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Sample records for pre-eclampsia

  1. Pre-eclampsia.

    PubMed

    Mol, Ben W J; Roberts, Claire T; Thangaratinam, Shakila; Magee, Laura A; de Groot, Christianne J M; Hofmeyr, G Justus

    2016-03-05

    Pre-eclampsia affects 3-5% of pregnancies and is traditionally diagnosed by the combined presentation of high blood pressure and proteinuria. New definitions also include maternal organ dysfunction, such as renal insufficiency, liver involvement, neurological or haematological complications, uteroplacental dysfunction, or fetal growth restriction. When left untreated, pre-eclampsia can be lethal, and in low-resource settings, this disorder is one of the main causes of maternal and child mortality. In the absence of curative treatment, the management of pre-eclampsia involves stabilisation of the mother and fetus, followed by delivery at an optimal time. Although algorithms to predict pre-eclampsia are promising, they have yet to become validated. Simple preventive measures, such as low-dose aspirin, calcium, and diet and lifestyle interventions, show potential but small benefit. Because pre-eclampsia predisposes mothers to cardiovascular disease later in life, pregnancy is also a window for future health. A collaborative approach to discovery and assessment of the available treatments will hasten our understanding of pre-eclampsia and is an effort much needed by the women and babies affected by its complications.

  2. [Pre-eclampsia].

    PubMed

    Post Uiterweer, E D; Veerbeek, J H W; Franx, A

    2015-02-01

    Pre-eclampsia or toxaemia of pregnancy is a multi-organ disorder in the second half of pregnancy. Approximately 1-3% of all pregnancies in the Netherlands are complicated by this condition. The disease is characterised by vascular damage resulting in hypertension and proteinuria with high morbidity for both mother and child. The underlying cause is a poorly developed placenta. To date the only real treatment comprises medicinal protection against complications and the disorder can be cured only through termination of pregnancy. Complications range from severe hypertension to maternal mortality due to cerebral haemorrhage. Long-term consequences can be severe for both mother and child. For instance, the risk of cardiovascular disease in mothers in later life is significantly increased. Many risk factors have been identified, including diabetes, BMI and an age of above 40. The association between periodontal disease and pre-eclampsia emphasises the importance of good oral hygiene in the periconceptional period.

  3. Update in pre-eclampsia.

    PubMed

    Chanprapaph, Pharuhas

    2004-10-01

    Pre-eclampsia, formerly called pregnancy-induced hypertension, refers to the new onset of hypertension (SBP > or = 140 mmHg or DBP > or = 90 mmHg) and proteinuria (> or = 0.3 g protein in a 24-hour urine specimen or 1+ on dipstick) after 20 weeks of gestation in a previously normotensive women. It is a life-threatening, multi-organ involvement disease and remains the leading cause of maternal death. Its clinical manifestations are the result of generalized vasospasm, activation of the coagulation system, and changes in several humoral and autoregulatory systems related to volume and blood pressure control. Pre-eclampsia is responsible for high perinatal mortality and morbidity rates, primarily due to early termination of pregnancy. Fetus growth restriction, oligohyrdramnios and non-reassuring fetal status are the consequences of chronic placental hypoperfusion. Pre-eclampsia does not appear to accelerate fetal maturation, as once believed. Delivery remains the definitive treatment of choice for pre-eclampsia and should be timely. Cesarean section is not necessary and reserved for the obstetrical indications only. The expectant management may be considered for women remote from term (< 32 to 34 weeks of gestation) with stable and uncomplicated severe disease. The supportive management such as blood pressure control, seizure prevention, and fetal well-being assessment are also important to ensure the satisfactory outcome. To date, no screening test has been proved to be reliable and cost-effective. The prevention of pre-eclampsia with antioxidant therapy (vitamin C, E) has shown promise, but large, randomized trials are needed. Although controversy exists, calcium supplementation has shown no benefit in large trials, and most evidence suggests little or no benefit for low-dose aspirin as prevention in women in the low-risk category.

  4. Pre-eclampsia: pathophysiology, diagnosis, and management.

    PubMed

    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.

  5. Severe hyponatraemia associated with pre-eclampsia.

    PubMed

    Anglim, Breffini; Levins, Kirk; Bussmann, Neidin; Imcha, Mendinaro

    2016-08-24

    Pre-eclampsia is a multisystem disorder with incidence rates ranging from 2% to 5%. Hyponatraemia is a rare complication of pre-eclampsia. A 41-year-old, para 0+1 in vitro fertilisation monochorionic diamniotic triplet pregnancy woman presented at 25 weeks with dyspnoea and general malaise. Her antenatal course was complicated by the diagnosis of intrauterine growth restriction in triplet one at 27 weeks of gestation. At 27+3 weeks gestation, she was diagnosed as having pre-eclampsia. Subsequent biochemical analysis demonstrated hyponatraemia with serum sodium falling steadily to 117 mmol/L over the next 19 days. She was admitted to intensive care unit for stabilisation of fulminant pre-eclampsia and severe hyponatraemia at 30+5 weeks of gestation. Hypertonic saline and intravenous labetolol were administered prior to delivery by caesarean section. She recovered well postdelivery with stabilisation of her blood pressure and normalisation of her sodium level to 135 mmol/L. Awareness and frequent monitoring of hyponatraemia should become an integral part of monitoring women with pre-eclampsia.

  6. Pre-eclampsia and childhood asthma.

    PubMed

    Magnus, Maria C; Håberg, Siri E; Magnus, Per; Engeland, Anders; Nafstad, Per; Karlstad, Øystein; Nystad, Wenche

    2016-12-01

    Studies of pre-eclampsia and childhood asthma are conflicting, and none have performed a formal mediation analysis of preterm birth.We examined the association between pre-eclampsia and asthma at 7 years using national registries, including all births in Norway from 1999 to 2006 (n=406 907), and a subsample of children in the Norwegian Mother and Child Cohort Study (MoBa) (n=45 028) using log-linear regression. We performed a mediation analysis of preterm birth, and a sibling comparison to evaluate unobserved confounding.There was a positive association between pre-eclampsia and asthma in the registry study, with an adjusted relative risk of 1.31 (95% CI 1.22-1.41), but not in MoBa, which had an adjusted relative risk of 1.19 (95% CI 0.99-1.44). The odds ratios for the direct effect not mediated through preterm birth and the indirect effect in the registry linkage were 1.19 (95% CI 1.10-1.29) and 1.12 (95% CI 1.11-1.14), respectively. The sibling comparison indicated no association between pre-eclampsia and asthma (adjusted OR 1.07, 95% CI 0.87-1.33).In this large study, which used different datasets and analytic approaches, there was little evidence for an association between pre-eclampsia and childhood asthma. The association was weak and largely explained by pre-term birth and confounders shared by siblings.

  7. 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

  8. Pre-eclampsia, diagnosis and treatment.

    PubMed

    Sunanda, G V; Johanson, R

    2001-11-01

    Pre-eclampsia is a multisystem disorder of pregnancy usually associated with raised blood pressure (BP) and proteinuria. The pathogenesis is not understood despite decades of research. Abnormal placentation related to immune mechanisms and maladaptation of the placenta may be the first step in the development of the disease. Although there are a number of risk factors and new innovatory tests (e.g., uterine artery Doppler) which can be used to predict pre-eclampsia, none fulfils standard diagnostic criteria. Of possible prophylactic value are antiplatelet agents, calcium supplementation and vitamins C and E. Prevention of eclampsia with magnesium sulfate is the subject of a current international randomised controlled trial (RCT), known as MAGPIE. Therapeutic strategies include avoidance of hypertensive injury and delivery of the baby and placenta. Further research into specific antihypertensive agents and conservative management strategies is required.

  9. Pre-eclampsia part 2: prediction, prevention and management.

    PubMed

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

    2014-09-01

    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.

  10. Maternal lipids in pre-eclampsia: innocent bystander or culprit?

    PubMed

    Barrett, Helen L; Dekker Nitert, Marloes; McIntyre, H David; Callaway, Leonie K

    2014-11-01

    Pre-eclampsia continues to be a challenge--to understand the underlying pathogenesis and to prevent or treat in the clinical setting. One area of potential therapies opening up is treatment of maternal lipids and clinical trials are underway using statins in early pre-eclampsia. At present, most potential therapies to treat lipids cannot be recommended for general use in pregnancy and if we were to target maternal lipids to reduce rates of pre-eclampsia, very large numbers of women may need to be treated. Prior to reaching that point, we first need to understand whether maternal lipids are pathogenic in the processes underlying pre-eclampsia. The aim of this review is to examine the role of lipids in the pathogenesis and outcomes of pre-eclampsia, how abnormal lipid genes may be implicated and consider whether treatment of hyperlipidemia has a more general place in the prevention or treatment of pre-eclampsia.

  11. Serum homocysteine in pre-eclampsia and eclampsia.

    PubMed

    Hoque, Md Mozammel; Bulbul, Tania; Mahal, Monzarin; Islam, Nur-A-Farzana; Ferdausi, Munira

    2008-04-01

    Pre-eclampsia and eclampsia are common obstetrical problem causing adverse effects on pregnancy outcome. Large bodies of evidences suggest that hyperhomocysteinemia is a causal factor of pre-eclampsia/eclampsia. This study designed to explore the association between hyperhomocysteinemia and pre-eclampsia/eclampsia, the knowledge of which expected to be used for prevention of pre-eclampsia and eclampsia. In a case-control study serum homocysteine was measured in 136 controls (healthy pregnant), 84 pre-eclamptic and 120 eclamptic pregnant women. Serum homocysteine in patients with pre-eclampsia (9.54 +/- 3.21 micromol/L) and eclampsia (10.57 +/- 3.39 micromol/L) found to be significantly increased compared to controls (6.86 +/- 2.47 micromol/L) (p < 0.001). Between pre-eclampsia and eclampsia, homocysteine found to be raised more in eclampsia compared to pre-eclampsia (p < 0.03). In conclusion, hyperhomocysteinemia is associated with pre-eclampsia as well as eclampsia, but in eclampsia the severity of homocysteine elevation is more compared to that in pre-eclampsia.

  12. Association between Asymptomatic Bacteriuria and Pre-Eclampsia

    PubMed Central

    Rezavand, Negin; Veisi, Firooze; Zangane, Mrayam; Amini, Roghaye; Almasi, Afshin

    2016-01-01

    Asymptomatic bacteriuria is one of the most common and important bacterial infections during pregnancy and can result in progressive infections and endanger maternal as well as fetal health. In this study, we assessed the relationship between asymptomatic bacteriuria and pre-eclampsia. In this case-control study, pregnant women who presented to Imam Reza Hospital in Kermanshah in 2013-14 were studied. The minimum sample size was calculated as 125 pregnant women in each group with a total of 250 subjects. There were 125 women with pre-eclampsia and 125 women without pre-eclampsia (control group). Matching was done for age, gestational age, and parity between case and control groups. Matching was verified by a P value of 0.061 for maternal age and gestational age and 0.77 for parity. The statistical analyses were done by applying the chi-squared test and determining odds ratio (OR) for having bacteriuria in univariate logistic regression as well as multivariate regression with adjusting the effect of maternal age, gestational age, and parity. Pyuria and bacteriuria were significantly more common in pre-eclampsia group than in control group. The results showed that a significant association existed between asymptomatic bacteriuria and pre-eclampsia. The rate of asymptomatic bacteriuria was 6.8 times higher in women with pre-eclampsia compared to those without pre-eclampsia. Further studies are required for better clarification of association between asymptomatic bacteriuria and pre-eclampsia. PMID:26925912

  13. Potential role of folate in pre-eclampsia.

    PubMed

    Singh, Mansi Dass; Thomas, Philip; Owens, Julie; Hague, William; Fenech, Michael

    2015-10-01

    Dietary deficiencies of folate and other B vitamin cofactors involved in one-carbon metabolism, together with genetic polymorphisms in key folate-methionine metabolic pathway enzymes, are associated with increases in circulating plasma homocysteine, reduction in DNA methylation patterns, and genome instability events. All of these biomarkers have also been associated with pre-eclampsia. The aim of this review was to explore the literature and identify potential knowledge gaps in relation to the role of folate at the genomic level in either the etiology or the prevention of pre-eclampsia. A systematic search strategy was designed to identify citations in electronic databases for the following terms: folic acid supplementation AND pre-eclampsia, folic acid supplementation AND genome stability, folate AND genome stability AND pre-eclampsia, folic acid supplementation AND DNA methylation, and folate AND DNA methylation AND pre-eclampsia. Forty-three articles were selected according to predefined selection criteria. The studies included in the present review were not homogeneous, which made pooled analysis of the data very difficult. The present review highlights associations between folate deficiency and certain biomarkers observed in various tissues of women at risk of pre-eclampsia. Further investigation is required to understand the role of folate in either the etiology or the prevention of pre-eclampsia.

  14. Transthoracic echocardiography in women with treated severe pre-eclampsia.

    PubMed

    Dennis, A T; Castro, J M

    2014-05-01

    The aim of this study was to investigate cardiac function and haemodynamic indices using transthoracic echocardiography in women with severe pre-eclampsia who had already received treatment interventions. Fifteen women with treated severe pre-eclampsia were studied using transthoracic echocardiography. Mean (SD) cardiac output in women with treated disease was 5690 (1708) ml.min(-1). Systolic function was preserved in women with treated disease evidenced by mean (SD) fractional shortening 41 (9)%, fractional area change 62 (12)% and septal s' velocities 9.0 (2.1) cm.s(-1). Left ventricle end-diastolic diameters were within healthy reference ranges at 4.7 (0.3) cm and the left ventricle was not dilated. Diastolic function was reduced, with a mean (SD) mitral valve E/septal e' ratio of 12.6 (4.1). Left ventricular mass was increased at 182.0 (44.4) g. There was large variability in haemodynamics in women with treated severe pre-eclampsia. Transthoracic echocardiography is acceptable and applicable and enables quantification of cardiac function in women with severe pre-eclampsia.

  15. Primary, secondary, and tertiary prevention of pre-eclampsia.

    PubMed

    Dekker, G; Sibai, B

    2001-01-20

    Pre-eclampsia remains one of the major obstetrical problems in less-developed countries. The causes of this condition are still unknown, thus effective primary prevention is not possible at this stage. Research in the past decade has identified some major risk factors for pre-eclampsia, and manipulation of these factors might result in a decrease in its frequency. In the early 1990s aspirin was thought to be the wonder drug in secondary prevention of pre-eclampsia. Results of large trials have shown that this is not the case: if there is an indication for using aspirin it is in the patient at a very high risk of developing severe early-onset disease. The calcium story followed a more or less similar pattern, with the difference that existing evidence shows that women with a low dietary calcium intake are likely to benefit from calcium supplementation. Proper antenatal care and timed delivery are of utmost importance in tertiary prevention of pre-eclampsia. There is evidence to suggest that the intrinsic direct effect of moderate degrees of maternal hypertension is beneficial to the fetus. Severe hypertension needs treatment. If antihypertensive is indicated, there is no clear choice of a drug. Hydralazine should no longer be thought of as the primary drug, most studies show a preference for calcium channel blockers.

  16. Management of pre-eclampsia: issues for anaesthetists.

    PubMed

    Dennis, A T

    2012-09-01

    Pre-eclampsia is a leading cause of maternal morbidity and mortality. Substandard care is often present and many deaths are preventable. The aim of this review is to summarise the key management issues for anaesthetists in the light of the current literature. A systematic literature search of electronic databases was undertaken including MEDLINE, EMBASE and the Cochrane Library using the key words obstetrics, pregnancy, pregnancy complications, maternal, pre-eclampsia, preeclampsia, cardiac function, haemodynamics, haemolysis, elevated liver enzymes, low platelets (HELLP), eclampsia, anaesthesia, anesthesia, neuraxial. Relevant Colleges and Societies websites were examined for pertinent guidelines. The disease is defined within the context of hypertensive diseases, and early recognition of pre-eclampsia and its complications, as well as multidisciplinary expert team management is highlighted. Accurate monitoring and recording of observations including the use of transthoracic echocardiography is discussed. The importance of the treatment of systolic blood pressure>180 mmHg and the use of intravenous antihypertensive medication as well as the use of parenteral magnesium sulphate for the treatment and prevention of eclampsia is emphasised . Restricted intravenous fluid therapy and avoidance of ergometrine is discussed. Neuraxial analgesia and anaesthesia, and general anaesthesia for birth is summarised as well as postpartum management including analgesia, thromboprophylaxis, management of acute pulmonary oedema and the use of pharmacological agents in the setting of breastfeeding.

  17. Clinical presentation, assessment and management of pre-eclampsia.

    PubMed

    Lavallee, Layla

    2015-07-08

    Pre-eclampsia is a complex and unpredictable disorder that may occur during pregnancy. Its presentation ranges from mild to severe, and the condition may lead to the death of the mother and/or the baby in extreme cases. The earlier the disorder is detected and managed, the better the outcome. This article provides an outline of the disorder and its management, within the framework of UK and international guidelines. A series of suggested activities encourages the reader to reflect on the information provided within the context of their practice.

  18. The Pre-Eclampsia Ontology: A Disease Ontology Representing the Domain Knowledge Specific to Pre-Eclampsia

    PubMed Central

    Mizuno, Satoshi; Ogishima, Soichi; Nishigori, Hidekazu; Jamieson, Daniel G.; Verspoor, Karin; Tanaka, Hiroshi; Yaegashi, Nobuo; Nakaya, Jun

    2016-01-01

    Pre-eclampsia (PE) is a clinical syndrome characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation, and is a leading cause of maternal and perinatal morbidity and mortality. Previous studies have gathered abundant data about PE such as risk factors and pathological findings. However, most of these data are not semantically structured. Clinical data on PE patients are often generated with semantic heterogeneity such as using disparate terminology to describe the same phenomena. In clinical studies, interoperability of heterogenic clinical data is required in various situations. In such a situation, it is necessary to develop an interoperable and standardized semantic framework to research the pathology of PE more comprehensively and to achieve interoperability of heterogenic clinical data of PE patients. In this study, we developed an ontology representing clinical features, treatments, genetic factors, environmental factors, and other aspects of the current knowledge in the domain of PE. We call this pre-eclampsia ontology “PEO”. To achieve interoperability with other ontologies, the core structure of PEO was compliant with the hierarchy of the Basic Formal Ontology (BFO). The PEO incorporates a wide range of key concepts and terms of PE from clinical and biomedical research in structuring the knowledge base that is specific to PE; therefore, PEO is expected to enhance PE-specific information retrieval and knowledge discovery in both clinical and biomedical research fields. PMID:27788142

  19. Pre-Eclampsia Increases the Risk of Postpartum Haemorrhage: A Nationwide Cohort Study in The Netherlands

    PubMed Central

    von Schmidt auf Altenstadt, Joost F.; Hukkelhoven, Chantal W. P. M.; van Roosmalen, Jos; Bloemenkamp, Kitty W. M.

    2013-01-01

    Background Postpartum haemorrhage is a leading cause of maternal morbidity and mortality worldwide. Identifying risk indicators for postpartum haemorrhage is crucial to predict this life threatening condition. Another major contributor to maternal morbidity and mortality is pre-eclampsia. Previous studies show conflicting results in the association between pre-eclampsia and postpartum haemorrhage. The primary objective of this study was to investigate the association between pre-eclampsia and postpartum haemorrhage. Our secondary objective was to identify other risk indicators for postpartum haemorrhage in the Netherlands. Methods A nationwide cohort was used, containing prospectively collected data of women giving birth after 19 completed weeks of gestation from January 2000 until January 2008 (n =  1 457 576). Data were extracted from the Netherlands Perinatal Registry, covering 96% of all deliveries in the Netherlands. The main outcome measure, postpartum haemorrhage, was defined as blood loss of ≥1000 ml in the 24 hours following delivery. The association between pre-eclampsia and postpartum haemorrhage was investigated with uni- and multivariable logistic regression analyses. Results Overall prevalence of postpartum haemorrhage was 4.3% and of pre-eclampsia 2.2%. From the 31 560 women with pre-eclampsia 2 347 (7.4%) developed postpartum haemorrhage, compared to 60 517 (4.2%) from the 1 426 016 women without pre-eclampsia (odds ratio 1.81; 95% CI 1.74 to 1.89). Risk of postpartum haemorrhage in women with pre-eclampsia remained increased after adjusting for confounders (adjusted odds ratio 1.53; 95% CI 1.46 to 1.60). Conclusion Women with pre-eclampsia have a 1.53 fold increased risk for postpartum haemorrhage. Clinicians should be aware of this and use this knowledge in the management of pre-eclampsia and the third stage of labour in order to reach the fifth Millenium Developmental Goal of reducing maternal mortality ratios with 75% by 2015. PMID

  20. [Gravidaprotective action of phenibut in experimental pre-eclampsia].

    PubMed

    Tiurenkov, I N; Perfilova, V N; Karamysheva, V I; Popova, T A; Lebedeva, S A; Mikhaĭlova, L I; Zhakupova, G A

    2014-01-01

    It was established that the replacement of drinking water by 1.8% NaCl solution in female rats during pregnancy causes experimental pre-eclampsia (EP), as evidenced by an increase in the blood pressure, proteinuria, and edema in the control group as compared to pregnant female rats with normal drinking regime. Animals with EP exhibited disturbance of vasodilating endothelial function, microcirculation disorder, and increased coagulation and thrombogenic potential of blood. In addition, the group with EP showed evidence of the activation of lipid peroxidation (LPO) due to lower activity of antioxidant enzymes. Daily oral administration ofphenibut (25 mg/kg) in female rats with EP during pregnancy prevents the increase in blood pressure and the severity of proteinuria and edemation. Phenibut improves the vasodilator and antithrombotic endothelial functions, increases uterine blood flow, improves microcirculation, limits LPO, and increases the activity of antioxidant enzymes.

  1. The effects and mechanisms of primiparity on the risk of pre-eclampsia: a systematic review.

    PubMed

    Luo, Zhong-Cheng; An, Na; Xu, Hai-Rong; Larante, Amelie; Audibert, Francois; Fraser, William D

    2007-07-01

    Pre-eclampsia has been dubbed as 'a disease of primiparity'. However, the effects and mechanisms of the association of primiparity with pre-eclampsia have not been clearly defined. We conducted a systematic review of studies evaluating the effect of primiparity on the risk of pre-eclampsia, and studies (published between January 1966 and July 2005) on the mechanisms underlying such an association. A total of 26 original studies were identified and a meta-analysis carried out for the risk of pre-eclampsia among primiparous vs. multiparous women. Variably (1.4-5.5 times) higher risks of pre-eclampsia were observed in primiparous women in all studies, with a summary odds ratio (OR) of 2.42 [95% CI 2.16, 2.71]. The adjusted ORs were larger than crude ORs in all but one study after various adjustments. Except for abundant epidemiological evidence in support of the immune maladaptation theory, only four original studies examined the actual mechanisms of such primiparity-associated risk. Two (small) studies suggested differences in immunological responses in the aetiology of pre-eclampsia in primiparous vs. multiparous women. Two recent studies indicated that differences in angiogenic factor profile or reactivity to insulin resistance in early pregnancy may explain the elevated pre-eclampsia risk in first pregnancies. In conclusion, primiparity is associated with approximately 2.4-fold elevated risk of pre-eclampsia. Although immune maladaptation is generally considered as the basis to explain such an elevated risk, few data are available on immune maladaptation parameters in primiparous vs. multiparous pregnancies. Available data are insufficient to interpret the mechanisms of such primiparity-associated excess risk of pre-eclampsia.

  2. Community-based home-care program for the management of pre-eclampsia: an alternative.

    PubMed Central

    Helewa, M; Heaman, M; Robinson, M A; Thompson, L

    1993-01-01

    OBJECTIVE: To evaluate the safety, acceptability and cost of a community-based home-care program for the management of mild pre-eclampsia. DESIGN: A descriptive study of outcomes between Apr. 1, 1985, and Dec. 31, 1989. SETTING: St. Boniface General Hospital, Winnipeg. PATIENTS: Urban Winnipeg residents between 27 and 40 weeks' gestation with mild pre-eclampsia who demonstrated acceptance and compliance with home-care management; 321 patients of 1330 were enrolled in the program. INTERVENTIONS: Bed rest at home with daily biochemical and biophysical follow-up protocol and weekly clinic visits; patient education; hospital admission for labour, induction, worsening pre-eclampsia or noncompliance with rest at home. OUTCOME MEASURES: Patterns of referral to the program; clinical, biochemical and biophysical profiles; incidence of severe complications; reduction in total hospital stay and cost analysis. RESULTS: As many women were referred from physicians' offices as were referred from the hospital's antepartum unit, the average gestational age at referral being 36 weeks. Most (205 [64%]) of the women were nulliparous. The average length of stay in the program was 11.5 days. The program's availability resulted in a reduction of 2 days (from 5.7 days to 3.7 days) on average in the length of hospital stay when analysed for all 1330 women with pre-eclampsia. Of the 321 patients in the program 137 (43%) were admitted to hospital for worsening pre-eclampsia; severe pre-eclampsia developed 4 days after admission in 9. No patient suffered eclampsia, disseminated intravascular coagulopathy, abruption or fetal loss related to pre-eclampsia while in the program. The estimated cost saving in the management of pre-eclampsia was over $700,000 over the study period. CONCLUSION: The community-based home-care program is a safe, feasible and less costly alternative to hospital admission in the management of mild pre-eclampsia. PMID:8374846

  3. 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

  4. Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia.

    PubMed

    Southcombe, J H; Redman, C W G; Sargent, I L; Granne, I

    2015-09-01

    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.

  5. Placenta previa and pre-eclampsia: analyses of 1645 cases at medani maternity hospital, Sudan.

    PubMed

    Adam, Ishag; Haggaz, Abdelrahium D; Mirghani, Omer A; Elhassan, Elhassan M

    2013-01-01

    A retrospective case-control study was conducted to investigate the risk factors for pre-eclampsia - including the protective effect of placenta previa - at Medani Maternity Hospital, Sudan. Medical files of the patients during the period 2003-2010 were reviewed for age, parity, education level, prenatal care, placenta previa, and hemoglobin level. Women with pre-eclampsia were the cases, and women with normal pregnancy were the controls. There were 54,339 singleton deliveries and 1765 women with pre-eclampsia in the hospital, giving the incidence of pre-eclampsia of 3.2%. The risk factors for pre-eclampsia were; women with age >35 years (OR = 1.4, 95% CI: 1.1-1.8), primiparity (OR = 3.3, 95% CI: 2.7-4.0), para >5 (OR = 3.1, 95% CI: 2.4-4.0), and anemia (OR = 3.3, 95% CI: 2.8-3.9). The risk of pre-eclampsia was inversely increased with education level and prenatal care attendance. The prevalence of placenta previa was 0 (0%) and 55 (3.3%), P < 0.001 in pre-eclamptic and control women, respectively. Placenta previa was a significant protective factor of pre-eclampsia (OR = 0.3, 95% CI: 0.1-0.7). Although, the socio-demographic risk factors for pre-eclampsia observed among women at Medani hospital were similar to those found in other settings; placenta previa was associated with decreased incidence of pre-eclampsia.

  6. Relationship between air pollution and pre-eclampsia in pregnant women: a case-control study.

    PubMed

    Nahidi, F; Gholami, R; Rashidi, Y; Majd, H Alavi

    2014-01-09

    Pre-eclampsia is the main cause of maternal and fetal death and disability worldwide. Its incidence in the Islamic Republic of Iran is 5%-12%. Air pollution has been reported to be one of the causative factors, and this case-control study determined its effect on pre-eclampsia in 195 pregnant women (65 with pre-eclampsia and 130 without) admitted to hospitals in Tehran. Women were divided into high and low exposure groups according to the mean density of exposure to pollutants during pregnancy. There was no statistically significant relationship between exposure to air pollutants including CO, particulate matter, SO2, NO2 and O3 and pre-eclampsia. The combined effect was also not significant. Air pollution is one of the problems of modern society and its avoidance is almost impossible for pregnant women. This study should reduce concern about pregnant women living in polluted cities.

  7. Placental ischaemia is a consequence rather than a cause of pre-eclampsia.

    PubMed

    Ayuk, Paul T-Y; Matijevic, Ratko

    2006-01-01

    The aetiology or pre-eclampsia remains unknown, but it is widely accepted that the disorder is placental in origin. Failed trophoblast invasion of the maternal spiral arteries is accepted to be a central pathogenetic mechanism. However, the concept of failed trophoblast invasion is based on an assumption rather than direct scientific observation and there are other likely explanations for this phenomenon. The criteria for disease causation, such as the Bradford-Hill criteria are central to the ascertainment of causal relationships in modern medicine and these criteria are used here to assess the relationship between the placenta and pre-eclampsia. There is a strong association between pre-eclampsia and small (rather than large) placentas and an appropriate dose-response relationship does not exist. Failed trophoblast invasion of the spiral arteries is not specific to pre-eclampsia and occurs in other pregnancy complications and in up to 40% of biopsies from normal pregnancies and the relationship between placental ischaemia and pre-eclampsia is very inconsistent. A placental cause for pre-eclampsia is not consistent with the pathogenesis of other pregnancy complications like gestational diabetes mellitus. If pre-eclampsia was a disease of trophoblast origin, the risk of the disease should be determined by trophoblast rather than maternal factors. However, evidence from assisted reproduction shows that the risk of a woman developing pre-eclampsia is almost entirely dependent on maternal factors and independent of the embryo from which the placenta develops. There is currently no plausible proven mechanism by which the placenta causes pre-eclampsia. The syndrome typically gets worse, and can arise de-novo after the placenta has been removed, calling into question the role of the placenta in its causation. Uterine artery ligation in humans, unlike in animal experiments, is not associated with an increased incidence of pre-eclampsia, calling into question the role of

  8. Understanding Pre-Eclampsia Using Alzheimer's Etiology: An Intriguing Viewpoint.

    PubMed

    Cheng, Shi-Bin; Nakashima, Akitoshi; Sharma, Surendra

    2016-03-01

    Characterized by hypertension and proteinuria after the 20th week of gestation, pre-eclampsia (PE) is a major cause of maternal, fetal, and neonatal morbidity and mortality. Despite being recognized for centuries, PE still lacks a reliable, early means of diagnosis or prediction, and a safe and effective therapy. We have recently reported that the event of toxic protein misfolding and aggregation is a critical etiological manifestation in PE. Using comparative proteomic analysis of gestational age-matched sera from PE and normal pregnancy, we identified several proteins that appeared to be dysregulated in PE. Our efforts so far have focused on transthyretin (TTR), a transporter of thyroxine and retinol, and amyloid precursor protein whose aggregates were detected in the PE placenta. Based on these results and detection of TTR aggregates in sera from PE patients, we proposed that PE could be a disease of protein misfolding and aggregation. Protein misfolding and aggregation have long been linked with many neurodegenerative diseases such as Alzheimer's disease. However, linkage of protein misfolding and aggregation with the PE pathogenesis is a new and novel concept. This review aims to understand the roles of aggregated proteins in PE using the cues from the Alzheimer's etiology.

  9. Exercise and physical activity in the prevention of pre-eclampsia: systematic review.

    PubMed

    Kasawara, Karina Tamy; do Nascimento, Simony Lira; Costa, Maria Laura; Surita, Fernanda Garanhani; e Silva, João Luiz Pinto

    2012-10-01

    Exercise and physical activity have been studied and suggested as a way to reduce or minimize the effects of pre-eclampsia. Our aim was to evaluate the association between exercise and/or physical activity and occurrence of pre-eclampsia. We conducted electronic searches without year of publication and language limitations. This was a systematic review designed according to PRISMA. Different databases accessed were as follows: PubMed®; Latin-American and Caribbean Literature in Health Sciences (LILACS); Scientific Electronic Library On-line (SciELO); Physiotherapy Evidence Database (PEDro); and ISI web of Knowledge(SM) . The Medical Subject Headings (MeSH) were as follows: ("exercise" OR "motor activity" OR "physical activity") AND ("pre-eclampsia" OR "eclampsia" OR "hypertension, pregnancy-induced"). Inclusion criteria were studies conducted in adults who were engaged in some physical activity. The selection and methodological evaluation were carried out by two independent reviewers. Risk assessment was made by the odds ratio (OR) and incidence of pre-eclampsia in the population who performed physical activity/exercise. A total of 231 articles were found, 214 of which were excluded based on title and full-text, so that 17 remained. Comparison of six case-control studies showed that physical activity had a protective effect on the development of pre-eclampsia [OR 0.77, 95% confidence interval (CI) 0.64-0.91, p < 0.01]. The 10 prospective cohort studies showed no significant difference (OR 0.99, 95% CI 0.93-1.05, p= 0.81). The only randomized clinical trial showed a protective effect on the development of pre-eclampsia in the stretching group (OR 6.34, 95% CI 0.72-55.37, p= 0.09). This systematic review indicates a trend toward a protective effect of physical activity in the prevention of pre-eclampsia.

  10. Excessive stimulation of poly(ADP-ribosyl)ation contributes to endothelial dysfunction in pre-eclampsia

    PubMed Central

    Crocker, Ian P; Kenny, Louise C; Thornton, Wayne A; Szabo, Csaba; Baker, Philip N

    2004-01-01

    Pre-eclampsia is a serious pregnancy disorder associated with widespread activation of the maternal vascular endothelium. Recent evidence implicates a role for oxidative stress in the aetiology of this condition. Reactive oxygen species, particularly superoxide anions, invokes endothelial cell activation through many pathways. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP) leading to endothelial dysfunction in various pathophysiological conditions (reperfusion, shock, diabetes). We have studied whether the loss of endothelial function in pre-eclampsia is dependent on PARP activity. Endothelium-dependent responses of myometrial arteries were tested following exposure to either plasma from women with pre-eclampsia or normal pregnant women in the presence and absence of a novel potent inhibitor of PARP, PJ34. Additional effects of plasma and PJ34 inhibition were identified in microvascular endothelial cell cultures. In myometrial arteries, PARP inhibition blocked the attenuation of endothelium-dependent responses following exposure to plasma from women with pre-eclampsia. In endothelial cell cultures, plasma from pre-eclamptics induced measurable oxidative stress and a concomitant increase in PARP activity and reduction in cellular ATP. Again, these biochemical changes were reversed by PJ34. These results suggest that PARP activity plays a pathogenic role in the development of endothelial dysfunction in pre-eclampsia and promotes PARP inhibition as a potential therapy in this condition. PMID:15778700

  11. Serum levels of lipids, lipoproteins and paraoxonase activity in pre-eclampsia.

    PubMed

    Demir, B; Demir, S; Atamer, Y; Guven, S; Atamer, A; Kocyigit, Y; Hekimoglu, A; Toprak, G

    2011-01-01

    Serum paraoxonase 1 (PON1) activity and the oxidation of lipoproteins were investigated in 35 women with pre-eclampsia and in 35 healthy control women with normal pregnancies. Blood pressure, body mass index (BMI), serum levels of total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein (a) (Lp[a]), and PON1 activity were assessed. There were no significant between-group differences in subject age, gestational age at diagnosis of pre-eclampsia, BMI, serum total cholesterol, triglycerides, LDL and ApoB levels. Mean systolic and diastolic blood pressures and serum Lp(a) were significantly higher in subjects with pre-eclampsia than in controls. Mean serum HDL, ApoA1 and PON1 activity were significantly lower in subjects with pre-eclampsia compared with controls. In conclusion, lipids and oxidized lipoproteins may play important roles in the pathogenesis of pre-eclampsia.

  12. How placental growth factor detection might improve diagnosis and management of pre-eclampsia.

    PubMed

    Duhig, Kate E; Chappell, Lucy C; Shennan, Andrew H

    2014-05-01

    Pre-eclampsia complicates around 5% of pregnancies and hypertensive disorders of pregnancy are responsible for over 60,000 maternal deaths worldwide annually. Identifying women with pre-eclampsia is a major goal of antenatal care in order to target increased surveillance, allow stabilizing therapies to be implemented and to enable timely delivery. Current risk assessment is based on clinical history, imperfect assessment of clinical signs (e.g., hypertension and proteinuria) and nonspecific biochemical markers, all of which are subject to considerable error. This is further confounded by underlying maternal disease such as chronic hypertension or renal pathology. Angiogenic factors reflect the underlying pathophysiology of pre-eclampsia and there is emerging evidence that they can now be used for more accurate risk assessment. The most promising of these factors include placental growth factor and soluble fms-like tyrosine kinase-1. Used at point of care, these can accurately discriminate true disease in suspected cases and subsequent need for delivery.

  13. Association between risk for pre-eclampsia and HLA DR4

    SciTech Connect

    Not Available

    1990-03-17

    Dr. Kilpatrick and colleagues report results of a family study showing an association between HLA DR4 and mild and proteinuric pre-eclampsia in a British (Edinburgh) maternal population. Among 76 parous sisters of women with protein uric pre-eclampsia, they found that sisters with pregnancy-induced hypertension (pre-eclampsia with or without proteinuria) had a higher frequency of HLA DR4 antigen than did normotensive sisters. In addition, they cited unpublished findings in which they found a higher frequency of HLA DR4 antigen in a large sample of pre-eclamptic women and their babies than in appropriate controls. The authors have completed a study of HLA antigens and pregnancy outcome among a coherent of 715 black (50.9%) and white (49.1%) primigravida who were delivered at a medical center in southern USA. HLA DR typing was done by the one-color fluorescence technique with reagents. On the basis of standard criteria for diagnosis of pre-eclampsia and eclampsia, 6.9 of the cohort had mild non-proteinuric pre-eclampsia, 8.8% had pregnancy-induced hypertension, and 9.5% had combined pre-eclampsia and eclampsia. Whereas black women had higher rates than white women in all three clinical categories (eg, pregnancy-induced hypertension 10.7% vs 6.8%, respectively), differences were not significant and frequencies of HLA DR4 antigen were higher among normotensives in both races (results not shown). They therefore pooled the two racial groups for analyses.

  14. Socio-Demographic and Other Risk Factors of Pre Eclampsia at a Tertiary Care Hospital, Karnataka: Case Control Study

    PubMed Central

    Gandhi, Sangeetha; Rao, Vishwas

    2014-01-01

    Background: Pre-eclampsia is one of the leading causes of maternal and infant morbidity and mortality worldwide. The aetiopathogenesis of this condition involves combination of genetic predisposition and environmental factors. The aim of the study was to determine the socio demographic and other risk factors of pre-eclampsia. Materials and Methods: A case control study was conducted at a tertiary care hospital, Karnataka among 100 cases of pre-eclampsia and 200 controls without pre eclampsia. Non probability purposive sampling technique was adopted to select the study subjects. Data was collected by using a pre tested semi structured questionnaire which included information related to socio-demographic and other known risk factors of pre eclampsia. Primary data was collected by interviewing study subjects and secondary data of cases was obtained from case records. Data was analysed using SPSS. Results: Study subjects included 100 cases and 200 controls. Age of less than 20 y (OR=3.8), monthly income of less than Rs4000 (OR=6.8), age of menarche of less than 12 y (OR=13.1), family h/o pre eclampsia (OR=36.0), family h/o Diabetes (OR=44.9), family h/o hypertension (OR=16.7) and previous h/o PIH (OR=58.5) are found to be significant risk factors of pre eclampsia. Conclusion: The significant risk factors may be used for screening pre-eclampsia during registration of pregnancy. PMID:25386463

  15. The characteristic of Indonesia's pre-eclampsia: From obstetric intensive care with ventilator until epidemiologic and its molecular biology profile of pulmonary edema in severe pre-eclampsia.

    PubMed

    Hermanto; Adityawarman; Sulistyono; Ardian, M; Dachlan, E G

    2014-07-01

    Pulmonary edema is among the least frequently diagnosed criteria for severe pre-eclampsia. A higher incidence of pulmonary edema was noted in older patients, multigravidas, and patients with underlying chronic hypertension that developed prior to delivery. The development of pulmonary edema was also associated with the administration of excess colloid or crystaloid infusion. Two hundreds and thirty millions people occupying Indonesia as tropical and coastal country gave rise the problem of highly maternal mortality rate of 225/100,000 deliveries where pre-eclampsia and eclampsia as most possible cause. Over 5years from the year 2005 through 2009 our 160 eclampsia study observed about significantly correlation between typical estafet referred case and maternal mortality (Odds ratio 19.1 and P=0.065). Specifically those referred eclampsia cases arriving lately to our tertiary hospital, complication of pulmonary edema also apparently became determinant factor to uphold the increased maternal mortality (Odds ratio 6.1 and P=0.083) We found at our teaching hospital Dr. Soetomo Surabaya as referral center along the year 2012, 477 pre-eclampsia-eclampsia cases which complicated by 27 cases of pulmonary from which we apply obstetric intensive care unit for tightly monitoring treatment. The majority use of ventilator were applied on 22 cases (81.4%), that most approximately 16 cases (72%) need 48h under ventilator use and the remaining 6 cases was not untill 5days of extubation. The etiology of pulmonary edema in preeclamptic patients involves multi-factors; abnormal COP-PWCP gradient, increased pulmonary capillary permeability, and left ventricular failure were identified causes. It has been well known that the pathogenesis of pulmonary edema in severe pre-eclampsia-eclampsia initiated by capillary alveolar leakage that leading increased capillary permeability and extravascular fluid oncotic as well as decreased plasma oncotic pressure. In severe pre-eclampsia appear that

  16. Case-control study of severe pre-eclampsia of early onset.

    PubMed

    Moore, M P; Redman, C W

    1983-08-27

    Twenty four women with severe pre-eclampsia diagnosed before 34 weeks' gestation were compared with 48 randomly selected controls matched for age and parity. Subjects were studied in the puerperium using a questionnaire, clinical examination, and review of case records. A history of infertility, headaches (particularly migraine), pre-eclampsia in a previous pregnancy, or a raised serum alpha-fetoprotein concentration at the time of screening for neural tube defect in the index pregnancy were all identified as significant risk factors in the pre-eclamptic women. Maternal age, a history of chronic hypertension or renal disease, or excessive maternal weight were not significantly associated with pre-eclampsia. Almost all the infants of pre-eclamptic women showed retarded growth: 18 were below the 10th centile and only one weighed more than the 25th centile. Four babies died. These observations indicate that pre-eclampsia of early onset may differ from the late onset disease not only in its very high perinatal morbidity and mortality but in its distinctive maternal risk factors.

  17. Placental Proteomics Provides Insights into Pathophysiology of Pre-Eclampsia and Predicts Possible Markers in Plasma.

    PubMed

    Mary, Sheon; Kulkarni, Mahesh J; Malakar, Dipankar; Joshi, Sadhana R; Mehendale, Savita S; Giri, Ashok P

    2017-02-03

    Pre-eclampsia is a hypertensive disorder characterized by the new onset of hypertension >140/90 mmHg and proteinuria after the 20th week of gestation. The disorder is multifactorial and originates with abnormal placentation. Comparison of the placental proteome of normotensive (n = 25) and pre-eclamptic (n = 25) patients by gel-free proteomic techniques identified a total of 2145 proteins in the placenta of which 180 were differentially expressed (>1.3 fold, p < 0.05). Gene ontology enrichment analysis of biological process suggested that the differentially expressed proteins belonged to various physiological processes such as angiogenesis, apoptosis, oxidative stress, hypoxia, and placental development, which are implicated in the pathophysiology of pre-eclampsia. Some of the differentially expressed proteins were monitored in the plasma by multiple reaction monitoring analysis, which showed an increase in apolipoproteins A-I and A-II in gestational weeks 26-30 (2-fold, p < 0.01), while haptoglobin and hemopexin decreased in gestational weeks 26-30 and week 40/at delivery (1.8 fold, p < 0.01) in pre-eclamptic patients. This study provides a proteomic insight into the pathophysiology of pre-eclampsia. Identified candidate proteins can be evaluated further for the development of potential biomarkers associated with pre-eclampsia pathogenesis.

  18. IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia?

    PubMed

    Redman, C W; Sargent, I L; Staff, A C

    2014-02-01

    Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as

  19. Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?

    PubMed

    Ahmed, Asif; Ramma, Wenda

    2015-03-01

    Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the 'two-stage model' of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the 'accelerator'. The 'braking system' includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-γ-lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator-brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti-angiogenic factors sFlt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line.

  20. Biomarkers for the management of pre-eclampsia in pregnant women.

    PubMed

    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.

  1. Development of mHealth applications for pre-eclampsia triage.

    PubMed

    Dunsmuir, Dustin T; Payne, Beth A; Cloete, Garth; Petersen, Christian Leth; Görges, Matthias; Lim, Joanne; von Dadelszen, Peter; Dumont, Guy A; Ansermino, J Mark

    2014-11-01

    The development of mobile applications for the diagnosis and management of pregnant women with pre-eclampsia is described. These applications are designed for use by community-based health care providers (c-HCPs) in health facilities and during home visits to collect symptoms and perform clinical measurements (including pulse oximeter readings). The clinical data collected in women with pre-eclampsia are used as the inputs to a predictive model providing a risk score for the development of adverse outcomes. Based on this risk, the applications provide recommendations on treatment, referral, and reassessment. c-HCPs can access patient records across multiple visits, using multiple devices that are synchronized using a secure Research Electronic Data Capture server. A unique feature of these applications is the ability to measure oxygen saturation with a pulse oximeter connected to a smartphone (Phone Oximeter). The mobile health application development process, including challenges encountered and solutions are described.

  2. Galectin-7 serum levels are altered prior to the onset of pre-eclampsia.

    PubMed

    Menkhorst, E; Koga, K; Van Sinderen, M; Dimitriadis, E

    2014-04-01

    Galectins regulate many cell functions important for placental development, however, the localization and role of galectin-7 is unknown. We hypothesized galectin-7 would be expressed by the placenta and detected in serum. Galectin-7 immunolocalized to syncytiotrophoblast, extravillous trophoblast and glandular epithelium in 1st trimester placenta/decidua and to syncytiotrophoblast and endothelial cells in term placenta, but in pre-eclamptic placentas endothelial staining was absent. Galectin-7 serum concentration was significantly elevated in women (weeks 10-12 and 17-20) who subsequently developed pre-eclampsia compared to women with healthy pregnancies. Galectin-7 is a promising prospective serum biomarker for pre-eclampsia and likely has important functions in placentation.

  3. Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model.

    PubMed

    Li, Heng; Ohta, Hidenobu; Tahara, Yu; Nakamura, Sakiko; Taguchi, Kazuaki; Nakagawa, Machiko; Oishi, Yoshihisa; Goto, Yu-Ichi; Wada, Keiji; Kaga, Makiko; Inagaki, Masumi; Otagiri, Masaki; Yokota, Hideo; Shibata, Shigenobu; Sakai, Hiromi; Okamura, Kunihiro; Yaegashi, Nobuo

    2015-10-16

    Pre-eclampsia affects approximately 5% of all pregnant women and remains a major cause of maternal and fetal morbidity and mortality. The hypertension associated with pre-eclampsia develops during pregnancy and remits after delivery, suggesting that the placenta is the most likely origin of this disease. The pathophysiology involves insufficient trophoblast invasion, resulting in incomplete narrow placental spiral artery remodeling. Placental insufficiency, which limits the maternal-fetal exchange of gas and nutrients, leads to fetal intrauterine growth restriction. In this study, in our attempt to develop a new therapy for pre-eclampsia, we directly rescued placental and fetal hypoxia with nano-scale size artificial oxygen carriers (hemoglobin vesicles). The present study is the first to demonstrate that artificial oxygen carriers successfully treat placental hypoxia, decrease maternal plasma levels of anti-angiogenic proteins and ameliorate fetal growth restriction in the pre-eclampsia rat model.

  4. Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model

    PubMed Central

    Li, Heng; Ohta, Hidenobu; Tahara, Yu; Nakamura, Sakiko; Taguchi, Kazuaki; Nakagawa, Machiko; Oishi, Yoshihisa; Goto, Yu-ichi; Wada, Keiji; Kaga, Makiko; Inagaki, Masumi; Otagiri, Masaki; Yokota, Hideo; Shibata, Shigenobu; Sakai, Hiromi; Okamura, Kunihiro; Yaegashi, Nobuo

    2015-01-01

    Pre-eclampsia affects approximately 5% of all pregnant women and remains a major cause of maternal and fetal morbidity and mortality. The hypertension associated with pre-eclampsia develops during pregnancy and remits after delivery, suggesting that the placenta is the most likely origin of this disease. The pathophysiology involves insufficient trophoblast invasion, resulting in incomplete narrow placental spiral artery remodeling. Placental insufficiency, which limits the maternal-fetal exchange of gas and nutrients, leads to fetal intrauterine growth restriction. In this study, in our attempt to develop a new therapy for pre-eclampsia, we directly rescued placental and fetal hypoxia with nano-scale size artificial oxygen carriers (hemoglobin vesicles). The present study is the first to demonstrate that artificial oxygen carriers successfully treat placental hypoxia, decrease maternal plasma levels of anti-angiogenic proteins and ameliorate fetal growth restriction in the pre-eclampsia rat model. PMID:26471339

  5. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies

    PubMed Central

    Duckitt, Kirsten; Harrington, Deborah

    2005-01-01

    Objective To determine the risk of pre-eclampsia associated with factors that may be present at antenatal booking. Design Systematic review of controlled studies published 1966-2002. Data synthesis Unadjusted relative risks were calculated from published data. Results Controlled cohort studies showed that the risk of pre-eclampsia is increased in women with a previous history of pre-eclampsia (relative risk 7.19, 95% confidence interval 5.85 to 8.83) and in those with antiphospholipids antibodies (9.72, 4.34 to 21.75), pre-existing diabetes (3.56, 2.54 to 4.99), multiple (twin) pregnancy (2.93, 2.04 to 4.21), nulliparity (2.91, 1.28 to 6.61), family history (2.90, 1.70 to 4.93), raised blood pressure (diastolic ≥ 80 mm Hg) at booking (1.38, 1.01 to 1.87), raised body mass index before pregnancy (2.47, 1.66 to 3.67) or at booking (1.55, 1.28 to 1.88), or maternal age ≥ 40 (1.96, 1.34 to 2.87, for multiparous women). Individual studies show that risk is also increased with an interval of 10 years or more since a previous pregnancy, autoimmune disease, renal disease, and chronic hypertension. Conclusions These factors and the underlying evidence base can be used to assess risk at booking so that a suitable surveillance routine to detect pre-eclampsia can be planned for the rest of the pregnancy. PMID:15743856

  6. Effect of Sildenafil on Pre-Eclampsia-Like Mouse Model Induced By L-Name.

    PubMed

    Motta, C; Grosso, C; Zanuzzi, C; Molinero, D; Picco, N; Bellingeri, R; Alustiza, F; Barbeito, C; Vivas, A; Romanini, M C

    2015-08-01

    N(omega)-nitro-L-arginine methyl ester (L-NAME) decreases the vasodilator effect of nitric oxide (NO) and induces pre-eclampsia in mouse. Sildenafil inhibits the degradation of nitric oxide and increases vasodilation. This study aimed to determine the effects of sildenafil citrate on angiogenesis and oxidative stress at the maternal foetal interface on pre-eclampsia-like mouse model induced by L-NAME. Twenty pregnant mice were divided into four groups: (i) vehicle control; (ii) L-NAME; (iii) sildenafil; (4) L-NAME+sildenafil. L-NAME was administered from day 7 of pregnancy and sildenafil from day 8 until day 16; animals were euthanized on day 17. Placental and foetal sizes and weights were measured; lipid peroxide levels and catalase activity in placental homogenates were determined, and placental vascular endothelia were identified by lectin-histochemistry using BSA-I lectin. Western blot analysis was used to determine VEGF expression in placental homogenates. No changes were seen in placental and foetal development in mice with normal pregnancies treated with sildenafil. Treatments with L-NAME reduced significantly the placental weight and average height and decreased the percentage of the endothelial surface. These alterations may be mediated by the reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L-NAME on nitric oxide synthase (NOS) synthesis. This effect was offset by the treatment with sildenafil, with an increase in the percentage of the endothelial surface. In conclusion, our results indicate that treatment with sildenafil on pre-eclampsia mouse model can be used without adverse effects on the concept and its use in the treatment of pre-eclampsia is promising.

  7. Pre-eclampsia and first-onset postpartum psychiatric episodes: a Danish population-based cohort study

    PubMed Central

    Bergink, V.; Laursen, T. M.; Johannsen, B. M. W.; Kushner, S. A.; Meltzer-Brody, S.; Munk-Olsen, T.

    2016-01-01

    Background Recent evidence suggests that postpartum psychiatric episodes may share similar etiological mechanisms with immune-related disorders. Pre-eclampsia is one of the most prevalent immune-related disorders of pregnancy. Multiple clinical features are shared between pre-eclampsia and postpartum psychiatric disorders, most prominently a strong link to first pregnancies. Therefore, we aimed to study if pre-eclampsia is a risk factor for first-onset postpartum psychiatric episodes. Method We conducted a cohort study using the Danish population registry, with a total of 400 717 primiparous women with a singleton delivery between 1995 and 2011. First-lifetime childbirth was the main exposure variable and the outcome of interest was first-onset postpartum psychiatric episodes. The main outcome measures were monthly incidence rate ratios (IRRs), with the period 11–12 months after birth as the reference category. Adjustments were made for age, calendar period, reproductive history, and perinatal maternal health including somatic and obstetric co-morbidity. Results Primiparous women were at particularly high risk of first-onset psychiatric episodes during the first month postpartum [IRR 2.93, 95% confidence interval (CI) 2.53–3.40] and pre-eclampsia added to that risk (IRR 4.21, 95% CI 2.89–6.13). Having both pre-eclampsia and a somatic co-morbidity resulted in the highest risk of psychiatric episodes during the 3-month period after childbirth (IRR 4.81, 95% CI 2.72–8.50). Conclusions We confirmed an association between pre-eclampsia and postpartum psychiatric episodes. The possible explanations for this association, which are not mutually exclusive, include the psychological impact of a serious medical condition such as pre-eclampsia and the neurobiological impact of pre-eclampsia-related vascular pathology and inflammation. PMID:26243040

  8. [Care plan for women with cesarean section and pre-eclampsia].

    PubMed

    Sabbagh-Sequera, Miriam; Loidi-García, Jose María; Romero-Vázquez, Gloria Maria

    2015-01-01

    Pregnancy pathologies in general, and pre-eclampsia in particular, are problems usually treated in post-anesthesia recovery and hospitalization units. Pre-eclampsia is the most frequent form of hypertension associated with pregnancy (50%). It affects from 7% to 10% of pregnant women. It is known as pregnancy and puerperium multisystem syndrome. It is due to a reduction of the systemic perfusion generated by the vasospasms and the activation of the coagulation systems. A clinical case is presented of the immediate post-surgery period of a patient, who has been operated on cesarean section after having been diagnosed with pre-eclampsia. A nursing care plan was prepared, based on Marjory Gordon functional patterns and guided by NANDA-NOC-NIC taxonomy, where 6 nursing diagnoses, which are the basis for the fulfillment of this nursing process, are identified: Risk of infection, excess fluid volume, risk of bleeding, insufficient knowledge about its pathological process, severe pain, and anxiety. The application of this care plan leads to an improvement in the patient care and in the work organization.

  9. 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.

  10. S-Nitrosoglutathione improves haemodynamics in early-onset pre-eclampsia

    PubMed Central

    Everett, Thomas R; Wilkinson, Ian B; Mahendru, Amita A; McEniery, Carmel M; Garner, Stephen F; Goodall, Alison H; Lees, Christoph C

    2014-01-01

    Aims To determine the effects of in vivo S-nitrosoglutathione (GSNO) infusion on cardiovascular function, platelet function, proteinuria and biomarker parameters in early-onset pre-eclampsia. Methods We performed an open-label dose-ranging study of GSNO in early-onset pre-eclampsia. Six women underwent GSNO infusion whilst receiving standard therapy. The dose of GSNO was increased incrementally to 100 μg min−1 whilst maintaining blood pressure of >140/80 mmHg. Aortic augmentation index, aortic pulse wave velocity, blood pressure and maternal–fetal Doppler parameters were measured at each dose. Platelet P-selectin, protein-to-creatinine ratio and soluble anti-angiogenic factors were measured pre- and postinfusion. Results Augmentation index fell at 30 μg min−1 S-nitrosoglutathione (−6%, 95% confidence interval 0.6 to 13%), a dose that did not affect blood pressure. Platelet P-selectin expression was reduced [mean (interquartile range), 6.3 (4.9–7.6) vs. 4.1 (3.1–5.7)% positive, P = 0.03]. Soluble endoglin levels showed borderline reduction (P = 0.06). There was a borderline significant change in pre-to-postinfusion protein-to-creatinine ratio [mean (interquartile range), 0.37 (0.09–0.82) vs. 0.23 (0.07–0.49) g mmol−1, P = 0.06]. Maternal uterine and fetal Doppler pulsatility indices were unchanged. Conclusions In early-onset pre-eclampsia, GSNO reduces augmentation index, a biomarker of small vessel tone and pulse wave reflection, prior to affecting blood pressure. Proteinuria and platelet activation are improved at doses that affect blood pressure minimally. These effects of GSNO may be of therapeutic potential in pre-eclampsia, a condition for which no specific treatment exists. Clinical studies of GSNO in early-onset pre-eclampsia will determine whether these findings translate to improvement in maternal and/or fetal outcome. PMID:24627995

  11. Reduced risk of pre-eclampsia with organic vegetable consumption: results from the prospective Norwegian Mother and Child Cohort Study

    PubMed Central

    Torjusen, Hanne; Brantsæter, Anne Lise; Haugen, Margaretha; Alexander, Jan; Bakketeig, Leiv S; Lieblein, Geir; Stigum, Hein; Næs, Tormod; Swartz, Jackie; Holmboe-Ottesen, Gerd; Roos, Gun; Meltzer, Helle Margrete

    2014-01-01

    Objective Little is known about the potential health effects of eating organic food either in the general population or during pregnancy. The aim of this study was to examine associations between organic food consumption during pregnancy and the risk of pre-eclampsia among nulliparous Norwegian women. Design Prospective cohort study. Setting Norway, years 2002–2008. Participants 28 192 pregnant women (nulliparous, answered food frequency questionnaire and general health questionnaire in mid-pregnancy and no missing information on height, body weight or gestational weight gain). Main outcome measure Relative risk was estimated as ORs by performing binary logistic regression with pre-eclampsia as the outcome and organic food consumption as the exposure. Results The prevalence of pre-eclampsia in the study sample was 5.3% (n=1491). Women who reported to have eaten organic vegetables ‘often’ or ‘mostly’ (n=2493, 8.8%) had lower risk of pre-eclampsia than those who reported ‘never/rarely’ or ‘sometimes’ (crude OR=0.76, 95% CI 0.61 to 0.96; adjusted OR=0.79, 95% CI 0.62 to 0.99). The lower risk associated with high organic vegetable consumption was evident also when adjusting for overall dietary quality, assessed as scores on a healthy food pattern derived by principal component analysis. No associations with pre-eclampsia were found for high intake of organic fruit, cereals, eggs or milk, or a combined index reflecting organic consumption. Conclusions These results show that choosing organically grown vegetables during pregnancy was associated with reduced risk of pre-eclampsia. Possible explanations for an association between pre-eclampsia and use of organic vegetables could be that organic vegetables may change the exposure to pesticides, secondary plant metabolites and/or influence the composition of the gut microbiota. PMID:25208850

  12. Mass spectrometry-based proteomics for pre-eclampsia and preterm birth.

    PubMed

    Law, Kai P; Han, Ting-Li; Tong, Chao; Baker, Philip N

    2015-05-14

    Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered.

  13. Cohort profile: the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC)

    PubMed Central

    Jääskeläinen, Tiina; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Laivuori, Hannele

    2016-01-01

    Purpose The Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) Study was established to set up a nationwide clinical and DNA database on women with and without pre-eclampsia (PE), including their partners and infants, in order to identify genetic risk factors for PE. Participants FINNPEC is a cross-sectional case–control cohort collected from 5 university hospitals in Finland during 2008–2011. A total of 1450 patients with PE and 1065 pregnant control women without PE (aged 18–47 years) were recruited. Altogether, there were 1377 full triads (625 PE and 752 control triads). Findings to date The established cohort holds both clinical and genetic information of mother–infant–father triads representing a valuable resource for studying the pathogenesis of the disease. Furthermore, maternal biological samples (first and third trimester serum and placenta) will provide additional information for PE research. Until now, research has encompassed studies on candidate genes, Sanger and next-generation sequencing, and various studies on the placenta. FINNPEC has also participated in the InterPregGen study, which is the largest investigation on maternal and fetal genetic factors underlying PE until now. Future plans Ongoing studies focus on elucidating the role of immunogenetic and metabolic factors in PE. Data on morbidity and mortality will be collected from mothers and fathers through links to the nationwide health registers. PMID:28067621

  14. Risk factors for pre-eclampsia/eclampsia among working women in Mexico City.

    PubMed

    Cerón-Mireles, P; Harlow, S D; Sánchez-Carrillo, C I; Núñez, R M

    2001-01-01

    This study examined risk factors for pre-eclampsia/eclampsia in a population-based sample of pregnant working women in Mexico City. Over a 3-month period, all women who gave birth at three major hospitals and who had worked for at least 3 months during pregnancy were interviewed. After excluding mothers with multiple gestations or infants with birth defects, and previous diagnoses of hypertension, chronic renal disease or diabetes, 131 of 2,436 women (5.4%) had been diagnosed with pre-eclampsia and/or eclampsia. The frequency was much higher among women of low socio-economic status: 12% of uninsured women (SSA) compared with 4.2% of private sector employees (IMSS) and 1.3% of public sector employees (ISSSTE). After adjusting for education, women working in services (OR = 1.68, 95% CI = 1.01, 2.81) and in retail (OR = 1.99, 95% CI = 1.18, 3.37), primiparae (OR = 2.64, 95% CI = 1.65, 4.21) and women whose pregestational weight was > or = 55 kg (OR = 2.02, 95% CI = 1.34, 3.04) were at increased risk. Efforts to develop and evaluate intervention programmes should target hospitals serving the uninsured (SSA) if reduction in the number of preventable maternal deaths in Mexico is to be achieved. Such programmes should also target service and retail workers and identify women with poor glycaemic control early in pregnancy.

  15. Immunological analogy between allograft rejection, recurrent abortion and pre-eclampsia - the same basic mechanism?

    PubMed

    Wilczyński, Jacek R

    2006-07-01

    There are still controversies concerning the role of immunological mechanisms engaged both in recurrent abortions (RA) and pre-eclampsia (PE). According to some opinions, recurrent miscarriage is comparable to organ-specific autoimmune disease. Analysis of immune reactions shows that graft rejection shares many similar mechanisms with RA and PE. This fact allows us to conclude that rejection of transplanted alloantigenic organs and pregnancy loss have probably the same evolutionary origin. Subsets and functions of immunocompetent cells (T CD4, suppressor gammadeltaT, cytotoxic T CD8, Treg, Tr1, uterine NK cells), over-activation of innate immunity (activation of NK cytotoxic cells, macrophages, neutrophils and complement), changes of Th1/Th2 cytokine balance (IL-2, IL-12, IL-15, IL-18, IFNgamma, TNFalpha vs. IL-4, IL-10, TGFbeta), importance of HLA-G molecule, CD200/CD200R interaction, over-expression of adhesion molecules, fgl2 prothrombinase activation and stimulation of IDO and HO expression, all suggest that RA and PE are syndromes of fetal allograft rejection, and not organ-specific autoimmune diseases. According to that supposition, an analogy might exist between acute graft rejection and recurrent abortion, and between chronic graft rejection and pre-eclampsia.

  16. Bilateral thalamic infarct caused by spontaneous vertebral artery dissection in pre-eclampsia with HELLP syndrome: a previously unreported association.

    PubMed

    Borelli, Paolo; Baldacci, Filippo; Vergallo, Andrea; Del Dotto, Paolo; Lucetti, Claudio; Nuti, Angelo; Bonuccelli, Ubaldo

    2012-11-01

    Cerebrovascular accidents are not rare during pregnancy and the postpartum period. Pre-eclampsia is a common condition that is characterized by proteinuria and de novo hypertension that may be complicated by hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Spontaneous cervical artery dissection has been rarely reported in the postpartum period but never in association with HELLP syndrome. We describe a case of pre-eclampsia and HELLP syndrome complicated in the postpartum period by bilateral thalamic infarct as result of left vertebral artery dissection. We speculated about the possible common etiopathologic mechanisms involved in this previously unreported association.

  17. Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion

    PubMed Central

    Garrido-Gomez, Tamara; Ona, Katherine; Kapidzic, Mirhan; Gormley, Matthew; Simón, Carlos; Genbacev, Olga

    2017-01-01

    Pre-eclampsia (PE), which affects ∼8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs normally upregulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g. placental proteins, markers of oxidative stress). We confirmed an sPE-related increase in production of PAPPA1, which releases IGF1 from its binding protein. IGF1 enhanced proliferation of smooth chorion CTBs, a possible explanation for expansion of this layer, which may partially compensate for the placental deficits. PMID:28232601

  18. TH17 cells in human recurrent pregnancy loss and pre-eclampsia.

    PubMed

    Fu, Binqing; Tian, Zhigang; Wei, Haiming

    2014-11-01

    T helper 17 (TH17) cells have been identified as a new lineage of helper T cells and have been shown to be important in host defense against extracellular infectious agents, autoimmune disease and chronic inflammatory diseases. Recently, TH17 cells have also been shown to participate in successful pregnancy, as well as in the pathogenesis of diseases of pregnancy, such as recurrent spontaneous abortion (RSA) and pre-eclampsia (PE). Here, we review our current knowledge of TH17 cells in human RSA and PE. We also discuss how the local uterine microenvironment affects the differentiation of TH17 cells and the mechanisms that regulate TH17 cells during pregnancy. Research into TH17 cells will not only advance our understanding of TH17-related pregnancy complications, but will also facilitate the design of novel therapies for reproductive diseases.

  19. Lower body nerve stretch: a role in essential hypertension or pre-eclampsia?

    PubMed

    Milne, B

    1996-10-01

    Despite the relatively high incidence of essential hypertension and pregnancy-induced hypertension, the etiologies of these disorders remain enigmatic. A link between stretching of neural structures in the lower body and the induction of hypertension in these disorders is hypothesized. Hypertension has been documented in patients undergoing femoral and tibial lengthening procedures; in experimental models the stretching of lower extremity nerves appeared to be responsible for the increase in blood pressure with bone lengthening. The upright posture of humans puts an added strain on nerves and an increased pressure on lumbar disks may put increasing tension on the nerve roots. The resultant nerve stretch in pregnant women may be exacerbated by the hormone relaxin. A possible link between the stretching of neural structures and the genesis of essential hypertension or pre-eclampsia/eclampsia is hypothesized.

  20. An Assessment of Fetal Cerebral and Hepatic Perfusion in Normal Pregnancy and Pre-Eclampsia Using Three-Dimensional Ultrasound

    PubMed Central

    Addley, Susan; Ali, Amanda

    2017-01-01

    Background Pre-eclampsia and placental causes of intrauterine growth restriction (IUGR) are part of the same spectrum of disorders. In IUGR, there is preferential shunting of blood to the fetal brain at the expense of other organs. We wanted to demonstrate that this also occurs in pre-eclampsia using three dimensional (3D) ultrasound. The 3D indices of perfusion are: flow index (FI), vascular index (VI) and vascularisation flow index (VFI) which reflect tissue vascularity and flow intensity. Methods Fourteen normal pregnant women and 14 with diagnosed pre-eclampsia were recruited. Scanning was conducted by 2 observers using a Voluson E8 machine. Perfusion was measured at a pre-defined position within the fetal brain and fetal liver. The power Doppler signals were quantified using the ‘histogram facility’ to generate 3 indices of vascularity: FI, VI and VFI. The unpaired t-test was used to compare differences between groups. The hypothesis was that fetal brain FI, VI and VFI would be similar between women with normal pregnancy and women with pre-eclampsia, but measurements would be reduced in the fetal liver in women with pre-eclampsia. Results Maternal characteristics of age, body mass index and gestation were not different between groups. The depth of insonnation did not differ between groups. Fetal cerebral perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 22.4 (5.7) vs. 21.1 (4.3) respectively (p=0.49). For VI, the mean (SD) was as 64.7 (40.4) vs. 79.1 (27.4) respectively (p=0.28). For VFI, the mean (SD) was 14.8 (10.3) vs. 16.1 (5.5) respectively (p = 0.66). Fetal hepatic perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 34.4 (19.9) vs. 27.8 (11.0) respectively (p = 0.28). For VI, mean (SD) was 67.6 (36.0) vs. 87.3 (25.8) respectively (p=0.11). For VFI, the mean (SD) was 19.6 (11.6) vs. 23.1 (10

  1. Can the laboratory assay of protein C activity assist in monitoring the hemostatic function in pre-eclampsia?

    PubMed

    He, S; Bremme, K; Blombäck, M

    1999-04-01

    Published reports do not agree about whether protein C activity is non-significantly changed or decreased in a hypercoagulable state induced by pre-eclampsia without hemolysis-elevated liver enzyme/low platelet (HELLP) syndrome. In order to assess the relationship between this anticoagulant and enhanced hemostasis, levels of protein C activity, thrombin-antithrombin complexes, soluble fibrin, fibrin D-dimers and antithrombin were determined in 30 pre-eclampsia patients without the HELLP syndrome, in 22 normal pregnant women in gestational weeks 30-35, and in 13 non-pregnant controls. Levels of thrombin-antithrombin complexes, soluble fibrin and D-dimers increased (P < 0.05) whereas antithrombin decreased (P < 0.05) in patients with pre-eclampsia, compared with normal pregnant women. Levels of protein C did not differ significantly between patients with pre-eclampsia, normal pregnant women and controls (P > 0.05). The 5th and 95th percentiles of protein C levels in normal pregnant women were 0.53 and 1.30 U/ml, respectively; levels between these two values could be considered physiological. When the pre-eclampsia patients were subdivided according to these percentiles, none belonged to the subgroup with protein C < or = 5th percentile; 23% (seven of 30) fell into the subgroup with protein C > or = 95th percentile. Elevated levels of hypercoagulation markers were shown in the groups whose protein C fell within 5th-95th or > or = 95th percentiles (P < 0.05), compared with normal pregnant women. Concentrations of protein C and thrombin-antithrombin complex were significantly correlated (r = 0.69, P > 0.05) in patients with pre-eclampsia. In summary, in subjects with pre-eclampsia without the HELLP syndrome, protein C activity may be similar to that in normal pregnant women. However, such a 'physiological' anticoagulant level in association with the enhanced thrombin generation and fibrin formation does not necessarily reflect a physiological capability of coagulation

  2. Absence of Factor V Leiden, thrombomodulin and prothrombin gene variants in Black South African women with pre-eclampsia and eclampsia.

    PubMed

    Hira, B; Pegoraro, R J; Rom, L; Moodley, J

    2003-03-01

    It has been suggested that gene aberrations may contribute to vascular endothelial dysfunction of pre-eclampsia in Caucasian and Japanese women. This study was undertaken to examine the association between pre-eclampsia in Black Zulu speaking South African women and the Factor 5 Leiden mutation. 100 patients with pre-eclampsia comprised the study group. The control group comprised 110 normotensive pregnant women of the same population group. Genotyping was performed to detect the G or A allele at residue 506 of the Factor V gene, and the C or T allele at residue 455 of the thrombomodulin gene. Our findings demonstrate that these particularly genetic loci are of little use in disease association studies for pre-eclampsia in homogenous Zulu speaking Africans.

  3. Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals.

    PubMed

    Elliot, Michael G; Crespi, Bernard J

    2015-03-05

    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.

  4. 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

  5. Syncytiotrophoblast Extracellular Vesicles from Pre-Eclampsia Placentas Differentially Affect Platelet Function

    PubMed Central

    Tannetta, Dionne S.; Hunt, Kathryn; Jones, Chris I.; Davidson, Naomi; Coxon, Carmen H.; Ferguson, David; Redman, Christopher W.; Gibbins, Jonathan M.; Sargent, Ian L.; Tucker, Katherine L.

    2015-01-01

    Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition. PMID:26551971

  6. A study of changes in homocysteine levels during normal pregnancy and pre-eclampsia.

    PubMed

    Singh, Urmila; Gupta, H P; Singh, R K; Shukla, Manju; Singh, Ranjana; Mehrotra, Seema Sinha Nee; Prasad, Shweta

    2008-08-01

    To find out changes in homocysteine levels that occur during normal pregnancy and pregnancy with pre-eclamptic toxaemia and also to find out correlation between homocysteine concentration and preeclamptic toxaemia a study was carried out among 90 women of which 30 were control which included normotensive non-pregnant women and the study group I comprised 30 pregnant normotensive women and the study group II comprised 30 pregnant women with pre-eclamptic toxaemia. Serum homocysteine was measured in all subjects using fluorescence polarisation immuno-assay. Control group had highest mean homocysteine levels while the study group I had least mean homocysteine levels (p < 0.001). Levels were significantly higher in subjects with BP > 146/100 mm Hg as compared to subjects with BP >140/90 and <146/100 mm Hg (p=0.017). There was significant difference between study group I and II at same gestational age. Hyperhomocysteinaemia was observed in pre-eclamptic females, also it was found that homocysteine levels were directly correlated with severity of pre-eclampsia.

