMed Central

Ertekin, Arif Aktuğ; Kapudere, Bilge; Eken, Meryem Kurek; İlhan, Gülşah; Dırman, Şükriye; Sargın, Mehmet Akif; Deniz, Engin; Karatekin, Güner; Çöğendez, Ebru; Api, Murat

2015-01-01

Objective: To compare and evaluate the influences of expectant and aggressive management of severe preeclampsia on the first year neurologic development of the infants in pregnancies between 27 and 34 weeks of pregnancy. Methods: Seventy women with severe preeclampsia between 27 and 34 weeks of gestation were included in the study. 37 patients were managed aggressively (Group 1) and 33 patients were managed expectantly (Group 2). Glucocorticoids, magnesium sulfate infusion and antihypertensive drugs were administered to each group. After glucocorticoid administration was completed Group 1 was delivered either by cesarean section or vaginal delivery. In Group 2 magnesium sulfate infusion was stopped after glucocorticoid administration was completed. Antihypertensive drugs were given, bed rest and intensive fetal monitorization were continued in this group. Results: The average weeks of gestation, one minute and five minute apgar scores and hospitalization time in intensive care unit were similar in both groups (P > 0.05). Three neonatal complications in Group 2 and five in Group 1 were detected according to the Denver Developmental Screening Test-II and one pathologic case was detected in both groups following neurologic examination. Neonatal mortality was seen in seven patients in Group 1 and one in Group 2. There were no significant differences between groups in terms of neonatal mortality and morbidity and maternal morbidity (P > 0.05). The average latency period was 3.45 ± 5.48 days in Group 2 and none in Group 1. Conclusion: There was no significant difference in the first year neurological development of infants whose mothers underwent either expectant and aggressive management for severe preeclampsia. PMID:26770571

Maternal rubella immunity status and pre-eclampsia.

PubMed

Lao, Terence T; Sahota, Daljit S; Law, Lai-Wa; Leung, Tak-Yeung

2017-07-01

To determine if maternal immune maladaptation associated with pre-eclampsia is reflected in the rubella immunity status. Incidence of pre-eclampsia was compared between rubella non-immune and immune gravidae carrying a singleton pregnancy beyond 24 weeks, taking into account maternal characteristics and reported risk factors for pre-eclampsia. The 9870 (10.4%) rubella non-immune gravidae among the 95 024 in the cohort exhibited no difference in incidence of underlying medical disorders, but they were slightly but significantly older, shorter, heavier, and had more pre-eclampsia (OR 1.24, 95% CI 1.05-1.47) despite having fewer nulliparas. Regression analysis confirmed an overall association between rubella non-immunity with pre-eclampsia (aOR 1.27, 95% CI 1.06-1.54), which was related to multiparas (aOR 1.42, 95% CI 1.05-1.91) and carrying a male fetus (aOR 1.37, 95% CI 1.06-1.78). The association between rubella non-immunity and pre-eclampsia reflects immune maladaptation in multiparas and toward a male fetus. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of subfoveal choroidal thickness in healthy pregnancy and pre-eclampsia

PubMed Central

Kim, J W; Park, M H; Kim, Y J; Kim, Y T

2016-01-01

Purpose Pregnancy is a known predisposing factor for central serous chorioretinopathy (CSC). Choroidal thickness (CT) increases in patients with CSC. This study was designed to evaluate CT in pregnant women. Patients and methods This was a prospective study. Fourteen healthy pregnant women and seven patients with pre-eclampsia were included. Twenty-one normal subjects were also recruited. CT was measured using enhanced-depth imaging optical coherence tomography. Results The mean CT of normal subjects, healthy pregnant women and patients with pre-eclampsia were 264.95±21.03, 274.23±29.30 and 389.79±25.13 μm, respectively (normal subjects vs healthy gravidas: P>0.05; normal subjects vs pre-eclampsia: P<0.001; healthy gravidas vs pre-eclampsia: P<0.001). CT decreased from 381.05±22.96 μm to 335.17±9.97 μm 1 week after delivery in patients with pre-eclampsia. Conclusions Pregnancy itself did not increase CT, whereas pre-eclampsia did appear to result in increased CT. This suggests that additional unknown factors induce hyperpermeability in pregnant women. PMID:26541086

Quantification of Maternal Serum Cell-Free Fetal DNA in Early-Onset Preeclampsia

PubMed Central

Yu, Hong; Shen, Yanting; Ge, Qinyu; He, Youji; Qiao, Dongyan; Ren, Mulan; Zhang, Jianqiong

2013-01-01

The aim of this study was to determine whether the increased serum cell-free fetal DNA (cffDNA) level of gravidas developed into early-onset preeclampsia (EOPE) subsequently in the early second trimesters is related to prenatal screening markers. Serum was collected from 1011 gravidas. The level of cffDNA and prenatal screening markers were analyzed in 20 cases with EOPE and 20 controls. All fetuses were male. The maternal serum cffDNA level was assessed by amplification of the Y chromosome specific gene. Correlations between the variables were examined. (Logged) cffDNA in EOPE (median, 3.08; interquartile range, 2.93–3.68) was higher than controls (median, 1.79; interquartile range, 1.46–2.53). The increased level of (logged) cffDNA was correlated significantly with the increased human chorionic gonadotropin (HCG) level (r = 0.628, p < 0.001). Significant reciprocal correlations between cffDNA and babies’ birth weight as well as gestation weeks at delivery were noted (r = −0.516, p = 0.001; r = −0.623, p < 0.001, respectively). The sensitivity and specificity of cffDNA to discriminate between the EOPE cases and the controls were 90% and 85%, respectively. CffDNA is a potential marker for EOPE, which had a significant reciprocal correlation with babies’ birth weight and gestation weeks at delivery. Moreover, it may help in indicating the underlying hypoxic condition in the placenta. PMID:23567271

What Are the Risks of Preeclampsia and Eclampsia to the Mother?

MedlinePlus

... mother? Share Facebook Twitter Pinterest Email Print What are the risks of preeclampsia & eclampsia to the mother? ... for the mother and infant. Women with preeclampsia are at increased risk for damage to the kidneys, ...

What Are the Symptoms of Preeclampsia, Eclampsia, and HELLP Syndrome?

MedlinePlus

... syndrome? Share Facebook Twitter Pinterest Email Print What are the symptoms of preeclampsia, eclampsia, & HELLP syndrome? Preeclampsia ... woman's feet might swell too, but swollen feet are common during pregnancy and may not signal a ...

Maternal and fetal plasma zinc in pre-eclampsia.

PubMed

Bassiouni, B A; Foda, A I; Rafei, A A

1979-04-01

Zinc is important for fetal growth and is involved in several important enzyme systems. Maternal and umbilical plasma zinc concentrations were determined in 52 parturient women with mild and severe pre-eclampsia, and were compared with those obtained from 20 women in labor whose pregnancies had progressed normally. A decrease in maternal as well as umbilical plasma zinc concentrations was observed in pre-eclamptic women, and this decrease was statistically significant in severe pre-eclampsia. The causes of these changes in plasma zinc concentrations in pre-eclampsia were discussed, and the possible adverse effects of zinc deficiency on the mother and fetus were mentioned. Low plasma zinc concentrations in pre-eclampsia may be a sign of zinc deficiency, implying possible risks to the mother and her fetus. It is recommended that maintenance of adequate dietary zinc nutrition during pregnancy, and particularly in pre-eclampsia, is important.

The nitric oxide pathway and possible therapeutic options in pre-eclampsia.

PubMed

Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

2014-08-01

Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide-soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3',5'-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. © 2013 The British Pharmacological Society.

The nitric oxide pathway and possible therapeutic options in pre-eclampsia

PubMed Central

Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

2014-01-01

Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide–soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3′,5′-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. PMID:24313856

Relationship between maternal immunological response during pregnancy and onset of preeclampsia.

PubMed

Martínez-Varea, Alicia; Pellicer, Begoña; Perales-Marín, Alfredo; Pellicer, Antonio

2014-01-01

Maternofetal immune tolerance is essential to maintain pregnancy. The maternal immunological tolerance to the semiallogeneic fetus becomes greater in egg donation pregnancies with unrelated donors as the complete fetal genome is allogeneic to the mother. Instead of being rejected, the allogeneic fetus is tolerated by the pregnant woman in egg donation pregnancies. It has been reported that maternal morbidity during egg donation pregnancies is higher as compared with spontaneous or in vitro fertilization pregnancies. Particularly, egg donation pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. Preeclampsia, a pregnancy-specific disease characterized by the development of both hypertension and proteinuria, remains the leading cause of maternal and perinatal mortality and morbidity. The aim of this review is to characterize and relate the maternofetal immunological tolerance phenomenon during pregnancies with a semiallogenic fetus, which are the spontaneously conceived pregnancies and in vitro fertilization pregnancies, and those with an allogeneic fetus or egg donation pregnancies. Maternofetal immune tolerance in uncomplicated pregnancies and pathological pregnancies, such as those with preeclampsia, has also been assessed. Moreover, whether an inadequate maternal immunological response to the allogenic fetus could lead to a higher prevalence of preeclampsia in egg donation pregnancies has been addressed.

Obesity in young age is a risk factor for preeclampsia: a facility based case-control study, northwest Ethiopia.

PubMed

Endeshaw, Mulualem; Abebe, Fantu; Worku, Solomon; Menber, Lalem; Assress, Muluken; Assefa, Muluken

2016-08-19

Preeclampsia is one of the most commonly encountered hypertensive disorders of pregnancy. For many years, obesity has been suggested to play a role in preeclampsia. However, the hypotheses have been diverse and often revealed inconsistent results. This study has aimed to estimate the effect of obesity and dietary habits on preeclampsia in Bahir Dar City, north-western Ethiopia. A facility-based unmatched case-control study was conducted on 453 (151 cases and 302 controls) pregnant women, attending antenatal care or skilled delivery at Bahir Dar City. Data were collected through face to face interviews and measurements of mid-upper-arm circumference (MUAC) at the time of the interviews. Data were cleaned and entered into IBM SPSS version 20 and later analyzed using STATA version 12. Univariate and multivariate logistic regression analyses were employed to estimate the effect of independent variables on preeclampsia. Stratified analysis was conducted to check for presence of confounding and/or effect modification between covariates. The odds of preeclampsia were higher among obese (MUAC ≥25 cm) women than their leaner counterparts (AOR = 3.33, 95 % CI: 1.87, 5.79). Obesity was also found to have a similar magnitude of risk for late onset preeclampsia (AOR = 3.63, 95 % CI: 1.89, 6.97). When stratified by age, the effect of obesity on overall and late onset preeclampsia was significant among young (age < 35 years) women (COR = 1.81, 95 % CI: 1.11, 2.99) and (COR = 2.09, 95 % CI: 1.16, 3.86), respectively. As the age groups became more homogenous through adjusted stratification, obesity showed a particularly significant effect in women age ≤24 and 25-29 years; (AOR = 2.31, 95 % CI: 1.06, 5.12) and (AOR = 3.66, 95 % CI: 1.37, 10.87) respectively. Similarly, the effect of obesity on late onset preeclampsia was evident among younger women age ≤24 and 25-29 years; (AOR = 3.16, 95 % CI: 1.21, 8.24) and (AOR = 1.98, 95 % CI: 1.16, 3.40) respectively. However, obesity has no significant effect on early onset of preeclampsia (AOR = 1.98, 95 % CI: 0.79, 4.94). On the other hand, compliance to folate supplementation during pregnancy and fruit consumption were associated with reduced risk of preeclampsia. Obesity in young age was found to be a risk factor for preeclampsia while compliance to folate supplement and adequate fruit consumption were found to be protective against preeclampsia. Promoting healthy life style, including body weight control, consumption of fruits and vegetables, and folate supplementation should be promoted to reduce the risk of preeclampsia.

Aspirin for Evidence-Based Preeclampsia Prevention trial: influence of compliance on beneficial effect of aspirin in prevention of preterm preeclampsia.

PubMed

Wright, David; Poon, Liona C; Rolnik, Daniel L; Syngelaki, Argyro; Delgado, Juan Luis; Vojtassakova, Denisa; de Alvarado, Mercedes; Kapeti, Evgenia; Rehal, Anoop; Pazos, Andrea; Carbone, Ilma Floriana; Dutemeyer, Vivien; Plasencia, Walter; Papantoniou, Nikos; Nicolaides, Kypros H

2017-12-01

The Aspirin for Evidence-Based Preeclampsia Prevention trial was a multicenter study in women with singleton pregnancies. Screening was carried out at 11-13 weeks' gestation with an algorithm that combines maternal factors and biomarkers (mean arterial pressure, uterine artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor). Those with an estimated risk for preterm preeclampsia of >1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg/d) vs placebo from 11-14 until 36 weeks' gestation. Preterm preeclampsia with delivery at <37 weeks' gestation, which was the primary outcome, occurred in 1.6% (13/798) participants in the aspirin group, as compared with 4.3% (35/822) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74). We sought to examine the influence of compliance on the beneficial effect of aspirin in prevention of preterm preeclampsia in the Aspirin for Evidence-Based Preeclampsia Prevention trial. This was a secondary analysis of data from the trial. The proportion of prescribed tablets taken was used as an overall measure of compliance. Logistic regression analysis was used to estimate the effect of aspirin on the incidence of preterm preeclampsia according to compliance of <90% and ≥90%, after adjustment for the estimated risk of preterm preeclampsia at screening and the participating center. The choice of cut-off of 90% was based on an exploratory analysis of the treatment effect. Logistic regression analysis was used to investigate predictors of compliance ≥90% among maternal characteristics and medical history. Preterm preeclampsia occurred in 5/555 (0.9%) participants in the aspirin group with compliance ≥90%, in 8/243 (3.3%) of participants in the aspirin group with compliance <90%, in 22/588 (3.7%) of participants in the placebo group with compliance ≥90%, and in 13/234 (5.6%) of participants in the placebo group with compliance <90%. The odds ratio in the aspirin group for preterm preeclampsia was 0.24 (95% confidence interval, 0.09-0.65) for compliance ≥90% and 0.59 (95% confidence interval, 0.23-1.53) for compliance <90%. Compliance was positively associated with family history of preeclampsia and negatively associated with smoking, maternal age <25 years, Afro-Caribbean and South Asian racial origin, and history of preeclampsia in a previous pregnancy. The beneficial effect of aspirin in the prevention of preterm preeclampsia appears to depend on compliance. Copyright © 2017 Elsevier Inc. All rights reserved.

Rubella, herpes simplex virus type 2 and preeclampsia.

PubMed

Alshareef, Shimos A; Eltom, Ahmed M; Nasr, Abubakr M; Hamdan, Hamdan Z; Adam, Ishag

2017-07-26

Preeclampsia is a major health problem. Although, the pathophysiology of preeclampsia is not fully understood, there are recent studies on association between infections and preeclampsia. The aim of the present study was to investigate the association between maternal seropositivity of rubella, Herpes simplex virus type 2 (HSV-2) and preeclampsia. A case -controls study (90 women in each arm) was conducted at Saad Abualila Maternity Hospital, Khartoum, Sudan. The cases were women with preeclampsia and the controls were healthy pregnant women. Rubella and HSV-2 IgG antibodies were analysed in the maternal sera of all of the participants using ELISA. There was no significant difference in the age, parity and gestational age between the two groups. Maternal serum IgG seropositivity for rubella (92.2% vs. 34.4%, P < 0.001) and HSV-2 (87.8% vs. 57.8%, P < 0.001) were significantly higher in preeclampsia than in the controls. There was no significant difference in the maternal serum IgM seropositivity for rubella (3.3% vs. 2.2%, P = 0.650) and HSV-2 (2.2% vs. 1.1%, P = 0.560). All the IgM seropositive cases were IgG seropositive too. In binary logistic regression women with rubella (OR = 4.93; 95% CI = 2.082-11.692, P < 0.001) and HSV-2 (OR = 5.54; 95% CI = 2.48-12.38, P < 0.001) IgG seropositivity were at higher risk for preeclampsia. In the current study rubella and HSV-2 IgG seropositivity is associated with preeclampsia. Preventive measure should be implemented.

The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP).

PubMed

Tranquilli, Andrea L; Brown, Mark A; Zeeman, Gerda G; Dekker, Gustaaf; Sibai, Baha M

2013-01-01

There is discrepancy in the literature on the definitions of severe and early-onset pre-eclampsia. We aimed to determine those definitions for clinical purposes and to introduce them in the classification of the hypertensive disorders of pregnancy for publication purposes. We circulated a questionnaire to the International Committee of the International Society for the Study of Hypertension in Pregnancy focusing on the thresholds for defining severe preeclampsia and the gestation at which to define early-onset preeclampsia, and on the definition and inclusion of the HELLP syndrome or other clinical features in severe preeclampsia. The questions were closed, but all answers had space for more open detailed comments. There was a general agreement to define preeclampsia as severe if blood pressure was >160mmHg systolic or 110mmHg diastolic. There was scarce agreement on the amount of proteinuria to define severity. The HELLP syndrome was considered a feature to include in the severe classification. Most investigators considered early-onset preeclampsia as that occurring before 34weeks. A definition of pre-eclampsia is paramount for driving good clinical practice. Classifications on the other hand are useful to enable international comparisons of clinical data and outcomes. We used the results of this survey to update our previous classification for the purposes of providing clinical research definitions of severe and early onset pre-eclampsia that will hopefully be accepted in the international literature. Copyright © 2012 International Society for the Study of Hypertension in Pregnancy. All rights reserved.

Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

PubMed Central

Weiler, Jane; Tong, Stephen; Palmer, Kirsten R.

2011-01-01

Background Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. Methods and Findings We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005–2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). Conclusions The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population. PMID:22046419

Diagnostic Performance of Placental Growth Factor in Women With Suspected Preeclampsia Attending Antenatal Facilities in Maputo, Mozambique.

PubMed

Ukah, U Vivian; Mbofana, Francisco; Rocha, Beatriz Manriquez; Loquiha, Osvaldo; Mudenyanga, Chishamiso; Usta, Momade; Urso, Marilena; Drebit, Sharla; Magee, Laura A; von Dadelszen, Peter

2017-03-01

In well-resourced settings, reduced circulating maternal-free placental growth factor (PlGF) aids in either predicting or confirming the diagnosis of preeclampsia, fetal growth restriction, stillbirth, preterm birth, and delivery within 14 days of testing when preeclampsia is suspected. This blinded, prospective cohort study of maternal plasma PlGF in women with suspected preeclampsia was conducted in antenatal clinics in Maputo, Mozambique. The primary outcome was the clinic-to-delivery interval. Other outcomes included: confirmed diagnosis of preeclampsia, transfer to higher care, mode of delivery, intrauterine fetal death, preterm birth, and low birth weight. Of 696 women, 95 (13.6%) and 601 (86.4%) women had either low (<100 pg/mL) or normal (≥100 pg/mL) plasma PlGF, respectively. The clinic-to-delivery interval was shorter in low PlGF, compared with normal PlGF, women (median 24 days [interquartile range, 10-49] versus 44 [24-81], P =0.0042). Also, low PlGF was associated with a confirmed diagnosis of preeclampsia, higher blood pressure, transfer for higher care, earlier gestational age delivery, delivery within 7 and 14 days, preterm birth, cesarean delivery, lower birth weight, and perinatal loss. In urban Mozambican women with symptoms or signs suggestive of preeclampsia, low maternal plasma PlGF concentrations are associated with increased risks of adverse pregnancy outcomes, whether the diagnosis of preeclampsia is confirmed. Therefore, PlGF should improve the provision of precision medicine to individual women and improve pregnancy outcomes for those with preeclampsia or related placenta-mediated complications. © 2017 American Heart Association, Inc.

Risk Factors for Pregnancy-Associated Stroke in Women With Preeclampsia.

PubMed

Miller, Eliza C; Gatollari, Hajere J; Too, Gloria; Boehme, Amelia K; Leffert, Lisa; Marshall, Randolph S; Elkind, Mitchell S V; Willey, Joshua Z

2017-07-01

Preeclampsia affects 3% to 8% of pregnancies and increases risk of pregnancy-associated stroke (PAS). Data are limited on which women with preeclampsia are at highest risk for PAS. Using billing data from the 2003 to 2012 New York State Department of Health inpatient database, we matched women with preeclampsia and PAS 1:3 to preeclamptic controls based on age and race/ethnicity. Pre-defined PAS risk factors included pregnancy complications, infection present on admission, vascular risk factors, prothrombotic states, and coagulopathies. We constructed multivariable conditional logistic regression models to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for independent risk factors for PAS. Among women aged 12 to 55 years admitted to New York State hospitals for any reason during the study period (n=3 373 114), 88 857 had preeclampsia, and 197 of whom (0.2%) had PAS. In multivariable analysis, women with preeclampsia and stroke were more likely than controls to have severe preeclampsia or eclampsia (OR, 7.2; 95% confidence interval [CI], 4.6-11.3), infections present on admission (OR, 3.0; 95% CI, 1.6-5.8), prothrombotic states (OR, 3.5; 95% CI, 1.3-9.2), coagulopathies (OR, 3.1; 95% CI, 1.3-7.1), or chronic hypertension (OR, 3.2; 95% CI, 1.8-5.5). Additional analyses matched and stratified by severity of preeclampsia confirmed these results. Infections, chronic hypertension, coagulopathies, and underlying prothrombotic conditions increase PAS risk in women with preeclampsia. These women may warrant closer monitoring. © 2017 American Heart Association, Inc.

