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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

    2016-03-01

    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. PMID:26342729

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

    PubMed Central

    2015-01-01

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

  3. Combined Screening for Early Detection of Pre-Eclampsia

    PubMed Central

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

    2015-01-01

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

  4. 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. PMID:26359215

  5. Prediction and primary prevention of pre-eclampsia.

    PubMed

    Thangaratinam, Shakila; Langenveld, Josie; Mol, Ben W; Khan, Khalid S

    2011-08-01

    Pre-eclampsia is associated with increased maternal and perinatal mortality and morbidity. Early recognition of women at risk of pre-eclampsia will enable the identification of high-risk women who may benefit from enhanced surveillance and prophylaxis. In this chapter, we summarise the accuracy of various tests used to predict the onset of pre-eclampsia and the effectiveness of preventative treatment. The tests used to predict pre-eclampsia include clinical history, examination findings, laboratory and haemodynamic tests. In general, tests in early pregnancy for predicting later development of pre-eclampsia have better specificity than sensitivity, as Body Mass Index greater than 34, alpha-fetoprotein, fibronectin and uterine artery Doppler (bilateral notching) all have specificities above 90%. Only uterine artery Doppler resistance index and combinations of indices have a sensitivity of over 60%. Test such as kallikreinuria not used in clinical practice, has shown high sensitivity above 80%, without compromising specificity, and require further investigation. None of the tests are sufficiently accurate to recommend them for routine use in clinical practice. The various treatment options for preventing pre-eclampsia include pharmacological agents, dietary supplementation and lifestyle modification. Antiplatelet agents, primarily low-dose aspirin, reduce the risk of pre-eclampsia by 10% (RR 0.90, 95% CI 0.84 to 0.97). Calcium effectively prevents pre-eclampsia (RR 0.45, 95% CI 0.31 to 0.65); the beneficial effect being observed in the high-risk group (RR 0.22; 95% CI 0.12 to 0.42) and in the group with low nutritional calcium intake (RR 0.36, 95% CI 0.20 to 0.65). Pharmacological agents, such as low molecular weight heparin, progesterone, nitric oxide donors, anti-hypertensive medication and diuretics are not effective in preventing pre-eclampsia. Dietary supplements, such as magnesium, anti-oxidants, marine oils and folic acid, do not reduce the incidence of pre-eclampsia. Evidence is lacking to support lifestyle preventative interventions for pre-eclampsia, such as rest, exercise and reduced dietary salt intake. PMID:21454131

  6. Does consanguinity affect the severity of pre-eclampsia?

    PubMed

    Badria, L Francis; Amarin, Z O

    2003-06-01

    To determine whether consanguinity is more likely to be associated with severe forms of pre-eclampsia/eclampsia. Presuming a pure genetic contribution, we speculated that consanguineous marriages would increase the occurrence of severe forms of pre-eclampsia/eclampsia, through an expected increased chance for homozygosity to the putative gene. The study is a clinical case series on pre-eclamptic/eclamptic primiparae delivered at Princess Badea Teaching Hospital, which is a tertiary referral center. The internationally accepted definitions for hypertension, proteinuria, mild and severe pre-eclampsia were adopted. The study included 77 primiparae. The incidence of consanguinity in the studied sample was 38%. Of them, 28 (36.4%) had mild pre-eclampsia, 45 (58.4%) had severe pre-eclampsia and four (5.2%) had eclampsia. There was no statistically significant difference in the occurrence of severe pre-eclampsia/eclampsia between primiparae married to a first cousin or a relative other than a first cousin and primiparae married to a non-relative, odds ratio 1.1 (95% CI 0.33-3.87), P value 0.94, odds ratio 2.6 (95% CI 0.45-27.6), P value 0.30, respectively. Also, there was no statistically significant difference in occurrence of severe pre-eclampsia/eclampsia between primiparae whose parents are first cousins or relatives other than a first cousin and primiparae whose parents are non-relatives, odds ratio 1.3 (95% CI 0.36-4.72), P value 0.81, odds ratio 1.61 (95% CI 0.23-18.4), P value 0.70, respectively. Our study did not support a causal relationship between consanguinity and the occurrence of severe pre-eclampsia/eclampsia. The role of more complex genetic, immunologic, metabolic, hemostatic or, possibly yet, other unknown factors have to be explored. PMID:12768302

  7. Antiphospholipid syndrome and pre-eclampsia.

    PubMed

    Heilmann, Lothar; Schorsch, Martin; Hahn, Thomas; Fareed, Jawed

    2011-03-01

    Antiphospholipid syndrome (APS) is defined as an autoimmune disorder characterized by recurrent thrombosis or obstetrical morbidity. These features are linked to the presence in blood of autoantibodies against negatively charged phospholipids or phospholipid-binding proteins. Obstetric morbidity includes recurrent abortion (early and late) and severe pre-eclampsia (P-EC)/hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and/or severe placental insufficiency. Criteria that define the major clinical and laboratory events were published in revised forms in the Sydney recommendations in 2006. We analyzed the blood of patients with severe P-EC according to the subgroups based on the 2006 revised criteria definition and compared these results with women after uncomplicated pregnancy and delivery. We found 20% elevated antiphospholipid antibodies (APAs) in women with severe P-EC (group I, 7.5%; group IIa, 5.0%; group IIb, 5.0%; group IIc, 2.5%). The increased APAs were observed only in women with severe P-EC (odds ratio: 2.45; 95% confidence interval, 1.01 to 4.3) and not in patients with severe P-EC at >34 weeks of gestation. According to our retrospective observation, we recommend the determination of anticardiolipin antibodies, lupus anticoagulant, and ?-2 glycoprotein-1 antibodies in patients with severe P-EC at <34 weeks of gestation. PMID:21370215

  8. Pre-eclampsia part 1: current understanding of its pathophysiology.

    PubMed

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

    2014-08-01

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

  9. Epidemiologic aspects of pre-eclampsia in Saudi Arabia.

    PubMed

    Lawoyin, T O; Ani, F

    1996-06-01

    Pre-eclampsia is pregnancy induced hypertension of unknown aetiology. There is a paucity of maternal data on the disease from this region and this study was undertaken to identify maternal and possible aetiologic factors associated with the disease in the north western region of Saudi Arabia. Seven hundred and five consecutive maternities which delivered from October 1990 till January 1991 at the Armed Forces Hospital were analysed. 2.8% of women in this community study developed pre-eclampsia. Women at extremes of maternal age, the nulliparous and high parity women; women with high body mass index, blood group O and those with no antenatal care or late booking in this study were at greater risk of developing pre-eclampsia when compared with controls who delivered in the same period. Of the babies born to mothers with pre-eclampsia, 46.7% were of low birthweight (< 2500g) while only 10.4% of controls were low birthweight. It is concluded that mothers with pre-eclampsia have to be identified early. Potential modifiable factors include reducing pregnancies at extremes of maternal age, among high parity women and encouraging early booking as well as regular attendance at the antenatal clinic. PMID:8840604

  10. Monocytes and Macrophages in Pregnancy and Pre-Eclampsia

    PubMed Central

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

    2014-01-01

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

  11. Diagnosis and management of pre-eclampsia: an update

    PubMed Central

    Turner, Judi A

    2010-01-01

    Pre-eclampsia is a significant, multifactorial, multiorgan disease affecting 5%8% of all pregnancies in the US where it is the third leading cause of maternal mortality. Despite improvements in the diagnosis and management of pre-eclampsia, severe complications can occur in both the mother and the fetus, and there is no effective method of prevention. Early detection and identification of pregnant women most at risk of developing the disease have proven challenging, but recent efforts combining biochemical and biophysical markers are promising. Efforts at prevention of pre-eclampsia with aspirin and calcium have had limited success, but research on modifiable risk factors, such as obesity surgery, are encouraging. Obstetric management of severe pre-eclampsia focuses on medical management of blood pressure and prevention of seizures using magnesium sulfate, but the ultimate cure remains delivery of the fetus and placenta. Timing of delivery depends on several factors, including gestational age, fetal lung maturity, and most importantly, disease severity. Anesthetic management includes regional anesthesia with careful evaluation of the patients airway, volume status, and coagulation status to reduce morbidity and mortality. The potential complications of general anesthesia, including intracranial hemorrhage, in these patients make regional anesthesia the preferred choice in many cases. Nevertheless, it is important to be aware of the contraindications to neuraxial anesthesia and to prepare always for the possibility of encountering a difficult airway. PMID:21151680

  12. Immunofluorescent Studies in Renal Biopsies in Pre-eclampsia

    PubMed Central

    Petrucco, O. M.; Thomson, N. M.; Lawrence, J. R.; Weldon, M. W.

    1974-01-01

    Renal biopsies were performed on 11 patients considered clinically and histologically to have pre-eclampsia. Immunofluorescent studies with fluorescein-labelled anti-IgG, IgA, IgM, and IgE complement, albumin, fibrin, and fibrinogen were carried out on the tissue obtained. Significant correlation was obtained between the clinical severity of the disease and the density and pattern of IgM and IgG deposition. Complement was found in glomeruli in severe cases, while complement deposition in the walls of afferent and efferent arterioles was a constant finding. These findings support the concept that an immunological mechanism may be responsible for the renal lesions in pre-eclampsia. If immunity does play a part in the pathogenesis of pre-eclampsia, possible mechanisms include the involvement of histocompatibility antigens and cross-reactivity of fetal and maternal tissues. Renal fibrin deposition in pre-eclampsia may be secondary to an immune process, an occurrence well-described in other forms of glomerulonephritis in man and other species. ImagesFIG. 1FIG. 2FIG. 3FIG. 4 PMID:4593706

  13. 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:24367496

  14. KIR2DL4 expression rather than its single nucleotide polymorphisms correlates with pre-eclampsia

    PubMed Central

    Wang, Dandan; Tian, Yuan; Zhao, Yanhui; Liu, Lianlian; Liu, Xianying; Wu, Fuju

    2015-01-01

    Objective: To evaluate the single nucleotide polymorphisms and expression of KIR2DL4 (killer cell immunoglobulin-like receptors) gene in pre-eclampsia patients. Methods: KIR2DL4 gene polymorphisms were detected in 100 patients with pre-eclampsia and 100 healthy pregnant women, respectively, by using PCR-SS. Then, the expression of KIR2DL4 was measured in 5 cases of placentas tissues with pre-eclampsia and normal pregnancies by using qRT-PCR. Results: Compared with healthy controls, 16 loci of single nucleotide polymorphisms (SNP) were identified in pre-eclampsia patients, including 7 new polymorphisms loci. But, no significant difference was found in genotype distributions and allele frequencies in pre-eclampsia and controls (P>0.05). However, qRT-PCR results showed that KIR2DL4 mRNA in placenta tissues with pre-eclampsia was significantly lower than those with normal pregnancy, and the difference was statistically significant. Conclusion: Decreased level of KIR2DL4 rather than its SNP is correlated with the susceptibility of pre-eclampsia. PMID:26823774

  15. Correlation between MTHFR gene methylation and pre-eclampsia, and its clinical significance.

    PubMed

    Ge, J; Wang, J; Zhang, F; Diao, B; Song, Z F; Shan, L L; Wang, W; Cao, H J; Li, X Q

    2015-01-01

    We investigated the correlation between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene methylation and pre-eclampsia, and its clinical significance, by comparing methylation in the MTHFR gene promoter of the placenta and peripheral venous blood in pre-eclampsia and normal gravidas. We enrolled 259 gravidas from the People's Liberation Army 202nd Hospital, China, between January 2011 and September 2011, including 127 pre-eclampsia and 132 nor-mal gravidas. Methylation levels of the MTHFR gene in placentas in two sets of gravidas were detected by methylation-specific polymerase chain reaction, plasma homocysteine levels were detected by enzyme-linked immunosorbent assay, and folic acid and vitamin B12 levels were detected by electrochemiluminescence. The chi-square test results were analyzed using the SPSS19.0 statistical software. In placentas, the methylation indices were 26.8% (34/127) and 15.2% (20/132) in the pre-eclampsia and normal groups, respectively (?(2) = 5.30, P < 0.05, odds ratio (OR) = 2.04, 95% confidence interval (95%CI) = 1.10-3.73). In peripheral venous blood, the methylation indices were 22.8% (29/127) and 12.1% (16/132) in pre-eclampsia and normal groups, respectively (?(2) = 5.17, P < 0.05, OR = 2.15, 95%CI = 1.11-4.15). The plasma methylation level of the pre-eclampsia group was consistent with the normal group. The plasma homocysteine level in the pre-eclampsia group was higher than in the normal group (P < 0.05). Levels of folic acid and vitamin B12 in the pre-eclampsia and normal groups were not statistically significant (P > 0.05). Patients with pre-eclampsia have hypermethylation in the MTHFR gene promoter, which may be one of its causes. PMID:26214484

  16. Reliable pre-eclampsia pathways based on multiple independent microarray data sets.

    PubMed

    Kawasaki, Kaoru; Kondoh, Eiji; Chigusa, Yoshitsugu; Ujita, Mari; Murakami, Ryusuke; Mogami, Haruta; Brown, J B; Okuno, Yasushi; Konishi, Ikuo

    2015-02-01

    Pre-eclampsia is a multifactorial disorder characterized by heterogeneous clinical manifestations. Gene expression profiling of preeclamptic placenta have provided different and even opposite results, partly due to data compromised by various experimental artefacts. Here we aimed to identify reliable pre-eclampsia-specific pathways using multiple independent microarray data sets. Gene expression data of control and preeclamptic placentas were obtained from Gene Expression Omnibus. Single-sample gene-set enrichment analysis was performed to generate gene-set activation scores of 9707 pathways obtained from the Molecular Signatures Database. Candidate pathways were identified by t-test-based screening using data sets, GSE10588, GSE14722 and GSE25906. Additionally, recursive feature elimination was applied to arrive at a further reduced set of pathways. To assess the validity of the pre-eclampsia pathways, a statistically-validated protocol was executed using five data sets including two independent other validation data sets, GSE30186, GSE44711. Quantitative real-time PCR was performed for genes in a panel of potential pre-eclampsia pathways using placentas of 20 women with normal or severe preeclamptic singleton pregnancies (n = 10, respectively). A panel of ten pathways were found to discriminate women with pre-eclampsia from controls with high accuracy. Among these were pathways not previously associated with pre-eclampsia, such as the GABA receptor pathway, as well as pathways that have already been linked to pre-eclampsia, such as the glutathione and CDKN1C pathways. mRNA expression of GABRA3 (GABA receptor pathway), GCLC and GCLM (glutathione metabolic pathway), and CDKN1C was significantly reduced in the preeclamptic placentas. In conclusion, ten accurate and reliable pre-eclampsia pathways were identified based on multiple independent microarray data sets. A pathway-based classification may be a worthwhile approach to elucidate the pathogenesis of pre-eclampsia. PMID:25323968

  17. 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

  18. Decidual Hemostasis, Inflammation, and Angiogenesis in Pre-Eclampsia

    PubMed Central

    Lockwood, Charles J.; Huang, S.J.; Krikun, Graciela; Caze, Rebeca; Rahman, Mizanur; Buchwalder, Lynn F.; Schatz, Frederick