  7. Association of anemia, pre-eclampsia and eclampsia with seasonality: a realist systematic review.

    PubMed

    Hlimi, Tina

    2015-01-01

    Seasonal patterns influencing maternal health have been documented globally and are of particular importance for women in developing countries who disproportionately suffer from anemia, pre-eclampsia and eclampsia. This paper adopts a realist systematic approach to investigate the maternal outcome of anemia and eclampsia in relation to seasonality. A review of 23 published studies shows a statistically significant link between these maternal disorders and seasonality in developing countries in Sub-Saharan Africa and Central and South Asia. Anemia and eclampsia tend to decrease during the dry season, only to increase with greater rainfall, low and cold temperatures. Numerous studies suggest that the seasonality of anemia and eclampsia is associated with changes in malaria transmission. This was observed during the rainy season, suggesting a potential seasonal relationship with malaria as a driver of these disorders in Sub-Saharan Africa. Anemia and eclampsia were principally exacerbated among primigravidae and young women. Food insecurity, access to antenatal care, poverty, and environmental factors may also play a crucial role in the predisposition to these disorders. More research is required to identify the seasonal link between malaria and eclampsia particularly as climate change may exacerbate the rate of the disorders in tropical and sub-tropical areas.

  8. Genetic polymorphisms of vascular endothelial growth factor in severe pre-eclampsia.

    PubMed

    Bányász, Ilona; Szabó, Szilvia; Bokodi, Géza; Vannay, Adám; Vásárhelyi, Barna; Szabó, András; Tulassay, Tivadar; Rigó, János

    2006-04-01

    Several lines of evidence support the hypothesis that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of pre-eclampsia (PE). VEGF is a key component in the regulation of vascular remodelling and the survival of cytotrophoblasts in the placenta. In this case-control study, we aimed to test whether VEGF genetic polymorphisms are associated with the risk of severe PE. We enrolled 84 nulliparous pregnant women with severe PE (PE group). Their VEGF G(+405)C and VEGF C(-2578)A genotypes were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) from venous blood samples and were compared with the corresponding VEGF genotypes of 96 nulliparous patients with uncomplicated pregnancies (control group). Carriers of the VEGF(+405)G allele occurred less frequently in PE than in the control group [P = 0.039; adjusted odds ratio (aOR) = 0.28, range: 0.08-0.93]. Hypertension and proteinuria were diagnosed earlier (by 1.6 weeks and 1.9 weeks, respectively) in PE patients with VEGF(-2578)A only after adjustment of this association for risk factors of PE. Our results suggest that carriers of VEGF(+405)G allele have a decreased susceptibility to PE and that the progression of PE may be modified by the presence of VEGF(-2578)A allele. Nevertheless, the clinical significance of these findings remains to be determined.

  9. Altered placental expression of kisspeptin and its receptor in pre-eclampsia.

    PubMed

    Cartwright, Judith E; Williams, Paula Juliet

    2012-07-01

    Kisspeptin, originally identified as metastatin, important in preventing cancer metastasis, has more recently been shown to be important in pregnancy. Roles indicated for kisspeptin in pregnancy include regulating trophoblast invasion and migration during placentation. The pregnancy-specific disorder pre-eclampsia (PE) is now accepted to begin with inadequate trophoblast invasion and the current study therefore sets out to characterise placental expression of both kisspeptin (KISS1) and its receptor (KISS1R) throughout pregnancy and in PE. Placental tissue was obtained from women undergoing elective surgical termination of early pregnancy (n=10) and from women following Caesarean section at term in normal pregnancy (n=10) and with PE (n=10). Immunohistochemistry of paraffin embedded sections and western immunoblotting were performed to assess protein localisation and expression. Quantitative real-time PCR was carried out to evaluate mRNA expression of both KISS1 and KISS1R. Protein and mRNA expression was found to mirror each other with KISS1 expression found to be reduced in PE compared with that in normal term pregnancy. Interestingly, KISS1R expression at both the mRNA and protein levels was found to be increased in PE compared with that in normal term pregnancy. The current findings of increased KISS1R expression may represent a mechanism by which functional activity of KISS1 is higher in PE than in normal pregnancy. Higher levels of activity of KISS1R may be involved in inhibition of trophoblast invasion and angiogenesis, which are associated with PE.

  10. Altered placental expression of kisspeptin and its receptor in pre-eclampsia

    PubMed Central

    Cartwright, Judith E; Williams, Paula Juliet

    2012-01-01

    Kisspeptin, originally identified as metastatin, important in preventing cancer metastasis, has more recently been shown to be important in pregnancy. Roles indicated for kisspeptin in pregnancy include regulating trophoblast invasion and migration during placentation. The pregnancy-specific disorder pre-eclampsia (PE) is now accepted to begin with inadequate trophoblast invasion and the current study therefore sets out to characterise placental expression of both kisspeptin (KISS1) and its receptor (KISS1R) throughout pregnancy and in PE. Placental tissue was obtained from women undergoing elective surgical termination of early pregnancy (n=10) and from women following Caesarean section at term in normal pregnancy (n=10) and with PE (n=10). Immunohistochemistry of paraffin embedded sections and western immunoblotting were performed to assess protein localisation and expression. Quantitative real-time PCR was carried out to evaluate mRNA expression of both KISS1 and KISS1R. Protein and mRNA expression was found to mirror each other with KISS1 expression found to be reduced in PE compared with that in normal term pregnancy. Interestingly, KISS1R expression at both the mRNA and protein levels was found to be increased in PE compared with that in normal term pregnancy. The current findings of increased KISS1R expression may represent a mechanism by which functional activity of KISS1 is higher in PE than in normal pregnancy. Higher levels of activity of KISS1R may be involved in inhibition of trophoblast invasion and angiogenesis, which are associated with PE. PMID:22526494

  11. Placental microRNA expression in pregnancies complicated by superimposed pre-eclampsia on chronic hypertension

    PubMed Central

    VASHUKOVA, ELENA S.; GLOTOV, ANDREY S.; FEDOTOV, PAVEL V.; EFIMOVA, OLGA A.; PAKIN, VLADIMIR S.; MOZGOVAYA, ELENA V.; PENDINA, ANNA A.; TIKHONOV, ANDREI V.; KOLTSOVA, ALLA S.; BARANOV, VLADISLAV S.

    2016-01-01

    Pre-eclampsia (PE) is a complication of pregnancy that affects 5–8% of women after 20 weeks of gestation. It is usually diagnosed based on the de novo onset of hypertension and proteinuria. Preexisting hypertension in women developing PE, also known as superimposed PE on chronic hypertension (SPE), leads to elevated risk of maternal and fetal mortality. PE is associated with an altered microRNA (miRNA) expression pattern in the placenta, suggesting that miRNA deregulation is involved in the pathogenesis of PE. Whether and how the miRNA expression pattern is changed in the SPE placenta remains unclear. The present study analyzed the placental miRNA expression profile in pregnancies complicated by SPE. miRNA expression profiles in SPE and normal placentas were investigated using an Ion Torrent sequencing system. Sequencing data were processed using a comprehensive analysis pipeline for deep miRNA sequencing (CAP-miRSeq). A total of 22 miRNAs were identified to be deregulated in placentas from patients with SPE. They included 16 miRNAs previously known to be associated with PE and 6 novel miRNAs. Among the 6 novel miRNAs, 4 were upregulated (miR-518a, miR-527, miR-518e and miR-4532) and 2 downregulated (miR-98 and miR-135b) in SPE placentas compared with controls. The present results suggest that SPE is associated with specific alterations in the placental miRNA expression pattern, which differ from alterations detected in PE placentas, and therefore, provide novel targets for further investigation of the molecular mechanisms underlying SPE pathogenesis. PMID:27176897

  12. Analysis of cardiovascular oscillations: A new approach to the early prediction of pre-eclampsia

    NASA Astrophysics Data System (ADS)

    Malberg, H.; Bauernschmitt, R.; Voss, A.; Walther, T.; Faber, R.; Stepan, H.; Wessel, N.

    2007-03-01

    Pre-eclampsia (PE) is a serious disorder with high morbidity and mortality occurring during pregnancy; 3%-5% of all pregnant women are affected. Early prediction is still insufficient in clinical practice. Although most pre-eclamptic patients show pathological uterine perfusion in the second trimester, this parameter has a positive predictive accuracy of only 30%, which makes it unsuitable for early, reliable prediction. The study is based on the hypothesis that alterations in cardiovascular regulatory behavior can be used to predict PE. Ninety-six pregnant women in whom Doppler investigation detected perfusion disorders of the uterine arteries were included in the study. Twenty-four of these pregnant women developed PE after the 30th week of gestation. During pregnancy, additional several noninvasive continuous blood pressure recordings were made over 30 min under resting conditions by means of a finger cuff. The time series extracted of systolic as well as diastolic beat-to-beat pressures and the heart rate were studied by variability and coupling analysis to find predictive factors preceding genesis of the disease. In the period between the 18th and 26th weeks of pregnancy, three special variability and baroreflex parameters were able to predict PE several weeks before clinical manifestation. Discriminant function analysis of these parameters was able to predict PE with a sensitivity and specificity of 87.5% and a positive predictive value of 70%. The combined clinical assessment of uterine perfusion and cardiovascular variability demonstrates the best current prediction several weeks before clinical manifestation of PE.

  13. Mechanism of vascular dysfunction due to circulating factors in women with pre-eclampsia.

    PubMed

    Kao, Cindy K; Morton, Jude S; Quon, Anita L; Reyes, Laura M; Lopez-Jaramillo, Patricio; Davidge, Sandra T

    2016-04-01

    Circulating factors have been proposed to play a major role in the pathophysiology of endothelial dysfunction in pre-eclampsia (PE), which is defined as new-onset hypertension with proteinuria after 20 weeks of gestation. However, the mechanisms leading to altered vascular reactivity remain unclear. We hypothesized that circulating factors lead to endothelial dysfunction by increasing oxidative stress and reducing nitric oxide (NO) and prostaglandin (PG) bioavailability. Pregnant rat uterine and mesenteric arteries were incubated overnight with 3% normotensive (NP) or PE plasma collected from women upon admission to hospital. Responses to methacholine (MCh) were obtained using wire myography to assess endothelial function pathways. Vascular superoxide level was measured via dihydroethidium staining and nitric oxide synthase (NOS) expression via Western blots. PE plasma significantly increased superoxide levels and impaired endothelial dysfunction in uterine arteries (Emax 79.9±5.6% compared with 44.9±6.3%, P=0.0004), which was restored in the presence of oxidant scavengers or PG synthesis inhibition. Uterine artery vasodilation was abolished in the presence of pan-NOS inhibitor (P<0.0001) in both NP- and PE-treated vessels, but inducible nitric oxide synthase (iNOS)-dependent vasodilation was present only in NP-treated arteries. Uterine arteries exposed to PE plasma exhibit an increased endothelial NOS expression and a decreased iNOS expression. PE plasma did not alter endothelial function in mesenteric arteries, suggesting that the effect of circulating factors was vascular-bed-specific. We have shown that circulating factors lead to endothelial dysfunction via altered oxidative stress and vasodilator pathways. The present study contributes to our understanding of the pathophysiology and finding a potential target for intervention in PE.

  14. Evidence of proteinuria, but no other characteristics of pre-eclampsia, in relaxin-deficient mice.

    PubMed

    O'Sullivan, Kelly P; Marshall, Sarah A; Cullen, Scott; Saunders, Tahnee; Hannan, Natalie J; Senadheera, Sevvandi N; Parry, Laura J

    2016-08-04

    Pre-eclampsia (PE) is a leading cause of maternal and fetal death, characterised by an imbalance of placental growth factors and hypertension at >20 weeks gestation. Impaired maternal systemic vascular adaptations and fetal growth restriction are features of both PE and pregnant relaxin-deficient (Rln-/-) mice. The aim of the present study was to investigate whether these phenotypes in Rln-/- mice are associated with abnormal placental growth factor expression, increased soluble fms-like tyrosine kinase-1 (sFlt-1), proteinuria and/or hypertension during pregnancy. In addition, we examined relaxin and relaxin receptor (relaxin/insulin like family peptide receptor 1 (RXFP1)) mRNA expression in placentas of women with PE. There was no significant difference in placental vascular endothelial growth factor A (VegfA) and placenta growth factor (Plgf) gene expression between Rln-/- and wild-type mice. Circulating plasma sFlt-1 concentrations in pregnant mice of both genotypes and ages were increased compared with non-pregnant mice but were lower in younger pregnant Rln-/- mice compared with aged-matched Rln+/+ mice. Aged pregnant Rln-/- mice had higher urinary albumin:creatinine ratios compared with age-matched Rln+/+ mice, indicative of proteinuria. Systolic and diastolic blood pressures did not differ between genotypes. In addition, PE in women was not associated with altered placental mRNA expression of RLN2 or RXFP1 at term. Overall, the data demonstrate that pregnant Rln-/- mice do not have the typical characteristics of PE. However, these mice show evidence of proteinuria, but we suggest that this results from systemic renal vascular dysfunction before pregnancy.

  15. Prospective assessment of neurodevelopment in children following a pregnancy complicated by severe pre-eclampsia

    PubMed Central

    Warshafsky, Chelsie; Walker, Mark; Wen, Shi-Wu; Smith, Graeme N

    2016-01-01

    Objective To prospectively examine whether children of women with a pregnancy affected by severe pre-eclampsia (PE), compared to children of women without a PE-affected pregnancy, have differences in neurodevelopmental performance up to 5 years of age. Design Prospective cohort study. Setting Tertiary care centre. Participants Women were recruited following a PE-affected pregnancy. After each PE participant was recruited, the next normotensive woman without a prior history of PE and matched by parity, maternal age and race was invited to participate. Women with a history of chronic hypertension, diabetes or renal disease were excluded. Total enrolment included 129 PE-affected and 140 normotensive mothers. Outcome measures The primary outcome measure was failure of the Ages and Stages Questionnaire (ASQ). The ASQ was completed yearly, until age 5. Results A significant difference was found in the proportion of ASQ categories failed in year 3 (p<0.05), and this approached significance in years 1 and 4 (p<0.10 and p<0.15, respectively). At year 1, the number of ASQ categories failed was significantly greater among children born to PE mothers. A subgroup analysis revealed that a significant proportion of PE children born preterm (<37 weeks) failed the ASQ in years 3 and 4 (p<0.05), and when failed, those who were preterm failed significantly more categories (p<0.05). A trend towards increased failure in the gross motor category was found. There was a significant positive correlation between maternal lifetime CVD risk score and number of ASQ categories failed at years 1 and 3 (p<0.05). Conclusions Severe PE is associated with other adverse pregnancy outcomes, including intrauterine growth restriction and preterm birth, all of which are associated with increased neurodevelopment delays. Thus, PE indicates a need for early screening and intervention at the neurodevelopmental level to improve children's long-term health, with larger studies required to tease out

  16. Serum FRAP Levels and Pre-eclampsia among Pregnant Women in a Rural Community of Northern India

    PubMed Central

    Gupta, Anant; Gupta, Sanjeev Kumar; Prakash, Shyam; Kalaivani, Mani; Pandav, Chandrakant S.; Rai, Sanjay Kumar; Misra, Puneet

    2016-01-01

    Introduction There is a balance between the oxidative and the anti-oxidative forces in human body. Some studies document decreased level of anti-oxidant in pre-eclampsia while other studies showed normal level of anti-oxidant in pre-eclampsia and the evidence is equivocal. Aim The aim of the present study was to assess enzymatic anti-oxidant activities in pre-eclamptic women and compare it with normotensive pregnant women with period of gestation between 28 to 36 weeks. Materials and Methods A community-based cross-sectional survey was conducted (from November 2012-December 2013) at the Ballabgarh Health and Demographic Surveillance System (HDSS) site which was managed by Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, India. All registered pregnant women with period of gestation between 28 weeks – 36 weeks were eligible for inclusion in the study. All eligible pregnant women were contacted through home visit. A total of 217 pregnant women were enrolled out of which 209 blood samples were collected from pregnant women. About three ml of blood from antecubital vein was drawn without use of tourniquet, under aseptic conditions. It was later analysed for the serum anti-oxidative measures {Malanoaldehyde, Vitamin C, Ferric Reducing Ability of Plasma (FRAP) levels}. Data were entered on Epi-Info version 3.5.4. Data management and analysis was carried out in Stata 11. The means were compared using t-test and p-value stated. Categorical data was analysed using chi-square test. Logistic regression was used and adjusted p-value was stated. Results A total of 217 pregnant women were eligible for the study and all were enrolled. Out of the 217 blood samples collected, eight samples accidently got destroyed. A total of 28 out of remaining 209 pregnant women (13.4%) had pre-eclampsia. Mean age (SD) was 22.4 (2.3) years, mean height (SD) was 156.6 (6.9) cm, mean weight (SD) was 65.1 (9.7) kg in pre-eclampsia group. In pre-eclampsia group mean

  17. Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia

    PubMed Central

    Maulucci, Giuseppe; Rolfo, Alessandro; Giuffrida, Domenica; Veglia, Manuela; De Spirito, Marco; Scambia, Giovanni; Todros, Tullia; Di Simone, Nicoletta

    2016-01-01

    Background Pre-eclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality worldwide. It is defined by new onset of hypertension and proteinuria after the 20th week of gestation and characterized by systemic exaggerated inflammatory response. D6 is a chemokines scavenger receptor that binds with high affinity CC chemokines, internalizes and targets the ligands for degradation. It is expressed in trophoblast-derived tissues and prevents excessive placenta leukocyte infiltration.The aim of this study was to investigate the expression and function of D6 in human placentae from pre-eclamptic and healthy pregnant women. Methods and Results Plasma levels of D6-binding CC chemokines (CCL-2, CCL-3, CCL-4, CCL-7, CCL-11) and pro-inflammatory cytokines (IL-6, TNF-α, CRP) were analyzed in 37 healthy pregnant women and 38 patients with PE by multiplex bead assay. Higher circulating levels of CCL7, CCL11, IL-6, (p<0.0001) and CRP (p<0.05) were observed in PE women compared to controls. Levels of circulating CCL4 were decreased in PE (p<0.001), while no significant differences of CCL2, CCL3 or TNF-α levels were detected. Immunofluorescent staining of placental sections showed higher expression of D6 receptor in the PE syncytiotrophoblast. Confocal and Western blot (WB) analyses revealed a prevalent distribution of D6 in trophoblast cells membranes in PE. Increased activation of D6 intracellular pathway was observed by Western blot analyses of p-LIMK and p-cofilin in trophoblast cell lysates. D6 functional assays showed reduced scavenging of CCL2 in PE cells compared to controls. Since actin filaments spatial assembling is essential for D6 intracellular trafficking and scavenging activity, we investigated by confocal microscopy trophoblast cytoskeleton organization and we observed a dramatic disarrangement in PE compared to controls. Conclusions our results suggest membrane distribution of D6 receptor on trophoblast cell membranes in PE, together with

  18. Could molecular assessment of calcium metabolism be a useful tool to early screen patients at risk for pre-eclampsia complicated pregnancy? Proposal and rationale.

    PubMed

    Gizzo, Salvatore; Noventa, Marco; Di Gangi, Stefania; Saccardi, Carlo; Cosmi, Erich; Nardelli, Giovanni Battista; Plebani, Mario

    2015-06-01

    One of the most frequent causes of maternal and perinatal morbidity is represented by hypertensive disorders during pregnancy. Women at high risk must be subjected to a more intensive antenatal surveillance and prophylactic treatments. Many genetic risk factors, clinical features and biomarkers have been proposed but none of these seems able to prevent pre-eclampsia onset. English literature review of manuscripts focused on calcium intake and hypertensive disorders during pregnancy was performed. We performed a critical analysis of evidences about maternal calcium metabolism pattern in pregnancy analyzing all possible bias affecting studies. Calcium supplementation seems to give beneficial effects on women with low calcium intake. Some evidence reported that calcium supplementation may drastically reduce the percentage of pre-eclampsia onset consequently improving the neonatal outcome. Starting from this evidence, it is intuitive that investigations on maternal calcium metabolism pattern in first trimester of pregnancy could represent a low cost, large scale tool to screen pregnant women and to identify those at increased risk of pre-eclampsia onset. We propose a biochemical screening of maternal calcium metabolism pattern in first trimester of pregnancy to discriminate patients who potentially may benefit from calcium supplementation. In a second step we propose to randomly allocate the sub-cohort of patients with calcium metabolism disorders in a treatment group (calcium supplementation) or in a control group (placebo) to define if calcium supplementation may represent a dietary mean to reduce pre-eclampsia onset and to improve pregnancy outcome.

  19. 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

  20. The effect of pre-eclampsia on the levels of coagulation and fibrinolysis factors in umbilical cord blood of newborns.

    PubMed

    Zanardo, Vincenzo; Savio, Valentina; Sabrina, Gavasso; Franzoi, Malida; Zerbinati, Patrizia; Fadin, Mariangela; Tognin, Giulio; Tormene, Daniela; Pagnan, Antonio; Simioni, Paolo

    2005-04-01

    The effect of pre-eclampsia on coagulation and fibrinolysis in newborns is still under investigation. We have evaluated several coagulation and fibrinolysis parameters in umbilical cord blood of 20 newborns from pre-eclamptic women and of 40 newborns from normotensive women with similar gestational age. Additionally, the presence of factor V Leiden and prothrombin G20210A mutation in cord blood has been assessed. Neonates from pre-eclamptic women exhibited significantly lower birth weight (2.48 +/- 0.92 versus 2.88 +/- 0.68 kg, P < 0.05) and were more frequently admitted to the neonatal intensive care unit (45 versus 20%, P < 0.01) as compared with neonates from normotensive women. Cord blood protein C antigen and activated protein C resistance mean levels were slightly higher in the group of neonates from pre-eclamptic mothers. Fibrinogen levels were lower in this group as compared with control newborns (132.17 +/- 46.97 versus 156.08 +/- 49.58 mg%, P < 0.02), and unrelated to birth weight. No significant differences between cases and controls were found in plasminogen activator inhibitor-1 or tissue plasminogen activator cord blood levels. Heterozygous prothrombin 20210A was found in three newborns from normotensive mothers, whereas no factor V Leiden mutation was found in either group. In conclusion, pre-eclampsia seems to have only mild effects on coagulation and fibrinolytic factors in the cord blood of newborns. Since no excess of common polymorphisms predisposing to thrombosis was found in newborns from pre-eclamptic mothers, it is unlikely that the carriership status of these genetic defects of newborns influences the adverse pregnancy/neonatal outcomes.

  1. Usability and Feasibility of PIERS on the Move: An mHealth App for Pre-Eclampsia Triage

    PubMed Central

    Cloete, Garth; Dunsmuir, Dustin T; Payne, Beth A; von Dadelszen, Peter; Dumont, Guy A; Ansermino, J Mark

    2015-01-01

    Background Pre-eclampsia is one of the leading causes of maternal death and morbidity in low-resource countries due to delays in case identification and a shortage of health workers trained to manage the disorder. Pre-eclampsia Integrated Estimate of RiSk (PIERS) on the Move (PotM) is a low cost, easy-to-use, mobile health (mHealth) platform that has been created to aid health workers in making decisions around the management of hypertensive pregnant women. PotM combines two previously successful innovations into a mHealth app: the miniPIERS risk assessment model and the Phone Oximeter. Objective The aim of this study was to assess the usability of PotM (with mid-level health workers) for iteratively refining the system. Methods Development of the PotM user interface involved usability testing with target end-users in South Africa. Users were asked to complete clinical scenario tasks, speaking aloud to give feedback on the interface and then complete a questionnaire. The tool was then evaluated in a pilot clinical evaluation in Tygerberg Hospital, Cape Town. Results After ethical approval and informed consent, 37 nurses and midwives evaluated the tool. During Study 1, major issues in the functionality of the touch-screen keyboard and date scroll wheels were identified (total errors n=212); during Study 2 major improvements in navigation of the app were suggested (total errors n=144). Overall, users felt the app was usable using the Computer Systems Usability Questionnaire; median (range) values for Study 1 = 2 (1-6) and Study 2 = 1 (1-7). To demonstrate feasibility, PotM was used by one research nurse for the pilot clinical study. In total, more than 500 evaluations were performed on more than 200 patients. The median (interquartile range) time to complete an evaluation was 4 min 55 sec (3 min 25 sec to 6 min 56 sec). Conclusions By including target end-users in the design and evaluation of PotM, we have developed an app that can be easily integrated into health

  2. Parallel decrease in arterial distensibility and in endothelium-dependent dilatation in young women with a history of pre-eclampsia.

    PubMed

    Pàez, Olga; Alfie, José; Gorosito, Marta; Puleio, Pablo; de Maria, Marcelo; Prieto, Noemì; Majul, Claudio

    2009-10-01

    Pre-eclampsia not only complicates 5 to 8% of pregnancies but also increases the risk of maternal cardiovascular disease and mortality later in life. We analyzed three different aspects of arterial function (pulse wave velocity, augmentation index, and flow-mediated dilatation), in 55 nonpregnant, normotensive women (18-33 years old) according to their gestational history: 15 nulliparous, 20 with a previous normotensive, and 20 formerly pre-eclamptic pregnancy. Former pre-eclamptic women showed a significantly higher augmentation index and pulse wave velocity (P < 0.001 and P < 0.05, respectively) and lower flow-mediated dilatation (p = 0.01) compared to control groups. In contrast, sublingual nitroglycerine elicited a comparable vasodilatory response in the three groups. The augmentation index correlated significantly with pulse wave velocity and flow-mediated dilatation (R = 0.28 and R = -0.32, respectively, P < 0.05 for both). No significant correlations were observed between augmentation index or flow-mediated dilatation with age, body mass index (BMI), brachial blood pressure, heart rate, or metabolic parameters (plasma cholesterol, glucose, insulin, or insulin resistance). Birth weight maintained a significantly inverse correlation with the augmentation index (R = -0.51, p < 0.002) but not with flow-mediated dilatation. Our findings revealed a parallel decrease in arterial distensibility and endothelium-dependent dilatation in women with a history of pre-eclampsia compared to nulliparous women and women with a previous normal pregnancy. A high augmentation index was the most consistent alteration associated with a history of pre-eclampsia. The study supports the current view that the generalized arterial dysfunction associated with pre-eclampsia persists subclinically after delivery.

  3. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for women at 2 years

    PubMed Central

    2007-01-01

    Objective The aim of this study was to assess long-term effects for women following the use of magnesium sulphate for pre-eclampsia. Design Assessment at 2–3 years after delivery for women recruited to the Magpie Trial (recruitment in 1998–2001, ISRCTN 86938761), which compared magnesium sulphate with placebo for pre-eclampsia. Setting Follow up after discharge from hospital at 125 centres in 19 countries across five continents. Population A total of 7927 women were randomised at the follow-up centres. Of these women, 2544 were not included for logistic reasons and 601 excluded (109 at a centre where <20% of women were contacted, 466 discharged without a surviving child and 26 opted out). Therefore, 4782 women were selected for follow-up, of whom 3375 (71%) were traced. Methods Questionnaire assessment was administered largely by post or in a dedicated clinic. Interview assessment of selected women was performed. Main outcome measures Death or serious morbidity potentially related to pre-eclampsia at follow up, other morbidity and use of health service resources. Results Median time from delivery to follow up was 26 months (interquartile range 19–36). Fifty-eight of 1650 (3.5%) women allocated magnesium sulphate died or had serious morbidity potentially related to pre-eclampsia compared with 72 of 1725 (4.2%) women allocated placebo (relative risk 0.84, 95% CI 0.60–1.18). Conclusions The reduction in the risk of eclampsia following prophylaxis with magnesium sulphate was not associated with an excess of death or disability for the women after 2 years. PMID:17166220

  4. Periconceptional folic acid fortification for the risk of gestational hypertension and pre-eclampsia: a meta-analysis of prospective studies.

    PubMed

    Yang, Xiaorong; Chen, Hui; Du, Yihui; Wang, Shuting; Wang, Zhiping

    2016-10-01

    Published literatures report controversial results about the association of folic acid-containing multivitamins with gestational hypertension and pre-eclampsia. A comprehensive search was performed to identify related prospective studies to assess the effect of folic acid fortification on gestational hypertension and pre-eclampsia. The Q test and I(2) statistic were used to examine between-study heterogeneity. Fixed or random effects models were selected based on study heterogeneity. A funnel plot and modified Egger linear regression test were used to estimate publication bias. Eleven studies conformed to the criteria. Pooled results indicated that folic acid fortification alone was not associated with the occurrence of gestational hypertension [relative risk (RR) = 1.03, 95% confidence interval (CI): 0.98-1.09, P = 0.267] and pre-eclampsia (RR = 0.99, 95% CI: 0.90-1.08, P = 0.738). However, supplementation of multivitamins containing folic acid could prevent gestational hypertension (RR = 0.57, 95% CI: 0.43-0.76, P < 0.001) and pre-eclampsia (RR = 0.64, 95% CI: 0.48-0.84, P = 0.001). The difference between folic acid fortification alone and multivitamins containing folic acid was significant. This meta-analysis suggests that periconceptional multivitamin supplementation with appropriate dose, not folic acid alone, is an appropriate recommendation for pregnant women. The effect should be further confirmed by conducting large-scale randomised controlled trials.

  5. Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease

    PubMed Central

    Johnson, Matthew P.; Brennecke, Shaun P.; East, Christine E.; Dyer, Thomas D.; Roten, Linda T.; Proffitt, J. Michael; Melton, Phillip E.; Fenstad, Mona H.; Aalto-Viljakainen, Tia; Mäkikallio, Kaarin; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K.; Pouta, Anneli; Kivinen, Katja; Ekholm, Eeva; Hietala, Reija; Sainio, Susanna; Saisto, Terhi; Uotila, Jukka; Klemetti, Miira; Inkeri Lokki, Anna; Georgiadis, Leena; Huovari, Elina; Kortelainen, Eija; Leminen, Satu; Lähdesmäki, Aija; Mehtälä, Susanna; Salmen, Christina

    2013-01-01

    Pre-eclampsia is an idiopathic pregnancy disorder promoting morbidity and mortality to both mother and child. Delivery of the fetus is the only means to resolve severe symptoms. Women with pre-eclamptic pregnancies demonstrate increased risk for later life cardiovascular disease (CVD) and good evidence suggests these two syndromes share several risk factors and pathophysiological mechanisms. To elucidate the genetic architecture of pre-eclampsia we have dissected our chromosome 2q22 susceptibility locus in an extended Australian and New Zealand familial cohort. Positional candidate genes were prioritized for exon-centric sequencing using bioinformatics, SNPing, transcriptional profiling and QTL-walking. In total, we interrogated 1598 variants from 52 genes. Four independent SNP associations satisfied our gene-centric multiple testing correction criteria: a missense LCT SNP (rs2322659, P = 0.0027), a synonymous LRP1B SNP (rs35821928, P = 0.0001), an UTR-3 RND3 SNP (rs115015150, P = 0.0024) and a missense GCA SNP (rs17783344, P = 0.0020). We replicated the LCT SNP association (P = 0.02) and observed a borderline association for the GCA SNP (P = 0.07) in an independent Australian case–control population. The LRP1B and RND3 SNP associations were not replicated in this same Australian singleton cohort. Moreover, these four SNP associations could not be replicated in two additional case–control populations from Norway and Finland. These four SNPs, however, exhibit pleiotropic effects with several quantitative CVD-related traits. Our results underscore the genetic complexity of pre-eclampsia and present novel empirical evidence of possible shared genetic mechanisms underlying both pre-eclampsia and other CVD-related risk factors. PMID:23420841

  6. Placental Growth Factor (PlGF) in Women with Suspected Pre-Eclampsia Prior to 35 Weeks’ Gestation: A Budget Impact Analysis

    PubMed Central

    Duckworth, Suzy; Seed, Paul T.; Mackillop, Lucy; Shennan, Andrew H.; Hunter, Rachael

    2016-01-01

    Objective To model the resource implications of placental growth factor (PlGF) testing in women with suspected pre-eclampsia prior to 35 weeks’ gestation as part of a management algorithm, compared with current practice. Methods Data on resource use from 132 women with suspected pre-eclampsia prior to 35 weeks’ gestation, enrolled in a prospective observational cohort study evaluating PlGF measurement within antenatal assessment units within two UK consultant-led maternity units was extracted by case note review. A decision analytic model was developed using these data to establish the budget impact of managing women with suspected pre-eclampsia for two weeks from the date of PlGF testing, using a clinical management algorithm and reference cost tariffs. The main outcome measures of resource use (numbers of outpatient appointments, ultrasound investigations and hospital admissions) were correlated to final diagnosis and used to calculate comparative management regimes. Results The mean cost saving associated with the PlGF test (in the PlGF plus management arm) was £35,087 (95% CI -£33,181 to -£36,992) per 1,000 women. This equated to a saving of £582 (95% CI -552 to -£613) per woman tested. In 94% of iterations, PlGF testing was associated with cost saving compared to current practice. Conclusions This analysis suggests PlGF used as part of a clinical management algorithm in women presenting with suspected pre-eclampsia prior to 35 weeks’ gestation could provide cost savings by reducing unnecessary resource use. Introduction of PlGF testing could be used to direct appropriate resource allocation and overall would be cost saving. PMID:27741259

  7. Ultrasound Microbubble-Mediated Delivery of Integrin-Linked Kinase Gene Improves Endothelial Progenitor Cells Dysfunction in Pre-Eclampsia

    PubMed Central

    Cui, Kai; Yan, Ting; Luo, Qingqing; Zheng, Yanfang; Liu, Xiaoxia; Huang, Xiaoyu

    2014-01-01

    Pre-eclampsia (PE) is a specific vascular complication in pregnancy whose precise mechanism is still unclear. We hypothesized that endothelial progenitor cells (EPCs), the precursor of endothelial cells, might be impaired in patients with PE and hold a great promise for the treatment of PE. In the present study, we analyzed the EPCs number and expression of integrin-linked kinase (ILK) in PE patients. We confirmed that both EPCs number and ILK expression were diminished in PE patients. Next, we transfected EPCs with ILK gene using ultrasonic microbubble technique (UMT) for the first time, as UMT is a novel type of gene transfer technology showing promising applications in stem cells apart from EPCs. To further investigate the transfection efficiency of UMT, RT-PCR analysis and western blot were used to examine the messenger RNA (mRNA) and protein level of ILK. After transfection of the ILK gene, EPCs function was tested to illustrate the role of ILK in cell proliferation, apoptosis, migration, and secretion. The results of the in vitro study suggested that UMT, a novel gene delivery system, could be considered a potent physical method for EPCs transfection. Moreover, the growth and angiogenetic properties of EPCs are enhanced by introducing ILK. This study may afford a new trend for EPCs transfection and gene therapy in PE. PMID:24564279

  8. Antibodies Anti-Caga Cross-React with Trophoblast Cells: A Risk Factor for Pre-Eclampsia?

    PubMed Central

    Franceschi, Francesco; Di Simone, Nicoletta; D’Ippolito, Silvia; Castellani, Roberta; Di Nicuolo, Fiorella; Gasbarrini, Giovanni; Yamaoka, Yoshio; Todros, Tullia; Scambia, Giovanni; Gasbarrini, Antonio

    2013-01-01

    Background Previous studies reported an epidemiological association between CagA-positive H. pylori strains and pre-eclampsia. As antibodies anti-CagA cross-react with endothelial cells and trophoblast cells show an endothelial phenotypic profile, we hypothesized that anti-CagA antibodies may recognize antigens of cytotrophoblast cells, thus impairing their function. Materials and Methods Placenta samples were obtained from healthy women. Cytotrophoblast cells were cultured in a medium containing increasing concentration of polyclonal anti-CagA antibodies. Binding of anti-CagA antibodies to cytotrophoblast cells was evaluated by cell ELISA and immunofluorescence assay. Invasive potential of those cells was assessed by an invasion culture system and by measuring of MMP-2. Protein sequencing was performed on antigens precipitated by anti-CagA antibodies. Measurement of phosphorylated ERK expression and NF-kB DNA-binding activity in trophoblast cells incubated with anti-CagA or irrelevant antibodies was also performed. Results Anti-CagA antibodies recognized β-actin of cytotrophoblast cells, showing a dose-dependent binding. Incubation of cytotrophoblast cells with increasing doses of anti-CagA antibodies significantly reduced their invasiveness and determined a significant decrease in phosphorylated ERK expression and a reduced NF-kB translocation activity. Conclusions This study shows that anti-CagA antibodies recognize β-actin of cytotrophoblast cells, reducing their invasiveness ability, possibly giving a biological explanation for the epidemiological association. PMID:23066738

  9. Increased plasma mRNAs of placenta-specific 1 (PLAC1) and glial cells-missing 1 (GCM1) in mothers with pre-eclampsia.

    PubMed

    Fujito, Naoya; Samura, Osamu; Miharu, Norio; Tanigawa, Miho; Hyodo, Maki; Kudo, Yoshiki

    2006-03-01

    In this study we have investigated whether quantitative analysis of placental mRNAs in maternal plasma provides a way to monitor placental status. We measured plasma concentrations of human chorionic gonadotropin beta-subunit (betahCG) and human placental lactogen (hPL) mRNAs as previously reported mRNAs and pregnancy associated plasma protein A (PAPP-A), placenta-specific 1 (PLAC1) and glial cells-missing 1 (GCM1) mRNAs, which have not been measured during the course of normal pregnancy. Firstly, peripheral blood was obtained at various times from healthy pregnant women to clarify the time course of placental mRNAs. Secondly, blood was obtained from women with pre-eclampsia and gestational age-matched controls to examine whether placental mRNAs change in pre-eclampsia. Plasma was separated from these samples for extraction of RNA, followed by reverse transcription polymerse chain reaction analysis. Median concentrations of PLAC1 and GCM1 mRNA in plasma of pre-eclamptic subjects respectively were 1625 and 2141 copies/ml, significantly higher than 195 and 881 copies/ml, the values for controls (Mann-Whitney test, p<0.001). No significant difference was seen in hPL, betahCG, or PAPP-A mRNA concentration between pre-eclamptic and control groups. Plasma PLAC1 and GCM1 mRNAs appear promising as noninvasively measurable molecular markers for pre-eclampsia.

  10. 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

  11. Predictive value of miR-210 as a novel biomarker for pre-eclampsia: a systematic review protocol

    PubMed Central

    Nikuei, Pooneh; Davoodian, Nahid; Tahamtan, Iman; Keshtkar, Abbas Ali

    2016-01-01

    Introduction Pre-eclampsia (PE) is a serious condition affecting 3–5% of all pregnancies worldwide. However, underlying molecular pathogenesis of this disease has largely remained unknown. Recently, several studies have indicated the possibility role of microRNAs, especially miR-210, in the aetiology of PE. The aim of this systematic review is to assess the possible role of miR-210 as a novel biomarker for the prediction of PE. Methods and analysis Using a combination of mesh terms ‘preeclampsia’, ‘microRNA’ and their equivalents, an electronic search will be performed for all observational studies (cross sectional, case–control and cohort) in PubMed, Web of Science, Scopus, Embase, Cochrane, LILACS and OvidSP MEDLINE from January 2005 to December 2015. Furthermore, other sources are searched, including grey literature, reference lists of relevant primary studies as well as key journals. Study selection, data extraction and quality assessment of studies will be performed independently by 2 reviewers, and any disagreement will be resolved by consensus. If sufficient data are available, it will be combined by either fixed or random effects models. We will investigate the source)s(and degree of heterogeneity using ‘Heterogeneity χ2’ and I2. Heterogeneity would be investigated through either subgroup analysis or metaregression. Stata V.11.1 will be used for data analysis. Ethics and dissemination The results of this study are disseminated in peer-reviewed journal articles and academic presentations. Formal ethical approval is not required, since the secondary data will be collected. Trial registration number CRD42015032345. PMID:27683514

  12. Mid-trimester fetal-placental velocimetry response to nifedipine may predict early the onset of pre-eclampsia.

    PubMed

    Cobellis, Luigi; De Luca, Antonio; Pecori, Emilia; Mastrogiacomo, Annunziata; Di Pietto, Laura; Iannella, Iolanda; Fornaro, Felice; Scaffa, Cono; Cobellis, Giovanni; Colacurci, Nicola

    2006-01-01

    The effect of nifedipine on fetal-placental blood flow at 22-24 weeks in patients with pregnancy-induced hypertension (PIH) was evaluated. Twenty patients with PIH were submitted to the Doppler evaluation of fetal-placental perfusion at 22-24 weeks. The systo-diastolic (SID) ratio and the pulsatility index (PI) of uterine, umbilical and middle cerebral arteries and systemic blood pressure were recorded before and 7 days after nifedipine administration (10 mg/ per os 3 times/day until delivery). Statistical analysis was performed with paired and unpaired t-test and the two-tailed Fisher exact test. Nifedipine significantly (p < 0.05) decreased the mean systolic pressure in all patients (from 146 to 135 mmHg): 8 patients developed pre-eclampsia (PE) complicated by fetal growth restriction (FGR) (PE group), whilst the remaining were only affected by PIH (PIH group). The gestational age at delivery, neonatal birthweight and 1- and 5-min Apgar scores were significantly (p < 0.001) lower in PE than in PIH women. Nifedipine treatment significantly changed the PI and S/D ratio (mean +/- SEM) of the uterine (PI from 0.66 +/- 0.01 to 0.51 + 0.01; SID ratio: from 2.00 +/- 0.09 to 1.79 + 0.05) and umbilical (PI: from 1.55 +/- 0.04 to 1.40 +/- 0.02; S/D ratio: from 2.45 +/- 0.09 to 2.31+/- 0.09) arteries and the middle cerebral PI (from 1.45 +/- 0.03 to 1.61 +/- 0.01) artery only in PIH, but not in PE patients. Fetal-placental blood flow changes after nifedipine may early identify patients at risk of PE.

  13. Increased endoplasmic reticulum stress in decidual tissue from pregnancies complicated by fetal growth restriction with and without pre-eclampsia

    PubMed Central

    Lian, I.A.; Løset, M.; Mundal, S.B.; Fenstad, M.H.; Johnson, M.P.; Eide, I.P.; Bjørge, L.; Freed, K.A.; Moses, E.K.; Austgulen, R.

    2011-01-01

    Objectives Endoplasmic reticulum (ER) stress has been implicated in both pre-eclampsia (PE) and fetal growth restriction (FGR), and is characterised by activation of three signalling branches: 1) PERK-pEIF2α, 2) ATF6 and 3) splicing of XBP1(U) into XBP1(S). To evaluate the contribution of ER stress in the pathogenesis of PE relative to FGR, we compared levels of ER stress markers in decidual tissue from pregnancies complicated by PE and/or FGR. Study design Whole-genome transcriptional profiling was performed on decidual tissue from women with PE (n = 13), FGR (n = 9), PE+FGR (n = 24) and controls (n = 58), and used for pathway- and targeted transcriptional analyses of ER stress markers. The expression and cellular localisation of ER stress markers was assesses by Western blot and immunofluorescence analyses. Results Increased ER stress was observed in FGR and PE+FGR, including both the PERK-pEIF2α and ATF6 signalling branches, whereas ER stress was less evident in isolated PE. However, these cases demonstrated elevated levels of XBP1(U) protein. ATF6 and XBP1 immunoreactivity was detected in most (> 80%) extravillous trophoblasts, decidual cells and macrophages. No difference in the proportion of immunopositive cells or staining pattern was observed between study groups. Conclusions Increased PERK-pEIF2α and ATF6 signalling have been associated with decreased cellular proliferation and may contribute to the impaired placental growth characterising pregnancies with FGR and PE+FGR. XBP1(U) has been proposed as a negative regulator of ER stress, and increased levels in PE may reflect a protective mechanism against the detrimental effects of ER stress. PMID:21907405

  14. Health system barriers to access and use of magnesium sulfate for women with severe pre-eclampsia and eclampsia in Pakistan: evidence for policy and practice.

    PubMed

    Bigdeli, Maryam; Zafar, Shamsa; Assad, Hafeez; Ghaffar, Adbul

    2013-01-01

    Severe pre-eclampsia and eclampsia are rare but serious complications of pregnancy that threaten the lives of mothers during childbirth. Evidence supports the use of magnesium sulfate (MgSO4) as the first line treatment option for severe pre-eclampsia and eclampsia. Eclampsia is the third major cause of maternal mortality in Pakistan. As in many other Low- and Middle-Income Countries (LMIC), it is suspected that MgSO4 is critically under-utilized in the country. There is however a lack of information on context-specific health system barriers that prevent optimal use of this life-saving medicine in Pakistan. Combining quantitative and qualitative methods, namely policy document review, key informant interviews, focus group discussions and direct observation at health facility, we explored context-specific health system barriers and enablers that affect access and use of MgSO4 for severe pre-eclampsia and eclampsia in Pakistan. Our study finds that while international recommendations on MgSO4 have been adequately translated in national policies in Pakistan, the gap remains in implementation of national policies into practice. Barriers to access to and effective use of MgSO4 occur at health facility level where the medicine was not available and health staff was reluctant to use it. Low price of the medicine and the small market related to its narrow indications acted as disincentives for effective marketing. Results of our survey were further discussed in a multi-stakeholder round-table meeting and an action plan for increasing access to this life-saving medicine was identified.

  15. Differentiation of ICOS+ and ICOS- recent thymic emigrant regulatory T cells (RTE T regs) during normal pregnancy, pre-eclampsia and HELLP syndrome.

    PubMed

    Wagner, M I; Jöst, M; Spratte, J; Schaier, M; Mahnke, K; Meuer, S; Zeier, M; Steinborn, A

    2016-01-01

    Two different subsets of naturally occurring regulatory T cells (nTregs), defined by their expression of the inducible co-stimulatory (ICOS) molecule, are produced by the human thymus. To examine the differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) recent thymic emigrant (RTE) T regs during normal pregnancy and in the presence of pre-eclampsia or haemolysis elevated liver enzymes low platelet (HELLP)-syndrome, we used six-colour flow cytometric analysis to determine the changes in the composition of the ICOS(+) and ICOS(-) T reg pools with CD45RA(+) CD31(+) RTE T regs, CD45RA(+) CD31(-) mature naive (MN) T regs, CD45RA(-) CD31(+) and CD45RA(-) CD31(-) memory Tregs. With the beginning of pregnancy until term, we observed a strong differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE, but not CD45RA(+) CD31(-) MN T regs, into CD45RA(-) CD31(-) memory T regs. At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS(+) CD45RA(-) CD31(-) memory T regs. However, in the presence of pre-eclampsia, there was a significantly increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs into CD45RA(-) CD31(+) memory T regs, wherein the lacking differentiation into CD45RA(-) CD31(-) memory T regs was partially replaced by the increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(-) MN Tregs into CD45RA(-) CD31(-) memory T regs. In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA(-) CD31(-) MN T regs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS(+) and ICOS(-) T regs, which were shown to be significantly less suppressive in pre-eclampsia patients, but not in HELLP syndrome patients. Hence, our findings propose that the regular differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs ensures a healthy pregnancy course, while their disturbed differentiation is

  16. Studies on the HLA-DRB1 genotypes in Japanese women with severe pre-eclampsia positive and negative for anticardiolipin antibody using a polymerase chain reaction-restriction fragment length polymorphism method.

    PubMed

    Takakuwa, K; Honda, K; Ishii, K; Hataya, I; Yasuda, M; Tanaka, K

    1999-12-01

    The human leukocyte antigen (HLA)-DR genotype was determined in 54 Japanese women with severe pre-eclampsia in order to elucidate the relationship between HLA-DR antigen systems and pre-eclampsia. The patients were divided into two groups according to positivity for the anticardiolipin antibody (ACA), i.e. one patient group negative for ACA (n = 41) and the other patient group positive for ACA (n = 13). The frequency of each HLA-DRB1 allele in both groups was compared with that in 81 normally fertile Japanese women who had not experienced pre-eclampsia. The genotypes of HLA-DR antigens were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequency of DRB1*04 and DRB1*0403 in the patient group positive for the ACA was significantly higher compared with that in the group of normal fertile women (P< 0.05). The frequency of each HLA-DRB1 allele was not significantly different between patient group with pre-eclampsia negative for ACA and group of normal fertile women. These results suggest a difference in the immunogenetic background between the patient groups with severe pre-eclampsia positive and negative for the ACA.

  17. The Effect of Multi mineral-Vitamin D Supplementation on Pregnancy Outcomes in Pregnant Women at Risk for Pre-eclampsia

    PubMed Central

    Asemi, Zatollah; Esmaillzadeh, Ahmad

    2015-01-01

    Background: The objective of this study was to determine the favorable effects of multi mineral-Vitamin D supplementation on pregnancy outcomes among women at risk for pre-eclampsia. Methods: This randomized double-blind controlled clinical trial was conducted among 46 women at risk for pre-eclampsia at 27 weeks’ gestation with positive roll-over test. Pregnant women were randomly assigned to receive either the multi mineral-Vitamin D supplements (n = 23) or the placebo (n = 23) for 9-week. Multi mineral-Vitamin D supplements were containing 800 mg calcium, 200 mg magnesium, 8 mg zinc, and 400 IU Vitamin D3. Fasting blood samples were taken at baseline and after 9-week intervention to measure related factors. Newborn's outcomes were determined. Results: Although no significant difference was seen in newborn's weight and head circumference between the two groups, mean newborns’ length (51.3 ± 1.7 vs. 50.3 ± 1.2 cm, P = 0.03) was significantly higher in multi mineral-Vitamin D group than that in the placebo group. Compared to the placebo, consumption of multi mineral-Vitamin D supplements resulted in increased levels of serum calcium (+0.19 vs. −0.08 mg/dL, P = 0.03), magnesium (+0.15 vs. −0.08 mg/dL, P = 0.03), zinc (+8.25 vs. −21.38 mg/dL, P = 0.001) and Vitamin D (+3.79 vs. −1.37 ng/ml, P = 0.01). In addition, taking multi mineral-Vitamin D supplements favorably influenced systolic blood pressure (SBP) (−1.08 vs. 6.08 mmHg, P = 0.001) and diastolic blood pressure (DBP) (−0.44 vs. 3.05 mmHg, P = 0.02). Conclusions: Multi mineral-Vitamin D supplementation for 9-week in pregnant women at risk for pre-eclampsia resulted in increased newborn's length, increased circulating levels of maternal serum calcium, magnesium, zinc and Vitamin D, and led to decreased maternal SBP and DBP. PMID:26288706

  18. Effects of High-Dose Vitamin D Supplementation on Metabolic Status and Pregnancy Outcomes in Pregnant Women at Risk for Pre-Eclampsia.

    PubMed

    Karamali, M; Beihaghi, E; Mohammadi, A A; Asemi, Z

    2015-11-01

    This study was designed to assess the beneficial effects of high-dose (cholecalciferol) vitamin D supplementation on metabolic profiles and pregnancy outcomes among pregnant women at risk for pre-eclampsia. This randomized double-blind placebo-controlled clinical trial was performed among 60 pregnant women at risk for pre-eclampsia according to abnormal uterine artery Doppler waveform. Subjects were randomly divided into 2 groups to receive 50 000 IU vitamin D supplements (n=30) or receive placebo (n=30) every 2 weeks from 20 to 32 weeks of gestation. Fasting blood samples were taken at baseline study and 12 weeks after the intervention to quantify relevant variables. Newborn's anthropometric measurements were determined. Pregnant women who received cholecalciferol supplements had significantly increased serum 25-hydroxyvitamin D concentrations (+17.92±2.28 vs. +0.27±3.19 ng/ml, p<0.001) compared with the placebo. The administration of cholecalciferol supplements, compared with the placebo, resulted in significant differences in serum insulin concentrations (+1.08±6.80 vs. +9.57±10.32 μIU/ml, p<0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (+0.19±1.47 vs. +2.10±2.67, p<0.001), homeostatic model assessment-beta cell function (HOMA-B) (+5.82±29.58 vs. +39.81±38.00, p<0.001) and quantitative insulin sensitivity check index (QUICKI) score (-0.009±0.03 vs. -0.04±0.03, p=0.004). Furthermore, cholecalciferol-supplemented pregnant women had increased HDL-cholesterol concentrations (+2.67 ± 8.83 vs. -3.23±7.76 mg/dl, p=0.008) compared with the placebo. Finally, cholecalciferol supplementation led to a significant rise in plasma total antioxidant capacity (TAC) concentrations (+79.00±136.69 vs. -66.91±176.02 mmol/l, p=0.001) compared with the placebo. Totally, the administration of cholecalciferol supplements among pregnant women at risk for pre-eclampsia for 12 weeks had favorable effects on insulin metabolism parameters

  19. The use of angiogenic and antiangiogenic factors in the differential diagnosis of pre-eclampsia, antiphospholipid syndrome nephropathy and lupus nephritis.

    PubMed

    de Jesus, G R; de Jesus, N R; Levy, R A; Klumb, E M

    2014-10-01

    Pre-eclampsia (PE) is a major cause of maternal mortality and morbidity, perinatal deaths, preterm birth and intrauterine growth restriction. Differential diagnosis with antiphospholipid syndrome (APS) nephropathy and systemic lupus erythematosus (SLE) nephritis during pregnancy is difficult, if not sometimes impossible, as all three diseases may present hypertension and proteinuria. Improvement in diagnosis of PE has also offered new paths for differential diagnosis with other conditions and the analysis of angiogenic (vascular endothelial growth factor, placental growth factor) and antiangiogenic factors (serum soluble fms-like tyrosine kinase 1, soluble endoglin) is promising for differentiation between PE, APS nephropathy and SLE nephritis. This article reviews published studies about those factors in non-pregnant and pregnant patients with APS and SLE, comparing with patterns described in PE.

  20. Acute presentation of gestational diabetes insipidus with pre-eclampsia complicated by cerebral vasoconstriction: a case report and review of the published work.

    PubMed

    Mor, Amir; Fuchs, Yael; Zafra, Kathleen; Haberman, Shoshana; Tal, Reshef

    2015-08-01

    Gestational diabetes insipidus (GDI) is a rare, self-limited complication of pregnancy. As it is related to excess placental vasopressinase enzyme activity, which is metabolized in the liver, GDI is more common in pregnancies complicated by conditions associated with liver dysfunction. We present a case of a 41-year-old woman at 38 weeks' gestation who presented with pre-eclampsia with severe features, including impaired liver function and renal insufficiency. Following cesarean section she was diagnosed with GDI, which was further complicated by cerebral vasoconstriction as demonstrated by magnetic resonance angiography. This case raises the possibility that cerebral vasoconstriction may be related to the cause of GDI. A high index of suspicion of GDI should be maintained in patients who present with typical signs and symptoms, especially in the setting of pregnancy complications associated with liver dysfunction.

  1. Association between the candidate susceptibility gene ACVR2A on chromosome 2q22 and pre-eclampsia in a large Norwegian population-based study (the HUNT study).

    PubMed

    Roten, Linda T; Johnson, Matthew P; Forsmo, Siri; Fitzpatrick, Elizabeth; Dyer, Thomas D; Brennecke, Shaun P; Blangero, John; Moses, Eric K; Austgulen, Rigmor

    2009-02-01

    Genome-wide scans in Icelandic, Australian/New Zealand and Finnish pedigrees have provided evidence for maternal susceptibility loci for pre-eclampsia on chromosome 2, although at different positions (Iceland: 2p13 and 2q23, Australia/New Zealand: 2p11-12 and 2q22, Finland: 2p25). In this project, a large population-based (n=65 000) nested case-control study was performed in Norway to further explore the association between positional candidate genes on chromosome 2q and pre-eclampsia, using single-nucleotide polymorphisms (SNPs). DNA samples from 1139 cases (women with one or more pre-eclamptic pregnancies) and 2269 controls (women with normal pregnancies) were genotyped using the Applied Biosystems SNPlex high-throughput genotyping assay. In total, 71 SNPs within positional candidate genes at 2q22-23 locus on chromosome 2 were genotyped in each individual. Genotype data were statistically analysed with the sequential oligogenic linkage analysis routines (SOLAR) computer package. Nominal evidence of association was found for six SNPs (rs1014064, rs17742134, rs1424941, rs2161983, rs3768687 and rs3764955) within the activin receptor type 2 gene (ACVR2A) (all P-values <0.05). The non-independence of statistical tests due to linkage disequilibrium between SNPs at a false discovery rate of 5% identifies our four best SNPs (rs1424941, rs1014064, rs2161983 and rs3768687) to remain statistically significant. The fact that populations with different ancestors (Iceland/Norway-Australia/New Zealand) demonstrate a common maternal pre-eclampsia susceptibility locus on chromosome 2q22-23, may suggest a general role of this locus, and possibly the ACVR2A gene, in pre-eclampsia pathogenesis.

  2. Differential placental expression profile of human Growth Hormone/Chorionic Somatomammotropin genes in pregnancies with pre-eclampsia and gestational diabetes mellitus

    PubMed Central

    Männik, Jaana; Vaas, Pille; Rull, Kristiina; Teesalu, Pille; Laan, Maris

    2012-01-01

    The human GH/CSH cluster consisting of one pituitary-expressed (GH1) and four placenta-expressed loci has been implicated in maternal metabolic adaptation to pregnancy, regulation of intrauterine and postnatal growth. We investigated how the mRNA expression profile of placental GH2, CSH1 and CSH2 genes and their alternative transcripts correlates with maternal pre-eclampsia (PE) and/or gestational diabetes mellitus (GD). The expression of studied genes in PE placentas (n = 17) compared to controls (n = 17) exhibited a trend for reduced transcript levels. The alternative transcripts retaining intron 4, GH2-2 and CSH1-2 showed significantly reduced expression in PE cases without growth restriction (P = 0.007, P = 0.008, respectively). In maternal GD (n = 23), a tendency of differential expression was detected only for the GH2 gene and in pregnancies with large-for-gestational-age newborns. Our results, together with those reported by others, are consistent with a pleiotropic effect of placental hGH/CSH genes at the maternal-fetal interface relating to the regulation of fetal growth and the risk of affected maternal metabolism. PMID:22387044

  3. Comparison of serum maternal adiponectin concentrations in women with isolated intrauterine growth retardation and intrauterine growth retardation concomitant with pre-eclampsia

    PubMed Central

    Büke, Barış; Topçu, Hasan Onur; Engin-Üstün, Yaprak; Danışman, Nuri

    2014-01-01

    Objective The aim of this study was to compare serum maternal adiponectin concentrations in pregnant women with isolated intrauterine growth retardation (IUGR) and in pregnant women with IUGR concomitant with pre-eclampsia (IUGRcwPE). Material and Methods Thirty patients with isolated IUGR (group 1), 20 patients with IUGRcwPE (group 2), and 30 healthy controls (group 3) between age 18–40 were included into the study. Venous blood samples of those patients were obtained in the starving state. Adiponectin concentrations were measured by enzyme-linked immunosorbent assay in serum obtained after centrifugation. To find the differences between the groups, student t-test and one-way ANOVA statistical methods were used. Results There were no differences between the groups in terms of age, body mass index, gestational age, and parity (p>0.05). The values of amniotic fluid index (p<0.001) and weight gained during pregnancy (p=0.017) were significantly different when compared among the three groups. The mean concentrations of adiponectin were 94.041 pg/mL in the IUGR group, 55.717 pg/mL in the IUGRcwPE group, and 51.831 pg/mL in the control group. Both of the differences between the IUGR and IUGRcwPE groups (p value; <0.05) and IUGR and control groups were statistically significant (p value; <0.001). However, there were no significant differences between the IUGRcwPE group and control group (p>0.05). Conclusion We found that IUGR increased maternal serum adiponectin concentrations; however, this rise does not occur in pregnant women with IUGRcwPE. PMID:25317046

  4. The effects of sildenafil citrate on urinary podocin and nephrin mRNA expression in an L-NAME model of pre-eclampsia.

    PubMed

    Baijnath, Sooraj; Murugesan, Saravanakumar; Mackraj, Irene; Gathiram, Prem; Moodley, Jagidesa

    2017-03-01

    We investigated the effects of sildenafil citrate (SC) on podocyturia in N (ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME) model of pre-eclampsia (PE). One hundred and twenty Sprague-Dawley rats (SDR) were divided into five groups like pregnant control (PC), early-onset PE (EOPE), late-onset PE(LOPE), early and late-onset PE with SC-treated groups [EOPE (SC); LOPE (SC)]. PE was induced in SDR by oral administration of L-NAME in drinking water for 4-8 days for EOPE and 8-14 day for LOPE. The blood pressure, urine volume and total urine protein were increased in EOPE and LOPE groups when compared to PC, and all the above parameters decreased in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The EOPE and LOPE groups showed an increase in urinary nephrin mRNA and podocin mRNA levels compared to PC group. Increases in serum and renal soluble fms-like tyrosine kinase-1 (sFlt-1) expression levels and decreases in renal vascular endothelial growth factor (VEGF) expression and serum placenta growth factor (PlGF) levels were observed in EOPE and LOPE groups when compared to PC group. In addition, decreases in serum and renal sFlt-1 expression levels and increases in renal VEGF expression and serum PlGF levels were observed in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The light microscopy showed that the renal tissue of L-NAME-treated rats had extensive glomerular damage, tubular damage and infiltration by mononuclear cells when compared to PC group. Therefore, SC ameliorated podocyturia through its effects on the antiangiogenic/angiogenic status in this animal model.

  5. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months

    PubMed Central

    2007-01-01

    Objective To assess the long-term effects of in utero exposure to magnesium sulphate for children whose mothers had pre-eclampsia. Design Assessment at 18 months of age for children whose mothers were recruited to the Magpie Trial (recruitment 1998–2001 ISRCTN 86938761), which compared magnesium sulphate with placebo. Setting Follow-up of children born at 125 centres in 19 countries across five continents. Population A total of 6922 children were born to women randomised before delivery at follow-up centres. Of these, 2271 were not included for logistic reasons and 168 were excluded (101 at a centre where <20% were contacted, 40 whose death or disability was due to a problem at conception or embryogenesis and 27 whose parent/s opted out). Therefore, 4483 children were included in follow-up, of whom 3283 (73%) were contacted. Methods Assessment by questionnaire, with interview and neurodevelopmental testing of selected children. Main outcome measures Death or neurosensory disability at age of 18 months. Results Of those allocated magnesium sulphate, 245/1635 (15.0%) were dead or had neurosensory disability at 18 months compared with 233/1648 (14.1%) allocated placebo (relative risk [RR] 1.06, 95% CI 0.90–1.25), and of survivors, 19/1409 (1.3%) had neurosensory disability at 18 months compared with 27/1442 (1.9%) (RR 0.72, 95% CI 0.40–1.29). There were no substantial differences in causes of death or in the risk of individual impairments or disabilities. Conclusions The lower risk of eclampsia following prophylaxis with magnesium sulphate was not associated with a clear difference in the risk of death or disability for children at 18 months. PMID:17166221

  6. The Effect of High Dose Folic Acid throughout Pregnancy on Homocysteine (Hcy) Concentration and Pre-Eclampsia: A Randomized Clinical Trial

    PubMed Central

    Sayyah-Melli, Manizheh; Ghorbanihaghjo, Amir; Alizadeh, Mahasti; Kazemi-Shishvan, Maryamalsadat; Ghojazadeh, Morteza; Bidadi, Sanam

    2016-01-01

    Pre-eclampsia is a pregnancy-related multi-systemic hypertensive disorder and affects at least 5% of pregnancies. This randomized clinical trial aimed at assessing the effect of low doses and high doses of folic acid on homocysteine (Hcy) levels, blood pressure, urea, creatinine and neonatal outcome. A randomized clinical trial was done at Alzahra Teaching Hospital, Tabriz University of Medical Sciences from April 2008 to March 2013. Four-hundred and sixty nulliparous pregnant women were randomly assigned into two groups. Group 1 (n = 230) received 0.5 mg of folic acid and group 2 (n = 230) received 5 mg of folic acid per daily. They were followed until delivery. Blood pressure and laboratory changes, including plasma Hcy levels, were measured and compared between the groups. Homocysteine concentrations were significantly higher at the time of delivery in group 1 (13.17±3.89 μmol/l) than in group 2 (10.31±3.54, μmol/l) (p<0.001). No statistically significant differences were observed in systolic and diastolic blood pressure (p = 0.84 and 0.15, respectively). Birth weight was significantly higher in group 2 (p = 0.031) and early abortion was significantly higher in group 1 than group 2 (p = 0.001). This study has provided evidence that a high dosage of folic acid supplements throughout pregnancy reduces Hcy concentrations at the time of delivery. Trial Registration: Iranian Registry of Clinical Trials IRCT201402175283N9 PMID:27166794

  7. Analysis of Polymorphisms in Interleukin-10, Interleukin-6, and Interleukin-1 Receptor Antagonist in Mexican-Mestizo Women with Pre-eclampsia

    PubMed Central

    Valencia Villalvazo, Elith Yazmin; Canto-Cetina, Thelma; Romero Arauz, Juan Fernando; Coral-Vázquez, Ramón Mauricio; Canizales-Quinteros, Samuel; Coronel, Agustín; Carlos Falcón, Juan; Hernández Rivera, Jaime; Ibarra, Roberto; Polanco Reyes, Lucila

    2012-01-01

    Due to the fact that studies seeking associations of polymorphisms in regulatory regions of cytokine genes with pre-eclampsia (PE) have not always been consistent in different population analyses, the aim of this study was to investigate the possible association between rs1800896 of interleukin-10 (IL-10), rs1800795 of interleukin-6 (IL-6), and the variable number of tandem repeats (VNTR) in intron 2 of interleukin-1 receptor antagonist (IL-1Ra), as well as gene–gene interactions between these three polymorphisms with the presence of PE in Mexican-Mestizo women and one Amerindian population from México (Maya). A case–control study was performed where 411 pre-eclamptic cases and 613 controls were genotyped. For the rs1800896 of IL-10 and rs1800795 of IL-6, we used real-time polymerase chain reaction (PCR) allelic discrimination and for the VNTR of IL-1Ra, PCR. Allele frequency differences were assessed by Chi-squared test; logistic regression was used to test for associations; a gene–gene interaction was conducted. Genotypic and allelic distribution of the polymorphisms was similar in our population. The estimated of the gene–gene interaction between the polymorphisms did not differ significantly. However, we observed important differences in the distribution of the alleles and genotypes of the three polymorphisms analyzed between Mestiza-Mexicanas and Maya-Mestizo women. In conclusion, we did not find an association between polymorphisms in IL-10, IL-6, and IL-1Ra and PE in Mexican-Mestizo and Maya-Mestizo women. To our knowledge, this is the first time that these three polymorphisms were analyzed together with gene–gene interaction in women with PE. PMID:23013217

  8. The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats

    PubMed Central

    Tian, Mei; Zhang, Yonghong; Liu, Zhaozhao; Sun, Guoqiang; Mor, Gil; Liao, Aihua

    2016-01-01

    The programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis by promoting regulatory T (Treg) development and inhibiting effector T (such as Th17) cell responses. However, the association between the PD-1/PD-L1 pathway and the Treg/Th17 imbalance has not been fully investigated in pre-eclampsia (PE). In this study, we observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 on the two subsets also changed in PE compared with normal pregnancy. We further explored their relationship in vivo using the L-NG-Nitroarginine Methyl Ester (L-NAME) induced PE-like rat models, also characterized by Treg/Th17 imbalance. Administration of PD-L1-Fc protein provides a protective effects on the pre-eclamptic models, both to the mother and the fetuses, by reversing Treg/Th17 imbalance through inhibiting PI3K/AKT/m-TOR signaling and enhancing PTEN expression. In addition, we also observed a protective effect of PD-L1-Fc on the placenta by reversing placental damages. These results suggested that altered PD-1/PD-L1 pathway contributed to Treg/Th17 imbalance in PE. Treatment with PD-L1-Fc posed protective effects on pre-eclamptic models, indicating that the use of PD-L1-Fc might be a potential therapeutic target in PE treatment. PMID:27277012

  9. Maternal and Newborn Health in Karnataka State, India: The Community Level Interventions for Pre-Eclampsia (CLIP) Trial’s Baseline Study Results

    PubMed Central

    Bellad, Mrutynjaya B.; Vidler, Marianne; Honnungar, Narayan V.; Mallapur, Ashalata; Ramadurg, Umesh; Charanthimath, Umesh; Katageri, Geetanjali; Bannale, Shashidhar; Kavi, Avinash; Karadiguddi, Chandrashekhar; Lee, Tang; Li, Jing; Payne, Beth; Magee, Laura; von Dadelszen, Peter; Derman, Richard; Goudar, Shivaprasad S.

    2017-01-01

    Existing vital health statistics registries in India have been unable to provide reliable estimates of maternal and newborn mortality and morbidity, and region-specific health estimates are essential to the planning and monitoring of health interventions. This study was designed to assess baseline rates as the precursor to a community-based cluster randomized control trial (cRCT)–Community Level Interventions for Pre-eclampsia (CLIP) Trial (NCT01911494; CTRI/2014/01/004352). The objective was to describe baseline demographics and health outcomes prior to initiation of the CLIP trial and to improve knowledge of population-level health, in particular of maternal and neonatal outcomes related to hypertensive disorders of pregnancy, in northern districts the state of Karnataka, India. The prospective population-based survey was conducted in eight clusters in Belgaum and Bagalkot districts in Karnataka State from 2013–2014. Data collection was undertaken by adapting the Maternal and Newborn Health registry platform, developed by the Global Network for Women’s and Child Health Studies. Descriptive statistics were completed using SAS and R. During the period of 2013–2014, prospective data was collected on 5,469 pregnant women with an average age of 23.2 (+/-3.3) years. Delivery outcomes were collected from 5,448 completed pregnancies. A majority of the women reported institutional deliveries (96.0%), largely attended by skilled birth attendants. The maternal mortality ratio of 103 (per 100,000 livebirths) was observed during this study, neonatal mortality ratio was 25 per 1,000 livebirths, and perinatal mortality ratio was 50 per 1,000 livebirths. Despite a high number of institutional deliveries, rates of stillbirth were 2.86%. Early enrollment and close follow-up and monitoring procedures established by the Maternal and Newborn Health registry allowed for negligible lost to follow-up. This population-level study provides regional rates of maternal and newborn

  10. Systematic Review of Micro-RNA Expression in Pre-Eclampsia Identifies a Number of Common Pathways Associated with the Disease

    PubMed Central

    Sheikh, Adam M.; Currie, Gemma; Delles, Christian

    2016-01-01

    Background Pre-eclampsia (PE) is a complex, multi-systemic condition of pregnancy which greatly impacts maternal and perinatal morbidity and mortality. MicroRNAs (miRs) are differentially expressed in PE and may be important in helping to understand the condition and its pathogenesis. Methods Case-control studies investigating expression of miRs in PE were collected through a systematic literature search. Data was extracted and compared from 58 studies to identify the most promising miRs associated with PE pathogenesis and identify areas of methodology which could account for often conflicting results. Results Some of the most frequently differentially expressed miRs in PE include miR-210, miR-223 and miR-126/126* which associate strongly with the etiological domains of hypoxia, immunology and angiogenesis. Members of the miR-515 family belonging to the imprinted chromosome 19 miR cluster with putative roles in trophoblast invasion were also found to be differentially expressed. Certain miRs appear to associate with more severe forms of PE such as miR-210 and the immune-related miR-181a and miR-15 families. Patterns of miR expression may help pinpoint key pathways (e.g. IL-6/miR-223/STAT3) and aid in untangling the heterogeneous nature of PE. The detectable presence of many PE-associated miRs in antenatal circulatory samples suggests their usefulness as predictive biomarkers. Further progress in ascertaining the clinical value of miRs and in understanding how they might contribute to pathogenesis is predicated upon resolving current methodological challenges in studies. These include differences in diagnostic criteria, cohort characteristics, sampling technique, RNA isolation and platform-dependent variation in miR profiling. Conclusion Reviewing studies of PE-associated miRs has revealed their potential as informants of underlying target genes and pathways relating to PE pathogenesis. However, the incongruity in results across current studies hampers their

  11. Vascular endothelial growth factor gene +813CC polymorphism of foetus is associated with preterm labour but not with pre-eclampsia in Turkish pregnant women.

    PubMed

    Atis, A; Oruc, O; Aydin, Y; Cetincelik, U; Goker, N

    2012-06-01

    We investigated the effect of polymorphism at +813 locus of vascular endothelial growth factor (VEGF) gene on predisposition to preterm labour and pre-eclampsia (PE). We examined polymorphism of the VEGF +813 gene of foetuses from umbilical cord blood in 31 cases of preterm labour, 34 pre-eclamptic and 58 healthy term labour. VEGF +813 gene polymorphisms were studied using a polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. In preterm group, foetal CC genotype was found at 80.6%, and CT genotype was seen at 19.4%. No any TT genotype was detected in preterm group. CC genotype of VEGF 813 gene was significantly more frequent than CT genotype (P = 0.04). Foetuses with CC genotype VEGF+813 gene have an increased risk for preterm labour. C allele frequency was 90.3 and 76.7% in preterm and control groups, respectively. T allele frequency was 9.7 and 23.3% in preterm and control groups, respectively. C allele was significantly associated with preterm labour (P = 0.02). OR of C and T alleles for preterm labour was 2.8 (CI: 1.1-7.2). In PE group, foetal CC genotype of +813 locus was found in 67.6%, and CT genotype was seen in 29.4%. Only one TT genotype was detected in 2.9% of PE group. There was no association between PE and VEGF gene genotypes and alleles at +813 locus. These results suggest that foetal VEGF gene polymorphism of +813 CC seems to be highly associated with preterm labour, whereas in PE, foetal VEGF gene polymorphism at +813 locus is not related. Especially, C allele was significantly associated with preterm labour. Carriage of the +813C allele of the VEGF gene has been found 2.8 times increased susceptibility to the development of preterm labour in Turkish women and may be an independent risk factor for prematurity. There was no association between PE and VEGF gene genotypes and alleles at +813 locus. We suggest to search for foetal aetiologies or genetic susceptibility in preterm labour, whereas in PE, not

  12. High-risk pregnancy in rhesus monkeys (Macaca mulatta): a case of ectopic, abdominal pregnancy with birth of a live, term infant, and a case of gestational diabetes complicated by pre-eclampsia

    PubMed Central

    Krugner-Higby, Lisa; Luck, Melissa; Hartley, Deborah; Crispen, Heather M.; Lubach, Gabriele R.; Coe, Christopher L.