Preeclampsia-Associated Hormonal Profiles and Reduced Breast Cancer Risk Among Older Mothers

DTIC Science & Technology

2003-04-01

Preeclampsia has been linked to reduced breast cancer risk, and this reduction may be especially marked among women who bear their first child later...in life. In this ongoing case-control study, we examine the hormonal profiles of older Colorado mothers with and without a history of preeclampsia in...premenopausal, and are free of serious chronic disease. Cases are 14 Denver area women who experienced preeclampsia in their first pregnancy; controls are 13

Diagnosis of preeclampsia with soluble Fms-like tyrosine kinase 1/placental growth factor ratio: an inter-assay comparison.

PubMed

Andersen, Louise Bjørkholt; Frederiksen-Møller, Britta; Work Havelund, Kathrine; Dechend, Ralf; Jørgensen, Jan Stener; Jensen, Boye L; Nielsen, Jan; Lykkedegn, Sine; Barington, Torben; Christesen, Henrik Thybo

2015-02-01

The angiogenic factor ratio soluble Fms-kinase 1 (sFlt-1)/placental growth factor (PlGF) is a novel diagnostic tool for preeclampsia. We compared the efficacy of the KRYPTOR (BRAHMS) automated assays for sFlt-1 and PlGF with the Elecsys (Roche) assays in a routine clinical setting. Preeclamptic women (n = 39) were included shortly after the time of diagnosis. Normotensive control pregnancies were matched by gestational age (n = 76). The KRYPTOR assays performed comparably or superior to Elecsys (sFlt-1/PlGF area under the curve 0.746 versus 0.735; P = .09; for non-obese 0.820 versus 0.805, P = .047). For early-onset preeclampsia, KRYPTOR area under the curve increased to 0.929 with a 100% specificity for preeclampsia at cut-off 85 and an 88.9% sensitivity for preeclampsia at cut-off 33. For women with preeclampsia and preterm delivery or Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome, the KRYPTOR sFlt-1/PlGF ratio was manifold increased (P < .01). The sFlt-1/PlGF ratio proved especially useful in early-onset preeclampsia, preeclampsia with preterm delivery or HELLP, and among non-obese women. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Neurokinin 3 receptor and phosphocholine transferase: missing factors for pathogenesis of C-reactive protein in preeclampsia.

PubMed

Parchim, Nicholas F; Wang, Wei; Iriyama, Takayuki; Ashimi, Olaide A; Siddiqui, Athar H; Blackwell, Sean; Sibai, Baha; Kellems, Rodney E; Xia, Yang

2015-02-01

C-reactive protein (CRP), an innate immune mediator, is elevated in the circulation before symptoms in patients with preeclampsia, a severe hypertensive pregnancy disorder with high mortality and morbidity. However, the specific sources underlying increased CRP and the role of elevated CRP in preeclampsia are undefined. Here, we report that circulating CRP levels are significantly increased in a large cohort of normotensive pregnant individuals when compared with nulligravid women and is further increased in patients with preeclampsia. These findings led us to discover further that placental syncytiotrophoblasts are previously unrecognized cellular sources of CRP and underlie elevated CRP in normotensive pregnant women and the additional increase in patients with preeclampsia. Next, we demonstrated that injection of CRP induces preeclampsia features, including hypertension (157 mm Hg CRP treated versus 119 mm Hg control), proteinuria (35.0 mg/μg CRP treated versus 14.1 mg/μg control), kidney, and placental damage and increased levels of sFlt-1 in pregnant mice but not in nonpregnant mice. Our study implicates that phosphocholine transferase, a placental-specific enzyme post-translationally modifying neurokinin B, is essential for the pathogenic role of CRP in preeclampsia through activation of the neurokinin 3 receptor. Overall, our studies have provided significant new insight on the pathogenic role of CRP in preeclampsia and highlighted innovative therapeutic strategies. © 2014 American Heart Association, Inc.

Effects of prenatal exposure to air pollution on preeclampsia in Shenzhen, China.

PubMed

Wang, Qiong; Zhang, Huanhuan; Liang, Qianhong; Knibbs, Luke D; Ren, Meng; Li, Changchang; Bao, Junzhe; Wang, Suhan; He, Yiling; Zhu, Lei; Wang, Xuemei; Zhao, Qingguo; Huang, Cunrui

2018-06-01

The impact of ambient air pollution on pregnant women is a concern in China. However, little is known about the association between air pollution and preeclampsia and the potential modifying effects of meteorological conditions have not been assessed. This study aimed to assess the effects of prenatal exposure to air pollution on preeclampsia, and to explore whether temperature and humidity modify the effects. We performed a retrospective cohort study based on 1.21 million singleton births from the birth registration system in Shenzhen, China, between 2005 and 2012. Daily average measurements of particulate matter <10 μm (PM 10 ), sulfur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), air temperature (T), and dew point (T d ) were collected. Logistic regression models were performed to estimate associations between air pollution and preeclampsia during the first and second trimesters, and during the entire pregnancy. In each time window, we observed a positive gradient of increasing preeclampsia risk with increasing quartiles of PM 10 and SO 2 exposure. When stratified by T and T d in three categories (<5th, 5th -95th, and >95th percentile), we found a significant interaction between PM 10 and T d on preeclampsia; the adverse effects of PM 10 increased with T d . During the entire pregnancy, there was a null association between PM 10 and preeclampsia under T d  < 5th percentile. Preeclampsia risk increased by 23% (95% CI: 19-26%) when 5th < T d  < 95th percentile, and by 34% (16-55%) when T d  > 95th percentile. We also found that air pollution effects on preeclampsia in autumn/winter seasons were stronger than those in the spring/summer. This is the first study to address modifying effects of meteorological factors on the association between air pollution and preeclampsia. Findings indicate that prenatal exposure to PM 10 and SO 2 increase preeclampsia risk in Shenzhen, China, and the effects could be modified by humidity. Pregnant women should limit air pollution exposure, particularly during humid periods. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acute Maternal Infection and Risk of Pre-Eclampsia: A Population-Based Case-Control Study

PubMed Central

Minassian, Caroline; Thomas, Sara L.; Williams, David J.; Campbell, Oona; Smeeth, Liam

2013-01-01

Background Infection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection) are associated with an increased risk of pre-eclampsia. Methods and Findings We used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls). Cases (n = 1533) were individually matched with up to ten controls (n = 14236) on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14–1.44) and in women with urinary tract infection (adjusted odds ratio 1.22;1.03–1.45). We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72–1.16). Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings. Conclusions Women who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying mechanism of this association and to determine whether, among women who acquire infections in pregnancy, prompt treatment or prophylaxis against infection might reduce the risk of pre-eclampsia. PMID:24019891

[Hellp syndrome. Presentation of a case and review of the literature].

PubMed

Vargas Hernández, V M; Romo Vázquez, L M; Oros Ramírez, J A

1991-07-01

A severe case of preeclampsia with Hellp Syndrome is reported. Clinical findings, laboratory abnormalities and pathogenesis, were discussed. We concluded that severe preeclampsia and Hellp Syndrome are not different diseases, but the natural course of preeclampsia per se.

Vitamin D status in early pregnancy and risk of preeclampsia

PubMed Central

Achkar, Madonna; Dodds, Linda; Giguère, Yves; Forest, Jean-Claude; Armson, B. Anthony; Woolcott, Christy; Agellon, Sherry; Spencer, Anne; Weiler, Hope A.

2016-01-01

OBJECTIVE We sought to examine the association between maternal serum 25-hydroxyvitamin D (25[OH]D) concentration in early pregnancy and the subsequent diagnosis of preeclampsia (PE). STUDY DESIGN This was a nested case-control study from 2 prospective Canadian cohorts conducted in Quebec City, Quebec, and Halifax, Nova Scotia, from 2002 through 2010. Participants were pregnant women (n=169 cases with PE and 1975 controls). Maternal serum was drawn <20 weeks of gestation, and 25(OH)D measurement was performed. Cases were ascertained from medical records. Logistic regression analysis was used to estimate adjusted odds ratios with 95% confidence intervals. RESULTS Women who developed PE had a significantly lower 25(OH)D concentration at a mean gestational age of 14 weeks compared with women in the control group (mean ± SD 25[OH]D 47.2 ± 17.7 vs 52.3 ± 17.2 nmol/L, P < .0001). Women with 25(OH)D <30 nmol/L compared to those with at least 50 nmol/L had a greater risk of developing PE (adjusted odds ratio, 2.23; 95% confidence interval, 1.29–3.83) after adjustment for prepregnancy body mass index, maternal age, smoking, parity, season and year of blood collection, gestational week at blood collection, and cohort site. Exploratory analysis with cubic splines demonstrated a dose-response relationship between maternal 25(OH)D and risk of PE, up to levels around 50 nmol/L, where the association appeared to plateau. CONCLUSION Maternal vitamin D deficiency early in pregnancy defined as 25(OH)D<30 nmol/L may be an independent risk factor for PE. The relevance of vitamin D supplementation for women of child-bearing age should be explored as a strategy for reducing PE and for promoting a healthier pregnancy. PMID:25446694

Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications

PubMed Central

Fan, Xiujun; Rai, Anshita; Kambham, Neeraja; Sung, Joyce F.; Singh, Nirbhai; Petitt, Matthew; Dhal, Sabita; Agrawal, Rani; Sutton, Richard E.; Druzin, Maurice L.; Gambhir, Sanjiv S.; Ambati, Balamurali K.; Cross, James C.; Nayak, Nihar R.

2014-01-01

There is strong evidence that overproduction of soluble fms-like tyrosine kinase-1 (sFLT1) in the placenta is a major cause of vascular dysfunction in preeclampsia through sFLT1-dependent antagonism of VEGF. However, the cause of placental sFLT1 upregulation is not known. Here we demonstrated that in women with preeclampsia, sFLT1 is upregulated in placental trophoblasts, while VEGF is upregulated in adjacent maternal decidual cells. In response to VEGF, expression of sFlt1 mRNA, but not full-length Flt1 mRNA, increased in cultured murine trophoblast stem cells. We developed a method for transgene expression specifically in mouse endometrium and found that endometrial-specific VEGF overexpression induced placental sFLT1 production and elevated sFLT1 levels in maternal serum. This led to pregnancy losses, placental vascular defects, and preeclampsia-like symptoms, including hypertension, proteinuria, and glomerular endotheliosis in the mother. Knockdown of placental sFlt1 with a trophoblast-specific transgene caused placental vascular changes that were consistent with excess VEGF activity. Moreover, sFlt1 knockdown in VEGF-overexpressing animals enhanced symptoms produced by VEGF overexpression alone. These findings indicate that sFLT1 plays an essential role in maintaining vascular integrity in the placenta by sequestering excess maternal VEGF and suggest that a local increase in VEGF can trigger placental overexpression of sFLT1, potentially contributing to the development of preeclampsia and other pregnancy complications. PMID:25329693

Activation of PAR-1/NADPH oxidase/ROS signaling pathways is crucial for the thrombin-induced sFlt-1 production in extravillous trophoblasts: possible involvement in the pathogenesis of preeclampsia.

PubMed

Huang, Qi-Tao; Chen, Jian-Hong; Hang, Li-Lin; Liu, Shi-San; Zhong, Mei

2015-01-01

Preeclampsia was characterized by excessive thrombin generation in placentas and previous researches showed that thrombin could enhance soluble Fms-like tyrosine kinase 1 (sFlt-1) expression in first trimester trophoblasts. However, the detailed mechanism for the sFlt-1 over-production induced by thrombin was largely unknown. The purpose of this study was to explore the possible signaling pathway of thrombin-induced sFlt-1 production in extravillous trophoblasts (EVT). An EVT cell line (HRT-8/SVneo) was treated with various concentrations of thrombin. The mRNA expression and protein secretion of sFlt-1 in EVT were detected with real-time polymerase chain reaction and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production were determined by DCFH-DA. Exposure of EVT to thrombin induced increased intracellular ROS generation and overexpression of sFlt-1 at both mRNA and protein levels in a dose dependent manner. Short interfering RNA (siRNA) directed against PAR-1 or apocynin (an inhibitor of NADPH oxidase) could decrease the intracellular ROS generation and subsequently suppressed the production of sFlt-1 at mRNA and protein levels. Our results suggested that thrombin increased sFlt-1 production in EVT via the PAR-1 /NADPH oxidase /ROS signaling pathway. This also highlights the PAR-1 / NADPH oxidase / ROS pathway might be a potential therapeutic target for the prevention of preeclampsia in the future. © 2015 S. Karger AG, Basel.

Pregnancy Complications as Markers for Subsequent Maternal Cardiovascular Disease: Validation of a Maternal Recall Questionnaire.

PubMed

Carter, Ebony Boyce; Stuart, Jennifer J; Farland, Leslie V; Rich-Edwards, Janet W; Zera, Chloe A; McElrath, Thomas F; Seely, Ellen W

2015-09-01

We designed and tested the validity of a questionnaire to characterize maternal recall of pregnancy complications associated with increased future cardiovascular disease risk, based on the 2011 American Heart Association (AHA) guidelines. A maternal recall questionnaire of pregnancy history was administered to 971 patients who had participated in a previous cohort study of 1,608 pregnant women. Medical records from the study pregnancy served as the gold standard. Prevalence, sensitivity (sens), specificity (spec), positive predictive value (PPV), negative predictive value (NPV), and/or Spearman's correlation coefficients (r) were calculated for each question. A total of 526 (54%) individuals recontacted responded. Respondents were more likely to be older, white, educated, and nulliparous and were less likely to deliver low-birthweight infants in the study pregnancy than were individuals who did not respond. Mean length of recall was 4.35 years (standard deviation [SD] 0.46) postpartum. Maternal recall was most accurate for gestational diabetes (sens: 92%, spec: 98%, PPV: 79%, NPV: 99%), infant birthweight (r=0.95), and gestation length (r=0.85). Maternal recall was modest for preeclampsia (sens: 79%, spec: 97%, PPV: 68%, NPV: 98%) and pregnancy-associated hypertension, including preeclampsia or gestational hypertension (sens: 60%, spec: 95%, PPV: 64%, NPV: 94%). This validation study demonstrated that the majority of women could accurately recall a history of gestational diabetes, infant birthweight, and gestational age at delivery, 4 years postpartum on average. Recall of preeclampsia and pregnancy-associated hypertension overall was modest. Maternal report of these pregnancy conditions may help clinicians identify women at increased risk for cardiovascular disease.

Revisiting the Table 2 fallacy: A motivating example examining preeclampsia and preterm birth.

PubMed

Bandoli, Gretchen; Palmsten, Kristin; Chambers, Christina D; Jelliffe-Pawlowski, Laura L; Baer, Rebecca J; Thompson, Caroline A

2018-05-21

A "Table Fallacy," as coined by Westreich and Greenland, reports multiple adjusted effect estimates from a single model. This practice, which remains common in published literature, can be problematic when different types of effect estimates are presented together in a single table. The purpose of this paper is to quantitatively illustrate this potential for misinterpretation with an example estimating the effects of preeclampsia on preterm birth. We analysed a retrospective population-based cohort of 2 963 888 singleton births in California between 2007 and 2012. We performed a modified Poisson regression to calculate the total effect of preeclampsia on the risk of PTB, adjusting for previous preterm birth. pregnancy alcohol abuse, maternal education, and maternal socio-demographic factors (Model 1). In subsequent models, we report the total effects of previous preterm birth, alcohol abuse, and education on the risk of PTB, comparing and contrasting the controlled direct effects, total effects, and confounded effect estimates, resulting from Model 1. The effect estimate for previous preterm birth (a controlled direct effect in Model 1) increased 10% when estimated as a total effect. The risk ratio for alcohol abuse, biased due to an uncontrolled confounder in Model 1, was reduced by 23% when adjusted for drug abuse. The risk ratio for maternal education, solely a predictor of the outcome, was essentially unchanged. Reporting multiple effect estimates from a single model may lead to misinterpretation and lack of reproducibility. This example highlights the need for careful consideration of the types of effects estimated in statistical models. © 2018 John Wiley & Sons Ltd.

Severe preeclampsia and eclampsia: incidence, complications, and perinatal outcomes at a low-resource setting, Mpilo Central Hospital, Bulawayo, Zimbabwe.

PubMed

Ngwenya, Solwayo

2017-01-01

Severe preeclampsia is a disorder of pregnancy characterized by high blood pressure and significant proteinuria after 20 weeks gestation. Severe preeclampsia and eclampsia have considerable adverse impacts on maternal, fetal, and neonatal health especially in low-resource countries. Hypertensive disorders of pregnancy are the third leading cause of maternal deaths in Sub-Saharan Africa. Significant avoidable maternal and neonatal morbidity and mortality may result. This study aimed 1) to determine the incidence of severe preeclampsia/eclampsia in a low-resource setting; 2) to determine the maternal complications of severe preeclampsia/eclampsia in a low-resource setting; 3) to determine the perinatal outcomes of severe preeclampsia/eclampsia in a low-resource setting. This was a retrospective descriptive cohort study carried out at Mpilo Central Hospital, a tertiary teaching referral government hospital in a low-resource setting in Bulawayo, Zimbabwe. Data were obtained from the birth registers in labor ward, intensive care unit, and neonatal intensive care unit of patients who had a diagnosis of severe preeclampsia or eclampsia for the period January 1, 2016, to December 31, 2016. The case notes were retrieved and the demographic, clinical, and outcome data were gathered. There were 9,086 deliveries at the institution during the period January 1, 2016, to December 31, 2016. There were 121 cases of severe preeclampsia/eclampsia. The incidence of severe preeclampsia/eclampsia was 1.3% at Mpilo Central Hospital. The most common major complication was HELLP syndrome (9.1%). Maternal mortality was 1.7%. There were 127 babies born with six sets of twins, 49.6% of the babies were lost through stillbirths and early neonatal deaths. The incidence of severe preeclampsia/eclampsia at Mpilo Central Hospital was 1.3%. The most common maternal complication was hemolysis elevated liver enzymes low platelet syndrome. Maternal mortality was 1.7% due to acute renal failure. Nearly half (49.6%) of the babies born were lost to stillbirths and early neonatal deaths.

Changes of placental syndecan-1 expression in preeclampsia and HELLP syndrome

PubMed Central

Szabo, Szilvia; Xu, Yi; Romero, Roberto; Fule, Tibor; Karaszi, Katalin; Bhatti, Gaurav; Varkonyi, Tibor; Varkonyi, Ildiko; Krenacs, Tibor; Dong, Zhong; Tarca, Adi L.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Papp, Zoltan; Kovalszky, Ilona; Than, Nandor Gabor

2014-01-01

Introduction Preeclampsia is characterized by maternal systemic anti-angiogenic and pro-inflammatory states. Syndecan-1 is a cell surface proteoglycan expressed by the syncytiotrophoblast, which plays an important role in angiogenesis and resolution of inflammation. Our aim was to examine placental syndecan-1 expression in preeclampsia with or without HELLP syndrome. Methods Placentas were obtained from women in the following groups: (1) late-onset preeclampsia (n=8); (2) early-onset preeclampsia without (n=7) and (3) with HELLP syndrome (n=8); (4) preterm controls (n=5); and (5) term controls (n=9). Tissue microarrays (TMAs) were constructed from paraffin-embedded placentas. TMA slides were immunostained for syndecan-1 and evaluated using microscopy, virtual microscopy, and semi-automated image analysis. Maternal sera from patients with preeclampsia (n=49) and controls (n=32) were immunoassayed for syndecan-1. BeWo cells were treated with Forskolin or Latrunculin-B, or kept in ischemic conditions. SDC1 expression and syndecan-1 production were investigated with qRT-PCR, confocal microscopy, and immunoassays. Results Syndecan-1 was localized to the syncytiotrophoblast apical membrane in normal placentas. Syndecan-1 immunoscores were higher in late-onset preeclampsia (p=0.0001) and early-onset preeclampsia with or without HELLP syndrome (p=0.02 for both) than in controls. Maternal serum syndecan-1 concentration was lower in preeclampsia (median: 673ng/ml, interquartile range: 459-1161ng/ml) than in controls (1158ng/ml, 622-1480ng/ml). SDC1 expression and syndecan-1 immunostainings in BeWo cells and syndecan-1 concentrations in supernatants increased during cell differentiation. Disruption of the actin cytoskeleton with Latrunculin-B decreased syndecan-1 release, while ischemic conditions increased it. Conclusions Syncytiotrophoblastic syndecan-1 expression depends on the differentiation of villous trophoblasts, and trophoblastic syndecan-1 release is decreased in preeclampsia and HELLP syndrome. This phenomenon may be related to the disturbed syncytiotrophoblastic cortical actin cytoskeleton, and associated with maternal anti-angiogenic and pro-inflammatory states in these syndromes. PMID:23807541

Mediators of the association between pre-eclampsia and cerebral palsy: population based cohort study

PubMed Central

Heimstad, Runa; Iversen, Ann-Charlotte; Austgulen, Rigmor; Lydersen, Stian; Andersen, Guro L; Irgens, Lorentz M; Vik, Torstein

2013-01-01

Objective To test the hypothesis that pre-eclampsia is a risk factor for cerebral palsy mediated through preterm birth and being born small for gestational age. Design Population based cohort study. Setting Clinical data from the Norwegian Cerebral Palsy Registry were linked with perinatal data prospectively recorded by the Medical Birth Registry of Norway. Participants All singleton babies who survived the neonatal period during 1996-2006 (849 children with cerebral palsy and 616 658 control children). Main outcome measures Cerebral palsy and cerebral palsy subtypes. Results Children exposed to pre-eclampsia had an excess risk of cerebral palsy (unadjusted odds ratio 2.5, 95% confidence interval 2.0 to 3.2) compared with unexposed children. Among children born at term (≥37 weeks), exposure to pre-eclampsia was not associated with an excess risk of cerebral palsy in babies not born small for gestational age (1.2, 0.7 to 2.0), whereas children exposed to pre-eclampsia and born small for gestational age had a significantly increased risk of cerebral palsy (3.2, 1.5 to 6.7). Non-small for gestational age babies born very preterm (<32 weeks) and exposed to pre-eclampsia had a reduced risk of cerebral palsy compared with unexposed children born at the same gestational age (0.5, 0.3 to 0.8), although the risk was not statistically significantly reduced among children exposed to pre-eclampsia and born small for gestational age (0.7, 0.4 to 1.3). Exposure to pre-eclampsia was not associated with a specific cerebral palsy subtype. Conclusions Exposure to pre-eclampsia was associated with an increased risk of cerebral palsy, and this association was mediated through the children being born preterm or small for gestational age, or both. Among children born at term, pre-eclampsia was a risk factor for cerebral palsy only when the children were small for gestational age. PMID:23838554

Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy.