    2013-01-01

    Invasion of the decidua by extravascular trophoblasts (EVTs) is accompanied by thrombin generation from decidual cell (DC) -expressed tissue factor (TF). This TF protects against hemorrhage as EVTs breach capillaries and subsequently invade and remodel spiral arteries and arterioles. Pre-eclampsia (P-EC) is the worlds leading cause of fetal and maternal morbidity and mortality. It is associated with decidual hemorrhage and maternal thrombophilias, which form excess thrombin from DCs, and with maternal infections and other inflammatory conditions that are associated with excess expression of the pro-inflammatory cytokines, interleukin-1 beta (IL-1b) and tumor necrosis factor alpha (TNF-a). In human first trimester leukocyte-free DCs: 1) thrombin enhances expression of soluble fms-like tyrosine kinase-1 (sFlt-1), a potent inhibitor of angiogenesis; 2) thrombin, IL-1b and TNF-a increase monocyte-recruiting chemokine expression leqading to a macrophage excess in the pre-eclamptic decidua. The pathogenesis of P-EC likely stems from shallow EVT invasion leading to impaired decidual vascular remodeling. The resulting reduced uteroplacental blood flow is associated with a hypoxic placenta, which appears to secrete excess sFlt-1 into the maternal plasma. A regulatory role for DCs in vascular remodeling is indicated since impaired decidual vascular remodeling could stem from an aberrant local anti-angiogenic milieu elicited by excess sFlt-1 and/or macrophage inhibited EVT decidual invasion. PMID:21370218

  19. 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. PMID:26585303

  20. Is Xanthine Oxidase, a Marker in Pre-eclampsia? A Case-Control Study

    PubMed Central

    Bambrana, Vanishree; Kotur, Pushpa P

    2015-01-01

    Introduction Pre-eclampsia is an obstetrics problem that affects multiple systemic functions and leads to the increased maternal and fetal morbidity and mortality. The objective of the study was to evaluate the plasma levels of Xanthine oxidase (XO) activity, uric acid and Nitric oxide (NO) levels in women with pre-eclampsia and normal pregnancy during antenatal and postpartum period. Materials and Methods A case control study was conducted in women with normal pregnancy (n=50) and pre-eclampsia (n=50) before and after delivery. XO activity, uric acid and NO levels were determined from samples at 30-39 weeks of gestation. The current study was conducted in association with Obstetrics and Gynecology Department of R.L. Jalappa Hospital and Research Center. The blood samples were analysed for assay of XO, uric acid and NO. The results were analysed by using SPSS software version 2013. P-value < 0.05 was considered as statistically significant. Results The plasma XO activity was elevated (p<0.001) in the pre-eclampsia compared to normotensive pregnant women before delivery and decreased after delivery (p<0.001) significantly. Uric acid level showed a significant increase in pre-eclampsia when compared to the control before delivery (p<0.001) however values were non-significant after delivery. Conclusion Placenta plays a key role in the pathophysiology of pre-eclampsia. Placenta removal leads to decrease trend of xanthine oxidase activity, uric acid and elevation of Nitric oxide as reversible changes in pre-eclampsia patients within 48 hours after delivery. PMID:26557508

  1. Including ethical considerations in models for first-trimester screening for pre-eclampsia.

    PubMed

    Jrgensen, J M; Hedley, P L; Gjerris, M; Christiansen, M

    2014-05-01

    Recent efforts to develop reliable and efficient early pregnancy screening programmes for pre-eclampsia have focused on combining clinical, biochemical and biophysical markers. The same model has been used for first-trimester screening for fetal aneuploidies i.e. prenatal diagnosis (PD), which is routinely offered to all pregnant women in many developed countries. Some studies suggest combining PD and pre-eclampsia screening, so women can be offered testing for a number of conditions at the same clinical visit. A combination of these tests may be practical in terms of saving time and resources; however, the combination raises ethical issues. First-trimester PD and pre-eclampsia screening entail qualitative differences which alter the requirements for disclosure, non-directedness and consent with regard to the informed consent process. This article explores the differences related to the ethical issues raised by PD and pre-eclampsia in order to elucidate which factors are relevant to deciding the type of information and consent required in each context from the perspective of the ethical principles of beneficence and autonomy. Furthermore, it argues that ensuring respect for patient autonomy is context dependent and, consequently, pre-eclampsia screening and PD should be performed independently of one another. PMID:24631382

  2. Hypertension Persisting after Pre-Eclampsia: A Prospective Cohort Study at Mulago Hospital, Uganda

    PubMed Central

    Nakimuli, Annettee; Elliott, Alison M.; Kaleebu, Pontiano; Moffett, Ashley; Mirembe, Florence

    2013-01-01

    Background Pre-eclampsia/eclampsia usually resolves after delivery but sometimes hypertension persists and cardiovascular disease develops later. Our objective was to determine the incidence and maternal socio-demographic and obstetric risk factors for persistence of hypertension in women with pre-eclampsia/eclampsia. Methods This was a prospective cohort study conducted from July 2009 to June 2011 at Mulago Hospital labour ward and postnatal clinics. We followed up 188 women admitted with pre-eclampsia/eclampsia until 3 months after delivery. Data was collected using interviewer-administered questionnaires, examination of participants and review of medical records. Stata (version12) software was used for data analysis. Univariable analysis was used to compute the relative risk of persistent hypertension at the 95% confidence level. This was followed by multivariable logistic regression analysis to determine factors independently associated with persistence of hypertension. Results 64 (34%) out of the 188 women analysed had persistent hypertension three months after delivery. Maternal age, gestational age at delivery and parity were predictors of persistent hypertension. Conclusion The proportion of women with pre-eclampsia/eclampsia at risk of persistent hypertension at three months after delivery was high, with nearly one of three mothers remaining hypertensive. Follow up of mothers who develop pre-eclampsia is important so that early diagnosis and management of chronic hypertension can be made to avoid long term morbidity and mortality. PMID:24392003

  3. Prediction of pre-eclampsia: a protocol for systematic reviews of test accuracy

    PubMed Central

    Cnossen, Jeltsje S; van der Post, Joris AM; Mol, Ben WJ; Khan, Khalid S; Meads, Catherine A; ter Riet, Gerben

    2006-01-01

    Background Pre-eclampsia, a syndrome of hypertension and proteinuria, is a major cause of maternal and perinatal morbidity and mortality. Accurate prediction of pre-eclampsia is important, since high risk women could benefit from intensive monitoring and preventive treatment. However, decision making is currently hampered due to lack of precise and up to date comprehensive evidence summaries on estimates of risk of developing pre-eclampsia. Methods/Design A series of systematic reviews and meta-analyses will be undertaken to determine, among women in early pregnancy, the accuracy of various tests (history, examinations and investigations) for predicting pre-eclampsia. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Reviewers working independently will select studies, extract data, and assess study validity according to established criteria. Language restrictions will not be applied. Bivariate meta-analysis of sensitivity and specificity will be considered for tests whose studies allow generation of 2 × 2 tables. Discussion The results of the test accuracy reviews will be integrated with results of effectiveness reviews of preventive interventions to assess the impact of test-intervention combinations for prevention of pre-eclampsia. PMID:17052339

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

    PubMed Central

    Williams, Paula J.; Broughton Pipkin, Fiona

    2011-01-01

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

  5. Placental morphogenesis in pregnancies with Down's syndrome might provide a clue to pre-eclampsia.

    PubMed

    Banerjee, S; Smallwood, A; Nargund, G; Campbell, S

    2002-01-01

    Insufficient perfusion of placenta in pre-eclampsia is commonly associated with oxidative stress leading to increased superoxide formation and reduced invasion of uterine spiral arteries by differentiated migratory cytotrophoblasts. The superoxide dismutase (SOD) level, responsible for eliminating toxic superoxides, drops significantly in pre-eclampsia. On the contrary, the SOD synthesis increases dramatically, compared to that of normal placenta, in pregnancies with trisomy 21 (T21) fetus. However, despite a low level of placental hypoplasia, the overall perfusion of T21 placentae is comparable to that of normal pregnancy. In the light of recent reports on alternative modes of SOD function and factors regulating pathways of cytotrophoblast differentiation, here we have attempted to reconcile the two seemingly disparate pregnancy conditions and suggest that trisomy 21 pregnancies might provide new insight into our understanding of placental morphogenesis in pre-eclampsia. PMID:11945083

  6. 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.

  7. Lack of consistency in research papers over the definition of pre-eclampsia.

    PubMed

    Chappell, L; Poulton, L; Halligan, A; Shennan, A H

    1999-09-01

    The most common definition of pre-eclampsia involves hypertension and proteinuria. This has changed little in over a hundred years despite advances in understanding the underlying pathological process. However, a number of variations in definition exist, and this paper demonstrates a lack of consistency in research articles in defining pre-eclampsia. A quarter of papers omit description, and many authors choose their own interpretation of the standard classification. Editors and reviewers should ensure that papers include a clear description of the definition used and an adequate description of the population studied to allow meaningful interpretation of research findings. PMID:10492114

  8. 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

  9. Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort

    PubMed Central

    2011-01-01

    Objectives To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated. Design Prospective multicentre cohort. Setting Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland. Participants 3572 healthy nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%). Main outcome measure Pre-eclampsia defined as ?140 mm Hg or diastolic blood pressure ?90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37+0 weeks gestation. In the stepwise logistic regression the comparison group was women without pre-eclampsia. Results Of the 3529 women, 186 (5.3%) developed pre-eclampsia, including 47 (1.3%) with preterm pre-eclampsia. Clinical risk factors at 14-16 weeks gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors. Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop pre-eclampsia. The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively. Conclusions The ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added. Trial registration ACTRN12607000551493. PMID:21474517

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

    PubMed Central

    Ahmed, Asif; Ramma, Wenda

    2015-01-01

    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. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 PMID:25303561

  11. 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 ?g min?1 whilst maintaining blood pressure of >140/80 mmHg. Aortic augmentation index, aortic pulse wave velocity, blood pressure and maternalfetal 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 ?g 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 (4.97.6) vs. 4.1 (3.15.7)% 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 (0.090.82) vs. 0.23 (0.070.49) 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

  12. ST2 and IL-33 in Pregnancy and Pre-Eclampsia

    PubMed Central

    Snider, James V.; Tannetta, Dionne S.; Child, Tim; Redman, Christopher W. G.; Sargent, Ian L.

    2011-01-01

    Normal pregnancy is associated with a mild systemic inflammatory response and an immune bias towards type 2 cytokine production, whereas pre-eclampsia is characterized by a more intense inflammatory response, associated with endothelial dysfunction and a type 1 cytokine dominance. Interleukin (IL)-33 is a newly described member of the IL-1 family, which binds its receptor ST2L to induce type 2 cytokines. A soluble variant of ST2 (sST2) acts as a decoy receptor to regulate the activity of IL-33. In this study circulating IL-33 and sST2 were measured in each trimester of normal pregnancy and in women with pre-eclampsia. While IL-33 did not change throughout normal pregnancy, or between non-pregnant, normal pregnant or pre-eclamptic women, sST2 was significantly altered. sST2 was increased in the third trimester of normal pregnancy (p<0.001) and was further increased in pre-eclampsia (p<0.001). This increase was seen prior to the onset of disease (p<0.01). Pre-eclampsia is a disease caused by placental derived factors, and we show that IL-33 and ST2 can be detected in lysates from both normal and pre-eclampsia placentas. ST2, but not IL-33, was identified on the syncytiotrophoblast layer, whereas IL-33 was expressed on perivascular tissue. In an in vitro placental perfusion model, sST2 was secreted by the placenta into the maternal eluate, and placental explants treated with pro-inflammatory cytokines or subjected to hypoxia/reperfusion injury release more sST2, suggesting the origin of at least some of the increased amounts of circulating sST2 in pre-eclamptic women is the placenta. These results suggest that sST2 may play a significant role in pregnancies complicated by pre-eclampsia and increased sST2 could contribute to the type 1 bias seen in this disorder. PMID:21949719

  13. 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

    2015-01-01

    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

  14. 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

  15. 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. PMID:24534543

  16. Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia.

    PubMed

    Williams, Paula Juliet; Mistry, Hiten D; Morgan, Linda

    2012-04-01

    The transport of folate across the placenta involves a number of different receptors including folate receptor-alpha (FR-?), reduced folate carrier (RFC) and proton coupled folate transporter (PCFT). In addition there are a number of ATP-dependent transporters which have also recently been shown to be involved in folate transport; these include ABCB1, ABCC2 and BCRP (ABCG2). The aim of the current study was to characterise the placental mRNA and protein expression of these folate transporters throughout gestation and also to see if expression is altered in pre-eclampsia. Placental tissue was collected from women undergoing termination of pregnancy (TOP) and from women undergoing elective Caesarean section. To investigate mRNA expression quantitative real time PCR was used with gene specific oligonucleotide primers to FR-?, RFC, PCFT, ABCB1, ABCC2, BCRP and the reference gene YWHAZ. Protein expression was also characterised using immunohistochemistry of paraffin embedded placental tissue. Both protein and mRNA expression of all transporters examined decreased as the gestation progressed. Expression of FR-? and PCFT mRNA and protein were decreased in pre-eclampsia compared with normal term pregnancy. The higher levels of expression of FR-?, RFC, PCFT, ABCB1, ABCC2 and BCRP in early pregnancy indicate that these transporters may have an important role in the establishment and development of the placenta, with expression reducing in preparation for parturition. Reductions in FR-? and PCFT in pre-eclampsia may be a mechanism involved in the pathogenesis of pre-eclampsia by limiting placental folate uptake resulting in reduced levels of angiogenesis, cell proliferation and antioxidant protection. PMID:26105097

  17. 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. PMID:25959785

  18. First trimester multivitamin/mineral use is associated with reduced risk of pre-eclampsia among overweight and obese women.