    2009-01-01

    Several cases of abdominal pregnancy have been described in nonhuman primates. These previous occurrences have been mummified fetuses found in the abdominal cavity. This report describes a case of abdominal pregnancy in a timed-bred rhesus monkey with delivery of a live term infant. The mother died 14 days later from complications of septic peritonitis. At necropsy, the monkey had an intestinal adenocarcinoma that may have allowed leakage of intestinal contents into the abdomen. The second case of pregnancy complication was a rhesus monkey found to have gestational diabetes that later developed pre-eclampsia. She was treated for 5 days with a regimen similar to that used in women, and a live infant was delivered at day 157 of gestation by Caesarian section. These cases of high-risk pregnancy underscore the value of timed-breeding and careful monitoring of pregnant monkeys and the similarities between pregnancy complications in women and in nonhuman primates. PMID:19490364

  13. Association between the SERPINE1 (PAI-1) 4G/5G insertion/deletion promoter polymorphism (rs1799889) and pre-eclampsia: a systematic review and meta-analysis.

    PubMed

    Zhao, Linlu; Bracken, Michael B; Dewan, Andrew T; Chen, Suzan

    2013-03-01

    The SERPINE1 -675 4G/5G promoter region insertion/deletion polymorphism (rs1799889) has been implicated in the pathogenesis of pre-eclampsia (PE), but the genetic association has been inconsistently replicated. To derive a more precise estimate of the association, a systematic review and meta-analysis was conducted. This study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed (MEDLINE), Scopus and HuGE Literature Finder literature databases were systematically searched for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the allelic comparison (4G versus 5G) and genotypic comparisons following the co-dominant (4G/4G versus 5G/5G and 4G/5G versus 5G/5G), dominant (4G/4G+4G/5G versus 5G/5G) and recessive (4G/4G versus 4G/5G+5G/5G) genetic models. Between-study heterogeneity was quantified by I(2) statistics and publication bias was appraised with funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. Meta-analysis of 11 studies involving 1297 PE cases and 1791 controls found a significant association between the SERPINE1 -675 4G/5G polymorphism and PE for the recessive genetic model (OR = 1.36, 95% CI: 1.13-1.64, P = 0.001), a robust finding according to sensitivity analysis. A low level of between-study heterogeneity was detected (I(2) = 20%) in this comparison, which may be explained by ethnic differences. Funnel plot inspection did not reveal evidence of publication bias. In conclusion, this study provides a comprehensive examination of the available literature on the association between SERPINE1 -675 4G/5G and PE. Meta-analysis results support this polymorphism as a likely susceptibility variant for PE.

  14. Epigenetic mechanisms regulate placental c-myc and hTERT in normal and pathological pregnancies; c-myc as a novel fetal DNA epigenetic marker for pre-eclampsia.

    PubMed

    Rahat, Beenish; Hamid, Abid; Ahmad Najar, Rauf; Bagga, Rashmi; Kaur, Jyotdeep

    2014-10-01

    Placental development is known for its resemblance with tumor development, such as in the expression of oncogenes (c-myc) and telomerase (hTERT). The expression of c-myc and hTERT is up-regulated during early pregnancy and gestational trophoblastic diseases (GTDs). To determine the role of DNA methylation [via methylation-sensitive high resolution melting (MS-HRM)] and histone modifications [via chromatin immunoprecipitation (ChIP assay)] in regulating the differential expression of c-myc and hTERT during normal gestation and their dysregulation during placental disorders, we obtained placental samples from 135 pregnant women, in five groups: normal first, second and third trimester (n = 30 each), pre-eclamptic pregnancy (n = 30) and molar pregnancy (n = 15). Two placental cell lines (JEG-3 and HTR-8/SVneo) and isolated first-trimester cytotrophoblasts were also studied. Quantitative RT-PCR revealed decreased mRNA expression levels of c-myc and hTERT, which were associated with a higher level of H3K9me3 (1.5-fold, P < 0.05) and H3K27me3 (1.9-fold, P < 0.05), respectively, in third-trimester placental villi versus first-trimester villi. A significantly lower level of H3K27me3 in molar placenta was associated with a higher mRNA expression of c-myc and hTERT. The development of pre-eclampsia (PE) was associated with increased methylation (P < 0.001) and H3K27me3 (P < 0.01) at the c-myc promoter and reduced H3K9me3 (P < 0.01) and H3K27me3 (P < 0.05) at the hTERT promoter. Further, mRNA expression of c-myc and hTERT was strongly correlated in molar villi (r = 0.88, P < 0.01) and JEG-3 cells (r = 0.99, P < 0.02). Moreover, on the basis of methylation data, we demonstrate the potential of c-myc as a fetal DNA epigenetic marker for pre-eclamptic pregnancies. Thus we suggest a role for epigenetic mechanisms in regulating differential expression of c-myc and hTERT during placental development and use of the c-myc promoter region as a potential fetal DNA marker in the case of

  15. Adequately Diversified Dietary Intake and Iron and Folic Acid Supplementation during Pregnancy Is Associated with Reduced Occurrence of Symptoms Suggestive of Pre-Eclampsia or Eclampsia in Indian Women

    PubMed Central

    Agrawal, Sutapa; Fledderjohann, Jasmine; Vellakkal, Sukumar; Stuckler, David

    2015-01-01

    Background/Objective Pre-eclampsia or Eclampsia (PE or E) accounts for 25% of cases of maternal mortality worldwide. There is some evidence of a link to dietary factors, but few studies have explored this association in developing countries, where the majority of the burden falls. We examined the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E in Indian women. Methods Cross-sectional data from India’s third National Family Health Survey (NFHS-3, 2005-06) was used for this study. Self-reported symptoms suggestive of PE or E during pregnancy were obtained from 39,657 women aged 15-49 years who had had a live birth in the five years preceding the survey. Multivariable logistic regression analysis was used to estimate the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E after adjusting for maternal, health and lifestyle factors, and socio-demographic characteristics of the mother. Results In their most recent pregnancy, 1.2% (n=456) of the study sample experienced symptoms suggestive of PE or E. Mothers who consumed an adequately diversified diet were 34% less likely (OR: 0.66; 95% CI: 0.51-0.87) to report PE or E symptoms than mothers with inadequately diversified dietary intake. The likelihood of reporting PE or E symptoms was also 36% lower (OR: 0.64; 95% CI: 0.47-0.88) among those mothers who consumed iron and folic acid supplementation for at least 90 days during their last pregnancy. As a sensitivity analysis, we stratified our models sequentially by education, wealth, antenatal care visits, birth interval, and parity. Our results remained largely unchanged: both adequately diversified dietary intake and iron and folic acid supplementation during pregnancy were associated with a reduced occurrence of PE or E symptoms. Conclusion Having a adequately diversified dietary

  16. Maternal serum placental growth factor and pregnancy-associated plasma protein A measured in the first trimester as parameters of subsequent pre-eclampsia and small-for-gestational-age infants: A prospective observational study

    PubMed Central

    Sung, Kyung Uk; Roh, Jeong A; Eoh, Kyung Jin

    2017-01-01

    Objective To examine the first-trimester maternal serum placental growth factor (PlGF) and pregnancy-associated plasma protein A (PAPP-A) levels in pregnancies associated with pre-eclampsia (PE) or small-for-gestational-age (SGA) infants, and determine the predictive accuracy of PlGF and of PAPP-A for either PE or SGA infants. Methods This prospective, observational study included 175 pregnant women, and of these women, due to participant withdrawal or loss to follow-up, delivery data were collected from the medical records of 155 women, including 4 who had twin pregnancies. The women's maternal history was recorded, and the PlGF and PAPP-A levels at 11 to 13 gestational weeks were measured. During the second trimester, the maternal uterine artery's systolic/diastolic ratio was measured. Multiples of the median (MoM) of PlGF and PAPP-A were determined, and the associations of these values with the risk factors of SGA and PE were evaluated. Logistic regression analysis was used to determine whether PlGF and PAPP-A are useful markers for predicting SGA infants. Results The PAPP-A MoM level was significantly lower in women with advanced maternal age, multipara women, and women with gestational diabetes than in their counterparts. The PlGF and PAPP-A MoM levels were higher in women with a twin pregnancy than in those with a singleton pregnancy. There was a significant relationship between the maternal serum PAPP-A MoM level in the first trimester and the uterine artery systolic/diastolic ratio in the second trimester. Results of logistic regression analysis showed that low PlGF and PAPP-A MoM levels were predictors of SGA infants (odds ratio, 0.143; 95% confidence interval, 0.025 to 0.806; odds ratio, 0.191; 95% confidence interval, 0.051 to 0.718, respectively). Conclusion PlGF and PAPP-A are potentially useful as first-trimester markers for SGA infants and some hypertensive disorders of pregnancy. PMID:28344956

  17. Pre-Eclampsia, Birth Weight, and Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Mann, Joshua R.; McDermott, Suzanne; Bao, Haikun; Hardin, James; Gregg, Anthony

    2010-01-01

    Autism spectrum disorders (ASD) are primarily inherited, but perinatal or other environmental factors may also be important. In an analysis of 87,677 births from 1996 through 2002, insured by the South Carolina Medicaid program, birth weight was significantly inversely associated with the odds of ASD (OR = 0.78, p = 0.001 for each additional…

  18. Are Maternal Genitourinary Infection and Pre-Eclampsia Associated with ADHD in School-Aged Children?

    ERIC Educational Resources Information Center

    Mann, Joshua R.; McDermott, Suzanne

    2011-01-01

    Objective: To investigate the hypothesis that maternal genitourinary infection (GU) infection is associated with increased risk of ADHD. Method: The authors obtained linked Medicaid billing data for pregnant women and their children in South Carolina, with births from 1996 through 2002 and follow-up data through 2008. Maternal GU infections and…

  19. [Acute renal failure secondary to hemolytic uremic syndrome in a pregnant woman with pre-eclampsia].

    PubMed

    García-Miguel, F J; Mirón Rodríguez, M F; Alsina Aser, M J

    2009-02-01

    Acute renal failure is a serious complication of pregnancy associated with a high rate of morbidity and mortality; the incidence is currently 1 per 10,000 pregnancies. The most common causes are gestational hypertension, bleeding, sepsis, and intrinsic renal disease. Other less common pregnancy-related syndromes, such as HELLP syndrome or thrombotic microangiopathy, may also lead to kidney failure. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are forms of thrombotic microangiopathy and although neither is specific to pregnancy, the incidence of these entities rises during gestation. The classic symptoms are fever, hemolytic microangiopathic anemia, thrombopenia, neurologic dysfunction, and kidney abnormalities. When renal involvement is the predominant manifestation, the diagnosis is usually hemolytic uremic syndrome.

  20. [Nursing practice in maternity intensive care units. Severe pre-eclampsia in a primigravida].

    PubMed

    Carmona-Guirado, A J; Escaño-Cardona, V; García-Cañedo, F J

    2015-01-01

    39 year old woman, pregnant for 31+5 weeks, who came to our intensive care unit (ICU) referred from the emergency department of the hospital, having swollen ankles, headache and fatigue at moderate effort. We proceeded to take blood pressure (158/96 mmHg) and assess lower limb edema. The fetal heart rate monitoring was normal. Knowledgeable and user of healthy guidelines during her pregnancy, she did not follow any treatment. Single mother, she worried about her fetus (achieved through in vitro fertilization), her mother offered to help for any mishap. We developed an Individualized Care Plan. For data collection we used: Rating 14 Virginia Henderson Needs and diagnostic taxonomy NANDA, NOC, NIC. Nursing diagnoses of "fluid volume excess" and "risk of impaired maternal-fetal dyad" were detected, as well as potential complications such as eclampsia and fetal prematurity. Our overall objectives (NOC) were to integrate the woman in the process she faced and that she knew how to recognize the risk factors inherent in her illness. Nursing interventions (NIC) contemplated the awareness and treatment of her illness and the creation of new healthy habits. The work of nursing Maternal ICU allowed women to help maintain maximum maternal and fetal well-being by satisfying any of her needs. Mishandling of the situation leads into a framework of high morbidity and mortality in our units.

  1. Impedance Cardiographic (ICG) Assessment of Pregnant Women With Severe Hypertension to Assess Impact of Standard Therapy

    ClinicalTrials.gov

    2013-12-11

    Pregnancy; Proteinuria, With Hypertension (Severe Pre-eclampsia); Delivery; Proteinuria, With Gestational Hypertension (Pre-eclampsia, Severe); Pregnancy; Hypertension, Gestational Hypertension, With Albuminuria (Severe Pre-eclampsia)

  2. 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; Hofmeyr, G Justus; 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.

  3. Ruptured subcapsular hematoma of the liver due to pre-eclampsia presenting as interstitial pregnancy and the role of intra-abdominal packing.

    PubMed

    Ngene, N C; Amin, N; Moodley, J

    2015-01-01

    Ruptured subcapsular hematoma of the liver (RSHL) can mimic ruptured interstitial pregnancy because each of these conditions occasionally presents at the same gestational period and both do manifest hemodynamic instability. The similarities between the two conditions pose a diagnostic challenge, especially in an un-booked patient. We report a case of an un-booked primigravida, at 21 weeks of gestation, who arrived at a regional hospital with evidence of intra-abdominal bleeding and hypovolemic shock. She was diagnosed as potentially having a ruptured interstitial pregnancy. During the ensuing emergency laparotomy, RSHL was discovered, the area around the ruptured liver capsule was packed with large abdominal swabs, and the patient recovered. This case report illustrates the need to consider RSHL in patients presenting with features of ruptured interstitial pregnancy, as this will assist in the planning of intraoperative care. We also describe abdominal packing and highlight the need for this essential surgical intervention to be taught to doctors practising in low-resource settings.

  4. IFPA Meeting 2013 Workshop Report II: use of 'omics' in understanding placental development, bioinformatics tools for gene expression analysis, planning and coordination of a placenta research network, placental imaging, evolutionary approaches to understanding pre-eclampsia.

    PubMed

    Ackerman, W E; Adamson, L; Carter, A M; Collins, S; Cox, B; Elliot, M G; Ermini, L; Gruslin, A; Hoodless, P A; Huang, J; Kniss, D A; McGowen, M R; Post, M; Rice, G; Robinson, W; Sadovsky, Y; Salafia, C; Salomon, C; Sled, J G; Todros, T; Wildman, D E; Zamudio, S; Lash, G E

    2014-02-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of 'omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution.

  5. Assessing the incremental value of blood oxygen saturation (SpO(2)) in the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Risk Prediction Model.

    PubMed

    Payne, Beth A; Hutcheon, Jennifer A; Dunsmuir, Dustin; Cloete, Garth; Dumont, Guy; Hall, David; Lim, Joanne; Magee, Laura A; Sikandar, Rozina; Qureshi, Rahat; van Papendorp, Erika; Ansermino, J Mark; von Dadelszen, Peter

    2015-01-01

    Objectif : Évaluer la valeur cumulative de la saturation en oxygène (SaO(2)) à titre de facteur prédictif dans le cadre du modèle miniPIERS, soit un modèle de prévision des risques en ce qui concerne les issues indésirables chez les femmes ayant obtenu un diagnostic de trouble hypertensif de la grossesse (THG) dans des milieux qui ne disposent que de faibles ressources. Méthodes : Grâce à des données issues d’une cohorte prospective ayant porté sur 852 femmes hospitalisées en raison d’un THG, l’association entre la SaO(2) et les issues indésirables maternelles a été évaluée au moyen d’une régression logistique. Le modèle miniPIERS a été recalibré et élargi de façon à inclure la SaO(2). La valeur cumulative de l’ajout de la SaO(2) à ce modèle a été mesurée en ayant recours à l’indice NRI (net reclassification index), à la sensibilité, à la spécificité, aux coefficients de prévision d’un test positif et d’un test négatif et aux rapports de vraisemblance. Résultats : La SaO(2) < 93 % a été associée à un risque 30 fois plus élevé (IC à 95 %, 14 - 68) de constater une issue maternelle indésirable, par comparaison avec une SaO(2) > 97 %. Après avoir été recalibré et élargi, le modèle miniPIERS comprenant la SaO(2) (par comparaison avec le modèle ne comprenant pas la SaO(2)) présentait une sensibilité améliorée (32,8 % vs 49,6 %); cela a toutefois mené à une baisse minime de la spécificité (91,5 % vs 96,2 %) en présence d’un indice NRI de 0,122. Conclusion : La SaO(2) constitue un facteur prédictif indépendant significatif pour ce qui est du risque auquel sont exposées les femmes qui présentent un THG. L’ajout de la SaO(2) au modèle miniPIERS a mené à l’amélioration de la capacité de ce dernier à identifier correctement les patientes exposées à des risques élevés qui tireraient le plus avantage de la tenue d’interventions.

  6. 32 CFR 732.16 - Emergency care requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... pregnancy in a manner that a delay, caused by referral to a USMTF or USTF, would jeopardize the welfare of... delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy...

  7. 32 CFR 732.16 - Emergency care requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pregnancy in a manner that a delay, caused by referral to a USMTF or USTF, would jeopardize the welfare of... delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy...

  8. 32 CFR 732.16 - Emergency care requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... pregnancy in a manner that a delay, caused by referral to a USMTF or USTF, would jeopardize the welfare of... delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy...

  9. 32 CFR 732.16 - Emergency care requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... pregnancy in a manner that a delay, caused by referral to a USMTF or USTF, would jeopardize the welfare of... delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy...

  10. Pregnancy with known syndrome of inappropriate antidiuretic hormone.

    PubMed

    Nawathe, A; Govind, A

    2013-01-01

    Syndrome of inappropriate antidiuretic hormone (SIADH) is rarely encountered in pregnancy. We report a case of severe hyponatraemia with idiopathic SIADH. A total of 18 cases of hyponatraemia in pregnancy have been reported; seven fit the criteria of SIADH. Unlike our case, none were diagnosed before pregnancy. Of the cases, 13 were associated with pre-eclampsia. Our patient developed intrauterine growth restriction (IUGR) but did not develop pre-eclampsia.

  11. 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

  12. Pregnancy-associated homeostasis and dysregulation: lessons from genetically modified animal models.

    PubMed

    Ishida, Junji; Matsuoka, Toshiki; Saito-Fujita, Tomoko; Inaba, Saki; Kunita, Satoshi; Sugiyama, Fumihiro; Yagami, Ken-ichi; Fukamizu, Akiyoshi

    2011-07-01

    Physiological alterations occur in many organ systems during pregnancy. These changes are necessary for the adaptation to pregnancy-specific physiological processes in mother and fetus, and the placenta plays a critical role in the maintenance of homeostasis in pregnancy. Dysregulation of these functional feto-maternal interactions leads to severe complications. There have been many attempts to create animal models that mimic the hypertensive disorders of pregnancy, especially pre-eclampsia. In this review, we summarize the physiology of pregnancy and placental function, and discuss the placental gene expression in normal pregnancy. In addition, we assess a number of established animal models focusing on a specific pathogenic mechanism of pre-eclampsia, including genetically modified mouse models involving the renin-angiotensin system. Validation of these animal models would contribute significantly to understanding the basic principles of pregnancy-associated homeostasis and the pathogenesis of pre-eclampsia.

  13. [Prognostic Value of Central Aortic Pressure in Pregnant Women With Hypertension].

    PubMed

    Chulkov, V S; Sinitsin, S P; Vereina, N K

    2015-01-01

    Prognostic value of central aortic pressure and peripheral blood pressure in relation to the development of pre-eclampsia was assessed in pregnant women with different forms of hypertension. It was shown that development of pre-eclampsia was associated with higher mean 24-hour systolic blood pressure (BP), time index of systolic BP, variability of diastolic BP, and pulse BP measured on weeks 16-22 of gestation. Pregnant women with hypertension, especially those with pre-eclampsia were characterized by absence of proper nocturnal BP lowering or BP elevation during night hours (non-dippers and night-peakers). Critical values for prediction of preeclampsia were daily average central (aortic) systolic BP higher than 115 mm Hg and a mean daily brachial systolic BP above 131 mm Hg.

  14. The hypertensive disorders of pregnancy (29.3).

    PubMed

    Magee, Laura A; Pels, Anouk; Helewa, Michael; Rey, Evelyne; von Dadelszen, Peter

    2015-07-01

    Hypertensive disorders are the most common medical complication of pregnancy. As such, a large part of antenatal care is dedicated to the detection of pre-eclampsia, the most dangerous of the hypertensive disorders. The highlights of this chapter include progress in the use of out-of-office blood pressure measurement as an adjunct to office blood pressure measurement, pre-eclampsia defined as proteinuria or relevant end-organ dysfunction, antihypertensive therapy for severe and non-severe hypertension and post-partum follow-up to mitigate the increased cardiovascular risk associated with any of the hypertensive disorders of pregnancy.

  15. Use of magnesium sulfate before 32 weeks of gestation: a European population-based cohort study

    PubMed Central

    Wolf, H T; Huusom, L; Weber, T; Piedvache, A; Schmidt, S; Norman, M; Zeitlin, J

    2017-01-01

    Objectives The use of magnesium sulfate (MgSO4) in European obstetric units is unknown. We aimed to describe reported policies and actual use of MgSO4 in women delivering before 32 weeks of gestation by indication. Methods We used data from the European Perinatal Intensive Care in Europe (EPICE) population-based cohort study of births before 32 weeks of gestation in 19 regions in 11 European countries. Data were collected from April 2011 to September 2012 from medical records and questionnaires. The study population comprised 720 women with severe pre-eclampsia, eclampsia or HELLP and 3658 without pre-eclampsia delivering from 24 to 31 weeks of gestation in 119 maternity units with 20 or more very preterm deliveries per year. Results Among women with severe pre-eclampsia, eclampsia or HELLP, 255 (35.4%) received MgSO4 before delivery. 41% of units reported use of MgSO4 whenever possible for pre-eclampsia and administered MgSO4 more often than units reporting use sometimes. In women without pre-eclampsia, 95 (2.6%) received MgSO4. 9 units (7.6%) reported using MgSO4 for fetal neuroprotection whenever possible. In these units, the median rate of MgSO4 use for deliveries without severe pre-eclampsia, eclampsia and HELLP was 14.3%. Only 1 unit reported using MgSO4 as a first-line tocolytic. Among women without pre-eclampsia, MgSO4 use was not higher in women hospitalised before delivery for preterm labour. Conclusions Severe pre-eclampsia, eclampsia or HELLP are not treated with MgSO4 as frequently as evidence-based medicine recommends. MgSO4 is seldom used for fetal neuroprotection, and is no longer used for tocolysis. To continuously lower morbidity, greater attention to use of MgSO4 is needed. PMID:28132012

  16. The herbal medicines Saireito and Boiogito improve the hypertension of pre-eclamptic rats induced by Nomega-Nitro-L-arginine methyl ester.

    PubMed

    Takei, Hisato; Nakai, Yoichiro; Hattori, Naoko; Yamamoto, Masahiro; Takeda, Shuichi; Yamamoto, Masako; Arishima, Kazuyoshi

    2007-09-01

    The chronic inhibition of nitric oxide (NO) synthesis with N(omega)-Nitro-L-arginine methyl ester (L-NAME) induces a pre-eclampsia-like syndrome including hypertension in pregnant rats. We tested the traditional herbal medicines Saireito (SR) and Boiogito (BO), which have been used clinically for the treatment of pre-eclampsia, in this model. L-NAME was infused subcutaneously into pregnant rats from gestational day 14 (G14). SR and BO (both at 1, 2g/kg) were administered by gavage from G14 to G20. Systolic blood pressure was measured on G19. SR and BO (both at 1, 2g/kg) inhibited L-NAME-induced hypertension. SR was effective in both pregnant and non-pregnant rats while BO was effective only in pregnant rats. BO increased blood levels of CGRP and decreased levels of endothelin-1; both are known to play important roles in regulation of blood pressure in pre-eclampsia. SR and BO may be beneficial for the treatment and prevention of hypertension in pre-eclampsia.

  17. Association of oxidative DNA damage, protein oxidation and antioxidant function with oxidative stress induced cellular injury in pre-eclamptic/eclamptic mothers during fetal circulation.

    PubMed

    Negi, Reena; Pande, Deepti; Karki, Kanchan; Kumar, Ashok; Khanna, Ranjana S; Khanna, Hari D

    2014-02-05

    Pre-eclampsia is a devastating multi system syndrome and a major cause of maternal, fetal, neonatal morbidity and mortality. Pre-eclampsia is associated with oxidative stress in the maternal circulation. To have an insight on the effect of pre-eclampsia/eclampsia on the neonates, the study was made to explore the oxidative status by quantification of byproducts generated during protein oxidation and oxidative DNA damage and deficient antioxidant activity in umbilical cord blood of pre-eclamptic/eclamptic mothers during fetal circulation. Umbilical cord blood during delivery from neonates born to 19 pre-eclamptic mothers, 14 eclamptic mothers and 18 normotensive mothers (uncomplicated pregnancy) as control cases was collected. 8-OHdG (8-hydroxy-2-deoxyguanosine), protein carbonyl, nitrite, catalase, non-enzymatic antioxidants (vitamin A, E, C), total antioxidant status and iron status were determined. Significant elevation in the levels of 8-OHdG, protein carbonyl, nitrite and iron along with decreased levels of catalase, vitamin A, E, C, total antioxidant status were observed in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies. These parameters might be influential variables for the risk of free radical damage in infants born to pre-eclamptic/eclamptic pregnancies. Increased oxidative stress causes oxidation of DNA and protein which alters antioxidant function. Excess iron level and decreased unsaturated iron binding capacity may be the important factor associated with oxidative stress and contribute in the pathogenesis of pre-eclampsia/eclampsia which is reflected in fetal circulation.

  18. Evaluation of a New Marker of the Ovarian Tumor Vasculature for Predicting Response to Treatment and as a Therapeutic Target

    DTIC Science & Technology

    2012-10-01

    The first cell type was promising because we found that the endothelial cells in human placentas express FSHR. We obtained placental endothelial...receptors in placenta microvascular endothelial cells from pre- eclampsia. Placenta . 2008; 29(9):816-25. 7. O’Connell K, Landman G, Farmer E, Edidin M

  19. Reversible posterior leukoencephalopathy syndrome in children with nephrotic syndrome: a case report.

    PubMed

    Liu, Sheng-da; Shen, Qing-min; Lv, Chun-feng

    2014-03-01

    REVERSIBLE posterior leukoencephalopathy syndrome (RPLS) is a rare neurological syndrome characterized by headache, altered mental status, seizures, and visual disturbance, associated with reversible white matter changes.1 It has been commonly reported in patients with severe hypertension and pre-eclampsia. Here we report a case with nephrotic syndrome complicated by RPLS.

  20. Spontaneous subdural hematoma associated with preeclampsia: a case report and litterature review

    PubMed Central

    Oudghiri, Nezha; Behat, Mehdi; Elchhab, Nada; Doumiri, Mouhssine; Tazi, Anas Saoud

    2014-01-01

    A patient with pre-eclampsia at 31 weeks’ gestation developed neurologic signs. Computerized tomography revealed a large cranial subdural hematoma. This diagnostic should be considered in any pre-eclamptic patient demonstrating neurological symptoms and must be treated effectively because of the poor maternel and fetal prognosis. Our patient was succesfully treated. PMID:25829978

  1. [Pericardial effusion and pleural serositis in patients with severe preeclampsia and HELLP syndrome].

    PubMed

    Quiroz, María Nayeli Salas; Rodríguez, Héctor Xavier Alfaro; Lara, Daniel S Zúñiga

    2009-11-01

    The syndrome pre-eclampsia/eclampsia is a frequent entity in the obstetrical pathology and acquires interest to take to the patients to a critical state. It has repercussion in all the organism by his complications. The definitive treatment of pre-eclampsia/eclampsia is the interruption of the pregnancy. The pericardial effussion as severe complication of pre-eclampsia and Sx de HELLP is a little frequent entity. Few cases reported in Literature exists. In the Hospital Angeles Pedregal, two cases of patients embarrassed without antecedents of previous picture hypertensive, complicated are reported with severe pre-eclampsia and HELLP syndrome class II of Martin which developed pericardial effussion without presence of tamponade. The knowledge of the behavior of this cardiovascular complication as well as the multidisciplinary and integral handling, are without a doubt the best form to modify the evolution and to avoid the appearance of tamponade. The acute pericardial effussion can get to mean a medical urgency that puts in danger the life. Mainly when the intrapericardic pressure so is lifted that the heart is compressed and the diastolic pressures ventricular lefts and right are increased and in the absence of preexisting cardiac pathology, these pressures get to equal itself. This complication little frequents must be had in mind like more of the haemodynamic complications.

  2. Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice.

    PubMed

    Chatterjee, Piyali; Chiasson, Valorie L; Pinzur, Lena; Raveh, Shani; Abraham, Eytan; Jones, Kathleen A; Bounds, Kelsey R; Ofir, Racheli; Flaishon, Liat; Chajut, Ayelet; Mitchell, Brett M

    2016-04-01

    Pre-eclampsia, the development of hypertension and proteinuria or end-organ damage during pregnancy, is a leading cause of both maternal and fetal morbidity and mortality, and there are no effective clinical treatments for pre-eclampsia aside from delivery. The development of pre-eclampsia is characterized by maladaptation of the maternal immune system, excessive inflammation and endothelial dysfunction. We have reported that detection of extracellular RNA by the Toll-like receptors (TLRs) 3 and 7 is a key initiating signal that contributes to the development of pre-eclampsia. PLacental eXpanded (PLX-PAD) cells are human placenta-derived, mesenchymal-like, adherent stromal cells that have anti-inflammatory, proangiogenic, cytoprotective and regenerative properties, secondary to paracrine secretion of various molecules in response to environmental stimulation. We hypothesized that PLX-PAD cells would reduce the associated inflammation and tissue damage and lower blood pressure in mice with pre-eclampsia induced by TLR3 or TLR7 activation. Injection of PLX-PAD cells on gestational day 14 significantly decreased systolic blood pressure by day 17 in TLR3-induced and TLR7-induced hypertensive mice (TLR3 144-111 mmHg; TLR7 145-106 mmHg; both P<0.05), and also normalized their elevated urinary protein:creatinine ratios (TLR3 5.68-3.72; TLR7 5.57-3.84; both P<0.05). On gestational day 17, aortic endothelium-dependent relaxation responses improved significantly in TLR3-induced and TLR7-induced hypertensive mice that received PLX-PAD cells on gestational day 14 (TLR3 35-65%; TLR7 37-63%; both P<0.05). In addition, markers of systemic inflammation and placental injury, increased markedly in both groups of TLR-induced hypertensive mice, were reduced by PLX-PAD cells. Importantly, PLX-PAD cell therapy had no effects on these measures in pregnant control mice or on the fetuses. These data demonstrate that PLX-PAD cell therapy can safely reverse pre-eclampsia-like features during

  3. Translating formative research findings into a behaviour change strategy to promote antenatal calcium and iron and folic acid supplementation in western Kenya.

    PubMed

    Martin, Stephanie L; Seim, Gretchen L; Wawire, Salome; Chapleau, Gina M; Young, Sera L; Dickin, Katherine L

    2017-01-01

    The World Health Organization now recommends integrating calcium supplements into antenatal micronutrient supplementation programmes to prevent pre-eclampsia, a leading cause of maternal mortality. As countries consider integrating calcium supplementation into antenatal care (ANC), it is important to identify context-specific barriers and facilitators to delivery and adherence. Such insights can be gained from women's and health workers' experiences with iron and folic acid (IFA) supplements. We conducted in-depth interviews with 22 pregnant and post-partum women and 20 community-based and facility-based health workers in Kenya to inform a calcium and IFA supplementation programme. Interviews assessed awareness of anaemia, pre-eclampsia and eclampsia; ANC attendance; and barriers and facilitators to IFA supplement delivery and adherence. We analyzed interviews inductively using the constant comparative method. Women and health workers identified poor diet quality in pregnancy as a major health concern. Neither women nor health workers identified pre-eclampsia, eclampsia, anaemia or related symptoms as serious health threats. Women and community-based health workers were unfamiliar with pre-eclampsia and eclampsia and considered anaemia symptoms normal. Most women had not received IFA supplements, and those who had received insufficient amounts and little information about supplement benefits. We then developed a multi-level (health facility, community, household and individual) behaviour change strategy to promote antenatal calcium and IFA supplementation. Formative research is an essential first step in guiding implementation of antenatal calcium supplementation programmes to reduce pre-eclampsia. Because evidence on how to implement successful calcium supplementation programmes is limited, experiences with antenatal IFA supplementation can be used to guide programme development.

  4. Vessel remodelling, pregnancy hormones and extravillous trophoblast function.

    PubMed

    Chen, Jessie Z-J; Sheehan, Penelope M; Brennecke, Shaun P; Keogh, Rosemary J

    2012-02-26

    During early human pregnancy, extravillous trophoblast (EVT) cells from the placenta invade the uterine decidual spiral arterioles and mediate the remodelling of these vessels such that a low pressure, high blood flow can be supplied to the placenta. This is essential to facilitate normal growth and development of the foetus. Defects in remodelling can manifest as the serious pregnancy complication pre-eclampsia. During the period of vessel remodelling three key pregnancy-associated hormones, human chorionic gonadotrophin (hCG), progesterone (P(4)) and oestradiol (E(2)), are found in high concentrations at the maternal-foetal interface. Potentially these hormones may control EVT movement and thus act as regulators of vessel remodelling. This review will discuss what is known about how these hormones affect EVT proliferation, migration and invasion during vascular remodelling and the potential relationship between hCG, P(4), E(2) and the development of pre-eclampsia.

  5. Cortical blindness in obstetric patients: case report of two different presentations.

    PubMed

    Edomwonyi, N P; Idehen, H

    2013-06-01

    Cortical blindness can complicate pre-eclampsia/eclampsia. This normally resolves between a few hours and days with full restoration of patients sight. In this case report, we present the clinical course of two women in whom eclampsia was further complicated with blindness. One had pre-partum blindness which resolved after few hours while the second developed post-partum blindness that occurred after an episode of ischaemic cerebrovascular accident (CVA) and it became persistent. The patients were managed by standard pre-eclampsia/ eclampsia regimen; these entail the use of intravenous magnesium sulphate, i/v hydralazine and fluid restriction, as well as expedite delivery. Diagnosis was further confirmed by computed tomography (CT) that demonstrated low density areas localised predominantly in the occipital areas.

  6. Observations on the alkaline phosphatase isoenzyme distribution in maternal and amniotic fluid compartments in Nigerian parturients.

    PubMed

    Okpere, E; Okorodudu, A; Gbinigie, O

    1988-01-01

    Estimation of the alkaline phosphates isoenzymes in paired maternal serum and amniotic fluids in term uncomplicated pregnancies and in patients with pre-eclampsia, showed poor correlation coefficients between the levels of both heat stable and heat labile isoenzymes. There was a statistically significant fall in AF (P less than .05) HSAP in pre-eclampsia and a highly significant rise of HLAP in meconial liquor. It is concluded that the poor correlation between the levels of HSAP in maternal serum and amniotic fluid (despite their common source of origin), the normal levels of HLAP in maternal serum in the presence of significantly high levels of HSAP in maternal serum in the presence of significantly diminished levels in amniotic fluid point to a state of relatively diminished permeability of the chorioamniotic membranes to the alkaline phosphatase isoenzymes in Nigerians.

  7. Health after pregnancy in the mother with diabetes.

    PubMed

    Kaaja, Risto; Gordin, Daniel

    2015-07-01

    Progression of retinopathy and nephropathy in women with diabetes occurs, at least temporarily, during pregnancy and postpartum. However, normotensive pregnancy seems to have no detrimental effects regarding the long-term progression of any microvascular complication. Increased risk from pregnancy induced hypertension without proteinuria and with proteinuria (pre-eclampsia) relates mainly to the association with kidney disease in diabetes, and poor glycemic control. A history of pre-eclampsia or pregnancy induced hypertension is an important prognostic factor for micro- and macro-vascular complications later in life. Data regarding the long-term effects of hypertensive pregnancies on late complications of diabetes suggest that women with diabetes should be monitored regularly and nephroprotective treatment initiated early.

  8. Prenatal Screening Using Maternal Markers

    PubMed Central

    Cuckle, Howard

    2014-01-01

    Maternal markers are widely used to screen for fetal neural tube defects (NTDs), chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening. PMID:26237388

  9. Inadequate vitamin D status in pregnancy: evidence for supplementation.

    PubMed

    Finer, Sarah; Khan, Khalid S; Hitman, Graham A; Griffiths, Chris; Martineau, Adrian; Meads, Catherine

    2012-02-01

    The role of vitamin D in maintaining a healthy pregnancy has seen emerging interest among clinicians and researchers in recent years. The functions of this hormone are widespread and complex, and during pregnancy and breastfeeding it facilitates crucial transfer of calcium from mother to child for skeletal development. Aside from the role of vitamin D in bone development and health, a myriad of other physiological actions are now known, and it is hypothesized that maternal deficiency may increase susceptibility to adverse pregnancy events during pregnancy such as pre-eclampsia. The role of vitamin D in pregnancy and breastfeeding is summarized and applied to the knowledge from studies associating vitamin D deficiency with a range of adverse pregnancy outcomes, including pre-eclampsia and childhood asthma. Current clinical guidelines for vitamin D supplementation in pregnancy are discussed in the context of the available evidence. The need for robust randomized controlled trials to address areas of existing uncertainty is highlighted.

  10. Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy

    PubMed Central

    Oudejans, Cees; Poutsma, Ankie; Michel, Omar; Mulders, Joyce; Visser, Allerdien; van Dijk, Marie; Nauta, Tessa; Bokslag, Anouk; Paulus, Walter; de Haas, Andreas; Koolwijk, Pieter; de Groot, Christianne J. M.

    2016-01-01

    Background The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia. Findings We assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters. Conclusion The current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies. PMID:26870946

  11. Liver abnormalities in pregnancy.

    PubMed

    Than, Nwe Ni; Neuberger, James

    2013-08-01

    Abnormalities of liver function (notably rise in alkaline phosphatase and fall in serum albumin) are common in normal pregnancy, whereas rise in serum bilirubin and aminotransferase suggest either exacerbation of underlying pre-existing liver disease, liver disease related to pregnancy or liver disease unrelated to pregnancy. Pregnant women appear to have a worse outcome when infected with Hepatitis E virus. Liver diseases associated with pregnancy include abnormalities associated hyperemesis gravidarum, acute fatty liver disease, pre-eclampsia, cholestasis of pregnancy and HELLP syndrome. Prompt investigation and diagnosis is important in ensuring a successful maternal and foetal outcome. In general, prompt delivery is the treatment of choice for acute fatty liver, pre-eclampsia and HELLP syndrome and ursodeoxycholic acid is used for cholestasis of pregnancy although it is not licenced for this indication.

  12. Management of hypertensive disorders in pregnancy.

    PubMed

    Moussa, Hind N; Arian, Sara E; Sibai, Baha M

    2014-07-01

    Hypertensive disorders are the most common medical complication of pregnancy, with an incidence of 5-10%, and a common cause of maternal mortality in the USA. Incidence of pre-eclampsia has increased by 25% in the past two decades. In addition to being among the lethal triad, there are likely up to 100 other women who experience 'near miss' significant maternal morbidity that stops short of death for every pre-eclampsia-related mortality. The purpose of this review is to present the new task force statement and novel definitions, as well as management approaches to each of the hypertensive disorders in pregnancy. The increased understanding of the pathophysiology of hypertension in pregnancy, as well as advances in medical therapy to minimize risks of fetal toxicity and teratogenicity, will improve our ability to prevent and treat hypertension in pregnancy. Fetal programming and fetal origins of adult disease theories extrapolate the benefit of such therapy to future generations.

  13. [Patient with postpartum seizures: differential diagnosis].

    PubMed

    Higueras, R; Beltrán, M; Peral, D; Ferrándiz, L; Barrachina, C; Barberá, M

    2007-03-01

    Pre-eclampsia is a serious obstetric complication associated with a high rate of maternal and fetal morbidity and mortality. We report the case of a woman with a medical history of insulin-dependent diabetes mellitus and seizures possibly related to hypoglycemia who was admitted for an emergency cesarian due to severe pre-eclampsia and macrosomic fetus. In the first hour after delivery she experienced loss of consciousness and seizure, with vaginal bleeding and hypovolemic shock. Maximum vigilance is required for a patient with several concomitant diseases and a high-risk pregnancy. All prophylactic measures to lower the risk to mother and fetus should be undertaken. We analyze preanesthetic assessment, differential diagnosis, and choice of anesthesia in relation to this case.

  14. [Up-to-date on the HELLP syndrome (Hemolysis, Elevated Liver enzymes and Low Platelets)].

    PubMed

    Medhioub Kaaniche, F; Chaari, A; Turki, O; Rgaieg, K; Baccouch, N; Zekri, M; Bahloul, M; Chelly, H; Ben Hamida, Ch; Bouaziz, M

    2016-06-01

    HELLP syndrome is an acronym for Hemolysis, Elevated Liver enzymes and Low Platelets. It is generally considered in the literature as a particular clinical form of pre-eclampsia, a severe complication of the second half of pregnancy. However, this syndrome can occur in isolation in the absence of pre-eclampsia symptoms. Its pathophysiology remains still unclear. The clinical picture is often incomplete and fruste at first. To date, its diagnosis and management is still the subject of much controversy. Associated or not with a vascular and renal manifestations, the HELLP syndrome is a high-risk maternal disorder. The objective of this article is to review the pathophysiological and clinical data and current treatment.

  15. Why is there a modifying effect of gestational age on risk factors for cerebral palsy?

    PubMed Central

    Greenwood, C; Yudkin, P; Sellers, S; Impey, L; Doyle, P

    2005-01-01

    Objective: To investigate risk factors for cerebral palsy in relation to gestational age. Design: Three case-control studies within a geographically defined cohort. Setting: The former Oxfordshire Health Authority. Participants: A total of 235 singleton children with cerebral palsy not of postnatal origin, born between 1984 and 1993, identified from the Oxford Register of Early Childhood Impairment; 646 controls matched for gestation in three bands: ⩽32 weeks; 33–36 weeks; ⩾37 weeks. Results: Markers of intrapartum hypoxia and infection were associated with an increased risk of cerebral palsy in term and preterm infants. The odds ratio (OR) for hypoxia was 12.2 (95% confidence interval 1.2 to 119) at ⩽32 weeks and 146 (7.4 to 3651) at ⩾37 weeks. Corresponding ORs for neonatal sepsis were 3.1 (1.8 to 5.4) and 10.6 (2.1 to 51.9). In contrast, pre-eclampsia carried an increased risk of cerebral palsy at ⩾37 weeks (OR 5.1 (2.2 to 12.0)) but a decreased risk at ⩽32 weeks (OR 0.4 (0.2 to 1.0)). However, all infants ⩽32 weeks with maternal pre-eclampsia were delivered electively, and their risk of cerebral palsy was no lower than that of other electively delivered ⩽32 week infants (OR 0.9 (0.3 to 2.7)). Nearly 60% of ⩽32 week controls were delivered after spontaneous preterm labour, itself an abnormal event. Conclusion: Inflammatory processes, including pre-eclampsia, are important in the aetiology of cerebral palsy. The apparent reduced risk of cerebral palsy associated with pre-eclampsia in very preterm infants is driven by the characteristics of the gestation matched control group. Use of the term "protective" in this context should be abandoned. PMID:15724038

  16. Capgras' syndrome with organic disorders.

    PubMed Central

    Collins, M. N.; Hawthorne, M. E.; Gribbin, N.; Jacobson, R.

    1990-01-01

    Capgras' syndrome, one form of the delusional misidentification syndromes, is described. Three patients with the syndrome are reported. The first had a right cerebral infarction, the second had nephrotic syndrome secondary to severe pre-eclampsia in the puerperium, and the third had uncontrolled diabetes mellitus with dementia. Evidence is reviewed regarding an organic aetiology for Capgras' syndrome. We conclude that, when the syndrome is present, a thorough search for organic disorder should be made. PMID:2084656

  17. An update on thrombophilia and placenta mediated pregnancy complications: what should we tell our patients?

    PubMed

    Rodger, Marc A

    2013-01-01

    The placenta mediated pregnancy complications, including pre-eclampsia, birth of a small for gestational age child, placental abruption or late pregnancy loss, are common and often devastating pregnancy complications leading to important maternal/fetal/neonatal morbidity and mortality. In this narrative review I examine two common questions related to women with prior placenta mediated pregnancy complications. Do thrombophilias cause placenta mediated pregnancy complications? Does low molecular weight heparin prevent recurrent placenta mediated pregnancy complications?

  18. Adiposity and hyperglycaemia in pregnancy and related health outcomes in European ethnic minorities of Asian and African origin: a review

    PubMed Central

    Jenum, Anne Karen; Sommer, Christine; Sletner, Line; Mørkrid, Kjersti; Bærug, Anne; Mosdøl, Annhild

    2013-01-01

    Background Ethnic minorities in Europe have high susceptibility to type 2 diabetes (T2DM) and, in some groups, also cardiovascular disease (CVD). Pregnancy can be considered a stress test that predicts future morbidity patterns in women and that affects future health of the child. Objective To review ethnic differences in: 1) adiposity, hyperglycaemia, and pre-eclampsia during pregnancy; 2) future risk in the mother of obesity, T2DM and CVD; and 3) prenatal development and possible influences of maternal obesity, hyperglycaemia, and pre-eclampsia on offspring's future disease risk, as relevant for ethnic minorities in Europe of Asian and African origin. Design Literature review. Results Maternal health among ethnic minorities is still sparsely documented. Higher pre-pregnant body mass index (BMI) is found in women of African and Middle Eastern descent, and lower BMI in women from East and South Asia compared with women from the majority population. Within study populations, risk of gestational diabetes mellitus (GDM) is considerably higher in many minority groups, particularly South Asians, than in the majority population. This increased risk is apparent at lower BMI and younger ages. Women of African origin have higher risk of pre-eclampsia. A GDM pregnancy implies approximately seven-fold higher risk of T2DM than normal pregnancies, and both GDM and pre-eclampsia increase later risk of CVD. Asian neonates have lower birth weights, and mostly also African neonates. This may translate into increased risks of later obesity, T2DM, and CVD. Foetal overgrowth can promote the same conditions. Breastfeeding represents a possible strategy to reduce risk of T2DM in both the mother and the child. Conclusions Ethnic minority women in Europe with Asian and African origin and their offspring seem to be at increased risk of T2DM and CVD, both currently and in the future. Pregnancy is an important window of opportunity for short and long-term disease prevention. PMID:23467680

  19. Hepatic infarction in a pregnant patient with the 'primary' antiphospholipid syndrome.

    PubMed

    Millán-Mon, A; Porto, J L; Novo, C; García-Martin, C; Guitián, D

    1993-08-01

    We describe a patient with previous venous thrombosis while using oral contraceptives and recurrent pregnancy loss, who presented with massive hepatic infarction in the last trimester of the fourth gestation. Thrombocytopenia, the lupus anticoagulant (LA) and the anticardiolipin antibody (aCL) were detected and a diagnosis of a 'primary' antiphospholipid syndrome (APS) was made. The clinical and histological manifestations and the differential diagnosis, especially with DIC and pre-eclampsia, are discussed.

  20. Thrombophilia and Pregnancy Complications.

    PubMed

    Simcox, Louise E; Ormesher, Laura; Tower, Clare; Greer, Ian A

    2015-11-30

    There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question.

  1. [Behavior of serum alkaline during pregnancy. II. Pathological pregnancy].

    PubMed

    Stark, K H; Nabel, H J; Kyank, H; Neumayer, E; Dässler, C G; Töwe, J

    1976-01-01

    832 estimations of heat stable alkaline phosphatase (HSAP) and of heat alkaline phosphatase (HLAP) were carried out simultaneously in late pregnant women at 25th to the 42nd weeks of pregnancy. 147 of them delivered children with normal birth-weight. All these women suffered from pre-eclampsia, hypertension or any kind of superimposed pre-eclampsia. 110 other pregnant women with or without symptoms of pre-eclampsia gave birth to small for dates babies. In addition, the values of these patients were compared with 372 estimations of the same enzymes carried out in 120 patients with normal pregnancy and outcome of normal weighted children. The site of the values of every group showed no typical correlation to the course and outcome of their pregnancy. Regarding four special criterions it was possible to give a good prediction by serial determinations for the weight of the newborn in 80 per cent of the cases. A correlation between the urinary excretion of total oestrogens as well as HLAP and the values of HSAP was to be found only in some groups of patients.

  2. Effects of matrix metalloproteinase (MMP)-2 polymorphisms on responsiveness to antihypertensive therapy of women with hypertensive disorders of pregnancy.

    PubMed

    Palei, Ana C T; Sandrim, Valeria C; Amaral, Lorena M; Machado, Jackeline S R; Cavalli, Ricardo C; Lacchini, Riccardo; Duarte, Geraldo; Tanus-Santos, Jose E

    2012-10-01

    Imbalanced matrix metalloproteinase (MMP) expression, including MMP-2, has been demonstrated in pre-eclampsia. However, little is known about the effect of polymorphisms in MMP-2 gene on hypertensive disorders of pregnancy. We examined whether two functional MMP-2 polymorphisms (g.-1306C>T and g.-735C>T) are associated with pre-eclampsia and/or gestational hypertension and whether these polymorphisms affect therapeutic responses in women with these conditions. We studied 216 healthy pregnant women (HP), 185 patients with gestational hypertension (GH) and 216 patients with pre-eclampsia (PE). They were stratified as responsive or non-responsive to antihypertensive therapy according to clinical and laboratorial parameters of therapeutic responsiveness. Genomic DNA was extracted from whole blood and genotypes for g-1306C>T and g.-735C>T polymorphisms were determined by real-time PCR using Taqman allele discrimination assays. Haplotype frequencies were inferred using the PHASE 2.1 program. The distributions of MMP-2 genotypes and haplotypes were similar in HP, GH and PE patients (p > 0.05). In addition, we found no significant differences in MMP-2 genotype or haplotype frequencies when GH or PE patients were classified as responsive or non-responsive to antihypertensive therapy (p > 0.05). Our results suggest that MMP-2 polymorphisms do not affect the susceptibility to hypertensive disorders of pregnancy. In parallel, MMP-2 polymorphisms apparently do not affect the responsiveness to antihypertensive therapy of women with these hypertensive disorders of pregnancy.

  3. A clinical characteristic analysis of pregnancy-associated intracranial haemorrhage in China

    PubMed Central

    Liang, Zhu-Wei; Lin, Li; Gao, Wan-Li; Feng, Li-Min

    2015-01-01

    Intracerebral haemorrhage (ICH) occurring during pregnancy and the puerperium is an infrequent but severe complication with a high mortality and poor prognosis. Until recently, previous studies have mainly focused on the effect of different treatments on prognosis. However, few studies have provided solid evidence to clarify the key predisposing factors affecting the prognosis of ICH. In the present study, based on a unique sample with a high ICH incidence and mortality rate, we described the main clinical characteristics of ICH patients and found that the prognosis of patients who underwent surgical intervention was not better than that of patients who received other treatment modalities. However, pre-eclampsia patients had higher maternal and neonatal mortality rates than other aetiology groups. Furthermore, univariate regression analysis identified onset to diagnosis time (O-D time) and pre-eclampsia as the only factors showing independent correlation with poor maternal outcomes (modified Rankin Scale, mRS ≥ 3), and only O-D time was identified as a predictor of maternal mortality. These results revealed that the aetiology of ICH and O-D time might be crucial predisposing factors to prognosis, especially for patients with pre-eclampsia. The study highlighted a novel direction to effectively improve the prognosis of pregnancy-associated ICH. PMID:25819941

  4. Hepatic infarctions during pregnancy are associated with the antiphospholipid syndrome and in addition with complete or incomplete HELLP syndrome.

    PubMed

    Pauzner, R; Dulitzky, M; Carp, H; Mayan, H; Kenett, R; Farfel, Z; Many, A

    2003-08-01

    Antiphospholipid antibody syndrome (APS) is associated with adverse pregnancy outcomes and maternal complications including thrombotic events and early pre-eclampsia. HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) represents a unique form in the spectrum of pre-eclampsia. This report describes four patients with pregnancy-associated hepatic infarctions. All four had APS and HELLP syndrome, which was complete in one patient and incomplete in three patients, with elevated liver enzymes in all, and either thrombocytopenia or hemolysis in two. In the literature, we found descriptions of an additional 24 patients who had 26 pregnancies with concomitant hepatic infarction. Of the total 28 patients, anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC) were assessed in 16 patients, out of whom 15 were found to be positive. Hepatic infartction during pregnancy was associated almost always with APS, with HELLP (2/3 complete, 1/3 incomplete), and only in one-third of the pregnancies with pre-eclampsia (PE).

  5. Hypothesis on the role of sub-clinical bacteria of the endometrium (bacteria endometrialis) in gynaecological and obstetric enigmas.

    PubMed

    Viniker, D A

    1999-01-01

    Unexplained infertility, recurrent abortion, dysfunctional uterine bleeding, pelvic pain, premenstrual syndrome, premature labour, placental insufficiency and pre-eclampsia are examples of common obstetric and gynaecological problems that frequently defy adequate explanation. Bacterial vaginosis, a non-inflammatory condition, is associated with premature labour, but antibiotics administered topically provide less effective prophylaxis than those administered orally. This would indicate that bacterial vaginosis might be a marker for significant genital tract bacteria, but some pathology is dependent on micro-organisms ascending out of reach of topical antibiotics. The author was led to consider the hypothesis that micro-organisms, possibly those associated with bacterial vaginosis, surreptitiously inhabit the uterine cavity (bacteria endometrialis) where they are culprits of some common gynaecological and obstetric enigmas. The objective of this review is to provide an initial theoretical examination of this hypothesis. Bacteria in the endometrium have been associated with infertility. Antiphospholipids have been linked to recurrent miscarriage and pre-eclampsia and with infections including Mycoplasma. Pre-eclampsia might be explained by an exaggerated host response to intrauterine micro-organisms or bacterial toxins. The hypothesis that one common factor, bacteria endometrialis, could provide a plausible explanation for a variety of obstetric and gynaecological mysteries is particularly intriguing. There is sufficient evidence to justify further investigation.

  6. 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

  7. Blood rheology at term in normal pregnancy and in patients with adverse outcome events.

    PubMed

    von Tempelhoff, Georg-Friedrich; Velten, Eva; Yilmaz, Asli; Hommel, Gerhard; Heilmann, Lothar; Koscielny, Jürgen

    2009-01-01

    Plasma volume expansion of more than 1.5 l and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.e. pre-eclampsia commonly coincide with hemo concentration and over activation of blood coagulation both of which alter blood rheology. On the basis of 4,985 consecutively recorded singleton pregnancies values range of blood rheological parameters in women with normal and complicated outcome of pregnancy at the time of their delivery were compared. Plasma viscosity (pv) was determined using KSPV 1 Fresenius and RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. Seventy-nine point four percent (n=3,959) had normal pregnancy outcome and 1,026 with adverse outcome of pregnancy had pre-eclampsia (8.4%; n=423), had newborn with a birth-weight < 2,500 g (9.5%; n=473), had early-birth before week 37 (9.3%; n=464), and/or were diagnosed with intra uterine growth retardation (IUGR) (5.0%; n=250). In women with normal pregnancy outcome mean (+/-SD) of pv was 1.31+/-0.09 mPa s, of E0 was 21.6+/-5.3, and of E1 was 38.4+/-7.9 while in women with adverse outcome means for rheological parameters were statistically significantly different i.e. pv: 1.32+/-0.08 mPa s; p=0.006, E0: 22.1+/-5.5; p=0.002 and E1: 39.5+/-8.5; p=0.0006. Subgroup analysis revealed statistical significant lower pv in women who either had pre term delivery or a low birth-weight child (p<0.005) as compared to women who had normal pregnancy outcome while patients with pre-eclampsia had markedly higher low shear and stasis RBC aggregation (p<0.0001). None of the rheological results at term were correlated with either maternal age (r<0.04), BMI (r<0.09), maternal weight gain until delivery (r<0.04), or fetal outcome such as APGAR-score (r<0.09) art. pH in the umbilical cord (-0.05

  8. Managing pregnancy with HIV, HELLP syndrome and low platelets.

    PubMed

    Onyangunga, O A; Moodley, J

    2012-02-01

    Management of pregnancies with human immunodeficiency virus, haemolytic anaemia, elevated liver enzymes, low platelets (HELLP) syndrome, and low platelets presents complexities in investigations and treatments, because these conditions and their treatment affect the mother and baby. Low platelets in severe pre-eclampsia, eclampsia and HELLP syndrome are relatively common, and should be detected early once the diagnosis of pre-eclampsia, HELLP syndrome, or both, are made. The mainstay of treatment is lowering of high blood pressure with rapid-acting antihypertensive agents, prevention of convulsions or further seizures with MgSO(4), use of steroids for fetal lung maturity if necessary, followed by delivery of the baby. The use of high-dose steroids for the rapid recovery of maternal platelet counts is controversial, and should not be used routinely in women with HELLP syndrome. The use of platelet transfusion in women with severe pre-eclampsia, eclampsia and HELLP syndrome is a temporising measure, and should only be justified if the clinical circumstances warrant their use (e.g. before caesarean section when the woman has a low platelet count with evidence of bruising or bleeding from venepuncture sites). Low platelets may be an isolated finding in asymptomatic pregnant women and warrant the offer of a human immunodeficiency virus test, as it may be the first sign of this infection. Isolated low platelets may also indicate gestational thrombocytopaenia or idiothrombocytopaenic purpura. Gestational thrombocytopaenia is a benign condition and a diagnosis of exclusion. All clinicians should be aware that low platelets warrant further investigations because of the above-mentioned issues.

  9. Advanced glycation end products as an upstream molecule triggers ROS-induced sFlt-1 production in extravillous trophoblasts: a novel bridge between oxidative stress and preeclampsia.

    PubMed

    Huang, Q T; Zhang, M; Zhong, M; Yu, Y H; Liang, W Z; Hang, L L; Gao, Y F; Huang, L P; Wang, Z J

    2013-12-01

    Although abnormal soluble fms-like tyrosine kinase-1 (sFlt-1) production is thought to be an important factor in the pathogenesis of pre-eclampsia, the mechanisms that regulate the production of sFlt-1 during pre-eclampsia are unclear. Accumulation of advanced glycation end products (AGEs) is prevalent in obesity, advanced maternal age, diabetes mellitus, and polycystic ovary syndrome. Alterations in the regulation and signaling of angiogenic pathways have been considered as a link between these conditions and pre-eclampsia. The purpose of this study was to explore the possible effects of AGEs on sFlt-1 secretion in extravillous trophoblasts (EVT). A EVT cell line (HRT-8/SVneo) was treated with various concentrations of AGEs-BSA. The mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in EVT were detected with real-time polymerase chain reaction. The secretion of sFlt-1, VEGF, and PlGF protein from EVT was measured with ELISA. The levels of intracellular reactive oxygen species (ROS) production were determined by DCFH-DA. Exposure of EVT to AGEs-BSA induced increased intracellular ROS generation and overexpression of sFlt-1 at mRNA and protein levels in a dose dependent manner. Anti-RAGE immunoglobulin G or apocynin (an inhibitors of NADPH oxidase) could decrease the intracellular ROS generation and subsequently suppressed the production of sFlt-1 at mRNA and protein levels. Our data suggested that AGEs may be a new class of important mediator in the regulation of angiogenic pathways of EVT. Accumulation of AGEs might contribute to the pathogenesis of preeclampsia by promoting sFlt-1 production through activation of RAGE/NADPH oxidase dependent pathway in EVT.

  10. Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution

    PubMed Central

    Jauniaux, Eric; Poston, Lucilla; Burton, Graham J.

    2007-01-01

    Miscarriage and pre-eclampsia are the most common disorders of human pregnancy. Both are placental-related and exceptional in other mammalian species. Ultrasound imaging has enabled events during early pregnancy to be visualized in vivo for the first time. As a result, a new understanding of the early materno–fetal relationship has emerged and, with it, new insight into the pathogenesis of these disorders. Unifying the two is the concept of placental oxidative stress, with associated necrosis and apoptosis of the trophoblastic epithelium of the placental villous tree. In normal pregnancies, the earliest stages of development take place in a low oxygen (O2) environment. This physiological hypoxia of the early gestational sac protects the developing fetus against the deleterious and teratogenic effects of O2 free radicals (OFRs). In miscarriage, development of the placento–decidual interface is severely impaired leading to early and widespread onset of maternal blood flow and major oxidative degeneration. This mechanism is common to all miscarriages, with the time at which it occurs in the first trimester depending on the aetiology. In contrast, in pre-eclampsia the trophoblastic invasion is sufficient to allow early pregnancy phases of placentation but too shallow for complete transformation of the arterial utero–placental circulation, predisposing to a repetitive ischaemia–reperfusion (I/R) phenomenon. We suggest that pre-eclampsia is a three-stage disorder with the primary pathology being an excessive or atypical maternal immune response. This would impair the placentation process leading to chronic oxidative stress in the placenta and finally to diffuse maternal endothelial cell dysfunction. PMID:16682385

  11. The novel inflammatory cytokine high mobility group box protein 1 (HMGB1) is expressed by human term placenta

    PubMed Central

    Holmlund, Ulrika; Wähämaa, Heidi; Bachmayer, Nora; Bremme, Katarina; Sverremark-Ekström, Eva; Palmblad, Karin

    2007-01-01

    High mobility group box protein 1 (HMGB1) was previously considered a strict nuclear protein, but lately data are accumulating on its extranuclear functions. In addition to its potent proinflammatory capacities, HMGB1 has a prominent role in a number of processes of specific interest for the placenta. Our overall aim was to investigate the expression of HMGB1 in human term placenta and elucidate a potential difference in HMGB1 expression comparing vaginal deliveries with elective Caesarean sections. In addition, placentas from normal pregnancies were compared with placentas from pregnancies complicated by pre-eclampsia. Twenty-five placentas, 12 from normal term pregnancies and 13 from pregnancies complicated by pre-eclampsia were analysed with immunohistochemistry for HMGB1 and its putative receptors; receptor for advanced glycation end-products (RAGE), Toll-like receptor 2 (TLR2) and TLR4. We present the novel finding that in addition to a strong nuclear HMGB1 expression in almost all cells in investigated placentas, an individual variation of cytoplasmic HMGB1 expression was detected in the syncytiotrophoblast covering the peripheral chorionic villi, by cells in the decidua and in amnion. Production of HMGB1 was confirmed by in situ hybridization. Although labour can be described as a controlled inflammatory-like process no differences in HMGB1 expression could be observed comparing active labour and elective Caesarean sections. However, a tendency towards a higher expression of cytoplasmic HMGB1 in the decidua from women with pre-eclampsia was demonstrated. The abundant expression of the receptors RAGE, TLR2 and TLR4 implicates a local capability to respond to HMGB1, although the precise role in the placenta remains to be elucidated. PMID:17617154

  12. [Detecting high risk pregnancy].

    PubMed

    Doret, Muriel; Gaucherand, Pascal

    2009-12-20

    Antenatal care is aiming to reduce maternal land foetal mortality and morbidity. Maternal and foetal mortality can be due to different causes. Their knowledge allows identifying pregnancy (high risk pregnancy) with factors associated with an increased risk for maternal and/or foetal mortality and serious morbidity. Identification of high risk pregnancies and initiation of appropriate treatment and/or surveillance should improve maternal and/or foetal outcome. New risk factors are continuously described thanks to improvement in antenatal care and development in biology and cytopathology, increasing complexity in identifying high risk pregnancies. Level of risk can change all over the pregnancy. Ideally, it should be evaluated prior to the pregnancy and at each antenatal visit. Clinical examination is able to screen for intra-uterin growth restriction, pre-eclampsia, threatened for preterm labour; ultrasounds help in the diagnosis of foetal morphological anomalies, foetal chromosomal anomalies, placenta praevia and abnormal foetal growth; biological exams are used to screen for pre-eclampsia, gestational diabetes, trisomy 21 (for which screening method just changed), rhesus immunisation, seroconversion for toxoplasmosis or rubeola, unknown infectious disease (syphilis, hepatitis B, VIH). During pregnancy, most of the preventive strategies have to be initiated during the first trimester or even before conception. Prevention for neural-tube defects, neonatal hypocalcemia and listeriosis should be performed for all women. On the opposite, some measures are concerning only women with risk factors such as prevention for toxoplasmosis, rhesus immunization (which recently changed), tobacco complications and pre-eclampsia and intra-uterine growth factor restriction.

  13. Pregnancy close to the edge: an immunosuppressive infiltrate in the chorionic plate of placentas from uncomplicated egg cell donation.

    PubMed

    Schonkeren, Dorrith; Swings, Godelieve; Roberts, Drucilla; Claas, Frans; de Heer, Emile; Scherjon, Sicco

    2012-01-01

    In pregnancies achieved after egg donation (ED) tolerance towards a completely allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of which numerous aspects are still unknown. A distinct lesion not described previously in the literature, was repeatedly found in the chorionic plate in a substantial portion of placentas from ED pregnancies, but never in placentas from normal term pregnancies. The aim of this study was to assess its origin and its cellular composition. The relation between the lesion, the clinical and histological parameters were assessed. In addition we investigated the relation with the number of HLA-mismatches and KIR genotype of mother and child.In ten out of twenty-six (38.5%) placentas from ED pregnancies an inflammatory lesion was present in the chorionic plate. A significantly lower incidence of pre-eclampsia was found in the group with the lesion; 0% versus 45.5%. A significant relation was found between this lesion and the presence of intervillositis, chronic deciduitis, presence of plasma cells and fibrin deposition in the decidua. Fluorescent in situ hybridisation with X/Y-chromosome probes showed that the majority of cells present in the lesion are of maternal origin. The expression of the macrophage marker CD14+ and of the type 2 macrophage (M2) marker CD163+ was significantly higher in the lesion. The incidence of a fetal HLA-C2 genotype was significantly higher in cases with a lesion compared to the group without the lesion. In conclusion, a striking relationship was observed between the presence of a not previously described inflammatory lesion in the chorionic plate and the absence of pre-eclampsia in ED pregnancies. The lesion consists of mainly maternal cells with a higher expression of the macrophage marker CD14+ and the M2 marker CD163+. These findings suggest a protective immune mechanism which might contribute to the prevention of severe clinical complications like pre-eclampsia.

  14. A multi-centre phase IIa clinical study of predictive testing for preeclampsia: improved pregnancy outcomes via early detection (IMPROvED)

    PubMed Central

    2013-01-01

    Background 5% of first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROvED Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The key objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia. Methods/Design We report the design of a multicentre, phase IIa clinical study aiming to recruit 5000 low risk primiparous women to assess and refine innovative prototype tests based on emerging metabolomic and proteomic technologies. Participation involves maternal phlebotomy at 15 and 20 weeks’ gestation, with optional testing and biobanking at 11 and 34 weeks. Blood samples will be analysed using two innovative, proprietary prototype platforms; one metabolomic based and one proteomic based, both of which outperform current biomarker based screening tests at comparable gestations. Analytical and clinical data will be collated and analysed via the Copenhagen Trials Unit. Discussion The IMPROvED study is expected to refine proteomic and metabolomic panels, combined with clinical parameters, and evaluate clinical applicability as an early pregnancy predictive test for pre-eclampsia. If ‘at risk’ patients can be identified, this will allow stratified care with personalised fetal and maternal surveillance, early diagnosis, timely intervention, and significant health economic savings. The IMPROvED biobank will be accessible to the European scientific community for high quality research into the cause and prevention of adverse pregnancy outcome. Trial registration Trial registration number NCT01891240 The IMPROvED project is funded by the seventh framework

  15. Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution.

    PubMed

    Jauniaux, Eric; Poston, Lucilla; Burton, Graham J

    2006-01-01

    Miscarriage and pre-eclampsia are the most common disorders of human pregnancy. Both are placental-related and exceptional in other mammalian species. Ultrasound imaging has enabled events during early pregnancy to be visualized in vivo for the first time. As a result, a new understanding of the early materno-fetal relationship has emerged and, with it, new insight into the pathogenesis of these disorders. Unifying the two is the concept of placental oxidative stress, with associated necrosis and apoptosis of the trophoblastic epithelium of the placental villous tree. In normal pregnancies, the earliest stages of development take place in a low oxygen (O2) environment. This physiological hypoxia of the early gestational sac protects the developing fetus against the deleterious and teratogenic effects of O2 free radicals (OFRs). In miscarriage, development of the placento-decidual interface is severely impaired leading to early and widespread onset of maternal blood flow and major oxidative degeneration. This mechanism is common to all miscarriages, with the time at which it occurs in the first trimester depending on the aetiology. In contrast, in pre-eclampsia the trophoblastic invasion is sufficient to allow early pregnancy phases of placentation but too shallow for complete transformation of the arterial utero-placental circulation, predisposing to a repetitive ischaemia-reperfusion (I/R) phenomenon. We suggest that pre-eclampsia is a three-stage disorder with the primary pathology being an excessive or atypical maternal immune response. This would impair the placentation process leading to chronic oxidative stress in the placenta and finally to diffuse maternal endothelial cell dysfunction.

  16. Abnormal expression of plasminogen activator inhibitors in patients with gestational trophoblastic disease.

    PubMed Central

    Estellés, A.; Grancha, S.; Gilabert, J.; Thinnes, T.; Chirivella, M.; España, F.; Aznar, J.; Loskutoff, D. J.

    1996-01-01

    We previously reported significantly elevated levels of plasminogen activator inhibitor type 1 (PAI-1) in plasma and placenta from pregnant women with severe pre-eclampsia, and pre-eclampsia is a frequent problem in molar pregnancies. As increases in PAI-1 may contribute to the placental alterations that occur in pre-eclampsia, we have begun to investigate changes in PAI-1 as well as PAI-2 and several other components of the fibrinolytic system in patients with trophoblastic disease. Significant increases in plasma PAI-1 and decreases in plasma PAI-2 levels were observed in molar pregnancies when compared with the levels in normal pregnant women of similar gestational age. PAI-1 antigen levels also were increased, and PAI-2 levels were decreased in placenta from women with molar pregnancies compared with placenta obtained by spontaneous abortion. Immunohistochemical analysis revealed strong positive and specific staining of PAI-1 in trophoblastic epithelium in molar pregnancies and relatively weak staining of PAI-2. No association between the distribution of PAI-1 and vitronectin was found, and no specific signal for tissue type PA, urokinase type PA, tumor necrosis factor-alpha, or interleukin-1 was detected. In situ hybridization revealed an increase in PAI-1 but not PAI-2 mRNAs in placenta from molar pregnancies in comparison with placenta from abortions. These results demonstrate increased PAI-1 protein and mRNA in trophoblastic disease and suggest that localized elevated levels of PAI-1 may contribute to the hemostatic problems associated with this disorder. Images Figure 1 Figure 2 Figure 3 PMID:8863672

  17. Evaluation of the effect of high-dose folic acid on endothelial dysfunction in pre-eclamptic patients: A randomized clinical trial

    PubMed Central

    Hashemi, Mohammad; Heshmat-ghahdarijani, Kiyan; Zarean, Elahe; Baktash, Forouz; Mortazavi, Zahra Sadat

    2016-01-01

    Background: Pre-eclampsia as a hypertensive disorder of pregnancy complicates up to 5–10% of pregnancies worldwide. Endothelial dysfunction plays an important role in the pathogenesis of pre-eclampsia. In this study, we aim to evaluate the effect of high-dose folic acid on endothelial dysfunction in pre-eclamptic patients. Materials and Methods: In this triple-blinded randomized clinical trial, the enrolled patients were divided randomly into two groups. Folic acid 5.0 mg or placebo was taken daily by oral administration from the initiation of diagnosis until 2 months after delivery by the participants. Every patient's flow-mediated dilation (FMD) was evaluated at the beginning of the study and 2 months after delivery with the same experienced operator at the same period of time (3–5 p.m.) by high-resolution B-mode ultrasonography. Potential confounding variables were included in the independent samples t-test. t-test or Mann–Whitney U-test was used in the comparison of means between the intervention and placebo groups. To compare FMD in each group, before and after the intervention, paired t-test was used. Results: Mean value of FMD in intervention (9.64 ± 5.57) and control group (9.30 ± 4.25) has no significant difference before the consumption of drugs (P > 0.05). FMD in intervention group (13.72 ± 7.89) significantly increases after daily consumption of 5 mg folic acid in comparison with control group (10.02 ± 4.81) after daily consumption of placebo (P = 0.002). Conclusion: Increased mean of FMD in intervention group shows that this supplement can improve endothelial function and can be significantly affected by maternal blood pressure during pregnancy and some endothelium-dependent disease such as pre-eclampsia and its associated adverse outcomes. PMID:28255322

  18. Facial nerve paralysis and partial brachial plexopathy after epidural blood patch: a case report and review of the literature

    PubMed Central

    Shahien, Radi; Bowirrat, Abdalla

    2011-01-01

    We report a complication related to epidural analgesia for delivery in a 24- year-old woman who was admitted with mild pre-eclampsia and for induction of labor. At the first postpartum day she developed a postdural puncture headache, which was unresponsive to conservative measures. On the fifth day an epidural blood patch was done, and her headache subsided. Sixteen hours later she developed paralysis of the right facial nerve, which was treated with prednisone. Seven days later she complained of pain in the left arm and the posterior region of the shoulder. She was later admitted and diagnosed with partial brachial plexopathy. PMID:21386953

  19. Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme.