PubMed

Wayhs, Sâmia Yasin; Wottrich, Joise; Uggeri, Douglas Prestes; Dias, Fernando Suparregui

2013-01-01

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and evere liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure management and treatment success.

Biomarkers for the management of pre-eclampsia in pregnant women

PubMed Central

Petla, Lakshmi Tanuja; Chikkala, Rosy; Ratnakar, K.S.; Kodati, Vijayalakshmi; Sritharan, V.

2013-01-01

Pre-eclampsia (PE) is a pregnancy related disorder characterized by hypertension and proteinuria noticeable after 20 wk of gestation. It is a leading cause of maternal and foetal mortality and morbidity worldwide. The aetiology of the disease is unknown, but recent studies have revealed that this disorder appears to originate in placenta and is characterized by widespread maternal endothelial dysfunction. Till date, delivery of placenta is the only cure for the disease. So, there is a need for the identification of highly specific and sensitive biochemical markers that would allow early identification of patients at risk and thus help in providing proper prenatal care. Several promising biomarkers have been proposed, alone or in combination, that may help in predicting women who are likely to develop PE. Maternal serum concentrations of these biomarkers either increase or decrease in PE during gestation. This review focuses on the various biomarkers available and their utility in predicting pre-eclampsia. PMID:24056556

Preeclampsia Risks in Kidney Donors and Recipients.

PubMed

Shah, Pratik B; Samra, Manpreet; Josephson, Michelle A

2018-06-08

To review the studies and practice guidelines on the preeclampsia risks in kidney donors and recipients. There is a small increased risk of gestational hypertension and preeclampsia in pregnancies that follow kidney donation. Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline (2017) and the 2015 American Society of Transplantation (AST) consensus conference statement recommends counseling kidney donors about this increased risk. There is no observed increase in fetal complications or eclampsia post-kidney donation. Preeclampsia is more commonly observed in kidney transplant recipients than the general population and these patients should be co-managed with an obstetrician with experience in managing high risk pregnancies. Although preeclampsia has not been found to have a deleterious effect on renal graft function, it can cause premature delivery. Risk calculators have been proposed and an elevated pre-pregnancy creatinine seems to be an important risk. KDIGO Clinical Practice Guidelines (2009) recommends attempting pregnancy when kidney function is stable with proteinuria of less than 1 g per day. The use of novel biomarkers for preeclampsia has not been published in this population. Preeclampsia is an important concern for female kidney donors and recipients of child-bearing age. These individuals should be appropriately counseled.

Clinical accuracy of inflationary oscillometry in pregnancy and pre-eclampsia: Omron-MIT Elite.

PubMed

Chung, Y; Brochut, M C; de Greeff, A; Shennan, A H

2012-10-01

To evaluate the accuracy of the Omron MIT Elite in pregnancy and pre-eclampsia according to the British Hypertension Society protocol (BHS). Prospective observational study. Antenatal clinics and wards at St. Thomas' Hospital (London, UK). Forty-five pregnant women including 15 with pre-eclampsia. Nine sequential same arm blood pressure (BP) measurements were taken from each woman by trained observers, alternating between mercury sphygmomanometry and the test device. Grading criteria of the BHS protocol (A/B grade=pass; C/D=fail). The Omron MIT Elite achieved a grade A/A in both pregnancy and pre-eclampsia. The mean difference (SD) between the mercury standard and the device in pregnancy was -1.1 (5.2)mmHg and 1.5 (4.8)mmHg for systolic and diastolic BP respectively compared to 0.2 (5.3)mmHg and 2.2 (5.5)mmHg in pre-eclampsia. The Omron MIT Elite can be recommended for use in pregnancy and pre-eclampsia according to the BHS protocol. To date, this is the most accurate automated BP device validated in pre-eclampsia. Copyright © 2012. Published by Elsevier B.V.

Working hours and risk of gestational hypertension and pre-eclampsia.

PubMed

Chang, Pei-Jen; Chu, Li-Ching; Hsieh, Wu-Shiun; Chuang, Yi-Li; Lin, Shio-Jean; Chen, Pau-Chung

2010-01-01

The potential impact of employment on maternal health, particularly in relation to gestational hypertension and pre-eclampsia, has been subject to research. However, there is limited evidence on associations between shift work and long working hours on the incidence of these conditions. To evaluate potential associations between maternal shift work and long working hours during pregnancy and gestational hypertension or pre-eclampsia. Multistage stratified systematic sampling was used to recruit 24 200 post-partum women from the Taiwan national birth registration database in 2005. Subjects underwent home interview 6 months after their deliveries by structured questionnaire to obtain characteristics of maternal employment and potential confounders. Diagnosis of gestational hypertension and pre-eclampsia was obtained from the birth registration. There was no association between employment status and gestational hypertension or pre-eclampsia. Also, no significant association between gestational hypertension or pre-eclampsia and maternal shift work or long working hours during pregnancy was found in all or primiparous women. There was no convincing evidence that maternal shift work or long working hours had a higher risk of gestational hypertension or pre-eclampsia. However, further research is warranted to confirm these negative findings.

Perinatal outcome in singleton pregnancies complicated with preeclampsia and eclampsia in Ecuador.

PubMed

Phoa, K Y N; Chedraui, P; Pérez-López, F R; Wendte, J F; Ghiabi, S; Vrijkotte, T; Pinto, P

2016-07-01

Preeclampsia in Ecuador is an understudied subject since available epidemiological data are scarce. The aim of this study was to describe perinatal outcomes among singleton pregnancies complicated with preeclampsia and eclampsia in a sample of low-income Ecuadorian women. Pregnant women complicated with preeclampsia (mild and severe) and eclampsia (defined according to criteria of the ACOG) delivering at the Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador were surveyed with a structured questionnaire containing maternal (socio-demographic) and neonatal data. Perinatal outcomes were compared according to severity of clinical presentation. A total of 163 women with preeclampsia [mild (23.9%), severe (68.7%) and eclampsia (7.4%)] were surveyed. Perinatal mortality and stillbirth rate was similar among studied groups (mild vs. severe preeclampsia/eclampsia cases). However, severe cases displayed higher rates of adverse perinatal outcomes: lower birth Apgar scores, more preterm births, and more low birth weight and small for gestational age infants. Caesarean-section rate and the number of admissions to intensive or intermediate neonatal care were higher in severe cases. A similar trend was found when analysis excluded preterm gestations. In conclusion, in this specific low-income Ecuadorian population perinatal outcome was adverse in pregnancies complicated with severe preeclampsia/eclampsia.

Increased leptin levels in preeclampsia: associations with BMI, estrogen and SHBG levels.

PubMed

Acromite, Michael; Ziotopoulou, Mary; Orlova, Christine; Mantzoros, Christos

2004-01-01

Leptin is secreted mainly by the white adipose tissue but is also synthesized in several non-adipose tissue organs including the placenta. Serum leptin levels are increased in normal pregnancies and are higher in preeclamptic than normal pregnant women. There is, however, a lack of empirical evidence of an independent association of serum leptin levels and preeclamsia. We have studied cross-sectionally 18 3rd trimester preeclamptic women, 28 3rd trimester and 30 2nd trimester control women to confirm the reported increase of serum leptin in preeclampsia and to assess whether elevated leptin levels in preeclampsia increase the variance explained by body mass index (BMI), androgens, estrogens and/or sex hormone binding globulin (SHBG). Anthropometric, demographic and hormonal data were analyzed using linear and logistic regression models. Leptin is significantly increased in preeclampsia by univariate analysis, but use of multivariate analysis indicates that the elevated leptin levels are not associated with preeclampsia independently from BMI, estrogens and SHBG. This study confirms that leptin levels are higher in women with preeclampsia than in controls and demonstrates that serum leptin levels do not add to the prediction of preeclampsia after accounting for BMI, estrogen and SHBG levels of preeclamptic women.

The role of nitrates in the prevention of preeclampsia: an update.

PubMed

Kalidindi, Madhavi; Velauthar, Luxmi; Khan, Khalid; Aquilina, Joseph

2012-12-01

Defective nitric oxide synthesis and nitric oxide-mediated vasodilatation is widely documented in the pathophysiology of preeclampsia, a leading cause of maternal and perinatal morbidity and mortality worldwide. Several studies demonstrated the beneficial role of nitric oxide agents, especially glyceryl trinitrate and L-arginine in reducing the blood pressure and improving the uteroplacental blood flow velocities. However, there is insufficient evidence on the efficacy and safety of these agents in the prevention of preeclampsia and its complications, as there are very few randomized controlled trials with small number of women. The aim of this review is to summarize and evaluate the role of nitrates in the prevention of preeclampsia based on the available evidence in the literature till date and suggestions for future research. Supplementation with L-arginine and antioxidant vitamins reduced the incidence of preeclampsia in women at high risk of preeclampsia [P < 0.001, absolute risk reduction 0.17 (confidence interval 0.12-0.21)]. On the basis of the recent evidence, nitric oxide agents may be beneficial in the prevention of preeclampsia. Randomized controlled trials initiated in the first trimester and using long-acting nitrates are needed in high-risk women to validate these findings.

The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis.

PubMed

Roberge, Stéphanie; Nicolaides, Kypros; Demers, Suzanne; Hyett, Jon; Chaillet, Nils; Bujold, Emmanuel

2017-02-01

Preeclampsia and fetal growth restriction are major causes of perinatal death and handicap in survivors. Randomized clinical trials have reported that the risk of preeclampsia, severe preeclampsia, and fetal growth restriction can be reduced by the prophylactic use of aspirin in high-risk women, but the appropriate dose of the drug to achieve this objective is not certain. We sought to estimate the impact of aspirin dosage on the prevention of preeclampsia, severe preeclampsia, and fetal growth restriction. We performed a systematic review and meta-analysis of randomized controlled trials comparing the effect of daily aspirin or placebo (or no treatment) during pregnancy. We searched MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials up to December 2015, and study bibliographies were reviewed. Authors were contacted to obtain additional data when needed. Relative risks for preeclampsia, severe preeclampsia, and fetal growth restriction were calculated with 95% confidence intervals using random-effect models. Dose-response effect was evaluated using meta-regression and reported as adjusted R 2 . Analyses were stratified according to gestational age at initiation of aspirin (≤16 and >16 weeks) and repeated after exclusion of studies at high risk of biases. In all, 45 randomized controlled trials included a total of 20,909 pregnant women randomized to between 50-150 mg of aspirin daily. When aspirin was initiated at ≤16 weeks, there was a significant reduction and a dose-response effect for the prevention of preeclampsia (relative risk, 0.57; 95% confidence interval, 0.43-0.75; P < .001; R 2 , 44%; P = .036), severe preeclampsia (relative risk, 0.47; 95% confidence interval, 0.26-0.83; P = .009; R 2 , 100%; P = .008), and fetal growth restriction (relative risk, 0.56; 95% confidence interval, 0.44-0.70; P < .001; R 2 , 100%; P = .044) with higher dosages of aspirin being associated with greater reduction of the 3 outcomes. Similar results were observed after the exclusion of studies at high risk of biases. When aspirin was initiated at >16 weeks, there was a smaller reduction of preeclampsia (relative risk, 0.81; 95% confidence interval, 0.66-0.99; P = .04) without relationship with aspirin dosage (R 2 , 0%; P = .941). Aspirin initiated at >16 weeks was not associated with a risk reduction or a dose-response effect for severe preeclampsia (relative risk, 0.85; 95% confidence interval, 0.64-1.14; P = .28; R 2 , 0%; P = .838) and fetal growth restriction (relative risk, 0.95; 95% confidence interval, 0.86-1.05; P = .34; R 2 , not available; P = .563). Prevention of preeclampsia and fetal growth restriction using aspirin in early pregnancy is associated with a dose-response effect. Low-dose aspirin initiated at >16 weeks' gestation has a modest or no impact on the risk of preeclampsia, severe preeclampsia, and fetal growth restriction. Women at high risk for those outcomes should be identified in early pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

Blood pressure self-monitoring in pregnancy: examining feasibility in a prospective cohort study.

PubMed

Tucker, Katherine L; Taylor, Kathryn S; Crawford, Carole; Hodgkinson, James A; Bankhead, Clare; Carver, Tricia; Ewers, Elizabeth; Glogowska, Margaret; Greenfield, Sheila M; Ingram, Lucy; Hinton, Lisa; Khan, Khalid S; Locock, Louise; Mackillop, Lucy; McCourt, Christine; Pirie, Alexander M; Stevens, Richard; McManus, Richard J

2017-12-28

Raised blood pressure (BP) affects approximately 10% of pregnancies worldwide, and a high proportion of affected women develop pre-eclampsia. This study aimed to evaluate the feasibility of self-monitoring of BP in pregnancy in women at higher risk of pre-eclampsia. This prospective cohort study of self-monitoring BP in pregnancy was carried out in two hospital trusts in Birmingham and Oxford and thirteen primary care practices in Oxfordshire. Eligible women were those defined by the UK National Institute for Health and Care Excellence (NICE) guidelines as at higher risk of pre-eclampsia. A total of 201 participants were recruited between 12 and 16 weeks of pregnancy and were asked to take two BP readings twice daily three times a week through their pregnancy. Primary outcomes were recruitment, retention and persistence of self-monitoring. Study recruitment and retention were analysed with descriptive statistics. Survival analysis was used to evaluate the persistence of self-monitoring and the performance of self-monitoring in the early detection of gestational hypertension, compared to clinic BP monitoring. Secondary outcomes were the mean clinic and self-monitored BP readings and the performance of self-monitoring in the detection of gestational hypertension and pre-eclampsia compared to clinic BP. Of 201 women recruited, 161 (80%) remained in the study at 36 weeks or to the end of their pregnancy, 162 (81%) provided any home readings suitable for analysis, 148 (74%) continued to self-monitor at 20 weeks and 107 (66%) at 36 weeks. Self-monitored readings were similar in value to contemporaneous matched clinic readings for both systolic and diastolic BP. Of the 23 who developed gestational hypertension or pre-eclampsia and self-monitored, 9 (39%) had a raised home BP prior to a raised clinic BP. Self-monitoring of BP in pregnancy is feasible and has potential to be useful in the early detection of gestational hypertensive disorders but maintaining self-monitoring throughout pregnancy requires support and probably enhanced training.

Decreased Nephrin and GLEPP-1, But Increased VEGF, Flt-1, and Nitrotyrosine, Expressions in Kidney Tissue Sections From Women With Preeclampsia

PubMed Central

Zhao, Shuang; Gu, Xin; Groome, Lynn J.; Wang, Yuping

2011-01-01

Renal injury is a common pathophysiological feature in women with preeclampsia as evidenced by increased protein leakage (proteinuria) and glomerular injury (glomerular endotheliosis). Recently, podocyturia was found in preeclampsia, suggesting podocyte shedding occurs in this pregnancy disorder. However, podocyte function in preeclampsia is poorly understood. In this study, the authors have examined podocyte-specific protein expressions for nephrin, glomerular epithelial protein 1 (GLEPP-1), and ezrin in kidney biopsy tissue sections from women with preeclampsia. Expressions for vascular endothelial growth factor (VEGF) and its receptor Flt-1 and oxidative stress marker nitrotyrosine and antioxidant CuZn-superoxide dismutase (CuZn-SOD) were also examined. Kidney tissue sections from nonhypertensive and chronic hypertensive participants were stained as controls. The findings were (1) nephrin and GLEPP-1 were mainly expressed in glomerular podocytes; (2) ezrin was expressed in both glomerular podocytes and tubular epithelial cells; (3) compared to tissue sections from nonhypertensive and chronic hypertensive participants, nephrin and GLEPP-1 expressions were much reduced in tissue sections from preeclampsia and ezrin expression was reduced in podocytes; (4) enhanced VEGF, Flt-1, and nitrotyrosine, but reduced CuZn-SOD, expressions were observed in both glomerular podocytes and endothelial cells in tissue sections from preeclampsia; and (5) the expression pattern for nephrin, GLEPP-1, ezrin, VEGF, Flt-1, and CuZn-SOD were similar between tissue sections from nonhypertensive and chronic hypertensive participants. Although the authors could not conclude from this biopsy study whether the podocyte injury is the cause or effect of the preeclampsia phenotype, the data provide compelling evidence that podocyte injury accompanied by altered angiogenesis process and increased oxidative stress occurs in kidney of patients with preeclampsia. PMID:19528353

GLYCOGEN PHOSPHORYLASE ISOENZYME BB PLASMA CONCENTRATION IS ELEVATED IN PREGNANCY AND PRETERM PREECLAMPSIA

PubMed Central

Lee, JoonHo; Romero, Roberto; Dong, Zhong; Lee, Deug-Chan; Dong, Yi; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai

2012-01-01

Glycogen phosphorylase is a key enzyme in glycogenolysis. Released with myocardial ischemia, blood concentration of glycogen phosphorylase isoenzyme BB (GPBB) is a marker of acute coronary syndromes. Pregnancy imposes metabolic stress, and preeclampsia is associated with cardiac complications. However, plasma GPBB concentration during pregnancy is unknown. This study was conducted to determine maternal plasma GPBB concentration in normal pregnancy and in preeclampsia. Plasma samples from six groups (n=396) were studied: non-pregnant women and pregnant women with normal term delivery, term preeclampsia, term small-for-gestational-age neonates, preterm preeclampsia, and preterm small-for-gestational-age neonates. GPBB concentration was measured with a specific immunoassay. Placental tissues (n=45) obtained from pregnant women with preterm and term preeclampsia, spontaneous preterm delivery, and normal term cases were analyzed for potential GPBB expression by immunoblotting. Median plasma GPBB concentration was higher in pregnant women than in non-pregnant women (38.7 ng/ml versus 9.2 ng/mL, P<0.001), which remained significant after adjusting for age, race, and parity. Maternal plasma GPBB concentrations did not change throughout gestation. Preterm but not term preeclampsia cases had higher median plasma GPBB concentration than gestational-age-matched normal pregnancy cases (72.6 ng/ml versus 26.0 ng/ml, P=0.001). Small-for-gestational-age neonates did not affect plasma GPBB concentration. GPBB was detected in the placenta and was less abundant in preterm preeclampsia than in preterm delivery cases (P<0.01). There is physiologic elevation of plasma GPBB concentration during pregnancy; an increase in maternal plasma GPBB is a novel phenotype of preterm preeclampsia. It is strongly suggested that these changes are attributed to GPBB of placental origin. PMID:22215716

Melatonin secretion is impaired in women with preeclampsia and an abnormal circadian blood pressure rhythm.

PubMed

Bouchlariotou, Sofia; Liakopoulos, Vassilios; Giannopoulou, Myrto; Arampatzis, Spyridon; Eleftheriadis, Theodoros; Mertens, Peter R; Zintzaras, Elias; Messinis, Ioannis E; Stefanidis, Ioannis

2014-08-01

Non-dipping circadian blood pressure (BP) is a common finding in preeclampsia, accompanied by adverse outcomes. Melatonin plays pivotal role in biological circadian rhythms. This study investigated the relationship between melatonin secretion and circadian BP rhythm in preeclampsia. Cases were women with preeclampsia treated between January 2006 and June 2007 in the University Hospital of Larissa. Volunteers with normal pregnancy, matched for chronological and gestational age, served as controls. Twenty-four hour ambulatory BP monitoring was applied. Serum melatonin and urine 6-sulfatoxymelatonin levels were determined in day and night time samples by enzyme-linked immunoassays. Measurements were repeated 2 months after delivery. Thirty-one women with preeclampsia and 20 controls were included. Twenty-one of the 31 women with preeclampsia were non-dippers. Compared to normal pregnancy, in preeclampsia there were significantly lower night time melatonin (48.4 ± 24.7 vs. 85.4 ± 26.9 pg/mL, p<0.001) levels. Adjustment for circadian BP rhythm status ascribed this finding exclusively to non-dippers (p<0.01). Two months after delivery, in 11 of the 21 non-dippers both circadian BP and melatonin secretion rhythm reappeared. In contrast, in cases with retained non-dipping status (n=10) melatonin secretion rhythm remained impaired: daytime versus night time melatonin (33.5 ± 13.0 vs. 28.0 ± 13.8 pg/mL, p=0.386). Urinary 6-sulfatoxymelatonin levels were, overall, similar to serum melatonin. Circadian BP and melatonin secretion rhythm follow parallel course in preeclampsia, both during pregnancy and, at least 2 months after delivery. Our findings may be not sufficient to implicate a putative therapeutic effect of melatonin, however, they clearly emphasize that its involvement in the pathogenesis of a non-dipping BP in preeclampsia needs intensive further investigation.