    PubMed

    Vanderlelie, Jessica; Scott, Rani; Shibl, Rania; Lewkowicz, Jessica; Perkins, Anthony; Scuffham, Paul A

    2016-04-01

    The use of pregnancy-specific multivitamin supplements is widely recommended to support maternal homeostasis during pregnancy. Our objective was to investigate whether multivitamin use during pregnancy is associated with a reduced risk of pre-eclampsia. The effect of multivitamin use on incidence of pre-eclampsia in lean and overweight/obese women was analysed using data collected between 2006 and 2011 as part of the Environments for Healthy Living Project, Griffith University, Australia. A total of 2261 pregnancies were included in the analysis with pre-eclampsia reported in 1.95% of subjects. Body mass index (BMI) ≥ 25 was associated with a 1.97-fold [95% confidence interval (CI): 0.93, 4.16] increase in pre-eclampsia risk. First trimester multivitamin use was reported by 31.8% of women and after adjustment, was associated with a 67% reduction in pre-eclampsia risk (95%CI: 0.14, 0.75). Stratification by BMI demonstrated a 55% reduction in pre-eclampsia risk (95%CI: 0.30, 0.86) in overweight (BMI: 25-29.9) and 62% risk reduction (95%CI: 0.16, 0.92) in obese (BMI: ≥30) cohorts that supplemented with multivitamins in the first trimester of pregnancy. This finding may be particular to the Australian population and reflect inherent nutritional deficits. First trimester folate supplementation was found to reduce pre-eclampsia incidence [adjusted odds ratios (AOR) 0.42 95%CI: 0.13, 0.98] and demonstrated significance upon stratification by overweight status for women with BMI >25 (AOR 0.55 95%CI: 0.31, 0.96). These results support the hypothesis that multivitamin supplementation may be beneficial in reducing the incidence of pre-eclampsia during pregnancy and be of particular importance for those with a BMI ≥25. PMID:24847942

  19. Serum anti-carbonic anhydrase II antibodies and oxidant-antioxidant balance in pre-eclampsia.

    PubMed

    Aliyazicioglu, Rezzan; Guven, Suleyman; Mentese, Ahmet; Kolayli, Sevgi; Cengiz, Sevil; Deger, Orhan; Alver, Ahmet

    2011-10-01

    PROBLEM? The aim of this study was to investigate the presence of anti-carbonic anhydrase II antibodies (anti-CA II) antibodies in pre-eclampsia and the relationships between the autoantibodies, total antioxidant capacity (TAC) and total oxidant capacity (TOC), malondialdehyde (MDA) and oxidative stres index (OSI) parameters. METHOD OF STUDY? We studied 40 early and late onset pre-eclamptic patients and 40 healthy pregnant control and 39 healthy non-pregnant control subjects. Serum CA II antibodies, TAC and TOC, and MDA parameters were studied by ELISA. RESULTS? The mean values for TAC, TOC, OSI, MDA, and anti-CA II were significantly increased in patients with pre-eclampsia compared to the other groups. The anti-CA II antibody levels for the pregnant control subjects were 0.129 0.04 and that for the pre-eclamptic patients were 0.282 0.18. In this study, any absorbance value higher than 0.136, the mean absorbance + 2 S.D. of pregnant control subjects, was defined as positive. Positive results were obtained in 29 of 40 pre-eclamptic patients (72.5%). There were significant positive correlations between serum anti-CA II antibodies and TOC, MDA levels, and OSI levels. CONCLUSION? The results suggest that anti-CA II antibodies and impairment in oxidant-antioxidant balance may be involved in multifactorial etiology of pre-eclampsia. PMID:21244564

  20. The nitric oxide pathway and possible therapeutic options in pre-eclampsia

    PubMed Central

    Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

    2014-01-01

    Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxidesoluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3?,5?-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. PMID:24313856

  1. Serum Calcium Status among Pregnancies Complicated By Pre-Eclampsia in Bangladesh.

    PubMed

    Akhter, S; Hoque, M R; Paul, U K; Hossain, M M

    2015-10-01

    This case control cross sectional study was carried out in the department of biochemistry, Mymensingh medical college in collaboration with the outpatient department, family planning model clinic and antenatal obstetric ward of Mymensingh medical college hospital, Mymensingh during the period of July 2003 to June 2004. The aim of the study was to explore the status of serum calcium among pregnancies complicated by pre-eclampsia in Bangladesh as a means to monitor the possibility of management of these patients. A total of 82 subjects were selected and were grouped as Group I (32 healthy women with uncomplicated pregnancy as control subjects) and Group II (50 pregnant women with pre-eclampsia as cases). Serum calcium was estimated by colorimetric method from each sample. Statistical analysis was done by using SPSS windows package. Among the groups, meanSD (Standard Deviation) of Group I and Group II serum calcium were 8.711.00 and 10.781.44 mg/dl respectively. By comparing Group I with Group II highly significant difference were found in case of serum calcium (P<0.001). It is evident from the study that serum calcium level significantly increases among pregnancies complicated by pre-eclampsia in Bangladesh. PMID:26619999

  2. The nitric oxide pathway and possible therapeutic options in pre-eclampsia.

    PubMed

    Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

    2014-08-01

    Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide-soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3',5'-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. PMID:24313856

  3. 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

  4. Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial.

    PubMed

    Rayman, Margaret P; Searle, Elizabeth; Kelly, Lynne; Johnsen, Sigurd; Bodman-Smith, Katherine; Bath, Sarah C; Mao, Jinyuan; Redman, Christopher W G

    2014-07-14

    Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 ?g/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial. PMID:24708917

  5. Methylenetetrahydrofolate reductase gene C677T, A1298C polymorphisms and pre-eclampsia risk: a meta-analysis.

    PubMed

    Li, Xing; Luo, Ya L; Zhang, Qiong H; Mao, Chen; Wang, Xi W; Liu, Shan; Chen, Qing

    2014-08-01

    To determine whether methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms are associated with pre-eclampsia susceptibility. Literature searches of the Pubmed, Embase, BIOSIS Previews and Web of Science were conducted to identify all eligible articles up to January 18th, 2013. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) of five genetic models were calculated by fixed-effects or random-effects model. Publication bias, subgroup analysis, meta-regression and sensitivity analysis were also performed. A number of 49 studies including 51 samples consisted of 18,009 subjects (6,238 patients and 11,771 controls) were finally included. MTHFR C677T allele (TT or CT) carriers were 1.12 times more likely to develop pre-eclampsia (95% CI 1.04-1.21) compared with 677CC homozygous individuals. Similar results were obtained under other genetic models. Restricted to severe pre-eclampsia, there was an increased risk for 677TT homozygotes compared with 677CC homozygotes (OR 1.43; 95% CI 1.12-1.83). Subgroup analysis revealed a significant positive association between the C677T polymorphism (TT or CT) and pre-eclampsia in Asians (OR 1.41; 95% CI 1.11-1.79) and white population (OR 1.14; 95% CI 1.03-1.25). Meta-regression showed that study population, blinded genotyping, matching of cases and controls were not substantial sources of heterogeneity. For the MTHFR A1298C, ORs for all genetic models yielded a null association. This meta-analysis suggests that the MTHFR 677T allele might be associated with increased pre-eclampsia risk in Asian and white ethnicity and the subgroup of severe pre-eclampsia, while no association is observed between the MTHFR A1298C polymorphism and pre-eclampsia. PMID:24898880

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

    PubMed

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

    2015-01-01

    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. PMID:26006232

  7. Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth

    PubMed Central

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

    2015-01-01

    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. PMID:26006232

  8. Low-dose calcium supplementation for preventing pre-eclampsia: a systematic review and commentary

    PubMed Central

    Hofmeyr, GJ; Belizn, JM; von Dadelszen, P

    2014-01-01

    Background Epidemiological data link low dietary calcium with pre-eclampsia. Current recommendations are for 1.52g/day calcium supplementation for low-intake pregnant women, based on randomised controlled trials of ?1g/day calcium supplementation from 20weeks of gestation. This is problematic logistically in low-resource settings; excessive calcium may be harmful; and 20weeks may be too late to alter outcomes. Objectives To review the impact of lower dose calcium supplementation on pre-eclampsia risk. Search strategy and selection criteria We searched PubMed and the Cochrane Pregnancy and Childbirth Group trials register. Data collection and analysis Two authors extracted data from eligible randomised and quasi-randomised trials of low-dose calcium (LDC, <1g/day), with or without other supplements. Main results Pre-eclampsia was reduced consistently with LDC with or without co-supplements (nine trials, 2234 women, relative risk [RR] 0.38; 95% confidence interval [95% CI] 0.280.52), as well as for subgroups: LDC alone (four trials, 980 women, RR 0.36; 95% CI 0.230.57]); LDC plus linoleic acid (two trials, 134 women, RR 0.23; 95% CI 0.090.60); LDC plus vitamin D (two trials, 1060 women, RR 0.49; 0.310.78) and a trend for LDC plus antioxidants (one trial, 60 women, RR 0.24; 95% CI 0.061.01). Overall results were consistent with the single quality trial of LDC alone (171 women, RR 0.30; 95% CI 0.061.38). LDC plus antioxidants commencing at 812weeks tended to reduce miscarriage (one trial, 60 women, RR 0.06; 95% CI 0.001.04). Conclusions These limited data are consistent with LDC reducing the risk of pre-eclampsia; confirming this in sufficiently powered randomised controlled trials would have implications for current guidelines and their global implementation. PMID:24621141

  9. Reduced Heart Rate Variability and Altered Cardiac Conduction after Pre-Eclampsia

    PubMed Central

    Murphy, Malia S. Q.; Seaborn, Geoffrey E. J.; Redfearn, Damian P.; Smith, Graeme N.

    2015-01-01

    Pre-eclampsia is a hypertensive disorder of pregnancy that is associated with elevated maternal risk for cardiovascular disease. The aims of this study were to determine the effect of normal pregnancy on postpartum parameters of the electrocardiogram, and furthermore to determine how a history of pre-eclampsia may affect these parameters. Ten-minute high-resolution (1000 Hz) orthogonal Holter electrocardiogram (ECG) recordings were used to measure heart rate variability (HRV). Signal-averaged P-wave and QRS complex durations were determined. Participants included non-pregnant controls, normotensive parous controls and women with a recent history of PE. While reductions in HRV induced by uncomplicated pregnancy returned to non-pregnant levels by 68 months postpartum HRV remained reduced in women with a history of PE compared to control groups. In addition, P-Wave and QRS complex durations were prolonged in PE subjects at 68 months postpartum compared to control groups. Only QRS duration was independent of differences in blood pressure. These results suggest increased sympathetic cardiac activity, and delayed myocardial conduction in women after PE; alterations consistent with cardiac remodeling and increased risk for arrhythmia. In examining the association between PE and cardiovascular disease, identification of ECG abnormalities soon after pregnancy in women with a history of PE highlights a unique opportunity for early identification and screening in this population before other risk factors become apparent. PMID:26407294

  10. Has consanguinity any impact on occurrence of pre-eclampsia and eclampsia?

    PubMed

    Badria, L F; Abu-Heija, A; Zayed, F; Ziadeh, S M; Alchalabi, H

    2001-07-01

    In this study we tested the hypothesis of an association between consanguinity and pre-eclampsia/eclampsia. This is a case-control study conducted at Princess Badea Teaching Hospital, Irbid-Jordan during the period May 1997-April 1998. The study population were Jordanian women delivered at Princess Badea Teaching Hospital with or without hypertensive disorders of pregnancy. The total number was 208 pre-eclamptic/eclamptic women (76 primiparous and 132 multiparous) and 618 randomly selected non-hypertensive women. In primiparous as well as multiparous women, it was evident that neither consanguinity nor the degree of the relationship to the husband in consanguineous marriages had an impact on the incidence of preeclampsia/eclampsia. However, comparing the incidence of consanguinity between pre-eclamptic/eclamptic and non-hypertensive, multiparous women married to a relative other than first cousin, the P value was 0.0248, which we explained as chance incidence. When we compared the incidence of consanguineous marriages as a whole between pre-eclamptic/eclamptic and non-hypertensive, multiparous women, there was no evidence of any impact of consanguinity on the incidence of pre-eclampsia/eclampsia. PMID:12521826

  11. Severe pre-eclampsia and infants of very low birth weight.

    PubMed Central

    Szymonowicz, W; Yu, V Y

    1987-01-01

    The effect of severe pre-eclampsia on the outcome of infants of very low birth weight was studied in a prospective case control study of 35 pairs of infants of comparable gestation. Significantly more infants were delivered before the onset of labour and by caesarean section in the group with pre-eclampsia. These babies tended to be smaller and had a higher incidence of hyaline membrane disease, patent ductus arteriosus, pulmonary air leak, and hypotension. They also required more intensive treatment with oxygen and mechanical ventilation. The significant difference in birth weight was still apparent at 2 years of age. Although the mean psychomotor developmental index and the incidence of specific neurodevelopmental impairments were not significantly different between the two groups, survivors in the group born to pre-eclamptic mothers had a significantly lower mean mental developmental index, and significantly more of these children had one or more impairments compared with the control group at 2 years of age. PMID:3632019

  12. Pre-eclampsia renamed and reframed: Intra-abdominal hypertension in pregnancy.

    PubMed

    Sawchuck, Diane J; Wittmann, Bernd K

    2014-11-01

    This hypothesis proposes pre-eclampsia is caused by intra-abdominal hypertension in pregnancy. Sustained or increasing intra-abdominal pressure ?12mmHg causes impaired venous return to the heart, systemic vascular resistance, ischemia reperfusion injury, intestinal permeability, translocation of lipopolysaccharide endotoxin to the liver, cytotoxic immune response, systemic inflammatory response, pressure transmission to thoracic and intra-cranial compartments, and multi-organ dysfunction. This hypothesis is predicated on Pascal's law, evidence founded in the intra-abdominal hypertension literature, and the adapted equation ?IAP-P=?IAVF/Cab, where ?IAP-P=change in intra-abdominal pressure in pregnancy, ?IAVF=change in intra-abdominal vector force (volume and force direction) and Cab=abdominal compliance. Factors causing increased intra-abdominal pressure in pregnancy include: progressive uterine expansion, obstetrical factors that increase intra-uterine volume excessively or acutely, maternal anthropometric measurements that affect intra-abdominal pressure thresholds, maternal postures that increase abdominal force direction, abdominal compliance that is decreased, diminished with advancing gestation, or has reached maximum expansion, habitation at high altitude, and rapid drops in barometric pressure. We postulate that the threshold for lipopolysaccharide translocation depends on the magnitude of intra-abdominal pressure, the intestinal microbiome complex, and the degree of intestinal permeability. We advance that delivery cures pre-eclampsia through the mechanism of abdominal decompression. PMID:25189485

  13. Stereological investigation of placental morphology in pregnancies complicated by pre-eclampsia with and without intrauterine growth restriction.

    PubMed

    Mayhew, T M; Ohadike, C; Baker, P N; Crocker, I P; Mitchell, C; Ong, S S

    2003-01-01

    The aim of this study was to quantify placental morphology in pregnancies complicated by pre-eclampsia with and without intrauterine growth restriction. Particular attention is given to the dimensions and composition of peripheral (intermediate+terminal) villi. Placentae from 9 control pregnancies, 5 cases of pre-eclampsia, 5 cases of intrauterine growth restriction and 5 cases of pre-eclampsia with intrauterine growth restriction were randomly sampled for location and position. Formalin-fixed, wax-embedded sections stained by the Masson trichrome method were subjected to stereological analysis in order to quantify the volumes of placental components and the surfaces and derived diameters for peripheral villi and fetal capillaries. Group comparisons were drawn using two-way analysis of variance. Fetal weights were reduced in all complicated pregnancies but only intrauterine growth restriction was accompanied by a significantly smaller placenta. Pre-eclampsia was not associated with main effects on placental morphology and (except for trophoblast thickness) there were no interaction effects involving pre-eclampsia. In contrast, intrauterine growth restriction was associated with a placenta which had reduced volumes of intervillous space and all types of villi (stem, intermediate, terminal). The impoverished growth of peripheral villi affected all tissues (trophoblast, stroma, capillaries) and was accompanied by smaller exchange surface areas and a thicker trophoblastic epithelium. The derived mean diameters of villi and capillaries were not affected. It is concluded that intrauterine growth restriction, but not pre-eclampsia, is associated with substantial changes in placental morphology including impoverished growth of villi and fetal vasculature. These changes are likely to reduce placental oxygen diffusive conductances and contribute to fetal hypoxic stress. PMID:12566249

  14. Promising biomarkers for superimposed pre-eclampsia in pregnant women with established hypertension and chronic kidney disease.