    PubMed

    John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

    2017-01-14

    Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome.

  20. Pregnancy outcome after illegal induced abortion in Nigeria: a retrospective controlled historical study.

    PubMed

    Okonofua, F E; Onwudiegwu, U; Odutayo, R

    1994-06-01

    The effect of illegal abortion on subsequent reproduction was studied in 46 Nigerian women who gave a history of illegal termination of pregnancy. There was a statistically significant increase in the incidences of premature rupture of membranes, premature labour and low birth weight when compared to 53 primigravida who gave no such history of abortion. The perinatal mortality was also significantly higher in the abortion group. In contrast, pre-eclampsia was less common in the abortion group. These findings indicate that illegal abortion has adverse effects on pregnancy outcome in Nigerian women.

  1. [Risk of maternal and fetal disease among women older than 40 years].

    PubMed

    Vanya, Melinda; Szili, Károly; Devosa, Iván; Bártfai, György

    2015-12-06

    A rising trend in advanced maternal age has been observed over the last few decades. Several studies have assessed the association between advanced maternal age and adverse pregnancy outcome, including miscarriage, stillbirth, pre-eclampsia, gestational hypertension, gestational diabetes mellitus, preterm birth, delivery of a small- or large-for-gestational-age neonates and elective or emergency Cesarean section. These studies reported contradictory findings. The aim of the present paper is to summarize the evidence-based information regarding advanced maternal age and pregnancy outcomes.

  2. [How to confirm acute fatty liver of pregnancy in case of emergency].

    PubMed

    Homer, L; Hebert, T; Nousbaum, J-B; Bacq, Y; Collet, M

    2009-03-01

    Acute fatty liver of pregnancy (AFLP) is a rare disease of which prognosis could be adverse if diagnosis is delayed. Certain diagnosis is sometimes made complex because of undercurrent symptoms with pre-eclampsia or hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome. Several reports announce an increase of incidence and illustrate cases confirmed by non-invasive methods. They permit early diagnosis and improve morbidity and mortality. Reviewing seven of the most important series of AFLP, we demonstrate how to use ultrasonography or computed tomography scan to confirm AFLP. However, liver biopsy should be realised after delivery in case of uncertain diagnosis.

  3. Triple-branched stent graft for arch repair in a pregnant woman with acute DeBakey type I aortic dissection.

    PubMed

    Zhang, Qian; Ma, Xiaochun; Wang, Zhengjun; Zou, Chengwei

    2017-03-12

    A woman aged 36 years at 36 weeks of pregnancy sought medical attention at the Shandong Provincial Hospital affiliated to Shandong University, Shandong, China, after experiencing acute chest pain. The patient was diagnosed with chronic hypertension, severe pre-eclampsia, acute aortic dissection, aortic regurgitation, and heart failure. Computed tomography examination demonstrated a DeBakey type I aortic dissection that involved the origin of the innominate artery, the left common carotid artery, and the left subclavian artery. This article is protected by copyright. All rights reserved.

  4. Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study.

    PubMed

    Moroni, Gabriella; Doria, Andrea; Giglio, Elisa; Imbasciati, Enrico; Tani, Chiara; Zen, Margherita; Strigini, Francesca; Zaina, Barbara; Tincani, Angela; Gatto, Mariele; de Liso, Federica; Grossi, Claudia; Meroni, Pier Luigi; Cabiddu, Gianfranca; Messa, Piergiorgio; Ravani, Pietro; Mosca, Marta

    2016-11-01

    Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling. This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes. Fourteen flares (19.7%), six cases of pre-eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP. In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal

  5. Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme

    PubMed Central

    John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

    2017-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome. PMID:28127211

  6. Successful management of discordant alobar holoprosencephaly in monochorionic diamniotic twins with normal karyotype: a case report.

    PubMed

    Zhang, J; Yang, T; Wang, X; Yu, H

    2015-01-01

    Holoprosencephaly (HPE), a complex brain malformation resulting from incomplete cleavage of the prosencephalon into distinct cerebral hemispheres, is rare in newborns. Two preterm male neonates were born at 34 weeks' and five days' gestation in the monochorionic diamniotic twin pregnancy complicated with pre-eclampsia and intrahepatic cholestasis of pregnancy, and one of them was prenatally diagnosed with alobar HPE by ultrasonography with frontal bossing, hydrocephaly, hypotelorism of eyes, flat nasal bridge, macroglossia, and cheilo/palatoschisis at birth. Karyotyping by G-banding of amniocentesis specimens in normal twin and fetal umbilical blood in both fetuses showed 46, XY. This report expands discordant alobar holoprosencephaly in monochorionic diamniotic twins.

  7. [The Course of Pregnancy in Women With Arterial Hypertension].

    PubMed

    V Brytkova, Ya; Stryuk, R I

    2017-01-01

    We included in this study 69 women with hypertension in the II trimester of pregnancy, of whom 52 (75%) had normal weight gain during the period of gestation, and 17 (25%) had abnormal weight gain. Comprehensive clinical and instrumental examination included calculation of body mass index before and during gestation, 24-hour ambulatory blood pressure (BP) monitoring, assessment of activity of sympathetic-adrenal system by quantification of -adrenoreception of erythrocytes cell membranes. Women with excessive weight gain during gestation were older, more often had increased body weight before pregnancy. They also more often had insufficient nocturnal BP lowering, hypersympathicotonia, premature labor, pre-eclampsia, and lower anthropometric parameters of newborns.

  8. Postpartum HELLP syndrome after a normotensive pregnancy.

    PubMed Central

    Esan, K; Moneim, T; Page, I J

    1997-01-01

    Severe pre-eclampsia, associated with HELLP syndrome, can occur after a normal delivery and birth in a woman whose blood pressure has remained normal throughout the antenatal period. Although rare, the syndrome can lead to pulmonary oedema or renal failure, and should be borne in mind when a woman develops epigastric or right upper-quadrant pain after a normal pregnancy and delivery. A significant fall in the platelet count in the antenatal period may be a useful indicator of risk. PMID:9281873

  9. Homocysteine, folate and pregnancy outcomes.

    PubMed

    Kim, M W; Hong, S-C; Choi, J S; Han, J-Y; Oh, M-J; Kim, H J; Nava-Ocampo, A; Koren, G

    2012-08-01

    The purpose of this study is to evaluate the relationship between maternal and/or cord blood folate/homocysteine concentrations and adverse pregnancy outcomes. The study population included a random sample of singleton pregnant women in whom we measured total homocysteine and folic acid in maternal or cord blood at deliveries. A total of 227 pregnant women were enrolled. The concentration of folate in maternal blood tended to be significantly lower in pre-term birth than in full-term delivery group (median (95% CI), 14.4 (3.6-73) vs 25 (7.3-105.5) p < 0.01). The total homocysteine in maternal and cord blood was significantly higher in the pre-eclampsia than in the normotensive group (7.9 (1.7-28.2) vs 5.9 (1.8-14.6) μmol/ml, p < 0.05; and 5.8 (2.6-14.4) vs 4.2 (0.7-7.9) ng/ml, p < 0.05, respectively). Lower maternal serum folate concentration is associated with pre-term delivery and higher maternal plasma homocysteine concentration with pre-eclampsia.

  10. Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators.

    PubMed

    Pourrat, O; Coudroy, R; Pierre, F

    2015-06-01

    Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe consequences for maternal health, and this can be fatal when thrombotic thrombocytopenic purpura is misdiagnosed as severe HELLP syndrome. The aim of this paper is to propose relevant markers to differentiate pre-eclampsia complicated by severe HELLP syndrome from its imitators, even in the worrying situation of apparently indistinguishable conditions, and thereby assist clinical decision-making regarding whether or not to commence plasma exchange. Relevant identifiers to establish the most accurate diagnosis include the frequency of each disease and anamnestic data. Frank hemolysis, need for dialysis, neurological involvement and absence of disseminated intravascular coagulation are indicative of thrombotic microangiopathy. The definitive marker for thrombotic thrombocytopenic purpura is undetectable ADAMTS 13 activity.

  11. Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome.

    PubMed

    Vaught, Arthur J; Gavriilaki, Eleni; Hueppchen, Nancy; Blakemore, Karin; Yuan, Xuan; Seifert, Sara M; York, Sarah; Brodsky, Robert A

    2016-05-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome.

  12. The Salivary Scavenger and Agglutinin (SALSA) in Healthy and Complicated Pregnancy.

    PubMed

    Reichhardt, Martin Parnov; Jarva, Hanna; Lokki, Anna Inkeri; Laivuori, Hannele; Vuorela, Piia; Loimaranta, Vuokko; Glasner, Andreas; Siwetz, Monika; Huppertz, Berthold; Meri, Seppo

    2016-01-01

    Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. The etiology is not clear, but an immune attack towards components of placenta or fetus has been indicated. This involves activation of the complement system in the placenta. We have previously described the presence of the complement-regulating protein salivary scavenger and agglutinin (SALSA) in amniotic fluid. In this study we investigated the potential role of SALSA in pregnancy by analyzing its presence in amniotic fluid and placental tissue during healthy and complicated pregnancies. SALSA levels in amniotic fluid increased during pregnancy. Before 20 weeks of gestation the levels were slightly higher in patients who later developed pre-eclampsia than in gestation age-matched controls. In the placenta of pre-eclamptic patients syncytial damage is often followed by the formation of fibrinoid structures. SALSA was found clustered into these fibrinoid structures in partial co-localization with complement C1q and fibronectin. In vitro analysis showed direct protein binding of SALSA to fibronectin. SALSA binds also to fibrin/fibrinogen but did not interfere with the blood clotting process in vitro. Thus, in addition to antimicrobial defense and epithelial differentiation, the data presented here suggest that SALSA, together with fibronectin and C1q, may be involved in the containment of injured placental structures into fibrinoids.

  13. Cerebral oxygen saturation evaluated by near-infrared time-resolved spectroscopy (TRS) in pregnant women during caesarean section - a promising new method of maternal monitoring.

    PubMed

    Yamazaki, Kaori; Suzuki, Kazunao; Itoh, Hiroaki; Muramatsu, Keiko; Nagahashi, Kotomi; Tamura, Naoaki; Uchida, Toshiyuki; Sugihara, Kazuhiro; Maeda, Hideki; Kanayama, Naohiro

    2013-03-01

    Time-resolved spectroscopy (TRS-20) measures tissue oxygen saturation (%) by evaluating the absolute concentrations of oxygenated, deoxygenated and total haemoglobin based on measurement of the transit time of individual photons through a tissue of interest. We measured tissue oxygen saturation in the prefrontal lobes of the brain by TRS-20 in eighteen pregnant women during caesarean section. In a case of placenta previa, massive bleeding immediately decreased cerebral oxygen saturation from 67·2% to 54·2%, but did not alter peripheral tissue oxygenation as measured by pulse oximetry. Four cases of pre-eclampsia revealed chronic changes in elevated base levels of cerebral oxygen saturation, though peripheral oxygen saturation was similar to that in normotensive pregnant women. Average cerebral oxygen saturation in the cases of pre-eclampsia before the introduction of anaesthesia was 73·6 ± 4·4 (SD)% (n = 4), significantly higher than in normotensive pregnant women, 67·2 ± 4·3% (n = 13, P<0·05). Z-scores of cerebral oxygen saturation prior to anaesthesia positively correlated with those of systolic or diastolic blood pressure. TRS-20 could detect acute as well as chronic changes in brain oxygen saturation in response to pregnancy-associated complications.

  14. PCSK6-mediated corin activation is essential for normal blood pressure.

    PubMed

    Chen, Shenghan; Cao, Pengxiu; Dong, Ningzheng; Peng, Jianhao; Zhang, Chunyi; Wang, Hao; Zhou, Tiantian; Yang, Junhua; Zhang, Yue; Martelli, Elizabeth E; Naga Prasad, Sathyamangla V; Miller, Rachel E; Malfait, Anne-Marie; Zhou, Yiqing; Wu, Qingyu

    2015-09-01

    Hypertension is the most common cardiovascular disease, afflicting >30% of adults. The cause of hypertension in most individuals remains unknown, suggesting that additional contributing factors have yet to be discovered. Corin is a serine protease that activates the natriuretic peptides, thereby regulating blood pressure. It is synthesized as a zymogen that is activated by proteolytic cleavage. CORIN variants and mutations impairing corin activation have been identified in people with hypertension and pre-eclampsia. To date, however, the identity of the protease that activates corin remains elusive. Here we show that proprotein convertase subtilisin/kexin-6 (PCSK6, also named PACE4; ref. 10) cleaves and activates corin. In cultured cells, we found that corin activation was inhibited by inhibitors of PCSK family proteases and by small interfering RNAs blocking PCSK6 expression. Conversely, PCSK6 overexpression enhanced corin activation. In addition, purified PCSK6 cleaved wild-type corin but not the R801A variant that lacks the conserved activation site. Pcsk6-knockout mice developed salt-sensitive hypertension, and corin activation and pro-atrial natriuretic peptide processing activity were undetectable in these mice. Moreover, we found that CORIN variants in individuals with hypertension and pre-eclampsia were defective in PCSK6-mediated activation. We also identified a PCSK6 mutation that impaired corin activation activity in a hypertensive patient. Our results indicate that PCSK6 is the long-sought corin activator and is important for sodium homeostasis and normal blood pressure.

  15. Blood pressure goals and treatment in pregnant patients with chronic kidney disease.

    PubMed

    Hussain, Asher; Karovitch, Alan; Carson, Michael P

    2015-03-01

    As the age of pregnant women and prevalence of obesity and diabetes are increasing, so is the prevalence of medical disorders during pregnancy, particularly hypertension and the associated CKD. Pregnancy can worsen kidney function in women with severe disease, and hypertension puts them at risk for pre-eclampsia and the associated complications. There are no specific guidelines for hypertension management in this population, and tight control will not prevent pre-eclampsia. Women with end-stage kidney disease should be placed on intense dialysis regimens to improve obstetric outcomes, and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are best avoided. This article will review the rationale for a management plan that includes a multidisciplinary team to discuss risks and develop a plan before conception, antepartum monitoring for maternal and fetal morbidity, individualization of medical management using medications with established records during pregnancy, and balancing the level of blood pressure control proved to protect kidney function against the potential effects that aggressive blood pressure control could have on the fetal-placental unit.

  16. Risk factors of hypertensive pregnancies in women with diabetes and the influence on their future life.

    PubMed

    Gordin, Daniel; Forsblom, Carol; Groop, Per-Henrik; Teramo, Kari; Kaaja, Risto

    2014-11-01

    Diabetic women carry a 2-4 times increased risk of a hypertensive pregnancy compared to non-diabetic people. This risk is related to presence of diabetic nephropathy, but also poor glycaemic control. Efforts to improve glycaemic control have decreased perinatal morbidity and mortality related to diabetic nephropathy. Despite good glycaemic control, overt nephropathy is associated with a variety of pregnancy complications, such as fetal growth restriction and pre-eclampsia. General population studies show that women with a history of pre-eclampsia are more prone to develop cardiovascular disease later in life than women with a history of normotensive pregnancy. Furthermore, recent data regarding the long-term effects of hypertensive pregnancies on late diabetic complications indicate that these women should be followed and treatment should be started early. In this review we summarize data on risk factors and long-term effects of hypertensive pregnancies on late diabetic complications that may be of clinical relevance in the prevention of these complications.

  17. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome

    PubMed Central

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-01-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome. PMID:26229389

  18. Reducing morbidity and mortality among pregnant obese.

    PubMed

    Harper, Ann

    2015-04-01

    Obesity is increasing; in the UK, almost 20% of pregnant women have a body mass index (BMI) of ≥30 kg/m(2). Obese mothers have increased risks of pregnancy complications including miscarriage, congenital anomaly, gestational diabetes, pre-eclampsia, macrosomia, induction of labour, caesarean section, anaesthetic and surgical complications, post-partum haemorrhage, infection and venous thromboembolism. Complications tend to be greater in those with the highest BMIs. In recent triennia, obesity (27-29%) was over-represented in maternal mortality figures. Strategies to reduce morbidity and mortality include calculating BMI at booking visit to identify obese mothers and plan their antenatal care and delivery. This should include nutritional and lifestyle advice, screening for gestational diabetes and pre-eclampsia, thromboembolism risk assessment, antenatal anaesthetic review if BMI is ≥ 40 kg/m(2), ensuring availability of robust theatre tables and other equipment and involving senior doctors, especially in the labour ward. Afterwards, continuing weight reduction should be encouraged to reduce future pregnancy and health risks.

  19. Intergenerational exchange and perinatal risks: a note on interpretation of generational recurrence risks.

    PubMed

    Lie, Rolv T

    2007-07-01

    Population-based data that cover reproductive health outcomes across two complete generations have recently become available in the Nordic countries. Such data enable estimation of recurrence risks from one generation to the next of different conditions such as birth defects or pre-eclampsia. Risks related to a singleton pregnancy involve the contribution of three individuals: the mother, the father and the fetus. A paternal contribution is mainly through the father's contribution of half of the alleles of the fetus. A maternal contribution may occur in three fundamentally different ways. First, the mother provides half of the genomic alleles to the fetus, with contribution of paternal alleles completing the whole genome. Second, the mother provides the fetal environment and possible susceptibility to complications during pregnancy which she may have inherited from her mother. Finally, she provides the fetal mitochondria. Because of these different contributions, recurrence from mother to offspring is fundamentally different from recurrence from father to offspring. How recurrence risks reflect and shape the underlying contributions to overall perinatal risk is illustrated through a review of published data from Norway on gestational age, pre-eclampsia and birth defects.

  20. Cord blood coagulation studies in infants of high-risk pregnant women.

    PubMed

    Hathaway, W E; Mahasandana, C; Makowski, E L

    1975-01-01

    A prospective study of cord blood for coagulability, evidence for disseminated intravascular coagulation (DIC), and hematocrit was done in 106 infants who were offspring of mothers with high-risk pregnancies (pre-eclampsia, diabets mellitus, third-trimester bleeders, severe erythroblastosis fetalis, maternal hypertension, fetal distress, and spontaneous premature labor). Significant changes of hypercoagulability (low AT-III and abnormal TEG) were seen in the third-trimester bleeder and premature labor groups which also had the highest incidence of IRDS and necrotizing. Infants undergoing "stress" (pre-eclampsia, fetal distress) had elevated levels of factors V and VIII but were not hypercoagulable or AT-III deficient. Except for mild thrombocytopenia, infants of the diabetic mothers, a group with increased thrombotic complications, did not show any cord blood abnormalities. Offspring of third-trimester bleeders were anemic. The EBF infants were also anemic, severely hypercoagulable, and showed coagulation changes compatible with severe liver disease and/or DIC. Mild changes compatible with intravascular coagulation were seen in six infants and were not related to the the development of IRDS.

  1. [Clinical guideline for detection and diagnosis of hypertensive pregnancy disease].

    PubMed

    Lagunes-Espinosa, Alma Luisa; Ríos-Castillo, Brenda; Peralta-Pedrero, María Luisa; del Rocío Cruz-Cruz, Polita; Sánchez-Ambríz, Slivia; Sánchez-Santana, Joaquín Renato; Ramírez-Mota, Carolina; Zavaleta-Vargas, Norma Octavia; López-Cisneros, Gabriela

    2011-01-01

    Hypertensive disorders in pregnancy (HDP) are the main complication and cause of maternal and perinatal death. Pre-eclampsia represents a 34%, according to the Secretaría de Salud de México. To offer the family physicians tools for the opportune detection and diagnosis of HDP a clinical guideline was developmented. Clinical questions were formulated and structured. A standardized sequence to search for Practice Guidelines, based on the key words: hypertensive disorders in pregnancy, pre-eclampsia. Tripdatabase, MDConsult, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, National Institute for Health and Clinical Excellence were used. In addition, Cochrane Library Plus, Science Direct and OVID were used. Most of the recommendations were taken from guidelines selected and supplemented with the remaining material. The information is expressed in levels of evidence and grade of recommendation according to the characteristics of the study design and type of publications. To reduce morbidity and mortality from HDP health professionals should identify risk factors; conduct a close monitoring and early diagnosis. It is essential to provide information to the pregnant patient on alarm data and behavior to follow. This clinical practice guide offers current evidence for screening and diagnosis of HDP in primary care.

  2. Maternal hypertensive pregnancy disorders and cognitive functioning of the offspring: a systematic review.

    PubMed

    Tuovinen, Soile; Eriksson, Johan G; Kajantie, Eero; Räikkönen, Katri

    2014-11-01

    Hypertensive pregnancy disorders may affect the fetal developmental milieu and thus hint at mechanisms that link prenatal conditions with later developmental outcomes of the offspring. Here, we systematically review studies that have tested whether maternal pre-eclampsia, gestational hypertension, and hypertensive pregnancy disorders as a single diagnostic entity are associated with cognitive functioning of the offspring. Twenty-six studies were eligible for this review. Of them, 19 provided detailed methodological information deemed necessary to be included for a more detailed review. An overall conclusion is that, in the general population, maternal hypertensive disorders may be associated with lower cognitive ability of the offspring. Studies that extend to adulthood show the most consistent pattern of findings. It is possible that the associations arise during the lifetime or that the findings reflect improvements in management of these disorders. Evidence is, however, insufficient to conclude whether these associations are dissimilar in the offspring exposed to maternal pre-eclampsia and gestational hypertension, due to the varied criteria used across the different studies to distinguish between these conditions. The existing studies also vary in the definition of control groups, and very few have taken into account important confounding factors, including maternal pre-pregnancy obesity and lifestyle behaviors. Given the mixed pattern of findings and limitations related to internal and external validity, further studies are clearly warranted to clarify the associations.

  3. Calcium supplementation reducing the risk of hypertensive disorders of pregnancy and related problems: A meta-analysis of multicentre randomized controlled trials.

    PubMed

    An, Li-bin; Li, Wen-tao; Xie, Tie-nan; Peng, Xin; Li, Bo; Xie, Shu-hong; Xu, Jing; Zhou, Xiao-hua; Guo, Shao-ning

    2015-05-01

    Hypertensive disorders of pregnancy are closely related to maternal mortality and morbidity. Calcium supplementation during pregnancy seems to reduce the risk of hypertensive disorders. No systematic review on multicentre RCTs of calcium supplementation during pregnancy has been published. The purpose of this study was to report a quantitative systematic review of the effectiveness of calcium supplementation during pregnancy on reducing the risk of hypertensive disorders of pregnancy and related problems. Publications over the years of 1991-2012 were searched through PubMed, Science Direct, EMBASE, CINAHL and Web of Science. The literatures were selected of the multicentre RCTs on calcium supplementation during pregnancy in prevention of hypertensive disorders and related problems. Reference lists from the studies were also examined for additional references. Studies were critically appraised by three independent reviewers, and the Cochrane Handbook was used to assess the quality of those included trials. Four studies were included in this systematic review. All included studies were high quality, with low risk of bias. There was an observed risk reduction in hypertension in calcium group. However, there was no reduction in the risk of severe gestational hypertension, pre-eclampsia, severe pre-eclampsia, preterm birth and low birthweight. Calcium supplementation appears to reduce the risk of hypertension in pregnancy.

  4. Preconception and pregnancy management of women with diabetic nephropathy on angiotensin converting enzyme inhibitors.

    PubMed

    Podymow, Tiina; Joseph, Geena

    2015-02-01

    Angiotensin converting enzyme (ACE) inhibitors are the mainstay of treatment for diabetic nephropathy to slow progression of disease. Diabetic women of childbearing age with nephropathy should be treated with ACE inhibitors as per guidelines in the pre-pregnancy period. ACE inhibitor use and exposure in the first trimester is controversial and requires counselling pre-pregnancy regarding the risks and benefits of use up to the first trimester, as well as the need to stop ACE inhibitors prior to the second trimester. Current evidence does not suggest that ACE inhibitors in the first trimester are associated with a greater risk of fetal malformations when compared to other antihypertensives. This topic is reviewed in depth, along with blood pressure targets in pregnant women with diabetic proteinuric disease, evidence for prevention of pre-eclampsia, self-monitoring of blood pressures at home in the latter half of pregnancy and the signs and symptoms of pre-eclampsia, proteinuria evolution in pregnancy, renal function prognosis, and restarting ACE inhibitors when breast feeding in the post-partum period.

  5. Relationship between ABO blood group and pregnancy complications: a systematic literature analysis

    PubMed Central

    Franchini, Massimo; Mengoli, Carlo; Lippi, Giuseppe

    2016-01-01

    Given the expression of ABO blood group antigens on the surface of a wide range of human cells and tissues, the putative interplay of the ABO system in human biology outside the area of transfusion and transplantation medicine constitutes an intriguing byway of research. Thanks to evidence accumulated over more than 50 years, the involvement of the ABO system in the pathogenesis of several human diseases, including cardiovascular, infectious and neoplastic disorders, is now acknowledged. However, there is controversial information on the potential association between ABO blood type and adverse pregnancy outcomes, including pre-eclampsia and related disorders (eclampsia, HELLP syndrome and intrauterine growth restriction), venous thromboembolism, post-partum haemorrhage and gestational diabetes. To elucidate the role of ABO antigens in pregnancy-related complications, we performed a systematic review of the literature published in the past 50 years. A meta-analytical approach was also applied to the existing literature on the association between ABO status and pre-eclampsia. The results of this systematic review are presented and critically discussed, along with the possible pathogenic implications. PMID:27177402

  6. Lupus nephritis and renal disease in pregnancy.

    PubMed

    Germain, S; Nelson-Piercy, C

    2006-01-01

    Management of pregnant women with renal disease involves awareness of, and allowance for, physiological changes including decreased serum creatinine and increased proteinuria. For women with systemic lupus erythematosus (SLE), pregnancy increases likelihood of flare. These can occur at any stage, and are more difficult to diagnose, as symptoms overlap those of normal pregnancy. Renal involvement is no more common in pregnancy. Worsening proteinuria may be lupus flare but differential includes pre-eclampsia. In women with chronic renal disease, pregnancy may accelerate decline in renal function and worsen hypertension and proteinuria, with increased risk of maternal (eg, pre-eclampsia) and fetal (eg, IUGR, IUD) complications, strongly correlating with degree of renal impairment peri-conception. Pregnancy success rate varies from 20% to 95% depending on base-line creatinine. Best outcome is obtained if disease was quiescent for >6 months pre-conception. Women on dialysis or with renal transplants can achieve successful pregnancy but have higher maternal and fetal complication rates. Acute on chronic renal failure can develop secondary to complications such as HELLP and AFLP. Management needs to be by a multidisciplinary team involving physicians and obstetricians, ideally beginning with pre-pregnancy counselling. Treatment of flares includes corticosteroids, hydroxychloroquine, azothioprine, NSAIDs and MME Blood pressure is controlled with methyldopa, nifedipine or hydralazine.

  7. Obstetric nephrology: lupus and lupus nephritis in pregnancy.

    PubMed

    Stanhope, Todd J; White, Wendy M; Moder, Kevin G; Smyth, Andrew; Garovic, Vesna D

    2012-12-01

    SLE is a multi-organ autoimmune disease that affects women of childbearing age. Renal involvement in the form of either active lupus nephritis (LN) at the time of conception, or a LN new onset or flare during pregnancy increases the risks of preterm delivery, pre-eclampsia, maternal mortality, fetal/neonatal demise, and intrauterine growth restriction. Consequently, current recommendations advise that the affected woman achieve a stable remission of her renal disease for at least 6 months before conception. Hormonal and immune system changes in pregnancy may affect disease activity and progression, and published evidence suggests that there is an increased risk for a LN flare during pregnancy. The major goal of immunosuppressive therapy in pregnancy is control of disease activity with medications that are relatively safe for a growing fetus. Therefore, the use of mycophenolate mofetil, due to increasing evidence supporting its teratogenicity, is contraindicated during pregnancy. Worsening proteinuria, which commonly occurs in proteinuric renal diseases toward the end of pregnancy, should be differentiated from a LN flare and/or pre-eclampsia, a pregnancy-specific condition clinically characterized by hypertension and proteinuria. These considerations present challenges that underscore the importance of a multidisciplinary team approach when caring for these patients, including a nephrologist, rheumatologist, and obstetrician who have experience with these pregnancy-related complications. This review discusses the pathogenesis, maternal and fetal risks, and management pertinent to SLE patients with new onset or a history of LN predating pregnancy.

  8. Misdiagnosis of obstetrical cases and the clinical and cost consequences to patients: a cross-sectional study of urban providers in the Philippines

    PubMed Central

    Shimkhada, Riti; Solon, Orville; Tamondong-Lachica, Diana; Peabody, John W.

    2016-01-01

    Background Misdiagnosis may be a significant and under-recognized quality of care problem. In birthing facilities located in anurban Philippine setting, we investigated the diagnostic accuracy for three obstetric conditions: cephalopelvic disproportion (CPD), post-partum hemorrhage (PPH), and pre-eclampsia. Design Identical simulated cases were used to measure diagnostic accuracy for every provider (n=103). We linked misdiagnosis – identified by the simulated cases – to obstetrical complications of the patients at the participating facilities. Patient-level data on health outcomes and costs were obtained from medical records and follow-home in-person interviews. Results The prevalence of misdiagnosis among obstetric providers was 29.8% overall, 25% for CPD, 33% for PPH, and 31% for pre-eclampsia. Linking provider decision-making to patients, we found those who misdiagnosed the simulated cases were more likely to have patients with a complication (OR 2.96; 95% CI 1.39–3.77) compared with those who did not misdiagnose. Complicated patients were significantly less likely to be referred to a hospital immediately, were more likely to be readmitted to a hospital after delivery, had significantly higher medical costs, and lost more income than non-complicated patients. Conclusion Diagnosis is arguably the most important task a clinician performs because it determines the subsequent course of evaluation and treatment, with the direct and indirect costs of diagnostic error, placing large financial burdens on the patient. PMID:27987297

  9. Pregnancy complications and birth outcomes of pregnant women with urinary tract infections and related drug treatments.

    PubMed

    Bánhidy, Ferenc; Acs, Nándor; Puhó, Erzsébet H; Czeizel, Andrew E

    2007-01-01

    Maternal urinary tract infections in pregnancy showed an association with a higher rate of preterm birth in previous studies. The aim of this study was to check this relationship, and in addition to evaluate the efficacy of recent medical treatments. The population-based large control (without any defects) data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities was evaluated. Of 38,151 newborn infants, 2188 (5.7%) had mothers with urinary tract infections during pregnancy, and 90% of these maternal diseases were prospectively and medically recorded. The prevalence of pre-eclampsia and polyhydramnios showed an association with urinary tract infections during pregnancy. Pregnant women with urinary tract infections in pregnancy had a somewhat shorter gestational age (0.1 week) and a higher proportion of preterm births (10.4% vs 9.1%). These differences were correlated with the severity of urinary tract infections. However, the preterm-inducing effect of maternal urinary tract infections is preventable by some antimicrobial drugs such as ampicillin, cefalexin and cotrimoxazole. In conclusion, maternal urinary tract infections during pregnancy increase pre-eclampsia and polyhydramnios, and in addition the rate of preterm birth; however, the latter is preventable by appropriate drug treatments.

  10. Relationship between ABO blood group and pregnancy complications: a systematic literature analysis.

    PubMed

    Franchini, Massimo; Mengoli, Carlo; Lippi, Giuseppe

    2016-09-01

    Given the expression of ABO blood group antigens on the surface of a wide range of human cells and tissues, the putative interplay of the ABO system in human biology outside the area of transfusion and transplantation medicine constitutes an intriguing byway of research. Thanks to evidence accumulated over more than 50 years, the involvement of the ABO system in the pathogenesis of several human diseases, including cardiovascular, infectious and neoplastic disorders, is now acknowledged. However, there is controversial information on the potential association between ABO blood type and adverse pregnancy outcomes, including pre-eclampsia and related disorders (eclampsia, HELLP syndrome and intrauterine growth restriction), venous thromboembolism, post-partum haemorrhage and gestational diabetes. To elucidate the role of ABO antigens in pregnancy-related complications, we performed a systematic review of the literature published in the past 50 years. A meta-analytical approach was also applied to the existing literature on the association between ABO status and pre-eclampsia. The results of this systematic review are presented and critically discussed, along with the possible pathogenic implications.

  11. Maternal body mass index and risk of birth and maternal health outcomes in low- and middle-income countries: a systematic review and meta-analysis.

    PubMed

    Rahman, M M; Abe, S K; Kanda, M; Narita, S; Rahman, M S; Bilano, V; Ota, E; Gilmour, S; Shibuya, K

    2015-09-01

    We conducted a systematic review and meta-analysis of population-based cohort studies of maternal body mass index (BMI) and risk of adverse birth and health outcomes in low- and middle-income countries. PubMed, Embase, CINAHL and the British Nursing Index were searched from inception to February 2014. Forty-two studies were included. Our study found that maternal underweight was significantly associated with higher risk of preterm birth (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01-1.27), low birthweight (OR, 1.66; 95% CI, 1.50-1.84) and small for gestational age (OR, 1.85; 95% CI, 1.69-2.02). Compared with mothers with normal BMI, overweight or obese mothers were at increased odds of gestational diabetes, pregnancy-induced hypertension, pre-eclampsia, caesarean delivery and post-partum haemorrhage. The population-attributable risk (PAR) indicated that if women were entirely unexposed to overweight or obesity during the pre-pregnancy or early pregnancy period, 14% to 35% fewer women would develop gestational diabetes, pre-eclampsia or pregnancy-induced hypertension in Brazil, China, India, Iran or Thailand. The highest PAR of low birthweight attributable to maternal underweight was found in Iran (20%), followed by India (18%), Thailand (10%) and China (8%). Treatment and prevention of maternal underweight, overweight or obesity may help reduce the burden on maternal and child health in developing countries.

  12. Role of calcium supplementation during pregnancy in reducing risk of developing gestational hypertensive disorders: a meta-analysis of studies from developing countries

    PubMed Central

    2011-01-01

    Background Hypertension in pregnancy stand alone or with proteinuria is one of the leading causes of maternal mortality and morbidity in the world. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy though the effect varies based on baseline calcium intake and pre-existing risk factors. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal mortality in developing countries. Methods A literature search was carried out on PubMed, Cochrane Library and WHO regional databases. Data were extracted into a standardized excel sheet. Identified studies were graded based on strengths and limitations of studies. All the included studies were from developing countries. Meta-analyses were generated where data were available from more than one study for an outcome. Primary outcomes were maternal mortality, eclampsia, pre-eclampsia, and severe preeclampsia. Neonatal outcomes like neonatal mortality, preterm birth, small for gestational age and low birth weight were also evaluated. We followed standardized guidelines of Child Health Epidemiology Reference Group (CHERG) to generate estimates of effectiveness of calcium supplementation during pregnancy in reducing maternal and neonatal mortality in developing countries, for inclusion in the Lives Saved Tool (LiST). Results Data from 10 randomized controlled trials were included in this review. Pooled analysis showed that calcium supplementation during pregnancy was associated with a significant reduction of 45% in risk of gestational hypertension [Relative risk (RR) 0.55; 95 % confidence interval (CI) 0.36-0.85] and 59% in the risk of pre-eclampsia [RR 0.41; 95 % CI 0.24-0.69] in developing countries. Calcium supplementation during pregnancy was also associated with a significant reduction in neonatal mortality

  13. Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands

    PubMed Central

    2014-01-01

    Background In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear. Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open. The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae. Methods/Design This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information. We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis. Discussion The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of

  14. Severe maternal morbidity in the intensive care unit of a havana teaching hospital,1998 to 2004.

    PubMed

    Pérez, Albadio; Bacallao, Jorge; Alcina, Serafín; Gómez, Yamilka

    2008-07-01

    Introduction In recent years, several reports have appeared in the international literature concerning evolution and prognosis for obstetric patients whose illnesses have led to admission to intensive care units (ICUs). The term severe maternal morbidity has been proposed to refer to life-threatening complications that occur during pregnancy, delivery or postpartum. Objective Characterize severe maternal morbidity in obstetric patients admitted to the ICU of the Enrique Cabrera General Teaching Hospital in Havana from 1998 to 2004. Methods From 1998 to 2004, we conducted a prospective, descriptive, and observational study of 312 patients admitted to the ICU of the Enrique Cabrera General Teaching Hospital in Havana, Cuba. Patients were included whose length of stay was >24 hours, and whose family members provided written informed consent. A data collection form was developed to record general characteristics, personal and family medical history, cause of ICU admission, diagnosis, obstetric condition at the onset of illness and at admission, pregnancy outcome, surgeries performed and patient's ICU discharge status (survivor or non-survivor), the latter a dependent variable. An Excel database was compiled and processed using SPSS 13.0. Percentages were used to summarize qualitative variables. A Chi-square test was used for univariate analysis between these qualitative variables and patient discharge status; t-test was used for quantitative analyses. Results Overall mortality in the cohort was 7.4% (23 patients), greater among women aged <20 years, those with a history of previous illnesses, and those subjected to several surgical interventions. Obstetric hemorrhage, pre-eclampsia/eclampsia, and postpartum sepsis were the most commonly diagnosed obstetric disorders. Non-obstetric disorders diagnosed included severe asthma, pneumonia and peritonitis. Amniotic fluid embolism, postpartum sepsis, early postpartum hemorrhage and pre-eclampsia/eclampsia were associated with

  15. A review of eclampsia in Qatar: A twenty-year study (from January 1991-December 2009)

    PubMed Central

    Sharara, Hussein Attia

    2012-01-01

    Objective: To determine the prevalence of eclampsia in Qatar, the associated maternal and perinatal outcomes for the period from January 1991 to December 2009 and to define any possible preventive measures to this potentially fatal complication. Methods: A retrospective case review was performed of all women with eclampsia admitted to the Women's Hospital and Obstetrics and Gynecology department at Al Khor Hospital for the period from January 1991 to December 2009. Details were collected by reviewing the files of the patients from the medical records. Data were analyzed by either X2 analysis or the unpaired student “t” test as appropriate. Results: During the period of the study there were 224,809 births. Seventy women developed eclampsia (0.31/1000 deliveries), 44.3% of them were antepartum, 31.4% postpartum and 24.3% intrapartum eclampsia. 34.3% of patients presented with fits, 38.5% presented with pre-eclampsia (PE) and 20% presented with severe pre eclampsia; 18.5% were mild PE and another 27.2% were admitted with different complaints. Symptoms of impending eclampsia were seen in 22.9% of the PE patients. Thirty percent had no antenatal care (ANC). Antihypertensive therapy was given to 72% of cases. Antiepileptic therapy was administered to 48% of cases and 58.5% received magnesium sulfate. Eclampsia was associated with increased rate of cesarean section (CS) (64.2%). There was one maternal death, and the rate of major maternal complications was 20%. The perinatal mortality rate was 12.8%. Conclusion: The incidence of eclampsia in Qatar is 0.31 per 1000 deliveries. Although rare, this condition is associated with increased maternal morbidity and perinatal mortality. However our result is lower than reported worldwide. Improvement of obstetric care by having high index of suspicion even with apparently low risk patients, using magnesium sulfate prophylaxis for all cases of severe pre-eclampsia, in addition to community based approach to improve community

  16. [Normotensive HELLP syndrome: report of one case].

    PubMed

    Garrido, María Fernanda; Carvajal, Jorge Andrés

    2013-11-01

    HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) represents a severe form of preeclampsia associated with serious maternal and fetal morbidities and even death. Usually HELLP syndrome appears during the evolution of a severe preeclampsia; however HELLP syndrome can have atypical clinical manifestations. We report a 22-year-old female who consulted at 20 weeks of pregnancy for lumbar pain, dysuria and fever. A urinalysis revealed the presence of white blood cells. The patient was admitted to hospital and treated with antimicrobials. Forty eight hours after admission a proteinuria of 440 mg/24 h was detected. A severe pre eclampsia-HELLP syndrome was diagnosed. However the patient remained with normal blood pressure. An elevation of liver enzymes and creatinine were observed. Five days later fetal death was confirmed and an abortion was induced. The patient required a platelet transfusion. Four days after the abortion, the patient was discharged in good conditions.

  17. HELLP syndrome: understanding and management of a pregnancy-specific disease.

    PubMed

    Aloizos, S; Seretis, C; Liakos, N; Aravosita, P; Mystakelli, C; Kanna, E; Gourgiotis, S

    2013-05-01

    HELLP, a syndrome characterised by haemolysis, elevated liver enzymes and low platelets, a variant of pre-eclampsia/eclampsia, is a multisystemic disorder with an incidence of up to 0.9% in all pregnancies and occurs in about one-quarter of pre-eclamptic patients. Most obstetricians presume that HELLP derives from an autoimmune reaction, leading to a materno- fetal imbalance, with accompanying aggregation of platelets, endothelial malfunction along with inborn errors of fatty acid oxidative metabolism. HELLP is characterised by high mortality and morbidity rates, leading to possibly life-threatening complications regarding both the mother and the fetus. Delivery is indicated if HELLP syndrome occurs after 34 gestational weeks or the fetal and/or maternal conditions deteriorate. Vaginal delivery is preferable. Standard corticosteroid treatment is of uncertain clinical value in maternal HELLP syndrome. Future observations and research results may shed more light on improving our understanding of the aspects of HELLP syndrome.

  18. HELLP syndrome with haemaglobin vasospasm.

    PubMed

    Gliemroth, J; Knopp, U; Kehler, U; Felberbaum, R; Nowak, G

    2000-01-01

    The syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) is a life threatening, severe complication of pre-eclampsia with typical laboratory findings. An unusual case of a 36-year-old woman with HELLP syndrome and the initial complication of intracerebral haemorrhage is presented. The diagnosis of HELLP syndrome was confirmed by elevated liver enzymes, low platelets, increased total bilirubin and increased lactate dehydrogenase. The intracranial haematoma was removed with good neurological recovery ensuing. However, this case was complicated by cerebral vasospasm on the eleventh day, confirmed by cerebral angiography and computer tomographic findings. The patient died from brain swelling. Possible vasospam should be considered during the treatment of patients with HELLP syndrome.

  19. [Pregnancy following oocyte donation].

    PubMed

    Boks, D E; Braat, D D

    1997-08-23

    Five women, aged 31, 26, 31, 34, and 28 years, became pregnant after oocyte donation and in-vitro fertilization. One was a carrier of Leber's optical atrophy, three had had an early menopause (in two because of chromosomal abnormalities), and one had had bilateral ovarian extirpation because of a cystadenoma and endometriosis. Three developed (pre-)eclampsia during pregnancy and one had a serious fluxus post partum. One twin died in utero, the other children were healthy. In the Netherlands in-vitro fertilization (with or without egg-donation) takes place up to the age of about 40. Regarding the high incidence of obstetrical complications in women under 40, raising the age limit could lead to even more pregnancy problems. Candidates for oocyte donation should be informed about these risks, furthermore they should not deliver at home.

  20. Clinical and Preclinical Use of LOX-1-Specific Antibodies in Diagnostics and Therapeutics.

    PubMed

    De Siqueira, Jonathan; Abdul Zani, Izma; Russell, David A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan; Homer-Vanniasinkam, Shervanthi

    2015-11-01

    Lectin-like oxidized low-density lipoprotein receptor-1 (SR-E1, LOX-1, OLR1) was first discovered as a vascular receptor for modified lipoprotein particles nearly 20 years ago. Since then, in vitro and in vivo studies have demonstrated an association between LOX-1, a soluble form (sLOX-1) and a number of diseases including atherosclerosis, arthritis, hypertension and pre-eclampsia. However, converting such discoveries into tools and drugs for routine clinical use is dependent on translational preclinical and clinical studies but such studies have only begun to emerge in the past decade. In this review, we identify the key clinical applications and corresponding criteria that need to be addressed for the effective use of LOX-1-related probes and molecules for patient benefit in different disease states.

  1. Acute fetal distress following tooth extraction and abscess drainage in a pregnant patient with maxillofacial infection.

    PubMed

    Çelebi, N; Kütük, M S; Taş, M; Soylu, E; Etöz, O A; Alkan, A

    2013-03-01

    Oral infections have been implicated in adverse pregnancy outcomes such as pre-eclampsia, premature delivery and growth retardation. A 28-year-old and 9 months pregnant otherwise healthy woman with a complaint of facial swelling and dental pain was referred to the Department of Oral and Maxillofacial Surgery. Oral examination revealed perimandibular and masticator space infection related to the left mandibular third molar tooth. Eight hours after surgical intervention, fetal distress developed. The patient was immediately taken into surgery and a male baby delivered by Caesarean section. The baby was then admitted to the intensive care unit. On the twelfth day of his admission, the baby was discharged in good health. Severe maxillofacial infection in pregnancy is a medically complicated situation which should be treated by an oral and maxillofacial surgeon in consultation with an obstetric and gynaecology service.

  2. Autoimmune lymphoproliferative syndrome in pregnancy: a case of favorable mother-fetal outcome in a well-controlled disease.

    PubMed

    Patti, Simona; Perrone, Giuseppina; De Pratti, Valentina; Quinti, Isabella; Milito, Cinzia; Brunelli, Roberto

    2015-03-01

    The autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by the dysregulation of the Fas apoptotic pathway. The Fas gene is expressed at the maternal-fetal interface and is involved in the regulation of immune response and implantation. Altered Fas expression may result in altered apoptosis and, ultimately, affect both the immune response and implantation; it is in fact associated with recurrent pregnancy loss, preterm premature rupture of membranes and pre-eclampsia. Currently, there are over 500 cases of ALPS reported worldwide from various racial and ethnic backgrounds. Up to date, the published work contains no specific reports on pregnancy outcome in women affected by ALPS. We present a case of full-term uneventful pregnancy in a patient affected by ALPS. A specific clinical follow-up in a pregnant woman with primary immunologic disease is suggested.

  3. [VITAMIN D AND PREGNANCY].

    PubMed

    Hitrova-Nikolova, St; Nikolov, A

    2015-01-01

    This arcicle reviews the role of vitimin D during pregnancy. Adequate intake of vitamin D during pregnancy is very important for the health of mother and infant. A number of epidemiological data worldwide show widespread suboptimal levels of vitamin D in pregnant women. Vitamin D deficiency may be associated with an increased risk of infection, bacterial vaginosis, pre-eclampsia, low serum vitamin D levels in the newborn and others. There are not universal recommendations for dosage and intake of vitamin D for pregnant women in the world. It is recommended that serum level of vitamin D in all pregnant women and its adequate supplementation. Normal maternal vitamin D levels would provide sufficient its accumulation in the fetus.

  4. Acute fatty liver of pregnancy with hypoglycaemia, diabetes insipidus and pancreatitis, preceded by intrahepatic cholestasis of pregnancy.

    PubMed

    English, Nicola; Rao, Jegajeeva

    2015-04-15

    We present the case of a 33-year-old woman in her first pregnancy. She presented with pruritus at 34 weeks gestation. A diagnosis of intrahepatic cholestasis of pregnancy was made based on elevated bile acids and elevated liver transaminases. She re-presented 4 days later, jaundiced with abdominal pain and nausea, and was hypertensive. Her bilirubin was now elevated and her creatinine had doubled. The differential diagnosis-included pre-eclampsia and Hemolysis Elevated Liver enzymes Low Platelet count (HELLP) syndrome, and delivery was expedited. Postnatally, the patient became coagulopathic, though not thrombocytopaenic; she had persistent hypoglycaemia, hyponatraemia, developed acute pancreatitis and had profound ascites and peripheral oedema. Management was supportive with multidisciplinary care and over a period of 3 weeks she made a full clinical and biochemical recovery.

  5. Posterior leukoencephalopathy syndrome as a cause of reversible blindness during pregnancy.

    PubMed

    Onderoglu, Lutfu S; Dursun, Polat; Gultekin, Murat; Celik, Nilufer Y

    2007-08-01

    Cortical blindness is a rare and dramatic complication of pre-eclampsia. The precise nature of the pathogenesis of this condition has not previously been understood. Three preeclamptic patients with unremarkable previous medical history presented with acute blindness between the 28th and 33rd weeks of pregnancy. They were all diagnosed as posterior leukoencephalopathy syndrome (PLES). In all these patients, MRI study revealed the typical feature of gray-white matter edema localized to the temporo-parieto-occipital areas. Vision and MRI findings were restored in all patients after delivery. Although PLES has been described as a puerperal clinicoradiologic entity, it may be seen in preeclamptic-eclamptic patients during the pregnancy. Therefore neuro-imaging studies should be carried out in pregnant patients with visual disturbances in order to exclude PLES. Prompt diagnosis, immediate control of blood pressure, and elimination of possible causes resolves clinical and imaging findings.

  6. FLT1 — EDRN Public Portal

    Cancer.gov

    From NCBI Gene: This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. The soluble isoforms are associated with the onset of pre-eclampsia.[provided by RefSeq, May 2009

  7. [Bariatric surgery and pregnancy: literature review].

    PubMed

    Ferrand Miranda, Pedro; Contreras Rivas, Tomas; Leigh Pacciarini, Stephanie

    2014-02-14

    Obesity has currently reached epidemic proportions, both in Chile and in the world. This condition is associated to a variety of maternal complications in all stages of the vital cycle and during pregnancy. Medical treatment has not proved successful thus resulting in an increase in bariatric surgery in recent years, even when it is not first line treatment. This literature review aims to report updated results of surgical treatment for obesity before and during pregnancy with respect to fertility, gestational diabetes, pre-eclampsia and pregnancy-induced hypertension. It also looks into the possible effects of surgery on fetal development, and its relation to premature delivery, fetal macrosomy, low birth weight and neural tube defects, as well as effects on maternal and fetal outcomes, mainly in nutrition. Lastly, we suggest some recommendations that arise from this review on the role of contraception, nutrition and time between surgery and pregnancy.

  8. Eczematous plaques related to unfractionated and low-molecular-weight heparin in pregnancy: cross-reaction with danaparoid sodium.

    PubMed

    Blickstein, Dorith; Hod, Moshe; Bar, Jacob

    2003-12-01

    The use of low-molecular-weight heparin has been expanded to prevent pregnancy complications such as pregnancy loss, intra-uterine growth restriction and severe early-onset pre-eclampsia in high-risk patients with evidence of acquired or congenital thrombophilia. Therefore, the number of patients with side effects from low-molecular-weight heparin is expected to increase. We describe two women with infiltrating patchy plaques that developed in reaction to low-molecular-weight heparin during pregnancy. In the first patient, a switch to other formulations of heparin and heparinoid failed; the second patient, however, did well when enoxaparin was replaced with dalteparin. This report confirms the risk of skin reactions to enoxaparin and dalteparin, and reports on a skin reaction associated with danaparoid sodium in a pregnant woman.

  9. Antiphospholipid Antibodies and Antiphospholipid Syndrome during Pregnancy: Diagnostic Concepts.

    PubMed

    Levy, Roger A; Dos Santos, Flavia Cunha; de Jesús, Guilherme R; de Jesús, Nilson R

    2015-01-01

    Antiphospholipid syndrome (APS) comprises of a wide spectrum of clinical and obstetric manifestations linked to the presence of antiphospholipid antibodies (aPL). APS was described in the context of lupus, and later as an isolated syndrome or primary APS. The presence of aPL, especially the lupus anticoagulant test, is associated with adverse pregnancy outcomes, such as fetal death, recurrent early miscarriages, pre-eclampsia, and placental insufficiency, but does not seem to influence infertility. High quality scientific data to support these associations, however, are lacking, and controversies arise about the definition of positive aPL (low vs medium-high titers) or even the definition of the adverse events. This review discusses APS classification criteria and the current debate about it.

  10. Pregnancy morbidity in antiphospholipid syndrome: what is the impact of treatment?

    PubMed

    de Jesús, Guilherme R; Rodrigues, Gustavo; de Jesús, Nilson R; Levy, Roger A

    2014-02-01

    Women with persistently circulating antiphospholipid antibodies (aPL) have a higher incidence of recurrent abortions, fetal losses, pre-eclampsia, and placental insufficiency. Current treatment of patients with antiphospholipid syndrome (APS) during pregnancy with heparin and aspirin can act by preventing clot formation and improving live birth rates, but other obstetric morbidities remain high, especially in patients with a history of thrombotic events. In addition to the classical thrombotic placental events, other factors involving inflammation and complement activation seem to play a role in certain complications. In this article, we will review how medications interfere in the pathogenic mechanisms of APS, discuss the impact of current recommended treatment on pregnancy morbidity, and analyze new promising therapies.

  11. [Antiphospholipid syndrome and pregnancy].

    PubMed

    Gadó, Klára; Domján, Gyula

    2012-08-05

    Antiphospholipid syndrome is characterized by arterial and venous thromboembolic events and persistent laboratory evidence of antiphospholipid antibodies. Obstetric complications such as recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, pre-eclampsia/eclampsia, and HELLP syndrome are also hallmarks of antiphospholipid syndrome. This syndrome is one of the diseases associated with the most severe thrombotic risk. Changes in the hemostatic system during normal pregnancy also result in a hypercoagulable state resulting in elevated thrombotic risk. Thromboembolic events are responsible of the vast majority of maternal and fetal deaths. Administration of appropriate thromboprophylaxis helps prevent thromboembolic complications during pregnancy in women with antiphospholipid syndrome and also give birth to healthy children. It is important to centralize the medication and management of these patients. It helps in the thoughtful care of these pregnant women encountering serious problems.

  12. Relationships between prenatal medical and nutritional measures, pregnancy outcome, and early infant development in an urban poverty setting. I. The role of nutritional intake.

    PubMed

    Osofsky, H J

    1975-12-01

    Repeated nutritional assessments were made on 118 low-income women who registered at an urban hospital clinic prior to the twenty-eighth week of pregnancy and then on 122 comparable women who were provided with protein-mineral supplementation. Demographic and background information were obtained. Medical assessments were carried out throughout pregnancy, labor, delivery, and the postpartum period. The infants were assessed both medically and with Brazelton Neonatal Behavioral Assessment Scales. In spite of their low-income status, the subjects did not appear nutritionally deprived. Few significant relationships were obtained between maternal nutritional intake and measures of maternal or infant medical status or infant psychological status. A limited number of consistent relationships were obtained when the supplemented and nonsupplemented groups were compared. Although consistent infant medical and psychological benefits were not noted, mothers in the supplemented group developed fewer parameters of pre-eclampsia and had fewer complications during labor and delivery.

  13. Management of aplastic anaemia in pregnancy in a resource poor centre

    PubMed Central

    John, Celestine Osita; Korubo, Kaladada; Ogu, Rosemary; Mmom, Chigozirim Faith; Mba, Alpheus Gogo; Chidiadi, Ezenwa-Ahanene; Akani, Chris

    2016-01-01

    Aplastic anaemia occurring in pregnancy is a rare event with life threatening challenges for both mother and child. We present a successful fetomaternal outcome despite the challenges in the management of this rare condition in a tertiary but resource poor centre. This is case of a 37 year old Nigerian woman G6P0+5managed with repeated blood transfusions from 28 weeks of gestation for bone marrow biopsy confirmed aplastic anaemia following presentation with weakness and gingival bleeds. She had a cesarean section at 37 weeks for pre-eclampsia and oligohydraminous with good feto-maternal outcome. She was managed entirely with fresh whole blood and received 21 units. Aplastic Anaemia in Pregnancy is a rare event with poor feto maternal prognosis. Successful management is possible with good multi-disciplinary approach and availability of supportive comprehensive obstetric care. PMID:28154632

  14. Anticoagulants to prevent recurrent placenta-mediated pregnancy complications: Is it time to put the needles away?

    PubMed

    Skeith, Leslie; Rodger, Marc

    2017-03-01

    Placenta-mediated pregnancy complications, such as pre-eclampsia, placental abruption, birth of a small-for-gestational age infant and late pregnancy loss, are common and carry significant morbidity and mortality. The etiology of placenta-mediated pregnancy complications is likely multifactorial and may include abnormal coagulation activation of the maternal-fetal interface. The use of antepartum low-molecular-weight heparin (LMWH) prophylaxis to prevent recurrent placenta-mediated pregnancy complications has become common practice despite limited and conflicting evidence to support its use. This paper reviews the evidence, including recently published data from an individual patient level meta-analysis, which challenges the role of LMWH in preventing recurrent placenta-mediated pregnancy complications. Incorporating this recent evidence, we recommend against the use of LMWH to prevent recurrent placenta-mediated pregnancy complications in women with and without inherited thrombophilia.

  15. Successful Pregnancy Following Assisted Reproduction in Woman With Systemic Lupus Erythematosus and Hypertension: A Case Report.

    PubMed

    de Macedo, José Fernando; de Macedo, Gustavo Capinzaiki; Campos, Luciana Aparecida; Baltatu, Ovidiu Constantin

    2015-09-01

    Patients with systemic lupus erythematosus have a poor prognosis of pregnancy, since it is associated with significant maternal and fetal morbidity, including spontaneous miscarriage, pre-eclampsia, intrauterine growth restriction, fetal death and pre-term delivery. We report a case with successful pregnancy in a patient with systemic lupus erythematosus and hypertension. A 39-year-old nulliparous woman presented with systemic lupus erythematosus with antinuclear and antiphospholipid antibodies, hypertension and recurrent pregnancy loss presented for assisted reproduction. The patient responded well to enoxaparin and prednisone during both assisted reproduction and prenatal treatment. This case report indicates that prescription of immunosuppressant and blood thinners can be safely recommended throughout the whole prenatal period in patients with systemic lupus erythematosus. Enoxaparin and prednisone may be prescribed concurrently during pregnancy.

  16. Impact of maternal obesity on perinatal and childhood outcomes.

    PubMed

    Santangeli, Louise; Sattar, Naveed; Huda, Shahzya S

    2015-04-01

    Maternal obesity is of major consequence, affecting every aspect of maternity care including both short- and long-term effects on the health of the offspring. Obese mothers are at a higher risk of developing gestational diabetes and pre-eclampsia, potentially exposing the foetus to an adverse intrauterine environment. Maternal obesity is linked to foetal macrosomia, resulting in increased neonatal and maternal morbidity. Foetal macrosomia is a result of a change in body composition in the neonate with an increase in both percentage fat and fat mass. Maternal obesity and gestational weight gain are associated with childhood obesity, and this effect extends into adulthood. Childhood obesity in turn increases chances of later life obesity, thus type 2 diabetes, and cardiovascular disease in the offspring. Further clinical trials of lifestyle and, potentially, pharmacological interventions in obese pregnant women are required to determine whether short- and long-term adverse effects for the mother and child can be reduced.

  17. Cimetidine in labour: absence of adverse effect on the high-risk fetus.

    PubMed

    McAuley, D M; Halliday, H L; Johnston, J R; Moore, J; Dundee, J W

    1985-04-01

    In a prospective randomized trial, 36 women received cimetidine and 32 magnesium trisilicate mixture BP as antacid therapy every 2 h in labour. The women belonged to a high-risk category and the infants born were less than 36 weeks gestation, or less than 2000 g birthweight or otherwise in jeopardy because of severe maternal pre-eclampsia or diabetes. Measurements of a wide range of haematological and biochemical variables revealed no differences between the two groups of babies. The frequency of complications found in the infants was similar, although infants born to the women who received magnesium trisilicate required oxygen therapy for a longer period. Cimetidine did not appear to affect the development of gastric acidity, or to increase bacterial colonization of the gastrointestinal tract in the infant.

  18. Endocrine oncology in pregnancy.

    PubMed

    Lansdown, A; Rees, D A

    2011-12-01

    Endocrine tumours occur rarely in pregnant women but present clinicians with unique challenges. A high index of suspicion is often required to make a diagnosis since the symptoms and signs associated with many of these tumours, including insulinoma, adrenocortical carcinoma and phaeochromocytoma, mimic those of normal pregnancy or its complications, such as pre-eclampsia. The evidence base which informs management is very limited hence decisions on investigation and therapy must be individualised and undertaken jointly by the multidisciplinary medical team and the patient. The optimal strategy will depend on the nature and stage of the endocrine tumour, gestational stage, treatments available and patient wishes. Thus, surgical intervention, appropriately timed, may be considered in pregnancy for resectable adrenocortical carcinoma or phaeochromocytoma, but delayed until the postpartum period for well-differentiated thyroid cancer. Medical therapy may be required to reduce the drive to tumour growth, control symptoms of hormone excess and to minimise the risks of surgery, anaesthesia or labour.

  19. A reversible posterior leucoencephalopathy syndrome including blindness caused by preeclampsia

    PubMed Central

    Vandenbossche, G; Maquet, J; Vroonen, P; Lambert, G; Nisolle, M; Kridelka, F; Emonts, E

    2016-01-01

    Complications of (pre)eclampsia may involve multiple systems and organs. Neurological symptoms may occur. Visual symptoms concern up to 25% the of patients with severe preeclampsia and 50% of the patients with eclampsia. An uncommon effect of severe preeclampsia is sudden blindness. Blindness may be part of a clinical and radiological presentation named Posterior Reversible Encephalopathy Syndrome (PRES). PRES may lead to permanent neurological deficit, recurrences or death. We report the case of a 24-year-old Caucasian patient, gravida 5 para 2 who developed preeclampsia and PRES complicated with blindness at 32 weeks of gestation. Optimal care allowed visual symptoms to resolve within 24 hours and a favourable maternal outcome and no long- term sequelae. We describe different causes and manifestations of PRES and highlight the need for immediate care in order to optimize the chance of symptoms reversibility. PMID:28003872

  20. A second delivery after heart transplantation – a case study

    PubMed Central

    Kalinka, Jarosław; Szubert, Maria; Zdziennicki, Andrzej; Chojnowski, Krzysztof; Maciejewski, Marek; Piestrzeniewicz, Katarzyna; Drożdż, Jarosław

    2014-01-01

    Pregnancy after organ transplantation is becoming relatively common. We present the case of a heart transplant recipient who gave birth to a second child. Despite the fact that the transplanted heart seems to adapt well to the changes caused by pregnancy, gestation in patients after heart transplantation may be complicated by hypertension, pre-eclampsia, or preterm labor. In this article, we consider the issues of preterm uterine contractions, anemia, thrombocytopenia, and several other complications in pregnant patients with transplanted hearts. We also present current opinions regarding the use of glucocorticoids as a form of preventing breathing disorders in neonates as well as breast-feeding by mothers receiving immunosuppressive agents. Pregnancies in heart transplant recipients should be considered high-risk. A second successful delivery of a healthy child remains a challenge for such patients and their doctors. PMID:26336446

  1. Management of aplastic anaemia in pregnancy in a resource poor centre.

    PubMed

    John, Celestine Osita; Korubo, Kaladada; Ogu, Rosemary; Mmom, Chigozirim Faith; Mba, Alpheus Gogo; Chidiadi, Ezenwa-Ahanene; Akani, Chris

    2016-01-01

    Aplastic anaemia occurring in pregnancy is a rare event with life threatening challenges for both mother and child. We present a successful fetomaternal outcome despite the challenges in the management of this rare condition in a tertiary but resource poor centre. This is case of a 37 year old Nigerian woman G6P0(+5)managed with repeated blood transfusions from 28 weeks of gestation for bone marrow biopsy confirmed aplastic anaemia following presentation with weakness and gingival bleeds. She had a cesarean section at 37 weeks for pre-eclampsia and oligohydraminous with good feto-maternal outcome. She was managed entirely with fresh whole blood and received 21 units. Aplastic Anaemia in Pregnancy is a rare event with poor feto maternal prognosis. Successful management is possible with good multi-disciplinary approach and availability of supportive comprehensive obstetric care.

  2. [Anaesthetic management of caesarean section in pregnancy with diabetes and hypertrophic myocardiopathy with restrictive diastolic dysfunction].

    PubMed

    Holgado, C M; Coves, S

    2013-02-01

    Haemodynamic changes that occur during pregnancy are maximal between 28 and 34 weeks. In the pregnant woman with several associated diseases, such as hypertensive myocardiopathy and pre-gestational diabetes, these changes can lead to a difficult control of pulmonary hypertension and acute pulmonary oedema. We report the case of a pregnant woman with long term type 1 diabetes mellitus who suffered pre-eclampsia in a previous pregnancy, and since then developed hypertensive cardiomyopathy. She was admitted at 30 week gestation for metabolic and blood pressure control, and developed congestive cardiac failure after the administration of betamethasone for foetal lung maturity. A transthoracic echocardiogram showed a non-dilated hypertrophic left ventricle with good systolic function, restrictive diastolic dysfunction and moderate pulmonary arterial hypertension. When her general condition improved, we performed a caesarean section under regional anaesthesia to prevent the complications of pulmonary and systemic hypertension. We present the anaesthetic management and resolution of complications after oxytocin administration.

  3. Pregnancy outcomes in Southeast Asian migrant workers at Southern Thailand.

    PubMed

    Hanprasertpong, T; Hanprasertpong, J

    2015-01-01

    This retrospective study was conducted to determine the pregnancy outcomes and identify predictive factors of adverse outcomes in pregnant migrant workers who delivered at Songklanagarind Hospital from January 2002 to December 2012. Two hundred and forty migrant worker pregnancies were enrolled. Pre-eclampsia, gestational diabetes mellitus, pre-term birth and foetal intrauterine growth restriction found were 15, 7.9, 13.7 and 3.7%, respectively. No stillbirth was found. Apgar score was

  4. Roles and regulation of the matrix metalloproteinase system in parturition.

    PubMed

    Geng, Junnan; Huang, Cong; Jiang, Siwen

    2016-04-01

    Significant tissue destruction, repair, and remodeling are involved in parturition, which involves fetal membrane rupture, cervical ripening, and uterine contraction and its subsequent involution. Extracellular matrix degradation and remodeling by proteolytic enzymes, such as matrix metalloproteinases (MMPs), are required for the final steps of parturition. MMPs participate in physiological degradation and remodeling through their proteolytic activities on specific substrates, and are balanced by the action of their inhibitors. Disruption to this balance can result in pathological stress that ends with preterm or post-term birth or pre-eclampsia. In this review, we examine the roles and regulation of the MMP system in physiological and pathological labor, and propose a model that illustrates the mechanisms by which the MMP system contributes to these processes.

  5. Microalbuminuria - A better marker in hypertensive disorders of pregnancy.

    PubMed

    Babu, Ruby P; Christy, Alap; Hegde, Anupama; Manjrekar, Poornima; Joseph, Maria

    2015-09-01

    To assess the role of microalbuminuria in pre-eclampsia (PE) as a diagnostic marker, we studied 40 PE cases and 40 normotensive controls at 24 ± 4 weeks of gestation in women 20-35 years of age. The patients with PE had significant microalbuminuria in comparison with the controls, in addition to deranged renal function tests. The receiver operating characteristic curve showed that microalbuminuria had the highest sensitivity (100%) and good specificity (77.6%). Microalbuminuria had the highest area under the curve (0.869) for both diagnosis of PE and renal function assessment. Microalbuminuria also had a good correlation with systolic blood pressure in the cases with mild grades of renal dysfunction. Microalbuminuria is a specific marker in PE and it also helps to assess the renal function status. Therefore, microalbuminuria may be used in the early diagnosis and management of PE patients in order to reduce the immediate and long-term complications.

  6. Idiopathic intracranial hypertension presenting as postpartum headache

    PubMed Central

    Mathew, Mariam; Salahuddin, Ayesha; Mathew, Namitha R.; Nandhagopal, Ramachandiran

    2016-01-01

    Postpartum headache is described as headache and neck or shoulder pain during the first 6 weeks after delivery. Common causes of headache in the puerperium are migraine headache and tension headache; other causes include pre-eclampsia/eclampsia, post-dural puncture headache, cortical vein thrombosis, subarachnoid hemorrhage, posterior reversible leukoencephalopathy syndrome, brain tumor, cerebral ischemia, meningitis, and so forth. Idiopathic intracranial hypertension (IIH) is a rare cause of postpartum headache. It is usually associated with papilledema, headache, and elevated intracranial pressure without any focal neurologic abnormality in an otherwise healthy person. It is more commonly seen in obese women of reproductive age group, but rare during pregnancy and postpartum. We present a case of IIH who presented to us 18 days after cesarean section with severe headache and was successfully managed. PMID:26818168

  7. The valuation of prenatal life in economic evaluations of perinatal interventions.

    PubMed

    Simon, Judit; Petrou, Stavros; Gray, Alastair

    2009-04-01

    Perinatal interventions delivered during the prenatal period have the potential to directly impact prenatal life. The decision on when to begin 'counting' the life of an infant in the calculus has received little attention in previous economic evaluations of perinatal interventions. We illustrate, using data from a recent trial-based economic evaluation of magnesium sulphate given to women with pre-eclampsia to prevent eclampsia, how different definitions of when human life commences can have a significant impact upon cost-effectiveness estimates based on composite outcome measures such as life years or quality-adjusted life years gained or disability-adjusted life years averted. Further, we suggest ways in which methods in this area can be improved.

  8. Adverse obstetric outcome in women with a history of infertility: a retrospective study.

    PubMed

    Yasmin, H; Hassan, I; Vanga, P; Subramanium, M; Adeghe, J H

    2006-01-01

    Women with a history of infertility are associated with a higher incidence of adverse pregnancy outcome. This retrospective study reviewed 105 women with a known history of infertility; of these 105 women, 77 (73%) conceived spontaneously and 28 (27%) had assisted conception. Our finding confirms higher perinatal complications; relative ratios (RR) for pre-eclampsia was 4.6 (95% CI=2.1-9.9), intrauterine growth restriction 4.8 (95% CI=1.9-12.0), gestational diabetes 1.8 (95% CI=0.5-5.8), pre-term premature rupture of membrane 2.3 (95% CI=0.6-8.8) and pre-term labour 2.6 (95% CI=1.1-5.9). We postulate that women with a history of infertility are at high risk of such obstetric complications and may benefit from intensified antenatal care.

  9. The eye and visual system in pregnancy, what to expect? An in-depth review

    PubMed Central

    Samra, Khawla Abu

    2013-01-01

    Pregnancy represents a real challenge to all body systems. Physiological changes can involve any of the body organs including the eye and visual system. The ocular effect of pregnancy involves a wide spectrum of physiologic and pathologic changes. The latter might be presenting for the first time during pregnancy such as corneal melting and corneal ectasia, or an already existing ocular pathologies that are modified by pregnancy such as diabetic retinopathy and glaucoma. In addition, pregnancy can affect vision through systemic disease that are either specific to the pregnant state itself such as the pre-eclampsia/eclampsia and Sheehan's syndrome, or systemic diseases that occur more frequently in relation to pregnancy such as Graves’ disease, idiopathic intracranial hypertension, anti-phospholipid syndrome, and disseminated intravascular coagulation. PMID:24082665

  10. Maternal morbidity and mortality associated with interpregnancy interval: cross sectional study

    PubMed Central

    Conde-Agudelo, Agustin; Belizán, José M

    2000-01-01

    Objective To study the impact of interpregnancy interval on maternal morbidity and mortality. Design Retrospective cross sectional study with data from the Perinatal Information System database of the Latin American Centre for Perinatology and Human Development, Montevideo, Uruguay. Setting Latin America and the Caribbean, 1985-97. Participants 456 889 parous women delivering singleton infants. Main outcome measures Crude and adjusted odds ratios of the effects of short and long interpregnancy intervals on maternal death, pre-eclampsia, eclampsia, gestational diabetes mellitus, third trimester bleeding, premature rupture of membranes, postpartum haemorrhage, puerperal endometritis, and anaemia. Results Short (<6 months) and long (>59 months) interpregnancy intervals were observed for 2.8% and 19.5% of women, respectively. After adjustment for major confounding factors, compared with those conceiving at 18 to 23 months after a previous birth, women with interpregnancy intervals of 5 months or less had higher risks for maternal death (odds ratio 2.54; 95% confidence interval 1.22 to 5.38), third trimester bleeding (1.73; 1.42 to 2.24), premature rupture of membranes (1.72; 1.53 to 1.93), puerperal endometritis (1.33; 1.22 to 1.45), and anaemia (1.30; 1.18 to 1.43). Compared with women with interpregnancy intervals of 18 to 23 months, women with interpregnancy intervals longer than 59 months had significantly increased risks of pre-eclampsia (1.83; 1.72 to 1.94) and eclampsia (1.80; 1.38 to 2.32). Conclusions Interpregnancy intervals less than 6 months and longer than 59 months are associated with an increased risk of adverse maternal outcomes. PMID:11082085

  11. Selenium and other elements in human maternal and umbilical serum, as determined simultaneously by proton-induced X-ray emission

    SciTech Connect

    Hyvoenen-Dabek, M.; Nikkinen-Vilkki, P.; Dabek, J.T.