Increased levels of copeptin before clinical diagnosis of preeclampsia.

PubMed

Yeung, Edwina H; Liu, Aiyi; Mills, James L; Zhang, Cuilin; Männistö, Tuija; Lu, Zhaohui; Tsai, Michael Y; Mendola, Pauline

2014-12-01

Copeptin, a surrogate biomarker of vasopressin, has been associated with renal function decline and may serve as a useful early biomarker for preeclampsia. We measured serum copeptin using samples collected longitudinally during pregnancy among unaffected controls (n=136) and cases of preeclampsia (n=169), gestational diabetes mellitus (n=92), gestational hypertension (n=101), and preterm birth (n=86) in the Calcium for Preeclampsia Prevention trial (1992-1995). Preeclampsia and gestational hypertension were defined as having a diastolic blood pressure≥90 mm Hg on 2 occasions with and without proteinuria, respectively. The risk of pregnancy complications associated with copeptin was estimated by logistic regression adjusting for maternal age, race, body mass index, insurance status, marital status, current smoking, and clinical site. Baseline copeptin levels, at mean 16 weeks of gestation, were associated with increased preeclampsia risk (adjusted odds ratios and 95% confidence interval being 1.55 per log unit; 1.03-2.31) when compared with controls (P=0.03). The association was stronger among cases diagnosed before 37 weeks (1.86; 1.08-3.20) than those diagnosed later (1.45; 0.91-2.32). Copeptin levels rose with increasing gestational age in both cases and controls but remained significantly higher among those who were diagnosed with preeclampsia. Differences in levels of copeptin between cases and controls became more apparent closer to time of diagnosis. No significant associations were found for gestational hypertension without proteinuria, gestational diabetes mellitus, or preterm birth without preeclampsia. Copeptin levels are elevated in pregnant women before diagnosis of preeclampsia with elevation specific to this pregnancy complication rather than hypertension alone. © 2014 American Heart Association, Inc.

Preeclampsia in autologous and oocyte donation pregnancy: is there a different pathophysiology?

PubMed

Lashley, Lisa E E L O; Buurma, Aletta; Swings, Godelieve M J S; Eikmans, Michael; Anholts, Jacqueline D H; Bakker, Jaap A; Claas, Frans H J

2015-06-01

Oocyte donation (OD) is a specific method of artificial reproductive technology that is accompanied by a higher risk of preeclampsia during pregnancy. The pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought to differ from preeclampsia in autologous pregnancies. As preeclampsia in autologous pregnancies is suggested to be associated with complement activation, we studied C4d deposition, circulating complement components and placental complement regulatory proteins in preeclamptic OD pregnancies. Women with uncomplicated and preeclamptic pregnancies after OD or spontaneous conception were selected. We stained the placentas for C4d, marker for complement activation, measured complement factors C1q, C3 and C4 in maternal sera and quantified the placental mRNA expression of complement regulatory proteins CD46, CD55 and CD59. A significantly (p < 0.03) higher incidence of C4d deposition was observed in placentas from women with preeclampsia compared with uncomplicated pregnancies, both OD and autologous. The level of complement factors in serum did not differ between the groups. Children born in the autologous preeclampsia group were significantly lower in birth weight (p < 10th percentile) compared with the preeclamptic OD group. In addition, the placental mRNA expression level of complement regulatory proteins was significantly lower in uncomplicated and preeclamptic OD compared with the autologous pregnancies. In line with autologous preeclampsia pregnancies, there is excessive activation of complement in preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this is not associated with counterbalancing upregulation of complement regulatory proteins. Furthermore, C4d deposition in OD pregnancies is not related to the severity of preeclampsia, suggesting another trigger or regulatory mechanism of placental C4d deposition in preeclamptic OD pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

PP128. Placental Caspase-3 gene polymorphisms is associated with preeclampsia.

PubMed

Hsu, C-D; Polavarapu, S; Parton, L

2012-07-01

Increased placental trophoblastic apoptosis (programmed cell death) was previously reported in pregnancies complicated by preeclampsia. Caspase-3 is one of the key executioners of apoptosis. Caspase are expressed in many tissues including human placental trophoblast and other tissues. Variations in the promoter area of the Caspase genes may modulate apoptotic signaling, contributing to an increased risk of preeclampsia To determine if gene polymorphisms of Caspase 3 proteins differ between patient with and without preeclampsia. Forty-three singleton placentas were studied. Twenty-two placentas were with preeclampsia and 21 were normotensive controls. DNA was extracted from placentas using QIAAmp DNA Minikit. Genotyping of Caspase 3 +567 was determined by real-time PCR using the Applied Biosystems Prism 7900 HT SDS machine. Chi-square and Fisher's exact tests were used for statistical analysis. There were no significant differences in maternal age, parity or race between the two groups. Preeclamptic placentas had higher frequency of wild type TT of Caspase-3 SNP (+567) as compared with normotensive controls (59% versus 28.5%). Preeclamptic placentas expressed significantly more genotype of TT of Caspase-3 SNP (+567) than normotensive patients when compared to CC (p=0.02). The alle frequencies of the Caspase SNP (+567) in preeclampstic placentas were 0.77 and 0.23 for T and C, respectively, as compared to 0.52 and 0.48, respectively, in placentas from normotensive pregnancies. Immune intolerance of maternal and placental interaction plays an important role in the pathogenesis of preeclampsia. Increased of placental apoptosis was reported in pregnancy complicated with preeclamsia. Our findings indicate placental Caspase 3 (+567) gene polymorphisms is associated with preeclampsia. Altered placental alle frequencies and caspase-3 SNP (+567) in preeclampsia further suggests preeclampsia is a trophoblastic disorder. Copyright © 2012. Published by Elsevier B.V.

Circulating and Placental Growth-Differentiation Factor 15 in Preeclampsia and in Pregnancy Complicated by Diabetes Mellitus

PubMed Central

Sugulle, Meryam; Dechend, Ralf; Herse, Florian; Weedon-Fekjaer, M. Susanne; Johnsen, Guro M.; Brosnihan, K. Bridget; Anton, Lauren; Luft, Friedrich C.; Wollert, Kai C.; Kempf, Tibor; Staff, Anne Cathrine

2014-01-01

Abstract Growth-differentiation factor 15 (GDF-15), a stress-responsive transforming growth factor-β–related cytokine, is emerging as a new risk marker in patients with cardiovascular disease. We explored GDF-15 in preeclampsia and in diabetic pregnancies, because these conditions are associated with augmented risk for cardiovascular disease, both in mother and in offspring. Plasma from pregnant women (n=267; controls: n=59, preeclampsia: n=85, diabetes mellitus: n=112, and superimposed preeclampsia in diabetes mellitus: n=11), fetal plasma (n=72), and amniotic fluid (n=99) were analyzed by immunoassay for GDF-15. Placental GDF-15 mRNA and protein expression levels were analyzed by quantitative real-time PCR and immunoblots in 78 and 18 pregnancies, respectively. Conditioned media from preeclamptic (n=6) and control (n=6) villous placenta explants were analyzed by immunoassay for GDF-15. Median maternal GDF-15 concentration was elevated in those with diabetes mellitus, as compared with controls (91 549 versus 79 875 ng/L; P=0.02). Median GDF-15 concentration was higher in patients with preeclampsia than in controls in term maternal blood samples (127 061 versus 80 319 ng/L; P<0.001). In the fetal circulation and amniotic fluid, GDF-15 was elevated in preeclampsia and superimposed preeclampsia in diabetes mellitus, as compared with controls. GDF-15 placental mRNA expression was elevated in preeclampsia, as compared with controls (P=0.002). Placenta immunoblots confirmed a single GDF-15 protein band, and a time-dependent increase in GDF-15 protein was detected in the conditioned media. Our study is the first to show that GDF-15 is dysregulated, both in preeclampsia and in diabetic pregnancies. The mechanisms and diagnostic implications of these findings remain to be explored. PMID:19470878

Expression of MicroRNA-146a and MicroRNA-155 in Placental Villi in Early- and Late-Onset Preeclampsia.

PubMed

Nizyaeva, N V; Kulikova, G V; Nagovitsyna, M N; Kan, N E; Prozorovskaya, K N; Shchegolev, A I; Sukhikh, G T

2017-07-01

We studied the expression of microRNA-146a and microRNA-155 in placental villi from 18 women (26-39 weeks of gestation) of reproductive age with early- or late-onset preeclampsia. The reference group consisted of women with physiological pregnancy and full-term gestation and with preterm birth after caesarian section on gestation week 26-31. MicroRNA-146a and microRNA-155 were detected by in situ hybridization with digoxigenin on paraffin sections. It was found that the expression of microRNA-146a in both syncytiotrophoblast of the intermediate villi and syncytial knots was lower at late-onset preeclampsia than at physiologic pregnancy of full-term period (p=0.037 and p=0.001 respectively). The expression of microRNA-155 in syncytiotrophoblast of intermediate placental villi in early-onset preeclampsia was higher than in group with preterm delivery (p=0.003). However, in syncytiotrophoblast of intermediate villi and in syncytial knots, the expression of microRNA-155 was lower at late-onset preeclampsia in comparison with full-term physiological pregnancy (p=0.005). In addition, the expression of microRNA-146a and microRNA-155 did not increase in the later terms in preeclampsia, while in the reference groups demonstrating gradual increase in the expression of these markers with increasing gestational age. Expression microRNA-146a and microRNA-155 little differed in early- and late-onset preeclampsia. These findings suggest that different variants of preeclampsia are probably characterized by common pathogenetic pathways. Damaged trophoblast cannot maintain of microRNAs synthesis at the required level, which determines the formation of a vicious circle in preeclampsia and further progression of the disease.

Maternal serum ratio of ghrelin to obestatin decreased in preeclampsia.

PubMed

Wu, Weiguang; Fan, Xiaobin; Yu, Yuecheng; Wang, Yingchun

2015-10-01

Ghrelin, an endogenous for the growth hormone secretagogue receptor, has been shown to participate in blood pressure regulation. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. We hypothesized that ghrelin/obestatin imbalance played a role in the pathogenesis. This study was designed to determine the alterations of ghrelin and obestatin concentrations and ghrelin/obestatin ratio in maternal serum in preeclampsia. This retrospective case-control study included 31 preeclampsia and 31 gestational week-matched normal pregnancies. Ghrelin and obestatin concentrations in maternal serum were determined by radioimmunoassay, and the ghrelin/obestatin ratio was calculated. The ghrelin concentration and ghrelin/obestatin ratio in maternal serum were significantly lower in preeclampsia than in normal pregnancies (214.34±14.27pg/mL vs 251.49±16.15pg/mL, P=0.041, 1.07±0.09 vs 0.82±0.08, P=0.023). The obestatin concentration in maternal serum was significantly higher in preeclampsia than in normal pregnancies (276.35±15.38pg/mL vs 223.53±18.61pg/mL, P=0.019). The systolic blood pressure in preeclampsia was negatively correlated with ghrelin concentration and ghrelin/obestatin ratio (r=-0.549, P=0.003; r=-0.491, P=0.004) and was positively correlated with obestatin concentrations in preeclampsia (r=0.388, P=0.013). The findings of this study suggested disturbance of ghrelin and obestatin in maternal serum in preeclampsia, and ghrelin/obestatin imbalance might play a role in the pathogenesis of preeclampsia. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Risk of preeclampsia after gestational exposure to selective serotonin reuptake inhibitors and other antidepressants: A study from The Norwegian Mother and Child Cohort Study.

PubMed

Lupattelli, Angela; Wood, Mollie; Lapane, Kate; Spigset, Olav; Nordeng, Hedvig

2017-10-01

To describe the risk of early- and late-onset preeclampsia across pregnancies exposed to antidepressants and to evaluate the impact of timing and length of gestational exposure to antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), on preeclampsia. The Norwegian Mother and Child Cohort, a prospective population-based study, and the Medical Birth Registry of Norway provided information on antidepressant exposure, depression, and anxiety symptoms in pregnancy, preeclampsia diagnoses, and important covariates. Within a pregnancy cohort of depressed women, we compared the risk of late-onset preeclampsia between SSRI-exposed and nonmedicated pregnancies using marginal structural models (weighted) and modified Poisson regression models. Of the 5887 pregnancies included, 11.1% were exposed at any time before week 34 to SSRIs, 1.3% to serotonin-norepinephrine reuptake inhibitors, 0.4% to tricyclic antidepressants, and 0.5% to other antidepressants. The risks of early- and late-onset preeclampsia by exposure status in pregnancy were 0.3% and 3.6% (nonmedicated), 0.4% and 3.7% (SSRIs), 1.5% and 4.1% (serotonin-norepinephrine reuptake inhibitors), and 7.1% and 10.0% (tricyclic antidepressants). Compared with nonmedicated pregnancies, SSRI-exposed in mid and late gestation had adjusted relative risks for late-onset mild preeclampsia of 0.76 (95% confidence interval, 0.38-1.53) and 1.56 (0.71-3.44) (weighted models), respectively. There was no association between SSRI exposure in pregnancy and severe late-onset preeclampsia. We have provided evidence that SSRI use in early and midpregnancy does not substantially increase the risk of late-onset preeclampsia. © 2017 The Authors. Pharmacoepidemiology & Drug Safety published by John Wiley & Sons Ltd.

Number of decidual natural killer cells & macrophages in pre-eclampsia

PubMed Central

Milosevic-Stevanovic, Jelena; Krstic, Miljan; Radovic-Janosevic, Dragana; Popovic, Jasmina; Tasic, Marija; Stojnev, Slavica

2016-01-01

Background & objectives: The process of human placentation is complex and still not well understood. This study was aimed to examine the relationship between clinical features of pre-eclampsia and degree of trophoblastic invasion after its immunohistochemical visualization in the context of possible alterations in the number of natural killer (NK) cells and macrophages in the decidua. Methods: This prospective study included a study group comprising 30 pregnant women with pre-eclampsia delivered by caesarean section and a control group comprising 20 healthy pregnant women also delivered by caesarean section. Samples of placental bed obtained during caesarean section were analyzed after immunohistochemical labelling CD56+ NK cells, CD68+ macrophages and cytokeratin 7 trophoblastic cells. Results: In pre-eclampsia, there was a significantly lower number of CD56+ NK cells in the decidua (P<0.001) and a higher number of CD68+ macrophages (P<0.001) compared to control group. In the subgroup of pre-eclampsia with intrauterine growth retardation (IUGR), a significantly greater number of NK cells (P<0.05) was recorded, as well as an increased number of macrophages, but not significantly compared to pre-eclampsia without IUGR. There was no significant difference in the distribution of these cells in the decidua in relation to the severity of pre-eclampsia. CD56+ NK cells were significantly less (P<0.05) and macrophages were more (P<0.05) in the group with poor trophoblastic invasion. Interpretation & conclusions: Alterations in the number of immune cells in relation to the degree of trophoblastic invasion indicated their role in aetiopathogenesis of pre-eclampsia, while the direct association between their number and severity of pre-eclampsia was not confirmed. PMID:28474619

Preeclampsia and Future Cardiovascular Health: A Systematic Review and Meta-Analysis.

PubMed

Wu, Pensée; Haththotuwa, Randula; Kwok, Chun Shing; Babu, Aswin; Kotronias, Rafail A; Rushton, Claire; Zaman, Azfar; Fryer, Anthony A; Kadam, Umesh; Chew-Graham, Carolyn A; Mamas, Mamas A

2017-02-01

Preeclampsia is a pregnancy-specific disorder resulting in hypertension and multiorgan dysfunction. There is growing evidence that these effects persist after pregnancy. We aimed to systematically evaluate and quantify the evidence on the relationship between preeclampsia and the future risk of cardiovascular diseases. We studied the future risk of heart failure, coronary heart disease, composite cardiovascular disease, death because of coronary heart or cardiovascular disease, stroke, and stroke death after preeclampsia. A systematic search of MEDLINE and EMBASE was performed to identify relevant studies. We used random-effects meta-analysis to determine the risk. Twenty-two studies were identified with >6.4 million women including >258 000 women with preeclampsia. Meta-analysis of studies that adjusted for potential confounders demonstrated that preeclampsia was independently associated with an increased risk of future heart failure (risk ratio [RR], 4.19; 95% confidence interval [CI], 2.09-8.38), coronary heart disease (RR, 2.50; 95% CI, 1.43-4.37), cardiovascular disease death (RR, 2.21; 95% CI, 1.83-2.66), and stroke (RR, 1.81; 95% CI, 1.29-2.55). Sensitivity analyses showed that preeclampsia continued to be associated with an increased risk of future coronary heart disease, heart failure, and stroke after adjusting for age (RR, 3.89; 95% CI, 1.83-8.26), body mass index (RR, 3.16; 95% CI, 1.41-7.07), and diabetes mellitus (RR, 4.19; 95% CI, 2.09-8.38). Preeclampsia is associated with a 4-fold increase in future incident heart failure and a 2-fold increased risk in coronary heart disease, stroke, and death because of coronary heart or cardiovascular disease. Our study highlights the importance of lifelong monitoring of cardiovascular risk factors in women with a history of preeclampsia. © 2017 American Heart Association, Inc.

Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.

PubMed

Mistry, Hiten D; Kurlak, Lesia O; Mansour, Yosef T; Zurkinden, Line; Mohaupt, Markus G; Escher, Geneviève

2017-06-01

Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples ( P < 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia ( P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia ( P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Low maternal 25-hydroxyvitamin D concentration increases the risk of severe and mild preeclampsia.

PubMed

Baca, Katharyn M; Simhan, Hyagriv N; Platt, Robert W; Bodnar, Lisa M

2016-12-01

The objective of this case-cohort study was to evaluate the relationship between maternal 25-hydroxyvitamin D (25(OH)D) concentration and preeclampsia overall and by severity. From an eligible cohort of 12,861 women who had serum banked from aneuploidy screening in Pittsburgh, Pennsylvania from 1999 to 2010, we randomly sampled a subcohort of 2327 pregnancies and all remaining preeclampsia cases (n = 650 cases). Preeclampsia (defined as new-onset hypertension and proteinuria) and its mild and severe forms were identified using ICD-9 codes. Maternal serum collected at 20 weeks or less gestation was measured for 25(OH)D. We used log-binomial regression with restricted cubic splines to estimate the association between 25(OH)D and preeclampsia after adjusting for confounders. Approximately 21% of the randomly selected sample had 25(OH)D less than 50 nmol per L. We found that the adjusted risk of preeclampsia declined as serum 25(OH)D increased to 50 nmol per L and then plateaued (test of nonlinearity P < .05). The adjusted preeclampsia risk ratios (95% confidence intervals) for 25(OH)D less than 25 nmol per L, 25 to 49.9 nmol per L, and 50 to 74.9 nmol per L were 2.4 (1.2-4.8), 1.1 (0.69-1.7), and 1.3 (0.89-1.8), respectively, compared with those with 25(OH)D 75 nmol per L and over. Similar associations were observed with severe and mild preeclampsia. Vitamin D deficiency increases risks of severe and mild forms of preeclampsia. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of mineral and vitamin supplements on pregnancy outcome.

PubMed

Hovdenak, Nils; Haram, Kjell

2012-10-01

The literature was searched for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcome. Maternal iron (Fe) deficiency has a direct impact on neonatal Fe stores and birth weight, and may cause cognitive and behavioural problems in childhood. Fe supplementation is recommended to low-income pregnant women, to pregnant women in developing countries, and in documented deficiency, but overtreatment should be avoided. Calcium (Ca) deficiency is associated with pre-eclampsia and intra-uterine growth restriction. Supplementation may reduce both the risk of low birth weight and the severity of pre-eclampsia. Gestational magnesium (Mg) deficiency may cause hematological and teratogenic damage. A Cochrane review showed a significant low birth weight risk reduction in Mg supplemented individuals. Intake of cereal-based diets rich in phytate, high intakes of supplemental Fe, or any gastrointestinal disease, may interfere with zinc (Zn) absorption. Zn deficiency in pregnant animals may limit fetal growth. Supplemental Zn may be prudent for women with poor gastrointestinal function, and in Zn deficient women, increasing birth weight and head circumference, but no evidence was found for beneficial effects of general Zn supplementation during pregnancy. Selenium (Se) is an antioxidant supporting humoral and cell-mediated immunity. Low Se status is associated with recurrent abortion, pre-eclampsia and IUGR, and although beneficial effects are suggested there is no evidence-based recommendation for supplementation. An average of 20-30% of pregnant women suffer from any vitamin deficiency, and without prophylaxis, about 75% of these would show a deficit of at least one vitamin. Vitamin B6 deficiency is associated with pre-eclampsia, gestational carbohydrate intolerance, hyperemesis gravidarum, and neurologic disease of infants. About 25% of pregnant women in India are folate deficient. Folate deficiency may lead to congenital malformations (neural tube damage, orofacial clefts, cardiac anomalies), anaemia and spontaneous abortions, and pre-eclampsia, IUGR and abruption placentae. Pregestational supplementation of folate prevents neural tube defects. A daily supplemental dose of 400 μg/day of folate is recommended when planning pregnancy. In developing countries diets are generally low in animal products and consequently in vitamin B12 content. An insufficient supply may cause reduced fetal growth. In vegetarian women, supplementation of vitamin B12 may be needed. Vitamin A deficiency is prevalent in the developing world, impairing Fe status and resistance to infections. The recommended upper limit for retinol supplements is 3000 IU/day. Vitamin A supplementation enhances birth weight and growth in infants born to HIV-infected women. Overdosing should be avoided. Low concentrations of vitamin C seem to increase the development of pre-eclampsia, and supplementation may be beneficial. Supplementation with vitamin D in the third trimester in vitamin D deficient women seems to be beneficial. The use of vitamins E, although generally considered "healthy", may be harmful to the pregnancy outcome by disrupting a physiologic oxidative gestational state and is consequently not recommended to prevent pre-eclampsia. Further studies on specific substances are needed as the basis for stratified, placebo-controlled analyses. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in coastal Bangladesh: a case-control study.