    PubMed

    Acharya, Anjali

    2016-04-01

    The incidence of pre-eclampsia is high in women with chronic kidney disease and hypertension and the diagnosis is particularly challenging. Bramham et al. (2016) studied various biomarkers with the primary aim of predicting superimposed pre-eclampsia requiring delivery within 14 days of sampling. Their findings of the utility of a single biomarker for diagnosis in this high-risk group is a major advance that has significant implications and holds promise for the future. PMID:26994571

  15. Transthoracic echocardiographic assessment of haemodynamics in severe pre-eclampsia and HIV in South Africa.

    PubMed

    Dennis, A T; Dyer, R A; Gibbs, M; Nel, L; Castro, J M; Swanevelder, J L

    2015-09-01

    Haemodynamic and cardiac structural changes in severe pre-eclampsia and in pregnant women with human immunodeficiency virus (HIV) infection have not been clearly established. We performed transthoracic echocardiography on 105 women. Women with pre-eclampsia demonstrated (mean (SD), untreated vs treated) preserved fractional shortening (40 (7.1)% vs. 41 (8.6)%), a non-dilated left ventricle (4.5 (0.49) cm vs. 4.4 (0.44) cm), increased mitral valve E/septal e' (10.5 (3.3) vs. 10.6 (2.8)), and preserved tricuspid annular plane systolic exertion (2.6 (0.36) cm vs. 2.4 (0.51) cm). Women with HIV infection demonstrated (mean (SD), HIV-positive vs healthy) a reduced cardiac index (2.8 (0.64) ml.min(-1) .m(-2) vs. 3.1 (0.7) ml.min(-1) .m(-2) , p = 0.029), reduced septal s' tissue Doppler velocity (8.5 (1.5) cm.s(-1) vs. 9.3 (1.7) cm.s(-1) , p = 0.042), increased left ventricular end-diastolic area (7.6 (2.1) cm2 vs. 6.3 (1.7) cm2 , p = 0.004), and reduced right ventricular s' and e' velocity (s' velocity 14.7 (3.1) cm.s(-1) vs. 7.0 (2.9) cm.s(-1) p = 0.001, e' velocity 16.3 (4.1) cm.s(-1) vs. 18.7 (3.4) cm.s(-1) , p = 0.013). The mitral value E/septal e' was > 8 in 39% of patients with HIV. Fractional shortening (< 28%) was reduced in 10% of healthy women, and mitral valve E/septal e' ratios were > 8 in 38% of that group. Women with pre-eclampsia demonstrated preserved systolic function, with diastolic dysfunction. Women with HIV demonstrated reduced left and right ventricular systolic function, with increased ventricular dilatation. PMID:25891669

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

    PubMed Central

    Fu, Binqing; Tian, Zhigang; Wei, Haiming

    2014-01-01

    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. PMID:25027967

  17. 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

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

    PubMed

    Elliot, Michael G; Crespi, Bernard J

    2015-03-01

    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

  19. Nitroso-Redox Balance and Mitochondrial Homeostasis Are Regulated by STOX1, a Pre-Eclampsia-Associated Gene

    PubMed Central

    Doridot, Ludivine; Chtre, Laurent; Ducat, Aurlien; Vilotte, Jean-Luc; Lombs, Anne; Mhats, Cline; Barbaux, Sandrine; Calicchio, Rosamaria

    2014-01-01

    Abstract Aims: Storkhead box 1 (STOX1) is a winged-helix transcription factor that is implicated in the genetic forms of a high-prevalence human gestational disease, pre-eclampsia. STOX1 overexpression confers pre-eclampsia-like transcriptomic features to trophoblastic cell lines and pre-eclampsia symptoms to pregnant mice. The aim of this work was to evaluate the impact of STOX1 on free radical equilibrium and mitochondrial function, both in vitro and in vivo. Results: Transcriptome analysis of STOX1-transgenic versus nontransgenic placentas at 16.5 days of gestation revealed alterations of mitochondria-related pathways. Placentas overexpressing STOX1 displayed altered mitochondrial mass and were severely biased toward protein nitration, indicating nitroso-redox imbalance in vivo. Trophoblast cells overexpressing STOX1 displayed an increased mitochondrial activity at 20% O2 and in hypoxia, despite reduction of the mitochondrial mass in the former. STOX1 overexpression is, therefore, associated with hyperactive mitochondria, resulting in increased free radical production. Moreover, nitric oxide (NO) production pathways were activated, resulting in peroxynitrite formation. At low oxygen pressure, STOX1 overexpression switched the free radical balance from reactive oxygen species (ROS) to reactive nitrogen species (RNS) in the placenta as well as in a trophoblast cell line. Innovation: In pre-eclamptic placentas, NO interacts with ROS and generates peroxynitrite and nitrated proteins as end products. This process will deprive the maternal organism of NO, a crucial vasodilator molecule. Conclusion: Our data posit STOX1 as a genetic switch in the ROS/RNS balance and suggest an explanation for elevated blood pressure in pre-eclampsia. Antioxid. Redox Signal. 21, 819834. PMID:24738702

  20. Are tests for predicting pre-eclampsia good enough to make screening viable? A review of reviews and critical appraisal.

    PubMed

    Cnossen, Jeltsje S; ter Riet, Gerben; Mol, Ben Willem; van der Post, Joris A; Leeflang, Mariska M; Meads, Catherine A; Hyde, Chris; Khan, Khalid S

    2009-01-01

    The aim of this article is to review the accuracy of tests purported to be predictive of pre-eclampsia, a major cause of maternal and perinatal mortality and morbidity worldwide. A review of systematic reviews was done. A total of 219 studies were evaluated for the accuracy of 27 tests for predicting pre-eclampsia. Study quality assessment and data abstraction were performed using piloted proformas. Bivariate meta-analyses were used to synthesize data. Levels of sensitivity and specificity were measured. There were deficiencies in many areas of methodology including blinding, test description, and reference standard adequacy. No test had a high level of both sensitivity and specificity of greater than 90%. Where multiple studies were available, only BMI > 34, alpha-fetoprotein, fibronectin (cellular and total), and uterine artery Doppler (bilateral notching) measurements reached specificity above 90%. Only Doppler (any/unilateral notching, resistance index, and combinations) measurements were over 60% sensitive. Studies were of variable quality and most tests performed poorly. Further research should focus on tests which offer much higher levels of sensitivity than tests currently available. High sensitivity is a more useful attribute in early detection of pre-eclampsia than specificity because consideration of benefits, harms and costs indicates a much greater preference for minimizing false negatives than false positives, although the ideal would be to avoid both. PMID:19488883

  1. Polymorphisms of the IL27 gene in a Chinese Han population complicated with pre-eclampsia

    PubMed Central

    Liu, Bin; Li, Yuan; Yao, Yuan; Li, Hua; Liang, Hongda; Xin, Miaomiao; Wang, Liqin; Zhao, Lei; Lin, Jizheng; Liu, Shiguo

    2016-01-01

    IL-27 could inhibit the development of Th17 cells, and the Th17/regulatory T-cell imbalance may reverse maternal tolerance in pre-eclampsia (PE). The aim of this study was to investigate the association between genetic polymorphisms in IL27 with PE. Three SNPs in IL27 (rs153109, rs17855750, and rs181206) were genotyped in a Chinese Han cohort of 1040 PE patients and 1247 normal pregnant women using the TaqMan allelic discrimination real-time PCR method. The CC genotypic distribution of rs153109 was significantly higher among cases than controls (19.1% versus 13.3%, odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.23–1.93, p < 0.001), and the CT genotype was found to be significantly lower in cases than controls (41.7% versus 49.0%, OR: 0.74, 95% CI: 0.63–0.88, p < 0.001), disputing existing reports indicating the allele frequency of rs153109 is not significantly different between PE patients and controls. Additionally, the CC genotype of rs153109 was significantly more prevalent in PE cases than controls using a recessive model (p < 0.001). The allelic and genotypic frequencies of rs17855750 and rs181206 were not significantly different between two groups. Our results reveal that IL27 polymorphisms may be involved in the development of PE in Chinese Han population. PMID:26971578

  2. Endocan of the maternal placenta tissue is increased in pre-eclampsia

    PubMed Central

    Chang, Xinwen; Bian, Yiding; Wu, Yanming; Huang, Yajing; Wang, Kai; Duan, Tao

    2015-01-01

    Purpose: Pre-eclampsia (PE) is associated with intravascular inflammation and endothelial dysfunction. Interestingly, endocan plays a predominant role in the vascular inflammation and is considered as a biomarker of endothelial dysfunction. The aim of this study was to explore whether the endocan levels in serum and placenta were different between pregnant women with PE and the normal pregnancies. Methods: Total 22 patients, including 10 normal pregnant women and 12 patients with PE, were included in this study. Immunohistochemistry was used to evaluate the location of endocan. Then, the mRNA and protein levels of endocan in placenta were detected using qRT-PCR and western blotting. Serum endocan concentration was measured by ELISA. Results: Endocan protein was present in the human placenta, and the mRNA and protein levels of placenta tissues were elevated (P < 0.05) in the normal pregnancy with third trimester than those with first trimester. Furthermore, the expression of endocan mRNA and protein were increased in the placenta tissues of PE compared with in the normal pregnancy (P < 0.05); however, the endocan concentration of maternal serum did not have significant differences. Conclusion: Endocan may play a role in the progression of pregnancy and has a potential to be a new marker for the detective of PE. PMID:26823798

  3. Restraint of Trophoblast Invasion of the Uterus by Decorin: Role in Pre-eclampsia.

    PubMed

    Nandi, Pinki; Siddiqui, Mohammad Fyyaz; Lala, Peeyush K

    2016-03-01

    Decorin (DCN) is a leucine-rich, TGF-β binding proteoglycan produced by mesenchymal cells including chondrocytes, dermal fibroblasts, and uterine decidual cells. It exerts multiple physiological functions including collagen fibrillogenesis, myogenesis, angiostasis, and restraining placental invasiveness. We discovered that decidua-derived DCN restrains proliferation, migration, and invasion of extravillous trophoblast (EVT) cells of the human placenta in a TGF-β-independent manner. These functions were differentially mediated by binding of DCN to multiple tyrosine kinase receptors (TKR) including EGFR, IGFR1, and VEGFR2. DCN blocked VEGFR-2 dependent EVT cell migration and endovascular differentiation by inhibiting P38MAPK and ERK1/2 pathways.We identified the avid VEGFR2 binding site in DCN protein as a 12 amino acids (LGTNPLKSSGIE) span in the Leucine-rich-repeat (LRR) 5 region of domain III. A single amino acid mutation (substitution of K to A) of DCN at this site abrogated VEGFR-2- dependent DCN actions. Also, DCN mRNA expression, measured with in situ hybridization, was selectively upregulated in decidual cells in placentas from mothers suffering from pre-eclampsia (PE), whereas the expression levels remained unchanged in chorionic villus mesenchymal cells. This difference between PE and control placentas was present at all gestational ages, indicating the pathogenic role of DCN in PE. We hypothesize that increased blood DCN levels could be a candidate biomarker for PE. PMID:26554635

  4. Pre-eclampsia: is it a different disease in primiparous and multiparous women?

    PubMed

    Badria, Layla Francis; Amarin, Zouhair Odeh

    2005-11-01

    The aim of this study was to evaluate differences in clinical and laboratory parameters and differences in the complication rates between pre-eclamptic primiparous and pre-eclamptic multiparous women. A prospective case series of 112 primiparous and 186 multiparous women with pre-eclampsia was conducted at Princess Badea Teaching Hospital; a large tertiary public health service hospital in Irbid, North Jordan. A uniform medical and surgical management protocol was implemented. The main outcome measures included antenatal, intrapartum and puerperal, maternal and foetal complications. Multiple maternal and foetal demographic, clinical and laboratory parameters were studied. As expected, the primiparous were younger than the multiparous women. After adjusting for maternal age, regression analysis revealed no difference in the systolic or diastolic blood pressure in the two groups. It was also demonstrated that there was no statistically significant difference in the clinical presentation, haematological and biochemical parameters or ultimate maternal outcome between the two groups. After adjusting for babies' sex and gestational age, it was demonstrated that there was no statistically significant difference in the following: gestational age at delivery, foetal weight, stillbirth, admission rate to neonatal intensive care unit, neonatal death rate within the first four weeks after birth and incidence of intrauterine growth restriction between the two groups. PMID:16001191

  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. 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. PMID:25555235

  7. Factors associated with pre-eclampsia and quality care of affected teenagers during labour within health region H. in Kwa-Zulu Natal.

    PubMed

    Dlamini, N J

    1997-12-01

    This is a descriptive, exploratory study which aimed at identifying the factors that are associated with pre-eclampsia in teenagers. The study also aimed at assessing the quality of midwifery care during labour in teenagers with pre-eclampsia so that recommendations can be made based on empirical findings. The study was done within Health Region H of KwaZulu-Natal Province in South Africa. A structured interview schedule was designed to tap information from pre-eclamptic teenagers in an attempt to identify factors associated with pre-eclampsia. A checklist was also designed and administered to assess the care of a pre-eclamptic teenager during labour. The study revealed that factors like age, nulliparity and socio-economic status were associated with pre-eclampsia. In as far as the rest of the factors, there was no relationship as indicated in previous studies. The study also revealed that teenagers affected by pre-eclampsia delayed in attending the antenatal clinic resulting in the control of the disease being difficult. In as far as midwifery care, the study revealed that psychological and social care, as well as the hygienic state of patients was not satisfactory. Based on the findings of the study, it is recommended that health education on prevention of pre-eclampsia should be done on an ongoing process, while carers for teenage mothers should be given inservice education programmes on psychosocial care. The physical environment for maternity units must be improved. PMID:9538699

  8. Maternal ophthalmic artery Doppler velocimetry in pre-eclampsia in Southwestern Nigeria

    PubMed Central

    Olatunji, Richard Busayo; Adekanmi, Ademola Joseph; Obajimi, Millicent Olubunmi; Roberts, Olumuyiwa Adebola; Ojo, Temitope Olumuyiwa

    2015-01-01

    Background Pre-eclampsia (PE) poses a serious challenge to maternal and fetal health in Africa. It is associated with hemodynamic changes that may affect the internal carotid/ophthalmic artery circulation with consequent neuro-ophthalmic manifestations. Ophthalmic artery Doppler (OAD) ultrasound is an important tool that can be used to detect hemodynamic changes in PE and monitor its severity. In this study, we evaluated hemodynamic changes on OAD ultrasound in the ophthalmic arteries of pre-eclamptic women and compared these with values in healthy pregnant women. Methods OAD parameters, such as, peak systolic velocity, peak diastolic velocity, end diastolic velocity, pulsatility index, and peak ratio, were measured on transorbital triplex ultrasound scan with a 710 MHz multifrequency linear transducer in 42 consenting pre-eclamptic patients and 41 pregnant controls matched for maternal age, gestational age, and parity at the Department of Radiology, University College Hospital, Ibadan. Univariate, bivariate, and receiver operating characteristic curve data analyses were performed. P<0.05 was considered to be statistically significant. Results Mean resistivity index, pulsatility index, and peak systolic velocity were significantly lower in pre-eclamptic patients than in the controls. Mean peak diastolic velocity, end diastolic velocity, and peak ratio were significantly higher in the pre-eclamptic group. The receiver operating characteristic curve showed that the resistivity index (sensitivity 75%, specificity 77.8%) could distinguish mild from severe PE while the peak ratio (sensitivity 90.5%, specificity 81.3%) could accurately detect PE. Conclusion OAD ultrasound can be used to monitor patients with PE for early detection of progression to severe forms before cerebral complications develop. OAD screening of patients at high risk for PE can also detect early changes of hemodynamic derangement. PMID:26229508

  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. PMID:22526494

  10. 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.