    1984-04-01

    Using PIXE (proton-induced X-ray emission), we simultaneously determined the concentrations of Se, Ca, Fe, Cu, Zn, Br, and Pb in blood serum from 56 pregnant women, 25 healthy controls, and 31 others with twin pregnancy or some complicating condition (diabetes, hypertension, epilepsy, hepatosis gravidarum, pre-eclampsia, small baby), and in cord-blood serum from 21 newborns. Pellets, pressed from the serum samples after addition of yttrium as an internal standard, mixing, and evaporating at 30 degrees C with or without reduced pressure (less than 1 kPa), were bombarded by 2.2 MeV protons from a Van de Graaff accelerator in the air and the induced X-rays collected by a Ge(Li) detector. Relative to mean Se values for early six- to 12-week pregnancy (0.045 ppm), those for 35-42 week pregnancy (0.028 ppm) were low (p less than 0.001). Umbilical cord blood serum showed even lower values (0.016 ppm, p less than 0.001)--findings in harmony with the incidence pattern of Keshan cardiomyopathy. Pb crossed the placenta; values for cord serum were not significantly different from those in pregnancy serum. Cu, Zn, Fe, and Ca showed the significant expected patterns in the different groups. Compared with the late-pregnancy controls, Fe was high in mothers of small-birth-weight babies (1.70 ppm, p less than 0.02). Br was high in pre-eclampsia (3.59 ppm, p less than 0.05) and mothers with twins (3.61 ppm, p less than 0.05).

  12. Placental weight and efficiency in relation to maternal body mass index and the risk of pregnancy complications in women delivering singleton babies.

    PubMed

    Wallace, J M; Horgan, G W; Bhattacharya, S

    2012-08-01

    Herein we report placental weight and efficiency in relation to maternal BMI and the risk of pregnancy complications in 55,105 pregnancies. Adjusted placental weight increased with increasing BMI through underweight, normal, overweight, obese and morbidly obese categories and accordingly underweight women were more likely to experience placental growth restriction [OR 1.69 (95% CI 1.46-1.95)], while placental hypertrophy was more common in overweight, obese and morbidly obese groups [OR 1.59 (95% CI 1.50-1.69), OR 1.97 (95% CI 1.81-2.15) and OR 2.34 (95% CI 2.08-2.63), respectively]. In contrast the ratio of fetal to placental weight (a proxy for placental efficiency) was lower (P < 0.001) in overweight, obese and morbidly obese than in both normal and underweight women which were equivalent. Relative to the middle tertile reference group (mean 622 g), placental weight in the lower tertile (mean 484 g) was associated with a higher risk of pre-eclampsia, induced labour, spontaneous preterm delivery, stillbirth and low birth weight (P < 0.001). Conversely placental weight in the upper tertile (mean 788 g) was associated with a higher risk of caesarean section, post-term delivery and high birth weight (P < 0.001). With respect to assumed placental efficiency a ratio in the lower tertile was associated with an increased risk of pre-eclampsia, induced labour, caesarean section and spontaneous preterm delivery (P < 0.001) and a ratio in both the lower and higher tertiles was associated with an increased risk of low birth weight (P < 0.001). Placental efficiency was not related to the risk of stillbirth or high birth weight. No interactions between maternal BMI and placental weight tertile were detected suggesting that both abnormal BMI and placental growth are independent risk factors for a range of pregnancy complications.

  13. Clinical profile and outcome of acute kidney injury related to pregnancy in developing countries: a single-center study from India.

    PubMed

    Godara, Suraj M; Kute, Vivek B; Trivedi, Hargovind L; Vanikar, Aruna V; Shah, Pankaj R; Gumber, Manoj R; Patel, Himanshu V; Gumber, Vandana M

    2014-07-01

    Acute kidney injury (AKI) is one of the most challenging and serious complications of pregnancy. We present our experience on the clinical profile and outcome of 57 patients with pregnancy-related AKI, of a total of 580 patients with AKI seen during the study period. This is a prospective single-center study in a civil hospital conducted from January to December 2010. The most common age group of the study patients was 20-25 years; 43.8% of the patients had received antenatal care. AKI was observed in the puerperium (n = 34), early pregnancy (n = 10) and late pregnancy (n = 13). The cause of AKI included puerperal sepsis (63.1%), pregnancy-induced hypertension (PIH) (33.33%), post-abortion (22.80%), ante-partum hemorrhage (APH) (14%) and post-partum hemorrhage (PPH) (8%). Complete, partial and no renal recovery was observed in 52.64%, 21.05% and 26.31% of the patients, respectively. Low platelet count and plasma fibrinogen and high bilirubin, D-dimer and activated partial thromboplast in time were observed more commonly in patients with partial recovery. Of the 57 patients, 50 received hemodialysis, three received peritoneal dialysis and seven patients were managed conservatively. A total of 13 patients developed cortical necrosis that was associated with sepsis in six, PPH and pre-eclampsia/eclampsia in three patients each and APH in one. Nine patients died, and the cause of death was septicemia in four, pre-eclampsia in three and APH and PPH in one patient each. In our study, puerperal sepsis was the most common etiological factor for pregnancy-related AKI. Prolonged oliguria or anuria were bad prognostic factors for renal recovery. Sepsis, thrombocytopenia, disseminated intra-vascular coagulation and liver involvement were associated with increased mortality.

  14. PCSK6-mediated corin activation is essential for normal blood pressure

    PubMed Central

    Chen, Shenghan; Cao, Pengxiu; Dong, Ningzheng; Peng, Jianhao; Zhang, Chunyi; Wang, Hao; Zhou, Tiantian; Yang, Junhua; Zhang, Yue; Martelli, Elizabeth E; Prasad, Sathyamangla V Naga; Miller, Rachel E; Malfait, Anne-Marie; Zhou, Yiqing; Wu, Qingyu

    2016-01-01

    Hypertension is the most common cardiovascular disease, afflicting >30% of adults1. The cause of hypertension in most individuals remains unknown2,3, suggesting that additional contributing factors have yet to be discovered. Corin is a serine protease that activates the natriuretic peptides, thereby regulating blood pressure4. It is synthesized as a zymogen that is activated by proteolytic cleavage. CORIN variants and mutations impairing corin activation have been identified in people with hypertension and pre-eclampsia5–9. To date, however, the identity of the protease that activates corin remains elusive. Here we show that proprotein convertase subtilisin/kexin-6 (PCSK6, also named PACE4; ref. 10) cleaves and activates corin. In cultured cells, we found that corin activation was inhibited by inhibitors of PCSK family proteases and by small interfering RNAs blocking PCSK6 expression. Conversely, PCSK6 overexpression enhanced corin activation. In addition, purified PCSK6 cleaved wild-type corin but not the R801A variant that lacks the conserved activation site. Pcsk6-knockout mice developed salt-sensitive hypertension, and corin activation and pro-atrial natriuretic peptide processing activity were undetectable in these mice. Moreover, we found that CORIN variants in individuals with hypertension and pre-eclampsia were defective in PCSK6-mediated activation. We also identified a PCSK6 mutation that impaired corin activation activity in a hypertensive patient. Our results indicate that PCSK6 is the long-sought corin activator and is important for sodium homeostasis and normal blood pressure. PMID:26259032

  15. Intensive care unit admission of obstetric cases: a single centre experience with contemporary update.

    PubMed

    Ng, Vivian K S; Lo, T K; Tsang, H H; Lau, W L; Leung, W C

    2014-02-01

    OBJECTIVES. To review the characteristics of a series of obstetric patients admitted to the intensive care unit in a regional hospital in 2006-2010, to compare them with those of a similar series reported from the same hospital in 1989-1995 and a series reported from another regional hospital in 1998-2007. DESIGN. Retrospective case series. SETTING. A regional hospital in Hong Kong. PATIENTS. Obstetric patients admitted to the Intensive Care Unit of Kwong Wah Hospital from 1 January 2006 to 31 December 2010. RESULTS. From 2006 to 2010, there were 67 such patients admitted to the intensive care unit (0.23% of total maternities and 2.34% of total intensive care unit admission), which was a higher incidence than reported in two other local studies. As in the latter studies, the majority were admitted postpartum (n=65, 97%), with postpartum haemorrhage (n=39, 58%) being the commonest cause followed by pre-eclampsia/eclampsia (n=17, 25%). In the current study, significantly more patients had had elective caesarean sections for placenta praevia but fewer had had a hysterectomy. The duration of intensive care unit stay was shorter (mean, 1.8 days) with fewer invasive procedures performed than in the two previous studies, but maternal and neonatal mortality was similar (3% and 6%, respectively). CONCLUSION. Postpartum haemorrhage and pregnancy-induced hypertension were still the most common reasons for intensive care unit admission. There was an increasing trend of intensive care unit admissions following elective caesarean section for placenta praevia and for early aggressive intervention of pre-eclampsia. Maternal mortality remained low but had not decreased. The intensive care unit admission rate by itself might not be a helpful indicator of obstetric performance.

  16. Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery.

    PubMed

    Lykke, Jacob A; Langhoff-Roos, Jens; Lockwood, Charles J; Triche, Elizabeth W; Paidas, Michael J

    2010-07-01

    The combined effects of preterm delivery, small-for-gestational-age offspring, hypertensive disorders of pregnancy, placental abruption and stillbirth on early maternal death from cardiovascular causes have not previously been described in a large cohort. We investigated the effects of pregnancy complications on early maternal death in a registry-based retrospective cohort study of 782 287 women with a first singleton delivery in Denmark 1978-2007, followed for a median of 14.8 years (range 0.25-30.2) accruing 11.6 million person-years. We employed Cox proportional hazard models of early death from cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non-cardiovascular causes. Severe pre-eclampsia was associated with death from cardiovascular causes only. There was a less than additive effect on cardiovascular mortality hazard ratios with increasing number of pregnancy complications: preterm delivery 1.90 [95% confidence intervals 1.49, 2.43]; preterm delivery and small-for-gestational-age offspring 3.30 [2.25, 4.84]; preterm delivery, small-for-gestational-age offspring and pre-eclampsia 3.85 [2.07, 7.19]. Thus, we conclude that, separately and combined, preterm delivery and small-for-gestational-age are strong markers of early maternal death from both cardiovascular and non-cardiovascular causes, while hypertensive disorders of pregnancy are markers of early death of mothers from cardiovascular causes.

  17. Diagnosis and management of non-criteria obstetric antiphospholipid syndrome.

    PubMed

    Arachchillage, Deepa R Jayakody; Machin, Samuel J; Mackie, Ian J; Cohen, Hannah

    2015-01-01

    Accurate diagnosis of obstetric antiphospholipid syndrome (APS) is a prerequisite for optimal clinical management. The international consensus (revised Sapporo) criteria for obstetric APS do not include low positive anticardiolipin (aCL) and anti β2 glycoprotein I (aβ2GPI) antibodies (< 99th centile) and/or certain clinical criteria such as two unexplained miscarriages, three non-consecutive miscarriages, late pre-eclampsia, placental abruption, late premature birth, or two or more unexplained in vitro fertilisation failures. In this review we examine the available evidence to address the question of whether patients who exhibit non-criteria clinical and/or laboratory manifestations should be included within the spectrum of obstetric APS. Prospective and retrospective cohort studies of women with pregnancy morbidity, particularly recurrent pregnancy loss, suggest that elimination of aCL and/or IgM aβ2GPI, or low positive positive aCL or aβ2GPI from APS laboratory diagnostic criteria may result in missing the diagnosis in a sizeable number of women who could be regarded to have obstetric APS. Such prospective and retrospective studies also suggest that women with non-criteria obstetric APS may benefit from standard treatment for obstetric APS with low-molecular-weight heparin plus low-dose aspirin, with good pregnancy outcomes. Thus, non-criteria manifestations of obstetric APS may be clinically relevant, and merit investigation of therapeutic approaches. Women with obstetric APS appear to be at a higher risk than other women of pre-eclampsia, placenta-mediated complications and neonatal mortality, and also at increased long-term risk of thrombotic events. The applicability of these observations to outcomes in women with non-criteria obstetric APS remains to be determined.

  18. Do uterine natural killer cell numbers in peri-implantation endometrium predict hypertensive disorder in pregnancy in women with a history of reproductive failure?

    PubMed

    Wong, Alice Wai Yee; Archer, Bethan; Mariee, Najat; Li, Tin Chiu; Laird, Susan M

    2014-12-01

    The aim of this study was to investigate whether or not increased uterine natural killer (uNK) cell numbers in the peri-implantation endometrium are associated with an increased risk of hypertensive disorders in a subsequent pregnancy. This is a retrospective study including 80 women with a history of unexplained recurrent miscarriage or recurrent implantation failure. Precisely timed endometrial biopsies were obtained from women 7-9 days after the luteinising hormone surge. uNK cells were immunostained for CD56+ and expressed as a percentage of total stromal cells. Patients were defined as having a high uNK cell count if the percentage of total stromal cells was more than 13.9%. Five out of 29 (17.2%) women in the high uNK cell count group and 5 out of 51 (9.8%) women in the normal uNK cell count group developed gestational hypertension. Pre-eclampsia was diagnosed in 2 (6.9%) patients in the high uNK cell count group and 1 (2.0%) patient from the normal uNK cell count group. There was no significant difference in the incidence of either gestational hypertension (P=0.483) and pre-eclampsia (P=0.296) between groups. The overall incidence of hypertensive disease in women with high uNK cell count (24.1%) was two times higher than women with normal uNK cell count (11.8%), but it was not statistically significant (P=0.208). An increased uNK cells count in the peri-implantation period in a cycle prior to conception did not appear to significantly increase the likelihood of hypertensive disease of pregnancy.

  19. MSX2 Induces Trophoblast Invasion in Human Placenta

    PubMed Central

    Lu, Junjie; Yang, Genling; Tian, Na; Wang, Xiaojie; Tan, Yi; Tan, Dongmei

    2016-01-01

    Normal implantation depends on appropriate trophoblast growth and invasion. Inadequate trophoblast invasion results in pregnancy-related disorders, such as early miscarriage and pre-eclampsia, which are dangerous to both the mother and fetus. Msh Homeobox 2 (MSX2), a member of the MSX family of homeobox proteins, plays a significant role in the proliferation and differentiation of various cells and tissues, including ectodermal organs, teeth, and chondrocytes. Recently, MSX2 was found to play important roles in the invasion of cancer cells into adjacent tissues via the epithelial-mesenchymal transition (EMT). However, the role of MSX2 in trophoblastic invasion during placental development has yet to be explored. In the present study, we detected MSX2 expression in cytotrophoblast, syncytiotrophoblast, and extravillous cytotrophoblast cells of first or third trimester human placentas via immunohistochemistry analysis. Furthermore, we found that the in vitro invasive ability of HTR8/SVneo cells was enhanced by exogenous overexpression of MSX2, and that this effect was accompanied by increased protein expression of matrix metalloproteinase-2 (MMP-2), vimentin, and β-catenin. Conversely, treatment of HTR8/SVneo cells with MSX2-specific siRNAs resulted in decreased protein expression of MMP-2, vimentin, and β-catenin, and reduced invasion levels in a Matrigel invasion test. Notably, however, treatment with the MSX2 overexpression plasmid and the MSX2 siRNAs had no effect on the mRNA expression levels of β-catenin. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may be associated

  20. Asthma and pregnancy: a prospective study of 198 pregnancies.

    PubMed Central

    Stenius-Aarniala, B; Piirilä, P; Teramo, K

    1988-01-01

    A study was designed to investigate whether asthma, when carefully managed, is associated with an increased risk of complications in connection with pregnancy. One hundred and eighty one asthmatic women were monitored during 198 pregnancies. Antiasthmatic treatment consisted of inhaled beta 2 adrenergic drugs, beclomethasone, sodium cromoglycate, oral theophylline, and systemic corticosteroids as needed. Postpartum information on asthmatic symptoms and infant feeding was collected by means of a questionnaire. A control group of 198 non-asthmatic pregnant women was matched for age and parity. Atopic women had less severe asthma than non-atopic women. During pregnancy 40% of the patients were managed with the same antiasthmatic medication as before pregnancy; 18% needed less and 42% more medication. Pre-eclampsia occurred more often in asthmatic than control subjects, especially in patients with severe asthma. Hypoglycaemia occurred more often in infants of mothers with severe asthma than in infants of mothers with less severe disease. Theophylline medication at term did not influence labour or delivery. Asthma caused no emergencies during labour. Among the asthmatic subjects 28% of babies were delivered by caesarean section compared with 17% in the control group. There was no difference between asthmatic and control subjects with regard to length of gestation, birth weight, incidence of perinatal deaths, low Apgar scores, neonatal respiratory difficulties, hyperbilirubinaemia, or malformations. It is concluded that severe asthma or systemic corticosteroid treatment (or both) during pregnancy seems to increase the incidence of mild pre-eclampsia in the mother and hypoglycaemia in the infant. The findings suggest that careful supervision of asthma during pregnancy and labour by obstetricians and chest physicians working in close collaboration should prevent most of the serious obstetric and neonatal complications of asthma in pregnancy reported by previous authors

  1. Adverse obstetrical and perinatal outcome in adolescent mothers associated with first birth: a hospital-based case-control study in a tertiary care hospital in North-East India

    PubMed Central

    Medhi, Robin; Das, Banani; Das, Arpana; Ahmed, Mansur; Bawri, Sonika; Rai, Suditi

    2016-01-01

    Purpose To analyze the adverse obstetrical and perinatal outcome of adolescent mothers associated with first birth. Patients and methods This prospective case-control study was conducted in a tertiary care teaching hospital of North-East India between January 2014 and December 2014. All adolescent primigravidae completing 28 weeks of gestation with singleton pregnancy and delivered at our institution were included in the study group. Primigravidae aged between 20 and 25 years were taken as a control group. Mothers having pregnancy complicated with diabetes mellitus, renal disorder, thyroid disorders, and cardiac diseases were excluded from the study. Demographic data, maternal complications like severe anemia, pre-eclampsia, eclampsia, gestational age at delivery, mode of delivery, and postpartum complications were compared. Among fetal complications, low-birth weight, preterm birth, neonatal intensive care unit admission, still birth, and early neonatal death were compared. All the patients were interviewed regarding contraceptive knowledge and its use preceding the pregnancy. Results Quality antenatal care was received by 80.6% of adolescent mothers. The adolescent mothers had a higher incidence of pre-eclampsia (odds ratio [OR] 2.017 95% confidence interval [CI]: 1.045–3.894, P=0.03), preterm deliveries (OR: 1.655, 95% CI: 1.039–2.636, P=0.03). Among fetal outcomes, the low- birth weight babies (OR: 1.59, 95% CI: 1.016–2.478), low mean birth weight (2,544.4±622.09 g versus 2,701.6±582.51 g), and higher admission to neonatal intensive care unit (OR: 1.957, 95% CI: 1.120–3.417) were significantly associated with adolescent mothers. There was no significant difference found regarding the mode of delivery, still birth, and early neonatal death. Moreover, contraceptive knowledge and its use were found to be poor among adolescent mothers. Conclusion With quality antenatal, intranatal, and postnatal care, the obstetric risk of childbirth in adolescent mothers

  2. A New Look at Care in Pregnancy: Simple, Effective Interventions for Neglected Populations

    PubMed Central

    Hodgins, Stephen; Tielsch, James; Rankin, Kristen; Robinson, Amber; Kearns, Annie; Caglia, Jacquelyn

    2016-01-01

    Background Although this is beginning to change, the content of antenatal care has been relatively neglected in safe-motherhood program efforts. This appears in part to be due to an unwarranted belief that interventions over this period have far less impact than those provided around the time of birth. In this par, we review available evidence for 21 interventions potentially deliverable during pregnancy at high coverage to neglected populations in low income countries, with regard to effectiveness in reducing risk of: maternal mortality, newborn mortality, stillbirth, prematurity and intrauterine growth restriction. Selection was restricted to interventions that can be provided by non-professional health auxiliaries and not requiring laboratory support. Methods In this narrative review, we included relevant Cochrane and other systematic reviews and did comprehensive bibliographic searches. Inclusion criteria varied by intervention; where available randomized controlled trial evidence was insufficient, observational study evidence was considered. For each intervention we focused on overall contribution to our outcomes of interest, across varying epidemiologies. Results In the aggregate, achieving high effective coverage for this set of interventions would very substantially reduce risk for our outcomes of interest and reduce outcome inequities. Certain specific interventions, if pushed to high coverage have significant potential impact across many settings. For example, reliable detection of pre-eclampsia followed by timely delivery could prevent up to ¼ of newborn and stillbirth deaths and over 90% of maternal eclampsia/pre-eclampsia deaths. Other interventions have potent effects in specific settings: in areas of high P falciparum burden, systematic use of insecticide-treated nets and/or intermittent presumptive therapy in pregnancy could reduce maternal mortality by up to 10%, newborn mortality by up to 20%, and stillbirths by up to 25–30%. Behavioral

  3. Excessive urinary tract dilatation and proteinuria in pregnancy: a common and overlooked association?

    PubMed Central

    2013-01-01

    Background Proteinuria and dilatation of the urinary tract are both relatively common in pregnancy, the latter with a spectrum of symptoms, from none to severe pain and infection. Proteinuria is a rare occurrence in acute obstructive nephropathy; it has been reported in pregnancy, where it may pose a challenging differential diagnosis with pre-eclampsia. The aim of the present study is to report on the incidence of proteinuria (≥0.3; ≥0.5 g/day) in association with symptomatic-severe urinary tract dilatation in pregnancy. Methods Case series. Setting: Nephrological-Obstetric Unit dedicated to pregnancy and kidney diseases (January 2000-April 2011). Source: database prospectively updated since the start of the Unit. Retrospective review of clinical charts identified as relevant on the database, by a nephrologist and an obstetrician. Results From January 2000 to April 2011, 262 pregnancies were referred. Urinary tract dilatation with or without infection was the main cause of referral in 26 cases (predominantly monolateral in 19 cases): 23 singletons, 1 lost to follow-up, 1 twin and 1 triplet. Patients were referred for urinary tract infection (15 cases) and/or renal pain (10 cases); 6 patients were treated by urologic interventions (“JJ” stenting). Among them, 11 singletons and 1 triple pregnancy developed proteinuria ≥0.3 g/day (46.1%). Proteinuria was ≥0.5 g/day in 6 singletons (23.1%). Proteinuria resolved after delivery in all cases. No patient developed hypertension; in none was an alternative cause of proteinuria evident. No significant demographic difference was observed in patients with renal dilatation who developed proteinuria versus those who did not. An association with the presence of “JJ” stenting was present (5/6 cases with proteinuria ≥0.5 g/day), which may reflect both severer obstruction and a role for vescico-ureteral reflux, induced by the stent. Conclusions Symptomatic urinary tract dilatation may be associated with

  4. Effects of anticoagulant therapy on pregnancy outcomes in patients with thrombophilia and previous poor obstetric history.

    PubMed

    Mutlu, Ilknur; Mutlu, Mehmet Firat; Biri, Aydan; Bulut, Berk; Erdem, Mehmet; Erdem, Ahmet

    2015-04-01

    This study investigates the effects of anticoagulant therapy on pregnancy outcomes in 204 patients with thrombophilia and previous poor obstetric outcomes. Patients with poor obstetric history (pre-eclampsia, intrauterine growth retardation, fetal death, placental abruption, recurrent pregnancy loss) and having hereditary thrombophilia were included in this study. Poor obstetric outcomes were observed more frequently in patients who had not taken anticogulant therapy compared with treated group. Live birth rate, gestational age at birth and Apgar scores were significantly higher in the treated group when compared with the untreated group. There were no significant differences in terms of birthweight, mode of delivery and admission rates to the neonatal intensive care unit (NICU). Low-molecular-weight heparin (LMWH) plus acetylsalicylic acid (ASA) had higher gestational age at birth, Apgar scores, live birth rate and a lower abortion rates when compared with controls; in contrast, no significant difference was observed in terms of birthweight, mode of delivery, obstetric complications and admission rates to NICU. There were no significant differences between control group and both LMWH only and ASA only groups in terms of gestational age at birth, Apgar scores, birthweight, mode of delivery, obstetric complications and admission rates to NICU. Only LMWH group had higher live birth rate as compared with control group. The use of only ASA did not seem to affect the perinatal complication rates and outcomes. In conclusion, anticoagulant therapy with both LMWH and ASA seems to provide better obstetric outcomes in pregnant women with thrombophilia and previous poor obstetric outcomes.

  5. Searching for genes involved in hypertension development in special populations: children and pre-eclamptic women. Where are we standing now?

    PubMed

    Danese, Elisa; Montagnana, Martina; Fava, Cristiano

    2013-12-01

    Primary hypertension is a very common disorder particularly in the aging population but hypertensive disorders can appear earlier in life, especially when obesity and unhealthy lifestyle are present. Also pregnant women can be at risk of developing gestational hypertension and/or pre-eclampsia, which causes complications in nearly 7% of pregnancies. These "special" populations could be regarded as natural models suited to reveal mechanisms of hypertension development which are either common to other forms of hypertension, including primary hypertension or specific to these populations. Recent studies in the field of genetics of primary hypertension have used new powerful tools, such as genome-wide association studies (GWAS) and sequencing, but studies about hypertension during childhood and in pregnancy have seldom used high-throughput technologies and the knowledge in this field comes mostly from the candidate gene approach. In this review we summarize some interesting results from genetic studies conducted in childhood and adolescence and during pregnancy and underline the need to apply modern technologies in these potentially very fruitful populations.

  6. Tim-3: Expression on immune cells and roles at the maternal-fetal interface.

    PubMed

    Hu, Xiao-Hui; Tang, Mao-Xing; Mor, Gil; Liao, Ai-Hua

    2016-11-01

    Successful pregnancy relies on the accurate regulation of the maternal-fetal immune system. Without enough tolerance in the uterine microenvironment, the mother and the hemiallogeneic fetus could not peacefully coexist. T cell immunoglobulin and mucin domain (Tim)-3 is a molecule originally regarded as to be expressed on terminally differentiated IFN-γ expressing CD4(+) T cells (Th1). The engagement of Tim-3 with its ligand, galectin-9 (Gal-9) could induce the exhaustion or apoptosis of effector T cells, and thus might regulate the tolerance. Tim-3 pathway also participates in regulating the activities of CD4(+) regulatory T cells, monocyte-macrophages, dendritic cells and natural killer cells. Dysregulation of Tim-3 expression can elicit excessive or inhibited inflammatory responses and ultimately result in autoimmune diseases, viral or tumor evasion and pregnancy complications. In this review, we will mainly focus on the expression of Tim-3 on local immune cells and its function in pregnancy. In addition, meaningful questions that need further investigation and the potential roles of Tim-3 in fetal tolerance will be discussed. Deeper understanding of the immune checkpoint receptor Tim-3 will shed new light on exploring the pathogenesis of some pregnancy complications, including pre-eclampsia, intrauterine growth restriction, recurrent spontaneous abortion and preterm birth. Tim-3 pathway might be a new target of immune therapy for pregnancy complications in the future.

  7. Maternal use of oral contraceptives and risk of hypospadias - a population-based case-control study.

    PubMed

    Wogelius, Pia; Horváth-Puhó, Erzsébet; Pedersen, Lars; Nørgaard, Mette; Czeizel, Andrew E; Sørensen, Henrik Toft

    2006-01-01

    The aim of this population-based case-control study was to examine the risk of isolated hypospadias in boys born to mothers who have used oral contraceptives in early pregnancy. The study was based on data from the Hungarian Case-Control Surveillance of Congenital Abnormalities from 1980 to 1996, and included 3,038 boys with hypospadias (cases), 24,799 boys without congenital abnormalities (CA-free controls), and 11,881 boys with abnormalities other than hypospadias. We used unconditional logistic regression to adjust for birth order, maternal age, maternal employment status, maternal diabetes, and pre-eclampsia. When comparing cases with CA-free controls the OR for maternal use of OC was 1.21 (95% CI: 0.67-2.17). When comparing cases with boys with other abnormalities, the OR for maternal use of OC was 0.83 (95% CI: 0.46-1.50). Our data showed that self-reported maternal use of oral contraceptives during pregnancy was not associated with an increased risk of hypospadias in the offspring.

  8. [Hypertension and pregnancy].

    PubMed

    Rosas, Martín; Lomelí, Catalina; Mendoza-González, Celso; Lorenzo, José Antonio; Méndez, Arturo; Férez Santander, Sergio Mario; Attie, Fause

    2008-01-01

    Increasing evidence indicates that hypertension in pregnancy is an under recognized risk factor for cardiovascular disease (CVD). Compared with women who have had normotensive pregnancies, those who are hypertensive during pregnancy are at greater risk of cardiovascular and cerebrovascular events and have a less favorable overall risk profile for CVD years after the affected pregnancies. One factor that might underlie this relationship is that hypertensive disorders of pregnancy (pre-eclampsia, in particular) and CVD share several common risk factors (e.g. obesity, diabetes mellitus and renal disease). Alternatively, hypertension in pregnancy could induce long-term metabolic and vascular abnormalities that might increase the overall risk of CVD later in life. In both cases, evidence regarding risk-reduction interventions specific to women who have had hypertensive pregnancies is lacking. While awaiting results of large-scale studies, hypertensive disorders of pregnancy should be screened for during assessment of a woman's overall risk profile for CVD. Women at high risk must be monitored closely for conventional risk factors that are common to both CVD and hypertensive disorders of pregnancy and treated according to current evidence-based national guidelines.

  9. A rare manifestation of neonatal alloimmune thrombocytopaenia.

    PubMed

    Jerónimo, Monica; Azenha, Cátia; Mesquita, Joana; Pereira, Dolores Faria

    2014-06-02

    Neonatal alloimmune thrombocytopaenia (NAIT) results from a fetomaternal incompatibility with maternal sensitisation against a fetal human platelet antigen (HPA) and antibodies transfer to the fetal circulation, leading to platelet destruction. The clinical presentation is variable and isolated intraocular haemorrhage is rare. We present the case of a male newborn, with intrauterine growth restriction, born at 29 weeks due to pre-eclampsia. He presented proptosis of the left eye, hyphaema and elevated intraocular pressure, with no other signs of haemorrhage. Severe thrombocytopaenia was found (27×10(9)/L). Perinatal infection and maternal thrombocytopaenia were excluded. Positive anti-HPA-1a and antihuman leucocyte antigen class I alloantibodies were found in the mother. Platelet crossmatch between the father's platelets and mother's plasma was positive. Platelet transfusions and intravenous immunoglobulin were given with favourable response. This case highlights an unusual presentation of NAIT, which should be suspected in the presence of severe thrombocytopaenia in the first 24-72 h of life.

  10. Toll-like receptors in the gonads and reproductive tract: emerging roles in reproductive physiology and pathology.

    PubMed

    Girling, Jane E; Hedger, Mark P

    2007-01-01

    Interactions between the immune system and reproductive system have important consequences for fertility and reproductive health in general. There is increasing evidence that many of the interactions between the immune and reproductive systems involve the Toll-like receptors (TLRs). While there is no doubt that TLRs are important in providing protection against infection in the reproductive tract, there is increasing evidence for the involvement of TLRs in more basic pathology and physiology of reproduction. In the female, TLRs have been implicated in critical aspects of ovarian, endometrial and placental function, as well as in ovarian cancer, pelvic inflammatory disease, intrauterine growth restriction, pre-eclampsia and preterm birth. In the male, TLRs appear to play a role in the control of testicular steroidogenesis and spermatogenesis in disease and, potentially, during normal function, as well. Recent studies also have begun to highlight the role of various TLRs in the aetiology of prostatitis and prostatic cancer. Given the nascent state of knowledge concerning this important area, it is clear that more studies are needed, which should provide valuable new insights into the biology of the TLRs and reproductive function in general.

  11. [Premature newborn: a case presentation].

    PubMed

    Pastor Rodríguez, Jesús David; Pastor Bravo, María Del Mar; López García, Visitación; Cotes Teruel, María Isabel; Mellado, Jesús Eulogio; Cárceles, José Jara

    2010-01-01

    A case is presented of a premature newborn of 27 weeks gestation and weighing 420 grams who was delivered as a result of a maternal pre-eclampsia and retarded intra-uterine growth. During the 125 days of hospitalisation, an individual care plan based on the Virginia Henderson model was devised and applied to both the child and her parents using NANDA diagnostics, interventions according to the NIC classification, and the expected results according to the NOC classification. The Marjory Gordon functional patterns were used for the initial assessment. By applying the pre-term newborn (PTNB) plan, all their needs were provided and were modified throughout the hospital stay, with new needs that were added to the established ones. These required a continuous assessment with the subsequent adapting of the care plan. Likewise, the care required by the parents varied from the initial grief due to the possible loss of their child to learning the alarm signs and the home care that their child would need. The child was finally discharged weighing 2900 grams and with normal neurological and psychomotor development, although with a lower weight appropriate to her age. Currently, at 2 years old, the child has a normal neurological and psychomotor development, but with weight and size lower than the P(3) percentile. She requires speech therapy treatment due to paralysis of the right vocal cord.

  12. The endocrine function of human placenta: an overview.

    PubMed

    Costa, Mariana A

    2016-01-01

    During pregnancy, several tightly coordinated and regulated processes take place to enable proper fetal development and gestational success. The formation and development of the placenta is one of these critical pregnancy events. This organ plays essential roles during gestation, including fetal nourishment, support and protection, gas exchange and production of several hormones and other mediators. Placental hormones are mainly secreted by the syncytiotrophoblast, in a highly and tightly regulated way. These hormones are important for pregnancy establishment and maintenance, exerting autocrine and paracrine effects that regulate decidualization, placental development, angiogenesis, endometrial receptivity, embryo implantation, immunotolerance and fetal development. In addition, because they are released into maternal circulation, the profile of their blood levels throughout pregnancy has been the target of intense research towards finding potential robust and reliable biomarkers to predict and diagnose pregnancy-associated complications. In fact, altered levels of these hormones have been associated with some pathologies, such as chromosomal anomalies or pre-eclampsia. This review proposes to revise and update the main pregnancy-related hormones, addressing their major characteristics, molecular targets, function throughout pregnancy, regulators of their expression and their potential clinical interest.

  13. Risk factors for small for gestational age infants.

    PubMed

    McCowan, Lesley; Horgan, Richard P

    2009-12-01

    There are many established risk factors for babies who are small for gestational age (SGA) by population birth weight centiles (usually defined as <10th centile). The confirmed maternal risk factors include short stature, low weight, Indian or Asian ethnicity, nulliparity, mother born SGA, cigarette smoking and cocaine use. Maternal medical history of: chronic hypertension, renal disease, anti-phospholipid syndrome and malaria are associated with increased SGA. Risk factors developing in pregnancy include heavy bleeding in early pregnancy, placental abruption, pre-eclampsia and gestational hypertension. A short or very long inter-pregnancy interval, previous SGA infant or previous stillbirth are also risk factors. Paternal factors including changed paternity, short stature and father born SGA also contribute. Factors associated with reduced risk of SGA or increased birth weight include high maternal milk consumption and high intakes of green leafy vegetables and fruit. Future studies need to investigate risk factors for babies SGA by customised centiles as these babies have greater morbidity and mortality than babies defined as SGA by population centiles.

  14. Pregnancy and kidney transplantation.

    PubMed

    Josephson, Michelle A; McKay, Dianne B

    2011-01-01

    Despite decades of experience with child bearing in women with kidney transplants, these pregnancies remain high risk with an increased prevalence of hypertension and pre-eclampsia. Infertility, common in women with end-stage renal disease, is rapidly restored after transplant although pregnancy rates appear lower in transplant recipients than the general public. Many unanswered questions exist, some old questions such as what is the optimal timing of pregnancy after transplant, whether breast feeding is safe, the long-term impact if any on the offspring, and whether pregnancy negatively affects the kidney graft; and some new questions such as whether to modify immunosuppression in a patient taking a mycophenolic acid-containing drug, whether kidney donation has a deleterious impact on future pregnancies, whether to use erythropoietin-stimulating agents, and the role of BK virus. Counseling about contraception and pregnancy after transplant should be initiated during the pretransplant evaluation process. It is important because of the rapid restoration of fertility that occurs after transplant as well as the many risks and unanswered questions that remain.

  15. Health implications of traditional female circumcision in pregnancy.

    PubMed

    Adetoro, O O; Ebomoyi, E

    1986-12-01

    A case of traditional female circumcision during pregnancy, as practiced by her ethnic group, the Igbomina-Ekiti of Kawra State, with loss of the fetus as a result of infection, is presented. The woman was circumcised at age 20 at approximately 34 weeks' gestation. She had bled profusely during the procedure and was treated locally with herbs and snail juice. She had 5 days of pain and purulent bloody discharge. On hospital admission the patient was febrile and anemic, her vulva was hemorrhagic and edematous with partially excised clitoris and labia minora. Fetal heart sounds were present. She was given 2 units of blood, anti-tetanus toxoid, and prophylactic antibiotics. 2 days later the infecting organisms and their antibiotic sensitivity were identified, pseudomonas pyocyanea and Staph. Aureus, sensitive to erythromycin and gentamycin. Her fever abated, but she developed pre-eclampsia and she went into labor spontaneously. At 3 cm dilation, labor failed to progress despite artificial rupture of the membranes. A fresh stillborn female preterm infant was delivered by cesarean section. It was felt that the fetus died because of the infection. In Nigeria, female circumcision may be done in infancy by the Yorubas in the Western States, at puberty by the Igbos in Abakaliki, before marriage by the Isoko in Bendel States and the Hausas in the North, and during the 1st pregnancy by the Ogbaru in Anambra State and the Igbomina-Ekiti in Kawra State.

  16. The use of gene therapy tools in reproductive immunology research.

    PubMed

    Zenclussen, Ana Claudia; Zenclussen, Maria L; Ritter, Thomas; Volk, Hans D

    2005-10-01

    Mammalian pregnancy is a complex phenomenon allowing the maternal immune system to support its allogeneic fetus, while still being effective against pathogens. Gene therapy approaches have the potential to treat devastating inherited diseases for which there is a little hope of finding a conventional cure. In reproductive medicine, experimental trials have been made so far only for correcting gene defects in utero. The use of gene therapy for improving pregnancy-rate success or avoiding pregnancy-related diseases i.e. miscarriage or pre-eclampsia, remains a very distant goal with unresolved moral and ethical aspects. However, gene therapy may help determining the role of several genes in supporting fetal growth and/or avoiding its rejection experimentally and might further help to identify new targets of intervention. Gene therapy strategies to avoid fetal rejection may include the transfer and expression of cyto-protective molecules locally at the fetal-placental interface. In addition, the ex-vivo genetic modification of immune cells for tolerance induction is a novel and tempting approach. In this regard, we have confirmed the role of the cyto-protective and immunomodulatory molecule Heme Oxygenase-1 (HO-1), by treating animals undergoing abortion with an adenovirus coding for HO-1. Since the sole application of a control vector did not provoke deleterious effects in pregnancy outcome, we propose the use of experimental gene therapy for unveiling molecular and cellular pathways leading to pregnancy success.

  17. Review of fortified food and beverage products for pregnant and lactating women and their impact on nutritional status.

    PubMed

    Yang, Zhenyu; Huffman, Sandra L

    2011-10-01

    Fortified beverages and supplementary foods, when given during pregnancy, have been shown to have positive effects on preventing maternal anaemia and iron deficiency. Studies show that use of micronutrient fortified supplementary foods, especially those containing milk and/or essential fatty acids during pregnancy, increase mean birthweight by around 60-73 g. A few studies have also shown that fortified supplementary foods have impacts on increasing birth length and reducing preterm delivery. Fortification levels have ranged generally from 50% to 100% of the recommended nutrient intake (RNI). Iron, zinc, copper, iodine, selenium, vitamins A, D, E, C, B1, B2, B6, and B12, folic acid, niacin and pantothenic acid are important nutrients that have been included in fortified beverages and supplemental foods for pregnant and lactating women. While calcium has been shown to reduce the risk of pre-eclampsia and maternal mortality, calcium, phosphorus, potassium, magnesium and manganese can have negative impacts on organoleptic properties, so many products tested have not included these nutrients or have done so in a limited way. Fortified food supplements containing milk and essential fatty acids offer benefits to improving maternal status and pregnancy outcome. Fortified beverages containing only multiple micronutrients have been shown to reduce micronutrient deficiencies such as anaemia and iron deficiency.

  18. Antiphospohlipid syndrome in obstetrics.

    PubMed

    Danza, Alvaro; Ruiz-Irastorza, Guillermo; Khamashta, Munther

    2012-02-01

    Antiphospholipid syndrome is characterised by a variety of clinical and immunological manifestations. The clinical hallmarks of this syndrome are thrombosis and poor obstetric outcomes, including miscarriages, fetal loss and severe pre-eclampsia. The main antiphospholipid antibodies include lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I. The combination of aspirin and heparin is considered the standard of care for women with antiphospholipid syndrome and embryo-fetal losses; however, aspirin in monotherapy may have a place in women with recurrent early miscarriage. A good benefit-risk ratio of low-molecular-weight heparin in pregnancy thrombosis treatment has been reported. Warfarin must be avoided if possible throughout the first trimester of pregnancy. Adequate pregnancy management of women with antiphospholipid syndrome should include co-ordinated medical-obstetrical care, a close follow-up protocol and a good neonatal unit. Close blood pressure control and early detection of proteinuria, together with Doppler studies of the utero-placental circulation should be included in the management protocol.

  19. Seasonal variation and hypertensive disorders of pregnancy in eastern Sudan.

    PubMed

    Ali, A A; Adam, G K; Abdallah, T M

    2015-02-01

    The aim of this study was to investigate the seasonal variation and hypertensive disorders of pregnancy in eastern Sudan, in the period between January 2008 and December 2010. The medical files of women attending at Kassala hospital, eastern Sudan with hypertension, with or without proteinuria were retrospectively retrieved. The data of patients with hypertensive disorders of pregnancy were compared with a similar number of controls that were normotensive and non-proteinuric. During the study period, there were 9,578 deliveries; 153 patients had hypertensive disorders of pregnancy, yielding an incidence rate of 1.6%. Of all cases and controls (306), there were 183 (59.8%) deliveries in winter, 84 (27.5%) in summer and 39 (12.7%) in autumn. The highest rate of pre-eclampsia was in winter (1.1%) (CI = 1.1-2.7, OR = 1.7, p = 0.004) and the lowest rate was in autumn (0.2%) (CI = 0.4-1.8, OR = 0.8, p = 0.758.). Our study revealed significant association between the incidence of hypertensive disorders of pregnancy and the winter season (103 (67.3%) vs 80 (52.3%), p = 0.001). Thus, more attention in the winter season might reduce the morbidity and mortality of hypertensive disorders of pregnancy.

  20. Is oxytocin a maternal-foetal signalling molecule at birth? Implications for development.

    PubMed

    Kenkel, W M; Yee, J R; Carter, C S

    2014-10-01

    The neuropeptide oxytocin was first noted for its capacity to promote uterine contractions and facilitate delivery in mammals. The study of oxytocin has grown to include awareness that this peptide is a neuromodulator with broad effects throughout the body. Accumulating evidence suggests that oxytocin is a powerful signal to the foetus, helping to prepare the offspring for the extrauterine environment. Concurrently, the use of exogenous oxytocin or other drugs to manipulate labour has become common practice. The use of oxytocin to expedite labour and minimise blood loss improves both infant and maternal survival under some conditions. However, further investigations are needed to assess the developmental consequences of changes in oxytocin, such as those associated with pre-eclampsia or obstetric manipulations associated with birth. This review focuses on the role of endogenous and exogenous oxytocin as a neurochemical signal to the foetal nervous system. We also examine the possible developmental consequences, including those associated with autism spectrum disorder, that arise from exogenous oxytocin supplementation during labour.

  1. CPD-Education and self-assessment: Epilepsy and pregnancy.

    PubMed

    Crawford, P

    2001-04-01

    Pregnancies in women with epilepsy are high risk and need careful management by both the medical and obstetric teams due to the increased incidence of complications and adverse outcomes of pregnancy. By the time a pregnant woman with epilepsy presents, the foetus is virtually fully formed and the opportunity for altering drug treatment has passed. Women need to be counselled and told to seek advice about their anticonvulsant therapy should they wish to become pregnant. All major anticonvulsant drugs are teratogenic but the main risk to the developing foetus appears to be when the mother is on polytherapy especially if sodium valproate forms part of the combination. Folate supplements (5 mg) before conception are advisable. There appears to be a minor but significant increased risk of maternal complications in women with epilepsy such as hyperemesis gravidarum, pre-eclampsia and eclampsia, vaginal bleeding and premature labour. In the majority of women seizure control will not alter during pregnancy. Oral vitamin K should be given to the mother receiving enzyme-inducing antiepileptic drugs. Post-natal infant development: there is an increased risk of prematurity (9-11%), stillbirth, neonatal and perinatal death, haemorrhagic disease of the newborn, low Apgar scores and low birth weight (7-10%). Breast feeding: virtually all the anticonvulsant drugs are excreted in breast milk in low concentrations. Feeding difficulties, irritability and lethargy can occur. However, the benefits of breast feeding usually far outweigh any minor risks to the baby.

  2. [Labor induction with an unfavorable cervix by the modified Krause method].

    PubMed

    Benavides de la Garza, L; Cerda Hinojosa, J; Benavides de Anda, L

    1994-09-01

    When delivery induction with an unfavorable cervix, is required, the traditional conduct has been to use oxitocin and more recently prostaglandins as gel. The purpose of this report is to communicate the experience of a prospective work with a group of 48 patients with amenorrhea from 16 to 42.5 weeks of gestation with an unfavorable cervix. The idea was to modify cervical features in order to facilitate delivery induction in patients with the following diagnosis: 1, Prolonged pregnancy in 32 patients. 2. Severe pre-eclampsia in seven. 3. High blood pressure in five. 4. Intrauterine growth retardation in four. All the patients were evaluated with a Bishop index of three or less. The procedure consisted of introduction of a No. 14 or 16 Foley catheter through the cervical canal, filling the balloon with 30 ml, and simultaneous application of intravenous oxitocin controlled with an infusion pump. Cervical maturation was seen in all the patients, time was from 2 to 24 hours. In all the cases Bishop's index was greater than five after the procedure. Delivery via was vaginal in 26 patients, and cesarean section in 22. There were no infectious complications, nor other type in women nor in newborns. It was concluded that despite criticism, this procedure has shown to be useful, dependable, to mature the cervix, its is available for all gyneco-obstetricians and easy to carry out.

  3. A review of inter- and intraspecific variation in the eutherian placenta

    PubMed Central

    Gundling, William E.; Wildman, Derek E.

    2015-01-01

    The placenta is one of the most morphologically variable mammalian organs. Four major characteristics are typically discussed when comparing the placentas of different eutherian species: placental shape, maternal–fetal interdigitation, intimacy of the maternal–fetal interface and the pattern of maternal–fetal blood flow. Here, we describe the evolution of three of these features as well as other key aspects of eutherian placentation. In addition to interspecific anatomical variation, there is also variation in placental anatomy and function within a single species. Much of this intraspecific variation occurs in response to different environmental conditions such as altitude and poor maternal nutrition. Examinations of variation in the placenta from both intra- and interspecies perspectives elucidate different aspects of placental function and dysfunction at the maternal–fetal interface. Comparisons within species identify candidate mechanisms that are activated in response to environmental stressors ultimately contributing to the aetiology of obstetric syndromes such as pre-eclampsia. Comparisons above the species level identify the evolutionary lineages on which the potential for the development of obstetric syndromes emerged. PMID:25602076

  4. Effect of mutations in XPD(ERCC2) on pregnancy and prenatal development in mothers of patients with trichothiodystrophy or xeroderma pigmentosum.

    PubMed

    Tamura, Deborah; Khan, Sikandar G; Merideth, Melissa; DiGiovanna, John J; Tucker, Margaret A; Goldstein, Alisa M; Oh, Kyu-Seon; Ueda, Takahiro; Boyle, Jennifer; Sarihan, Mansi; Kraemer, Kenneth H

    2012-12-01

    The XPD(ERCC2) gene encodes a DNA helicase involved in DNA repair and transcription. Patients with mutations in XPD may have different autosomal recessive phenotypes including trichothiodystrophy (TTD) or xeroderma pigmentosum (XP). TTD patients have sulfur-deficient, brittle hair, short stature and developmental delay. In contrast, XP patients have freckle-like pigmentation and a greatly increased risk of sun-induced skin cancers. Mothers of TTD patients have been reported to have a high frequency of pregnancy and neonatal complications. We performed a molecular epidemiological study of 15 mothers of 17 TTD patients and 13 mothers of 17 XP patients, all with XPD mutations. We found that 94% (16/17) of the TTD pregnancies had pre-term delivery, pre-eclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, prematurity or low birth weight. None of the 17 XP pregnancies had these complications (P<0.001). As mutations in XPD may have differential effects on DNA repair and transcription, these observations should provide insights into the role of XPD in human pregnancy and fetal development.

  5. Evidence for No Significant Impact of Müllerian Anomalies on Reproductive Outcomes of Twin Pregnancy in Korean Women.

    PubMed

    Shim, Sohyun; Hur, Yoon-Mi; Kim, Da Hee; Seong, Seok Ju; Kim, Mi-La; Shin, Joong Sik

    2016-04-01

    The present article aimed to evaluate the impact of congenital Müllerian anomalies (MA) on twin pregnancy after 24 gestational weeks in Korean women. All records of twin pregnancies in a large maternity hospital in Korea between January 2005 and July 2013 were analyzed. Patients with monochorionic monoamniotic (MCMA) twins, non-Korean patients, patients with twins delivered prior to 24 gestational weeks, and patients with miscarriage of one fetus or intrauterine fetal death (IUFD) before 24 gestational weeks were excluded from data analysis. In total, 1,422 women with twin pregnancy were eligible for data analysis, including 17 (1.2%) who had a known congenital MA (septate uterus, bicornuate uterus, arcuate uterus, and unicornuate uterus). Except for the mode of conception, baseline demographics were similar between women with MA and those without MA. No significant differences were found in pregnancy outcomes of gestational age at delivery (p = .86), birth weight of smaller and larger twins (p = .54 and p = .65), and number of twins with birth weight <5th percentile for gestational age (p = .43).The rates of obstetrical complications such as pre-eclampsia, gestational diabetes mellitus (GDM), placenta previa, cerclage, IUFD, and postpartum hemorrhage were not significantly different between the two groups either. We concluded that the presence of congenital MA may not increase obstetrical risks in outcomes of pregnancy of twins delivered after 24 gestational weeks.

  6. [The Millennium project of the United Nations, focusing on adequate postpartum care to reduce maternal and neonatal mortality world-wide].

    PubMed

    Lagro, M G P; Stekelenburg, J

    2006-05-20

    One of the goals of the Millennium project of the United Nations is to reduce maternal and infant mortality. This includes adequate care for mothers and newborns during childbirth. Most maternal deaths occur during the post-partum period. Postpartum haemorrhage, eclampsia and sepsis are the main causes of maternal death. Preventive measures include active management of the third stage of labour, use of magnesium sulphate in pre-eclampsia, and implementing hygienic birth practices and the use of antibiotics, respectively. Major causes of neonatal mortality are pre- and dysmaturity, infections, congenital abnormalities and birth trauma, including asphyxia. The kangaroo-method can reduce morbidity in premature infants. The use of hygienic practices and antibiotics decreases the number of newborn deaths due to infection. Antiretroviral therapy is effective in preventing mother-to-child transmission of HIV. In many resource poor countries formula feeding is not feasible and the WHO advises exclusive breastfeeding for HIV positive women in these settings. A formula of 6 hours, 6 days, 6 weeks and 6 months after birth is recommended by the WHO to check the condition of mother and baby. This should be integrated in mother and child health clinics and also includes child vaccinations and counselling the mother on family planning and prevention of sexually transmitted diseases.

  7. Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature

    PubMed Central

    Chow, A K; Cena, J; Schulz, R

    2007-01-01

    Matrix metalloproteinases (MMPs) have been shown to play significant roles in a number of physiological as well as pathological processes. Best known to proteolyse components of the extracellular matrix, MMPs have recently been discovered to also target a growing list of proteins apart from these, both inside and outside the cell. MMPs have also been traditionally thought of as enzymes involved in chronic processes such as angiogenesis, remodelling and atherosclerosis on a days-week time-scale. However they are now understood to also act acutely in response to oxidative stress on a minutes time-scale on non-extracellular matrix substrates. This review focuses on the acute actions and both extracellular and intracellular targets of two prominent MMP family members, MMP-2 and -9, in cardiovascular diseases including ischaemia/reperfusion injury, inflammatory heart disease, septic shock and pre-eclampsia. Also discussed are various ways of regulating MMP activity, including post-translational mechanisms, the endogenous tissue inhibitors of metalloproteinases and pharmacological inhibitors. A comprehensive understanding of MMP biology is necessary for the development of novel pharmacological therapies to combat the impact of cardiovascular disease. PMID:17592511

  8. Maternal-fetal impact of vitamin D deficiency: a critical review.

    PubMed

    Weinert, Letícia Schwerz; Silveiro, Sandra Pinho

    2015-01-01

    Research into the extra-skeletal functions of vitamin D has been expanding in recent years. During pregnancy, maternal vitamin D status may be of concern because of the key role of this vitamin in fetal skeletal development and due to the association between hypovitaminosis D and adverse maternal-fetal outcomes. Therefore, the objective of this manuscript was to review the maternal-fetal impact of gestational vitamin D deficiency and the benefits of vitamin D supplementation during pregnancy. A literature search was performed in PubMed and Embase employing the following keywords: vitamin D deficiency, pregnancy, 25-hydroxyvitamin D, and hypovitaminosis D. All relevant articles in English language published since 1980 were analysed by the two authors. Neonatal complications derived from vitamin D deficiency include low birth weight, growth restriction, and respiratory tract infection. In the mother, vitamin D deficiency has been associated with altered glucose homeostasis and increased incidence of gestational diabetes mellitus, pre-eclampsia, and bacterial vaginosis. However, the current state of the evidence is controversial for some other endpoints and the actual benefit of vitamin D supplementation in pregnancy remains unclear. Additional longitudinal studies may clarify the actual impact of vitamin D deficiency during pregnancy, and randomised trials are required to define the benefits of vitamin D supplementation in reducing the incidence of adverse outcomes in the mother and infant.

  9. Monocyte Subpopulations from Pre-Eclamptic Patients Are Abnormally Skewed and Exhibit Exaggerated Responses to Toll-Like Receptor Ligands

    PubMed Central

    Al-ofi, Ebtisam

    2012-01-01

    The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14lowCD16+ monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14highCD16+ and CD14lowCD16+ monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP controls. These data suggest that PE monocytes are hyper-responsive to TLR ligands and this may contribute to exacerbation of the disease. PMID:22848746

  10. Monocyte subpopulations from pre-eclamptic patients are abnormally skewed and exhibit exaggerated responses to Toll-like receptor ligands.

    PubMed

    Al-ofi, Ebtisam; Coffelt, Seth B; Anumba, Dilly O

    2012-01-01

    The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14(low)CD16(+) monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14(high)CD16(+) and CD14(low)CD16(+) monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP controls. These data suggest that PE monocytes are hyper-responsive to TLR ligands and this may contribute to exacerbation of the disease.

  11. Fibrinogen, an endogenous ligand of Toll-like receptor 4, activates monocytes in pre-eclamptic patients.

    PubMed

    Al-ofi, Ebtisam; Coffelt, Seth B; Anumba, Dilly O

    2014-06-01

    Pre-eclampsia (PE) remains the leading cause of pregnancy-associated mortality and morbidity, urging the need for a better understanding of its aetiology and pathophysiological progression. A key characteristic of PE is a systemic, exaggerated, inflammatory condition involving abnormal cytokine levels in serum, altered immune cell phenotype and Th1/Th2-type immunological imbalance. However, it is unknown how this heightened inflammatory condition manifests. We previously reported increased expression of the lipopolysaccharide receptor, Toll-like receptor 4 (TLR4), on monocytes from PE patients compared with normotensive, pregnant patients (NP). This upregulation of TLR4 on PE monocytes was accompanied by a hyper-responsiveness to bacterial TLR4 ligands. To determine whether non-microbial, endogenous TLR4 ligands also activate monocytes from PE patients, we investigated the expression of host-derived TLR4 ligands and the response of monocytes to these endogenous ligands. Plasma levels of fibrinogen - but not fibronectin or heparan sulphate - were higher in PE patients than in NP. Exposure to fibrinogen was associated with significantly increased production of inflammatory cytokines by monocytes from PE patients. Interestingly, this effect was not observed with NP monocytes. Our findings suggest that the fibrinogen-TLR4 axis might play an important role in the atypical activation of monocytes observed in PE patients that may contribute to the exaggerated inflammatory condition.

  12. Effects of organic food consumption on human health; the jury is still out!

    PubMed Central

    Barański, Marcin; Rempelos, Leonidas; Iversen, Per Ole; Leifert, Carlo

    2017-01-01

    ABSTRACT The most recent systematic literature reviews and meta-analyses have indicated significant and nutritionally-relevant composition differences between organic and conventional foods. This included higher antioxidant, but lower cadmium and pesticide levels in organic crops, and higher omega-3 fatty acids concentrations in organic meat and dairy products. Also, results from a small number of human cohort studies indicate that there are positive associations between organic food consumption and reduced risk/incidence of certain acute diseases (e.g. pre-eclampsia, hypospadias) and obesity. Concerns about potential negative health impacts of organic food consumption (e.g. risks linked to lower iodine levels in organic milk) have also been raised, but are not currently supported by evidence from human cohort studies. However, there is virtually no published data from (1) long-term cohort studies focusing on chronic diseases (e.g. cardiovascular disease, diabetes, cancer, and neurodegenerative conditions) and (2) controlled human dietary intervention studies comparing effects of organic and conventional diets. It is therefore currently not possible to quantify to what extent organic food consumption may affect human health. PMID:28326003

  13. Does 'soluble' HLA-G really exist? Another twist to the tale.

    PubMed

    Sargent, I L

    2005-10-01

    HLA-G is thought to play a key role in implantation by modulating cytokine secretion to control trophoblast invasion and to maintain a local immunosuppressive state. It differs from other class I molecules in that the gene can be alternatively spliced to produce four membrane-bound (G1, G2, G3 and G4) and three soluble isoforms (G5, G6 and G7). The soluble isoforms have recently attracted attention as their levels may be diagnostic of poor trophoblast invasion in miscarriage or pre-eclampsia and the implantation potential of IVF embryos. Although the expression and function of HLA-G2, G3, G4 and G7 has previously been a matter of debate, until now it has been generally accepted that soluble HLA-G5 and HLA-G6 are both expressed and secreted by trophoblast. However, Blaschitz et al. (2005) have reinvestigated this question and come to the surprising conclusion that they are not. They have shown that trophoblast only expresses the membrane-bound HLA-G1 isoform and not soluble HLA-G5 and -G6. Furthermore, although soluble HLA-G could be found in trophoblast culture supernatants, it appears not to be derived by alternative splicing but by the cleavage of HLA-G1. The source of the soluble HLA-G may not matter from a diagnostic perspective, but these findings, if confirmed, have important implications for our understanding of the biology of HLA-G.

  14. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases

    PubMed Central

    Perrone, Serafina; Santacroce, Antonino; Picardi, Anna; Buonocore, Giuseppe

    2016-01-01

    Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity. PMID:27170927

  15. Antioxidants and fetal protection against ethanol teratogenicity. I. Review of the experimental data and implications to humans.

    PubMed

    Cohen-Kerem, Raanan; Koren, Gideon

    2003-01-01

    Ethanol is the most common human teratogen, and heavy drinking during pregnancy can result in serious adverse outcomes to the fetus. The cellular mechanisms by which ethanol induces damage in utero are not well understood, while induction of oxidative stress is believed to be one putative mechanism. Our objective is to review the data of antioxidant effects in experimental models of fetal alcohol syndrome. Prior to the description of the available experimental data, we will briefly review the mechanisms leading to ethanol-induced oxidative stress. Ethanol-induced oxidative damage to the fetus could be attenuated by a variety of antioxidants as was documented in whole animal and tissue culture studies. Experiments, retrieved from the literature search, are described and criticized. Although experimental data are still limited, the application of a treatment strategy that includes antioxidants is justified since antioxidant treatment in human pregnancy for pre-eclampsia was demonstrated to be safe and effective. The available experimental evidence and the safety of vitamins C and E in pregnancy suggest that experimental use of antioxidants in alcohol-consuming mothers should be seriously considered to reduce fetal alcohol damage.

  16. A pilot study using laser-based technique for non-invasive diagnostics of hypertensive conditions in mice

    NASA Astrophysics Data System (ADS)

    Litvinova, Karina S.; Ahmad, Shakil; Wang, Keqing; Rafailov, Ilya E.; Sokolovski, Sergei G.; Zhang, Lin; Rafailov, Edik U.; Ahmed, Asif

    2016-02-01

    Endothelial dysfunction is directly linked to preeclampsia, a maternal hypertensive condition that is life threating for both the mother and the baby. Epidemiological studies show that women with a history of pre-eclampsia have an elevated risk for cardiovascular disease. Here we report a new non-invasive diagnostic test for preeclampsia in mice that allows us to non-invasively assess the condition of the animals during the experiment and treatment in established models of preeclampsia. A laser-based multifunctional diagnostics system (LAKK-M) was chosen to carry out non-invasive analysis of multiple parameters. The device was used to simultaneously record the microcirculatory blood flow and oxygen saturation, as well as fluorescence levels of endogenous fluorophores. Preliminary experiments were conducted on adenoviral (Ad-)- mediated overexpression of sFlt-1 (Ad-sFlt-1) to mimic preeclampsialike symptoms in mice. The recorded data displayed the ability of the LAKK-M diagnostics device to detect significant differences in perfusion measurements between the control and Ad-sFlt-1 treatment. Preliminary results provide a potential avenue to employ these diagnostics technology to monitor and aid in maintaining control of live animal conditions throughout the experiment and treatment.

  17. Anticoagulant prophylaxis for placenta mediated pregnancy complications.

    PubMed

    Rodger, Marc A

    2011-02-01

    Thrombophilias are not yet established as a cause of the placenta-mediated pregnancy complications (pregnancy loss, pre-eclampsia, small for gestational age and placental abruption). A thrombophilia may be only one of many factors that lead to development of these complications. Our recent large systematic review of prospective cohort studies highlight that the association between thrombophilia and placenta mediated pregnancy complications is far from proven. The small step of previously describing an association in case control studies has led a large number of clinicians and opinion leaders to take the large leap of accepting this relationship as being causal and potentially treatable with anticoagulant interventions. Furthermore, while data in women with prior severe pre-eclpamsia, abruption and small for gestational age births without thrombophilia suggests some promise for anticoagulant prophylaxis to prevent complications in subsequent pregnancies in these women, in the absence of large well done and generalisable "no intervention" controlled studies adopting anticoagulant prophylaxis to prevent these complications is premature. The absence of strong evidence, coupled with the small potential for harm from anticoagulant prophylaxis suggests that these drugs should be considered experimental in thrombophilic and non-thrombophilic women with prior placenta mediated pregnancy complications.

  18. Meta-analysis of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications.

    PubMed

    Rodger, Marc A; Carrier, Marc; Le Gal, Grégoire; Martinelli, Ida; Perna, Annalisa; Rey, Evelyne; de Vries, J I P; Gris, Jean-Christophe

    2014-02-06

    A 35-year-old woman with recurrent severe placenta-mediated pregnancy complications in her 2 pregnancies asks: Will low-molecular-weight heparin help prevent recurrent placenta-mediated pregnancy complications in my next pregnancy? We performed a meta-analysis of randomized controlled trials (RCTs) comparing low-molecular-weight heparin (LMWH) vs no LMWH for the prevention of recurrent placenta-mediated pregnancy complications. We identified six RCTs that included a total of 848 pregnant women with prior placenta-mediated pregnancy complications. The primary outcome was a composite of pre-eclampsia (PE), birth of a small-for-gestational-age (SGA) newborn (<10th percentile), placental abruption, or pregnancy loss >20 weeks. Overall, 67 (18.7%) of 358 of women being given prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction, 0.52; 95% CI, 0.32 to 0.86; P = .01; I(2), 69%, indicating moderate heterogeneity). We identified similar relative risk reductions with LMWH for individual outcomes, including any PE, severe PE, SGA <10th percentile, SGA <5th percentile, preterm delivery <37 weeks, and preterm delivery <34 weeks with minimal heterogeneity. LMWH may be a promising therapy for recurrent, especially severe, placenta-mediated pregnancy complications, but further research is required.

  19. Nutritional management of the low birth weight/preterm infant in community settings: a perspective from the developing world.

    PubMed

    Imdad, Aamer; Bhutta, Zulfiqar A

    2013-03-01

    Globally, about 20 million infants are born with low birth weight (LBW; <2500 g). Of all LBW infants, approximately 95% are born in developing countries. The greatest incidence of LBW occurs in South-Central Asia; the second greatest is in Africa. The two main reasons for LBW are preterm birth (<37 weeks) and intrauterine growth restriction (IUGR), which are risk factors for increased morbidity and mortality in newborn infants. Maternal nutrition status is one of the most important risk factors for LBW/IUGR. Providing balanced protein energy and multiple micronutrient supplements to pregnant women will reduce incidence of IUGR. Calcium supplementation during pregnancy will reduce the incidence of pre-eclampsia and preterm birth in developing countries. Exclusive breastfeeding is protective for a mother and her infant and has been shown to reduce morbidity and mortality in infancy. Kangaroo mother care for preterm infants will reduce severe morbidity and mortality as well. Community-based intervention packages are among the most effective methods of reducing morbidity and mortality in mothers and children. Future research should focus on improving triage of preterm and IUGR infants. Exclusive breastfeeding should be promoted, and appropriate alternative food supplements should be provided when breastfeeding is not possible.

  20. Can we fix it? Evaluating the potential of placental stem cells for the treatment of pregnancy disorders.

    PubMed

    James, J L; Srinivasan, S; Alexander, M; Chamley, L W

    2014-02-01

    In pregnancy disorders such as pre-eclampsia, intrauterine growth restriction (IUGR) and recurrent miscarriage a poorly functioning placenta is thought to be a major component of the disease process. However, despite their prevalence, we currently have no way to fix dysfunctional placentae or directly treat these disorders. Over the past two decades our understanding of the role that stem cells play in organ development and regeneration has expanded rapidly, and over the past 5 years the therapeutic use of stem cells to both regenerate damaged tissues, and act as potent modulators of diseased microenvironments, has become a reality in many organs including the heart, kidney, liver, skin and eye. Over its short lifespan the placenta undergoes rapid and continuous growth and differentiation, meaning that placental 'organogenesis' only truly ends at delivery, and thus stem cells are likely to play important roles in placental function for the duration of pregnancy. Two populations of stem cells exist in the placenta that contribute to this on-going growth and differentiation: trophoblast stem cells and mesenchymal stem cells. This review will address our current understanding of how each of these stem cell populations contributes to successful placental function, how epithelial and mesenchymal stem cell populations are being translated to the clinic in other fields, and whether these advances can teach us anything about how placental stem cells could be used to fix faulty placentae in the future.

  1. Pregnancy outcomes and the effect of metformin treatment in women with polycystic ovary syndrome: an overview.

    PubMed

    Ghazeeri, Ghina S; Nassar, Anwar H; Younes, Zeina; Awwad, Johnny T

    2012-06-01

    This article is a review of the literature assessing pregnancy outcomes and the effect of metformin treatment among women with polycystic ovary syndrome (PCOS). A review of research published in English was undertaken using PubMed and MEDLINE databases. The weight of the available evidence suggests that pregnant women with PCOS are at an increased risk of developing gestational diabetes, hypertensive disorders of pregnancy, preterm birth and early pregnancy loss. Obesity is a contributory factor for the increased risk of gestational diabetes in this group of women and is estimated to affect 5-40% of pregnant women with PCOS. The prevalence of other obstetric complications is estimated at 10-30% for gestational hypertension, 8-15% for pre-eclampsia and 6-15% for preterm birth. The association between PCOS and early pregnancy loss may not be direct, wherein the presence of PCOS-associated hyperinsulinemia, leading to hyperandrogenemia, has been implicated in the pathophysiology of early pregnancy loss. Apart from the role of metformin in improving the metabolic consequences accompanying PCOS, it has been shown to improve pregnancy rates in women with PCOS who are resistant to clomiphene citrate. In conclusion, pregnancy in women with PCOS is associated with adverse obstetric outcomes (multiple adverse obstetric risk). Whether metformin should be administered throughout pregnancy still remains controversial. Further prospective studies that foster a larger number of participants and adjust for all potentially confounding factors are needed.

  2. Indications and outcome for obstetric patients' admission to intensive care unit: a 7-year review.

    PubMed

    Lataifeh, I; Amarin, Z; Zayed, F; Al-Mehaisen, L; Alchalabi, H; Khader, Y

    2010-05-01

    The objective of this retrospective study was to investigate the indications, interventions and clinical outcome of pregnant and newly delivered women admitted to the multidisciplinary intensive care unit at the King Abdullah University Hospital in Jordan over a 7-year period from January 2002 to December 2008. The collected data included demographic characteristics of the patients, mode of delivery, pre-existing medical conditions, reason for admission, specific intervention, length of stay and maternal outcome. A total of 43 women required admission to the intensive care unit (ICU), which represented 0.37% of all deliveries. The majority (95.3%) of patients were admitted to the ICU postpartum. The most common reasons for admissions were (pre)eclampsia (48.8%) and obstetric haemorrhage (37.2). The remainder included adult respiratory distress syndrome (6.9%), pulmonary embolism (2.3%) and neurological disorders (4.6%). Mechanical ventilation was required to support 18.6% of patients and transfusion of red blood cells was needed for 48.8% of patients. There were three maternal deaths (6.9%). A multidisciplinary team approach is essential to improve the management of hypertensive disorders and postpartum haemorrhage to achieve significant improvements in maternal outcome. A large, prospective study to know which women are at high risk of admission to the intensive care units and to prevent serious maternal morbidity and mortality is warranted.

  3. Predictors of Fetal and Maternal Outcome in the Crucible of Hepatic Dysfunction During Pregnancy

    PubMed Central

    Suresh, Indrajit; TR, Vijaykumar; HP, Nandeesh

    2017-01-01

    Background Hepatic dysfunction during pregnancy places both the mother and the fetus at risk. Investigations which are efficient, cost effective and easily available for prognostication are required to tackle this global problem. We studied the etiologies and evaluated investigations for predictive efficiency. Methods One hundred ninety-seven pregnant women with hepatic dysfunction during pregnancy were identified. All patients were followed up till 8 weeks after termination of pregnancy or death. Clinico-demographic, biochemical and hematological data were collected and analyzed. Results One hundred ninety-seven of 6,122 females had abnormal liver function tests. Pre-eclampsia (57%), eclampsia (19%), HELLP syndrome (8%), viral infection (6%), hyperemesis gravidarum (5%), intrahepatic cholestasis of pregnancy (4%), chronic liver disease (1%) and sepsis were encountered. There were 41 fetal deaths, 42% preterm deliveries, and NICU admission rate was 27%. Five maternal deaths occurred. Maternal anemia, thrombocytopenia, hyperbilirubinemia and coagulopathy were statistically significant in adverse fetal outcomes. Serum bilirubin performed better than INR as a predictor of both maternal and fetal outcomes. Conclusions Hepatic dysfunction during pregnancy is associated with adverse events for both the mother and the fetus and hypertensive disorders remain the major cause. Maternal bilirubin levels and INR have a role in predicting adverse feto-maternal outcome. PMID:28270873

  4. Identifying implementation bottlenecks for maternal and newborn health interventions in rural districts of the United Republic of Tanzania

    PubMed Central

    Peterson, Stefan; Marchant, Tanya; Mbaruku, Godfrey; Temu, Silas; Manzi, Fatuma; Hanson, Claudia

    2015-01-01

    Abstract Objective To estimate effective coverage of maternal and newborn health interventions and to identify bottlenecks in their implementation in rural districts of the United Republic of Tanzania. Methods Cross-sectional data from households and health facilities in Tandahimba and Newala districts were used in the analysis. We adapted Tanahashi’s model to estimate intervention coverage in conditional stages and to identify implementation bottlenecks in access, health facility readiness and clinical practice. The interventions studied were syphilis and pre-eclampsia screening, partograph use, active management of the third stage of labour and postpartum care. Findings Effective coverage was low in both districts, ranging from only 3% for postpartum care in Tandahimba to 49% for active management of the third stage of labour in Newala. In Tandahimba, health facility readiness was the largest bottleneck for most interventions, whereas in Newala, it was access. Clinical practice was another large bottleneck for syphilis screening in both districts. Conclusion The poor effective coverage of maternal and newborn health interventions in rural districts of the United Republic of Tanzania reinforces the need to prioritize health service quality. Access to high-quality local data by decision-makers would assist planning and prioritization. The approach of estimating effective coverage and identifying bottlenecks described here could facilitate progress towards universal health coverage for any area of care and in any context. PMID:26240459

  5. Complications in cesarean and non-cesarean deliveries: United States, 1980.

    PubMed Central

    Taffel, S M; Placek, P J

    1983-01-01

    Using 1980 National Hospital Discharge Survey data, complications reported for cesarean and non-cesarean deliveries coded by the Ninth Revision ICD-CM are compared. While over 16 per cent of all deliveries in 1980 were by C-section, 94 per cent of the deliveries where maternal-infant disproportion was noted were by C-section, and this complication was noted in one-fourth of all C-section deliveries. Similarly, where malposition or malpresentation of the fetus was evident, 59 per cent of the mothers were delivered by C-section, and this complication was noted in one-sixth of all C-section deliveries. C-sections were also associated with placenta praevia, pre-eclampsia, infections of the genito-urinary tract, anemia, multiple births, and were almost universal for mothers who had had a previous C-section delivery. Competing explanations for the rise in C-sections from 5.5 per cent of deliveries in 1970 to 16.5 per cent in 1980 are discussed in the context of these findings. PMID:6869637

  6. Magnesium Metabolism and its Disorders

    PubMed Central

    Swaminathan, R

    2003-01-01

    Magnesium is the fourth most abundant cation in the body and plays an important physiological role in many of its functions. Magnesium balance is maintained by renal regulation of magnesium reabsorption. The exact mechanism of the renal regulation is not fully understood. Magnesium deficiency is a common problem in hospital patients, with a prevalence of about 10%. There are no readily available and easy methods to assess magnesium status. Serum magnesium and the magnesium tolerance test are the most widely used. Measurement of ionised magnesium may become more widely available with the availability of ion selective electrodes. Magnesium deficiency and hypomagnesaemia can result from a variety of causes including gastrointestinal and renal losses. Magnesium deficiency can cause a wide variety of features including hypocalcaemia, hypokalaemia and cardiac and neurological manifestations. Chronic low magnesium state has been associated with a number of chronic diseases including diabetes, hypertension, coronary heart disease, and osteoporosis. The use of magnesium as a therapeutic agent in asthma, myocardial infarction, and pre-eclampsia is also discussed. Hypermagnesaemia is less frequent than hypomagnesaemia and results from failure of excretion or increased intake. Hypermagnesaemia can lead to hypotension and other cardiovascular effects as well as neuromuscular manifestations. Causes and management of hypermagnesaemia are discussed. PMID:18568054

  7. [Diabetes insipidus and pregnancy].