PubMed

Khan, Aneire Ehmar; Scheelbeek, Pauline Franka Denise; Shilpi, Asma Begum; Chan, Queenie; Mojumder, Sontosh Kumar; Rahman, Atiq; Haines, Andy; Vineis, Paolo

2014-01-01

Hypertensive disorders in pregnancy are among the leading causes of maternal and perinatal death in low-income countries, but the aetiology remains unclear. We investigated the relationship between salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in a coastal community. A population-based case-control study was conducted in Dacope, Bangladesh among 202 pregnant women with (pre)eclampsia or gestational hypertension, enrolled from the community served by the Upazilla Health Complex, Dacope and 1,006 matched controls from the same area. Epidemiological and clinical data were obtained from all participants. Urinary sodium and sodium levels in drinking water were measured. Logistic regression was used to calculate odds ratios, and 95% confidence intervals. Drinking water sources had exceptionally high sodium levels (mean 516.6 mg/L, S.D 524.2). Women consuming tube-well (groundwater) were at a higher disease risk than rainwater users (p<0.001). Adjusted risks for (pre)eclampsia and gestational hypertension considered together increased in a dose-response manner for increasing sodium concentrations (300.01-600 mg/L, 600.1-900 mg/L, >900.01 mg/L, compared to <300 mg/L) in drinking water (ORs 3.30 [95% CI 2.00-5.51], 4.40 [2.70-7.25] and 5.48 [3.30-9.11] (p-trend<0.001). Significant associations were seen for both (pre)eclampsia and gestational hypertension separately. Salinity in drinking water is associated with increased risk of (pre)eclampsia and gestational hypertension in this population. Given that coastal populations in countries such as Bangladesh are confronted with high salinity exposure, which is predicted to further increase as a result of sea level rise and other environmental influences, it is imperative to develop and evaluate affordable approaches to providing water with low salt content.

Salinity in Drinking Water and the Risk of (Pre)Eclampsia and Gestational Hypertension in Coastal Bangladesh: A Case-Control Study

PubMed Central

Khan, Aneire Ehmar; Scheelbeek, Pauline Franka Denise; Shilpi, Asma Begum; Chan, Queenie; Mojumder, Sontosh Kumar; Rahman, Atiq; Haines, Andy; Vineis, Paolo

2014-01-01

Background Hypertensive disorders in pregnancy are among the leading causes of maternal and perinatal death in low-income countries, but the aetiology remains unclear. We investigated the relationship between salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in a coastal community. Methods A population-based case-control study was conducted in Dacope, Bangladesh among 202 pregnant women with (pre)eclampsia or gestational hypertension, enrolled from the community served by the Upazilla Health Complex, Dacope and 1,006 matched controls from the same area. Epidemiological and clinical data were obtained from all participants. Urinary sodium and sodium levels in drinking water were measured. Logistic regression was used to calculate odds ratios, and 95% confidence intervals. Findings Drinking water sources had exceptionally high sodium levels (mean 516.6 mg/L, S.D 524.2). Women consuming tube-well (groundwater) were at a higher disease risk than rainwater users (p<0.001). Adjusted risks for (pre)eclampsia and gestational hypertension considered together increased in a dose-response manner for increasing sodium concentrations (300.01–600 mg/L, 600.1–900 mg/L, >900.01 mg/L, compared to <300 mg/L) in drinking water (ORs 3.30 [95% CI 2.00–5.51], 4.40 [2.70–7.25] and 5.48 [3.30–9.11] (p-trend<0.001). Significant associations were seen for both (pre)eclampsia and gestational hypertension separately. Interpretation Salinity in drinking water is associated with increased risk of (pre)eclampsia and gestational hypertension in this population. Given that coastal populations in countries such as Bangladesh are confronted with high salinity exposure, which is predicted to further increase as a result of sea level rise and other environmental influences, it is imperative to develop and evaluate affordable approaches to providing water with low salt content. PMID:25268785

Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia.

PubMed

Zhang, Qiong; Huang, Yinping; Zhang, Keke; Huang, Yanjun; Yan, Yan; Wang, Fan; Wu, Jie; Wang, Xiao; Xu, Zhangye; Chen, Yongtao; Cheng, Xue; Li, Yong; Jiao, Jinyu; Ye, Duyun

2016-11-01

With increased industrial development, cadmium is an increasingly important environmental pollutant. Studies have identified various adverse effects of cadmium on human beings. However, the relationships between cadmium pollution and the pathogenesis of preeclampsia remain elusive. The objective of this study is to explore the effects of cadmium on immune system among preeclamptic patients and rats. The results showed that the cadmium levels in the peripheral blood of preeclamptic patients were significantly higher than those observed in normal pregnancy. Based on it, a novel rat model of preeclampsia was established by the intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg body weight) on gestational days 9-14. Key features of preeclampsia, including hypertension, proteinuria, placental abnormalities and small foetal size, appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies (AT1-AA), by increasing the expression of activation-induced cytosine deaminase (AID) in B cells. AID is critical for the maturation of antibody and autoantibody responses. In addition, angiotensin II type 1-receptor-agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, was responsible for the deposition of complement component 5 (C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R) activation. C5a is a fragment of C5 that is released during C5 activation. Selectively interfering with C5a signalling by a complement C5a receptor-specific antagonist significantly attenuated hypertension and proteinuria in Cd-injected pregnant rats. Our results suggest that cadmium induces immune abnormalities that may be a key pathogenic contributor to preeclampsia and provide new insights into treatment strategies of preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal serum anti-Müllerian hormone in Sudanese women with preeclampsia.

PubMed

Agabain, Eiman; Mohamed, Hameed; Elsheikh, Anas E; Hamdan, Hamdan Z; Adam, Ishag

2017-06-24

A case-control study was conducted at Omdurman Maternity Tertiary Hospital, Sudan, during the period from May to August 2014 to investigate AMH level in women with preeclampsia compared to healthy controls. The cases were women with preeclampsia and healthy pregnant women were the controls. The obstetrics and medical history was gathered using a questionnaire. AMH level was measured using ELISA. There was no significant difference between the two groups (40 in each arm of the study) in the age, parity and gestational age. Thirty-three of the 40 cases were patients with severe preeclampsia. There was no significant difference in median inter-quartile of the AMH level between the women with preeclampsia and the controls [0.700 (0.225-1.500) vs. 0.700 (0.400-1.275) ng/ml, P = 0.967]. In a linear regression model there was no association between the log of AMH and age, parity, gestational age, BMI, hemoglobin level and preeclampsia.

Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia.

PubMed

McLaughlin, Kelsey; Baczyk, Dora; Potts, Audrey; Hladunewich, Michelle; Parker, John D; Kingdom, John C P

2017-01-01

Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks' gestation underwent baseline cardiovascular assessments. High-risk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. The in vitro endothelial effects of patient serum and exogenous LMWH on human umbilical venous endothelial cells were determined. High-risk women demonstrated a reduced cardiac output, high resistance hemodynamic profile with impaired radial artery flow-mediated dilation compared with controls. LMWH increased flow-mediated dilation in high-risk women 3 hours after randomization compared with baseline and increased plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, and myeloperoxidase. Serum from high-risk women impaired endothelial cell angiogenesis and increased PlGF-1 and PlGF-2 transcription compared with serum from low-risk controls. Coexposure of high-risk serum with LMWH improved the in vitro angiogenic response such that it was equivalent to that of low-risk serum and promoted placental growth factor secretion. LMWH improves maternal endothelial function in pregnant women at high risk of developing preeclampsia, possibly mediated through increased placental growth factor bioavailability. © 2016 American Heart Association, Inc.

Placental invasion, preeclampsia risk and adaptive molecular evolution at the origin of the great apes: evidence from genome-wide analyses.

PubMed

Crosley, E J; Elliot, M G; Christians, J K; Crespi, B J

2013-02-01

Recent evidence from chimpanzees and gorillas has raised doubts that preeclampsia is a uniquely human disease. The deep extravillous trophoblast (EVT) invasion and spiral artery remodeling that characterizes our placenta (and is abnormal in preeclampsia) is shared within great apes, setting Homininae apart from Hylobatidae and Old World Monkeys, which show much shallower trophoblast invasion and limited spiral artery remodeling. We hypothesize that the evolution of a more invasive placenta in the lineage ancestral to the great apes involved positive selection on genes crucial to EVT invasion and spiral artery remodeling. Furthermore, identification of placentally-expressed genes under selection in this lineage may identify novel genes involved in placental development. We tested for positive selection in approximately 18,000 genes using the ratio of non-synonymous to synonymous amino acid substitution for protein-coding DNA. DAVID Bioinformatics Resources identified biological processes enriched in positively selected genes, including processes related to EVT invasion and spiral artery remodeling. Analyses revealed 295 and 264 genes under significant positive selection on the branches ancestral to Hominidae (Human, Chimp, Gorilla, Orangutan) and Homininae (Human, Chimp, Gorilla), respectively. Gene ontology analysis of these gene sets demonstrated significant enrichments for several functional gene clusters relevant to preeclampsia risk, and sets of placentally-expressed genes that have been linked with preeclampsia and/or trophoblast invasion in other studies. Our study represents a novel approach to the identification of candidate genes and amino acid residues involved in placental pathologies by implicating them in the evolution of highly-invasive placenta. Copyright © 2012 Elsevier Ltd. All rights reserved.

Preeclampsia

PubMed Central

Lee, Soo Bong; Wong, Amy P.; Kanasaki, Keizo; Xu, Yong; Shenoy, Vivek K.; McElrath, Thomas F.; Whitesides, George M.; Kalluri, Raghu

2010-01-01

Inadequate invasion of the uterus by cytotrophoblasts is speculated to result in pregnancy-induced disorders such as preeclampsia. However, the molecular mechanisms that govern appropriate invasion of cytotrophoblasts are unknown. Here, we demonstrate that under low-oxygen conditions (2.5% oxygen), 2-methoxyestradiol (2-ME), which is a metabolite of estradiol and is generated by catechol-o-methyltransferase (COMT), induces invasion of cytotrophoblasts into a naturally-derived, extracellular matrix. Neither low-oxygen conditions nor 2-ME alone induces the invasion of cytotrophoblasts in this system; however, low-oxygen conditions combined with 2-ME result in the appropriate invasion of cytotrophoblasts into the extracellular matrix. Cytotrophoblast invasion under these conditions is also associated with a decrease in the expression of hypoxia-inducible factor-1α (HIF-1α), transforming growth factor-β3 (TGF-β3), and tissue inhibitor of metalloproteinases-2 (TIMP-2). Pregnant COMT-deficient mice with hypoxic placentas and preeclampsia-like features demonstrate an up-regulation of HIF-1α, TGF-β3, and TIMP-2 when compared with wild-type mice; normal levels are restored on administration of 2-ME, which also results in the resolution of preeclampsia-like features in these mice. Indeed, placentas from patients with preeclampsia reveal lower levels of COMT and higher levels of HIF-1α, TGF-β3, and TIMP-2 when compared with those from normal pregnant women. We demonstrate that low-oxygen conditions of the placenta are a critical co-stimulator along with 2-ME for the proper invasion of cytotrophoblasts to facilitate appropriate vascular development and oxygenation during pregnancy. PMID:20075204

Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals

PubMed Central

Elliot, Michael G.; Crespi, Bernard J.

2015-01-01

The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification. PMID:25602073

Placental ischemia-induced increases in brain water content and cerebrovascular permeability: role of TNF-α

PubMed Central

Warrington, Junie P.; Drummond, Heather A.; Granger, Joey P.

2015-01-01

Cerebrovascular complications and increased risk of encephalopathies are characteristic of preeclampsia and contribute to 40% of preeclampsia/eclampsia-related deaths. Circulating tumor necrosis factor-α (TNF-α) is elevated in preeclamptic women, and infusion of TNF-α into pregnant rats mimics characteristics of preeclampsia. While this suggests that TNF-α has a mechanistic role to promote preeclampsia, the impact of TNF-α on the cerebral vasculature during pregnancy remains unclear. We tested the hypothesis that TNF-α contributes to cerebrovascular abnormalities during placental ischemia by first infusing TNF-α in pregnant rats (200 ng/day ip, from gestational day 14 to 19) at levels to mimic those reported in preeclamptic women. TNF-α increased mean arterial pressure (MAP, P < 0.05) and brain water content in the anterior cerebrum (P < 0.05); however, TNF-α infusion had no effect on blood-brain barrier (BBB) permeability in the anterior cerebrum or posterior cerebrum. We then assessed the role of endogenous TNF-α in mediating these abnormalities in a model of placental ischemia induced by reducing uterine perfusion pressure followed by treatment with the soluble TNF-α receptor (etanercept, 0.8 mg/kg sc) on gestational day 18. Etanercept reduced placental ischemia-mediated increases in MAP, anterior brain water content (P < 0.05), and BBB permeability (202 ± 44% in placental ischemic rats to 101 ± 28% of normal pregnant rats). Our results indicate that TNF-α mechanistically contributes to cerebral edema by increasing BBB permeability and is an underlying factor in the development of cerebrovascular abnormalities associated with preeclampsia complicated by placental ischemia. PMID:26400187

Heart Disease, Hypertension, Gestational Diabetes Mellitus, and Preeclampsia/Eclampsia in Mothers With Juvenile Arthritis: A Nested Case-Control Study.

PubMed

Feldman, Debbie E; Vinet, Évelyne; Bérard, Anick; Duffy, Ciarán; Hazel, Beth; Meshefedjian, Garbis; Sylvestre, Marie-Pierre; Bernatsky, Sasha

2017-02-01

To determine whether women with a history of juvenile arthritis are at higher risk for heart disease and hypertension and for developing adverse maternal outcomes: gestational diabetes mellitus, maternal hypertension, and preeclampsia/eclampsia. We designed a nested case-control study from a cohort of first-time mothers with prior physician billing codes suggesting juvenile arthritis, and a matched comparison group without juvenile arthritis. For the nested case-control design, we selected 3 controls for each case for the outcomes of heart disease (n = 403), prepregnancy hypertension (n = 66), gestational diabetes mellitus (n = 285), maternal hypertension (n = 561), and preeclampsia/eclampsia (n = 236). We used conditional logistic regression, adjusting for maternal age and education. Having juvenile arthritis was associated with heart disease (odds ratio [OR] 2.44 [95% confidence interval (95% CI) 1.15-5.15]) but not with gestational hypertension, diabetes mellitus, or preeclampsia/eclampsia. All 66 cases of prepregnancy hypertension had juvenile arthritis. Having prepregnancy hypertension was strongly associated with preeclampsia/eclampsia (OR 8.05 [95% CI 2.69-24.07]). Women with a history of juvenile arthritis had a higher risk of heart disease. This risk signals the potential importance of cardiac prevention strategies in juvenile arthritis. As this was a retrospective study, it was not possible to correct for some relevant potential confounders. Further studies should assess the impact of medications, disease severity, and other factors (e.g., obesity) on cardiac outcomes in juvenile arthritis. © 2016, American College of Rheumatology.

Recreational physical activity during pregnancy and risk of preeclampsia.

PubMed

Sorensen, Tanya K; Williams, Michelle A; Lee, I-Min; Dashow, Edward E; Thompson, Mary Lou; Luthy, David A

2003-06-01

The potential benefits and risks of physical activity before and during pregnancy are not well studied. We studied the relation between recreational physical activity and the risk of preeclampsia in a case-control study of 201 preeclamptic and 383 normotensive pregnant women. Participants provided information about the type, intensity, frequency, and duration of physical activity performed during the first 20 weeks of pregnancy and during the year before pregnancy. Women who engaged in any regular physical activity during early pregnancy, compared with inactive women, experienced a 35% reduced risk of preeclampsia (odds ratio, 0.65; 95% confidence interval [CI], 0.43 to 0.99). Compared with inactive women, those engaged in light or moderate activities (ie, activities with metabolic-equivalent scores <6) experienced a 24% reduced risk of preeclampsia (95% CI, 0.48 to 1.20). The corresponding reduction for women participating in vigorous activities (metabolic equivalent scores > or =6) was 54% (95% CI, 0.27 to 0.79). Brisk walking (average walking pace > or =3 mi/h), when compared with no walking at all, was associated with a 30% to 33% reduction in preeclampsia risk. Stair climbing was inversely associated with the risk of preeclampsia (P for trend=0.039). Recreational physical activity performed during the year before pregnancy was associated with similar reductions in preeclampsia risk. These data suggest that regular physical activity, particularly when performed during the year before pregnancy and during early pregnancy, is associated with a reduced risk of preeclampsia.

Urinary spot albumin:creatinine ratio for documenting proteinuria in women with preeclampsia.

PubMed

Huang, Qitao; Gao, Yunfei; Yu, Yanhong; Wang, Wei; Wang, Shuoshi; Zhong, Mei

2012-01-01

To assess whether a single urinary spot urinary albumin:creatinine ratio (ACR) can be used to estimate 24-hour urinary protein excretion in women with preeclampsia. ACR and 24-hour urinary protein excretion were measured in 50 consecutive patients with preeclampsia. ACR was determined in a spot midstream urine sample and the amount of protein excretion was quantified in a 24-hour urine collection performed the following day. The correlation between the spot ACR and 24-hour urine protein excretion was assessed, and the diagnostic value of ACR was expressed in terms of specificity and sensitivity. Receiver operating characteristic curve analysis was used to determine the best cutoff values of the spot ACR for mild preeclampsia (proteinuria ≥ 0.3 g/24 h) and severe preeclampsia (defined in China as proteinuria ≥ 2 g/24 h). A strong correlation was evident between the spot ACR and 24-hour urinary protein excretion (r = .938; P < .001). The optimal spot ACR cutoff point was 22.8 mg/mmol for 0.3 g/24 h of protein excretion (mild preeclampsia) with a sensitivity and specificity of 82.4% and 99.4%, respectively, and 155.6 mg/mmol for 2 g/24 h of protein excretion (severe preeclampsia) with a sensitivity and specificity of 90.6% and 99.6%, respectively. Compared with 24-hour urinary protein excretion, the spot urinary ACR may be a simple, convenient, and accurate indicator of significant proteinuria in women with preeclampsia.

Fetal tissue Doppler imaging in pregnancies complicated with preeclampsia with or without intrauterine growth restriction.

PubMed

Zhou, Qiongjie; Ren, Yunyun; Yan, Yingliu; Chu, Chen; Gui, Yonghao; Li, Xiaotian

2012-11-01

This study's aim was to evaluate the effect of preeclampsia and intrauterine growth restriction (IUGR) on fetal cardiac function, and the relationship of the latter with adverse pregnancy outcomes. We did a cross-sectional study of 132 women with uncomplicated singleton pregnancies, 34 with preeclampsia without IUGR, and 12 with preeclampsia and IUGR. Fetal cardiac structure and function were evaluated using fetal two-dimension ultrasound, pulsed wave Doppler and tissue Doppler imaging (TDI). Data were analyzed by t-tests, ANOVA, Chi-square tests, or Wilcoxon rank-sum test. Compared with the normal pregnancy group, mitral/tricuspid early systolic peak velocity of annulus/late diastolic peak velocity of annulus (Sa) and left ventricular (LV)/right ventricular (RV) early diastolic peak velocity at the annulus (Ea) in TDI decreased in preeclampsia with or without IUGR (P < 0.05). LV/RV Ea underwent a gestational decrease in preeclampsia with or without IUGR (P < 0.05). The changes in mitral/tricuspid Sa and LV Sa associated with preeclampsia were even more pronounced with preterm delivery at less than 34 gestational weeks and stillbirth (P < 0.05). Intrauterine growth restriction influences fetal cardiac function in the presence of preeclampsia, and TDI may be a sensitive and preferable method to detect such changes. Fetal LV/RV Ea is a potential marker for early fetal cardiac diastolic impairment, and mitral/tricuspid Sa and LV Sa may be predictors for adverse pregnancy outcomes. © 2012 John Wiley & Sons, Ltd.