  11. Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis

    PubMed Central

    Wu, Pensée; van den Berg, Caroline; Alfirevic, Zarko; O’Brien, Shaughn; Röthlisberger, Maria; Baker, Philip Newton; Kenny, Louise C.; Kublickiene, Karolina; Duvekot, Johannes J.

    2015-01-01

    Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE. PMID:26404264

  12. 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. PMID:26733722

  13. Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

    PubMed Central

    Myatt, L; Clifton, RG; Roberts, JM; Spong, CY; Wapner, RJ; Thorp, JM; Mercer, BM; Peaceman, AM; Ramin, SM; Carpenter, MW; Sciscione, A; Tolosa, JE; Saade, G; Sorokin, Y; Anderson, GD

    2014-01-01

    Objective To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. Design A nested case–control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. Setting A multicentre study in 16 academic medical centres in the USA. Population Low-risk nulliparous women. Methods Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9–12, 15–18 and 23–26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. Main outcome measures Change in PlGF, sFlt-1 and sEng. Results Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64–99%), 77% (95% CI 50–93%) and 77% (95%CI 50–93%) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. Conclusion Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia. PMID:23331974

  14. Risk of prematurity, low birthweight and pre?eclampsia in relation to working hours and physical activities: a systematic review

    PubMed Central

    Bonzini, Matteo; Coggon, David; Palmer, Keith T

    2007-01-01

    Background Occupational activities are suspected of having an adverse impact on outcomes of pregnancy. Aim To assess the evidence relating three major adverse outcomes (preterm delivery, low birthweight (LBW) and pre?eclampsia/gestational hypertension) to five common occupational exposures (prolonged working hours, shift work, lifting, standing and heavy physical workload). Methods A systematic search of Medline and Embase (1966December 2005) using combinations of keywords and medical subject heading terms was conducted. For each relevant paper, standard details were abstracted that were then used to summarise the design features of studies, to rate their methodological quality (completeness of reporting and potential for important bias or confounding) and to provide estimates of effect. For studies with similar definitions of exposure and outcome, pooled estimates of relative risk (RR) in meta?analysis were calculated. Results 53 reports were identified35 on preterm delivery, 34 on birth weight and 9 on pre?eclampsia or gestational hypertension. These included 21 cohort investigations. For pre?term delivery, extensive evidence relating to each of the exposures of interest was found. Findings were generally consistent and tended to rule out a more than moderate effect size (RR >1.4). The larger and most complete studies were less positive, and pooled estimates of risk pointed to only modest or null effects. For small?for?gestational age, the position was similar, but the evidence base was more limited. For pre?eclampsia and gestational hypertension, it was too small to allow firm conclusions. Conclusions The balance of evidence is not sufficiently compelling to justify mandatory restrictions on any of the activities considered in this review. However, given some uncertainties in the evidence base and the apparent absence of important beneficial effects, it may be prudent to advise against long working hours, prolonged standing and heavy physical work, particularly late in pregnancy. Our review identifies several priorities for future investigation. PMID:17095552

  15. eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1Induced Pre-EclampsiaLike Phenotype

    PubMed Central

    Li, Feng; Hagaman, John R.; Kim, Hyung-Suk; Maeda, Nobuyo; Jennette, J. Charles; Faber, James E.; Karumanchi, S. Ananth; Smithies, Oliver

    2012-01-01

    Excess soluble fms-like tyrosine kinase 1 (sFlt-1) of vascular endothelial growth factor receptor 1 secreted from the placenta causes pre-eclampsialike features by antagonizing vascular endothelial growth factor signaling, which can lead to reduced endothelial nitric oxide synthase (eNOS) activity; the effect of this concomitant decrease in eNOS activity is unknown. We tested whether the decrease in nitric oxide occurring in female mice lacking eNOS aggravates the pre-eclampsialike phenotype induced by increased sFlt-1. Untreated eNOS-deficient female mice had higher BP than wild-type mice. Adenovirus-mediated overexpression of sFlt-1 increased systolic BP by approximately 27 mmHg and led to severe loss of fenestration of glomerular capillary endothelial cells in both eNOS-deficient and wild-type mice. However, only the eNOS-deficient sFlt-1 mice exhibited severe foot process effacement. Compared with wild-type sFlt-1 mice, eNOS-deficient sFlt-1 mice also showed markedly higher urinary albumin excretion (46774 versus 17423 ?g/d), lower creatinine clearance (12629 versus 45263 ?l/min), and more severe endotheliosis. Expression of preproendothelin-1 (ET-1) and its ETA receptor in the kidney was higher in eNOS-deficient sFlt-1 mice than in wild-type sFlt-1 mice. Furthermore, the selective ETA receptor antagonist ambrisentan attenuated the increases in BP and urinary albumin excretion and ameliorated endotheliosis in both wild-type and eNOS-deficient sFlt-1 mice. Ambrisentan improved creatinine clearance and podocyte effacement in eNOS-deficient sFlt-1 mice. In conclusion, reduced maternal eNOS/nitric oxide exacerbates the sFlt1-related pre-eclampsialike phenotype through activation of the endothelin system. PMID:22282588

  16. The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model.

    PubMed

    Turgut, Nergiz Hacer; Temiz, Tijen Kaya; Bagcivan, Ihsan; Turgut, Bulent; Gulturk, Sefa; Karadas, Baris

    2008-07-28

    The pathophysiology of pre-eclampsia is still unknown thus effective primary prevention is not possible at the stage. The present study was conducted to research the smooth muscle responses in the pre-eclampsia model with suramin treated rats and the effect of phosphodiesterase-5 (PDE5) inhibitor on these responses. Rats of three groups; control, suramin and suramin+sildenafil were given intraperitoneal injections of saline, suramin or sildenafil citrate. Suramin injections caused increased blood pressure, protein in urine and caused fetal growth retardation. The use of sildenafil citrate straightened significantly both blood pressure and average fetus weight, but did not reach to control values. At the end of pregnancy, thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction responses, sodium nitroprusside and papaverine relaxation responses were similar in three groups. Contraction responses of phenylephrine, increased significantly in suramin group. Relaxation responses of acethylcholine and bradykinin decreased in suramin group. The use of sildenafil citrate partially straightened both relaxation and contraction responses, but did not reach to control values. In all groups in the presence of L-nitromonomethylarginine (L-NAME), 1H-(1, 2, 4) oxadiazole (4, 3-a) guinoxalin-1-one (ODQ) and indomethacin decreased the relaxation responses of acetylcholine and bradykinin. The cyclic guanosine monophosphate (cGMP) content of thoracic aorta tissue was determined by radioimmunoassay technique. The content of cGMP in suramin group decreased and use of sildenafil citrate increased the cGMP content but did not reach to control values. We conclude that in pre-eclampsia, the increase of contraction responses, the decrease of relaxation responses and the decrease of cGMP content can depend on insufficiency about synthesis or release of relaxant factors which was released from the vessel endothelium. The results in this study show that in pre-eclampsia; PDE5 inhibitors enhance endothelial function and may be used for protection. Further studies are needed to clear the efficiency and safety of PDE5 inhibitors. PMID:18538317

  17. Clinical accuracy of a low cost portable blood pressure device in pregnancy and pre-eclampsia: the Nissei DS-400.

    PubMed

    de Greeff, Annemarie; Shennan, Andrew H

    2015-07-01

    Hypertensive disorders of pregnancy cause significant maternal morbidity and mortality worldwide, particularly in developing countries. This study evaluated the accuracy of the Nissei DS-400, a low cost blood pressure (BP) device, in pregnancy according to the British Hypertension Society protocol. Forty-five pregnant women (15 with pre-eclampsia), were recruited from a large teaching hospital. Nine sequential same-arm BP measurements were taken from each woman by trained observers, alternating between mercury sphygmomanometry and the device. The Nissei DS-400 achieved the highest accuracy grade (A/A) in all subjects (n = 45) and in pregnancy alone (n = 30). The mean difference standard deviation between the standard and the device in pregnancy were -1.0 5.1 mmHg and -1.1 5.0 mmHg for systolic and diastolic BP, respectively, and -2.6 5.9 mmHg and -3.4 5.8 mmHg in all subjects. The Nissei-DS 400 can be recommended for clinical use in pregnancy and has potential as a good screening tool for pre-eclampsia in low resource settings. PMID:25911652

  18. The role of maternal serumbeta-HCG and PAPP-A levels at gestational weeks 10 to 14 in the prediction of pre-eclampsia

    PubMed Central

    Ozdamar, Ozkan; Gun, Ismet; Keskin, Ugur; Kocak, Necmettin; Mungen, Ercument

    2014-01-01

    Objective: We aimed to detect whether maternal serum free ?-hCG and PAPP-A levels and NT measurements vary between normal pregnancies and those that subsequently develop pre-eclampsia and to evaluate the role of these screening serum analytes in the prediction of pre-eclampsia. Methods: Using a case-control study design, we identified all women who had been screened by double test within 11+0 and 13+6 weeks of gestation and who had developed pre-eclampsia during the subsequent pregnancy course, over a 6-year period between January 2006 and December 2012 at two tertiary referral hospital. All women who had undergone a double test during that time, without a diagnosis of pre-eclampsia and who had not had any adverse obstetric outcomes, were also identified, and three women among them were randomly selected as controls for each case. Maternal and neonatal data were abstracted from the medical records and PAPP-A, ?-hCG, NT and CRL MoM values were compared between the two groups. Results: Although ?-hCG values show no statistically significant difference (p=0.882), PAPP-A levels were significantly reduced in the pre-eclampsia group compared to the control group (p<0.001). NT and CRL values showed no significant difference between the two groups (p=0.674 and p=0.558, respectively). Conclusion: Measuring PAPP-A in the first trimester may be useful in the prediction of pre-eclampsia. PMID:24948981

  19. Retinal Vein Occlusion and Pregnancy, Pre-Eclampsia, and Eclampsia: The Results from a Nationwide, Population-Based Study Using the National Claim Database

    PubMed Central

    Seo, Kyung Ha; Park, Kyu Hyung; Woo, Se Joon

    2015-01-01

    Objective To investigate the incidence of retinal vein occlusion (RVO) in pregnant women and in the subpopulation of pregnant women with pre-eclampsia/eclampsia compared to that in the age-matched general female population to determine if there is increased risk of RVO in pregnancy. Design Nationwide population-based retrospective study using data entered into the Korean national health claims database from 2007 to 2011. Setting and Participants Of the incident RVO cases in the database, RVO cases that occurred during the pregnancy-associated period, which spanned a 52-week period from 40-weeks-before to 12-weeks-after childbirth, were identified. Of these cases, the presence of pre-eclampsia/eclampsia was determined. Main Outcome and Measure The standardized incidence ratios (SIRs) of RVO in the general pregnant population and in the pregnant population with pre-eclampsia/eclampsia were determined with respect to the age-matched general female population. Results Pregnancy-related RVO was identified in 33 cases from the 1.8 million women who experience childbirth during the study period, while the expected number of cases calculated by the direct standardization to the age-matched general population was 113. Of the 33 patients, 12 patients (36.4%) had pre-eclampsia or eclampsia. The SIR for the general pregnant population in reference to the age-matched general female population was 0.29 (95% CI, 0.200.41). In contrast, the SIR for the pregnant population with pre-eclampsia/eclampsia in reference to the age-matched general female population and the age-matched general pregnant population was 67.50 (95% CI, 34.88117.92) and 246.50 (95% CI, 127.37430.59), respectively. Conclusions and Relevance The results suggest that pre-eclampsia/eclampsia is a risk factor for RVO, while pregnancy itself may not be a risk factor for RVO. PMID:25774513

  20. Maternal outcomes of magnesium sulphate and diazepam use in women with severe pre-eclampsia and eclampsia in Ethiopia

    PubMed Central

    Kassie, Gizat M.; Negussie, Dereje; Ahmed, Jemal H.

    2013-01-01

    Background Preferred anticonvulsant used to treat and prevent fits in eclampsia currently is magnesium sulphate. Clinical monitoring of tendon reflexes, respiration rate and measuring hourly urine output should be done to ensures safe administration of magnesium sulphate Objective This study was conducted to evaluate maternal outcomes of magnesium sulphate and diazepam use in the management of severe pre-eclampsia and eclampsia in Jimma University Specialized Hospital. Methods A retrospective hospital based cross-sectional comparative study was conducted using data collection format. Data was collected from the hospital delivery care register and patient chart records of all pregnant women who presented with the diagnosis of severe pre-eclampsia and eclampsia in two years and three months period from January, 2010 to April, 2012. Data analysis was done by SPSS version 16.0. A P-value of <0.05 was considered statistically significant in all tests. Results A total of 357 patient charts, 217 from magnesium sulphate and 140 from diazepam treated pregnant women group, were reviewed and analyzed. Three pregnant women from the magnesium sulphate treated group and eleven pregnant women from diazepam treated group had at least one convulsion after taking the drug. Greater proportion of patients in the magnesium sulphate treated group had less than four days postpartum stay as compared to the diazepam treated patients (82.3% versus 66.2%). Seizure occurrence, duration of postpartum hospital stays and birth outcome had a statistically significant association with the type of anticonvulsant used. Conclusions Magnesium sulphate is more effective than diazepam in the management of severe pre-eclamptic and eclamptic pregnant women in terms of seizure prevention, shortening postpartum hospital stay and reducing maternal morbidities. PMID:25035717

  1. Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial

    PubMed Central

    McCance, David R; Holmes, Valerie A; Maresh, Michael JA; Patterson, Christopher C; Walker, James D; Pearson, Donald WM; Young, Ian S

    2010-01-01

    Summary Background Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes. Methods We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (?-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045. Findings Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 081, 95% CI 059112). No adverse maternal or neonatal outcomes were reported. Interpretation Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing. Funding The Wellcome Trust. PMID:20580423

  2. 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 care settings in low- and middle-income countries. Usability problems were often related to mobile phone features (eg, scroll wheels, touch screen use). Larger scale evaluation of the clinical impact of this tool is underway. PMID:25887292

  3. 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; Mkikallio, 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; Lhdesmki, Aija; Mehtl, 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 casecontrol 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 casecontrol 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

  4. Improved Assay for Quantifying a Redox Form of Angiotensinogen as a Biomarker for Pre-Eclampsia: A Case-Control Study

    PubMed Central

    Rahgozar, Soheila; Amirian, Tayebeh; Qi, Miao; Shahshahan, Zahra; Entezar-E-Ghaem, Mansureh; Ghasemi Tehrani, Hatav; Miroliaei, Mehran

    2015-01-01

    Objective Angiotensinogen exists in two distinct redox forms in plasma, the oxidized sulfhydryl-bridge form and the reduced, unbridged, free thiol form. The oxidized form of angiotensinogen compared to the free thiol form preferentially interacts with renin resulting in increased generation of angiotensin. The predictive potential of the ratio of free-thiol to oxidized angiotensinogen in the plasma for pre-eclampsia was first suggested by the Read group in ref 10. We propose an improved method for determining the ratio and validate the method in a larger cohort of pregnant women. Methods Plasma samples from 115 individuals with pre-eclampsia and from 55 healthy pregnant control subjects were collected sequentially over a 2 year period. Using two distinct enzyme-linked immunosorbent assays (ELISAs) the plasma levels of total and free thiol angiotensinogen were quantified. The oxidized angiotensinogen plasma level is derived by subtracting the level of free thiol, reduced angiotensinogen from the total angiotensinogen levels in the plasma. Results The relative proportion of free thiol angiotensinogen, expressed as a percentage of that observed with an in-house standard, is significantly decreased in pre-eclamptic patients (70.85% ± 29.49%) (mean ± SD) as compared to healthy pregnant controls (92.98 ± 24.93%) (mean ± SD) p ≤ 0.0001. The levels of total angiotensinogen did not differ between the two groups. Conclusion Patients with pre-eclampsia had substantially lower levels of free thiol angiotensinogen compared to healthy pregnant controls, whilst maintaining similar total angiotensinogen levels in the plasma. Hence, elevated levels of plasma oxidized angiotensinogen may be a contributing factor to hypertension in the setting of pre-eclampsia. PMID:26312482

  5. 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

  6. Early Onset Pre-Eclampsia Is Associated with Altered DNA Methylation of Cortisol-Signalling and Steroidogenic Genes in the Placenta

    PubMed Central

    Hogg, Kirsten; Blair, John D.; McFadden, Deborah E.; von Dadelszen, Peter; Robinson, Wendy P.