    PubMed

    Gutiérrez Cruz, Oswaldo; Careaga Benítez, Ricardo

    2007-04-01

    Diabetes insipidus is an uncommon pathology; its incidence varies from two to six cases in 100,000 pregnancies. It has multiple etiologies and it is classified in central and neurogenic. Patients with diabetes insipidus generally show intense thirst, polyuria, neurologic symptoms and hypernatremia. It does not seem to alter the patient's fertility. Diabetes insipidus is usually associated with pre-eclampsia, HELLP syndrome, and fatty liver disease of pregnancy. This is a report of a case seen at the Hospital General de Cholula, in Puebla, Mexico. A 19 year-old female, with 37.2 weeks of pregnancy, had a history of Langerhans cell histiocytosis since she was four years. Patient was treated with intranasal desmopressin until 2005. She went to an obstetric evaluation; laboratory and cabinet studies were obtained. A healthy 1900 g female was obtained through vaginal delivery, with a 7/9 Apgar score. We should be familiarized with this uncommon pathology because of its association with several obstetric emergencies.

  8. Advances in understanding and treating liver diseases during pregnancy: A review.

    PubMed

    Kamimura, Kenya; Abe, Hiroyuki; Kawai, Hirokazu; Kamimura, Hiroteru; Kobayashi, Yuji; Nomoto, Minoru; Aoyagi, Yutaka; Terai, Shuji

    2015-05-07

    Liver disease in pregnancy is rare but pregnancy-related liver diseases may cause threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia; haemolysis, elevated liver enzymes, and low platelets syndrome; acute fatty liver of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy. Recent basic researches have shown the various etiologies involved in this disease entity. With these advances, rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival. The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention. Therefore, correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis. Therefore, here we review and summarized recent advances in understanding the etiologies, clinical courses and management of liver disease in pregnancy. This information will contribute to physicians for diagnosis of disease and optimum management of patients.

  9. Acute liver failure, multiorgan failure, cerebral oedema, and activation of proangiogenic and antiangiogenic factors in a case of Marburg haemorrhagic fever.

    PubMed

    van Paassen, Judith; Bauer, Martijn P; Arbous, M Sesmu; Visser, Leo G; Schmidt-Chanasit, Jonas; Schilling, Stefan; Ölschläger, Stephan; Rieger, Toni; Emmerich, Petra; Schmetz, Christel; van de Berkmortel, Franchette; van Hoek, Bart; van Burgel, Nathalie D; Osterhaus, Albert D; Vossen, Ann Ctm; Günther, Stephan; van Dissel, Jaap T

    2012-08-01

    A woman developed Marburg haemorrhagic fever in the Netherlands, most likely as a consequence of being exposed to virus-infected bats in the python cave in Maramagambo Forest during a visit to Uganda. The clinical syndrome was dominated by acute liver failure with secondary coagulopathy, followed by a severe systemic inflammatory response, multiorgan failure, and fatal cerebral oedema. A high blood viral load persisted during the course of the disease. The initial systemic inflammatory response coincided with peaks in interferon-γ and tumour necrosis factor-α concentrations in the blood. A terminal rise in interleukin-6, placental growth factor (PlGF), and soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) seemed to suggest an advanced pathophysiological stage of Marburg haemorrhagic fever associated with vascular endothelial dysfunction and fatal cerebral oedema. The excess of circulating sVEGF-R1 and the high sVEGF-R1:PlGF ratio shortly before death resemble pathophysiological changes thought to play a causative part in pre-eclampsia. Aggressive critical-care treatment with renal replacement therapy and use of the molecular absorbent recirculation system appeared able to stabilise--at least temporarily--the patient's condition.

  10. Dizygotic twins discordant for early-onset Citrobacter koseri and group B streptococcal sepsis.

    PubMed

    Lin, Wei-Jen; Wang, Chih-Chien; Lo, Wen-Tsung; Chu, Mong-Ling; Lee, Chuen-Ming

    2005-05-01

    Early-onset neonatal sepsis is usually a multisystem fulminant illness with prominent respiratory symptoms, and typically the infant has acquired the organism from the maternal genital tract during the intrapartum period. In this article, we report a rare case of dizygotic twins where each individual suffered early-onset sepsis caused by a different pathogen. Group B streptococcal (GBS) sepsis was diagnosed in twin A 1 day after birth; sepsis and meningitis caused by Citrobacter koseri was diagnosed in twin B at the age of the 4 days. The mother developed pre-eclampsia and fever and the twins were delivered via cesarean section at 35 week's gestation. Twin A received ampicillin treatment for 14 days and recovered fully. Twin B was treated with ceftriaxone for 4 weeks and follow-up brain ultrasound revealed persistent enlargement of the bilateral-lateral ventricles. When empiric antibiotic is considered for the symptomatic twin of a sibling with early-onset GBS infection, samples of blood and cerebrospinal fluid (CSF) should be obtained for culture study before treatment. Adjustment of antibiotic treatment based on the results of cultures and CSF Gram stain and antibiotic susceptibility test is essential.

  11. Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews.

    PubMed

    Marchi, J; Berg, M; Dencker, A; Olander, E K; Begley, C

    2015-08-01

    Maternal obesity is linked with adverse outcomes for mothers and babies. To get an overview of risks related to obesity in pregnant women, a systematic review of reviews was conducted. For inclusion, reviews had to compare pregnant women of healthy weight with women with obesity, and measure a health outcome for mother and/or baby. Authors conducted full-text screening, quality assurance using the AMSTAR tool and data extraction steps in pairs. Narrative analysis of the 22 reviews included show gestational diabetes, pre-eclampsia, gestational hypertension, depression, instrumental and caesarean birth, and surgical site infection to be more likely to occur in pregnant women with obesity compared with women with a healthy weight. Maternal obesity is also linked to greater risk of preterm birth, large-for-gestational-age babies, foetal defects, congenital anomalies and perinatal death. Furthermore, breastfeeding initiation rates are lower and there is greater risk of early breastfeeding cessation in women with obesity compared with healthy weight women. These adverse outcomes may result in longer duration of hospital stay, with concomitant resource implications. It is crucial to reduce the burden of adverse maternal and foetal/child outcomes caused by maternal obesity. Women with obesity need support to lose weight before they conceive, and to minimize their weight gain in pregnancy.

  12. Three-dimensional ultrasound evaluation of the placenta.

    PubMed

    Hata, T; Tanaka, H; Noguchi, J; Hata, K

    2011-02-01

    Conventional two-dimensional (2D) ultrasound has been widely used for the evaluation of the placenta during pregnancy. This 2D ultrasound evaluation includes the morphology, anatomy, location, implantation, anomaly, size, and color/power and pulsed Doppler sonographic assessment of the placenta. The introduction of three-dimensional (3D) ultrasound would facilitate the novel assessment of the placenta, such as surface-rendered imaging and volume measurement. With the recent advances in 3D power Doppler (3DPD) ultrasound as well as quantitative 3DPD histogram analysis, quantitative and qualitative assessments of the vascularization and blood flow of the placenta have become feasible. These novel techniques may assist in the evaluation of the feto-placental function, and offer potential advantages relative to conventional 2D sonographic assessments. 3D ultrasound may be an important modality in future placental research, in the evaluation of feto-placental insufficiency in clinical practice, and in the prediction of fetal growth restriction and pre-eclampsia, although some limitations regarding the assessment of the placenta employing 3D ultrasound still remain unresolved.

  13. Thrombophilia and Damage of Kidney During Pregnancy

    PubMed Central

    Giovanni, Larciprete; Maria, Liumbruno Giancarlo; Mauro, Rongioletti; Carlotta, Montagnoli; Federica, Rossi; Fabrizio, Papa; Sheba, Jarvis; Giuseppe, Di Pierro; Alessandro, Bompiani; Elio, Cirese; Herbert, Valensise

    2011-01-01

    Objectives It’s known that heritable thrombophilias are a risk factor for the development of obstetrics complications associated to inadequate uterine-placental circulation, as pre-eclampsia/eclampsia, HELLP syndrome, placental abruption and intrauterine growth restriction (IUGR), however it was never investigated the role that they could have in the renal failure associated to such conditions. The purpose of this study is to evaluate if thrombophilia itself that predispose to a possible renal damage or if its occurrence determines a more severe involvement of the kidneys in the course of these obstetric pathologies. Methods In the study were enrolled 301 pregnant women, who carried a thrombophilic state, 125 of whom (B group) has had an obstetric complication. In all the women the renal function was assessed taking into consideration proteinuria, creatininaemia and hypalbuminaemia. Results Of the three parameters which have been considered as evidence of a severe renal involvement the hypalbuminaemia appears statistically significant compared to the controls. Even creatinaemia is significantly increased in pregnant women with an Anthithrombin deficiency, and increased levels are detected in women with Factor V Leiden. Conclusions In obstetric complications associated to thrombophilic state could be a more severe involvement of the kidney. PMID:22905298

  14. Pregnancy-triggered antiphospholipid syndrome in a patient with multiple late miscarriages.

    PubMed

    Honig, Arnd; Engel, Joerg B; Segerer, Sabine E; Kranke, Peter; Häusler, Sebastian; Würfel, Wolfgang

    2010-11-01

    Antiphospholipid syndrome (APS) is a multisystemic disorder of coagulation-causing thrombosis in the arterial and venous system as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery and pre-eclampsia. The disease is characterized by the autoimmune production of antibodies against phospholipid, a substance found in the cell membrane. We here report the case of a patient with four second trimester miscarriages, who apart from a heterozygous plasminogen activator-inhibitor-1 mutation, had no risk factors explaining her condition. In the subsequent pregnancy she was therefore put on low-molecular-weight heparin, aspirin and granulocyte colony-stimulating factor. Antiphospholipid antibodies (APL), which had been negative before gestation, increased and remained high throughout pregnancy, thus suggesting a pregnancy-induced or -aggravated APS. The patient was kept on the above-mentioned medication and delivered a healthy male baby by Caesarean section after an otherwise uneventful pregnancy. Thus, in order to diagnose and treat pregnancy-triggered APS in patients with unexplained recurrent miscarriage, screening for APL should also be performed at several time points after conception.

  15. Obstetric antiphospholipid syndrome: a recent classification for an old defined disorder.

    PubMed

    D'Ippolito, Silvia; Meroni, Pier Luigi; Koike, Takao; Veglia, Manuela; Scambia, Giovanni; Di Simone, Nicoletta

    2014-09-01

    Obstetric antiphospholipid syndrome (APS) is now being recognized as a distinct entity from vascular APS. Pregnancy morbidity includes >3 consecutive and spontaneous early miscarriages before 10weeks of gestation; at least one unexplained fetal death after the 10th week of gestation of a morphologically normal fetus; a premature birth before the 34th week of gestation of a normal neonate due to eclampsia or severe pre-eclampsia or placental insufficiency. It is not well understood how antiphospholipid antibodies (aPLs), beyond their diagnostic and prognostic role, contribute to pregnancy manifestations. Indeed aPL-mediated thrombotic events cannot explain the obstetric manifestations and additional pathogenic mechanisms, such as a placental aPL mediated complement activation and a direct effect of aPLs on placental development, have been reported. Still debated is the possible association between aPLs and infertility and the effect of maternal autoantibodies on non-vascular manifestations in the babies. Combination of low dose aspirin and unfractionated or low molecular weight heparin is the effective treatment in most of the cases. However, pregnancy complications, in spite of this therapy, can occur in up to 20% of the patients. Novel alternative therapies able to abrogate the aPL pathogenic action either by interfering with aPL binding at the placental level or by inhibiting the aPL-mediated detrimental effect are under active investigation.

  16. Getting too sweet: galectin-1 dysregulation in gestational diabetes mellitus.

    PubMed

    Blois, Sandra M; Gueuvoghlanian-Silva, Barbara Y; Tirado-González, Irene; Torloni, Maria R; Freitag, Nancy; Mattar, Rosiane; Conrad, Melanie L; Unverdorben, Laura; Barrientos, Gabriela; Knabl, Julia; Toldi, Gergely; Molvarec, Attila; Rose, Matthias; Markert, Udo R; Jeschke, Udo; Daher, Silvia

    2014-07-01

    Galectin-1 (gal-1) is a prototype carbohydrate-binding protein, whose dysregulation is associated with adverse pregnancy outcomes such as spontaneous abortion and pre-eclampsia. Furthermore, it is known that faulty gal-1 protein production or gene regulation can be caused by single-nucleotide polymorphisms in the LGALS1 gene. Gestational diabetes mellitus (GDM) is also an adverse pregnancy outcome and the most common metabolic disorder during gestation. However, gal-1 expression patterns during GDM remain largely unknown. Our aims were to define local and peripheral gal-1 expression patterns during pregnancy, and to investigate LGALS1 gene polymorphisms in GDM patients. Circulating gal-1 levels were determined by ELISA in GDM patients and normal pregnant controls, and LGALS1 gene polymorphisms were assessed for association with GDM. Placental tissues were collected from control and GDM term pregnancies to evaluate local gal-1 expression by immunofluorescence. Our results show that GDM is associated with a failure to increase circulating gal-1 levels during the second and third trimester, as well as overexpression of gal-1 in placental tissue. Additionally, the LGALS1 polymorphism rs4820294 was associated with the development of GDM. In pregnancies complicated by GDM, we observed gal-1 dysregulation both locally in the placenta and peripherally in the circulation. Furthermore, the association between the LGALS1 polymorphism and GDM may indicate a genetic contribution to this adverse pregnancy outcome.

  17. Essential basic and emergency obstetric and newborn care: from education and training to service delivery and quality of care.

    PubMed

    Otolorin, Emmanuel; Gomez, Patricia; Currie, Sheena; Thapa, Kusum; Dao, Blami

    2015-06-01

    Approximately 15% of expected births worldwide will result in life-threatening complications during pregnancy, delivery, or the postpartum period. Providers skilled in emergency obstetric and newborn care (EmONC) services are essential, particularly in countries with a high burden of maternal and newborn mortality. Jhpiego and its consortia partners have implemented three global programs to build provider capacity to provide comprehensive EmONC services to women and newborns in these resource-poor settings. Providers have been educated to deliver high-impact maternal and newborn health interventions, such as prevention and treatment of postpartum hemorrhage and pre-eclampsia/eclampsia and management of birth asphyxia, within the broader context of quality health services. This article describes Jhpiego's programming efforts within the framework of the basic and expanded signal functions that serve as indicators of high-quality basic and emergency care services. Lessons learned include the importance of health facility strengthening, competency-based provider education, global leadership, and strong government ownership and coordination as essential precursors to scale-up of high impact evidence-based maternal and newborn interventions in low-resource settings.

  18. Gene expression in term placentas is regulated more by spinal or epidural anesthesia than by late-onset preeclampsia or gestational diabetes mellitus

    PubMed Central

    Lekva, Tove; Lyle, Robert; Roland, Marie Cecilie Paasche; Friis, Camilla; Bianchi, Diana W.; Jaffe, Iris Z.; Norwitz, Errol R.; Bollerslev, Jens; Henriksen, Tore; Ueland, Thor

    2016-01-01

    Pre-eclampsia (PE) and gestational diabetes mellitus (GDM) are common complications of pregnancy, but the mechanisms underlying these disorders remain unclear. The aim was to identify the extent of altered gene expression in term placentas from pregnant women with late-onset PE and GDM compared to controls. RNAseq identified few significantly differentially regulated genes in placental biopsies between PE, GDM, or uncomplicated pregnancy (n = 10 each group). Five genes were altered in placentas from PE including 4 non-coding genes and Angiopoietin 2 (ANGPT2). No genes were significantly regulated by GDM. In contrast, many genes were significantly regulated by fetal, maternal and delivery-specific variables, particularly spinal and epidural anesthesia. We selected ANGPT2 and Chemokine (C-X-C motif) ligand 14 (CXCL14) to test with qPCR in a larger set of placentas (n = 475) and found no differences between the groups. However, regression analysis revealed a stronger association between placental ANGPT2 and CXCL14 mRNA expression and fetal, maternal and delivery-specific variables than diagnostic group. To conclude, the gene expression in term placentas are highly affected by fetal, maternal and delivery specific variables. Few regulated genes were found in late-onset PE and GDM placentas, which may suggest that these conditions could be more affected by maternal factors. PMID:27405415

  19. Severe maternal morbidity among immigrant women in the Netherlands: patients' perspectives.

    PubMed

    Jonkers, Marina; Richters, Annemiek; Zwart, Joost; Öry, Ferko; van Roosmalen, Jos

    2011-05-01

    This 2006 study investigated ethnicity-related factors contributing to sub-standard maternity care and the effects on severe maternal morbidity among immigrant women in the Netherlands. In-depth interviews were carried out with 40 immigrant and 10 native Dutch women. The immigrant women reported that health care providers often paid insufficient attention to their pregnancy-related complaints, especially in cases of pre-eclampsia. They also reported delays in receiving information about diagnosis and treatment. Obstetricians who reviewed 20 of these cases judged sub-standard care to have played a role in the development of complications in 16 of them. The women themselves had problems identifying medically significant complications, presenting their complaints to health care providers effectively, and taking an active role as patients. Even highly educated migrant women showed low health literacy skills in their interaction with doctors. Patients' perspectives are valuable as one of the tools to evaluate the quality of maternity care. Communication by maternal health professionals can be improved through more sensitivity to social factors that affect immigrant women's health problems. Women with limited health literacy should be empowered through education about danger signs in pregnancy and information about preferences and policies in obstetrics in the Netherlands. They should also be invited to participate in medical decision-making.

  20. The pathogenesis of eclampsia: the 'magnesium ischaemia' hypothesis.

    PubMed

    Newman, J C; Amarasingham, J L

    1993-04-01

    'Magnesium ischaemia' is a term used to denote the functional impairment of the ATP-dependent sodium/potassium and calcium pumps in the cell membranes and within the cell itself. The production of ATP and the functioning of these pumps is magnesium-dependent and is critically sensitive to acidosis. Zinc and iron deficiencies may secondarily impair these pumps and thus contribute to 'magnesium ischaemia' (as does acidosis). This term is two-dimensional at its simplest; it refers to a functional magnesium deficiency, whether actual or induced. It is argued that chronic acidosis is the most common inducing factor. This simple hypothesis can begin to unify diverse pathophysiologies: some spontaneous abortions, aspects of Type II and gestational diabetes and the curious observation that heroin addicts become diabetic. It can also unify clinical thinking about pregnancy-induced hypertension, pre-eclampsia/eclampsia and acute fatty liver of pregnancy, as well as the coagulopathy of pregnancy. It makes important predictions about perinatal morbidity and suggests that early supplementation might prevent much pregnancy-induced disease.

  1. [Pregnancy, labour, and puerperium in heroin addicted women, with reference to experience and the present state of knowledge (author's transl)].

    PubMed

    Stauber, M; Schwerdt, M; Hollenbach, B

    1982-05-01

    The mounting problems of drug addiction now also confront the obstetrician and pediatrician. 1/3 of the 60,000 addicts to opiates in the Federal Republic of Germany are women. Of these 80% are in the reproductive age group. Despite endocrine problems pregnancies do occur and are high risk pregnancies because of hepatitis, venereal disease, malnutrition, phlebitis, abscesses, premature deliveries, premature rupture of the membranes, malpresentations, dysmaturity, pre-eclampsia, and numerous other social and psychological problems. Because of the varying content of heroin on the black market the fetus runs the risk of acute overdose or withdrawal. Withdrawal results in extremely marked fetal movements, with increased oxygen consumption and a danger of intra-uterine asphyxia sometimes resulting in intra-uterine fetal death. Most newborns develop a withdrawal syndrome with irritability, high pitched cries, shivering, tachycardia, perspirations, fever and generalized seizures. The experience of the Department for Women for the Free University in Berlin-Charlottenburg are presented and compared to a review of the literature. The medical, social, and psychological aspects of the problem are discussed.

  2. Physiological relevance of GPCR oligomerization and its impact on drug discovery.

    PubMed

    Panetta, Rosemarie; Greenwood, Michael T

    2008-12-01

    The potentially large functional and physiological diversity of G-protein coupled receptor (GPCR) dimers has generated a great deal of excitement about the opportunity that dimerization provides for enabling novel drug discovery. The discovery of physiologically relevant GPCR dimers suggests that new drug targets for diseases such as schizophrenia and pre-eclampsia can be developed by targeting dimers. Most of the previous work on GPCR dimers made use of the overexpression of differentially tagged GPCRs in heterologous cell systems. Current emphasis on the development of physiologically relevant cell systems that endogenously express the appropriate combination of GPCR dimers and accessory proteins is leading to dramatic increases in our understanding of GPCR dimers. These and other new tools such as GPCR-specific antibodies will be required to develop GPCR dimer specific drugs. Given that ligands are available for only a small percentage of the large number of potentially druggable GPCRs, the use of GPCR dimers might provide the necessary targets to increase the breadth and depth of receptors available for therapeutic interventions.

  3. Placental Nutrient Transport and Intrauterine Growth Restriction

    PubMed Central

    Gaccioli, Francesca; Lager, Susanne

    2016-01-01

    Intrauterine growth restriction refers to the inability of the fetus to reach its genetically determined potential size. Fetal growth restriction affects approximately 5–15% of all pregnancies in the United States and Europe. In developing countries the occurrence varies widely between 10 and 55%, impacting about 30 million newborns per year. Besides having high perinatal mortality rates these infants are at greater risk for severe adverse outcomes, such as hypoxic ischemic encephalopathy and cerebral palsy. Moreover, reduced fetal growth has lifelong health consequences, including higher risks of developing metabolic and cardiovascular diseases in adulthood. Numerous reports indicate placental insufficiency as one of the underlying causes leading to altered fetal growth and impaired placental capacity of delivering nutrients to the fetus has been shown to contribute to the etiology of intrauterine growth restriction. Indeed, reduced expression and/or activity of placental nutrient transporters have been demonstrated in several conditions associated with an increased risk of delivering a small or growth restricted infant. This review focuses on human pregnancies and summarizes the changes in placental amino acid, fatty acid, and glucose transport reported in conditions associated with intrauterine growth restriction, such as maternal undernutrition, pre-eclampsia, young maternal age, high altitude and infection. PMID:26909042

  4. Prognostic value of creatine kinase BB-isoenzyme in high risk newborn infants.

    PubMed Central

    Ruth, V J

    1989-01-01

    Serum creatine kinase BB-isoenzyme (CK-BB) activity was studied on the first day of life in 31 acutely asphyxiated infants, 70 infants born after high risk pregnancies (pre-eclampsia or intrauterine growth retardation, or both), and 47 very low birthweight infants. Neuro-developmental evaluation was carried out at 2.2-2.5 years. Eight infants died with, and eight without, hypoxic-ischaemic lesions of the brain, 14 had cerebral palsy, 16 had mild motor impairment, six had developmental delay without motor impairment, and 96 were normal at follow up. Infants who died with brain injury had significantly higher CK-BB activity than infants with normal outcomes (geometric mean 12 U/l); the mean difference was 82 U/l with a 95% confidence interval from 31 to 219 U/l. CK-BB in infants with cerebral palsy and mild motor impairment (geometric means 12 and 15 U/l, respectively) were similar to controls. CK-BB activity after birth is predictive of neonatal death but not of neurological damage in survivors. PMID:2751331

  5. Blood Pressure Mobile Monitoring for Pregnant Woman Based Android System

    NASA Astrophysics Data System (ADS)

    Supriyanti, Retno; Erfayanto, Uji; Ramadani, Yogi; Murdyantoro, Eko; Widodo, Haris B.

    2016-01-01

    Currently, at least 18,000 women die every year in Indonesia due to pregnancy or childbirth. It means that every half hour a woman dies due to pregnancy or childbirth. As a result, every year 36,000 children became orphans. The high maternal mortality rate was put Indonesia on top in ASEAN. The main causes of maternal mortality are high-risk pregnancy. Mothers who have diseases like high blood pressure, pre-eclampsia, diabetes, hyperthyroidism, and already over 40 years old and infectious diseases such as rubella, hepatitis and HIV can be factors that lead to high-risk pregnancy. This paper will discuss the development of a blood pressure monitoring device that is suitable for pregnant women. It is based on convenience for pregnant women to get the equipment that is flexible with her presence. Results indicate that the equipment is in use daily support for pregnant women therefore, one of the causes of maternal mortality can be detected earlier.

  6. Immunohistochemical detection of terminal complement complex and S protein in normal and pre-eclamptic placentae.

    PubMed

    Tedesco, F; Radillo, O; Candussi, G; Nazzaro, A; Mollnes, T E; Pecorari, D

    1990-05-01

    Terminal complement complex and S protein were searched for in term placentae obtained from 13 women with normal pregnancy and 15 patients with moderate or severe form of pre-eclampsia. Terminal complement complex was found to localize in the fibrinoid material of the decidua of the basal plate, in the stroma of the chorionic villi and in the vessel walls, as subendothelial deposits. S protein had a quite different distribution, being detected in the syncytiotrophoblast located both in the chorionic villi and in the decidua of the basal plate (DBP) and also on the endothelial cells of fetal stem vessels. Mild deposits of C3 were found in the decidua of the basal plate and also in the stroma and on the basal membranes of the villi. Reactivity for C9 neoantigen was also observed in the cytoplasm of some cells, which were recognized to be macrophages by the presence in their cytoplasm of acid phosphatase and by their reaction with a monoclonal antibody specific for macrophages. Differences in complement deposition in normal and pre-eclamptic placentae were essentially quantitative. Possible mechanisms of complement activation are discussed.

  7. Immunohistochemical detection of terminal complement complex and S protein in normal and pre-eclamptic placentae.

    PubMed Central

    Tedesco, F; Radillo, O; Candussi, G; Nazzaro, A; Mollnes, T E; Pecorari, D

    1990-01-01

    Terminal complement complex and S protein were searched for in term placentae obtained from 13 women with normal pregnancy and 15 patients with moderate or severe form of pre-eclampsia. Terminal complement complex was found to localize in the fibrinoid material of the decidua of the basal plate, in the stroma of the chorionic villi and in the vessel walls, as subendothelial deposits. S protein had a quite different distribution, being detected in the syncytiotrophoblast located both in the chorionic villi and in the decidua of the basal plate (DBP) and also on the endothelial cells of fetal stem vessels. Mild deposits of C3 were found in the decidua of the basal plate and also in the stroma and on the basal membranes of the villi. Reactivity for C9 neoantigen was also observed in the cytoplasm of some cells, which were recognized to be macrophages by the presence in their cytoplasm of acid phosphatase and by their reaction with a monoclonal antibody specific for macrophages. Differences in complement deposition in normal and pre-eclamptic placentae were essentially quantitative. Possible mechanisms of complement activation are discussed. Images p238-a PMID:2357851

  8. Advanced Poincaré plot analysis differentiates between hypertensive pregnancy disorders.

    PubMed

    Seeck, A; Baumert, M; Fischer, C; Khandoker, A; Faber, R; Voss, A

    2011-10-01

    Hypertensive pregnancy disorders affect 6% to 8% of all pregnancies and can result in severe complications for the mother and the foetus of which pre-eclampsia (PE) has the worst perinatal outcome. Several studies suggested that the autonomic nervous system plays an important role in the process of developing hypertensive pregnancy disorders, especially PE. The aim of this retrospective study was to investigate whether women with PE could be differentiated from women with various other hypertensive pregnancy disorders, by employing an enhanced Poincaré plot analysis (PPA), the segmented Poincaré plot analysis (SPPA), to their beat-to-beat interval and blood pressure signals. Sixty-nine pregnant women with hypertensive disorders (29 PE, 40 with chronic or gestational hypertension) were included. The SPPA as well as the traditional PPA found significant differences between PE and other hypertensive disorders of diastolic blood pressure (p < 0.001 versus p < 0.001) but only the SPPA method revealed significant differences (p < 0.001) also of the systolic blood pressure. Further on, linear discrimination analysis demonstrated that indices derived from SPPA are more suitable for differentiation between chronic and gestational hypertension and PE than those from traditional PPA (area under the ROC curve 0.85 versus 0.69). Therefore this procedure could contribute to the differential diagnosis of hypertensive pregnancy disorders.

  9. [Hypertension during pregnancy--how to manage effectively?].

    PubMed

    Klocek, Marek; Czarnecka, Danuta

    2015-01-01

    Arterial hypertension affects 5-10% of all pregnant women and may be present in women with pre-existing primary or secondary chronic hypertension, and in women who develop newonset hypertension in the second half of pregnancy. Hypertensive disorders during pregnancy carry risks for the woman and the baby. Hypertension in pregnancy is diagnosed when SBP is > or = 140 or/and DBP > or = 90 mmHg. According to the guidelines, the decision to start pharmacological treatment of hypertension in pregnancy depends on the type of hypertension: in pregnancy-induced hypertension, developing after 20 weeks of pregnancy (with or without proteinuria) drug treatment is indicated when BP is > or = 140/90 mmHg, in chronic hypertension observed before pregnancy pharmacotherapy is indicated when BP is > or = 150/95 mmHg. For pregnant women with severe hypertension (> or =160 / 110 mmHg) antihypertensive therapy should be initiated immediately. Oral methyldopa, labetalol, other beta-adrenoreceptor blockers and calcium channel blockers are used most commonly. In pre-eclampsia parental labetalol, nitroglycerine, urapidyl and other drugs may also be needed.

  10. Serious foetal growth restriction is associated with reduced proportions of natural killer cells in decidua basalis.

    PubMed

    Eide, Irina P; Rolfseng, Toril; Isaksen, Christina V; Mecsei, Reidun; Roald, Borghild; Lydersen, Stian; Salvesen, Kjell A; Harsem, Nina K; Austgulen, Rigmor

    2006-03-01

    Extravillous trophoblasts are major participants in placental development and remodelling of spiral arteries. Trophoblast invasion is regulated by maternal immune cells, and abnormal leucocyte subpopulation composition has been reported in implantation failure. In pre-eclampsia (PE), with or without foetal growth restriction (FGR), superficial trophoblast invasion and insufficient remodelling of spiral arteries are common findings. In the present study, we have compared spiral artery remodelling and leucocyte composition in decidual tissue from 30 cases (PE=8, FGR=5, PE + FGR=17) and 31 controls. Six histological remodelling criteria were established, and each pregnancy obtained a remodelling score. Numbers of natural killer (NK) cells (CD56+), T cells (CD3+) and activated (CD25+ or CD69+) leucocytes were determined and related to total leucocyte (CD45+) numbers in serial sections. Cases demonstrated significantly impaired spiral artery remodelling, inappropriate placental growth and reduced NK cell proportions, as compared to controls (P=0.02, P<0.001 and P=0.01, respectively). Reduced NK cell proportion was primarily found in pregnancies complicated by FGR, with or without PE, and a significant positive correlation was observed between NK cell proportion, trophoblast infiltration and placental growth. Our in vivo observations support the hypothesized association between NK cells, impaired placental development and pathogenesis of PE/FGR.

  11. Pregnancy in Sickle Cell-Haemoglobin C (SC) Disease, A Retrospective Study of Birth Size and Maternal Weight Gain

    PubMed Central

    Thame, Minerva M.; Singh-Minott, Indira; Osmond, Clive; Melbourne-Chambers, Roxanne H.; Serjeant, Graham R

    2017-01-01

    Objective To assess pregnancy and fetal outcomes in Jamaican subjects with sickle cell-haemoglobin C (SC) disease. Study Design A retrospective chart review over 21 years (1992-2012) of all pregnancies in SC disease and a comparison group matched by gender and date of delivery in mothers with a normal haemoglobin (AA) phenotype at the University Hospital of the West Indies, Jamaica. There were 118 pregnancies in 81 patients with SC disease and 110 pregnancies in 110 in the normal comparison group. Corrections were made for repeat pregnancies from the same mother. Outcome measures included maternal weight at 20, 25, 30, 35 and 38 weeks gestation, maternal pregnancy complications, birth weight, head circumference and crown heel length and were used to analyse possible predictors of birth weight. Results First antenatal visits occurred later in women with SC disease, who also had lower haemoglobin level and lower systolic blood pressure. The prevalence of pregnancy-induced hypertension, pre-eclampsia, ante-partum or postpartum haemorrhage did not differ between genotypes. Maternal weight gain was significantly lower in SC disease and there was a significantly lower birth weight, head circumference, and gestational age. Conclusions Pregnancy in SC disease is generally benign but mothers had lower weight gain and lower birth weight babies, the difference persisting after correction for gestational age. PMID:27235631

  12. Role of leptin in pregnancy--a review.

    PubMed

    Sagawa, N; Yura, S; Itoh, H; Mise, H; Kakui, K; Korita, D; Takemura, M; Nuamah, M A; Ogawa, Y; Masuzaki, H; Nakao, K; Fujii, S

    2002-04-01

    Leptin is an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. In rodents, it also modulates glucose metabolism by increasing insulin sensitivity. We previously reported that leptin is produced by human placental trophoblasts. We also revealed that leptin gene expression in the placenta was augmented in severe pre-eclampsia, and suggested that placental hypoxia may play a role in this augmentation. Maternal plasma leptin levels correlated well with mean blood pressure, but not with body mass index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than those without IUGR (P< 0.05). We further examined the effects of hyperleptinemia on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin. In pregnant Tg mice, food intake was significantly less than non-Tg, and the fetal body weights were reduced to approximately 70 per cent of those of non-Tg. Resistin is a novel adipocyte-derived hormone that decreases insulin sensitivity and increases plasma glucose concentration, thus contributing the development of obesity-related type II diabetes mellitus. We recently found that resistin gene is expressed in the human placenta as well as adipose tissue. In this review, possible roles of placental leptin and resistin are discussed.

  13. Thrombophilia, thrombosis and pregnancy.

    PubMed

    Eldor, A

    2001-07-01

    The risk of venous thromboembolism (VTE) in pregnancy is 0.05-1.8%, six times greater than in the non-pregnant state, and pulmonary embolism remains the most common cause of maternal death. Maternal age, previous history of VTE, Caesarean section and the presence of thrombophilia, significantly increase the risk of VTE. Acquired or hereditary thrombophilia occur in almost two-thirds of women presenting with recurrent miscarriages, pre-eclampsia, intrauterine growth restriction, abruptio placentae, or stillbirth, which are associated with microvascular thrombosis in placental blood vessels. Women with VTE during pregnancy and especially those with thrombophilia require individualized management, based on the type of defect, the family history and the presence of additional risk factors. These factors are important in determining the dose and duration of antithrombotic therapy during pregnancy and the puerperium, and the thromboprophylactic strategy for future pregnancies. Oral anticoagulants are now seldom used during pregnancy because of their significant side effects. Low-molecular-weight heparins (LMWHs) are increasingly replacing unfractionated heparin in the prevention and treatment of VTE during pregnancy. LMWHs have also been shown to be effective in improving the outcome of pregnancy in women with previous obstetric complications.

  14. Unexplored territories in the nonsurgical patient: a look at pregnancy.

    PubMed

    Eldor, A

    2001-04-01

    Venous thromboembolism (VTE) remains the most common cause of maternal death during pregnancy and the puerperium. The risk is increased in women older than 35 years and those with obesity, previous VTE, operative delivery, and underlying thrombophilia. Anticoagulant therapy is indicated for short-term treatment of VTE and as thromboprophylaxis in high-risk patients. Warfarin is contraindicated during the first trimester because of fetotoxicity; unfractionated heparin (UFH) is associated with practical disadvantages and a risk of heparin-induced thrombocytopoenia (HIT) and osteoporosis with long-term use. Low-molecular-weight heparins (LMWHs) are convenient to use, do not cross the placenta, carry a lower risk of HIT and osteoporosis, and have been shown to be safe and effective during treatment of approximately 500 pregnant women. LMHWs are increasingly replacing UFH as the anticoagulant of choice during pregnancy; further studies are required to determine optimal therapeutic and thromboprophylactic doses. Women with inherited or acquired thrombophilia are at increased risk of severe pregnancy complications, including recurrent miscarriage, pre-eclampsia, fetal growth restriction, abruptio placentae, and stillbirth; uteroplacental microvascular thrombosis caused by thrombophilia appears to be the pathophysiologic link. LMWHs have been shown to improve pregnancy outcome in women with a history of obstetric complications and confirmed thrombophilia.

  15. Pregnancy as a critical window for blood pressure regulation in mother and child: programming and reprogramming.

    PubMed

    Paauw, N D; van Rijn, B B; Lely, A T; Joles, J A

    2017-01-01

    Pregnancy is a critical time for long-term blood pressure regulation in both mother and child. Pregnancies complicated by placental insufficiency, resulting in pre-eclampsia and intrauterine growth restriction, are associated with a threefold increased risk of the mother to develop hypertension later in life. In addition, these complications create an adverse intrauterine environment, which programmes the foetus and the second generation to develop hypertension in adult life. Female offspring born to a pregnancy complicated by placental insufficiency are at risk for pregnancy complications during their own pregnancies as well, resulting in a vicious circle with programmed risk for hypertension passing from generation to generation. Here, we review the epidemiology and mechanisms leading to the altered programming of blood pressure trajectories after pregnancies complicated by placental insufficiency. Although the underlying mechanisms leading to hypertension remain the subject of investigation, several abnormalities in angiotensin sensitivity, sodium handling, sympathetic activity, endothelial function and metabolic pathways are found in the mother after exposure to placental insufficiency. In the child, epigenetic modifications and disrupted organ development play a crucial role in programming of hypertension. We emphasize that pregnancy can be viewed as a window of opportunity to improve long-term cardiovascular health of both mother and child, and outline potential gains expected of improved preconceptional, perinatal and post-natal care to reduce the development of hypertension and the burden of cardiovascular disease later in life. Perinatal therapies aimed at reprogramming hypertension are a promising strategy to break the vicious circle of intergenerational programming of hypertension.

  16. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases.

    PubMed

    Perrone, Serafina; Santacroce, Antonino; Picardi, Anna; Buonocore, Giuseppe

    2016-05-08

    Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.

  17. Leptin in pregnancy.

    PubMed

    Henson, M C; Castracane, V D

    2000-11-01

    Leptin is a polypeptide hormone that aids in the regulation of body weight and energy homeostasis and is linked to a variety of reproductive processes in both animals and humans. Thus, leptin may help regulate ovarian development and steroidogenesis and serve as either a primary signal initiating puberty or as a permissive regulator of sexual maturation. Perhaps significantly, peripheral leptin concentrations, adjusted for adiposity, are dramatically higher in females than in males throughout life. During primate pregnancy, maternal levels that arise from adipose stores and perhaps the placenta increase with advancing gestational age. Proposed physiological roles for leptin in pregnancy include the regulation of conceptus growth and development, fetal/placental angiogenesis, embryonic hematopoiesis, and hormone biosynthesis within the maternal-fetoplacental unit. The specific localization of both leptin and its receptor in the syncytiotrophoblast implies autocrine and/or paracrine relationships in this endocrinologically active tissue. Interactions of leptin with mechanisms regulating pre-eclampsia and maternal diabetes have also been suggested. Collectively, therefore, reports suggest that a better understanding of the regulation of leptin and its role(s) throughout gestation may eventually impact those causes of human perinatal morbidity and mortality that are exacerbated by intrauterine growth retardation, macrosomia, placental insufficiency, or prematurity.

  18. Effects of organic food consumption on human health; the jury is still out!

    PubMed

    Barański, Marcin; Rempelos, Leonidas; Iversen, Per Ole; Leifert, Carlo

    2017-01-01

    The most recent systematic literature reviews and meta-analyses have indicated significant and nutritionally-relevant composition differences between organic and conventional foods. This included higher antioxidant, but lower cadmium and pesticide levels in organic crops, and higher omega-3 fatty acids concentrations in organic meat and dairy products. Also, results from a small number of human cohort studies indicate that there are positive associations between organic food consumption and reduced risk/incidence of certain acute diseases (e.g. pre-eclampsia, hypospadias) and obesity. Concerns about potential negative health impacts of organic food consumption (e.g. risks linked to lower iodine levels in organic milk) have also been raised, but are not currently supported by evidence from human cohort studies. However, there is virtually no published data from (1) long-term cohort studies focusing on chronic diseases (e.g. cardiovascular disease, diabetes, cancer, and neurodegenerative conditions) and (2) controlled human dietary intervention studies comparing effects of organic and conventional diets. It is therefore currently not possible to quantify to what extent organic food consumption may affect human health.

  19. Human leukocyte antigen-G in the male reproductive system and in seminal plasma.

    PubMed

    Larsen, Margit Hørup; Bzorek, Michael; Pass, Malene B; Larsen, Lise Grupe; Nielsen, Mette Weidinger; Svendsen, Signe Goul; Lindhard, Anette; Hviid, Thomas Vauvert F

    2011-12-01

    One of the non-classical human leukocyte antigen (HLA) class Ib proteins, HLA-G, is believed to exert important immunoregulatory functions, especially during pregnancy. The presence of HLA protein in paternal seminal fluid has been suggested to have an influence on the risk of developing pre-eclampsia. We have investigated whether HLA-G protein is present in human seminal plasma and in different tissue samples of the male reproductive system. Western blot technique and a soluble HLA-G (sHLA-G) assay were used to detect sHLA-G in human seminal plasma samples. Immunohistochemical staining was performed on paraffin-embedded tissue samples. We detected sHLA-G protein in seminal plasma, and HLA-G expression in normal testis and in epididymal tissue of the male reproductive system but not in the seminal vesicle. Furthermore, the results indicated a weak expression of HLA-G in hyperplastic prostatic tissue. In summary, several of the findings reported in this study suggest an immunoregulatory role of HLA-G in the male reproductive system and in seminal plasma.

  20. [Placental 3D Doppler angiography: current and upcoming applications].

    PubMed

    Duan, J; Perdriolle-Galet, E; Chabot-Lecoanet, A-C; Callec, R; Beaumont, M; Chavatte-Palmer, P; Tsatsaris, V; Morel, O

    2015-02-01

    The placental dysfunction, which seems to be caused by a defect of trophoblastic invasion and impaired uterine vascular remodeling since the first trimester, is responsible in a non-exclusive way for the chronic placental hypoxia, resulting secondarily in the intra-uterine growth restriction (IUGR) and/or pre-eclampsia (PE). The quality of utero-placental vasculature is essential for a proper fetal development and a successful progress of pregnancy. However, the in vivo assessment of placental vascularization with non-invasive methods is complicated by the small size of placental terminal vessel and its complex architecture. Moreover, imaging with contrast agent is not recommended to pregnant women. Until recently, the fetal and maternal vascularization could only be evaluated through pulse Doppler of uterine arteries during pregnancy, which has little clinical value for utero-placental vascularization defects assessment. Recently, a non-invasive study, without use of contrast agent for vasculature evaluation of an organ of interest has become possible by the development of 3D Doppler angiography technique. The objective of this review was to make an inventory of its current and future applications for utero-placental vasculature quantification. The main findings of the literature on the assessment of utero-placental vascularization in physiological situation and major placental vascular dysfunction pathologies such as PE and IUGR were widely discussed.

  1. Intravenous infusion of magnesium sulphate during subarachnoid anaesthesia in hip surgery and its effect on postoperative analgesia: our experience.

    PubMed

    Pastore, A; Lanna, M; Lombardo, N; Policastro, C; Iacovazzo, C

    2013-01-01

    The treatment of degenerative hip joint disease involves modern operative techniques and the use of prosthetic devices individualized on each patient. Being a surgery of considerable importance, great attention is always given by the anaesthesiologist to postoperative analgesia. In general, our goal is to limit the doses of NSAIDs, known to be associated with haemostasis interference and alteration of gastrointestinal apparatus; component of our baseline analgesic protocols after arthroplasty is morphine given parenterally. In order to steadily improve analgesic techniques, which directly impact on patient outcome, we experimented the use of a continuous infusion of magnesium sulphate during subarachnoid anaesthesia. Magnesium sulphate is the drug of choice in case of eclampsia, and pre-eclampsia (for the risk of evolution in eclampsia). According to the most recent findings, this drug has also analgesic properties: its use as an adjunct to analgesia is based on a non-competitive antagonism towards the NMDA receptor and on the blocking of calcium channels: these properties prevent the mechanisms of central sensitization due to nociceptive stimulation of peripheral nerves.

  2. Effect of subacute exposure to lead and estrogen on immature pre-weaning rat leukocytes

    SciTech Connect

    Villagra, R.; Tchernitchin, N.N.; Tchernitchin, A.N.

    1997-02-01

    Lead is an environmental pollutant known to cause damage to human health, affecting specially the central nervous system, reproductive organs, the immune system and kidney. From the perspective or reproduction, lead affects both men and women. Reported effects in women include infertility, miscarriage, pre-eclampsia, pregnancy hypertension and premature delivery. In experimental animals, lead affects female reproductive organs through different mechanisms. The heavy metal may interact at the enzyme level. It may interfere with the action of reproductive hormones at the target organ, modifying the activity of estrogen receptors in the pregnant uterus and inhibiting responses where estrogens play a role. Lead may induce imprinting mechanism, causing persistent changes in uterine estrogen receptors and ovary LH receptors following perinatal exposure. Finally, it may interfere at the level of hypothalamus-pituitary, decreasing pituitary response to growth hormone releasing factor, affecting levels of FSH and LH and increasing blood levels of glucocorticoids, which modify the action of estrogens in the uterus. This study examines the mechanisms of lead-induced interference with female reproductive and immune functions. 33 refs., 2 figs., 2 tabs.

  3. [Sodium restriction during pregnancy: an outdated advice].

    PubMed

    de Leeuw, P W; Peeters, L L

    1999-10-23

    Even in an early phase of pregnancy marked haemodynamic changes occur, including a fall in vascular resistance and blood pressure and a rise in cardiac output. To compensate for the increased intravascular capacity the kidney retains more sodium and water. Apparently, the set point of sodium homeostasis shifts to a higher level at the expense of an expansion of extracellular volume. Studies during the normal menstrual cycle have shown that these changes, albeit smaller, also occur during the luteal phase. These fluctuations with the menstrual cycle are less apparent if salt intake is low, suggesting that a high salt intake is needed to facilitate the process of sodium retention. In pregnancies complicated by hypertension and/or pre-eclampsia body fluid volumes are low with an enhanced tendency to retain sodium after a volume challenge. These data, together with the lack of an apparent benefit of sodium restriction, suggest that the practice of prescribing a low-salt diet to hypertensive pregnant women should be abandoned.

  4. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study.

    PubMed

    Kabbali, Nadia; Tachfouti, Nabil; Arrayhani, Mohammed; Harandou, Mustapha; Tagnaouti, Mounia; Bentata, Yassamine; Laouad, Inass; Ramdani, Benyounes; Bayahia, Rabia; Oualim, Zouhair; Houssaini, Tarik Sqalli

    2015-01-01

    Acute kidney injury (AKI) is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%). Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases), hemorrhagic shock (six cases) and septic events (five cases). We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6%) cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care.

  5. Post-partum acute kidney injury.

    PubMed

    Pahwa, Naresh; Bharani, Rajesh; Kumar, Ravindra

    2014-11-01

    To determine the risk factors, course of hospital stay and mortality rate among women with post-partum acute kidney injury (AKI), we studied (of 752 patients with AKI admitted to a tertiary care center during the study period between November 2009 and August 2012) 27 (3.59%) women with post-partum AKI. The data regarding age, parity, cause of renal failure, course of hospital stay and requirement of dialysis were recorded. Sepsis was the major cause (70.3%) of post-partum AKI. Other causes included disseminated intravascular coagulation (55.5%), pre-eclampsia/eclampsia (40.7%), ante- and post-partum hemorrhage (40.7% and 22.2%) and hemolytic anemia and elevated liver enzymes and low platelet count syndrome (29.6%); most patients had more than one cause of AKI. We found a very high prevalence (18.5%) of cortical necrosis in our study patients. A significant correlation was also found between the creatinine level on admission and the period of onset of disease after delivery. In conclusion, several factors are involved in causing post-partum AKI in our population, and sepsis was the most common of them.

  6. Pregnancy Weight Gain Limitation by a Supervised Nutritional Program Influences Placental NF-κB/IKK Complex Expression and Oxidative Stress

    PubMed Central

    Zerón, Hugo Mendieta; Flores, Alejandro Parada; Chávez, Araceli Amaya; Alanís, Adriana Garduño; Ferreyra, María del Carmen Colín; Benítez, Jonnathan Guadalupe Santillán; Castañeda, Violeta Saraí Morales; García, Ma. Victoria Domínguez

    2013-01-01

    Objective Nuclear factor kappa B (NF-κB) pathway and oxidative stress participate in endothelial dysfunction, which is one of the causes of pre-eclampsia. Among the human antioxidant mechanisms, there are the enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). Our aim was to measure NF-κB, its inhibitor (IKK) and oxidative stress in placenta and umbilical cord of pregnant women submitted to a supervised nutritional program. Methods Two groups were conformed: A) 14 pregnant women with individualized nutritional counseling, and B) 12 pregnant women without nutritional guidance. NF-κB and IKK were assessed by real time PCR (RT-PCR). Enzymatic activity of CAT, GPx, lipoperoxidation (LPO) and SOD were also evaluated. Results Pregnant women that followed a supervised nutritional program had lower levels of systolic (p=0.03) and diastolic pressure (p=0.043) although they were heavier than the control group (p=0.048). Among all the women, the Spearman correlation was positive between weight gain and placental NF-κB expression (1, p≤0.01). In the placenta, women with nutritional advice had lower enzymatic activity of GPx (p≤0.038) and showed a tendency of IKK to be higher than in women without a nutritional supervised program. Conclusion A supervised nutritional program in pregnancy offers a proven option to control weight gain, hypertension, NF-κB/IKK complex expression and oxidative stress reactions in the placenta. PMID:23772281

  7. Noncoding RNA-regulated gain-of-function of STOX2 in Finnish pre-eclamptic families

    PubMed Central

    Oudejans, Cees BM; Poutsma, Ankie; Michel, Omar J.; Thulluru, Hari K.; Mulders, Joyce; van de Vrugt, Henri J.; Sistermans, Erik A.; van Dijk, Marie

    2016-01-01

    The familial forms of early onset pre-eclampsia and related syndromes (HELLP) present with hypertension and proteinuria in the mother and growth restriction of the fetus. Genetically, these clinically similar entities are caused by different founder-dependent, placentally-expressed paralogous genes. All susceptibility genes (STOX1, lincHELLP, INO80B) identified so far are master control genes that regulate an essential trophoblast differentiation pathway, but act at different entry points. Many genes remain to be identified. Here we demonstrate that a long non-coding RNA (lncRNA) within intron 3 of the STOX2 gene on 4q35.1 acts as a permissive cis-acting regulator of alternative splicing of STOX2. When this lncRNA is mutated or absent, an alternative exon (3B) of STOX2 is included. This introduces a stop codon resulting in the deletion of a highly conserved domain of 64 amino acids in the C-terminal of the STOX2 protein. A mutation present within a regulatory region within intron 1 of STOX2 has the same effect after blocking with CRISPR technology: transcripts with exon 3B are upregulated. This proces appears related to transcriptional control by a chromatin-splicing adaptor complex as described for FGFR2. For STOX2, CHD5, coding for a chromodomain helicase DNA binding protein, qualifies as the chromatin modifier in this process. PMID:27555360

  8. PubMed Central

    Ménard, L; Gagnon, R

    1994-01-01

    OBJECTIVE: To determine, through a review of published articles, whether a higher prevalence of pregnancy complications is associated with residency in medicine. DATA SOURCES: Articles published between January 1980 and December 1992 found through a MEDLINE search using the MeSH terms "pregnancy complications" and "internship and residency" and through a review of the bibliographies of articles found. STUDY SELECTION: Of the 17 articles found, 6 contained data on the prevalence of pregnancy complications in residents. DATA EXTRACTION: The methodologic quality of the studies was evaluated systematically with the use of a grid. Data on the prevalence of the six most common pregnancy complications were retained. DATA SYNTHESIS: Four of the six articles had methodologic weaknesses (missing or inappropriate control groups, poorly controlled historical bias). The best study showed a higher prevalence of premature labour, pre-eclampsia and voluntary abortion in the residents than in the control subjects. CONCLUSIONS: It is difficult to draw definitive conclusions from a single study that met the criteria for methodologic quality. More and better-controlled studies involving larger numbers of subjects are needed. PMID:8199955

  9. Haplotype M2 in the annexin A5 (ANXA5) gene and the occurrence of obstetric complications.

    PubMed

    Tiscia, Giovanni; Colaizzo, Donatella; Chinni, Elena; Pisanelli, Daniela; Sciannamè, Natale; Favuzzi, Giovanni; Margaglione, Maurizio; Grandone, Elvira

    2009-08-01

    Inherited or acquired thrombophilias have been largely explored as a cause of pregnancy complications. However, pathogenesis of obstetric complications, as fetal loss and pregnancy-related hypertensive disorders is still partly unexplained. Recently, a common haplotype (M2) within the annexin A5 (ANXA5) gene has been described as a risk factor in recurrent fetal losses (RFL). It has been demonstrated to reduce the promoter activity of the ANXA5 promoter in luciferase reporter assays. Aim of this study was to investigate the prevalence of M2 haplotype in three different settings of women with previous obstetric complications: RFL, intra-uterine fetal death (IUFD) and pregnancy-related hypertension (gestational hypertension [GH] and pre-eclampsia [PE]). One hundred three patients with previous RFL, 54 with IUFD, 158 with hypertensive disease (67 GH, 91 PE) were investigated. As controls, 195 women from the same ethnic background with uneventful pregnancies were enrolled. Logistic regression, correcting for age, gravidity and parity showed that the ANXA5 haplotype is significantly and independently associated with the occurrence of RFL (3.1; 95%CI: 1.1-9.5; p = 0.047) and pregnancy-related hypertensive disorders (2.1; 95%CI: 1.2-3.5; p = 0.008). The M2 haplotype might be a new and relevant risk factor for obstetric complications.

  10. Adipokine Serum visfatin level in pregnancy induced hypertension and uncomplicated pregnancy

    PubMed Central

    Shaheen, Asmat; Nazli, Rubina; Fatima, Sadia; Ali, Roshan; Khan, Ihsanullah; Khattak, Salim

    2016-01-01

    Background and Objectives: Hypertensive disorder in pregnancy is the significant disease that badly affects the maternal and fetal prognosis and lead to higher mortality and morbidity in the prenatal period. Visfatin, potentially a new adipokine has emerged having high contribution in pathogenesis of pre-eclampsia. The objective of the study was to find the level of Visfatin in pregnancy induced hypertension and normal pregnant women. Methods: This study was carried out in tertiary care hospitals, Peshawar from March-October 2014. A total of 234 pregnant women (gestational age >20 weeks) were included in the study with distribution as Preeclampsia (PE=86), Eclampsia (E=74) and control (N=74). Blood was taken for measuring Visfatin level by Enzyme Linked Immunosorbent Assay (ELISA) technique. SPSS version 19 was used for statistical analysis. Student’s t test was performed to evaluate the mean differences in patients and control. Results: Serum level of visfatin was significantly higher in pregnancy induced hypertension when compared with control (P value<0.001).: Comparisons of mean value of visfatin with age group of 21-40 years, body mass index (BMI), primary parous and parity 2-4, gestational age of >36 weeks and both systolic and diastolic blood pressure were highly significant in pregnancy induced hypertension when compared with control (p value<0.001). Conclusion: Pregnancy induced hypertensive women showed increased level of serum Visfatin than normal pregnant women. PMID:28083037

  11. Review: Sexual dimorphism in the formation, function and adaptation of the placenta.

    PubMed

    Kalisch-Smith, J I; Simmons, D G; Dickinson, H; Moritz, K M

    2016-12-08

    Exposure of the embryo or fetus to perturbations in utero can result in intrauterine growth restriction, a primary risk factor for the development of adult disease. However, despite similar exposures, males and females often have altered disease susceptibility or progression from different stages of life. Fetal growth is largely mediated by the placenta, which, like the fetus is genetically XX or XY. The placenta and its associated trophoblast lineages originate from the trophectoderm (TE) of the early embryo. Rodent models (rat, mouse, spiny mouse), have been used extensively to examine placenta development and these have demonstrated the growth trajectory of the placenta in females is generally slower compared to males, and also shows altered adaptive responses to stressful environments. These placental adaptations are likely to depend on the type of stressor, duration, severity and the window of exposure during development. Here we describe the divergent developmental pathways between the male and female placenta contributing to altered differentiation of the TE derived trophoblast subtypes, placental growth, and formation of the placental architecture. Our focus is primarily genetic or environmental perturbations in rodent models which show altered placental responsiveness between sexes. We suggest that perturbations during early placental development may have greater impact on viability and growth of the female fetus whilst those occurring later in gestation may preferentially affect the male fetus. This may be of great relevance to human pregnancies which result from assisted reproductive technologies or complications such as pre-eclampsia and diabetes.

  12. Position of the Academy of Nutrition and Dietetics: Obesity, Reproduction, and Pregnancy Outcomes.

    PubMed

    Stang, Jamie; Huffman, Laurel G

    2016-04-01

    It is the position of the Academy of Nutrition and Dietetics that all women of reproductive age receive education about maternal and fetal risks associated with prepregnancy obesity, excessive gestational weight gain, and significant postpartum weight retention, including potential benefits of lifestyle changes. Behavioral counseling to improve dietary intake and physical activity should be provided to overweight and obese women, beginning in the preconception period and continuing throughout pregnancy, for at least 12 to 18 months postpartum. Weight loss before pregnancy may improve fertility and reduce the risk of poor maternal-fetal outcomes, such as preterm birth, gestational diabetes, gestational hypertension, pre-eclampsia, assisted delivery, and select congenital anomalies. Lifestyle interventions that moderate gestational weight gain may reduce the risk of poor pregnancy outcomes, such as gestational diabetes, gestational hypertension, large for gestational age, and macrosomia, as well as lower the risk for significant postpartum retention. Postpartum interventions that promote healthy diet and physical activity behaviors may reduce postpartum weight retention and decrease obesity-related risks in subsequent pregnancies. Analysis of the evidence suggests that there is good evidence to support the role of diet, physical activity, and behavior changes in promoting optimal weight gain during pregnancy; however, there is currently a relative lack of evidence in other areas related to reproductive outcomes.

  13. Probing the mechanical properties of TNF-α stimulated endothelial cell with atomic force microscopy

    PubMed Central

    Lee, Sei-Young; Zaske, Ana-Maria; Novellino, Tommaso; Danila, Delia; Ferrari, Mauro; Conyers, Jodie; Decuzzi, Paolo

    2011-01-01

    TNF-α (tumor necrosis factor-α) is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-α is elevated (> 1 pg/mL) in several pathologies, including rheumatoid arthritis, atherosclerosis, cancer, pre-eclampsia; in obese individuals; and in trauma patients. To test whether circulating TNF-α could induce similar alterations in different districts along the vascular system, three endothelial cell lines, namely HUVEC, HPMEC, and HCAEC, were characterized in terms of 1) mechanical properties, employing atomic force microscopy; 2) cytoskeletal organization, through fluorescence microscopy; and 3) membrane overexpression of adhesion molecules, employing ELISA and immunostaining. Upon stimulation with TNF-α (10 ng/mL for 20 h), for all three endothelial cells, the mechanical stiffness increased by about 50% with a mean apparent elastic modulus of E ~5 ± 0.5 kPa (~3.3 ± 0.35 kPa for the control cells); the density of F-actin filaments increased in the apical and median planes; and the ICAM-1 receptors were overexpressed compared with controls. Collectively, these results demonstrate that sufficiently high levels of circulating TNF-α have similar effects on different endothelial districts, and provide additional information for unraveling the possible correlations between circulating pro-inflammatory cytokines and systemic vascular dysfunction. PMID:21499414

  14. Extravillous trophoblast-associated ADAM12 exerts pro-invasive properties, including induction of integrin beta 1-mediated cellular spreading.

    PubMed

    Biadasiewicz, Katarzyna; Fock, Valerie; Dekan, Sabine; Proestling, Katharina; Velicky, Philipp; Haider, Sandra; Knöfler, Martin; Fröhlich, Camilla; Pollheimer, Jürgen

    2014-05-01

    ADAM12, consisting of a membrane-bound (ADAM12L) and a secreted (ADAM12S) form, is expressed exclusively in regenerating and developing tissue as well as in certain cancer types. Strong ADAM12 expression levels have been noticed in the human placenta, and deregulated ADAM12S levels were associated with various pregnancy-related disorders including pre-eclampsia and intrauterine growth restriction. However, the role of ADAM12 in trophoblast motility has not been investigated so far. Hence, the present study aimed to investigate the specific function of the protease by using different primary trophoblast cell models. Immunofluorescence and Western blot analyses of first trimester placental tissue and differentiating primary first trimester cytotrophoblasts (CTBs) indicated strong upregulation of both of the ADAM12 isoforms during extravillous trophoblast differentiation. Functional assays involving short interfering RNA (siRNA)-mediated knockdown studies in primary CTBs and first trimester explant cultures revealed a significant repression of trophoblast motility upon partial loss of ADAM12. Conversely, isoform-specific overexpression in the ADAM12-negative trophoblast cell line SGHPL-5 enhanced the invasive capacity of these cells. We further confirmed proteolytic activity of trophoblast-derived ADAM12S by demonstrating its potential to degrade insulin-like growth factor-binding protein 3. Finally, we suggest that ADAM12S exerts its pro-migratory function in trophoblasts by inducing integrin beta 1-mediated cellular spreading.

  15. The effect of diazepam administration during pregnancy or labor on the heart rate variability of the newborn infant.

    PubMed

    van Geijn, H P; Jongsma, H W; Doesburg, W H; Lemmens, W A; de Haan, J; Eskes, T K

    1980-03-01

    Maternal diazepam medication during labor reduces beat-to-beat variability of the fetal heart rate. In this study, the prolongation of the effect was examined in the newborn. The mother received diazepam: (A) during labor as a tranquilizer, (B) daily in low doses at the end of pregnancy, or (C) in high doses i.v. for (pre-)eclampsia. A control group had no analgesic or sedative during pregnancy or labor. The electrocardiogram (ECG) was recorded daily from each newborn during the first 6 days after birth. After preprocessing of the ECG, the median R-R interval, the long-term irregularity index (LTI index) and the interval difference index (ID index) were calculated. A cubic spline interpolation method was applied to compare the various groups with respect to these heart rate parameters. The median R-R interval showed no particular differences in trend for all groups. The LTI index was decreased in the first days after birth in the chronic diazepam (B), and in the diazepam infusion groups (C), but statistical significance was not reached. The ID index was significantly decreased in the first 1-2 days in the newborns of the acute and chronic diazepam group. In the diazepam infusion group, an even longer lasting effect was observed. Maternal diazepam medication affects the beat-to-beat variability in the newborn. The duration of the effect is dependent on dosage and route of administration.

  16. Obstetric nephrology: pregnancy in women with diabetic nephropathy--the role of antihypertensive treatment.

    PubMed

    Mathiesen, Elisabeth R; Ringholm, Lene; Feldt-Rasmussen, Bo; Clausen, Peter; Damm, Peter

    2012-12-01

    This review highlights factors of importance for the clinical care of pregnant women with pregestational diabetes and microalbuminuria or diabetic nephropathy with particular focus on the role of intensive antihypertensive treatment during pregnancy. Most information in the literature comes from women with type 1 diabetes and diabetic nephropathy, but this is probably also valid for women with type 2 diabetes. Careful counseling of women with diabetic nephropathy before pregnancy with estimation of the risk for the mother and fetus is important. Pregnancy does not result in worsening of kidney function in women with diabetic nephropathy and normal serum creatinine, but pregnancy complications such as pre-eclampsia and preterm delivery are common. Intensive metabolic control before and during pregnancy, low-dose aspirin from 12 gestational weeks onward, and intensive antihypertensive treatment are important. Methyldopa, labetalol, and nifedipine are regarded safe in pregnancy, whereas angiotensin converting enzyme inhibitors, AngII antagonists, or statins should be paused before pregnancy. Case series and pathophysiological studies support the use of a stringent goal for BP and albumin excretion in pregnant women with diabetic nephropathy. Screening for diabetic retinopathy before and during pregnancy is mandatory and laser treatment should be performed if indicated. Pregnancy outcome in women with diabetic nephropathy has improved considerably with a take-home-baby rate of approximately 95%. Further research on the benefits and risks of intensive antihypertensive treatment in this population is needed.

  17. Mothers in stress: consequences for the offspring.

    PubMed

    Knackstedt, Maike Katharina; Hamelmann, Eckard; Arck, Petra Clara

    2005-08-01

    No memories exist on one's time before birth. However, this does not imply that the developing fetus is not susceptible to external impulses. On the contrary, the fetus is extremely vulnerable e.g. to environmental challenges, and a wealth of data reveals that conditions in utero affect the health of the fetus before and after birth. Threats for the growing fetus include psychological challenges perceived by the mother, e.g. high levels of stress during pregnancy. However, stress experienced during pregnancy not only leads to pregnancy complications like miscarriage, pre-eclampsia, preterm parturition, low birth weight or major congenital malformations, stress also increases the risk of the child to develop diseases in the subsequent periods of life. This condition is termed fetal programming of adult disease. Programming agents seem to include growth factors, cytokines and hormones, all of which can be altered by stress. As a consequence, such 'stress-modified' systems of the offspring are more susceptible to environmental influences during later life, e.g. the development of atopic diseases upon exposure to antigens. The present review illuminates the complexity of stress perception on fetal programming focusing predominately on the onset of atopic diseases on the background of published evidence from immunology, endocrinology, neurobiology and neonatology.

  18. DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

    PubMed

    Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

    2014-09-01

    Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia.

  19. Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy

    PubMed Central

    Woudstra, Douglas M; Chandra, Sue; Hofmeyr, G Justus; Dowswell, Therese

    2014-01-01

    Background Pre-eclampsia is a relatively common complication of pregnancy. HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a severe manifestation of pre-eclampsia with significant morbidity and mortality for pregnant women and their children. Corticosteroids are commonly used in the treatment of HELLP syndrome in the belief that they improve outcomes. Objectives To determine the effects of corticosteroids on women with HELLP syndrome and their children. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 June 2010). Selection criteria Randomized controlled trials comparing any corticosteroid with placebo, no treatment, or other drug; or comparing one corticosteroid with another corticosteroid or dosage in women with HELLP syndrome. Data collection and analysis Two review authors assessed trial quality and extracted data independently. Main results Eleven trials (550 women) compared corticosteroids with placebo or no treatment. There was no difference in the risk of maternal death (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.28 to 3.21), maternal death or severe maternal morbidity (RR 0.27, 95% CI 0.03 to 2.12), or perinatal/infant death (RR 0.64, 95% CI 0.21 to 1.97). The only clear effect of treatment on individual outcomes was improved platelet count (standardized mean difference (SMD) 0.67, 95% CI 0.24 to 1.10). The effect on platelet count was strongest for women who commenced treatment antenatally (SMD 0.80, 95% CI 0.25 to 1.35). Two trials (76 women) compared dexamethasone with betamethasone. There was no clear evidence of a difference between groups in respect to perinatal/infant death (RR 0.95, 95% CI 0.15 to 6.17) or severe perinatal/infant morbidity or death (RR 0.64, 95% CI 0.27 to 1.48). Maternal death and severe maternal morbidity were not reported. In respect to platelet count, dexamethasone was superior to betamethasone (MD 6.02, 95% CI 1.71 to 10.33), both when treatment was

  20. Pregnancy-related acute kidney injury: An analysis of 165 cases

    PubMed Central

    Mahesh, E.; Puri, S.; Varma, V.; Madhyastha, P. R.; Bande, S.; Gurudev, K. C.

    2017-01-01

    Pregnancy-related acute kidney injury (PRAKI) contributes to 3–7% of overall acute kidney injury (AKI) cases in Indian subcontinent. The aim of this study was to determine the outcomes of PRAKI and risk factors associated with renal injury and maternal mortality. One hundred and sixty-five patients with PRAKI, seen at M. S. Ramaiah Medical College between 2005 and 2014, were included in this, observational study. AKI was analyzed in terms of maximal stage of renal injury attained as per Risk, Injury, Failure, Loss of function, and End-stage renal disease (RIFLE) criteria. Outcomes included requirement for renal replacement therapy (RRT), maternal, and fetal mortality. Incidence of PRAKI was 1.56%, and the mean age of the study population was 25 years. Fifty percent of the patients were diagnosed with PRAKI during their first pregnancy. PRAKI was observed most commonly in the postpartum period (60%), followed by third trimester (32%); as per RIFLE criteria, failure was seen in 36% and injury in 34%. Thirty percent of cases required RRT. Sepsis (59%), pre-eclampsia, and eclampsia (56%) were the leading causes of PRAKI, while sepsis was the leading cause of maternal mortality. Maternal and fetal mortality were 20% and 22%, respectively. In univariate analysis, shock, hemorrhage requiring transfusion of >5 units packed red blood cells, oliguria, and “Loss” category of RIFLE were significantly associated with mortality. Majority of the patients (57%) required Intensive Care Unit care with a mean duration of admission at 7.3 days, and 75% was diagnosed with AKI at the time of admission. We report the lowest incidence of PRAKI in contemporary Indian literature. PRAKI was associated with high maternal and fetal mortality, with sepsis being the leading cause. No association was noted between mortality and initial stages of RIFLE criteria. PMID:28356662

  1. Pregnancy outcome at 24-31 weeks' gestation: mortality.

    PubMed Central

    Wariyar, U; Richmond, S; Hey, E

    1989-01-01

    A study of all the mothers in the Northern region in 1983 whose pregnancies ended at between 24 and 31 weeks' gestation was undertaken. These pregnancies accounted for 1.3% of all the births and 44% of all the fetal and neonatal deaths in pregnancies that lasted more than 23 weeks. Most of the 389 singleton deliveries without malformations between 24 and 31 weeks were caused by spontaneous premature labour (n = 119, 31%), placental abruption (n = 79, 20%), pre-eclampsia (n = 56, 14%), and premature rupture of membranes (n = 48, 12%). The percentages of babies alive at the onset of delivery who survived the neonatal period were 66, 84, 78, and 73, respectively and the percentages of neonatal survivors with severe disabilities were 19, 13, 3, and 6, respectively. A further 65 (17%) of these babies died before the onset of labour for no obvious reason. The mode of delivery did not correlate with the outcome once the period of gestation at delivery was taken into account. The results highlight the inadequacy of the perinatal mortality index currently used in the United Kingdom, which identified 10.7 deaths/1000 registered births in 1983; 20% of the babies delivered at 24-31 weeks were excluded by this index because the birth went unregistered, as were 21% of all the babies born alive who died before discharge. An index that accounted for all babies weighing 500 g or more at birth irrespective of the period of gestation, and all neonatal (0-27 days) deaths, would be more appropriate and would bring reporting more into line with recommended international practice. PMID:2730121

  2. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome.

    PubMed

    Boomsma, C M; Eijkemans, M J C; Hughes, E G; Visser, G H A; Fauser, B C J M; Macklon, N S

    2006-01-01

    Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with many characteristic features, including hyperandrogenaemia, insulin resistance and obesity which may have significant implications for pregnancy outcomes and long-term health of the woman. This meta-analysis was conducted to evaluate the risk of pregnancy and neonatal complications in women with PCOS. Electronic databases were searched for the following MeSH headings: PCOS, hyperandrogenism, pregnancy outcome, pregnancy complications, diabetes mellitus, type II. A handsearch of human reproduction and fertility and sterility was also conducted. Studies in which pregnancy outcomes in women with PCOS were compared with controls were considered for inclusion in this meta-analysis. Fifteen of 525 identified studies were included, involving 720 women presenting with PCOS and 4505 controls. Women with PCOS demonstrated a significantly higher risk of developing gestational diabetes [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08], pregnancy-induced hypertension (OR 3.67; 95% CI: 1.98-6.81), pre-eclampsia (OR 3.47; 95% CI: 1.95-6.17) and preterm birth (OR 1.75; 95% CI: 1.16-2.62). Their babies had a significantly higher risk of admission to a neonatal intensive care unit (OR 2.31; 95% CI: 1.25-4.26) and a higher perinatal mortality (OR 3.07; 95% CI: 1.03-9.21), unrelated to multiple births. In conclusion, women with PCOS are at increased risk of pregnancy and neonatal complications. Pre-pregnancy, antenatal and intrapartum care should be aimed at reducing these risks.