Relationship between insulin resistance and tissue blood flow in preeclampsia.

PubMed

Anim-Nyame, Nick; Gamble, John; Sooranna, Suren R; Johnson, Mark R; Steer, Philip J

2015-05-01

Preeclampsia is characterized by generalized endothelial dysfunction and impaired maternal tissue perfusion, and insulin resistance is a prominent feature of this disease. The aim of this study was to test the hypothesis that insulin resistance in preeclampsia is related to the reduced resting tissue blood flow. We used venous occlusion plethysmography to compare the resting calf muscle blood flow (measured as QaU) in 20 nulliparous women with preeclampsia and 20 normal pregnant controls matched for maternal age, gestational age, parity and BMI during the third trimester. Fasting blood samples were obtained to measure the plasma concentrations of insulin and glucose, and to calculate the fasting insulin resistance index (FIRI), a measure of insulin resistance in both groups of women. Calf blood flow was significantly reduced in the preeclampsia group (1.93 ± 0.86 QaU), compared with normal pregnant controls (3.94 ± 1.1 QaU, P < 0.001). Fasting insulin concentrations and Insulin Resistance Index were significantly higher in preeclampsia compared with normal pregnancy (P < 0.001 for both variables). There were significant inverse correlations between resting calf blood flow and fasting insulin concentrations (r = -0.57, P = 0.008) and FIRI (r = -0.59, P = 0.006) in preeclampsia, but not in normal pregnancy. These findings support our hypothesis and raise the possibility that reduced tissue blood flow may a play a role in the increased insulin resistance seen in preeclampsia.

Shear wave elastography of placenta: in vivo quantitation of placental elasticity in preeclampsia

PubMed Central

Kılıç, Fahrettin; Kayadibi, Yasemin; Yüksel, Mehmet Aytaç; Adaletli, İbrahim; Ustabaşıoğlu, Fethi Emre; Öncül, Mahmut; Madazlı, Rıza; Yılmaz, Mehmet Halit; Mihmanlı, İsmail; Kantarcı, Fatih

2015-01-01

PURPOSE We aimed to evaluate the utility of shear wave elastography (SWE) for assessing the placenta in preeclampsia disease. METHODS A total of 50 pregnant women in the second or third trimester (23 preeclampsia patients and 27 healthy control subjects) were enrolled in the study. Obstetrical grayscale and Doppler ultrasonography, SWE findings of placenta, and prenatal/postnatal clinical data were analyzed and the best SWE cutoff value which represents the diagnosis of preeclampsia was determined. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of preeclampsia were calculated based on SWE measurements. RESULTS Mean stiffness values were much higher in preeclamptic placentas in all regions and layers than in normal controls. The most significant difference was observed in the central placental area facing the fetus where the umbilical cord inserts, with a median of 21 kPa (range, 3–71 kPa) for preeclampsia and 4 kPa (range, 1.5–14 kPa) for the control group (P < 0.01). The SWE data showed a moderate correlation with the uterine artery resistivity and pulsatility indices. The cutoff value maximizing the accuracy of diagnosis was 7.35 kPa (area under curve, 0.895; 95% confidence interval, 0.791–0.998); sensitivity, specificity, PPV, NPV, and accuracy were 90%, 86%, 82%, 92%, and 88%, respectively. CONCLUSION Stiffness of the placenta is significantly higher in patients with preeclampsia. SWE appears to be an assistive diagnostic technique for placenta evaluation in preeclampsia. PMID:25858523

Unmethylated-maspin DNA in maternal plasma is associated with severe preeclampsia.

PubMed

Qi, Yan-Hua; Teng, Fei; Zhou, Qi; Liu, Yu-Xin; Wu, Jin-Fang; Yu, Shan-Shan; Zhang, Xin; Ma, Miao-Yan; Zhou, Ni; Chen, Li-Juan

2015-09-01

Cell-free fetal DNA in maternal plasma is associated with complications of pregnancy, including preeclampsia. Determination of levels is affected by fetal gender and genetic polymorphisms. Unmethylated maspin (u-maspin) is present in the placenta, and is placental-specific. The purpose of this study was to determine whether u-maspin DNA in maternal blood could serve as a marker of preeclampsia by measuring levels in different trimesters of normal pregnancies and in those complicated by preeclampsia. This case-control study was set in a tertiary care hospital. The population consisted of 45 women with normal pregnancies (15 in the 1st trimester, 15 in the 2nd trimester, 15 in the 3rd trimester), 20 women with mild preeclampsia, 25 women with severe preeclampsia, and six women with gestational trophoblastic disease. Peripheral blood was collected and methylation-specific PCR and fluorescence quantitative PCR were performed to measure the content of u-maspin DNA in maternal blood. U-maspin DNA was 5.5-fold higher in women with severe preeclampsia than in those with a normal 3rd trimester pregnancy (p < 0.05). During normal pregnancy, u-maspin DNA in maternal plasma tended to increase with advancing gestational age (p = 0.06). U-maspin DNA was not detected in healthy non-pregnant women or those with gestational trophoblastic disease. U-maspin DNA in maternal blood is associated with severe preeclampsia. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Increased prevalence of preeclampsia among women undergoing procedural intervention for renal artery fibromuscular dysplasia.

PubMed

Vance, Chardonnay J; Taylor, Robert N; Craven, Timothy E; Edwards, Matthew S; Corriere, Matthew A

2015-08-01

Renal artery fibromuscular dysplasia (RA-FMD) has a higher prevalence among women and a presumed hormonal etiology. Although preeclampsia has a clinical presentation similar to symptomatic RA-FMD and occurs exclusively in women, associations between these 2 diseases have not been characterized. To explore epidemiologic associations between RA-FMD and preeclampsia, we administered a validated screening instrument for preeclampsia to a cohort of women with a history of pregnancy who had previously been treated with procedural intervention for symptomatic RA stenosis. Women with a history of pregnancy who had previously undergone procedural intervention (including angioplasty and/or bypass) for symptomatic RA stenosis were identified from a prospectively maintained operative registry and screened for remote history of preeclampsia using a validated survey instrument. Univariable associations between RA-FMD and preeclampsia among participants with a history of pregnancy were evaluated using t-tests for continuous factors and chi-squared tests for dichotomous factors. Multivariable associations were evaluated using logistic regression models. A total of 144 women were identified who met the study inclusion criteria, including 94 with atherosclerotic RA stenosis and 50 with RA-FMD. Sixty-nine patients were contacted, 59 consented to participate, and 52 had a history of pregnancy (and therefore were at risk for preeclampsia). Participants completed the survey instrument at a mean of 7.1 ± 3.1 vs. 6.9 ± 3.6 years after RA procedural intervention, respectively. Survey responses indicated a history of preeclampsia in 19/52 (36.5%) of participants overall, including 14/27 (51.9%) with RA-FMD versus 5/20 (20.0%) with RA atherosclerosis (P = 0.02). Preeclampsia remained associated with FMD in a multivariable model adjusting for smoking status, age at time of surgery, and estimated glomerular filtration rate (odds ratio [OR] 9.51, 95% confidence interval [CI] 1.49-60.6, P = 0.017); age at the time of surgery (OR 2.78, 95% CI 1.04-7.42, P = 0.041) and estimated glomerular filtration rate (OR 3.31, 95% CI 1.29-8.52, P = 0.013) were also associated with FMD in the multivariable model. Women with a history of procedural intervention for symptomatic RA stenosis have an overall prevalence of preeclampsia which greatly exceeds that expected in the general population, and our results suggest that preeclampsia is specifically associated with RA-FMD. Further investigation is needed to characterize the mechanistic relationships between FMD and preeclampsia and may have potential to decrease related cardiovascular morbidity and mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

[Assessment of maternal cerebral blood flow in patients with preeclampsia].

PubMed

Mandić, Vesna; Miković, Zeljko; Dukić, Milan; Vasiljević, Mladenko; Filimonović, Dejan; Bogavac, Mirjana

2005-01-01

Systemic vasoconstriction in preeclamptic patients increases vascular resistance, and is manifested by increased arterial blood flow velocity. The aim of the study is to evaluate if there is a change of Doppler indices in maternal medial cerbral artery (MCA) in severe preeclampsia due to: 1) severity of clinical symptoms, 2) the begining of eclamptic attack and 3) the application of anticonvulsive therapy. A prospective clinical study included 92 pregnant women, gestational age 28-36 weeks. They were divided into three groups: normotensive (n=30), mild preeclampsia (n=33), and severe preeclampsia (n=29). We investigated maternal cerebral circulation by assessing the MCA. We registrated: pulsatility index (Pi), resistance index (Ri), systolic/diastolic ratio (S/D), and the maximum systolic, end diastolic and medium velocity. Patients with severe preeclampsia were divided into two subgroups. subgroup 1 included patients without symptoms of threatening eclampsia (n=18; 62.06%); while subgroup 2 included those with symptoms of preeclampsia (n=11; 37.94%). All patients with severe preeclampsia were treated with magnesium sulfate (MgSO4), and cerebral blood flow was measured before and after the treatment. Statistical analysis was done by oneway ANOVA, Student t-test and t-paired sample test. The difference was considered to be significant if p<0.05. Significantly increased Pi, Ri and all velocities were established in the group of patients with severe preeclampsia compared with the other two groups. In the group with severe preeclamsia we registrated significantly increased values of all velocities (patients with signs of threatening eclampsia). After MgSO4 treatment in patients with severe preeclampsia significantly decreased values of Pi, Ri, S/D ratio and all velocities were registered. In the studied group of patients with severe preclampsia we found increased velocity values, Pi and Ri, especially in patients with signs of threatened eclampsia, suggesting that blood vessels changes are most prominent in severe preeclampsia. Cerebral blood flow meassurements can be used as a clinical test for the prediction of eclampsia. Magnesium-sulfate (MgSO4) has a signifficant role in prophylaxis and treatment of eclampsia, and, therefore, positive influence on reduction of cerebral ishemic lesions can be expected. We can conclude that changes of the cerebral blood flow can be evaluated by evaluating blood flow velocities in the medial cerebral artery. Velocities tend to increase in severe preeclampsia, especially with signs of threatening eclampsia, and decrease after treatment with mgnesium sulfate. Serial measurements of blood flow in medial cerebral artery in patients with severe preeclampsia may be used in prediction of eclampsia and in evaluation of magnesium sulfate therapy effects.

Using the angiogenic factors sFlt-1 and PlGF with Doppler ultrasound of the uterine artery for confirming preeclampsia.

PubMed

Bahlmann, Franz; Al Naimi, Ammar

2016-11-01

The aim of this study is to assess the value of the angiogenic factors for diagnosing preeclampsia and predicting the severity of manifestation. A secondary aim is assessing the combination of the uterine artery Doppler with the angiogenic factors for improving the diagnostic power. This is a prospective single center study in a tertiary referral hospital. This study includes 728 individual patients. Inclusion criteria were singleton pregnancies, a referral to the hospital with suspicion of preeclampsia and any one or combination of the following symptoms: headache, upper abdominal pain, edema, and hypertension. Patients with complications that would affect the course of the pregnancy, such as placenta praevia, premature preterm rupture of membranes, breech presentation, and fetal chromosomal or structural anomalies, were excluded from the study. Blood samples collection and uterine artery Doppler ultrasound were performed at time of recruitment. The differences in sFlt-1, PlGF, and their quotient among normal collective and patients with preeclampsia were analyzed. Doppler ultrasound was performed by one of four highly qualified sonographers. Wilcoxon-Mann-Whitney U test, Spearman's rank correlation, receiver operating characteristic curves, Chi-square test, and logistic regression were used in the analysis. A total of 1003 individual samples for the angiogenic factors were included in the analysis. 584 out of the recruited 728 patients had follow-up data with delivery information at the study hospital. Patients with preeclampsia show a significant increase in sFlt-1, which directly correlate with the increased severity of manifestation (Spearman's ρ 0.49). The sFlt-1 cut-off value of 5424 pg/ml confirms preeclampsia with 83.7 % sensitivity, 68.1 % specificity, and 24 % misclassification rate. Preeclampsia patients also show a significant decrease in PlGF, which negatively correlates with the increased severity of manifestation (Spearman's ρ -0.39). A PlGF cut-off value of 118 pg/ml confirms preeclampsia with 47.6 % sensitivity, 71.4 % specificity, and 27 % misclassification rate. Logistic regression shows that a combination of the quotient from sFlt-1/PlGF with notching and uterine artery PI provides a valid model for diagnosing preeclampsia with a diagnostic power of 74.4 %. The study confirms the use of the sFlt-1 and PlGF for diagnosing preeclampsia. It also shows their significance in differentiating between different categories of preeclampsia according to severity. This study shows that the use of angiogenic factors in combination with ultrasound findings provides valid models for confirming preeclampsia.

G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention.

PubMed

Conrad, Kirk P

2016-09-01

Important roles for G-protein-coupled receptors (GPCRs) have been identified in the maternal physiological adaptations to pregnancy and in the pathogenesis of preeclampsia. On this basis, GPCRs are potential therapeutic targets for preeclampsia. In this review, vasopressin and apelin are initially considered in this context before the focus on the hormone relaxin and its cognate receptor, the relaxin/insulin-like family peptide receptor 1 (RXFP1). Based on both compelling scientific rationale and a promising safety profile, the relaxin ligand-receptor system is comprehensively evaluated as a potential therapeutic endpoint in preeclampsia. The published literature relating to the topic was searched through January 2016 using PubMed. Relaxin is a peptide hormone secreted by the corpus luteum; it circulates in the luteal phase and during pregnancy. Activation of RXFP1 is vasodilatory; thus, relaxin supplementation is expected to at least partly restore the fundamental vasodilatory changes of normal pregnancy, thereby alleviating maternal organ hypoperfusion, which is a major pathogenic manifestation of severe preeclampsia. Specifically, by exploiting its pleiotropic hemodynamic attributes in preeclampsia, relaxin administration is predicted to (i) reverse robust arterial myogenic constriction; (ii) blunt systemic and renal vasoconstriction in response to activation of the angiotensin II receptor, type 1; (iii) mollify the action of endogenous vasoconstrictors on uterine spiral arteries with failed remodeling and retained smooth muscle; (iv) increase arterial compliance; (v) enhance insulin-mediated glucose disposal by promoting skeletal muscle vasodilation and (vi) mobilize and activate bone marrow-derived angiogenic progenitor cells, thereby repairing injured endothelium and improving maternal vascularity in organs such as breast, uterus, pancreas, skin and fat. By exploiting its pleiotropic molecular attributes in preeclampsia, relaxin supplementation is expected to (i) enhance endothelial nitric oxide synthesis and bioactivity, as well as directly reduce vascular smooth muscle cytosolic calcium, thus promoting vasodilation; (ii) improve the local angiogenic balance by augmenting arterial vascular endothelial and placental growth factor (VEGF and PLGF) activities; (iii) ameliorate vascular inflammation; (iv) enhance placental peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PCG1α) expression, and hence, peroxisome proliferator-activated receptor gamma (PPAR-γ) activity and (v) confer cytotrophoblast and endothelial cytoprotection. Insofar as impaired endometrial maturation (decidualization) predisposes to the development of preeclampsia, relaxin administration in the late secretory phase and during early pregnancy would be anticipated to improve decidualization, and hence trophoblast invasion and spiral artery remodeling, thereby reducing the risk of preeclampsia. Relaxin has a favorable safety profile both in the non-pregnant condition and during pregnancy. There is a strong scientific rationale for RXFP1 activation in severe preeclampsia by administration of relaxin, relaxin analogs or small molecule mimetics, in order to mollify the disease pathogenesis for safe prolongation of pregnancy, thus allowing time for more complete fetal maturation, which is a primary therapeutic endpoint in treating the disease. In light of recent data implicating deficient or defective decidualization as a potential etiological factor in preeclampsia and the capacity of relaxin to promote endometrial maturation, the prophylactic application of relaxin to reduce the risk of preeclampsia is a plausible therapeutic approach to consider. Finally, given its pleiotropic and beneficial attributes particularly in the cardiovascular system, relaxin, although traditionally considered as a 'pregnancy' hormone, is likely to prove salutary for several disease indications in the non-pregnant population. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The incidence of preeclampsia and eclampsia and associated maternal mortality in Australia from population-linked datasets: 2000-2008.

PubMed

Thornton, Charlene; Dahlen, Hannah; Korda, Andrew; Hennessy, Annemarie

2013-06-01

To determine the incidence of preeclampsia and eclampsia and associated mortality in Australia between 2000 and 2008. Analysis of statutorily collected datasets of singleton births in New South Wales using International Classification of Disease coding. Analyzed using cross tabulation, logistic regression, and means testing, where appropriate. The overall incidence of preeclampsia was 3.3% with a decrease from 4.6% to 2.3%. The overall rate of eclampsia was 8.6/10,000 births or 2.6% of preeclampsia cases, with an increase from 2.3% to 4.2%. The relative risk of eclampsia in preeclamptic women in 2008 was 1.9 (95% confidence interval, 1.28-2.92) when compared with the year 2000. The relative risk of a woman with preeclampsia/eclampsia dying in the first 12 months following birth compared with normotensive women is 5.1 (95% confidence interval, 3.07-8.60). Falling rates of preeclampsia have not equated to a decline in the incidence of eclampsia. An accurate rate of both preeclampsia and eclampsia is vital considering the considerable contribution that these diseases make to maternal mortality. The identification and treatment of eclampsia should remain a priority in the clinical setting. Copyright © 2013 Mosby, Inc. All rights reserved.

Induced Abortions and the Risk of Preeclampsia Among Nulliparous Women

PubMed Central

Parker, Samantha E.; Gissler, Mika; Ananth, Cande V.; Werler, Martha M.

2015-01-01

Induced abortion (IA) has been associated with a lower risk of preeclampsia among nulliparous women, but it remains unclear whether this association differs by method (either surgical or medical) or timing of IA. We performed a nested case-control study of 12,650 preeclampsia cases and 50,600 matched control deliveries identified in the Medical Birth Register of Finland from 1996 to 2010. Data on number, method, and timing of IAs were obtained through a linkage with the Registry of Induced Abortions. Odds ratios and 95% confidence intervals were calculated. Overall, prior IA was associated with a lower risk of preeclampsia, with odds ratios of 0.9 (95% confidence interval (CI): 0.9, 1.0) for 1 prior IA and 0.7 (95% CI: 0.5, 1.0) for 3 or more IAs. Differences in the associations between IA and preeclampsia by timing and method of IA were small, with odds ratios of 0.8 (95% CI: 0.6, 1.1) for late (≥12 gestation weeks) surgical abortion and 0.9 (95% CI: 0.7, 1.2) for late medical abortion. There was no association between IA in combination with a history of spontaneous abortion and risk of preeclampsia. In conclusion, prior IA only was associated with a slight reduction in the risk of preeclampsia. PMID:26377957

Relationship of neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin levels with the presence and severity of the preeclampsia.

PubMed

Artunc-Ulkumen, Burcu; Guvenc, Yesim; Goker, Asli; Gozukara, Ceyhun

2015-11-01

The aim of the present study was to evaluate changes in maternal serum neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin (PCT) concentrations in preeclampsia. This case-control study consisted of 40 preeclamptic and 40 healthy singleton pregnancies matched for age and body mass index. Serum NGAL and PCT levels were compared between the groups. Diagnostic performance and clinical association of these markers were evaluated. NGAL and PCT concentrations were significantly higher in preeclamptic group (p < 0.0001 and p = 0.001, respectively) and their levels were correlated with the severity of the preeclampsia. There were significant positive correlation between these markers and mean arterial pressure (MAP) and spot urine protein excretion. There was negative correlation between NGAL and apgar scores and fetal birth weight. Pregnancies with higher NGAL (OR: 4.89; 95% CI: 1.81-13.21) and higher PCT (OR: 6.67; 95% CI: 2.44-18.21) concentrations had higher risk for preeclampsia. NGAL and PCT may be potential biomarkers for preeclampsia. Their levels increase significantly in preeclampsia and they are related to the severity of the disease. These results are in agreement with the generalized endothelial damage and persistant inflammatory status in preeclampsia. NGAL may also be an indicator for adverse neonatal outcomes with decreased placental hypoperfusion.

Synthesis of sFlt-1 by platelet-monocyte aggregates contributes to the pathogenesis of preeclampsia

PubMed Central

Major, Heather D.; Cambell, Robert A.; Silver, Robert M.; Branch, D. Ware; Weyrich, Andrew S.

2014-01-01

Objective Soluble fms-like tyrosine kinase (sFlt-1) is an important mediator in the pathogenesis of preeclampsia. We sought to determine if platelet-monocyte aggregates (PMAs) produced sFlt-1 and if PMAs contributed to sFlt-1 production in preeclampsia. Study Design Case-control study of sFlt-1 release from PMAs using blood samples from women with preeclampsia matched by gestational age to pregnant controls. A third group of nonpregnant, reproductive-age women comprised an additional control group. Experiments were also performed using blood from non-pregnant women to elucidate if inducing PMAs could stimulate sFlt-1 production, and if so, to determine the necessary receptors and pathways. Results Women with preeclampsia had increased total Flt-1 concentrations in platelets and monocytes at baseline compared to pregnant controls (25 vs. 10 pg/ml, p=0.0003). sFlt-1 production was elicited from monocytes incubated with thrombin-activated platelets from non-pregnant women. sFlt-1 production was regulated at the transcriptional level by p38 and NF-κB dependent pathways. Conclusion Activated platelets in preeclampsia bind monocytes to generate sFlt-1. PMAs are a previously unrecognized source of sFlt-1 that may contribute to endothelial dysfunction and systemic inflammation commonly observed in preeclampsia. PMID:24440566

Contribution of genome-environment interaction to pre-eclampsia in a Havana Maternity Hospital.