    2013-01-01

    Placental cortisol is inactivated in normotensive pregnancies, but is frequently present in pre-eclampsia associated placentae. Since glucocorticoids are strongly associated with the programming of long-term health, we assessed DNA methylation of genes involved in cortisol signalling and bioavailability, and hormonal signalling in the placenta of normotensive and hypertensive pregnancies. Candidate genes/CpG sites were selected through analysis of Illumina Infinium HumanMethylation450 BeadChip array data on control (n = 19) and early onset pre-eclampsia (EOPET; n = 19) placental samples. DNA methylation was further quantified by bisulfite pyrosequencing in a larger cohort of control (n = 111) cases, in addition to EOPET (n = 19), late onset pre-eclampsia (LOPET; n = 18) and normotensive intrauterine growth restriction (nIUGR; n = 13) cases. DNA methylation (percentage points) was increased at CpG sites within genes encoding the glucocorticoid receptor (NR3C1 exon 1D promoter; +8.46%; P<0.01) and corticotropin releasing hormone (CRH) binding protein (CRHBP intron 3; +9.14%; P<0.05), and decreased within CRH (5′ UTR; −4.30%; P = 0.11) in EOPET-associated placentae, but not in LOPET nor nIUGR cases, compared to controls. Differential DNA methylation was not observed among groups at the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene promoter. Significant hypomethylation was observed in pre-eclampsia but not nIUGR placentae for steroidogenic genes, including CYP11A1 (exon1; EOPET; −9.66%; P<0.00001, and LOPET; −5.77%; P<0.001), 3β-hydroxy-delta-5-steroid dehydrogenase type 1 (HSD3B1 exon 2; EOPET; −12.49%; P<0.00001, and LOPET; −6.88%; P<0.001), TEA domain family member 3 (TEAD3 intron 1; EOPET; −12.56%; P<0.00001) and CYP19 (placental-specific exon 1.1 promoter; EOPET; −10.62%, P<0.0001). These data represent dysregulation of the placental epigenome in pre-eclampsia related to genes involved in maintaining the hormonal environment during pregnancy and highlights particular susceptibility in the early onset syndrome. PMID:23667551

  7. Placental hypoxia, endoplasmic reticulum stress and maternal endothelial sensitisation by sFLT1 in pre-eclampsia.

    PubMed

    Charnock-Jones, D Stephen

    2016-04-01

    The human placenta is a multifunctional organ that grows and adapts to increasing fetal demand and fluctuations in the intrauterine environment. It is subjected to physiological and pathological changes in local oxygenation, both of which induce adaptive changes. In early pregnancy a low PO2 is the normal physiological state and this is not hypoxic-there is no perturbation of ATP/ADP ratios and, if the placenta is sampled very rapidly, little HIF1α is detected in human first-trimester placental villi. Nonetheless, HIF1α can be increased and activated by culture. However, the placenta does show evidence of stress under pathological conditions. For example, in cases of pre-eclampsia where delivery by caesarean section is necessitated for maternal well-being before 34 weeks' gestation, placental endoplasmic reticulum stress is evident. Cases delivered ≥34 weeks are indistinguishable from normal term controls. One consequence of placental stress, whether oxidative, related to the endoplasmic reticulum or immunological, is that factors are released into the maternal circulation, which affects the endothelium, leading to the maternal syndrome. Soluble FLT1 may contribute directly to this and the most likely mechanism is direct action on the maternal endothelium. sFLT1 is able to form a heterodimer with cell surface VEGF receptors and is therefore able to have a dominant negative effect (in addition to acting as a competitive inhibitor by simply binding vascular endothelial growth factor A [VEGFA] and placental growth factor [PlGF]). This leads in vitro to the sensitisation of endothelial cells to low levels of TNFα. PMID:26228018

  8. 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 Central

    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. PMID:23555626

  9. Criteria-Based Audit of Quality of Care to Women with Severe Pre-Eclampsia and Eclampsia in a Referral Hospital in Accra, Ghana

    PubMed Central

    Srofenyoh, Emmanuel K.; Grobbee, Diederick E.; Klipstein-Grobusch, Kerstin

    2015-01-01

    Objectives Severe pre-eclampsia and eclampsia are one of the major causes of maternal mortality globally. Reducing maternal morbidity and mortality demands optimizing quality of care. Criteria-based audits are a tool to define, assess and improve quality of care. The aim of this study was to determine applicability of a criteria-based audit to assess quality of care delivered to women with severe hypertensive disorders in pregnancy, and to assess adherence to protocols and quality of care provided at a regional hospital in Accra, Ghana. Methods Checklists for management of severe preeclampsia, hypertensive emergency and eclampsia were developed in an audit cycle based on nine existing key clinical care protocols. Fifty cases were audited to assess quality of care, defined as adherence to protocols. Analysis was stratified for complicated cases, defined as (imminent) eclampsia, perinatal mortality and/or one or more WHO maternal near miss C-criteria. Results Mean adherence to the nine protocols ranged from 1585%. Protocols for plan for delivery and magnesium sulphate administration were best adhered to (85%), followed by adherence to protocols for eclampsia (64%), severe pre-eclampsia at admission (60%), severe pre-eclampsia ward follow-up (53%) and hypertensive emergency (53%). Protocols for monitoring were least adhered to (15%). No difference was observed for severe disease. Increased awareness, protocol-based training of staff, and clear task assignment were identified as contributors to better adherence. Conclusion A criteria-based audit is an effective tool to determine quality of care, identify gaps in standard of care, and allow for monitoring and evaluation in a health facility, ultimately resulting in improved quality of care provided and reduced maternal morbidity and mortality. In our audit, good adherence was observed for plan for delivery and treatment with magnesium sulphate. Substandard adherence to a number of protocols was identified, and points towards opportunities for targeted improvement strategies. PMID:25923663

  10. Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts

    PubMed Central

    Silverwood, Richard J; de Stavola, Bianca L; Inskip, Hazel; Cooper, Cyrus; Godfrey, Keith M; Crozier, Sarah; Fraser, Abigail; Nelson, Scott M; Lawlor, Debbie A; Tilling, Kate

    2015-01-01

    Study question Can routine antenatal blood pressure measurements between 20 and 36 weeks’ gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes? Methods This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women’s Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks. Study answer and limitations The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice. What this study adds The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care. Funding, competing interests, data sharing UK Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. Other funding sources for authors are detailed in the full online paper. With the exceptions of CM-W, HMI, and KMG there were no competing interests. PMID:26578347

  11. Differentiation of ICOS(+) and ICOS(-) recent thymic emigrant regulatory T cells (RTE Tregs ) 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) Tregs 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(-) Treg pools with CD45RA(+) CD31(+) RTE Tregs , CD45RA(+) CD31(-) mature naive (MN) Tregs , 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 Tregs , into CD45RA(-) CD31(-) memory Tregs . At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS(+) CD45RA(-) CD31(-) memory Tregs . However, in the presence of pre-eclampsia, there was a significantly increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE Tregs into CD45RA(-) CD31(+) memory Tregs , wherein the lacking differentiation into CD45RA(-) CD31(-) memory Tregs was partially replaced by the increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(-) MN Tregs into CD45RA(-) CD31(-) memory Tregs . In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA(-) CD31(-) MN Tregs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS(+) and ICOS(-) Tregs , 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 Tregs ensures a healthy pregnancy course, while their disturbed differentiation is associated with the occurrence of pre-eclampsia and HELLP syndrome. PMID:26285098

  12. Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration

    PubMed Central

    Khan, Gulafshana Hafeez; Galazis, Nicolas; Docheva, Nikolina; Layfield, Robert; Atiomo, William

    2015-01-01

    STUDY QUESTION Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). SUMMARY ANSWER Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls. WHAT IS KNOWN ALREADY Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known. STUDY DESIGN, SIZE, DURATION A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192. MAIN RESULTS AND THE ROLE OF CHANCE Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies. LIMITATIONS, REASONS FOR CAUTION The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues. WIDER IMPLICATIONS OF THE FINDINGS This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a well co-ordinated multidisciplinary collaboration of clinicians, basic scientists and mathematicians is vital. STUDY FUNDING/COMPETING INTEREST(S) No financial support was obtained for this project. There are no conflicts of interest. PMID:25351721

  13. Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol

    PubMed Central

    Cluver, Catherine A; Walker, Susan P; Mol, Ben W; Theron, Gerard B; Hall, David R; Hiscock, Richard; Hannan, N; Tong, S

    2015-01-01

    Introduction Pre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than delivery. A drug that can quench the disease process could be useful to treat early onset pre-eclampsia, as it could allow pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have generated preclinical data to show esomeprazole, a proton pump inhibitor used for gastric reflux, has potent biological effects that makes it a worthwhile therapeutic candidate. Esomeprazole potently decreases soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin secretion from placenta and endothelial cells, and has biological actions to mitigate endothelial dysfunction and oxidative stress. Methods and analysis We propose undertaking a phase II, double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. We will recruit 120 women (gestational age of 26+0 to 31+6 weeks) who will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. Secondary outcomes include maternal, fetal and neonatal composite and individual outcomes. Maternal outcomes include maternal death, eclampsia, pulmonary oedema, severe renal impairment, cerebral vascular events and liver haematoma or rupture. Neonatal outcomes include neonatal death within 6 weeks after the due date, intraventricular haemorrhage, necrotising enterocolitis and bronchopulmonary dysplasia. We will examine whether esomeprazole can decrease serum sFlt-1 and soluble endoglin levels and we will record the safety of esomeprazole in these pregnancies. Ethics and dissemination This study has ethical approval (Protocol V.2.4, M14/09/038, Federal Wide assurance Number 00001372, IRB0005239), and is registered with NHREC (ID 3649) and the Pan African Clinical Trial Registry (PACTR201504000771349). Data will be presented at international conferences and published in peer-reviewed journals. PMID:26510725

  14. 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

  15. A Comprehensive Survey of miRNA Repertoire and 3? Addition Events in the Placentas of Patients with Pre-Eclampsia from High-Throughput Sequencing

    PubMed Central

    Lu, Jiafeng; Li, Hailing; Ge, Qinyu; Gu, Wanjun; Bai, Yunfei; Lu, Zuhong

    2011-01-01

    Background To gain insight into potential roles of isomiR spectrum and isomiRs with 3? additions in pre-eclampsia, we performed a comprehensive survey of miRNA repertoire and 3? addition events from placental samples with different degrees of pre-eclampsia by applying SOLiD sequencing platform. Principal Findings Over 30% isomiRs were detected with 3? non-template additional nucleotides, especially for additional nucleotide of adenosine. However, these modified isomiRs showed a lower percentage of total miRNA expression (<15%). Generally, 1-3 abundant isomiRs from a given miRNA locus were identified, but none of them was detected with 3? additions. Different miRNAs indicated various isomiR spectrums and expression patterns. The most abundant isomiR spectrum, isomiR profile and expression pattern always were stability, but herein we found several exceptions across samples, especially between normal and diseased samples. At isomiR level, we detected a distinct subset of differentially expressed modified isomiRs between normal and diseased samples or between mild and severe samples. Gene Ontology analysis of their experimentally validated target genes revealed enrichment for specific biological process categories. Conclusions The phenomenon of multiple isomiRs, especially for isomiRs with 3? additions, is not a random event during pre-miRNA processing. Varieties of isomiRs and expression patterns reveal potential functional implication and should be taken into account. The study enriches association of miRNAs and human disease, including potential roles of various miRNA variants and 3? addition events. PMID:21731650

  16. Regulation of fatty acid binding proteins by hypoxia inducible factors 1? and 2? in the placenta: relevance to pre-eclampsia.

    PubMed

    Jadoon, Ayesha; Cunningham, Phil; McDermott, Lindsay C

    2015-02-01

    Pre-eclampsia is characterized by placental hypoxia and dyslipidemia. Arachidonic and docosahexanoic acids are essential maternal nutrients for fetal development. They are transported via placental trophoblast cells by membrane and cytosolic fatty acid binding proteins. Others report the expressions of these proteins which are increased in hypoxic trophoblasts. Using bioinformatics, BeWo cells, reporter assays, quantitative real-time PCR and immunoblotting we tested the hypothesis that hypoxia inducible factors 1? (HIF-1?) and/or 2? (HIF-2?) regulate the expressions of FABP1, FABP3, FABP4 and FATP2 proteins. Three hypoxia responsive elements (HRE) were identified in FABP1 which cumulatively responded strongly to HIF-1? and weakly to HIF-2?. FABP3 expression partially responded to HIF-1?. Two putative HRE were validated in FABP4 both of which responded weakly to HIF-1? and HIF-2?. FATP2 protein expression reacted positively to hypoxia. Thus, fetal essential fatty acid supply via the placenta is protected under hypoxia. It will be interesting to determine if our findings are replicated in human pre-eclamptic placenta. PMID:25305177

  17. Fish Oil Supplementation does not Reduce Risks of Gestational Diabetes Mellitus, Pregnancy-Induced Hypertension, or Pre-Eclampsia: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Chen, Bing; Ji, Xinran; Zhang, Lei; Hou, Zhaohui; Li, Chundong; Tong, Ying

    2015-01-01

    Background The effects of gestational supplementation with fish oil on risks for gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and pre-eclampsia (PE) have not been confirmed. In this study, a meta-analysis was performed to evaluate the effect of fish oil supplementation on these gestational complications. Material/Methods Randomized controlled human trials that investigated the effects of fish oil supplementation in pregnant women were identified by a systematic search of Medline, Embase, and Cochranes Library, and references of related reviews and studies up to December 2014. Relative risks (RRs) for GDM, PIH, and PE were the outcomes of interest. Fixed-effects or random-effects models were applied according to the heterogeneity. Results Thirteen comparisons from 11 published articles, including more than 5000 participants, were included. The results showed that fish oil supplementation was not associated with reduced risks for GDM (RR=1.06, 95% confidence interval [CI]: 0.851.32, p=0.60), PIH (RR=1.03, 95% CI: 0.891.20, p=0.66), or PE (RR=0.93, 95% CI: 0.741.16, p=0.51). No statistically significant heterogeneity was detected for the comparison of each outcome. The effects of fish oil on these gestational complications were consistent between women with low-risk and high-risk pregnancies. Conclusions Gestational supplementation with fish oil during the second or third trimester of pregnancy is not associated with reduced risks for GDM, PIH, or PE. Other possible benefits of fish oil supplementation during pregnancy warrant further evaluation. PMID:26256041

  18. A Label-free Selected Reaction Monitoring Workflow Identifies a Subset of Pregnancy Specific Glycoproteins as Potential Predictive Markers of Early-onset Pre-eclampsia*

    PubMed Central

    Blankley, Richard T.; Fisher, Christal; Westwood, Melissa; North, Robyn; Baker, Philip N.; Walker, Michael J.; Williamson, Andrew; Whetton, Anthony D.; Lin, Wanchang; McCowan, Lesley; Roberts, Claire T.; Cooper, Garth J. S.; Unwin, Richard D.; Myers, Jenny E.