  3. Platelet count and platelet indices in women with preeclampsia

    PubMed Central

    AlSheeha, Muneera A; Alaboudi, Rafi S; Alghasham, Mohammad A; Iqbal, Javed; Adam, Ishag

    2016-01-01

    Background Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia. Objective 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. Setting Qassim Hospital, Kingdom of Saudi Arabia. Design A case–control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls. Results 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 248.0×103/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 <248.010×103/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%). Conclusion PC <248.010×103/µL and PC to MPV ratio 31.2 are valid predictors of preeclampsia. PMID:27920548

  4. Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model.

    PubMed

    Thompson, Loren P; Pence, Laramie; Pinkas, Gerald; Song, Hong; Telugu, Bhanu P

    2016-12-01

    Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O2) from 20 day gestation until midterm (39-40 days) or term (60-65 days). At term, HPX (10.5% O2) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction.

  5. Animal models of human placentation--a review.

    PubMed

    Carter, A M

    2007-04-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however, substantive differences, including a different mode of implantation, a prominent yolk sac placenta, and fewer placental hormones in the mouse. Crucially, trophoblast invasion is very limited in the mouse and transformation of uterine arteries depends on maternal factors. The mouse also has a short gestation and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial, there is no trophoblast invasion of uterine vessels, and the immunology of pregnancy may be quite different. We conclude that continued research on non-human primates is needed to clarify embryonic-endometrial interactions. The interstitial implantation of human is unusual, but the initial interaction between trophoblast and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque, baboon and human. Non-human primates are therefore important models for understanding the dysfunction that has been linked to pre-eclampsia and fetal growth restriction. Models that are likely to be established in the wake of comparative genomics include the marmoset, tree shrew, hedgehog tenrec and nine-banded armadillo.

  6. Study protocol for the randomised controlled trial: combined multimarker screening and randomised patient treatment with ASpirin for evidence-based PREeclampsia prevention (ASPRE)

    PubMed Central

    O'Gorman, Neil; Wright, David; Rolnik, Daniel L; Nicolaides, Kypros H; Poon, Liona C

    2016-01-01

    Introduction Pre-eclampsia (PE) affects 2–3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. Prophylactic use of low-dose aspirin in women at risk for PE may substantially reduce the prevalence of the disease. Effective screening for PE requiring delivery before 37 weeks (preterm PE) can be provided by a combination of maternal factors, uterine artery Doppler, mean arterial pressure, maternal serum pregnancy-associated plasma protein A and placental growth factor at 11–13 weeks' gestation, with a detection rate of 75% at a false-positive rate of 10%. We present a protocol (V.6, date 25 January 2016) for the ASpirin for evidence-based PREeclampsia prevention (ASPRE) trial, which is a double-blinded, placebo-controlled, randomised controlled trial (RCT) that uses an effective PE screening programme to determine whether low-dose aspirin given to women from 11 to 13 weeks' gestation will reduce the incidence of preterm PE. Methods and analysis All eligible women attending for their first trimester scan will be invited to participate in the screening study for preterm PE. Those found to be at high risk of developing preterm PE will be invited to participate in the RCT. Further scans will be conducted for assessment of fetal growth and biomarkers. Pregnancy and neonatal outcomes will be collected and analysed. The first enrolment for the pilot study was in April 2014. As of April 2016, 26 670 women have been screened and 1760 recruited to the RCT. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. Trial registration number ISRCTN13633058. PMID:27354081

  7. Comparison of Normal and Pre-Eclamptic Placental Gene Expression: A Systematic Review with Meta-Analysis

    PubMed Central

    2016-01-01

    Pre-eclampsia (PE) is a serious multi-factorial disorder of human pregnancy. It is associated with changes in the expression of placental genes. Recent transcription profiling of placental genes with microarray analyses have offered better opportunities to define the molecular pathology of this disorder. However, the extent to which placental gene expression changes in PE is not fully understood. We conducted a systematic review of published PE and normal pregnancy (NP) control placental RNA microarrays to describe the similarities and differences between NP and PE placental gene expression, and examined how these differences could contribute to the molecular pathology of the disease. A total of 167 microarray samples were available for meta-analysis. We found the expression pattern of one group of genes was the same in PE and NP. The review also identified a set of genes (PE unique genes) including a subset, that were significantly (p < 0.05) down-regulated in pre-eclamptic placentae only. Using class prediction analysis, we further identified the expression of 88 genes that were highly associated with PE (p < 0.05), 10 of which (LEP, HTRA4, SPAG4, LHB, TREM1, FSTL3, CGB, INHA, PROCR, and LTF) were significant at p < 0.001. Our review also suggested that about 30% of genes currently being investigated as possibly of importance in PE placenta were not consistently and significantly affected in the PE placentae. We recommend further work to confirm the roles of the PE unique and associated genes, currently not being investigated in the molecular pathology of the disease. PMID:27560381

  8. Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?

    PubMed Central

    Miles, Brodie; Abdel-Ghaffar, Khaled A.; Gamal, Ahmed Y.; Baban, Babak; Cutler, Christopher W.

    2014-01-01

    The majority of risk factors for chronic inflammatory diseases are unknown. This makes personalized medicine for assessment, prognosis, and choice of therapy very difficult. It is becoming increasingly clear, however, that low-grade subclinical infections may be an underlying cause of many chronic inflammatory diseases and thus may contribute to secondary outcomes (e.g., cancer). Many diseases are now categorized as inflammatory-mediated diseases that stem from a dysregulation in host immunity. There is a growing need to study the links between low-grade infections, the immune responses they elicit, and how this impacts overall health. One such link explored in detail here is the extreme sensitivity of myeloid dendritic cells (mDCs) in peripheral blood to chronic low-grade infections and the role that these mDCs play in arbitrating the resulting immune responses. We find that emerging evidence supports a role for pathogen-induced mDCs in chronic inflammation leading to increased risk of secondary clinical disease. The mDCs that are elevated in the blood as a result of low-grade bacteremia often do not trigger a productive immune response, but can disseminate the pathogen throughout the host. This aberrant trafficking of mDCs can accelerate systemic inflammatory disease progression. Conversely, restoration of dendritic cell homeostasis may aid in pathogen elimination and minimize dissemination. Thus it would seem prudent when assessing chronic inflammatory disease risk to consider blood mDC numbers, and the microbial content (microbiome) and activation state of these mDCs. These may provide important clues (“the canary in the coal mine”) of high inflammatory disease risk. This will facilitate development of novel immunotherapies to eliminate such smoldering infections in atherosclerosis, cancer, rheumatoid arthritis, and pre-eclampsia. PMID:24478766

  9. Chronic infection during placental malaria is associated with up-regulation of cycloxygenase-2

    PubMed Central

    2010-01-01

    Background Placental malaria (PM) is associated with poor foetal development, but the pathophysiological processes involved are poorly understood. Cyclooxygenase (COX) and lipoxygenase (LOX) which convert fatty acids to prostaglandins and leukotrienes, play important roles in pregnancy and foetal development. COX-2, currently targeted by specific drugs, plays a dual role as it associates with both pre-eclampsia pathology and recovery during infection. The role of COX during PM was questioned by quantifying at delivery COX-1, COX-2, 15-LOX, and IL-10 expression in two groups of malaria infected and uninfected placenta. Methods Placental biopsies were collected at delivery for mRNA isolation and quantification, using real time PCR. Results COX-2 and IL-10 mRNAs increased mainly during chronic infections (nine- and five-times, respectively), whereas COX-1 transcripts remained constant. COX-2 over-expression was associated with a higher birth weight of the baby, but with a lower rate of haemoglobin of the mother. It was associated with a macrophage infiltration of the placenta and with a low haemozoin infiltration. In the opposite way, placental infection was associated with lower expression of 15-LOX mRNA. A high degree of haemozoin deposition correlates with low birth weight and decreased expression of COX-2. Conclusion These data provide evidence that COX-2 and IL-10 are highly induced during chronic infection of the placenta, but were not associated with preterm delivery or low birth weight. The data support the involvement of COX-2 in the recovery phase of the placental infection. PMID:20144201

  10. Zinc, copper and selenium in reproduction.

    PubMed

    Bedwal, R S; Bahuguna, A

    1994-07-15

    Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body. Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis. Defects in spermatozoa are frequently observed in the zinc-deficient rat. Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa. Zinc deficiency in the female can lead to such problems as impaired synthesis/secretion of (FSH) and (LH), abnormal ovarian development, disruption of the estrous cycle, frequent abortion, a prolonged gestation period, teratogenicity, stillbirths, difficulty in parturition, pre-eclampsia, toxemia and low birth weights of infants. The level of testosterone in the male has been suggested to play a role in the severity of copper deficiency. Copper-deficient female rats are protected against mortality due to copper deficiency, and the protection has been suggested to be provided by estrogens, since estrogens alter the subcellular distribution of copper in the liver and increase plasma copper levels by inducing ceruloplasmin synthesis. The selenium content of male gonads increases during pubertal maturation. Selenium is localized in the mitochondrial capsule protein (MCP) of the midpiece. Maximal incorporation in MCP occurs at steps 7 and 12 of spermatogenesis and uptake decreases by step 15. Selenium deficiency in females results in infertility, abortions and retention of the placenta. The newborns from a selenium-deficient mother suffer from muscular weakness, but the concentration of selenium during pregnancy does not have any effect on the weight of the baby or length of pregnancy. The selenium requirements of a pregnant and lactating mother are increased as a result of selenium transport to the fetus via

  11. The role of obesity in the development of polycystic ovary syndrome.

    PubMed

    Motta, Alicia Beatriz

    2012-01-01

    Polycystic Ovary Syndrome (PCOS) is one of the common endocrine diseases that affects women in their reproductive age. PCOS has diverse clinical implications that include reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, cardiovascular diseases) and psychological features (increased anxiety, depression and worsened quality of life). The exact patho-physiology of PCOS is complex and remains largely unclear. The prevalence of PCOS is estimated at 4-18%, depending on diverse factors discussed ahead. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and body weight. During the last decades, obesity and excess weight are major chronic diseases all around the word. Obesity increases some features of PCOS such as hyperandrogenism, hirsutism, infertility and pregnancy complications. Both obesity and insulin resistance increase diabetes mellitus type 2 and cardiovascular diseases. Moreover, obesity impairs insulin resistance and exacerbates reproductive and metabolic features of PCOS. It is well known that obesity is associated with anovulation, pregnancy loss and late pregnancy complications (pre-eclampsia, gestational diabetes). Obesity in PCOS is also linked to failure or delayed response to the various treatments including clomiphene citrate, gonadotropins and laparoscopic ovarian diathermy. It has been reported that, after losing as little as 5 % of initial body weight obese women with PCOS improved spontaneous ovulation rates and spontaneous pregnancy. Therefore, the weight loss prior to conception improves live birth rate in obese women with or without PCOS. The treatment of obesity may include lifestyle therapy (diet and exercise), pharmacological treatment and bariatric surgery. In summary, weight loss is considered the first-line therapy in obese women with PCOS. In the present review, the consequence and

  12. Inter-Pregnancy Weight Change and the Risk of Recurrent Pregnancy Complications

    PubMed Central

    Wallace, Jacqueline M.; Bhattacharya, Sohinee; Campbell, Doris M.; Horgan, Graham W.

    2016-01-01

    Women with specific adverse pregnancy outcomes in their first pregnancy may be receptive to inter-pregnancy weight management guidance aimed at preventing these complications reoccurring in subsequent pregnancies. Thus the association between inter-pregnancy weight change and the risk of recurrent pregnancy complications at the second pregnancy was investigated in a retrospective cohort study of 24,520 women with their first-ever and second consecutive deliveries in Aberdeen using logistic regression. Compared with women who were weight stable, weight loss (>2BMI units) between pregnancies was associated with an increased risk of recurrent small for gestational age (SGA) birth and elective Cesarean-section, and was protective against recurrent pre-eclampsia, placental oversize and large for gestational age (LGA) birth. Conversely weight gain (>2BMI units) between pregnancies increased the risk of recurrent gestational hypertension, placental oversize and LGA birth and was protective against recurrent low placental weight and SGA birth. The relationships between weight gain, and placental and birth weight extremes were evident only in women with a healthy weight at first pregnancy (BMI<25units), while that between weight gain and the increased risk of recurrent gestational hypertension was largely independent of first pregnancy BMI. No relationship was detected between inter-pregnancy weight change and the risk of recurrent spontaneous preterm delivery, labour induction, instrumental delivery, emergency Cesarean-section or postpartum hemorrhage. Therefor inter-pregnancy weight change impacts the risk of recurrent hypertensive disorders, SGA and LGA birth and women with a prior history of these specific conditions may benefit from targeted nutritional advice to either lose or gain weight after their first pregnancy. PMID:27145132

  13. Essential pre-pregnancy and pregnancy interventions for improved maternal, newborn and child health

    PubMed Central

    2014-01-01

    The statistics related to pregnancy and its outcomes are staggering: annually, an estimated 250000-280000 women die during childbirth. Unfortunately, a large number of women receive little or no care during or before pregnancy. At a period of critical vulnerability, interventions can be effectively delivered to improve the health of women and their newborns and also to make their pregnancy safe. This paper reviews the interventions that are most effective during preconception and pregnancy period and synergistically improve maternal and neonatal outcomes. Among pre-pregnancy interventions, family planning and advocating pregnancies at appropriate intervals; prevention and management of sexually transmitted infections including HIV; and peri-conceptual folic-acid supplementation have shown significant impact on reducing maternal and neonatal morbidity and mortality. During pregnancy, interventions including antenatal care visit model; iron and folic acid supplementation; tetanus Immunisation; prevention and management of malaria; prevention and management of HIV and PMTCT; calcium for hypertension; anti-Platelet agents (low dose aspirin) for prevention of Pre-eclampsia; anti-hypertensives for treating severe hypertension; management of pregnancy-induced hypertension/eclampsia; external cephalic version for breech presentation at term (>36 weeks); management of preterm, premature rupture of membranes; management of unintended pregnancy; and home visits for women and children across the continuum of care have shown maximum impact on reducing the burden of maternal and newborn morbidity and mortality. All of the interventions summarized in this paper have the potential to improve maternal mortality rates and also contribute to better health care practices during preconception and periconception period. PMID:25178042

  14. What health professionals should know about the health effects of air pollution and climate change on children and pregnant mothers

    PubMed Central

    Poursafa, Parinaz; Kelishadi, Roya

    2011-01-01

    BACKGROUND: Health professionals face the adverse health effects of climate change and air pollution in their practices. This review underscores the effects of these environmental factors on maternal and children's health, as the most vulnerable groups to climate change and air pollution. METHODS: We reviewed electronic databases for a search of the literature to find relevant studies published in English from 1990 to 2011. RESULTS: Environmental factors, notably climate change and air pollution influence children's health before conception and continue during pregnancy, childhood, and adolescence. Experts have suggested that such health hazards may represent the greatest public health challenge that humanity has faced. The accumulation of greenhouse gases such as carbon dioxide, primarily from burning fossil fuels, results in warming which has an impact on air pollution particularly on levels of ozone and particulates. Heat-related health effects include increased rates of pregnancy complications, pre-eclampsia, eclampsia, low birth weight, renal effects, vector-borne diseases as malaria and dengue, increased diarrheal and respiratory disease, food insecurity, decreased quality of foods (notably grains), malnutrition, water scarcity, exposures to toxic chemicals, worsened poverty, natural disasters and population displacement. Air pollution has many adverse health effects for mothers and children. In addition to short-term effects like premature labour, intrauterine growth retardation, neonatal and infant mortality rate, malignancies (notably leukaemia and Hodgkin lymphoma), respiratory diseases, allergic disorders and anaemia, exposure to criteria air pollutants from early life might be associated with increase in stress oxidative, inflammation and endothelial dysfunction which in turn might have long-term effects on chronic non-communicable diseases. CONCLUSIONS: Health professionals have an exclusive capability to help prevent and reduce the harmful effects of

  15. Global alteration in gene expression profiles of deciduas from women with idiopathic recurrent pregnancy loss

    PubMed Central

    Krieg, S.A.; Fan, X.; Hong, Y.; Sang, Q.-X.; Giaccia, A.; Westphal, L.M.; Lathi, R.B.; Krieg, A.J.; Nayak, N.R.

    2012-01-01

    Recurrent pregnancy loss (RPL) occurs in ∼5% of women. However, the etiology is still poorly understood. Defects in decidualization of the endometrium during early pregnancy contribute to several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction (IUGR), and are believed to be important in the pathogenesis of idiopathic RPL. We performed microarray analysis to identify gene expression alterations in the deciduas of idiopathic RPL patients. Control patients had one antecedent term delivery, but were undergoing dilation and curettage for current aneuploid miscarriage. Gene expression differences were evaluated using both pathway and gene ontology (GO) analysis. Selected genes were validated using quantitative reverse transcription–polymerase chain reaction (qRT–PCR). A total of 155 genes were found to be significantly dysregulated in the deciduas of RPL patients (>2-fold change, P < 0.05), with 22 genes up-regulated and 133 genes down-regulated. GO analysis linked a large percentage of genes to discrete biological functions, including immune response (23%), cell signaling (18%) and cell invasion (17.1%), and pathway analysis revealed consistent changes in both the interleukin 1 (IL-1) and IL-8 pathways. All genes in the IL-8 pathway were up-regulated while genes in the IL-1 pathway were down-regulated. Although both pathways can promote inflammation, IL-1 pathway activity is important for normal implantation. Additionally, genes known to be critical for degradation of the extracellular matrix, including matrix metalloproteinase 26 and serine peptidase inhibitor Kazal-type 1, were also highly up-regulated. In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage. PMID:22505054

  16. Development and validation of risk prediction model for venous thromboembolism in postpartum women: multinational cohort study

    PubMed Central

    Sultan, Alyshah Abdul; West, Joe; Grainge, Matthew J; Riley, Richard D; Tata, Laila J; Stephansson, Olof; Fleming, Kate M; Nelson-Piercy, Catherine; Ludvigsson, Jonas F

    2016-01-01

    Objective To develop and validate a risk prediction model for venous thromboembolism in the first six weeks after delivery (early postpartum). Design Cohort study. Setting Records from England based Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and data from Sweden based registry. Participants All pregnant women registered with CPRD-HES linked data between 1997 and 2014 and Swedish medical birth registry between 2005 and 2011 with postpartum follow-up. Main outcome measure Multivariable logistic regression analysis was used to develop a risk prediction model for postpartum venous thromboembolism based on the English data, which was externally validated in the Swedish data. Results 433 353 deliveries were identified in the English cohort and 662 387 in the Swedish cohort. The absolute rate of venous thromboembolism was 7.2 per 10 000 deliveries in the English cohort and 7.9 per 10 000 in the Swedish cohort. Emergency caesarean delivery, stillbirth, varicose veins, pre-eclampsia/eclampsia, postpartum infection, and comorbidities were the strongest predictors of venous thromboembolism in the final multivariable model. Discrimination of the model was similar in both cohorts, with a C statistic above 0.70, with excellent calibration of observed and predicted risks. The model identified more venous thromboembolism events than the existing national English (sensitivity 68% v 63%) and Swedish guidelines (30% v 21%) at similar thresholds. Conclusion A new prediction model that quantifies absolute risk of postpartum venous thromboembolism has been developed and externally validated. It is based on clinical variables that are available in many developed countries at the point of delivery and could serve as the basis for real time decisions on obstetric thromboprophylaxis. PMID:27919934

  17. Monitoring fetal maturation - objectives, techniques and indices of autonomic function.

    PubMed

    Hoyer, Dirk; Zebrowski, Jan; Cysarz, Dirk; Goncalves, Hernani; Pytlik, Adelina; Amorim-Costa, Celia; Bernardes, Joao; Ayres-de-Campos, Diogo; Witte, Otto; Schleussner, Ekkehard; Stroux, Lisa; Redman, Christopher; Georgieva, Antoniya; Payne, Stephen; Clifford, Gari; Signorini, Maria; Magenes, Giovanni; Andreotti, Fernando; Malberg, Hagen; Zaunseder, Sebastian; Lakhno, Igor; Schneider, Uwe

    2017-02-10

    Monitoring the fetal behavior does not only have implications for acute care but also for identifying developmental disturbances that burden the entire later life. The concept, of "fetal programming", also known as "developmental origins of adult disease hypothesis", e.g. applies for cardiovascular, metabolic, hyperkinetic, cognitive disorders. Since the autonomic nervous system is involved in all of those systems, cardiac autonomic control may provide relevant functional diagnostic and prognostic information. The fetal heart rate patterns (HRP) are one of the few functional signals in the prenatal period that relate to autonomic control and, therefore, is predestinated for its evaluation. The development of sensitive markers of fetal maturation and its disturbances requires the consideration of physiological fundamentals, recording technology and HRP parameters of autonomic control. Based on the ESGCO2016 special session on monitoring the fetal maturation we herein report the most recent results on: (i) functional fetal autonomic brain age score (fABAS), Recurrence Quantitative Analysis and Binary Symbolic Dynamics of complex HRP resolve specific maturation periods, (ii) magnetocardiography (MCG) based fABAS was validated for cardiotocography (CTG), (iii) 30 min recordings are sufficient for obtaining episodes of high variability, important for intrauterine growth restriction (IUGR) detection in handheld Doppler, (iv) novel parameters from PRSA to identify Intra IUGR fetuses, (v) Electrocardiographic (ECG) recordings allowed a stable heart beat detection in the maturation periods between 20 to 28 weeks of gestation only, (vi) correlation between maternal and fetal HRV is disturbed in pre-eclampsia. The reported novel developments significantly extend the possibilities for the established CTG methodology. Novel HRP indices improve the accuracy of assessment due to their more appropriate consideration of complex autonomic processes across the recording technologies

  18. Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - Liquid biopsies for monitoring complications of pregnancy.

    PubMed

    Truong, Grace; Guanzon, Dominic; Kinhal, Vyjayanthi; Elfeky, Omar; Lai, Andrew; Longo, Sherri; Nuzhat, Zarin; Palma, Carlos; Scholz-Romero, Katherin; Menon, Ramkumar; Mol, Ben W; Rice, Gregory E; Salomon, Carlos

    2017-01-01

    Our understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT) cells, modifying their bioactivity on endothelial cells (EC). Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™) was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation (<18 weeks) and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly higher in EVT cultured under 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, whilst exosomes cultured at 1% oxygen decreased EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of unique miRNAs in exosomes from EVT cultured at 1% oxygen and exosomes isolated from the circulation of mothers at early gestation, who later developed PE and SPTB. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically relevant biomarker of pregnancy complications.

  19. Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells – Liquid biopsies for monitoring complications of pregnancy

    PubMed Central

    Truong, Grace; Guanzon, Dominic; Kinhal, Vyjayanthi; Elfeky, Omar; Lai, Andrew; Longo, Sherri; Nuzhat, Zarin; Palma, Carlos; Scholz-Romero, Katherin; Menon, Ramkumar; Mol, Ben W.; Rice, Gregory E.; Salomon, Carlos

    2017-01-01

    Our understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT) cells, modifying their bioactivity on endothelial cells (EC). Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™) was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation (<18 weeks) and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly higher in EVT cultured under 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, whilst exosomes cultured at 1% oxygen decreased EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of unique miRNAs in exosomes from EVT cultured at 1% oxygen and exosomes isolated from the circulation of mothers at early gestation, who later developed PE and SPTB. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically relevant biomarker of pregnancy complications. PMID:28350871

  20. Sleep disordered breathing in pregnancy

    PubMed Central

    2015-01-01

    Key points Sleep disordered breathing (SDB) is common and the severity increases as pregnancy progresses. Frequent snoring, older age and high pre-pregnancy body mass index (>25 kg⋅m−2) could be reliable indicators for SDB in early pregnancy. SDB screening tools, including questionnaires, used in the nonpregnant population have poor predictive ability in pregnancy. Accumulating evidence suggests that SDB during pregnancy may be associated with increased risk of adverse pregnancy outcomes, including gestational diabetes and pre-eclampsia. However, the results should be interpreted cautiously because several studies failed to adjust for potential maternal confounders and have other study limitations. There are no pregnancy-specific practice guidelines for SDB treatment. Many clinicians and practices follow recommendations for the treatment in the general population. Women with pre-existing SDB might need to be reassessed, particularly after the sixth month of pregnancy, because symptoms can worsen with nasal congestion and weight gain. Educational aims To highlight the prevalence and severity of sleep disordered breathing (SDB) in the pregnant population. To inform readers about risk factors for SDB in pregnancy. To explore the impact of SDB on adverse maternal and fetal outcomes, and biological pathways for associated adverse maternal and fetal outcomes. To introduce current management options for SDB in pregnancy, including medical and behavioural approaches. Sleep disordered breathing (SDB) is very common during pregnancy, and is most likely explained by hormonal, physiological and physical changes. Maternal obesity, one of the major risk factors for SDB, together with physiological changes in pregnancy may predispose women to develop SDB. SDB has been associated with poor maternal and fetal outcomes. Thus, early identification, diagnosis and treatment of SDB are important in pregnancy. This article reviews the pregnancy-related changes affecting the

  1. A simple-potentiometric method for determination of acid and alkaline phosphatase enzymes in biological fluids and dairy products using a nitrophenylphosphate plastic membrane sensor.

    PubMed

    Hassan, Saad S M; Sayour, Hossam E M; Kamel, Ayman H

    2009-04-27

    A novel poly(vinyl chloride) matrix membrane sensor responsive to 4-nitrophenylphosphate (4-NPP) substrate is described, characterized and used for the potentiometric assay of acid (ACP) and alkaline (ALP) phosphatase enzymes. The sensor is based on the use of the ion-association complex of 4-NPP anion with nickel(II)-bathophenanthroline cation as an electroactive material and nitrophenyloctyl ether (NPOE) as a solvent mediator. The sensor displays good selectivity and stability and demonstrates a near-Nernstian response for 4-NPP over the concentration range 9.6x10(-6) to 1.0x10(-2) M with an anionic slope of 28.6+/-0.3 mV decade(-1) and a detection limit of 6.3x10(-6) M over the pH range 4.5-10. The sensor is used to measure the decrease of a fixed concentration of 4-NPP substrate as a function of acid and alkaline phosphatase enzyme activities at optimized conditions of pH and temperature. A linear relationship between the initial rate of 4-NPP substrate hydrolysis and enzyme activity holds over 0.05-3.0 and 0.03-3.4 IU L(-1) of ACP and ALP enzymes, respectively. Validation of the method by measuring the lower detection limit, range, accuracy, precision, within-day repeatability and between-day-variability reveals good performance characteristics of the proposed sensor. The sensor is used for the determination of acid and alkaline phosphatase enzyme activities in biological fluids of some patients suffering from alcoholic cirrhosis, acute myelocytic leukemia, pre-eclampsia and prostatic cancer. The sensor is also utilized for assessment of alkaline phosphatase enzyme in milk and dairy products. The results obtained agree fairly well with data obtained by the standard spectrophotometric methods.

  2. Spectrum of Factors Triggering Endothelial Dysfunction in PIH

    PubMed Central

    Jammalamadaga, Visala Sree

    2016-01-01

    Introduction Pre-eclampsia (PE) is a major cause of maternal and fetal/neonatal mortality and morbidity. The aetiology and pathogenesis of PE is yet to be completely understood. Evidence shows that, Endothelial Dysfunction (ED) plays a pivotal role in the genesis of this multi-system disorder that develops in PE and eclampsia. Aim To determine the circulating levels of factors Malondialdehyde (MDA), Ferric Reducing Ability of Plasma-α (FRAP), Tumour Necrosis Factor (TNF-α), sFlt-1, VEGF, PlGF, Nitric Oxide (NO) that influence the ED. Materials and Methods Study groups consisted of Normotensive pregnant women (N), preeclamptic women (PE) and eclamptic women (E) with 100 subjects in each group in the 3rd trimester of pregnancy. They were investigated for MDA, FRAP, TNF-α, sFlt-1, VEGF, PlGF, NO. Statistical analysis was done using Analysis of Variance (ANOVA). Results When compared to controls MDA, TNF-α, sFlt-1 levels were found to be significantly high and FRAP, VEGF, PIGF and NO levels were significantly low in PE and E group. E showed a significantly high level of MDA, TNF-α, sFlt-1 and low levels of FRAP, VEGF, PIGF, NO when compared to PE group. Conclusion Our study substantiated the fact, that oxidative stress, imbalance between anti-angiogenic factors and pro- angiogenic factors exists in Pregnancy Induced Hypertension (PIH) condition. This imbalance is directly related to the ED, the hallmark of PE. So oxidative stress, VEGF, PlGF and sFlt-1 can be used as markers to analyze the onset and progression of the disease. PMID:28208844

  3. Chronic sleep loss during pregnancy as a determinant of stress: impact on pregnancy outcome.

    PubMed

    Palagini, Laura; Gemignani, Angelo; Banti, Susanna; Manconi, Mauro; Mauri, Mauro; Riemann, Dieter

    2014-08-01

    Short sleep duration, poor sleep quality, and insomnia frequently characterize sleep in pregnancy during all three trimesters. We aimed: (i) to review the clinical evidence of the association between conditions of sleep loss during pregnancy and adverse pregnancy outcomes; and (ii) to discuss the potential pathophysiological mechanisms that may be involved. A systematic search of cross-sectional, longitudinal studies using Medline, Embase, and PsychINFO, and MeSH headings and key words for conditions of sleep loss such as 'insomnia', 'poor sleep quality', 'short sleep duration', and 'pregnancy outcome' was made for papers published between January 1, 1960 and July 2013. Twenty studies met inclusion criteria for sleep loss and pregnancy outcome: seven studies on prenatal depression, three on gestational diabetes, three on hypertension, pre-eclampsia/eclampsia, six on length of labor/type of delivery, eight on preterm birth, and three on birth grow/birth weight. Two main results emerged: (i) conditions of chronic sleep loss are related to adverse pregnancy outcomes; and (ii) chronic sleep loss yields a stress-related hypothalamic-pituitary-adrenal axis and abnormal immune/inflammatory, reaction, which, in turn, influences pregnancy outcome negatively. Chronic sleep loss frequently characterizes sleep throughout the course of pregnancy and may contribute to adverse pregnancy outcomes. Common pathophysiological mechanisms emerged as being related to stress system activation. We propose that in accordance to the allostatic load hypothesis, chronic sleep loss during pregnancy may also be regarded as both a result of stress and a physiological stressor per se, leading to stress 'overload'. It may account for adverse pregnancy outcomes and somatic and mental disorders in pregnancy.

  4. VEGF and its soluble receptor VEGFR-2 in hypertensive disorders during pregnancy: the Indian scenario.

    PubMed

    Rath, G; Tripathi, R

    2012-03-01

    Hypertensive disorders are the most common medical problem encountered during pregnancy due to defective angiogenesis during placental development. Vascular endothelial growth factor (VEGF) is one of the angiogenic growth factors that stimulates angiogenesis. The recombinant form of its soluble receptor VEGF receptor-2 (sVEGFR-2) has anti-angiogenic activity. However, there is a paucity of information on serum VEGF and sVEGFR-2 concentrations in different sub-groups of hypertensive disorders during pregnancy. In this cross-sectional study, we evaluated the concentrations and the diagnostic utility of VEGF and sVEGFR-2 in gestational hypertension (GH, n=90), pre-eclampsia (PE, n=180), eclampsia (n=90) and control (n=180) pregnancy at different gestations. VEGF levels were significantly higher in PE and eclamptic (median=19.53 pg ml(-1); 60.36 pg ml(-1), P=0.0001) groups as compared with the control ones (median=18 pg ml(-1)). But, the serum sVEGFR-2 levels were found to be significantly decreased from GH to eclampsia groups (median=5196; 3972 pg ml(-1)) as compared with control groups (median=7417 pg ml(-1)). As the gestation advanced, there was an inverse association in the serum concentrations of sVEGFR-2 among the control, GH, PE and eclampsia groups. At both 34 and >34 weeks of gestations, higher sensitivity and specificity were observed for sVEGFR-2 in differentiating GH (50.8, 50%; 76.6, 76.6%), PE (63, 63%; 90, 90%) and eclampsia (65, 66.6%; 90, 90%) from the control pregnancy. This upregulation of VEGF and downregulation of sVEGFR-2 concentrations in different study groups may be due to hypoxia and could be involved intimately in the pathogenesis of these disorders. This study may contribute in understanding etio-pathogenesis of different hypertensive disorders during pregnancy.

  5. Pregnancy-Associated Heart Failure: A Comparison of Clinical Presentation and Outcome between Hypertensive Heart Failure of Pregnancy and Idiopathic Peripartum Cardiomyopathy

    PubMed Central

    Ntusi, Ntobeko B. A.; Badri, Motasim; Gumedze, Freedom; Sliwa, Karen; Mayosi, Bongani M.

    2015-01-01

    Aims There is controversy regarding the inclusion of patients with hypertension among cases of peripartum cardiomyopathy (PPCM), as the practice has contributed significantly to the discrepancy in reported characteristics of PPCM. We sought to determine whether hypertensive heart failure of pregnancy (HHFP) (i.e., peripartum cardiac failure associated with any form of hypertension) and PPCM have similar or different clinical features and outcome. Methods and Results We compared the time of onset of symptoms, clinical profile (including electrocardiographic [ECG] and echocardiographic features) and outcome of patients with HHFP (n = 53; age 29.6 ± 6.6 years) and PPCM (n = 30; age 31.5 ± 7.5 years). The onset of symptoms was postpartum in all PPCM patients, whereas it was antepartum in 85% of HHFP cases (p<0.001). PPCM was more significantly associated with the following features than HHFP (p<0.05): twin pregnancy, smoking, cardiomegaly with lower left ventricular ejection fraction on echocardiography, and longer QRS duration, QRS abnormalities, left atrial hypertrophy, left bundle branch block, T wave inversion and atrial fibrillation on ECG. By contrast, HHFP patients were significantly more likely (p<0.05) to have a family history of hypertension, hypertension and pre-eclampsia in a previous pregnancy, tachycardia at presentation on ECG, and left ventricular hypertrophy on echocardiography. Chronic heart failure, intra-cardiac thrombus and pulmonary hypertension were found significantly more commonly in PPCM than in HHFP (p<0.05). There were 5 deaths in the PPCM group compared to none among HHFP cases (p = 0.005) during follow-up. Conclusion There are significant differences in the time of onset of heart failure, clinical, ECG and echocardiographic features, and outcome of HHFP compared to PPCM, indicating that the presence of hypertension in pregnancy-associated heart failure may not fit the case definition of idiopathic PPCM. PMID:26252951

  6. Alterations in Polyadenylation and Its Implications for Endocrine Disease

    PubMed Central

    Rehfeld, Anders; Plass, Mireya; Krogh, Anders; Friis-Hansen, Lennart

    2013-01-01

    Introduction: Polyadenylation is the process in which the pre-mRNA is cleaved at the poly(A) site and a poly(A) tail is added – a process necessary for normal mRNA formation. Genes with multiple poly(A) sites can undergo alternative polyadenylation (APA), producing distinct mRNA isoforms with different 3′ untranslated regions (3′ UTRs) and in some cases different coding regions. Two thirds of all human genes undergo APA. The efficiency of the polyadenylation process regulates gene expression and APA plays an important part in post-transcriptional regulation, as the 3′ UTR contains various cis-elements associated with post-transcriptional regulation, such as target sites for micro-RNAs and RNA-binding proteins. Implications of alterations in polyadenylation for endocrine disease: Alterations in polyadenylation have been found to be causative of neonatal diabetes and IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked) and to be associated with type I and II diabetes, pre-eclampsia, fragile X-associated premature ovarian insufficiency, ectopic Cushing syndrome, and many cancer diseases, including several types of endocrine tumor diseases. Perspectives: Recent developments in high-throughput sequencing have made it possible to characterize polyadenylation genome-wide. Antisense elements inhibiting or enhancing specific poly(A) site usage can induce desired alterations in polyadenylation, and thus hold the promise of new therapeutic approaches. Summary: This review gives a detailed description of alterations in polyadenylation in endocrine disease, an overview of the current literature on polyadenylation and summarizes the clinical implications of the current state of research in this field. PMID:23658553

  7. Placental Microparticles and MicroRNAs in Pregnant Women with Plasmodium falciparum or HIV Infection

    PubMed Central

    Moro, Laura; Bardají, Azucena; Macete, Eusebio; Barrios, Diana; Morales-Prieto, Diana M.; España, Carolina; Mandomando, Inacio; Sigaúque, Betuel; Dobaño, Carlota; Markert, Udo R.; Benitez-Ribas, Daniel; Alonso, Pedro L.; Menéndez, Clara; Mayor, Alfredo

    2016-01-01

    Background During pregnancy, syncytiotrophoblast vesicles contribute to maternal tolerance towards the fetus, but also to pathologies such as pre-eclampsia. The aim of the study was to address whether Plasmodium falciparum and HIV infections in pregnancy affect the secretion, microRNA content and function of trophoblast microparticles. Methods Microparticles were isolated and characterized from 122 peripheral plasmas of Mozambican pregnant women, malaria- and/or HIV-infected and non-infected. Expression of placenta-related microRNAs in microparticles was analysed by qPCR and the effect of circulating microparticles on dendritic cells assessed by phenotype analysis and cytokine/chemokine measurement. Results Concentrations of total and trophoblast microparticles detected by flow cytometry were higher in HIV-positive (P = 0.005 and P = 0.030, respectively) compared to non-infected mothers, as well as in women delivering low birthweight newborns (P = 0.032 and P = 0.021, respectively). miR-517c was overexpressed in mothers with placental malaria (P = 0.034), compared to non-infected. Microparticles from HIV-positive induced a higher expression of MHCII (P = 0.021) and lower production of MCP1 (P = 0.008) than microparticles from non-infected women. Conclusions In summary, alterations in total and trophoblast microparticles associated with malaria and HIV in pregnant women may have an immunopathogenic role. The potential for placental-derived vesicles and microRNAs as biomarkers of adverse outcomes during pregnancy and malaria infection should be confirmed in future studies. PMID:26757431

  8. Maternal History and Uterine Artery Doppler in the Assessment of Risk for Development of Early- and Late-Onset Preeclampsia and Intrauterine Growth Restriction

    PubMed Central

    Llurba, Elisa; Carreras, Elena; Gratacós, Eduard; Juan, Miquel; Astor, Judith; Vives, Angels; Hermosilla, Eduard; Calero, Ines; Millán, Pilar; García-Valdecasas, Bárbara; Cabero, Lluís

    2009-01-01

    Objective. To examine the value of one-step uterine artery Doppler at 20 weeks of gestation in the prediction pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). Methods. A prospective multicentre study that included all women with singleton pregnancies at 19–22 weeks of gestation (w). The mean pulsatility index (mPI) of both uterine arteries was calculated. Receiver-operating characteristics curves (ROC) were drawn to compare uterine artery Doppler and maternal risk factors for the prediction of early-onset PE and/or IUGR (before 32 w) and late-onset PE and/or IUGR. Results. 6,586 women were included in the study. Complete outcome data was recorded for 6,035 of these women (91.6%). PE developed in 75 (1.2%) and IUGR in 69 (1.1%) cases. Uterine Doppler mPI was 0.99 and the 90th centile was 1.40. For 10% false-positive rate, uterine Doppler mPI identified 70.6% of pregnancies that subsequently developed early-onset PE and 73.3% of pregnancies that developed early-onset IUGR. The test had a lower detection rate for the late-onset forms of the disease (23.5% for PE and 30% for IUGR). Maternal history has a low sensitivity in the detection of early-onset cases, although it is better at detecting late-onset PE. Conclusion. Uterine artery Doppler and maternal risk factors seem to select two different populations - early and late-onset PE which might suggest a different pathogenesis. PMID:19936122

  9. Interventions with vitamins B6, B12 and C in pregnancy.

    PubMed

    Dror, Daphna K; Allen, Lindsay H

    2012-07-01

    The water-soluble vitamins B6, B12 and C play important roles in maternal health as well as fetal development and physiology during gestation. This systematic review evaluates the risks and benefits of interventions with vitamins B6, B12 and C during pregnancy on maternal, neonatal and child health and nutrition outcomes. Relevant publications were identified by searching PubMed, Popline and Web of Science databases. Meta-analyses were conducted for outcomes where results from at least three controlled trials were available. Potential benefits of vitamin B6 supplementation were reduction in nausea and vomiting, improvement in dental health, and treatment of some cases of anaemia. In meta-analysis based on three small studies, vitamin B6 supplementation had a significant positive effect on birthweight (d = 217 g [95% confidence interval (CI) 130, 304]). Interventions with vitamin C alone or combined with vitamin E did not systematically reduce the incidence of pre-eclampsia, premature rupture of membranes, or other adverse pregnancy outcomes. In meta-analyses, vitamins C and E increased the risk of pregnancy-related hypertension (relative risk 1.10 [95% CI 1.02, 1.19]). Effects of vitamin B6 or C intervention on other neonatal outcomes, including preterm birth, low birthweight, and perinatal morbidity and mortality, were not significant. Data on child health outcomes were lacking. Despite the prevalence of vitamin B12 deficiency amongst populations with limited intake of animal source foods, no intervention trials have evaluated vitamin B12 supplementation before or during pregnancy. In conclusion, existing evidence does not justify vitamin C supplementation during pregnancy. Additional studies are needed to confirm positive effects of vitamin B6 supplementation on infant birthweight and other outcomes. While vitamin B12 supplementation may reduce the incidence of neural tube defects in the offspring based on theoretical considerations, research is needed to support

  10. Intra-vaginal use of misoprostol for induction of labour in intrauterine death.

    PubMed

    Easmin, S; Nahar, K; Jahan, M K; Rahim, R; Nila, T A; Nigar, K; Khan, N A

    2011-10-01

    This prospective study was done in the Department of Obstetric & Gynaecology in Mymensingh Medical College & Hospital during the period of February 2006 to January 2007, to assess the efficacy of vaginal misoprostol for induction of labour in intrauterine foetal death cases and to detect any intrapartum or postpartum complications. For this study, 50 cases of IUD were selected among admitted patients who were diagnosed by detailed history, clinical examination and by USG. Fifty microgram of misoprostol was given per vaginally, which was repeated 4 hours interval upto effective uterine contraction to a maximum six doses. All the informations were recorded in a predesigned structured data collection sheet and data had been interpreted through appropriate statistical analysis. In this study, 46% patients were within 18-25 years of age and gestational age between 28-37 weeks was 80%. Regarding causes of IUD, commonest was idiopathic (52%), next was gestational hypertension, pre-eclampsia, impending eclampsia (28%). Most of the patients (80%) had no history of antenatal checkup and belongs to below average socioeconomic status. Most case (64%) had less Bishop's score (<3) & all cases had unfavourable cervix, score <6. Vaginal delivery was 98% and 2% needed caesarean section. Mean induction delivery interval was 11.8 hours. Induction delivery interval was within 6-23 hours and 66% cases needed 2-3 doses of vaginal misoprostol. Complications were found in a minor group of patients. Nausea, vomiting, occurred in 12% of cases. Others were fever (2%), shivering (6%), PPH (4%), chorioamniotitis (2%) etc. Vaginal misoprostol for cervical ripening and labour induction is very effective and shorten the time of induction delivery interval. On the other hand, misoprostol is quite cheap, easy to administer, well tolerability and less side effects.

  11. Maternal and perinatal outcomes amongst haemoglobinopathy carriers: a systematic review.

    PubMed

    Jans, S M P J; de Jonge, A; Lagro-Janssen, A L M

    2010-11-01

    With the introduction of screening programmes for haemoglobinopathies (HbP), more women will be aware of their HbP status. The genetic risk for women who are carriers of HbP is well known. However, midwives and obstetricians need to know whether there are other risks involved in the pregnancies of women who are carriers of HbP. The objective of this study was to investigate the hypothesis that being a carrier of HbP has no consequences for the health of pregnant women and the outcome of their pregnancies. A systematic search was carried out until August 2008 in the Cochrane Library, Medline, EMBASE and CINAHL databases. All references were inspected to identify further studies. The authors of key publications were contacted for any unpublished research. Selection of studies was made on the basis of the following criteria: Cohort and case-control studies, pregnant women with a singleton pregnancy, exposure: HbAS or thalassaemia minor and the following outcomes: urinary tract infection (UTI), anaemia, (pre-)eclampsia, gestational diabetes, premature labour, low birth weight, intrauterine growth retardation, miscarriage, neonatal death, low Apgar score, neural tube defects. Quality assessment and data extraction were carried out by two researchers. A total of 780 subjects were identified of which nine were included in the study. A protective effect of sickle cell trait was found for premature birth, low Apgar score and perinatal mortality rate. No significant effect was found for low birth weight, growth retardation, UTI or high blood pressure. The risk of anaemia and bacteriuria was increased. In conclusion, the risks amongst pregnant HbP carriers are low. Midwives and obstetricians need to be aware of the risk of anaemia and UTI.

  12. Protocadherin-12 Cleavage Is a Regulated Process Mediated by ADAM10 Protein

    PubMed Central

    Bouillot, Stéphanie; Tillet, Emmanuelle; Carmona, Guillaume; Prandini, Marie-Hélène; Gauchez, Anne-Sophie; Hoffmann, Pascale; Alfaidy, Nadia; Cand, Francine; Huber, Philippe

    2011-01-01

    Protocadherins are a group of transmembrane proteins with homophilic binding activity, members of the cadherin superfamily. Apart from their role in adhesion, the cellular functions of protocadherins are essentially unknown. Protocadherin (PCDH)12 was previously identified in invasive trophoblasts and endothelial and mesangial cells in the mouse. Invalidation studies revealed that the protein was required for optimal placental development. In this article, we show that its human homolog is abundantly expressed in various trophoblast subtypes of the human placenta and at lower levels in endothelial cells. We demonstrate that PCDH12 is shed at high rates in vitro. The shedding mechanism depends on ADAM10 and results in reduced cellular adhesion in a cell migration assay. PCDH12 is subsequently cleaved by the γ-secretase complex, and its cytoplasmic domain is rapidly degraded by the proteasome. PCDH12 shedding is regulated by interlinked intracellular pathways, including those involving protein kinase C, PI3K, and cAMP, that either increase or inhibit cleavage. In endothelial cells, VEGF, prostaglandin E2, or histamine regulates PCDH12 shedding. The extracellular domain of PCDH12 was also detected in human serum and urine, thus providing evidence of PCDH12 shedding in vivo. Importantly, we observed an increase in circulating PCDH12 in pregnant women who later developed a pre-eclampsia, a frequent pregnancy syndrome and a major cause of maternal and fetal morbidity and mortality. In conclusion, we speculate that, like in mice, PCDH12 may play an important role in human placental development and that proteolytic cleavage in response to external factors, such as cytokines and pathological settings, regulates its activity. PMID:21402705

  13. Psychosocial deprivation in women with gestational diabetes mellitus is associated with poor fetomaternal prognoses: an observational study

    PubMed Central

    Cosson, Emmanuel; Bihan, Hélène; Reach, Gérard; Vittaz, Laurence; Carbillon, Lionel; Valensi, Paul

    2015-01-01

    Objective To evaluate the prognoses associated with psychosocial deprivation in women with gestational diabetes mellitus (GDM). Design Observational study considering the 1498 multiethnic women with GDM who gave birth between January 2009 and February 2012. Setting Four largest maternity units in the northeastern suburban area of Paris. Participants The 994 women who completed the Evaluation of Precarity and Inequalities in Health Examination Centers (EPICES) questionnaire. Main outcome measure Main complications of GDM (large infant for gestational age (LGA), shoulder dystocia, caesarean section, pre-eclampsia). Results Psychosocial deprivation (EPICES score ≥30.17) affected 577 women (56%) and was positively associated with overweight/obesity, parity and non-European origin, and negatively associated with family history of diabetes, fruit and vegetable consumption and working status. The psychosocially deprived women were diagnosed with GDM earlier, received insulin treatment during pregnancy more often and were more likely to have LGA infants (15.1% vs 10.6%, OR=1.5 (95% CI 1.02 to 2.2), p<0.05) and shoulder dystocia (3.1% vs 1.2%, OR=2.7 (0.97 to 7.2), p<0.05). In addition to psychosocial deprivation, LGA was associated with greater parity, obesity, history of GDM, ethnicity, excessive gestational weight gain and insulin therapy. A multivariate analysis using these covariates revealed that the EPICES score was independently associated with LGA infants (per 10 units, OR=1.12 (1.03 to 1.20), p<0.01). Conclusions In our area, psychosocial deprivation is common in women with GDM and is associated with earlier GDM diagnoses and greater insulin treatment, an increased likelihood of shoulder dystocia and, independently of obesity, gestational weight gain and other confounders with LGA infants. PMID:25748416

  14. The lost children.

    PubMed

    Smith, S

    1999-03-01

    Women who have lost children to perinatal complications, are subjected to pain and grief continuously; however their agony increases on remembrance days such as birthdate, or on Mother's Day. Fathers, siblings and grandparents suffer too. Common disorders of pregnancy, such as pregnancy-induced hypertension (PIH), or the more serious pre-eclampsia, HELLP syndrome, or eclampsia, can lead to devastating effects such as miscarriage, stillbirth, or neonatal death; or at the very least, a sick infant. With many of these consequences, the loss of the dreams, hopes and plans that parents have made is imminent. The investigation of the psychosocial aspects of 'high-risk' pregnancy has never been fully addressed. However, the threat of loss, or the actual experience, may provoke the onset of a potential psychological crisis during the perinatal period. Therefore, it is important that these issues be addressed by the nurse in order to aid the development of coping mechanisms to enable women and their families to deal with what may happen. This may be done by predicting the stages of the bereavement process experienced by these women and their family members, as outlined in the Kubler-Ross model of bereavement (1969), which is indicative of many types of grief reactions. Other issues including the restriction in activity, uncertainty of pregnancy outcomes, disruption in work or career activities, financial strains, and reduced labour and birthing options, become concerns for high-risk pregnant women. The way women deal with these issues and the pathways nurses can take to help these women develop effective coping strategies, will be addressed also.

  15. Integrating psychotherapy with obstetrics and gynaecology.

    PubMed

    Linder, Rupert

    2007-01-01

    As a specialist Obstetrics and Gynaecology I then became a specialist also in psychotherapy, including: psychodynamic therapy, group therapy, hypnotherapy, and body-therapy. In the last nineteen years I have been working to integrate the medical and psychotherapeutic approach, including attention to psychosocial factors. After some years, I found our German rate of premature birth to be 7%. This amazed me because prematurity very rarely occurred in my patients, which was down to about 1%. In France they did some surveys and studies. By informing the mothers how to live, and reducing smoking and drugs, they reduced their prematurity rate to about half, but still much above my rate of 1%. I have described my method in articles. This is vital work, because serious prematurity is responsible for most damage and death amongst the children. A mother's complaint may be an early suggestion of danger. We then check it with the regular obstetric assessments. Even before birth symptoms can indicate a problem, such as premature labour, much as postnatal problems while breast feeding are indicated by symptoms. And before birth, as well as after birth stress and emotional problems can be the cause for serious somatic illness. It is really an effect of one relationship on the other. The way a woman relates to her child depends on her feeling of security among all who support her. All her relationships are important: how she grew up with her parents; her work: her other children. Further problems that experience of psychotherapy can help to reduce are: exceeding the estimated date of delivery: pre-eclampsia: HELLP-syndrome (Hemolysis, Elevated Liver enzymes and Low Platelets). The lectures we offer on the subject are also relevant to psychotherapeutic understanding and in guiding to treatment.

  16. The underrated benefits of oral contraception: consequences of pregnancy and induced abortion in teenagers.

    PubMed

    Dreyfus, R

    1992-01-01

    If complications occur within a pregnancy planned and brought to term, they often can be dealt with and accepted. They are even more traumatic when they occur in an unwanted pregnancy that could have been prevented through contraception. Teenagers, because of their physical and psychological immaturity and also because of their social environment, seem to suffer with undue frequency from the complications of induced abortion. Its result, for the teenager, is a handicapped future in comparison to other women. Hence, access to contraception is important for all women, and especially for teenagers, in order to avoid such prejudicial situations. It is important, then, to prescribe oral contraception for its efficacy and its short- and long-term innocuousness. Because of her immaturity, the pregnant teenager is at risk: of spontaneous abortion, pre-eclampsia, anemia, hemorrhage, and prematurity. She is also at risk because of the social difficulties she will be facing. This is particularly true in families from developing countries. From birth, the child is also at risk: of low birth weight for the term, mortality in the first year of life, and all risks linked to abandonment, or education by a third party. In a proportion of 13 to 30% in western countries and in a proportion of 3% in East Asia or in Northwest Africa (Maghreb), induced abortions are a reflection of the following: early sexual activity without contraception even if fertility is still low in very young teenagers, absence of social protection or social independence, refusal of forced marriage, and presence or absence of liberal legislation.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. [Pregnancy and antiphospholipid syndrome].

    PubMed

    Costedoat-Chalumeau, N; Guettrot-Imbert, G; Leguern, V; Leroux, G; Le Thi Huong, D; Wechsler, B; Morel, N; Vauthier-Brouzes, D; Dommergues, M; Cornet, A; Aumaître, O; Pourrat, O; Piette, J-C; Nizard, J

    2012-04-01

    Antiphospholipid syndrome (APS) is associated with a risk of obstetrical complications, affecting both the mother and the fetus. Obstetrical APS is defined by a history of three consecutive spontaneous miscarriages before 10 weeks of gestation (WG), an intra-uterine fetal death after 10 WG, or a premature birth before 34 WG because of severe pre-eclampsia, eclampsia or placental adverse outcomes (intrauterine growth retardation, oligohydramnios). Pregnancy in women with a diagnosis of obstetric APS is at increased risk for placental abruption, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome and thrombosis that may be part of a catastrophic antiphospholipid syndrome (CAPS). A previous thrombosis and the presence of a lupus anticoagulant are risk factors for pregnancy failure. A multidisciplinary approach, associating the internist, the anesthesiologist and the obstetrician, is recommended for these high-risk pregnancies. Preconception counseling is proposed to identify pregnancy contraindications, and to define and adapt the treatment prior and during the upcoming pregnancy. Heparin and low-dose aspirin are the main treatments. The choice between therapeutic or prophylactic doses of heparin will depend on the patient's medical history. The anticoagulant therapeutic window for delivery should be as narrow as possible and adapted to maternal thrombotic risk. There is a persistent maternal risk in the postpartum period (thrombosis, HELLP syndrome, CAPS) justifying an antithrombotic coverage during this period. We suggest a monthly clinical and biological monitoring which can be more frequent towards the end of pregnancy. The persistence of notches at the Doppler-ultrasound evaluation seems to be the best predictor for a higher risk of placental vascular complications. Treatment optimization and multidisciplinary antenatal care improve the prognosis of pregnancies in women with obstetric APS, leading to a favorable outcome most of the time.

  18. Three-Dimensional Segmented Poincaré Plot Analyses SPPA3 Investigates Cardiovascular and Cardiorespiratory Couplings in Hypertensive Pregnancy Disorders.

    PubMed

    Fischer, Claudia; Voss, Andreas

    2014-01-01

    Hypertensive pregnancy disorders affect 6-8% of gestations representing the most common complication of pregnancy for both mother and fetus. The aim of this study was to introduce a new three-dimensional coupling analysis methods - the three-dimensional segmented Poincaré plot analyses (SPPA3) - to establish an effective approach for the detection of hypertensive pregnancy disorders and especially pre-eclampsia (PE). A cubic box model representing the three-dimensional phase space is subdivided into 12 × 12 × 12 equal predefined cubelets according to the range of the SD of each investigated signal. Additionally, we investigated the influence of rotating the cloud of points and the size of the cubelets (adapted or predefined). All single probabilities of occurring points in a specific cubelet related to the total number of points are calculated. In this study, 10 healthy non-pregnant women, 66 healthy pregnant women, and 56 hypertensive pregnant women (chronic hypertension, pregnancy-induced hypertension, and PE) were investigated. From all subjects, 30 min of beat-to-beat intervals (BBI), respiration (RESP), non-invasive systolic (SBP), and diastolic blood pressure (DBP) were continuously recorded and analyzed. Non-rotated adapted SPPA3 discriminated best between hypertensive pregnancy disorders and PE concerning coupling analysis of two or three different systems (BBI, DBP, RESP and BBI, SBP, DBP) reaching an accuracy of up to 82.9%. This could be increased to an accuracy of up to 91.2% applying multivariate analysis differentiating between all pregnant women and PE. In conclusion, SPPA3 could be a useful method for enhanced risk stratification in pregnant women.

  19. Is the Mean Platelet Volume a Predictive Marker of a Low Apgar Score and Insulin Resistance in Gestational Diabetes Mellitus? A Retrospective Case-Control Study

    PubMed Central

    Kebapcilar, Ayse Gul; Ilhan, Tolgay Tuyan; Ipekci, Suleyman Hilmi; Baldane, Suleyman; Pekin, Aybike; Kulaksizoglu, Mustafa; Celik, Cetin

    2016-01-01

    Introduction Gestational diabetes is defined as various degrees of glucose intolerance diagnosed or detected for the first time during pregnancy and is the most common metabolic complication of pregnancy. Early diagnosis and adequate treatment are important to prevent complications. Pre-eclampsia, polyhydramnios, fetalmacrosomia, and operative delivery are some of the complications seen in pregnant women diagnosed with Gestational Diabetes Mellitus (GDM). Aim The present study was designed to determine whether there was an association between Mean Platelet Volume (MPV) in predicting poor fetal outcome, insulin resistance, neonatal Apgar scores and gestational age for women with GDM. Materials and Methods In this retrospective study, we enrolled 101 pregnant women with GDM together with a group of 138 healthy controls. MPV, insulin and homeostatic model assessment (HOMA-IR) values were measured at 24–28 weeks of the pregnancy. An independent samples t-test was used to compare MPV values. Multivariate linear regression models were used to establish relations between MPV values, HOMA-IR, insulin levels and Apgar score. Results There was a significant positive correlation between MPV values, HOMA-IR and Insulin levels and a negative correlation with Apgar score at 1 min and 5 min in the GDM group (r=0.227, p=0.02; r=0.206, p=0.03; r=-0.485, p<0.001; and r=-0.399, p<0.001, respectively). In the multivariate logistic regression analysis, a high MPV value was most consistently associated with a low Apgar 1 min score (β=-0.387, p=0.003) in the GDM group. An MPV of >8.0 fL had a sensitivity of 82% and a specificity of 75% for the prediction of GDM. Conclusion We investigated the potential of MPV values in predicting low Apgar scores and insulin resistance in women with GDM. PMID:27891368

  20. In-depth Medical Nutrition Therapy for a Woman with Diabetes: From Pregnancy to Delivery

    PubMed Central

    2016-01-01

    Diabetes in pregnancy is associated with higher rates of miscarriage, pre-eclampsia, preterm labor, and fetal malformation. To prevent these obstetric and perinatal complications, women with diabetes have to control levels of blood sugar, both prior to and during pregnancy. Thus, individualized medical nutrition therapy for each stage of pregnancy is essential. We provided in-depth medical nutrition therapy to a 38-year-old pregnant woman with diabetes at all stages of pregnancy up to delivery. She underwent radiation therapy after surgery for breast cancer and was diagnosed with diabetes. At the time of diagnosis, her glycated hemoglobin level was 8.3% and she was planning her pregnancy. She started taking an oral hypoglycemic agent and received education regarding the management of diabetes and preconception care. She became pregnant while maintaining a glycated hemoglobin level of less than 6%. We provided education program for diabetes management during the pregnancy, together with insulin therapy. She experienced weight loss and ketones were detected; furthermore, she was taking in less than the recommended amount of foods for the regulation of blood sugar levels. By giving emotional support, we continued the counseling and achieved not only glycemic control but also instilled an appreciation of the importance of appropriate weight gain and coping with difficulties. Through careful diabetes management, the woman had a successful outcome for her pregnancy, other than entering preterm labor at 34 weeks. This study implicated that the important things in medical nutrition therapy for pregnant women with diabetes are frequent follow-up care and emotional approach through the pregnancy process. PMID:27812519

  1. Safety of Tdap vaccine in pregnant women: an observational study

    PubMed Central

    Petousis-Harris, Helen; Walls, Tony; Watson, Donna; Paynter, Janine; Graham, Patricia; Turner, Nikki

    2016-01-01

    Objectives Actively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination. Design and settings A prospective observational study conducted in 2 New Zealand regions. Participants Women in their 28th–38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Tdap administration. Telephone interviews were conducted at 48 h and 4 weeks postvaccination. Main outcomes measures Outcomes were injection site reactions, systemic symptoms and serious adverse events (SAEs). Where available, data have been classified and reported according to Brighton Collaboration definitions. Results 793 women participated with 27.9% receiving trivalent inactivated influenza vaccine concomitantly. 79% of participants reported mild or moderate pain and 2.6% severe pain. Any swelling was reported by 7.6%, induration by 12.0% (collected from 1 site only, n=326), and erythema by 5.8% of participants. Fever was reported by 17 (2.1%) participants, 14 of these occurred within 24 h. Headache, dizziness, nausea, myalgia or arthralgia was reported by <4% of participants, respectively, and fatigue by 8.4%. During the study period, there were 115 adverse events in 113 participants, most of which were minor. At the end of the reporting period, 31 events were classified as serious (eg, obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia). All had variable onset time from vaccination. There were two perinatal deaths. Clinician assessment of all SAEs found none likely to be vaccine related. Conclusions Vaccination with Tdap in pregnant women was well tolerated with no SAE likely to be caused by the vaccine. Trial registration number ACTRN12613001045707. PMID:27091823

  2. Epidemiology and Related Risk Factors of Preterm Labor as an obstetrics emergency

    PubMed Central

    Halimi asl, Ali asghar; Safari, Saeed; Parvareshi Hamrah, Mohsen

    2017-01-01

    Introduction: Preterm birth is still a major health problem throughout the world, which results in 75% of neonatal mortality. Preterm labor not only inflicts financial and emotional distress, it may also lead to permanent disability. The present study was conducted to determine the related risk factors and preventive measures of preterm labor. Methods: This retrospective cross-sectional study assessed all preterm labors, as well as an equal number of term labors, during seven years, at an educational hospital. Probable risk factors of preterm labor were collected using medical profiles of participants by the aid of a pre-designed checklist. Significant related factors of preterm labor were used for multivariate logistic regression analysis with SPSS 21.0. Result: 810 cases with the mean age of 28.33 ± 6.1 years were evaluated (48.7% preterm). Multipartite; fetal anomaly; prenatal care; smoking; not consuming folic acid and iron supplements; in vitro fertilization; history of infertility, caesarian section, trauma, systemic disease, and hypertension; amniotic fluid leak; rupture of membranes; cephalic presentation; vaginal bleeding; placenta decolman; oligohydramnios; pre-eclampsia; chorioamnionitis; uterine abnormalities; cervical insufficiency; intercourse during the previous week; short time since last delivery; and mother’s weight significantly correlated with preterm labor. Conclusion: Based on the results of the present study, intercourse during the previous week, multipartite, short time from last delivery, preeclampsia, fetal anomaly, rupture of membranes, hypertension, and amniotic fluid leak, respectively, were risk factors for preterm labor. On the other hand, iron consumption, cephalic presentation, systematic disease, history of caesarian section, prenatal care, and mother’s weight could be considered as protective factors. PMID:28286810

  3. Oxidative stress markers in hypertensive states of pregnancy: preterm and term disease.

    PubMed

    Kurlak, Lesia O; Green, Amanda; Loughna, Pamela; Broughton Pipkin, Fiona

    2014-01-01

    Discussion continues as to whether de novo hypertension in pregnancy with significant proteinuria (pre-eclampsia; PE) and non-proteinuric new hypertension (gestational hypertension; GH) are parts of the same disease spectrum or represent different conditions. Non-pregnant hypertension, pregnancy and PE are all associated with oxidative stress. We have established a 6 weeks postpartum clinic for women who experienced a hypertensive pregnancy. We hypothesized that PE and GH could be distinguished by markers of oxidative stress; thiobarbituric acid reactive substances (TBARS) and antioxidants (ferric ion reducing ability of plasma; FRAP). Since the severity of PE and GH is greater pre-term, we also compared pre-term and term disease. Fifty-eight women had term PE, 23 pre-term PE, 60 had term GH and 6 pre-term GH, 11 pre-existing (essential) hypertension (EH) without PE. Limited data were available from normotensive pregnancies (n = 7) and non-pregnant controls (n = 14). There were no differences in postpartum TBARS or FRAP between hypertensive states; TBARS (P = 0.001) and FRAP (P = 0.009) were lower in plasma of non-pregnant controls compared to recently-pregnant women. Interestingly FRAP was higher in preterm than term GH (P = 0.013). In PE and GH, TBARS correlated with low density lipoprotein (LDL)-cholesterol (P = 0.036); this association strengthened with inclusion of EH (P = 0.011). The 10 year Framingham index for cardiovascular risk was positively associated with TBARS (P = 0.003). Oxidative stress profiles do not differ between hypertensive states but appear to distinguish between recently-pregnant and non-pregnant states. This suggests that pregnancy may alter vascular integrity with changes remaining 6 weeks postpartum. LDL-cholesterol is a known determinant of oxidative stress in cardiovascular disease and we have shown this association to be present in hypertensive pregnancy further emphasizing that such a pregnancy may be revealing a pre

  4. [How to manage a patient with chronic arterial hypertension during pregnancy and the postpartum period].

    PubMed

    Pourrat, O

    2015-03-01

    The management of chronic arterial hypertension during pregnancy and postpartum requires first to estimate the risk of the pregnancy, linked with the severity of hypertension, with cardiac and renal involvement, with its cause as well as with the background (obesity, diabetes, possible history of placental vascular pathology). On a very practical approach, antihypertensive drug has to be started or increased if systolic pressure reaches or exceeds 160 mmHg or if diastolic pressure reaches or exceeds 105 mmHg. Below this level, there are no evidence-based medicine data, but it seems reasonable to treat if pressure increases over 150/100 mmHg (140/90 mmHg in case of ambulatory monitoring). Excessive pressure figures control must be avoided as much as insufficient ones: in practice, it is necessary to decrease the treatment dose if figures are below 130/80 mmHg. Three antihypertensive drugs are consensually recommended today: alphametyldopa, calcium-channel blockers and labetalol. Monotherapy is most often sufficient; if needed, two of these drugs can easily be associated, and even three if necessary. Converting enzyme inhibitors and angiotensin receptor II antagonists should not be prescribed to pregnant women. Betablockers and diuretics are not recommended. Whatever is the antihypertensive drug used, it is necessary to detect the signs of bad placenta blood circulation with uterine Doppler ultrasound and regular controls of fetal growth, and to check for appearance of proteinuria, defining then over-imposed pre-eclampsia needing immediate admission to the maternity. After delivery, lacatation suppresion with bromocriptin should not be prescribed.

  5. Adenoviral Delivery of VEGF121 Early in Pregnancy Prevents Spontaneous Development of Preeclampsia in BPH/5 Mice

    PubMed Central

    Woods, Ashley K.; Hoffmann, Darren S.; Weydert, Christine J.; Butler, Scott D.; Zhou, Yi; Sharma, Ram V.; Davisson, Robin L.

    2011-01-01

    An imbalance in circulating pro-angiogenic and anti-angiogenic factors is postulated to play a causal role in pre-eclampsia (PE). We have described an inbred mouse strain, BPH/5, which spontaneously develops a PE-like syndrome including late-gestational hypertension, proteinuria, and poor feto-placental outcomes. Here we tested the hypothesis that an angiogenic imbalance during pregnancy in BPH/5 mice leads to the development of PE-like phenotypes in this model. Similar to clinical findings, plasma from pregnant BPH/5 showed reduced levels of free vascular endothelial growth factor (VEGF) and placental growth factor (PGF) compared to C57BL/6 controls. This was paralleled by a marked decrease in VEGF protein and Pgf mRNA in BPH/5 placentae. Surprisingly, antagonism by the soluble form of the FLT1 receptor (sFLT1) did not appear to be the cause of this reduction, as sFLT1 levels were unchanged or even reduced in BPH/5 compared to controls. Adenoviral-mediated delivery of VEGF121 (Ad-VEGF) via tail vein at e7.5 normalized both the plasma free VEGF levels in BPH/5 and restored the in vitro angiogenic capacity of serum from these mice. Ad-VEGF also reduced the incidence of fetal resorptions and prevented the late-gestational spike in blood pressure and proteinuria observed in BPH/5. These data underscore the importance of dysregulation of angiogenic factors in the pathogenesis of PE, and suggest the potential utility of early pro-angiogenic therapies in treating this disease. PMID:21079047

  6. Transcriptional regulation of human thromboxane synthase gene expression

    SciTech Connect

    Lee, K.D.; Baek, S.J.; Fleischer, T

    1994-09-01

    The human thromboxane synthase (TS) gene encodes a microsomal enzyme catalyzing the conversion of prostaglandin endoperoxide into thromboxane A{sub 2}(TxA{sub 2}), a potent inducer of vasoconstriction and platelet aggregation. A deficiency in platelet TS activity results in bleeding disorders, but the underlying molecular mechanism remains to be elucidated. Increased TxA{sub 2} has been associated with many pathophysiological conditions such as cardiovascular disease, pulmonary hypertension, pre-eclampsia, and thrombosis in sickle cell patients. Since the formation of TxA{sub 2} is dependent upon TS, the regulation of TS gene expression may presumably play a crucial role in vivo. Abrogation of the regulatory mechanism in TS gene expression might contribute, in part, to the above clinical manifestations. To gain insight into TS gene regulation, a 1.7 kb promoter of the human TS gene was cloned and sequenced. RNase protection assay and 5{prime} RACE protocols were used to map the transcription initiation site to nucleotide A, 30 bp downstream from a canonical TATA box. Several transcription factor binding sites, including AP-1, PU.1, and PEA3, were identified within this sequence. Transient expression studies in HL-60 cells transfected with constructs containing various lengths (0.2 to 5.5 kb) of the TS promoter/luciferase fusion gene indicated the presence of multiple repressor elements within the 5.5 kb TS promoter. However, a lineage-specific up-regulation of TS gene expression was observed in HL-60 cells induced by TPA to differentiate along the macrophage lineage. The increase in TS transcription was not detectable until 36 hr after addition of the inducer. These results suggest that expression of the human TS gene may be regulated by a mechanism involving repression and derepression of the TS promoter.

  7. [Hypothyroidism: from the desire for pregnancy to delivery].

    PubMed

    Ouzounian, S; Bringer-Deutsch, S; Jablonski, C; Théron-Gérard, L; Snaifer, E; Cédrin-Durnerin, I; Hugues, J-N

    2007-03-01

    The link between hypothyroidism and infertility is still a matter of debate. Hypothyroidism can result in cycle disturbances, such as oligomennorhea and functional bleeding. Additionally, several studies have shown that thyroid autoimmunity (detection of anti peroxydase antibodies) may account for the occurrence of repetitive miscarriages. In infertility work-up, screening thyroid function should be specifically recommended for women with clinical hypothyroidism, with a personal, familial history of thyroid or other auto immune diseases (such as type I diabetes) as well as for women with unexplained anovulation or functional bleeding. Moreover, detection of thyroid antibody seems to be worthwhile for the assessment of recurrent miscarriages, due to the potential benefit of thyroid supplementation. In pregnant women, assessment of thyroid function seems specifically crucial to ensure adequate foetal development. Indeed, it has been well established that untreated maternal hypothyroidism may be associated with disturbances of brain development and low intellectual quotient. Additionally, other foetal (growth deficiency, premature birth, low birth weight) as well as maternal (gestational hypertension, pre-eclampsia...) complications have been also reported in pregnant women with untreated hypothyroidism. Consequently, screening of thyroid function should be performed in every woman at risk of thyroid disease. Recent studies even advocate that thyroid screening should be extended to the overall pregnant population. The objective is to adjust L-thyroxin supplementation to maintain serum TSH concentrations below the threshold of 2.5 mUI/l. Finally, iodine deficiency, currently observed in pregnant women, should be prevented by iodine supply prior to conception, during pregnancy and during breast feeding as well.

  8. Reversal with sugammadex for rocuronium-induced deep neuromuscular block after pretreatment of magnesium sulfate in rabbits

    PubMed Central

    Kang, Woon Seok; Song, Shin Mi

    2017-01-01

    Background Magnesium sulfate (MgSO4) has been used in the treatment of pre-eclampsia, hypertension and arrhythmia. Magnesium enhances the neuromuscular block of rocuronium. This study has been conducted to evaluate the reversal efficacy of sugammadex from deep rocuronium-induced neuromuscular block (NMB) during consistent pretreatment of MgSO4 in rabbits. Methods Twenty-eight rabbits were randomly assigned to four groups, a control group or study groups (50% MgSO4 150–200 mg/kg and 25 mg/kg/h IV), and received rocuronium 0.6 mg/kg. When post-tetanic count 1–2 appeared, sugammadex 2, 4, and 8 mg/kg was administered in the 2-mg group, control and 4-mg group, and 8-mg group, respectively. The recovery course after reversal of sugammadex administration was evaluated in each group. Results The mean serum concentration of magnesium was maintained at more than 2 mmol/L in the study groups, and the total dose of MgSO4 was more than 590 mg. The reversal effect of sugammadex on rocuronium-induced NMB in pretreated MgSO4 was not different from that in the group without MgSO4. The recovery time to train-of-four ratio 0.9 after sugammadex administration in the 2-mg group was longer than in the other groups (P < 0.001); there were no other significant differences among the groups. Conclusions The reversal of sugammadex from a deep rocuronium-induced NMB during large pretreatment of MgSO4 was not affected. However, we should consider that the reversal effect of sugammadex varied depending on the dose. PMID:28367292

  9. The influence of mode of delivery, obstetric analgesia and anaesthesia on the response of isolated human chorionic plate arteries to angiotensin II.