PubMed

Lardoeyt, Roberto; Vargas, Gerardo; Lumpuy, Jairo; García, Ramón; Torres, Yuselis

2013-07-01

Pre-eclampsia is a major cause of morbidity and mortality during pregnancy worldwide and is among the leading causes of maternal mortality in Cuba. It is a complex, multifactoral disease, in which interaction of genetic and environmental factors should not be overlooked if the goal is proper risk assessment to support personalized preventive genetic counseling and more effective prenatal care to prevent pregnancy complications. Determine the contribution to pre-eclampsia of interaction between a predisposing genome and adverse environmental factors in pregnant women in a Havana maternity hospital. This was the exploratory phase of a hospital-based case-control study, using January 2007-December 2009 patient records from the Eusebio Hernández University Hospital, a provincial maternity hospital in Havana. Eighty pregnant women diagnosed with pre-eclampsia and 160 controls were studied. The main variables were age, parity, nutritional status (measured by BMI), alcohol use, tobacco use, and history of pre-eclampsia in relatives of the pregnant woman (proband) or of her partner. Pearson chi square and Fisher exact test were used to assess statistical significance of associations between variables and odds ratio as a measure of association strength. Familial aggregation was studied and a case-control design used to assess gene-environment interaction, using multiplicative and additive models. Among the environmental risk factors studied, alcohol showed the strongest effect on pre-eclampsia risk (OR 3.87, 95% CI 1.64-9.13). Familial pre-eclampsia clustering was observed; risk was increased for both first-degree (OR 2.43, 95% CI 1.62-3.73) and second-degree (OR 1.89, 95% CI 1.34-2.68) relatives as well as for husband's relatives (OR 2.32, 95% CI 1.40-3.86). There was evidence of interaction between alcohol consumption and family history. Familial aggregation of the disorder was demonstrated, the first Cuban epidemiological evidence of genetic and enviromental contributions to pre-eclampsia risk. Familial clustering among the husband's relatives demonstrates the fetal genome's importance in genesis of pre-eclampsia. The interaction of environmental risk factors with genetic ones produces increased pre-eclampsia risk, compared to expectations based on independent action of these variables. KEYWORDS Pre-eclampsia, toxemia of pregnancy, pregnancy outcome, environment, genetics, genome-environment interaction, genetic epidemiology, Cuba.

Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease

PubMed Central

Zhang, Yi; Fei, Mingyu; Xue, Geng; Zhou, Qi; Jia, Yin; Li, Li; Xin, Hong; Sun, Shuhan

2012-01-01

Abstract Pre-eclampsia is a leading cause of maternal and foetal morbidity and mortality worldwide. Insufficient uteroplacental oxygenation is believed to be responsible for the disease. However, what molecular events involve in hypoxic responses and how they affect placental development remain unclear. Recently, miRNAs have emerged as a new class of molecules in response to hypoxia. We show here that the expression of microRNA-210 (mir-210) is up-regulated in patients with pre-eclampsia, as well as in trophoblast cells cultured under hypoxic conditions. Ectopic expression of mir-210 inhibited the migration and invasion capability of trophoblast cells. Ephrin-A3 and Homeobox-A9, which related with cell migration and vascular remodelling, were then experimentally validated as the functional targets of mir-210 both in vivo and in vitro. Using luciferase reporter, chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) experiments, we finally identified a new transcriptional mechanism that the overexpression of mir-210 under hypoxia was regulated by NF-κB transcriptional factor p50, apart from the well-known HIF 1α. Taken together, our study implicates an important role for mir-210 in the molecular mechanism of pre-eclampsia. PMID:21388517

Endocan, a putative endothelial cell marker, is elevated in preeclampsia, decreased in acute pyelonephritis, and unchanged in other obstetrical syndromes

PubMed Central

Adekola, Henry; Romero, Roberto; Chaemsaithong, Piya; Korzeniewski, Steven J.; Dong, Zhong; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn

2015-01-01

Abstract Objective: Endocan, a dermatan sulphate proteoglycan produced by endothelial cells, is considered a biomarker for endothelial cell activation/dysfunction. Preeclampsia is characterized by systemic vascular inflammation, and endothelial cell activation/dysfunction. Therefore, the objectives of this study were to determine whether: (1) plasma endocan concentrations in preeclampsia differ from those in uncomplicated pregnancies; (2) changes in plasma endocan concentration relate to the severity of preeclampsia, and whether these changes are specific or observed in other obstetrical syndromes such as small-for-gestational age (SGA), fetal death (FD), preterm labor (PTL) or preterm prelabor rupture of membranes (PROM); (3) a correlation exists between plasma concentration of endocan and angiogenic (placental growth factor or PlGF)/anti-angiogenic factors (soluble vascular endothelial growth factor receptor or sVEGFR-1, and soluble endoglin or sEng) among pregnancies complicated by preeclampsia; and (4) plasma endocan concentrations in patients with preeclampsia and acute pyelonephritis (both conditions in which there is endothelial cell activation) differ. Method: This cross-sectional study included the following groups: (1) uncomplicated pregnancy (n = 130); (2) preeclampsia (n = 102); (3) pregnant women without preeclampsia who delivered an SGA neonate (n = 51); (4) FD (n = 49); (5) acute pyelonephritis (AP; n = 35); (6) spontaneous PTL (n = 75); and (7) preterm PROM (n = 64). Plasma endocan concentrations were determined in all groups, and PIGF, sEng and VEGFR-1 plasma concentrations were measured by ELISA in the preeclampsia group. Results: (1) Women with preeclampsia had a significantly higher median plasma endocan concentration than those with uncomplicated pregnancies (p = 0.004); (2) among women with preeclampsia, the median plasma endocan concentration did not differ significantly according to disease severity (p = 0.1), abnormal uterine artery Doppler velocimetry (p = 0.7) or whether diagnosis was made before or after 34 weeks gestational age (p = 0.3); (3) plasma endocan concentration in women with preeclampsia correlated positively with plasma anti-angiogenic factor concentrations [sVEGFR-1: Spearman rho 0.34, p = 0.001 and sEng: Spearman rho 0.30, p = 0.003]; (4) pregnancies complicated by acute pyelonephritis with bacteremia had a lower median plasma endocan concentration than pregnancies complicated by acute pyelonephritis without bacteremia (p = 0.004), as well as uncomplicated pregnancies (p = 0.001); and (5) there was no significant difference in the median plasma endocan concentration between uncomplicated pregnancies and those complicated by FD, delivery of an SGA neonate, PTL or preterm PROM (other members of the “great obstetrical syndromes”; each p > 0.05). Conclusion: Median maternal plasma endocan concentrations were higher preeclampsia and lower in acute pyelonephritis with bacteremia than in uncomplicated pregnancy. No significant difference was observed in the median plasma endocan concentration between other great obstetrical syndromes and uncomplicated pregnancies. The difference in the direction of change of endocan in preeclampsia and acute pyelonephritis with bacteremia may be consistent with the view that both disease entities differ in pathogenic mechanisms, despite their associations with systemic vascular inflammation and endothelial cell activation/dysfunction. PMID:25211383

Association between pre-eclampsia and locally derived traffic-related air pollution: a retrospective cohort study.

PubMed

Pereira, Gavin; Haggar, Fatima; Shand, Antonia W; Bower, Carol; Cook, Angus; Nassar, Natasha

2013-02-01

Pre-eclampsia is a common complication of pregnancy and is a major cause of fetal-maternal mortality and morbidity. Despite a number of plausible mechanisms by which air pollutants might contribute to this process, few studies have investigated the association between pre-eclampsia and traffic emissions, a major contributor to air pollution in urban areas. The authors investigated the association between traffic-related air pollution and risk of pre-eclampsia in a maternal population in the urban centre of Perth, Western Australia. The authors estimated maternal residential exposure to a marker for traffic-related air pollution (nitrogen dioxide, NO(2)) during pregnancy for 23 452 births using temporally adjusted land-use regression. Logistic regression was used to investigate associations with pre-eclampsia. Each IQR increase in levels of traffic-related air pollution in whole pregnancy and third trimester was associated with a 12% (1%-25%) and 30% (7%-58%) increased risk of pre-eclampsia, respectively. The largest effect sizes were observed for women aged younger than 20 years or 40 years or older, aboriginal women and women with pre-existing and gestational diabetes, for whom an IQR increase in traffic-related air pollution in whole pregnancy was associated with a 34% (5%-72%), 35% (0%-82%) and 53% (7%-219%) increase in risk of pre-eclampsia, respectively. Elevated exposure to traffic-related air pollution in pregnancy was associated with increased risk of pre-eclampsia. Effect sizes were highest for elevated exposures in third trimester and among younger and older women, aboriginal women and women with diabetes.

Preconception Cardiovascular Risk Factor Differences Between Gestational Hypertension and Preeclampsia

PubMed Central

Klungsøyr, Kari; Øyen, Nina; Tell, Grethe S.; Næss, Øyvind; Skjærven, Rolv

2016-01-01

Preconception predictors of gestational hypertension and preeclampsia may identify opportunities for early detection and improve our understanding of the pathogenesis and life course epidemiology of these conditions. Female participants in community-based Cohort Norway health surveys, 1994 to 2003, were prospectively followed through 2012 via record linkages to Medical Birth Registry of Norway. Analyses included 13 217 singleton pregnancies (average of 1.59 births to 8321 women) without preexisting hypertension. Outcomes were gestational hypertension without proteinuria (n=237) and preeclampsia (n=429). Mean age (SD) at baseline was 27.9 years (4.5), and median follow-up was 4.8 years (interquartile range 2.6–7.8). Gestational hypertension and preeclampsia shared several baseline risk factors: family history of diabetes mellitus, pregravid diabetes mellitus, a high total cholesterol/high-density lipoprotein cholesterol ratio (>5), overweight and obesity, and elevated blood pressure status. For preeclampsia, a family history of myocardial infarction before 60 years of age and elevated triglyceride levels (≥1.7 mmol/L) also predicted risk while physical activity was protective. Preterm preeclampsia was predicted by past-year binge drinking (≥5 drinks on one occasion) with an adjusted odds ratio of 3.7 (95% confidence interval 1.3–10.8) and by past-year physical activity of ≥3 hours per week with an adjusted odds ratio of 0.5 (95% confidence interval 0.3–0.8). The results suggest similarities and important differences between gestational hypertension, preeclampsia, and preterm preeclampsia. Modifiable risk factors could be targeted for improving pregnancy outcomes and the short- and long-term sequelae for mothers and offspring. PMID:27113053

Blood lead and preeclampsia: A meta-analysis and review of implications.

PubMed

Poropat, Arthur E; Laidlaw, Mark A S; Lanphear, Bruce; Ball, Andrew; Mielke, Howard W

2018-01-01

Multiple cross-sectional studies suggest that there is an association between blood lead and preeclampsia. We performed a systematic review and meta-analysis to summarize information on the association between preeclampsia and lead poisoning. Searches of Medline, Web of Science, Scopus, Pubmed, Science Direct and ProQuest (dissertations and theses) identified 2089 reports, 46 of which were downloaded after reviewing the abstracts, and 11 studies were evaluated as meeting the selection criteria. Evaluation using the ROBINS-I template (Sterne, et al., 2016), indicated moderate risk of bias in all studies. We found that blood lead concentrations were significantly and substantially associated with preeclampsia (k = 12; N = 6069; Cohen's d = 1.26; odds ratio = 9.81; odds ratio LCL = 8.01; odds ratio UCL = 12.02; p = 0.005). Eliminating one study produced a homogeneous meta-analysis and stronger estimates, despite the remaining studies coming from eight separate countries and having countervailing risks of bias. Blood lead concentrations in pregnant women are a major risk factor for preeclampsia, with an increase of 1μg/dL associated with a 1.6% increase in likelihood of preeclampsia, which appears to be the strongest risk factor for preeclampsia yet reported. Pregnant women with historical lead exposure should routinely have blood lead concentrations tested, especially after mid-term. Women with concentrations higher than 5μg/dL should be actively monitored for preeclampsia and be advised to take prophylactic calcium supplementation. All pregnant women should be advised to actively avoid lead exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of Nitric Oxide Synthase and Matrix Metalloprotease Single Nucleotide Polymorphisms with Preeclampsia and Its Complications

PubMed Central

Leonardo, Daniela P.; Albuquerque, Dulcinéia M.; Lanaro, Carolina; Baptista, Letícia C.; Cecatti, José G.; Surita, Fernanda G.; Parpinelli, Mary A.; Costa, Fernando F.; Franco-Penteado, Carla F.; Fertrin, Kleber Y.; Costa, Maria Laura

2015-01-01

Background Preeclampsia is one of the leading causes of maternal and neonatal morbidity and mortality in the world, but its appearance is still unpredictable and its pathophysiology has not been entirely elucidated. Genetic studies have associated single nucleotide polymorphisms in genes encoding nitric oxide synthase and matrix metalloproteases with preeclampsia, but the results are largely inconclusive across different populations. Objectives To investigate the association of single nucleotide polymorphisms (SNPs) in NOS3 (G894T, T-786C, and a variable number of tandem repetitions VNTR in intron 4), MMP2 (C-1306T), and MMP9 (C-1562T) genes with preeclampsia in patients from Southeastern Brazil. Methods This prospective case-control study enrolled 77 women with preeclampsia and 266 control pregnant women. Clinical data were collected to assess risk factors and the presence of severe complications, such as eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Results We found a significant association between the single nucleotide polymorphism NOS3 T-786C and preeclampsia, independently from age, height, weight, or the other SNPs studied, and no association was found with the other polymorphisms. Age and history of preeclampsia were also identified as risk factors. The presence of at least one polymorphic allele for NOS3 T-786C was also associated with the occurrence of eclampsia or HELLP syndrome among preeclamptic women. Conclusions Our data support that the NOS3 T-786C SNP is associated with preeclampsia and the severity of its complications. PMID:26317342

Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study.

PubMed

Nelander, Maria; Weis, Jan; Bergman, Lina; Larsson, Anders; Wikström, Anna-Karin; Wikström, Johan

2017-07-01

Magnesium sulfate (MgSO4) is used as a prophylaxis for eclamptic seizures. The exact mechanism of action is not fully established. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to investigate if cerebral magnesium (Mg2+) levels differ between women with preeclampsia, normal pregnant, and nonpregnant women. This cross-sectional study comprised 28 women with preeclampsia, 30 women with normal pregnancies in corresponding gestational week (range: 23-41 weeks) and 11 nonpregnant healthy controls. All women underwent 31P-MRS from the parieto-occipital region of the brain and were interviewed about cerebral symptoms. Differences between groups were assessed by analysis of variance and Tukey's post-hoc test. Correlations between Mg2+ levels and specific neurological symptoms were estimated with Spearman's rank test. Mean maternal cerebral Mg2+ levels were lower in women with preeclampsia (0.12 mM ± 0.02) compared to normal pregnant controls (0.14 mM ± 0.03) (P = 0.04). Nonpregnant and normal pregnant women did not differ in Mg2+ levels. Among women with preeclampsia, lower Mg2+ levels correlated with presence of visual disturbances (P = 0.04). Plasma levels of Mg2+ did not differ between preeclampsia and normal pregnancy. Women with preeclampsia have reduced cerebral Mg2+ levels, which could explain the potent antiseizure prophylactic properties of MgSO4. Within the preeclampsia group, women with visual disturbances have lower levels of Mg2+ than those without such symptoms. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

[Application of the concetrations ratio of soluble receptor tyrosine kinase type 1, and placental growth factor for short-term prediction and diagnosis of preeclampsia].

PubMed

Bubeníková, Š; Cíchová, A; Roubalová, L; Durdová, V; Vlk, R

Bring a comprehensive overview of the available information about applications of the concetration ratio of soluble receptor tyrosine kinase type 1 (sFlt-1), and placental growth factor for short-term prediction and diagnosis of preeclampsia. Overview study. Department of Midwifery, Faculty of Health Sciences, Olomouc; Department of Clinical Biochemistry, University Hospital Olomouc; Department of Obstetrics and Gynecology, University Hospital Olomouc; Department of Obstetrics and Gynecology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital. Analysis of literary sources and databases Ovid, Medline (2001-2016). Preeclampsia is a multisystem disease with not fully understood etiology. This disease occurs in 2-5% of pregnant women. Preeclampsia is one of the main causes of global maternal and perinatal morbidity and mortality. It manifests itself as a newborn hypertension and proteinuria after 20 weeks of pregnancy in previously normotensive women. The only effective treatment is the delivery of the child. Diagnosis of preeclampsia comprises measuring blood pressure and proteinuria. These indicators have low diagnostic sensitivity and specificity. In preeclampsia, there is a decrease of serum levels of placental growth factor (PlGF). Soluble receptor tyrosine kinase type 1 (sFlt-1) is an antagonist of PlGF. Increased levels of sFlt-1 in proportion to the reduced level of PlGF are associated with an increased risk of preeclampsia. The sFlt-1/PlGF ratio can be a better predictive marker in the diagnosis of pre-eclampsia after 20 weeks of gestation.

Assessment of relationships between novel inflammatory markers and presence and severity of preeclampsia: Epicardial fat thickness, pentraxin-3, and neutrophil-to-lymphocyte ratio.

PubMed

Cakmak, Huseyin Altug; Dincgez Cakmak, Burcu; Abide Yayla, Cigdem; Inci Coskun, Ebru; Erturk, Mehmet; Keles, Ibrahim

2017-08-01

The aim of this study was to evaluate the relation of three new inflammatory markers with presence and severity of preeclampsia and to compare the predictive values of all markers for presence of this setting. In this study, a total of 100 consecutive pregnants with a diagnosis of preeclampsia and 40 healthy pregnants between October 2014 and April 2015 were included. Epicardial fat tissue was calculated by two-dimensional transthoracic echocardiography, and pentraxin-3 and neutrophil-to-lymphocyte ratio were measured by using an enzyme-linked immunosorbent assay method and routine blood count analysis, respectively. Epicardial fat thickness (p < 0.001), pentraxin-3 (p < 0.001), and neutrophil-to-lymphocyte ratio (p < 0.001) were found to be significantly increased in the preeclampsia as compared to the healthy pregnants. Furthermore, epicardial fat thickness (p = 0.002), pentraxin-3 (p < 0.001), and neutrophil-to-lymphocyte ratio (p < 0.001) were significantly elevated in the severe preeclampsia compared to mild preeclampsia. In the multivariate analysis, epicardial fat thickness (p = 0.013), pentraxin-3 (p = 0.04), and neutrophil-to-lymphocyte ratio (p < 0.001) were found as significant independent predictors of presence of preeclampsia after adjusting for other risk factors. Epicardial fat thickness, neutrophil-to-lymphocyte ratio, and pentraxin-3 are important markers that provide an additional information beyond that provided by conventional methods in predicting presence and severity of preeclampsia.

Short-term costs of preeclampsia to the United States health care system.

PubMed

Stevens, Warren; Shih, Tiffany; Incerti, Devin; Ton, Thanh G N; Lee, Henry C; Peneva, Desi; Macones, George A; Sibai, Baha M; Jena, Anupam B

2017-09-01

Preeclampsia is a leading cause of maternal morbidity and mortality and adverse neonatal outcomes. Little is known about the extent of the health and cost burden of preeclampsia in the United States. This study sought to quantify the annual epidemiological and health care cost burden of preeclampsia to both mothers and infants in the United States in 2012. We used epidemiological and econometric methods to assess the annual cost of preeclampsia in the United States using a combination of population-based and administrative data sets: the National Center for Health Statistics Vital Statistics on Births, the California Perinatal Quality Care Collaborative Databases, the US Health Care Cost and Utilization Project database, and a commercial claims data set. Preeclampsia increased the probability of an adverse event from 4.6% to 10.1% for mothers and from 7.8% to 15.4% for infants while lowering gestational age by 1.7 weeks (P < .001). Overall, the total cost burden of preeclampsia during the first 12 months after birth was $1.03 billion for mothers and $1.15 billion for infants. The cost burden per infant is dependent on gestational age, ranging from $150,000 at 26 weeks gestational age to $1311 at 36 weeks gestational age. In 2012, the cost of preeclampsia within the first 12 months of delivery was $2.18 billion in the United States ($1.03 billion for mothers and $1.15 billion for infants), and was disproportionately borne by births of low gestational age. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Pregnancy on the Army Physical Fitness Test

DTIC Science & Technology

2003-05-01

preeclampsia , and premature labor (Lombardi, Wilson, Peniston, 1999). The most relevant finding was that women who exercised during pregnancy retained...preterm labor, pregnancy induced hypertension, preeclampsia , deep vein thrombosis, premature contractions, or intrauterine growth retardation. (Table...fetal distress, low forceps delivery, pregnancy induced hypertension, preeclampsia , nuchal cord, oligohydramnios, hyperemesis, anemia, and

Significantly higher number of fetal cells in the maternal circulation of women with pre-eclampsia.