    2013-01-01

    Pre-eclampsia (PE) is a serious complication of pregnancy with potentially life threatening consequences for both mother and baby. Presently there is no test with the required performance to predict which healthy first-time mothers will go on to develop PE. The high specificity, sensitivity, and multiplexed nature of selected reaction monitoring holds great potential as a tool for the verification and validation of putative candidate biomarkersfor disease states. Realization of this potential involves establishing a high throughput, cost effective, reproducible sample preparation workflow. We have developed a semi-automated HPLC-based sample preparation workflow before a label-free selected reaction monitoring approach. This workflow has been applied to the search for novel predictive biomarkers for PE. To discover novel candidate biomarkers for PE, we used isobaric tagging to identify several potential biomarker proteins in plasma obtained at 15 weeks gestation from nulliparous women who later developed PE compared with pregnant women who remained healthy. Such a study generates a number of candidate biomarkers that require further testing in larger patient cohorts. As proof-of-principle, two of these proteins were taken forward for verification in a 100 women (58 PE, 42 controls) using label-free SRM. We obtained reproducible protein quantitation across the 100 samples and demonstrated significant changes in protein levels, even with as little as 20% change in protein concentration. The SRM data correlated with a commercial ELISA, suggesting that this is a robust workflow suitable for rapid, affordable, label-free verification of which candidate biomarkers should be taken forward for thorough investigation. A subset of pregnancy-specific glycoproteins (PSGs) had value as novel predictive markers for PE. PMID:23897580

  19. TGFB1 Functional Gene Polymorphisms (C-509T and T869C) in the Maternal Susceptibility to Pre-eclampsia in South Indian Women.

    PubMed

    Deepthi, Goske; Chaithri, Ponnaluri Kamakshi; Latha, Prasanna; Rani, Vital Usha; Rahman, Police Fazul; Jahan, Parveen

    2015-10-01

    Pre-eclampsia (PE), a pregnancy-specific vascular disorder characterized by hypertension and proteinuria, is hypothesized to be the result of inadequate placental angiogenesis with attendant systemic inflammation. The pleiotropic cytokine, Transforming Growth Factor-?1 (TGF-?1), is considered to be a key candidate gene in the molecular pathogenesis of PE by virtue of its ability to not only regulate angiogenesis and apoptosis of target cells, but also by acting as a master controller of Th1/Th2 cytokine balance and production of the anti-inflammatory peripheral regulatory T cells (FOXP3+ Tregs). Based on this presumption, we screened a total of 469 pregnant women from South India that include 239 patients with PE and 230 healthy controls for the two functional polymorphisms of TGFB1 gene (C-509T and T869C). The genotype frequencies of these two polymorphisms differed significantly between the PE and control groups (P = 0.01 and P = 0.002, for the TGFB1 C-509T and T869C polymorphisms, respectively). Under the over-dominant model, the CT genotype of the TGFB1 C509T polymorphism showed a high protective effect (P = 3e-04), while the TT genotype of the same variant appeared to be the predisposing genotype (P = 0.003). The T-T and C-C haplotypes were found to be the risk haplotypes blocks towards PE (OR = 4.72; P = 0.031, OR = 5.39; P = 0.03), respectively. Strong linkage disequilibrium was seen between the two polymorphisms. Our investigations revealed a significant influence of TGFB1 C-509T and T869C polymorphisms on the PE risk in South Indian women. The study represents one of the first of its kind from the Indian subcontinent. PMID:26173679

  20. 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-Vzquez, Ramn Mauricio; Canizales-Quinteros, Samuel; Coronel, Agustn; Carlos Falcn, Juan; Hernndez 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 genegene interactions between these three polymorphisms with the presence of PE in Mexican-Mestizo women and one Amerindian population from Mxico (Maya). A casecontrol 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 genegene interaction was conducted. Genotypic and allelic distribution of the polymorphisms was similar in our population. The estimated of the genegene 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 genegene interaction in women with PE. PMID:23013217

  1. Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population

    PubMed Central

    Best, Lyle G.; Saxena, Richa; Anderson, Cindy M.; Barnes, Michael R.; Hakonarson, Hakon; Falcon, Gilbert; Martin, Candelaria; Castillo, Berta Almoguera; Karumanchi, Ananth; Keplin, Kylie; Pearson, Nichole; Lamb, Felicia; Bercier, Shellee; Keating, Brendan J.

    2013-01-01

    Background The etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease. Methods This study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped. Results A nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother's age, nulliparity and BMI attenuated the effect (OR 1.58, P?=?0.066, 95% CI 0.972.58) for rs876538 and (OR 2.59, P?=?0.050, 95% CI 1.006.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P?=?0.013, 95% CI 1.163.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR?=?1.55, P?=?0.01, 95% CI 2.161.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants. Conclusion The CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE. PMID:23940726

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

    PubMed Central

    Daniels, Karen; Lewin, Simon

    2008-01-01

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

  3. A Risk Prediction Model for the Assessment and Triage of Women with Hypertensive Disorders of Pregnancy in Low-Resourced Settings: The miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Multi-country Prospective Cohort Study

    PubMed Central

    Payne, Beth A.; Hutcheon, Jennifer A.; Ansermino, J. Mark; Hall, David R.; Bhutta, Zulfiqar A.; Bhutta, Shereen Z.; Biryabarema, Christine; Grobman, William A.; Groen, Henk; Li, Jing; Magee, Laura A.; Merialdi, Mario; Nakimuli, Annettee; Qu, Ziguang; Sikandar, Rozina; Sass, Nelson; Sawchuck, Diane; Steyn, D. Wilhelm; Widmer, Mariana; Zhou, Jian; von Dadelszen, Peter

    2014-01-01

    Background Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. Methods and Findings From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.7350.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.6580.768). A predicted probability ?25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. Conclusions The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care. Please see later in the article for the Editors' Summary PMID:24465185

  4. Effectiveness and safety of 1 vs 4?h blood pressure profile with clinical and laboratory assessment for the exclusion of gestational hypertension and pre-eclampsia: a retrospective study in a university affiliated maternity hospital

    PubMed Central

    McCarthy, Elizabeth Anne; Carins, Thomas A; Hannigan, Yolanda; Bardien, Nadia; Shub, Alexis; Walker, Susan P

    2015-01-01

    Objective We asked whether 60 compared with 240?min observation is sufficiently informative and safe for pregnancy day assessment (PDAC) of suspected pre-eclampsia (PE). Design A retrospective study of 209 pregnant women (475 PDAC assessments, 6?months) with routinely collected blood pressure (BP), symptom and laboratory information. We proposed a 60?min screening algorithm comprising: absence of symptoms, normal laboratory parameters and ?1high-BP reading (systolic blood pressure, SBP 140?mm?Hg or higher or diastolic blood pressure, DBP 90?mm?Hg or higher). We also evaluated two less inclusive screening algorithms. We determined short-term outcomes (within 4?h): severe hypertension, proteinuric hypertension and pregnancy-induced hypertension, as well as long-term outcome: PE-related diagnoses up to the early puerperium. We assessed performance of alternate screening algorithms performance using 22 tables. Results 1 in 3 women met all screen negative criteria at 1?h. Their risk of hypertension requiring treatment in the next 3?h was 1.8% and of failing to diagnose proteinuric hypertensive PE at 4?h was 5.1%. If BP triggers were 5?mm?Hg lower, 1 in 6 women would be screen-negative of whom 1.1% subsequently develops treatment-requiring hypertension and 4.5% demonstrate short-term proteinuric hypertension. We present sensitivity, specificity, negative and positive likelihood ratios for alternate screening algorithms. Conclusions We endorse further research into the safest screening test where women are considered for discharge after 60?min. Safety, patient and staff satisfaction should be assessed prospectively. Any screening test should be used in conjunction with good clinical care to minimise maternal and perinatal hazards of PE. PMID:26582404

  5. 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 intake and iron and folic acid supplementation in pregnancy was associated with a reduced occurrence of symptoms suggestive of PE or E in Indian women. PMID:25785774

  6. 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 PE. PMID:25024139

  7. [Conservative management in severe pre-eclampsia].

    PubMed

    Romero Arauz, J F; Lara González, A L; Izquierdo Puente, C

    2000-02-01

    A total of 58 women with severe preeclampsia between 28-33 weeks of gestation were studied during the period from 1 October 1996 to 1 October 1997. Twenty-four women (42%) developed maternal or fetal indications necessitating early delivery within 48 hours, meanwhile the other 34 patients (58%) received expectant management. The average pregnancy prolongation period in the conservative management group was 6.4 days (range 3 to 18). The primary indications for delivery in this group were maternal indications 16 (47%), fetal compromise 13 (39%), 34 weeks of gestation 3 (8%), abruption placentae 1 (3%) and preterm labor 1 (3%). The mean birth weight and Apgar score at 5 minutes were 1520 +/- 310 g and 8, respectively. Expectant management was not associated with fetal death or maternal complications. The only neonatal death was related with sepsis and prematurity. The women in the early delivery group totaled two stillbirths and three neonatal deaths. PMID:10774104

  8. Management of pre-eclampsia/eclampsia.

    PubMed

    Ababneh, Mo

    2004-06-01

    Preclampsia/eclampsia affects only a small proportion of all pregnancies, yet it is associated with significant morbidity and mortality for mother and baby, with post partum resolution. The disorder is triggered by a placental pathology followed by a wide spectrum of maternal systemic response. However, there remains controversy in practically every aspect of the condition. A full understanding of the condition, its variable presentation allows the consulting anesthetist to optimize a plan for anesthetic management. PMID:15449750

  9. Pre-eclampsia - The "uterine reinnervation" view.

    PubMed

    Quinn, M J

    2014-11-01

    Difficult vaginal deliveries, gynaecological surgery, and, persistent straining during defaecation injure uterine nerves. Cytokines released from injured, uterine nerves cause regeneration of new nerves with altered structures and functions. In structural terms, these new nerves proliferate in chaotic and dysfunctional patterns with abnormal, cross-sectional profiles. In functional terms they are particularly sensitive to "stretch" or mechanosensory transduction. Release of neural cytokines also causes hyperplasia of the walls of adjacent, denervated uterine arterioles that may reduce uteroplacental blood flow during pregnancy. In the "uterine reinnervation" view, "stretch" applied to injured uterine nerves triggers uterorenal nerves to cause vasoconstriction in the renal cortex, hypertension and proteinuria i.e. the key features of preeclampsia. There are two intrauterine mechanisms that stretch injured, uterine nerves (a) in the placental bed, (b) in the extraplacental myometrium, respectively. In "early-onset" preeclampsia (<34weeks), continuing increases in maternal plasma volume, increase blood flow through denervated, and, narrowed uterine arterioles in the placental bed, stretching injured perivascular nerves resulting in preeclampsia with a small-for-gestational-age fetus. In "late-onset" preeclampsia (>34weeks), nulliparity, multiple pregnancy, concealed abruption and polyhydramnios increase myometrial tension and results in preeclampsia with an appropriate-for-gestational-age fetus. Widespread activation of autonomic nerves results in multi-system features of these syndromes. Changes in placental site and circulatory compliance may contribute to different phenotypes of the preeclamptic syndromes in subsequent pregnancies. The "uterine reinnervation" view offers an explanation of the common clinical features of the preeclamptic syndromes through a single pathophysiological mechanism, namely, prepregnancy injury to uterine nerves. Importantly, it offers an explanation for resolution of the symptoms and signs of preeclampsia with delivery of the fetus, the "early" and "late-onset" preeclamptic syndromes, and, the established clinical associations of the condition including nulliparity, hydramnios, multiple pregnancy, molar pregnancy, concealed abruption, etc. Establishing the presence of injured nerves expressing mechanoreceptors in the uterus, and, neural cytokines in thickened, uterine arterioles, will assist in developing this view. However, myometrial hyperplasia during the second half of pregnancy separates injured uterine nerves from injured uterine arterioles ensuring that the key pathoanatomical relationship in preeclampsia will be difficult to demonstrate. PMID:25216751

  10. 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…

  11. Role of volume expansion in severe pre-eclampsia.

    PubMed

    Kirshon, B; Moise, K J; Cotton, D B; Longmire, S; Jones, M; Tessem, J; Joyce, T A

    1988-11-01

    Fifteen primigravid patients with severe pregnancy-induced hypertension were studied by catheterization of the right side of the heart. A hemodynamic protocol was implemented that required maintaining colloid osmotic pressure above 17 millimeters of mercury, pulmonary capillary wedge pressure below 15 millimeters of mercury and the mean arterial pressure in a very narrow range throughout labor and delivery and for 48 hours postpartum. The initial colloid osmotic pressures and pulmonary capillary wedge pressures were 18.0 +/- 2.6 and 10.5 +/- 4.0 millimeters of mercury, respectively, and remained essentially unchanged throughout the post partum period. The only benefit derived from volume expansion in these patients appeared to be the absence of acute fetal distress after the initiation of antihypertensive therapy. Six of 15 patients had late fetal stress develop during labor, suggesting that aggressive volume repletion and colloid osmotic pressure correction in pregnancy-induced hypertension does not effect the over-all incidence of fetal distress. We recommend that correction of colloid osmotic pressure be restricted to instances in which extremely low values (less than 12 millimeters of mercury) or a prolonged negative colloid osmotic pressure to pulmonary capillary wedge pressure gradient are identified. Finally, the benefit of volume expansion in pregnancy-induced hypertension appears to be the prevention of sudden and profound drops in blood pressure with antihypertensive therapy--not the prevention of fetal distress during labor. PMID:3140400

  12. The global impact of pre-eclampsia and eclampsia.

    PubMed

    Duley, Lelia

    2009-06-01

    Over half a million women die each year from pregnancy related causes, 99% in low and middle income countries. In many low income countries, complications of pregnancy and childbirth are the leading cause of death amongst women of reproductive years. The Millennium Development Goals have placed maternal health at the core of the struggle against poverty and inequality, as a matter of human rights. Ten percent of women have high blood pressure during pregnancy, and preeclampsia complicates 2% to 8% of pregnancies. Preeclampsia can lead to problems in the liver, kidneys, brain and the clotting system. Risks for the baby include poor growth and prematurity. Although outcome is often good, preeclampsia can be devastating and life threatening. Overall, 10% to 15% of direct maternal deaths are associated with preeclampsia and eclampsia. Where maternal mortality is high, most of deaths are attributable to eclampsia, rather than preeclampsia. Perinatal mortality is high following preeclampsia, and even higher following eclampsia. In low and middle income countries many public hospitals have limited access to neonatal intensive care, and so the mortality and morbidity is likely to be considerably higher than in settings where such facilities are available. The only interventions shown to prevent preeclampsia are antiplatelet agents, primarily low dose aspirin, and calcium supplementation. Treatment is largely symptomatic. Antihypertensive drugs are mandatory for very high blood pressure. Plasma volume expansion, corticosteroids and antioxidant agents have been suggested for severe preeclampsia, but trials to date have not shown benefit. Optimal timing for delivery of women with severe preeclampsia before 32 to 34 weeks' gestation remains a dilemma. Magnesium sulfate can prevent and control eclamptic seizures. For preeclampsia, it more than halves the risk of eclampsia (number needed to treat 100, 95% confidence interval 50 to 100) and probably reduces the risk of maternal death. A quarter of women have side effects, primarily flushing. With clinical monitoring serious adverse effects are rare. Magnesium sulfate is the anticonvulsant of choice for treating eclampsia; more effective than diazepam, phenytoin, or lytic cocktail. Although it is a low cost effective treatment, magnesium sulfate is not available in all low and middle income countries; scaling up its use for eclampsia and severe preeclampsia will contribute to achieving the Millennium Development Goals. PMID:19464502

  13. 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

  14. 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

  15. Genome-Wide Transcriptome Directed Pathway Analysis of Maternal Pre-Eclampsia Susceptibility Genes

    PubMed Central

    Yong, Hannah E. J.; Melton, Phillip E.; Johnson, Matthew P.; Freed, Katy A.; Kalionis, Bill; Murthi, Padma; Brennecke, Shaun P.; Keogh, Rosemary J.; Moses, Eric K.