    PubMed

    Odum, C U; Pipkins, F B

    1989-01-01

    A six point concentration: response curved of the contractile effect of angiotensin II (AII) on helically-cut strips of human chorionic plate artery strips were established at final concentrations of between 10(-14) to 10(-9) M. The tissues were obtained from the placentae of primigravid patients who had normal pregnancy, and also from those with pregnancy induced hypertension (PIH). The tissue response were then related to mode of delivery, obstetric analgesia, and anaesthesia. A total of 36 chorionic plate arteries from 12 primigravid patients were studied. i) The overall initial EC50s of the tissues ranged from 8.0 x 10(-13) M and 4.5 x 10(-13) M. The tissues from PIH patients were significantly more sensitive to AII, when compared with tissues from the normotensive subjects (P greater than or equal to 0.01 less than or equal to 0.05). ii) The tissues from epidural vaginal deliveries were also significantly more sensitive to AII, than those from both normal vaginal deliveries and caesarean deliveries respectively. The median gradients of the semi-log transformed concentration response curved were 2.4 +/- 0.18; 1.27 +/- 0.37, and 1.5 +/- 0.49, for epidural, Caeserean and normal vaginal deliveries respectively. iii) It is suggested that whilst Lumbar epidural analgesia may be of great value in pain relief in labour and in the control of intrapartum hypertension in pre-eclampsia, this procedure may be associated with hypersensitivity and perhaps vasospasm of the placental vasculature to vasoactive agents invivo.

  10. Cesarean Section Rates and Indications in Sub-Saharan Africa: A Multi-Country Study from Medecins sans Frontieres

    PubMed Central

    Chu, Kathryn; Cortier, Hilde; Maldonado, Fernando; Mashant, Tshiteng; Ford, Nathan; Trelles, Miguel

    2012-01-01

    Objectives The World Health Organization considers Cesarean section rates of 5–15% to be the optimal range for targeted provision of this life saving intervention. However, access to safe Cesarean section in resource-limited settings is much lower, estimated at 1–2% reported in sub-Saharan Africa. This study reports Cesarean sections rates and indications in Democratic Republic of Congo, Burundi, and Sierra Leone, and describe the main parameters associated with maternal and early neonatal mortality. Methods Women undergoing Cesarean section from August 1 2010 to January 31 2011 were included in this prospective study. Logistic regression was used to model determinants of maternal and early neonatal mortality. Results 1276 women underwent a Cesarean section, giving a frequency of 6.2% (range 4.1–16.8%). The most common indications were obstructed labor (399, 31%), poor presentation (233, 18%), previous Cesarean section (184, 14%), and fetal distress (128, 10%), uterine rupture (117, 9%) and antepartum hemorrhage (101, 8%). Parity >6 (adjusted odds ratio [aOR] = 8.6, P = 0.015), uterine rupture (aOR = 20.5; P = .010), antepartum hemorrhage (aOR = 13.1; P = .045), and pre-eclampsia/eclampsia (aOR = 42.9; P = .017) were associated with maternal death. Uterine rupture (aOR = 6.6, P<0.001), anterpartum hemorrhage (aOR = 3.6, P<0.001), and cord prolapse (aOR = 2.7, P = 0.017) were associated with early neonatal death. Conclusions This study demonstrates that target Cesarean section rates can be achieved in sub-Saharan Africa. Identifying the common indications for Cesarean section and associations with mortality can target improvements in antenatal services and emergency obstetric care. PMID:22962616

  11. [Automatic application of clinical guidelines - from theory to practice].

    PubMed

    Shalom, Erez; Shahar, Yuval; Lunenfeld, Eitan

    2013-05-01

    ClinicaL guidelines (GLs) have been shown to be a powerful tool for enhancing the uniformity and quality of care, reducing its costs. However, since they are typically represented in free text, this leads to low rates of compliance. Therefore, physicians might benefit from GL automated decision support. It should be noted that not many studies evaluate the effect of providing support for the application of GLs over significant stretches of time on the quality of medical decisions. In this paper, we will describe the general architecture of medical decision support systems, review several known GL application frameworks, and focus on the research performed in the medicaL informatics research center at Ben-Gurion University [BGU] of the Negev which developed the Digital ELectronic Guideline Library, called DeGeL. In particular, we will describe a new GL application framework called PICARD that is intended for GL application over time, while ensuring that the GLs recommendations were followed. We will briefly introduce a technical evaluation of PICARD in the cardiology domain to manage patients according to a Coumadin [Warfarin] protocoL, and a functional evaluation in a complex pre-eclampsia/ eclampsia GL in the OB/GYN domain, which we performed with 36 physicians. The results showed that the PICARD creates independence in the quality of the decisions from any particular physician, level of expertise, clinicaL scenario, or decision type within the scenarios. CurrentLy, PICARD is a core component in the EU Mobiguide project, which focuses on remote monitoring and care of chronic patients, using mobile devices to send alerts and recommendations.

  12. Effect of simple, targeted diet in pregnant women with metabolic risk factors on maternal and fetal outcomes (ESTEEM): study protocol for a pragmatic multicentre randomised trial

    PubMed Central

    Al Wattar, Bassel H; Dodds, Julie; Placzek, Anna; Spyreli, Eleni; Moore, Amanda; Hooper, Richard; Beresford, Lee; Roseboom, Tessa J; Bes-Rastrollo, Maira; Hitman, Graham; Khan, Khalid S; Thangaratinam, Shakila

    2016-01-01

    Introduction Women with metabolic risk factors are at higher risk of adverse pregnancy outcomes. Mediterranean-based dietary interventions have the potential to minimise these risks. We aim to evaluate the effectiveness of a simple, targeted intervention modelled on Mediterranean diet in preventing maternal and fetal complications in pregnant women with metabolic risk factors. Methods and analysis Pregnant women with a singleton pregnancy <18 weeks gestation, and without pre-existing diabetes, chronic renal disease and autoimmune diseases will be recruited. Women with metabolic risk factors will be randomised to receive a dietary intervention based on a Mediterranean pattern, supplemented with extra virgin olive oil and mixed nuts until delivery. The intervention will be delivered through a series of one to one and group sessions. The primary outcome is a composite maternal outcome of pre-eclampsia or gestational diabetes and a composite fetal outcome of stillbirth, small for gestational age fetus or admission to the neonatal intensive care unit. Secondary outcomes include maternal, fetal, dietary and laboratory outcomes. We aim to randomise 1230 eligible women with metabolic risk factors. We will also compare the outcomes in women with and without these risk factors. The sample size will provide us with 80% power at 5% significance, assuming a 20% loss to follow-up to detect a 30% reduction in maternal and fetal complications. Ethics and dissemination The ESTEEM trial is designed to provide a definitive estimate of the effects of Mediterranean dietary pattern in pregnancy on maternal and fetal outcomes. The pragmatic nature of ESTEEM ensures the applicability of its findings into clinical practice. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings and congresses. Ethical approval was granted by the NHS Research Ethics Committees (14/EE/1048). Trial registration number NCT02218931

  13. Risk of preterm delivery and hypertensive disorders of pregnancy in relation to maternal co-morbid mood and migraine disorders during pregnancy.

    PubMed

    Cripe, Swee May; Frederick, Ihunnaya O; Qiu, Chunfang; Williams, Michelle A

    2011-03-01

    We evaluated the risks of preterm delivery and hypertensive disorders of pregnancy among pregnant women with mood and migraine disorders, using a cohort study of 3432 pregnant women. Maternal pre-pregnancy or early pregnancy (<20 weeks gestation) mood disorder and pre-pregnancy migraine diagnoses were ascertained from interview and medical record review. We fitted generalised linear models to derive risk ratios (RR) and 95% confidence intervals (CI) of preterm delivery and hypertensive disorders of pregnancy for women with isolated mood, isolated migraine and co-morbid mood-migraine disorders, respectively. Reported RR were adjusted for maternal age, race/ethnicity, marital status, parity, smoking status, chronic hypertension or pre-existing diabetes mellitus, and pre-pregnancy body mass index. Women without mood or migraine disorders were defined as the reference group. The risks for preterm delivery and hypertensive disorders of pregnancy were more consistently elevated among women with co-morbid mood-migraine disorders than among women with isolated mood or migraine disorder. Women with co-morbid disorders were almost twice as likely to deliver preterm (adjusted RR=1.87, 95% CI 1.05, 3.34) compared with the reference group. There was no clear evidence of increased risks of preterm delivery and its subtypes with isolated migraine disorder. Women with mood disorder had elevated risks of pre-eclampsia (adjusted RR=3.57, 95% CI 1.83, 6.99). Our results suggest an association between isolated migraine disorder and pregnancy-induced hypertension (adjusted RR=1.42, 95% CI 1.00, 2.01). This is the first study examining perinatal outcomes in women with co-morbid mood-migraine disorders. Pregnant women with a history of migraine may benefit from screening for depression during prenatal care and vigilant monitoring, especially for women with co-morbid mood and migraine disorders.

  14. Preterm Prelabor Rupture of Membranes and Outcome of Very-Low-Birth-Weight Infants in the German Neonatal Network

    PubMed Central

    Hanke, Kathrin; Hartz, Annika; Manz, Maike; Bendiks, Meike; Heitmann, Friedhelm; Orlikowsky, Thorsten; Müller, Andreas; Olbertz, Dirk; Kühn, Thomas; Siegel, Jens; von der Wense, Axel; Wieg, Christian; Kribs, Angela; Stein, Anja; Pagel, Julia; Herting, Egbert; Göpel, Wolfgang; Härtel, Christoph

    2015-01-01

    Objective It was the aim of our study to evaluate the independent effect of preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on mortality during primary hospital stay and significant morbidities in very-low-birth-weight (VLBW) infants < 32 weeks of gestation. Design Observational, epidemiological study design. Setting Population-based cohort, German Neonatal Network (GNN). Population 6102 VLBW infants were enrolled in GNN from 2009-2012, n=4120 fulfilled criteria for primary analysis (< 32 gestational weeks, no pre-eclampsia, HELLP (highly elevated liver enzymes and low platelets syndrome) or placental abruption as cause of preterm birth). Methods Multivariable logistic regression analyses included PPROM as potential risk factors for adverse outcomes and well established items such as gestational age in weeks, birth weight, antenatal steroids, center, inborn delivery, multiple birth, gender and being small-for-gestational-age. Results PPROM as cause of preterm delivery had no independent effect on the risk of early-onset sepsis, clinical sepsis and blood-culture proven sepsis, while gestational age proved to be the most important contributor to sepsis risk. The diagnosis of PPROM was associated with an increased risk for bronchopulmonary dysplasia (BPD; OR: 1.25, 95% CI: 1.02-1.55, p=0.03) but not with other major outcomes. Conclusions The diagnosis of PPROM per se is not associated with adverse outcome in VLBW infants < 32 weeks apart from a moderately increased risk for BPD. Randomized controlled trials with primary neonatal outcomes are needed to determine which subgroup of VLBW infants benefit from expectant or intentional management of PPROM. PMID:25856083

  15. Availability and use of emergency obstetric care services in four districts of West Bengal, India.

    PubMed

    Biswas, Akhil Bandhu; Das, Dilip Kumar; Misra, Raghunath; Roy, Rabindra Nath; Ghosh, Debdatta; Mitra, Kaninika

    2005-09-01

    Process indicators have been recommended for monitoring the availability and use of emergency obstetric care (EmOC) services. A health facility-based study was carried out in 2002 in four districts of West Bengal, India, to analyze these process indicators. Relevant records and registers for 2001 of all studied facilities in the districts were reviewed to collect data using a pre-designed schedule. The numbers of basic and comprehensive EmOC facilities were inadequate in all the four districts compared to the minimum acceptable level. Overall, 26.2% of estimated annual births took place in the EmOC facilities (ranged from 16.2% to 45.8% in 4 districts) against the required minimum of 15%. The rate of caesarean section calculated for all expected births in the population varied from 3.5% to 4.4% in the four districts with an overall rate of 4%, which is less than the minimum target of 5%. Only 29.9% of the estimated number of complications (which is 15% of all births) was managed in the EmOC facilities. The combined case-fatality rate in the basic/comprehensive EmOC facilities was 1.7%. Major obstetric complications contributed to 85.7% of maternal deaths, and pre-eclampsia/eclampsia was the most common cause. It can be concluded that all the process indicators, except proportion of deliveries in the EmOC facilities, were below the acceptable level. Certain priority measures, such as making facilities fully functional, effective referral and monitoring system, skill-based training, etc., are to be emphasized to improve the situation.

  16. Risk Factors for Birth Asphyxia in an Urban Health Facility in Cameroon

    PubMed Central

    CHIABI, Andreas; NGUEFACK, Seraphin; MAH, Evelyne; NODEM, Sostenne; MBUAGBAW, Lawrence; MBONDA, Elie; TCHOKOTEU, Pierre-Fernand; DOH FRCOG, Anderson

    2013-01-01

    Objective The World Health Organization (WHO) estimates that 4 million children are born with asphyxia every year, of which 1 million die and an equal number survive with severe neurologic sequelae. The purpose of this study was to identify the risk factors of birth asphyxia and the hospital outcome of affected neonates. Materials & Methods This study was a prospective case-control study on term neonates in a tertiary hospital in Yaounde, with an Apgar score of < 7 at the 5th minute as the case group, that were matched with neonates with an Apgar score of ≥ 7 at the 5th minute as control group. Statistical analysis of relevant variables of the mother and neonates was carried out to determine the significant risk factors. Results The prevalence of neonatal asphyxia was 80.5 per 1000 live births. Statistically significant risk factors were the single matrimonial status, place of antenatal visits, malaria, pre-eclampsia/eclampsia, prolonged labor, arrest of labour, prolonged rupture of membranes, and non-cephalic presentation. Hospital mortality was 6.7%, that 12.2% of them had neurologic deficits and/or abnormal transfontanellar ultrasound/electroencephalogram on discharge, and 81.1% had a satisfactory outcome. Conclusion The incidence of birth asphyxia in this study was 80.5% per1000 live birth with a mortality of 6.7%. Antepartum risk factors were: place of antenatal visit, malaria during pregnancy, and preeclampsia/eclampsia. Whereas prolonged labor, stationary labor, and term prolonged rupture of membranes were intrapartum risk faktors. Preventive measures during prenatal visits through informing and communicating with pregnant women should be reinforced. PMID:24665306

  17. Water intoxication presenting as maternal and neonatal seizures: a case report

    PubMed Central

    Chapman, Timothy H; Hamilton, Mark

    2008-01-01

    Introduction We present an unusual case of fitting in the mother and newborn child, and the challenges faced in the management of their hyponatraemia due to water intoxication. Case presentation A previously well 37-year-old, primigravid Caucasian woman presented with features mimicking eclampsia during labour. These included confusion, reduced consciousness and seizures but without a significant history of hypertension, proteinuria or other features of pre-eclampsia. Her serum sodium was noted to be low at 111 mmol/litre as was that of her newborn baby. She needed anti-convulsants with subsequent intubation to stop the fitting and was commenced on a hypertonic saline infusion with frequent monitoring of serum sodium. There is a risk of long-term neurological damage from central pontine myelinolysis if the hyponatraemia is corrected too rapidly. Mother and baby went on to make a full recovery without any long-term neurological complications. Conclusion There is little consensus on the treatment of life-threatening hyponatraemia. Previous articles have outlined several possible management strategies as well as their risks. After literature review, an increase in serum sodium concentration of no more than 8–10 mmol/litre in 24 hours is felt to be safe but can be exceeded with extreme caution if life-threatening symptoms do not resolve. Formulae exist to calculate the amount of sodium needed and how much hypertonic intravenous fluid will be required to allow safer correction. We hypothesise the possible causes of hyponatraemia in this patient and underline its similarity in symptom presentation to eclampsia. PMID:19055802

  18. Activation of endocrine-related gene expression in placental choriocarcinoma cell lines following DNA methylation knock-down.

    PubMed

    Hogg, K; Robinson, W P; Beristain, A G

    2014-07-01

    Increasingly, placental DNA methylation is assessed as a factor in pregnancy-related complications, yet the transcriptional impact of such findings is not always clear. Using a proliferative in vitro placental model, the effect of DNA methylation loss on gene activation was evaluated at a number of genes selected for being differentially methylated in pre-eclampsia-associated placentae in vivo. We aimed to determine whether reduced DNA methylation at specific loci was associated with transcriptional changes at the corresponding gene, thus providing mechanistic underpinnings for previous clinical findings and to assess the degree of transcriptional response amongst our candidate genes. BeWo and JEG3 choriocarcinoma cells were exposed to 1 μM 5-Aza-2'-deoxycytidine (5-Aza-CdR) or vehicle control for 48 h, and re-plated and cultured for a further 72 h in normal media before cells were harvested for RNA and DNA. Bisulphite pyrosequencing confirmed that DNA methylation was reduced by ∼30-50% points at the selected loci studied in both cell lines. Gene activation, measured by qRT-PCR, was highly variable and transcript specific, indicating differential sensitivity to DNA methylation. Most notably, loss of DNA methylation at the leptin (LEP) promoter corresponded to a 200-fold and 40-fold increase in LEP expression in BeWo and JEG3 cells, respectively (P < 0.01). Transcripts of steroidogenic pathway enzymes CYP11A1 and HSD3B1 were up-regulated ∼40-fold in response to 5-Aza-CdR exposure in BeWo cells (P < 0.01). Other transcripts, including aromatase (CYP19), HSD11B2, inhibin (INHBA) and glucocorticoid receptor (NR3C1) were more moderately, although significantly, affected by loss of associated DNA methylation. These data present a mixed effect of DNA methylation changes at selected loci supporting cautionary interpretation of DNA methylation results in the absence of functional data.

  19. Nutrition and maternal, neonatal, and child health.

    PubMed

    Christian, Parul; Mullany, Luke C; Hurley, Kristen M; Katz, Joanne; Black, Robert E

    2015-08-01

    This article reviews the central role of nutrition in advancing the maternal, newborn, and child health agenda with a focus on evidence for effective interventions generated using randomized controlled trials in low- and middle-income countries (LMIC). The 1000 days spanning from conception to 2 years of life are a critical period of time when nutritional needs must be ensured; failure to do so can lead to adverse impacts on short-term survival as well as long-term health and development [corrected]. The burden of maternal mortality continues to be high in many under-resourced settings; prenatal calcium supplementation in populations with low intakes can reduce the risk of pre-eclampsia and eclampsia morbidity and mortality and is recommended, and antenatal iron-folic acid use in many countries may reduce anemia, a condition that may be an underlying factor in postpartum hemorrhage. Sufficient evidence exists to promote multiple micronutrient supplementation during pregnancy to reduce fetal growth restriction and low birth weight. Early initiation of breastfeeding (within an hour), exclusive breastfeeding in the first 6 months of life, and vitamin A supplementation in the first few days of life in Asia (but not in Africa) reduce infant mortality. Biannual large-dose vitamin A supplements to children 6-59 months of age and zinc for treatment of diarrhea continue to be important strategies for improving child health and survival. Early nutrition and micronutrient status can influence child development but should be integrated with early responsive learning interventions. Future research is needed that goes beyond the 1000 days to ensure adequate preconceptional nutrition and health, with special emphasis on adolescents who contribute to a large proportion of first births in many LMIC. Thus, we make the case for integrating proven nutrition interventions with those for health in pregnant women, and with those for health and child development in neonates, infants, and

  20. Polycystic ovary syndrome and endometrial hyperplasia: an overview of the role of bariatric surgery in female fertility.

    PubMed

    Charalampakis, Vasileios; Tahrani, Abd A; Helmy, Ahmed; Gupta, Janesh K; Singhal, Rishi

    2016-12-01

    One of the most effective methods to tackle obesity and its related comorbidities is bariatric surgery. Polycystic ovary syndrome (PCOS) and endometrial hyperplasia (EH), which are associated with increased risk of endometrial carcinoma, have been identified as potentially new indications for bariatric surgery. PCOS is the most common endocrine disorder in women in the reproductive age and is associated with several components of the metabolic syndrome such as obesity, insulin resistance and hypertension. EH is a pre-cancerous condition which arises in the presence of chronic exposure to estrogen unopposed by progesterone such as both in PCOS and obesity. The main bariatric procedures are Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding. These procedures are well established and when correctly selected and performed by experienced bariatric surgeons, they can achieve significant weight loss and remission of obesity related co-morbidities. Studies have shown that bariatric surgery can play an important role in the management of patients with PCOS and improve fertility. Similarly, bariatric surgery has a positive effect on endometrial hyperplasia, making surgically induced weight loss a potentially attractive option for endometrial cancer prevention and treatment. Obesity has an adverse impact on spontaneous pregnancy, assisted reproduction methods and feto-maternal outcomes. After bariatric surgery obese women with subfertility can achieve spontaneous pregnancy. However, while bariatric surgery reduces the risk of pre-eclampsia and gestational diabetes, there is an increased risk of small for gestational age and possible increased risk of stillborn or neonatal death. In this article we will review the evidence regarding the use of bariatric surgery as a treatment modality in patients with PCOS and EH. We also provide an overview of the common bariatric procedures.

  1. Mood disorders and parity – A clue to the aetiology of the postpartum trigger

    PubMed Central

    Di Florio, Arianna; Jones, Lisa; Forty, Liz; Gordon-Smith, Katherine; Robertson Blackmore, Emma; Heron, Jess; Craddock, Nick; Jones, Ian

    2014-01-01

    Background Episodes of postpartum psychosis have been associated with first pregnancies in women with bipolar I disorder. It is unclear, however, if the effect extends to episodes at other times in relation to childbirth and to women with other mood disorders such as major depression and bipolar II disorder. This primiparity effect, which is also seen in other pregnancy related conditions such as pre-eclampsia, is a potentially important clue to the aetiology of childbirth related mood episodes. Methods Participants were interviewed and case notes reviewed. Best-estimate diagnoses were made according to DSM-IV criteria. Data on the occurrence of episodes in pregnancy and the postpartum were available on 3345 full term deliveries from 1667 participants, 934 with bipolar I disorder (BD-I), 278 with bipolar II disorder (BD-II) and 455 with recurrent major depression (RMD). Results Onsets of psychosis/mania within 6 weeks of childbirth were overrepresented in primiparae (p=0.007) with BD-I. Although primiparity was not associated with perinatal bipolar depression, there was an association with the onset of depression within 6 weeks in women with RMD (p=0.035). Whilst women experiencing a postpartum episode were less likely to go on to have further children, this did not account for the association with primiparity. Limitations Data were collected retrospectively. Information on pharmacological treatment was not available. Conclusions Primiparity is associated not only with postpartum psychosis/mania in BD-I, but also with postpartum depression in RMD. Psychosocial factors and biological differences between first and subsequent pregnancies may play a role and are candidates for examination in further studies. PMID:24446553

  2. Obstetric complications in women with IVF conceived pregnancies and polycystic ovarian syndrome.

    PubMed

    Tandulwadkar, Sunita R; Lodha, Pooja A; Mangeshikar, Nirzari T

    2014-01-01

    Polycystic ovarian syndrome (PCOS) is often accompanied by infertility that necessitates ovulation induction using clomiphene citrate, gonadotropins or even in vitro fertilization (IVF). These treatment methods are known to increase the incidence of multiple pregnancies as well as some negative consequences, including a rise in the risk for gestational diabetes mellitus, pre-eclampsia, etc., Furthermore, pregnancies established after IVF carry an increased risk for maternal complications. However, the increased risk of developing adverse obstetric complications has been suggested to occur independently of obesity as well as in populations without assisted reproductive techniques. Many studies have been performed to study the effect of PCOS on pregnancy and the effect of pregnancy on PCOS. The hormonal milieu that is exaggerated in PCOS women is quite well understood at the biochemical and genetic levels. The maternal and neonatal outcomes of PCOS women who have undergone in vitro fertilization-embryo transfer (IVF-ET) have not been widely studied till date. This review aims to evaluate the current evidence regarding adverse obstetric outcomes of PCOS women undergoing IVF-ET. The rationale of this review is to study whether the adverse obstetric outcomes are increased in PCOS women in general, or particularly in those PCOS women who are undergoing IVF-ET. It is also important to analyze via a literature review whether the increased adverse outcomes are due to infertility in general or PCOS per se. An attempt has been made to give evidence regarding preventive strategies for obstetric complications in PCOS women who have undergone IVF-ET.

  3. Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment

    PubMed Central

    Maraka, Spyridoula; Mwangi, Raphael; Yao, Xiaoxi; Sangaralingham, Lindsey R; Singh Ospina, Naykky M; O’Keeffe, Derek T; De Ycaza, Ana E Espinosa; Rodriguez-Gutierrez, Rene; Coddington, Charles C; Stan, Marius N; Brito, Juan P; Montori, Victor M

    2017-01-01

    Objective To estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism. Design Retrospective cohort study. Setting Large US administrative database between 1 January 2010 and 31 December 2014. Participants 5405 pregnant women with subclinical hypothyroidism, defined as untreated thyroid stimulating hormone (TSH) concentration 2.5-10 mIU/L. Exposure Thyroid hormone therapy. Main outcome measure Pregnancy loss and other pre-specified maternal and fetal pregnancy related adverse outcomes. Results Among 5405 pregnant women with subclinical hypothyroidism, 843 with a mean pre-treatment TSH concentration of 4.8 (SD 1.7) mIU/L were treated with thyroid hormone and 4562 with a mean baseline TSH concentration of 3.3 (SD 0.9) mIU/L were not treated (P<0.01). Pregnancy loss was significantly less common among treated women (n=89; 10.6%) than among untreated women (n=614; 13.5%) (P<0.01). Compared with the untreated group, treated women had lower adjusted odds of pregnancy loss (odds ratio 0.62, 95% confidence interval 0.48 to 0.82) but higher odds of preterm delivery (1.60, 1.14 to 2.24), gestational diabetes (1.37, 1.05 to 1.79), and pre-eclampsia (1.61, 1.10 to 2.37); other pregnancy related adverse outcomes were similar between the two groups. The adjusted odds of pregnancy loss were lower in treated women than in untreated women if their pre-treatment TSH concentration was 4.1-10 mIU/L (odds ratio 0.45, 0.30 to 0.65) but not if it was 2.5-4.0 mIU/L (0.91, 0.65 to 1.23) (P<0.01). Conclusion Thyroid hormone treatment was associated with decreased risk of pregnancy loss among women with subclinical hypothyroidism, especially those with pre-treatment TSH concentrations of 4.1-10 mIU/L. However, the increased risk of other pregnancy related adverse outcomes calls for additional studies evaluating the safety of thyroid hormone treatment in this patient population. PMID:28122781

  4. Roll-to-roll, shrink-induced superhydrophobic surfaces for antibacterial applications, enhanced point-of-care detection, and blood anticoagulation

    NASA Astrophysics Data System (ADS)

    Nokes, Jolie McLane

    Superhydrophobic (SH) surfaces are desirable because of their unique anti-wetting behavior. Fluid prefers to bead up (contact angle >150°) and roll off (contact angle hysteresis <10°) a SH surface because micro- and nanostructure features trap air pockets. Fluid only adheres to the peaks of the structures, causing minimal adhesion to the surface. Here, shrink-induced SH plastics are fabricated for a plethora of applications, including antibacterial applications, enhanced point-of-care (POC) detection, and reduced blood coagulation. Additionally, these purely structural SH surfaces are achieved in a roll-to-roll (R2R) platform for scalable manufacturing. Because their self-cleaning and water resistant properties, structurally modified SH surfaces prohibit bacterial growth and obviate bacterial chemical resistance. Antibacterial properties are demonstrated in a variety of SH plastics by preventing gram-negative Escherichia coli (E. coli) bacterial growth >150x compared to flat when fluid is rinsed and >20x without rinsing. Therefore, a robust and stable means to prevent bacteria growth is possible. Next, protein in urine is detected using a simple colorimetric output by evaporating droplets on a SH surface. Contrary to evaporation on a flat surface, evaporation on a SH surface allows fluid to dramatically concentrate because the weak adhesion constantly decreases the footprint area. On a SH surface, molecules in solution are confined to a footprint area 8.5x smaller than the original. By concentrating molecules, greater than 160x improvements in detection sensitivity are achieved compared to controls. Utility is demonstrated by detecting protein in urine in the pre-eclampsia range (150-300microgmL -1) for pregnant women. Further, SH surfaces repel bodily fluids including blood, urine, and saliva. Importantly, the surfaces minimize blood adhesion, leading to reduced blood coagulation without the need for anticoagulants. SH surfaces have >4200x and >28x reduction of

  5. Differential effects of complement activation products c3a and c5a on cardiovascular function in hypertensive pregnant rats.

    PubMed

    Lillegard, Kathryn E; Loeks-Johnson, Alex C; Opacich, Jonathan W; Peterson, Jenna M; Bauer, Ashley J; Elmquist, Barbara J; Regal, Ronald R; Gilbert, Jeffrey S; Regal, Jean F

    2014-11-01

    Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia-induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension. On gestational day (GD) 14, rats underwent sham surgery or vascular clip placement on ovarian arteries and abdominal aorta (RUPP). Rats were treated once daily with the C5a receptor antagonist (C5aRA), PMX51 (acetyl-F-[Orn-P-(D-Cha)-WR]), the C3a receptor antagonist (C3aRA), SB290157 (N(2)-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14-18. Both the C3aRA and C5aRA attenuated placental ischemia-induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia-induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia-induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia-induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti

  6. Evidence-based management for preeclampsia.

    PubMed

    von Dadelszen, Peter; Menzies, Jennifer; Gilgoff, Sarah; Xie, Fang; Douglas, M Joanne; Sawchuck, Diane; Magee, Laura A

    2007-05-01

    This review reflects both the variable presentation and the systemic nature of preeclampsia. Recommendations for the comprehensive evaluation and management of organ dysfunction associated with pre-eclampsia are included. The main points in the review are that: (1) Preeclampsia is a systemic disorder that may affect many organ systems. (2) For preeclampsia remote from term (<34 weeks), expectant management improves perinatal outcomes, but requires obsessive surveillance to mitigate maternal risks and is a "package." (3) Initial assessment and ongoing surveillance of women with preeclampsia should include assessment of all vulnerable maternal organs as well as of the fetus. (4) Initiate antihypertensive drug treatment immediately if sBP >160 mmHg or dBP more than 110 mmHg, or if sBP 140-159 mmHg and/or dBP 85-109 mmHg (prepregnancy renal disease or diabetes). (5) The treatment of nonsevere pregnancy hypertension should include a treatment goal of dBP 80-105 mmHg (depending on practitioner preference), with one of the following agents, Methyldopa, Labetalol, Nifedipine, or, with special indications (renal or cardiac diseases), diuretics. (6) Drugs to avoid: angiotensin-converting enzyme inhibitors; angiotensin II receptor antagonists; and atenolol. (7) For the acute management of severe hypertension, initially reduce dBP by 10 mmHg and maintain the blood pressure at or below that level with either Nifedipine or Labetalol. (8) For both prophylaxis against and treatment of eclampsia, MgSO4 (4 g IV stat, then 1 g/hr). (9) For recurrent seizures, MgSO4 (2g IV stat, then increase to 1.5 g/hr). (10) Total fluid intake should not exceed 80 ml/hr; tolerate urine outputs as low as 10 ml/hr. (11) Early-onset and/or severe preeclampsia predict later cardiovascular morbidity and mortality; it would seem prudent to offer such women screening and lipid lowering interventions.

  7. Placental endoplasmic reticulum stress negatively regulates transcription of placental growth factor via ATF4 and ATF6β: implications for the pathophysiology of human pregnancy complications.

    PubMed

    Mizuuchi, Masahito; Cindrova-Davies, Tereza; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J; Yung, Hong Wa

    2016-03-01

    Low maternal circulating concentrations of placental growth factor (PlGF) are one of the hallmarks of human pregnancy complications, including fetal growth restriction (FGR) and early-onset pre-eclampsia (PE). Currently, PlGF is used clinically with other biomarkers to screen for high-risk cases, although the mechanisms underlying its regulation are largely unknown. Placental endoplasmic reticulum (ER) stress has recently been found to be elevated in cases of FGR, and to an even greater extent in early-onset PE complicated with FGR. ER stress activates the unfolded protein response (UPR); attenuation of protein translation and a reduction in cell growth and proliferation play crucial roles in the pathophysiology of these complications of pregnancy. In this study, we further identified that ER stress regulates release of PlGF. We first observed that down-regulation of PlGF protein was associated with nuclear localization of ATF4, ATF6α and ATF6β in the syncytiotrophoblast of placentae from PE patients. Transcript analysis showed a decrease of PlGF mRNA, and an increase from genes encoding those UPR transcription factors in placentae from cases of early-onset PE, but not of late-onset (>34 weeks) PE, compared to term controls. Further investigations indicated a strong correlation between ATF4 and PlGF mRNA levels only (r = - 0.73, p < 0.05). These results could be recapitulated in trophoblast-like cells exposed to chemical inducers of ER stress or hypoxia-reoxygenation. The stability of PlGF transcripts was unchanged. The use of small interfering RNA specific for transcription factors in the UPR pathways revealed that ATF4 and ATF6β, but not ATF6α, modulate PlGF transcription. To conclude, ATF4 and ATF6β act synergistically in the negative regulation of PlGF mRNA expression, resulting in reduced PlGF secretion by the trophoblast in response to stress. Therefore, these results further support the targeting of placental ER stress as a potential new therapeutic

  8. Frequency of the CCR5-delta32 allele in Brazilian populations: A systematic literature review and meta-analysis.

    PubMed

    Silva-Carvalho, Wlisses Henrique Veloso; de Moura, Ronald Rodrigues; Coelho, Antonio Victor Campos; Crovella, Sergio; Guimarães, Rafael Lima

    2016-09-01

    The CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp deletion in the CCR5 gene (CCR5-delta32) that produces a truncated non-functional protein not expressed on the cell surface. This polymorphism, known to be associated with susceptibility to infectious and inflammatory diseases, such as osteomyelitis, pre-eclampsia, systemic lupus erythematous, juvenile idiopathic arthritis, rheumatoid arthritis and HIV/AIDS, is more commonly found in European populations with average frequency of 10%. However, it is also possible to observe a significant frequency in other world populations, such as the Brazilian one. We performed a systematic review and meta-analysis of CCR5-delta32 genetic association studies in Brazilian populations throughout the country to estimate the frequency of this polymorphism. We also compared CCR5-delta32 frequencies across Brazilian regions. The systematic literature reviewed studies involving delta32 allele in Brazilian populations published from 1995 to 2015. Among the reviewed literature, 25 studies including 30 Brazilian populations distributed between the North, Northeast, South and Southeast regions were included in our meta-analysis. We observed an overall allelic frequency of 4% (95%-CI, 0.03-0.05), that was considered moderate and, notably, higher than some European populations, such as Cyprus (2.8%), Italy (3%) and Greece (2.4%). Regarding the regional frequency comparisons between North-Northeast (N-NE) and South-Southeast (S-SE) regions, we observed an allelic frequency of 3% (95%-CI, 0.02-0.04) and 4% (95%-CI, 0.03-0.05), respectively. The populations from S-SE regions had a slightly higher CCR5-delta32 frequency than N-NE regions (OR=1.41, p=0.002). Although there are several studies about the CCR5-delta32 polymorphism and its effect on the immune response of some infectious diseases, this report is the first meta

  9. Acute renal failure in pregnancy: our experience.

    PubMed

    Aggarwal, Rohina S; Mishra, Vineet V; Jasani, Anil F; Gumber, Manoj

    2014-03-01

    Acute renal failure (ARF) is a serious medical complication during pregnancy, and, in the post-partum period, is associated with significant maternal morbidity and mortality as well as fetal loss. The objective of our study is to find the etiology and maternal outcome of ARF during pregnancy. The study was conducted at the Obstetrics and Gynecology Department of the Institute of Kidney Disease and Research Center, Ahmedabad, India from January 2009 to January 2011. Fifty previously healthy patients who developed ARF, diagnosed on oliguria and serum creatinine >2 mg%, were included in the study. Patients with a known history of renal disease, diabetes and hypertension were excluded from the study. All patients were followed-up for a period of six months. Patient re-cords, demographic data, urine output on admission and preceding history of antepartum hemorrhage (APH), post-partum hemorrhage (PPH), septicemia, operative interventions and retained product of conception were noted and need for dialysis was considered. Patients were thoroughly examined and baseline biochemical investigations and renal and obstetrical ultrasound were performed on each patient and bacterial culture sensitivity on blood, urine or vaginal swabs were performed in selected patients. The age range was 19-38 years (mean 26 ± 3.8). The first trimester, second trimester and puerperal groups comprised of four (8%), 25 (50%) and 21 patients (42%), respectively. Hemorrhage was the etiology for ARF in 15 (30%), APH in ten (20%) and PPH in five (10%) patients. Eleven (22%) patients had lower segment cesarian section (LSCS) while 36 (78%) patients had normal vaginal delivery. In 20 (40%) patients, puerperal sepsis was the etiological factor, while pre-eclampsia, eclampsia and HELLP syndrome accounted for 18 (36%) patients. Two (4%) patients had disseminated intravascular coagulation on presentation while one (2%) patient was diagnosed with hemolytic uremic syndrome. Maternal mortality was 12% (n = 6

  10. Angiotensin II activates the calcineurin/NFAT signaling pathway and induces cyclooxygenase-2 expression in rat endometrial stromal cells.

    PubMed

    Abraham, Florencia; Sacerdoti, Flavia; De León, Romina; Gentile, Teresa; Canellada, Andrea

    2012-01-01

    Cyclooxygenase (COX)-2, the inducible isoform of cyclooxygenase, plays a role in the process of uterine decidualization and blastocyst attachment. On the other hand, overexpression of COX-2 is involved in the proliferation of the endometrial tissue during endometriosis. Deregulation of the renin-angiotensin-system plays a role in the pathophysiology of endometriosis and pre-eclampsia. Angiotensin II increases intracellular Ca(2+) concentration by targeting phospholypase C-gamma in endometrial stromal cells (ESC). A key element of the cellular response to Ca(2+) signals is the activity of the Ca(2+)- and calmodulin-dependent phosphatase calcineurin. Our first aim was to study whether angiotensin II stimulated Cox-2 gene expression in rat ESC and to analyze whether calcineurin activity was involved. In cells isolated from non-pregnant uteri, COX-2 expression--both mRNA and protein--was induced by co-stimulation with phorbol ester and calcium ionophore (PIo), as well as by angiotensin II. Pretreatment with the calcineurin inhibitor cyclosporin A inhibited this induction. We further analyzed the role of the calcineurin/NFAT signaling pathway in the induction of Cox-2 gene expression in non-pregnant rat ESC. Cyclosporin A abolished NFATc1 dephosphorylation and translocation to the nucleus. Cyclosporin A also inhibited the transcriptional activity driven by the Cox-2 promoter. Exogenous expression of the peptide VIVIT -specific inhibitor of calcineurin/NFAT binding- blocked the activation of Cox-2 promoter and the up-regulation of COX-2 protein in these cells. Finally we analyzed Cox-2 gene expression in ESC of early-pregnant rats. COX-2 expression--both mRNA and protein--was induced by stimulation with PIo as well as by angiotensin II. This induction appears to be calcineurin independent, since it was not abrogated by cyclosporin A. In conclusion, angiotensin II induced Cox-2 gene expression by activating the calcineurin/NFAT signaling pathway in endometrial stromal

  11. Reducing stillbirths: interventions during labour

    PubMed Central

    Darmstadt, Gary L; Yakoob, Mohammad Yawar; Haws, Rachel A; Menezes, Esme V; Soomro, Tanya; Bhutta, Zulfiqar A

    2009-01-01

    Background Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined. Methods We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies. Results We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact

  12. Hypertensive disorders of pregnancy and risk of diabetes in Indian women: a cross-sectional study

    PubMed Central

    Agrawal, Sutapa; Fledderjohann, Jasmine

    2016-01-01

    Background Epidemiological data from high-income countries suggest that women with hypertensive disorders of pregnancy (HDP) are more likely to develop diabetes later in life. Objective We investigated the association between pre-eclampsia and eclampsia (PE&E) during pregnancy and the risk of diabetes in Indian women. Design Cross-sectional study. Setting India. Methods Data from India's third National Family Health Survey (NFHS-3, 2005–2006), a cross-sectional survey of women aged 15–49 years, are used. Self-reported symptoms suggestive of PE&E were obtained from 39 657 women who had a live birth in the 5 years preceding the survey. The association between PE&E and self-reported diabetes status was assessed using multivariable logistic regression models adjusting for dietary intake, body mass index (BMI), tobacco smoking, alcohol drinking, frequency of TV watching, sociodemographic characteristics and geographic region. Results The prevalence of symptoms suggestive of PE&E in women with diabetes was 1.8% (n=207; 95% CI 1.5 to 2.0; p<0.0001) and 2.1% (n=85; 95% CI 1.8 to 2.3; p<0.0001), respectively, compared with 1.1% (n=304; 95% CI 1.0 to 1.4) and 1.2% (n=426; 95% CI 1.1 to 1.5) in women who did not report any PE&E symptoms. In the multivariable analysis, PE&E was associated with 1.6 times (OR=1.59; 95% CI 1.31 to 1.94; p<0.0001) and 1.4 times (OR=1.36; 95% CI 1.05 to 1.77; p=0.001) higher risk for self-reported diabetes even after controlling for dietary intake, BMI and sociodemographic characteristics. Conclusions HDP is strongly associated with the risk of diabetes in a large nationally representative sample of Indian women. These findings are important for a country which is already tackling the burden of young onset of diabetes in the population. However, longitudinal medical histories and a clinical measurement of diabetes are needed in this low-resource setting. PMID:27496230

  13. Vitamin D during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis

    PubMed Central

    Thorne-Lyman, Andrew; Fawzi, Wafaie W.

    2013-01-01

    Summary Vitamin D has well-defined classical functions related to calcium metabolism and bone health but also has non-classical effects that may influence other aspects of health. There has been considerable recent interest in the role of vitamin D on outcomes related to pregnancy and young child health but few efforts have been made to systematically consolidate this evidence to inform the research and policy agenda for low income countries. A systematic review was undertaken to identify intervention and observational studies of vitamin D supplementation, intake, or status (25-hydroxy-vitamin D) during pregnancy on perinatal and infant health outcomes. Data from trials and observational studies isolating the effect of vitamin D supplementation and intake were extracted and study quality was evaluated. Meta-analysis was used to pool effect estimates. We identified 5 randomized trials with outcomes of relevance to our review. All had small sample size and dosage amount, duration, and frequency varied as did the ability to correct deficiency. Pooled analysis of trials using fixed effects models suggested protective effects of supplementation on low birthweight (3 trials, Risk ratio (RR)=0.40 [95% confidence interval (CI), 0.23, 0.71]) and non-significant but suggestive effects of daily supplementation on small-for-gestational age (SGA) (2 trials, RR=0.67, [0.40, 1.11]. No effect on preterm delivery (<37 weeks) was evident (2 trials, RR=0.77 [0.35, 1.66]). Little evidence from trials exists to evaluate the effect of vitamin D supplementation during pregnancy on maternal, perinatal or infant health outcomes. Based on both trials and observational studies, we recommend that future research explore SGA, preterm delivery, pre-eclampsia, and maternal and childhood infections, as outcomes of interest. Trials should focus on populations with a high prevalence of vitamin D deficiency, explore the relevance of timing of supplementation, and the dosage used in such trials

  14. Placental Growth Measures in Relation to Birth Weight in a Latin American Population.

    PubMed

    Grandi, Carlos; Veiga, Angélica; Mazzitelli, Nancy; Cavalli, Ricardo de Carvalho; Cardoso, Viviane

    2016-08-01

    Introduction The placenta, translates how the fetus experiences the maternal environment and is a principal influence on birth weight (BW). Objective To explore the relationship between placental growth measures (PGMs) and BW in a public maternity hospital. Methods Observational retrospective study of 870 singleton live born infants at Hospital Maternidad Sardá, Universidad de Buenos Aires, Argentina, between January 2011 and August 2012 with complete data of PGMs. Details of history, clinical and obstetrical maternal data, labor and delivery and neonatal outcome data, including placental measures derived from the records, were evaluated. The following manual measurements of the placenta according to standard methods were performed: placental weight (PW, g), larger and smaller diameters (cm), eccentricity, width (cm), shape, area (cm(2)), BW/PW ratio (BPR) and PW/BW ratio (PBR), and efficiency. Associations between BW and PGMs were examined using multiple linear regression. Results Birth weight was correlated with placental weight (R(2) = 0.49, p < 0.001), whereas gestational age was moderately correlated with placental weight (R(2) = 0.64, p < 0.001). By gestational age, there was a positive trend for PW and BPR, but an inverse relationship with PBR (p < 0.001). Placental weight alone accounted for 49% of birth weight variability (p < 0,001), whereas all PGMs accounted for 52% (p < 0,001). Combined, PGMs, maternal characteristics (parity, pre-eclampsia, tobacco use), gestational age and gender explained 77.8% of BW variations (p < 0,001). Among preterm births, 59% of BW variances were accounted for by PGMs, compared with 44% at term. All placental measures except BPR were consistently higher in females than in males, which was also not significant. Indices of placental efficiency showed weakly clinical relevance. Conclusions Reliable measures of placental growth estimate 53.6% of BW variances and project this outcome to a

  15. Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production.

    PubMed

    Tulppala, M; Marttunen, M; Söderstrom-Anttila, V; Foudila, T; Ailus, K; Palosuo, T; Ylikorkala, O

    1997-07-01

    women receiving PLA (13.0%) developed pre-eclampsia (not significant). Therefore, although treatment with LDA caused a desirable biochemical effect, it did not improve pregnancy outcome in RSA women with or without detectable ACA.

  16. Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM)

    PubMed Central

    2014-01-01

    Background Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications. Methods/Design We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy. Discussion The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and

  17. Interventions for the control of diarrhoeal diseases among young children: prevention of low birth weight*

    PubMed Central

    Ashworth, Ann; Feachem, R. G.

    1985-01-01

    The effect of low birth weight (LBW) on diarrhoea morbidity and mortality is analysed and interventions to increase birth weights are reviewed. Birth weight is a major determinant of infant mortality and, in developed countries at least, its effect on neonatal mortality is independent of socioeconomic status. We have located no satisfactory data on LBW as a determinant of diarrhoea mortality or morbidity. The strong association between LBW and mortality, however, makes it likely that there is an association between LBW and diarrhoea mortality in developing countries where diarrhoea is a major cause of infant death. Poor maternal nutrition, certain infections, pre-eclampsia, arduous work after mid-pregnancy, short birth intervals, and teenage pregnancy are likely to be causally associated with LBW in developing countries. Tobacco and alcohol consumption are additional risk factors. Of the interventions examined, maternal food supplementation has been the most studied. If targeted to mothers at nutritional risk, and if the food is consumed in addition to the usual diet, the prevalence of LBW can be expected to be reduced. However, food supplementation can be expensive and the results from carefully supervised feeding trials may be better than those that can be achieved in national programmes. The effect of supplementation with iron, zinc or folate requires further study. If it were possible to intervene in maternal nutrition, health and life-style in a developing country in a way that reduced the prevalence of LBW from around 30% to around 15%, a fall in the infant mortality rate of around 26% would be expected. The fall in infant diarrhoea mortality rate might be similar. The scarce data on relative risk of morbidity by birth weight do not allow any comparable computations for morbidity reductions to be made. This review confirms that whatever its association with diarrhoea, LBW is an important determinant of infant mortality. For the more general goal of reducing

  18. The Impact of Macronutrients on Retinal Microvasculature among Singapore Pregnant Women during the Mid-Late Gestation

    PubMed Central

    Li, Ling-Jun; Ong, Peng Guan; Colega, Marjorelee T.; Han, Chad Yixian; Chen, Ling Wei; Man Eyn Kidd, Ryan; Lamoureux, Ecosse; Gluckman, Peter; Kwek, Kenneth; Chong, Yap Seng; Saw, Seang Mei; Godfrey, Keith M.; Wong, Tien Yin; Chong Foong-Fong, Mary

    2016-01-01

    Background Imbalanced macronutrient intakes can induce impairment of endothelial and vascular function, and further lead to metabolic and cardiovascular disease. However, little is known about the influence of such diets on endothelial and vascular dysfunction in pregnant women, even though high-fat diet is a known risk for pregnancy complications such as gestational diabetes and pre-eclampsia. Objective We aimed to assess the association between maternal macronutrient intakes (protein, fat and carbohydrates), dietary quality and retinal microvascular changes in a multi-ethnic Asian mother-offspring cohort. Methods Pregnant women (n = 614) with singleton pregnancies were recruited during their first trimester from June 2009 to Sep 2010. Maternal diet quality and macronutrient intakes, expressed as a percentage of total energy during pregnancy, were ascertained using 24 hr recalls and 3 d food diaries at 26–28 weeks gestation. Retinal examination was completed at the same clinic visit. Dietary quality was assessed and scored using the Health Eating Index in Asian Pregnant women (HEI-AP), while macronutrients intakes ware expressed as percentages of total energy and further log transformed for analysis. Associations were examined cross-sectionally by substitution models with the use of multiple linear regression. Results In adjusted model, each 20 points decrease in HEI-AP score was associated with a significant increase of 1.70 μm (p<0.05) in retinal venular calibre. Each 0.1 log increase in percentage of total fat intake was associated with a significant increment of 1.84 μm (p<0.05) in retinal venular caliber. Additionally, each 0.1 log increase in percentage of mono-unsaturated fat intake was associated with an increment of 1.84 μm (p<0.01) in retinal venular caliber. Conclusions In this cross-sectional study, we found that women with higher fat and lower protein intakes, and lower diet quality tended to have wider retinal venular caliber, which is

  19. Strengthening the emergency healthcare system for mothers and children in The Gambia

    PubMed Central

    2010-01-01

    A system to improve the management of emergencies during pregnancy, childbirth, infancy and childhood in a region of The Gambia (Brikama) with a population of approximately 250,000 has been developed. This was accomplished through formal partnership between the Gambian Ministry of Health, the World Health Organisation, Maternal Childhealth Advocacy International and the Advanced Life Support Group. Since October 2006, the hospital in Brikama has been renovated and equipped and more efficiently provided with emergency medicines. An emergency ambulance service now links the community with the hospital through a mobile telephone system. Health professionals from community to hospital have been trained in obstetric, neonatal and paediatric emergency management using skills' based education. The programme was evaluated in log books detailing individual resuscitations and by external assessment. The hospital now has constant water and electricity, a functioning operating theatre and emergency room; the maternity unit and children's wards have better emergency equipment and there is a more reliable supply of oxygen and emergency drugs, including misoprostol (for treating post partum haemorrhage) and magnesium sulphate (for severe pre-eclampsia). There is also a blood transfusion service. Countrywide, 217 doctors, nurses, and midwives have undergone accredited training in the provision of emergency maternal, newborn and child care, including for major trauma. 33 have received additional education through Generic Instructor Courses and 15 have reached full instructor status. 83 Traditional Birth Attendants and 48 Village Health Workers have been trained in the recognition and initial management of emergencies, including resuscitation of the newborn. Eleven and ten nurses underwent training in peri-operative nursing and anaesthetics respectively, to address the acute shortage required for emergency Caesarean section. Between May 2007 and March 2010, 109 patients, mostly

  20. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results

    PubMed Central

    Yelnik, Cecile M; Laskin, Carl A; Porter, T Flint; Branch, D Ware; Buyon, Jill P; Guerra, Marta M; Lockshin, Michael D; Petri, Michelle; Merrill, Joan T; Sammaritano, Lisa R; Kim, Mimi Y; Salmon, Jane E

    2016-01-01

    Objective We previously reported that lupus anticoagulant (LAC) is the main predictor of poor pregnancy outcome in antiphospholipid antibody (aPL)-positive patients. We sought to confirm this finding in an independent group of patients who were subsequently recruited into the PROMISSE study. Methods The PROMISSE study is a multicentre, prospective, observational study of pregnancy outcomes in women with aPL and/or systemic lupus erythematosus (SLE) that enrolled patients from 2003 to 2015. All consecutive, aPL-positive patients from the PROMISSE study who completed their pregnancy between April 2011 and January 2015 (after the previous PROMISSE report) are included in the current report. Patients were followed monthly until delivery, and aPL was tested at first, second and third trimesters of pregnancy and at 12 weeks post partum. Adverse pregnancy outcomes (APOs) were defined as fetal death after 12 weeks of gestation, neonatal death, delivery prior to 36 weeks of gestation due to pre-eclampsia or placental insufficiency or small-for-gestational age (birth weight <5th percentile). Results Forty-four aPL-positive patients are included in this paper. Thirteen patients had APOs, which occurred in 80% of cases during the second trimester of pregnancy. LAC was present in 69% of patients with APOs compared with 27% of patients without APOs (p=0.01). No association was found between anticardiolipin antibodies (aCL) or anti-β2 glycoprotein I antibodies (aβ2GPI) IgG or IgM positivity and APOs. Definite antiphospholipid syndrome (history of thrombosis and/or pregnancy morbidity and aPL) was found in 92% of patients with any APOs compared with 45% of patients without APOs (p=0.004). Conversely, the frequency of SLE was not statistically different between those with and without APOs (30% vs 39%). Conclusions Our findings, in an independent group of aPL-positive patients from the PROMISSE study, confirm that LAC, but not aCL and aβ2GPI, is predictive of poor pregnancy

  1. A systematic review of the relationship between severe maternal morbidity and post-traumatic stress disorder

    PubMed Central

    2012-01-01

    Background The incidence of severe maternal morbidity is increasing in high-income countries as a consequence, in part, of increased obstetric intervention and increasingly complex medical needs of women who become pregnant. Access to emergency obstetric care means that for the majority of women in these countries, an experience of severe maternal morbidity is unlikely to result in loss of life. However, little is known about the subsequent impact on postnatal psychological health resulting in an evidence gap to support provision of appropriate care for these women. There has recently been increasing recognition that childbirth can be a cause of post-traumatic stress disorder (PTSD). The combination of experiencing a life-threatening complication and its management may culminate in psychological trauma. This systematic review examined the association between women’s experience of severe maternal morbidity during labour, at the time of giving birth or within the first week following birth, and PTSD and its symptoms. Methods Relevant literature was identified through multiple databases, including MEDLINE, PsycINFO, EMBASE, CINAHL, British Nursing Index, Web of Science, Cochrane library and the British Library, using predetermined search strategies. The search terms included "post-traumatic stress disorder", "PTSD", "stress disorders, post-traumatic", "maternal morbidity", “pregnancy complications” “puerperal disorders”, "obstetric labo(u)r complication", "postpartum h(a)emorrhage", "eclampsia”. Studies identified were categorised according to pre-defined inclusion and exclusion criteria. The quality of included studies was assessed using the relevant CASP appraisal tools. Results Eleven primary studies met review criteria. Evidence of a relationship between severe maternal morbidity and PTSD/PTSD symptoms was inconsistent and findings varied between studies. Nevertheless, there is some evidence that severe pre-eclampsia is a risk factor for PTSD and its

  2. O-glycoside biomarker of apolipoprotein C3: responsiveness to obesity, bariatric surgery, and therapy with metformin, to chronic or severe liver disease and to mortality in severe sepsis and graft vs host disease.

    PubMed

    Harvey, Stephen B; Zhang, Yan; Wilson-Grady, Joshua; Monkkonen, Teresa; Nelsestuen, Gary L; Kasthuri, Raj S; Verneris, Michael R; Lund, Troy C; Ely, E Wesley; Bernard, Gordon R; Zeisler, Harald; Homoncik, Monika; Jilma, Bernd; Swan, Therese; Kellogg, Todd A

    2009-02-01

    The glyco-isoforms of intact apolipoprotein C3 (ApoC3) were used to probe glycomic changes associated with obesity and recovery following bariatric surgery, liver diseases such as chronic hepatitis C (CHC) and alcoholic liver cirrhosis, as well as severe, multiorgan diseases such as sepsis and graft vs host disease (GVHD). ApoC3 glyco-isoform ratios responded to unique stimuli that did not correlate with serum lipids or with other blood components measured in either a control population or a group of extremely obese individuals. However, glyco-isoform ratios correlated with obesity with a 1.8-fold change among subjects eligible for bariatric surgery relative to a nonobese control population. Bariatric surgery resulted in rapid change of isoform distribution to that of nonobese individuals, after which the distribution was stable in each individual. Although multiple simultaneous factors complicated effector attribution, the isoform ratios of very obese individuals were nearly normal for diabetic individuals on metformin therapy. Glyco-isoform ratios were sensitive to liver diseases such as chronic hepatitis C and alcoholic liver cirrhosis. The correlation coefficient with fibrosis was superior to that of current assays of serum enzyme levels. Diseases of pregnancy that can result in liver damage, HELLP syndrome and pre-eclampsia, did not alter ApoC3 glyco-isoform ratios. Early after umbilical cord blood transplantation the isoform ratios changed and returned to normal in long-term survivors. Larger changes were observed in persons who died. GVHD had little effect. Persons with severe sepsis showed altered ratios. Similar cut-points for mortality (3.5-fold difference from controls) were found for UCBT and sepsis. Similar values characterized liver cirrhosis. Overall, while changes of glyco-isoform ratios occurred in many situations, individual stability of isoform distribution was evident and large changes were limited to high-level disease. If ratio changes

  3. Hypertensive disorders of pregnancy are an evolutionary adaptation to mitigate the reproductive consequences of the human physique.

    PubMed

    Ayuk, Paul T-Y

    2006-01-01

    cause a rise in maternal blood pressure are multiple and produced in disease-causing concentrations in all pregnancies. Disease arises as a consequence of abnormalities in the maternal regulatory mechanism as occurs in say gestational diabetes mellitus. The search for a placental cause for pre-eclampsia is therefore futile. Research should focus on normal pregnancy and the identification of the factor that regulates maternal blood pressure in the second half of pregnancy. This factor will cause hypotension and prevent endothelial activation and have a role analogous to insulin in the regulation of glycaemia and the development of gestational diabetes mellitus.

  4. Expression of AT1R, AT2R and AT4R and their roles in extravillous trophoblast invasion in the human.

    PubMed

    Williams, P J; Mistry, H D; Innes, B A; Bulmer, J N; Broughton Pipkin, F

    2010-05-01

    The placental renin-angiotensin system (RAS) is active from early pregnancy and may have a role in placentation. Angiotensin II (AngII) acts via binding to receptor types AT1R and AT2R. Recently smaller peptide members of the angiotensin family have been recognised as having biological relevance. Angiotensin (3-8) (AngIV) has a specific receptor (AT4R) and evokes hypertrophy, vasodilatation and vascular inflammatory response. The aim of this study was to characterise placental expression of AT1R, AT2R and AT4R, and to determine whether AngII and AngIV regulate extravillous trophoblast (EVT) invasion, apoptosis and proliferation. Placental samples were obtained from women undergoing elective surgical termination of pregnancy (TOP) at 8-10 weeks gestation (early TOP), 12-14 weeks gestation (mid TOP) or at delivery following normal pregnancy or with pre-eclampsia (PE). Immunohistochemistry and qRT-PCR were performed to determine placental mRNA and protein expression of AT1R, AT2R and AT4R at all gestational ages. EVT invasion following culture with AngII or AngIV was assessed in early placental tissue using Matrigel invasion assays. Invasion was assessed on day 6 of culture and placental explants were harvested for immunohistochemical analysis of apoptosis and proliferation. The results from qRT-PCR and immunohistochemistry showed placental AT1R expression which did not vary with gestation. The highest levels of expression of AT2R were found in early and mid TOP placentae compared to term pregnancy. Expression of AT4R was increased in term placentae, with a significant reduction in PE placentae. Moreover, culture with AngIV or AngII increased EVT invasion from placental explants, which showed increased trophoblast proliferation and reduced apoptosis. This study has characterised expression of AT4R and AT1R and AT2R in human placenta throughout normal pregnancy and in PE. Both AngIV and AngII may play an important role in normal pregnancy.

  5. Isolated elevation of IgA anti-beta2glycoprotein I antibodies with manifestations of antiphospholipid syndrome: a case series of five patients.

    PubMed

    Kumar, S; Papalardo, E; Sunkureddi, P; Najam, S; González, E B; Pierangeli, S S

    2009-10-01

    Current diagnostic classification criteria recommend elevated titres of anti-cardiolipin (aCL) and/or anti-beta(2)GPI antibody by ELISA IgG or IgM and/or lupus anticoagulant (LA) to confirm antiphospholipid syndrome (APS). Although IgA aPL antibodies have been shown to be pathogenic in animal models of APS, their clinical significance has remained elusive. We report four cases of exclusive IgA anti-beta(2)GPI antibody sero-positivity with concomitant clinical manifestations associated with APS. Four of the five patients were LA negative. 1) Thirty-eight-year-old African-American female with SLE presented with resolving digital ulcers. Serum IgA anti-beta(2)GPI antibody titres were 118.5 SAU (normal range: 0-20 SAU). 2) Twenty-seven-year-old African-American woman with SLE was evaluated for recent onset of severe headaches, unresponsive to analgesics and anti-migraine medications. MRI of the brain revealed hyper-intensities in the white matter in the frontal lobes. Serum IgA anti-beta(2)GPI antibody titres were 29.1 Standard A Units (SAU). 3) Thirty-two-year-old Hispanic female with history of two unexplained miscarriages and negative serologies for SLE. Serum IgA anti-beta(2)GPI antibody titres were 102.0 SAU. 4) Twenty-five-year-old white female with history of recent unexplained miscarriage in the 11th week of gestation and associated complaints of numbness and tingling in her hands. Her IgA anti-beta(2)GPI antibody titre was 62.0 SAU. 5) Twenty-five-year-old African-American woman with SLE, positive for anti-Ro antibodies with a history of ischemic fingers, a pregnancy loss and recent pregnancy complicated due to pre-eclampsia. Her LA was positive and her IgA anti-beta(2)GPI antibody titer was 186.0 SAU. This case series supports that elevated IgA anti-beta(2)GPI antibody titres may identify additional patients who have clinical features of APS but who do not meet current diagnostic criteria.

  6. Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis

    PubMed Central

    Simmonds, Mark; Bryant, Maria; Sheldon, Trevor A; Tuffnell, Derek; Golder, Su; Dunne, Fidelma; Lawlor, Debbie A

    2016-01-01

    Objectives To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified. Design Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials. Data sources Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts. Eligibility criteria for selecting studies Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome. Appraisal and data extraction Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools. Results 25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of

  7. Exercise, vascular wall and cardiovascular diseases: an update (Part 1).

    PubMed

    Leung, Fung Ping; Yung, Lai Ming; Laher, Ismail; Yao, Xiaoqiang; Chen, Zhen Yu; Huang, Yu

    2008-01-01

    shock transcription factor 1 activity; (v) inflammation by reducing serum inflammatory cytokines such as high-sensitivity C-reactive protein (hCRP), interleukin (IL)-6, IL-18 and tumour necrosis factor-alpha and by regulating Toll-like receptor 4 pathway. Exercise also alters vascular remodelling, which involves two forms of vessel growth including angiogenesis and arteriogenesis. Angiogenesis refers to the formation of new capillary networks. Arteriogenesis refers to the growth of pre-existent collateral arterioles leading to formation of large conductance arteries that are well capable to compensate for the loss of function of occluded arteries. Another aim of this review is to focus on exercise-related cardiovascular protection against CVD and associated risk factors such as aging, coronary heart disease, hypertension, heart failure, diabetes mellitus and peripheral arterial diseases mediated by vascular remodelling. Lastly, this review examines the benefits of exercise in mitigating pre-eclampsia during pregnancy by mechanisms that include improved blood flow, reduced blood pressure, enhanced placental growth and vascularity, increased activity of antioxidant enzymes, reduced oxidative stress and restored vascular endothelial dysfunction.

  8. Uric Acid as a predictor of adverse maternal and perinatal outcomes in women hospitalized with preeclampsia.

    PubMed

    Livingston, Joel R; Payne, Beth; Brown, Mark; Roberts, James M; Côté, Anne-Marie; Magee, Laura A; von Dadelszen, Peter

    2014-10-01

    Objectif : Bien qu’un taux sérique élevé d’acide urique soit couramment constaté chez les femmes qui présentent une prééclampsie, son utilité pour ce qui est de la prévision des issues indésirables a récemment été remise en question. Nous avions pour objectif d’analyser les données issues d’une importante cohorte de femmes présentant une prééclampsie, afin de déterminer l’utilité du taux sérique d’acide urique pour ce qui est de la prévision des issues indésirables maternelles et périnatales. Méthodes : Les données ont été tirées d’une étude prospective internationale toujours en cours qui porte sur des femmes hospitalisées présentant une prééclampsie (Pre-eclampsia Integrated Estimate of RiSk). Une régression logistique univariée a été utilisée pour déterminer la relation entre la concentration sérique en acide urique (tant absolue que corrigée en fonction de l’âge gestationnel [score Z]) et les issues indésirables (maternelles et périnatales). Des analyses ont été menées pour comparer des cohortes de femmes présentant une prééclampsie définie par l’hypertension et la protéinurie à des cohortes de femmes présentant une prééclampsie définie par l’hypertension et l’hyperuricémie. Résultats : Le score Z quant à l’acide urique était associé à des issues périnatales indésirables (RC, 1,5; IC à 95 %, 1,4 - 1,7) et comptait une estimation ponctuelle > 0,7 (surface sous la courbe de la fonction d’efficacité de l’observateur, 0,72; IC à 95 %, 0,69 - 0,74). Une association significative a également été constatée entre la concentration sérique en acide urique et des issues indésirables maternelles; toutefois, l’estimation ponctuelle était < 0,7. Aucune différence significative n’a été constatée entre les groupes « prééclampsie définie par l’hypertension et la protéinurie » et « prééclampsie définie par l’hypertension et l

  9. Endothelin-1 down-regulates matrix metalloproteinase 14 and 15 expression in human first trimester trophoblasts via endothelin receptor type B

    PubMed Central

    Majali-Martinez, Alejandro; Velicky, Philipp; Pollheimer, Jürgen; Knöfler, Martin; Yung, Hong wa; Burton, Graham J.; Tabrizi-Wizsy, Nassim Ghaffari; Lang, Uwe; Hiden, Ursula; Desoye, Gernot; Dieber-Rotheneder, Martina

    2017-01-01

    STUDY QUESTION Does endothelin-1 (ET-1) regulate matrix metalloproteinase (MMP) 14 and 15 production and invasion of human first trimester trophoblasts? SUMMARY ANSWER ET-1 in pathophysiological concentrations down-regulates MMP14 and MMP15 expression via endothelin receptor (ETR) type B and decreases trophoblast migration and invasion. WHAT IS KNOWN ALREADY MMP14 and MMP15 are involved in trophoblast invasion. Impairment of invasion has been linked to pregnancy complications such as pre-eclampsia (PE). ET-1 is up-regulated in PE. STUDY DESIGN, SIZE, DURATION In vitro study using primary human trophoblasts from 50 first trimester placentas (gestational week 7–12). PARTICIPANTS/MATERIALS, SETTING, METHODS Trophoblasts were cultured in the absence or presence of 10–100 nM ET-1. MMP14 and MMP15 mRNA and protein were quantified by RT-qPCR and Western blotting, respectively. Selective antagonists for ETRA (BQ-123) or ETRB (BQ-788) were used to identify ETR subtypes involved. Functional ET-1 effects were tested in first trimester chorionic villous explants and transwell invasion assays. The roles of tumor necrosis factor (TNF)-α (25 ng/ml) and oxygen (1%) in ET-1 regulation of MMP14 and 15 expression were assessed by Western blotting. MAIN RESULTS AND THE ROLE OF CHANCE ET-1 down-regulated MMP14 and MMP15 mRNA (−21% and −26%, respectively, P < 0.05) and protein levels (–18% and –22%, respectively, P < 0.05). This effect was mediated via ETRB. ET-1 decreased trophoblast outgrowth in placental explants (−24%, P < 0.05) and trophoblast invasion (−26%, P ≤ 0.01). TNF-α enhanced ET-1 mediated MMP15 down-regulation (by 10%, P < 0.05), whereas hypoxia abolished the effect of ET-1 on both MMPs. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Only primary trophoblasts were used in this study. Since trophoblast yield from first trimester placental material is limited, further aspects of MMP14 and 15 regulation could not be characterized. Other anti

  10. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME - PART 2.

    PubMed

    Goodman, Neil F; Cobin, Rhoda H; Futterweit, Walter; Glueck, Jennifer S; Legro, Richard S; Carmina, Enrico

    2015-12-01

    . Assessment of a woman with PCOS for infertility involves evaluating for preconceptional issues that may affect response to therapy or lead to adverse pregnancy outcomes and evaluating the couple for other common infertility issues that may affect the choice of therapy, such as a semen analysis. Women with PCOS have multiple factors that may lead to an elevated risk of pregnancy, including a high prevalence of IGT--a clear risk factor for gestational diabetes--and MetS with hypertension, which increases the risk for pre-eclampsia and placental abruption. Women should be screened and treated for hypertension and diabetes prior to attempting conception. Women should be counseled about weight loss prior to attempting conception, although there are limited clinical trial data demonstrating a benefit to this recommendation. Treatment for women with PCOS and anovulatory infertility should begin with an oral agent such as clomiphene citrate or letrozole, an aromatase inhibitor.

  11. Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner

    PubMed Central

    Vasilopoulou, E.; Loubière, L.S.; Lash, G.E.; Ohizua, O.; McCabe, C.J.; Franklyn, J.A.; Kilby, M.D.; Chan, S.Y.

    2014-01-01

    STUDY QUESTION Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? SUMMARY ANSWER T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. WHAT IS KNOWN ALREADY Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. STUDY DESIGN, SIZE, DURATION This laboratory-based study used human decidua from first (8–11 weeks; n = 18) and second (12–16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10−) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel® was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRα1

  12. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary.

    PubMed

    Magee, Laura A; Pels, Anouk; Helewa, Michael; Rey, Evelyne; von Dadelszen, Peter

    2014-05-01

    Objectif : Le présent résumé directif présente un sommaire des données qui ont été évaluées dans le cadre de la directive clinique rédigée par le groupe de travail canadien sur les troubles hypertensifs de la grossesse et publiée dans Pregnancy Hypertension (http://www.pregnancyhypertension.org/article/S2210-7789(14)00004-X/fulltext), en vue d’offrir une approche raisonnable envers le diagnostic, l’évaluation et la prise en charge des troubles hypertensifs de la grossesse. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans Medline, CINAHL et The Cochrane Library en mars 2012 au moyen d’un vocabulaire contrôlé (p. ex. « pregnancy », « hypertension », « pre-eclampsia », « pregnancy toxemias ») et de mots clés (p. ex. « diagnosis », « evaluation », « classification », « prediction », « prevention », « prognosis », « treatment », « post-partum follow-up ») appropriés. Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles rédigés en anglais ou en français entre janvier 2006 et février 2012. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu’en septembre 2013. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d’organismes s’intéressant à l’évaluation des technologies dans le domaine de la santé et d’organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d’étude canadien sur les soins de santé préventifs (Tableau). Recommandations Chapitre 1

  13. In Vitro Fertilization and Multiple Pregnancies

    PubMed Central

    2006-01-01

    Executive Summary Objective The objective of this health technology policy assessment was to determine the clinical effectiveness and cost-effectiveness of IVF for infertility treatment, as well as the role of IVF in reducing the rate of multiple pregnancies. Clinical Need: Target Population and Condition Typically defined as a failure to conceive after a year of regular unprotected intercourse, infertility affects 8% to 16% of reproductive age couples. The condition can be caused by disruptions at various steps of the reproductive process. Major causes of infertility include abnormalities of sperm, tubal obstruction, endometriosis, ovulatory disorder, and idiopathic infertility. Depending on the cause and patient characteristics, management options range from pharmacologic treatment to more advanced techniques referred to as assisted reproductive technologies (ART). ART include IVF and IVF-related procedures such as intra-cytoplasmic sperm injection (ICSI) and, according to some definitions, intra-uterine insemination (IUI), also known as artificial insemination. Almost invariably, an initial step in ART is controlled ovarian stimulation (COS), which leads to a significantly higher rate of multiple pregnancies after ART compared with that following natural conception. Multiple pregnancies are associated with a broad range of negative consequences for both mother and fetuses. Maternal complications include increased risk of pregnancy-induced hypertension, pre-eclampsia, polyhydramnios, gestational diabetes, fetal malpresentation requiring Caesarean section, postpartum haemorrhage, and postpartum depression. Babies from multiple pregnancies are at a significantly higher risk of early death, prematurity, and low birth weight, as well as mental and physical disabilities related to prematurity. Increased maternal and fetal morbidity leads to higher perinatal and neonatal costs of multiple pregnancies, as well as subsequent lifelong costs due to disabilities and an