PubMed

Jansen, M W; Korver-Hakkennes, K; van Leenen, D; Visser, W; in 't Veld, P A; de Groot, C J; Wladimiroff, J W

2001-12-01

Although the pathophysiology of pre-eclampsia is unknown, several studies have indicated that abnormal placentation early in pregnancy might play a key role. It has recently been suggested that this abnormal placentation may result in transfusion of fetal cells (feto-maternal transfusion) in women with pre-eclampsia. In the present study, fetal nucleated red blood cells were isolated from 20 women with pre-eclampsia and 20 controls using a very efficient magnetic activated cell sorting (MACS) protocol. The number of male cells was determined using two-color fluorescence in situ hybridization (FISH) for X and Y chromosomes. Significantly more XY cells could be detected in women with pre-eclampsia (0.61+/-1.2 XY cells/ml blood) compared to women with uncomplicated pregnancies (0.02+/-0.04 XY cells/ml blood) (Mann-Whitney U-test, p<0.001). These results suggest that fetal cell trafficking is enhanced in women with pre-eclampsia, and this finding may contribute to the understanding of the pathophysiology of the disease. Copyright 2001 John Wiley & Sons, Ltd.

Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study

PubMed Central

Ford, Jane B; Algert, Charles S; Antonsen, Sussie; Chalmers, James; Cnattingius, Sven; Gokhale, Manjusha; Kotelchuck, Milton; Melve, Kari K; Langridge, Amanda; Morris, Carole; Morris, Jonathan M; Nassar, Natasha; Norman, Jane E; Norrie, John; Sørensen, Henrik Toft; Walker, Robin; Weir, Christopher J

2011-01-01

Objective The objective of this study was to compare international trends in pre-eclampsia rates and in overall pregnancy hypertension rates (including gestational hypertension, pre-eclampsia and eclampsia). Design Population data (from birth and/or hospital records) on all women giving birth were available from Australia (two states), Canada (Alberta), Denmark, Norway, Scotland, Sweden and the USA (Massachusetts) for a minimum of 6 years from 1997 to 2007. All countries used the 10th revision of the International Classification of Diseases, except Massachusetts which used the 9th revision. There were no major changes to the diagnostic criteria or methods of data collection in any country during the study period. Population characteristics as well as rates of pregnancy hypertension and pre-eclampsia were compared. Results Absolute rates varied across the populations as follows: pregnancy hypertension (3.6% to 9.1%), pre-eclampsia (1.4% to 4.0%) and early-onset pre-eclampsia (0.3% to 0.7%). Pregnancy hypertension and/or pre-eclampsia rates declined over time in most populations. This was unexpected given that factors associated with pregnancy hypertension such as pre-pregnancy obesity and maternal age are generally increasing. However, there was also a downward shift in gestational age with fewer pregnancies reaching 40 weeks. Conclusion The rate of pregnancy hypertension and pre-eclampsia decreased in northern Europe and Australia from 1997 to 2007, but increased in Massachusetts. The use of a different International Classification of Diseases coding version in Massachusetts may contribute to the difference in trend. Elective delivery prior to the due date is the most likely explanation for the decrease observed in Europe and Australia. Also, the use of interventions that reduce the risk of pregnancy hypertension and/or progression to pre-eclampsia (low-dose aspirin, calcium supplementation and early delivery for mild hypertension) may have contributed to the decline. PMID:22021762

Hypoxia-independent upregulation of placental hypoxia inducible factor-1α gene expression contributes to the pathogenesis of preeclampsia.

PubMed

Iriyama, Takayuki; Wang, Wei; Parchim, Nicholas F; Song, Anren; Blackwell, Sean C; Sibai, Baha M; Kellems, Rodney E; Xia, Yang

2015-06-01

Accumulation of hypoxia inducible factor-1α (HIF-1α) is commonly an acute and beneficial response to hypoxia, whereas chronically elevated HIF-1α is associated with multiple disease conditions, including preeclampsia, a serious hypertensive disease of pregnancy. However, the molecular basis underlying the persistent elevation of placental HIF-1α in preeclampsia and its role in the pathogenesis of preeclampsia are poorly understood. Here we report that Hif-1α mRNA and HIF-1α protein were elevated in the placentas of pregnant mice infused with angiotensin II type I receptor agonistic autoantibody, a pathogenic factor in preeclampsia. Knockdown of placental Hif-1α mRNA by specific siRNA significantly attenuated hallmark features of preeclampsia induced by angiotensin II type I receptor agonistic autoantibody in pregnant mice, including hypertension, proteinuria, kidney damage, impaired placental vasculature, and elevated maternal circulating soluble fms-like tyrosine kinase-1 levels. Next, we discovered that Hif-1α mRNA levels and HIF-1α protein levels were induced in an independent preeclampsia model with infusion of the inflammatory cytokine tumor necrosis factor superfamily member 14 (LIGHT). SiRNA knockdown experiments also demonstrated that elevated HIF-1α contributed to LIGHT-induced preeclampsia features. Translational studies with human placentas showed that angiotensin II type I receptor agonistic autoantibody or LIGHT is capable of inducing HIF-1α in a hypoxia-independent manner. Moreover, increased HIF-1α was found to be responsible for angiotensin II type I receptor agonistic autoantibody or LIGHT-induced elevation of Flt-1 gene expression and production of soluble fms-like tyrosine kinase-1 in human villous explants. Overall, we demonstrated that hypoxia-independent stimulation of HIF-1α gene expression in the placenta is a common pathogenic mechanism promoting disease progression. Our findings reveal new insight to preeclampsia and highlight novel therapeutic possibilities for the disease. © 2015 American Heart Association, Inc.

Longitudinal Discriminant Analysis of Hemoglobin Level for Predicting Preeclampsia

PubMed Central

Nasiri, Malihe; Faghihzadeh, Soghrat; Alavi Majd, Hamid; Zayeri, Farid; Kariman, Noorosadat; Safavi Ardebili, Nastaran

2015-01-01

Background: Preeclampsia is one of the most serious complications during pregnancy with important effects on health of mother and fetus that causes maternal and fetal morbidity and mortality. This study was performed to evaluate whether high levels of hemoglobin may increase the risk of preeclampsia. Objectives: The present study aimed to predict preeclampsia by the hemoglobin profiles through longitudinal discriminant analysis and comparing the error rate of discrimination in longitudinal and cross sectional data. Patients and Methods: In a prospective cohort study from October 2010 to July 2011, 650 pregnant women referred to the prenatal clinic of Milad Hospital in Tehran were evaluated in 3 stages. The hemoglobin level of each woman was measured in the first, second, and third trimester of pregnancy by an expert technician. The subjects were followed up to delivery and preeclampsia was the main outcome under study. The covariance pattern and linear-mixed effects models are common methods that were applied for discriminant analysis of longitudinal data. Also Student t, Mann-Whitney U, and chi-square tests were used for comparing the demographic and clinical characteristics between two groups. Statistical analyses were performed using the SAS software version 9.1. Results: The prevalence rate of preeclampsia was 7.2% (47 women). The women with preeclampsia had a higher mean of hemoglobin values and the difference was 0.46 g/dL (P = 0.003). Also the mean of hemoglobin in the first trimester was higher than that of the second trimester, and was lower than that of the third trimester and the differences were significant (P = 0.015 and P < 0.001, respectively). The sensitivity for longitudinal data and cross-sectional data in three trimesters was 90%, 67%, 72%, and 54% and the specificity was 88%, 55%, 63%, and 50%, respectively. Conclusions: The levels of hemoglobin can be used to predict preeclampsia and monitoring the pregnant women and its regular measure in 3 trimesters help us to identify women at risk for preeclampsia. PMID:26019901

Impact of Road Traffic Pollution on Pre-eclampsia and Pregnancy-induced Hypertensive Disorders

PubMed Central

Halldorsson, Thorhallur I.; Olsen, Sjurdur F.; Hjortebjerg, Dorrit; Ketzel, Matthias; Grandström, Charlotta; Raaschou-Nielsen, Ole; Sørensen, Mette

2017-01-01

Background: Road traffic is a major source of air pollution and noise. Both exposures have been associated with hypertension in adults, but pregnant women have been less studied. Methods: We examined single and joint effects of ambient air pollution and road traffic noise on pre-eclampsia and pregnancy-induced hypertensive disorders among 72,745 singleton pregnancies (1997–2002) from the Danish National Birth Cohort with complete covariate data and residential address history from conception until live born birth. Nitrogen dioxide (NO2) and noise from road traffic (Lden) were modeled at all addresses. Outcome and covariate data were derived from registries, hospital records, and questionnaires. Results: A 10-µg/m3 increase in NO2 exposure during first trimester was associated with increased risk of pre-eclampsia (n = 1,880, adjusted odds ratio = 1.07 [95% confidence interval = 1.01, 1.14]) and pregnancy-induced hypertensive disorders (n = 2,430, adjusted odds ratio = 1.07 [1.01, 1.13]). A 10 dB higher road traffic noise was also associated with increased risk of pre-eclampsia (1.10 [1.02, 1.18]) and pregnancy-induced hypertensive disorders (1.08 [1.02, 1.15]). For both exposures, the associations were strongest for mild pre-eclampsia (n = 1,393) and early-onset pre-eclampsia (n = 671), whereas higher risk for severe pre-eclampsia (n = 487) was not evident. In mutually adjusted models, estimates for both exposures decreased and only the association between NO2 and mild pre-eclampsia remained. Conclusions: Road traffic may increase the risk of pre-eclampsia and hypertensive disorders in pregnancy through exposure to both ambient air pollution and noise, although associations with the two exposures were generally not found to be independent of one another. See video abstract, http://links.lww.com/EDE/B112. PMID:27648591

[The usefulness of routine laboratory tests in the evaluation of sudden threat of pregnant woman and fetus in pre-eclampsia].

PubMed

Malarewicz, Andrzej; Gruszka, Olga; Szymkiewicz, Jadwiga; Rogala, Jerzy

2006-04-01

The fact that the progress of pre-eclampsia is highly unpredictable is the reason to run necessary monitoring, among others, by means of laboratory tests. Their aim is to determine explicitly if the pregnancy can be continued and terminated naturally or should be terminated by pre-term induced delivery or Caesarean section. There is a wide range of laboratory investigations recommended in pregnancy complicated by pre-eclampsia. The results reported in the literature though are controversial and inexplicit. The purpose of the research was to verify routine lab tests results used in decision making for emergency termination of pregnancy as a result of increased threatening clinical symptoms and to evaluate their usefulness in decision making to start delivery. The investigation covered 152 women who were divided into three groups. One consisted of 62 pregnant women with light form of pre-eclampsia, the other of 24 pregnant women with severe form of pre-eclampsia. The control group consisted of 66 healthy pregnant women. All pregnant women with pre-eclampsia diagnosed delivered by Caesarean section. The decision to perform the operation was based on biophysical findings of the fetus. At the moment of decision-making, blood was drawn for laboratory testing of the following parameters: systemic blood, coagulation parameters, total protein and protein fractios, non-protein nitrogen blood components, glucose, electrolytes, indicating enzymes and excretory enzymes of protein metabolism, lipid fractions. Routine lab tests performed in pre-eclampsia do not indicate distinct abnormalities the moment fetus life threatening clinical symptoms occur that enforce the decision of immediate delivery, the exception are the indicating enzymes. Acute clinical symptoms that endanger fetus life in pre-eclampsia correlate with distinct activity of AspAT, AIAT and LDH. Laboratory tests are of no prognostic value in the prediction of sudden worsening of the fetus condition in pre-eclampsia.

Racial/ethnic disparities in the association between preeclampsia risk factors and preeclampsia among women residing in Hawaii

PubMed Central

Nakagawa, Kazuma; Lim, Eunjung; Harvey, Scott; Miyamura, Jill; Juarez, Deborah T.

2016-01-01

Objective To assess differences in the rates of preeclampsia among a multiethnic population in Hawaii. Methods We performed a retrospective study on statewide inpatient data for delivery hospitalizations in Hawaii between January 1995 and December 2013. Multivariable logistic regression was used to assess the impact of maternal race/ethnicity on the rates of preeclampsia after adjusting for age, multiple gestation, multiparity, chronic hypertension, pregestational diabetes, obesity and smoking. Results A total of 271,569 hospital discharges for delivery were studied. The rates of preeclampsia ranged from 2.0% for Chinese to 4.6% for Filipinos. Preeclampsia rates were higher among Native Hawaiians who are age <35 and non-obese (OR, 1.54; 95% CI, 1.43-1.66), age ≥35 and non-obese (OR, 2.31; 95% CI, 2.00-2.68), age ≥35 and obese (OR, 1.80; 95% CI, 1.24-2.60); other Pacific Islanders who are age <35 and non-obese (OR, 1.40; 95% CI, 1.27-1.54), age ≥35 and non-obese (OR, 2.18; 95% CI, 1.79-2.64), age ≥35 and obese (OR, 1.68; 95% CI, 1.14-2.49); and Filipinos who are age <35 and non-obese (OR, 1.55; 95% CI, 1.43-1.67), age ≥35 and non-obese (OR, 2.26; 95% CI, 1.97-2.60), age ≥35 and obese (OR, 1.64; 95% CI, 1.04-2.59) compared to whites. Pregestational diabetes (OR, 3.41; 95% CI, 3.02-3.85), chronic hypertension (OR, 5.98; 95% CI, 4.98-7.18), and smoking (OR, 1.19; 95% CI, 1.07-1.33) were also independently associated with preeclampsia. Conclusion In Hawaii, Native Hawaiians, other Pacific Islanders and Filipinos have a higher risk of preeclampsia compared to whites. For these high-risk ethnic groups, more frequent monitoring for preeclampsia may be needed. PMID:27000850

Maternal overweight and obesity and risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes.

PubMed

Persson, Martina; Cnattingius, Sven; Wikström, Anna-Karin; Johansson, Stefan

2016-10-01

Women with type 1 or type 2 diabetes are at increased risk of pre-eclampsia. Overweight and obesity are associated with an increased risk of pre-eclampsia in women without diabetes. The aim of the study was to investigate the impact of maternal overweight and obesity on the risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes. In a population-based cohort study including singleton births in Sweden, we estimated the risk of pre-eclampsia among women with type 1 diabetes (n = 7062) and type 2 diabetes (n = 886), and investigated whether maternal overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI ≥30.0 kg/m(2)) modified the risk. Logistic regression analyses were used to estimate crude and adjusted ORs with 95% CIs, using women without diabetes as the reference group (n = 1,509,525). Compared with women without diabetes, the adjusted ORs for pre-eclampsia in women with type 1 and type 2 diabetes were 5.74 (95% CI 5.31, 6.20) and 2.11 (95% CI 1.65, 2.70), respectively. The corresponding risks of pre-eclampsia combined with preterm birth were even higher. Risks of pre-eclampsia increased with maternal overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI ≥30.0 kg/m(2)), foremost in women without diabetes, to a lesser extent in women with type 1 diabetes but not in women with type 2 diabetes. Maternal overweight and obesity increased risks of pre-eclampsia in women with type 1 diabetes but not in women with type 2 diabetes. Even so, considering associations between maternal BMI and overall maternal and offspring risk, all women (with and without diabetes) should aim for a normal weight before pregnancy.

Placental Vesicles Carry Active Endothelial Nitric Oxide Synthase and Their Activity is Reduced in Preeclampsia.

PubMed

Motta-Mejia, Carolina; Kandzija, Neva; Zhang, Wei; Mhlomi, Vuyane; Cerdeira, Ana Sofia; Burdujan, Alexandra; Tannetta, Dionne; Dragovic, Rebecca; Sargent, Ian L; Redman, Christopher W; Kishore, Uday; Vatish, Manu

2017-08-01

Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprising microvesicles (STBMV) and exosomes, carry signals from the syncytiotrophoblast to the mother. We hypothesized that STBEV-bound eNOS (STBEV-eNOS), capable of producing NO, are released into the maternal circulation. Dual-lobe ex vivo placental perfusion and differential centrifugation was used to isolate STBEV from preeclampsia (n=8) and normal pregnancies (NP; n=11). Plasma samples of gestational age-matched preeclampsia and NP (n=6) were used to isolate circulating STBMV. STBEV expressed placental alkaline phosphatase, confirming placental origin. STBEV coexpressed eNOS, but not inducible nitric oxide synthase, confirmed using Western blot, flow cytometry, and immunodepletion. STBEV-eNOS produced NO, which was significantly inhibited by N   G -nitro-l-arginine methyl ester (eNOS inhibitor; P <0.05) but not by N -(3-(aminomethyl) bezyl) acetamidine) (inducible nitric oxide synthase inhibitor). STBEV-eNOS catalytic activity was confirmed by visualizing eNOS dimerization. STBEV-eNOS was more abundant in uterine vein compared with peripheral blood, indicating placental origin. STBEV isolated from preeclampsia-perfused placentae had lower levels of STBEV-eNOS (STBMV; P <0.05) and overall lower NO activity (STBMV, not significant; syncytiotrophoblast extracellular exosomes, P <0.05) compared with those from NP. Circulating plasma STBMV from preeclampsia women had lower STBEV-eNOS expression compared with that from NP women ( P <0.01). This is the first observation of functional eNOS expressed on STBEV from NP and preeclampsia placentae, as well as in plasma. The lower STBEV-eNOS NO production seen in preeclampsia may contribute to the decreased NO bioavailability in this disease. © 2017 The Authors.

Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia.

PubMed

Stanhewicz, Anna E; Jandu, Sandeep; Santhanam, Lakshmi; Alexander, Lacy M

2017-08-01

Women who have had preeclampsia have increased cardiovascular disease risk; however, the mechanism(s) responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist postpartum. The putative mechanisms mediating this dysfunction include a reduction in NO-dependent dilation and an increased sensitivity to angiotensin II. In this study, we evaluated endothelium-dependent dilation, angiotensin II sensitivity, and the therapeutic effect of angiotensin II receptor blockade (losartan) on endothelium-dependent dilation in vivo in the microvasculature of women with a history of preeclampsia (n=12) and control women who had a healthy pregnancy (n=12). We hypothesized that preeclampsia would have (1) reduced endothelium-dependent dilation, (2) reduced NO-mediated dilation, and (3) increased sensitivity to angiotensin II. We further hypothesized that localized losartan would increase endothelium-dependent vasodilation in preeclampsia. We assessed microvascular endothelium-dependent vasodilator function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (acetylcholine; 10 -7 -102 mmol/L) and a standardized local heating protocol in control sites and sites treated with 15 mmol/L L-NAME ( N G -nitro-l-arginine methyl ester; NO-synthase inhibitor) or 43 µmol/L losartan. Further, we assessed microvascular vasoconstrictor sensitivity to angiotensin II (10 -20 -10 -4 mol/L). Preeclampsia had significantly reduced endothelium-dependent dilation (-0.3±0.5 versus -1.0±0.4 log EC50 ; P <0.001) and NO-dependent dilation (16±3% versus 39±6%; P =0.006). Preeclampsia also had augmented vasoconstrictor sensitivity to angiotensin II (-10.2±1.3 versus -8.3±0.5; P =0.006). Angiotensin II type I receptor inhibition augmented endothelium-dependent vasodilation and NO-dependent dilation in preeclampsia but had no effect in healthy pregnancy. These data suggest that women who have had preeclampsia have persistent microvascular dysfunction postpartum, mediated, in part, by increased sensitivity to angiotensin II. © 2017 American Heart Association, Inc.

Maternal Cadmium Levels During Pregnancy and the Relationship with Preeclampsia and Fetal Biometric Parameters.

PubMed

Wang, Fan; Fan, Fengyun; Wang, Lianyun; Ye, Wen; Zhang, Qiong; Xie, Shuangshuang

2018-04-12

Preeclampsia, which is caused by multiple factors, still remains one of the most serious complications of pregnancy. This study was designed to determine cadmium levels in women with preeclampsia compared to those of normotensive women. In this case-control study, maternal blood, umbilical cord blood, and placental cadmium levels were measured by an inductively coupled plasma mass spectrometry system in 51 women presenting consecutively with preeclampsia and 51 normotensive pregnant women. Groups were matched for maternal age, parity, and gestational age. Birth outcomes were recorded, such as gestational age at delivery, birth weight, and Apgar score. Median (interquartile range [IQR]) blood cadmium concentration was 1.21 μg/L (0.76-1.84 μg/L) and 1.09 μg/L (0.72-1.31 μg/L) in women with preeclampsia and normotensive, respectively; values for placental cadmium levels of women with preeclampsia and normotensive were 3.61 μg/kg (2.19-4.37 μg/kg) and 4.28 μg/kg (3.06-5.71 μg/kg), respectively. We observed a statistically significant increase in blood and placental cadmium levels in women with preeclampsia compared to healthy pregnant women. After adjusting for pre-pregnancy body mass index, maternal age, parity, gestational age at sample collection, and maternal calcium and magnesium levels, the odds ratio of having preeclampsia in the high tertile was markedly increased (odds ratio, 7.83 [95% CI, 1.64-37.26]) compared with the low tertile. Interestingly, there was no difference in the cadmium level in umbilical cord blood between the groups. Within the preeclamptic group, higher cadmium status was significantly associated with decreased birth weight. Our study suggested that elevated cadmium level in the maternal circulation could potentially increase the risk of preeclampsia. The results also demonstrate that higher cadmium status may contribute to fetal growth restriction in preeclamptic patients.