    2015-01-01

    Background Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associated with PE. We have thus taken a novel integrative bioinformatics approach of analysing pathways common to the susceptibility genes and the PE transcriptome. Methods Using Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. The R software package libraries lumi and limma were used to preprocess transcript data for pathway analysis. Pathways were analysed and constructed using Pathway Studio. We examined ten candidate genes, which are from these functional groups: activin/inhibin signallingACVR1, ACVR1C, ACVR2A, INHA, INHBB; structural componentsCOL4A1, COL4A2 and M1 family aminopeptidasesERAP1, ERAP2 and LNPEP. Results/Conclusion Major common regulators/targets of these susceptibility genes identified were AGT, IFNG, IL6, INHBA, SERPINE1, TGFB1 and VEGFA. The top two categories of pathways associated with the susceptibility genes, which were significantly altered in the PE decidual transcriptome, were apoptosis and cell signaling (p < 0.001). Thus, susceptibility genes from distinct functional groups share similar downstream pathways through common regulators/targets, some of which are altered in PE. This study contributes to a better understanding of how susceptibility genes may interact in the development of PE. With this knowledge, more targeted functional analyses of PE susceptibility genes in these key pathways can be performed to examine their contributions to the pathogenesis and severity of PE. PMID:26010865

  16. 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…

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

    PubMed

    Carmona-Guirado, A J; Escao-Cardona, V; Garca-Caedo, 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. PMID:25600462

  18. [Reduced and oxidized glutathione of the placenta in pregnancy complicated by pre-eclampsia].

    PubMed

    Neves, J; Cruz, A S; Azevedo, I; Vaz, A C; Vasco, P; Santos, P J; Bicho, M P

    1997-05-01

    Significative enhancement of free radical formation (FRO) in vivo is an important feature of hypertensive disorders of pregnancy (HDP), namely preeclampsia (PIH). The latest investigations about the pathology of HDP, showed the contribution of placental circulation to the development and evolution of such disease. The placental bed can be a potential source of FRO or activation of cells that can produce FRO. Glutathione, is an important molecule for cellular protection against damage, is a cofactor of many enzymes, in particular, for the glutathione peroxidase of the placental tissue; this enzyme in the placenta bed prevent the production of thromboxan and lipoperoxides; the latter are potentially damaging to the endothelium cells and can cause vasoconstriction, the most important feature of PIH. The activity of that enzyme is deficient in PIH. We studied, by fluorometric assay, the concentrations of the two states of glutathione in placental homogenates (PLH) from pregnant women without pathology (PWN) and from pregnant women with PIH (PWPIH). The data showed significant low concentrations in the PLH of the two states of glutathione in the PWN against high concentrations of this molecule in the PLH from PWPIH. This feature can result from a deficient user of the glutathione by the cellular mechanism for prevention against oxidative factors. In addition, our study shows a biochemical marker that is suggestive that the placental bed is a potential source of FRO production in PIH. PMID:9312980

  19. [Changes in the thrombophilic status in patients with pre-eclampsia].

    PubMed

    Baptista-Gonzlez, H A; Rosenfeld-Mann, F; Saavedra-Trejo, M R; Castro-Lpez, J L; Peuela-Olaya, M A

    1999-04-01

    The object of this study was to evaluate the changes in fibrinolysis and clotting inhibitors in patients with preeclampsia and to describe the connection between preeclampsia and blood pressure values. Two groups of pregnant women were prospectively studied at delivery: group 1 women without preeclampsia and group 2 patients with preeclampsia. The variables that were registered are: diastolic blood pressure (DBP), systolic blood pressure (SBP), mean blood pressure (MBP), hemoglobin (Hb), platelet count (Plt), lupus like inhibitor, anticardiolipin antibodies (ACA), antinuclear antibodies (ANA), fibronectina, D dimer, protein S (PS), protein C (PC) and vo Willebrand factor (vWF). 62 pregnant women were included. The patients of group 2 presented high values of Hb (p 0.01), fibronectin (p 0.0001), D-dimer (p 0.01) and lower PC (p 0.04). We found an association between fibronectin and higher values of SBP, DBP, MBP and Hb (p 0.0007) versus lower values of VFW and PC (p 0.002). The low values of total PS were associated with high D-dimer and SBP results (p 0.04 and 0.002 respectively). All patients were ACA/ANA negative. In preclampsia there is a increased hemoconcentration and drop in clotting inhibitors (PC), without fibrinolytic compensatory response (lower D-dimer) and remarked vasopressive effect (hig fibronectin). This changes depend on the stratification of blood pressure. Th SBP and MBP values depend on the haemodynamic changes (Hb, fibronectin), while the increase in DBP expresses a non compensated thrombophilic state. PMID:10363418

  20. [Pre-eclampsia from the perspective of inter-professional collaboration].

    PubMed

    Jank?, P; Jank?, K; Unzeitig, V

    2009-12-01

    Preeclampsia-eclampsia is a syndrome which covers the area of influence belonging to gynecologists-obstetricians. However the internists, especially those who work as consultants in obstetric departments, are interested in diagnostics and therapy of this problem as well. Though internists working in the outdoor-departments do not face the problems of preeclampsia so often, it will be usefull to inform them about the latest trends in diagnostics and therapy ofthis syndrome, which may be very risky in pregnancy. The physicians in general (except the gynecologists) consider preeclampsia mostely as one form of hypertension that appears sometimes during gravidity and they do not realy appreciate the complex danger ofthis illness for the both, mother and child. The objective ofthis paper is to inform the general medical public, especially the internists and general practitioners about the modern view ofthe main problems of preeclampsia e.g. the pathogenesis, diagnostics and the up to day therapy of this high risky syndrome joined with pregnancy. PMID:20070032

  1. Oxygenation of the placenta and its role in pre-eclampsia.

    PubMed

    Huppertz, Berthold

    2014-07-01

    Proper oxygenation of the placenta and hence the embryo/fetus is essential for a successful pregnancy. During the first trimester of pregnancy the partial pressure of oxygen in the placenta and the embryo is very low and does not exceed 20mmHg. At the end of the first trimester maternal blood flow towards the placenta is established leading to a sudden increase in placental oxygenation to about 50-60mmHg. This level of oxygenation is keptuntil delivery. One of the numerous hypotheses to describe the etiology of preeclampsia, which is still the most cited hypothesis today, is based on a failure of extravillous trophoblast to invade the uterine spiral arteries in the placental bed. This in turn is believed to result in placental hypoxia and subsequently to damage of the villous trophoblast. Following this hypothesis, there is a series of events following these hypoxic conditions of the placenta. There is a large number of articles published that have investigated the effect of different oxygen concentrations on the phenotype of trophoblasts in vitro and have used this data to corroborate the hypothesis above. Unfortunately, one important aspect has not been addressed until recently: What is the placental oxygen concentration in placental pathologies such as preeclampsia in vivo? All studies that have tried to elucidate the placental oxygen concentration have done this indirectly, since direct measurements of placental oxygen in the third trimester of pregnancy have been defined as unethical. Not a single of such studies has revealed that oxygenation of the placenta in pregnancy pathologies is decreased. At the same time a number of studies have shown that in intra-uterine growth restriction (IUGR) placental oxygenation is increased rather than decreased. This has been shown to be true in the presence and absence of preeclampsia. This data clearly disprove the above hypothesis and should open our minds to decipherthe realcauses of preeclampsia. PMID:26104644

  2. 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)

  3. Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion

    PubMed Central

    Na, Kyu-Hwan; Choi, Jong Ho; Kim, Chun-Hyung; Kim, Kwang-Soo

    2013-01-01

    Objective We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. Methods NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. Results NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. Conclusion NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development. PMID:23614111

  4. Magnesium Therapy in Pre-eclampsia Prolongs Analgesia Following Spinal Anaesthesia with Fentanyl and Bupivacaine: An Observational Study

    PubMed Central

    Seyhan, Tülay Özkan; Bezen, Olgaç; Sungur, Mukadder Orhan; Kalelioğlu, İbrahim; Karadeniz, Meltem; Koltka, Kemalettin

    2014-01-01

    Background: Magnesium has anti-nociceptive effects and potentiates opioid analgesia following its systemic and neuraxial administration. However, there is no study evaluating the effects of intravenous (IV) magnesium sulphate (MgSO4) therapy on spinal anaesthesia characteristics in severely pre-eclamptic patients. Aims: The aim of this study was to compare spinal anaesthesia characteristics in severely pre-eclamptic parturients treated with MgSO4 and healthy preterm parturients undergoing caesarean section. Thus, our primary outcome was regarded as the time to first analgesic request following spinal anaesthesia. Study Design: Case-control Study. Methods: Following approval of Institutional Clinical Research Ethics Committee and informed consent of the patients, 44 parturients undergoing caesarean section with spinal anaesthesia were enrolled in the study in two groups: Healthy preterm parturients (Group C) and severely pre-eclamptic parturients with IV MgSO4 therapy (Group Mg). Following blood and cerebrospinal fluid (CSF) sampling, spinal anaesthesia was induced with 9 mg hyperbaric bupivacaine and 20 μg fentanyl. Serum and CSF magnesium levels, onset of sensory block at T4 level, highest sensory block level, motor block characteristics, time to first analgesic request, maternal haemodynamics as well as side effects were evaluated. Results: Blood and CSF magnesium levels were higher in Group Mg. Sensory block onset at T4 were 257.1±77.5 and 194.5±80.1 sec in Group C and Mg respectively (p=0.015). Time to first postoperative analgesic request was significantly prolonged in Group Mg than in Group C (246.1±52.8 and 137.4±30.5 min, respectively, p<0.001; with a mean difference of 108.6 min and 95% CI between 81.6 and 135.7). Side effects were similar in both groups. Group C required significantly more fluids. Conclusion: Treatment with IV MgSO4 in severe pre-eclamptic parturients significantly prolonged the time to first analgesic request compared to healthy preterm parturients, which might be attributed to the opioid potentiation of magnesium. PMID:25207186

  5. Morphometric evidence that villous development and fetoplacental angiogenesis are compromised by intrauterine growth restriction but not by pre-eclampsia.

    PubMed

    Mayhew, T M; Wijesekara, J; Baker, P N; Ong, S S

    2004-11-01

    The aim of this study was to compare morphometric measures of villous development, villous capillarization, fetoplacental angiogenesis and capillary lumen remodelling in normal pregnancies with those complicated by intrauterine growth restriction (IUGR) with and without preeclampsia (PE). To this end, term placentas from control pregnancies (n = 9) and cases of IUGR alone (n = 5), PE alone (n = 5) and IUGR with PE (n = 5) provided random samples of tissue. These were fixed in formalin and Masson trichrome-stained wax sections were analysed stereologically. Overall growth of peripheral villi and fetal capillaries was assessed by estimating total volumes, surface areas and lengths. Villous capillarization was monitored using volume, surface and length densities and capillary:villus surface and length ratios. Measures of villous maturation and capillary lumen remodelling comprised mean cross-sectional areas, perimeters and shapes (perimeter(2)/area). Between-group comparisons were drawn using two-way analysis of variance. IUGR was associated with abnormal growth of villi and fetal capillaries. Reduced villous growth was not accompanied by changes in measures of villous capillarization or maturation and reduced capillary growth was not accompanied by changes in lumen calibre or shape. In contrast, PE was not associated with any main or interaction effects on placental morphometry. It is concluded that IUGR, but not PE, is associated with impoverished villous development and fetoplacental angiogenesis. The latter is due to production of fewer and/or shorter capillary segments (rather than a decrease in capillary calibre), does not affect villous capillarization and is not accompanied by luminal remodelling. PMID:15451198

  6. A post-partum hemolytic-uremic-like-syndrome in a patient with pre-eclampsia: description of a clinical case.

    PubMed

    Iannuzzi, Mariarosaria; Siconolfi, Patrizia; D'Angelillo, Antonio; Capuano, Maria; Tufano, Luigi; Macri, Michela

    2006-02-01

    HEMOLYTIC UREMIC SYNDROME POST-PARTUM: We describe a case of a 37-year-old woman admitted for severe renal failure to our hospital immediately after the delivery by caesarean section of twins. She had anuria, anemia, and moderate thrombocytopenia. A diagnosis of hemolytic-uremic syndrome was made. Plasma exchange was started, substitution was performed with fresh frozen plasma and eight consecutive plasmapheresis sessions were given. She received hydrocortisone and ACE inhibitors. After about fifteen days from the beginning of the illness, signs of active haemolysis disappeared and renal function was partially recovered. A genetic study demonstrated the absence of HF1 and MCP mutations but a polymorphic variant of the HF1 gene (C-257T promoter region). This polymorphism is strongly associated with non-diarrhoea-HUS (D-HUS). Post-partum HUS is quite a rare syndrome and has a poor outcome; however prompt diagnosis and efficacious therapy could save lives without clinical consequences. The excellent outcome of this patient seems to corroborate this concept. PMID:16427809

  7. Cytokine production by non-stimulated peripheral blood NK cells and lymphocytes in early-onset severe pre-eclampsia without HELLP.

    PubMed

    Bueno-Snchez, J C; Agudelo-Jaramillo, B; Escobar-Aguilerae, L F; Lopera, A; Cadavid-Jaramillo, A P; Chaouat, G; Maldonado-Estrada, J G

    2013-04-01

    Preeclampsia involves an exacerbated maternal inflammatory response that suggests a possible role of innate immunity. NK cells can promote this kind of response through cytokine production and the expression of activating or inhibitory receptors. The aims of the present study were to explore cytokine production by peripheral blood mononuclear cells, as well as cytotoxic ability and receptor expression for HLA-E and HLA-G molecules in peripheral natural killer (NK) cells of women with early-onset severe preeclampsia without HELLP (hemolysis, elevated liver enzyme levels and a low platelet count) syndrome. The expression of the ILT2, KIRDL4, NKG2A, and NKG2C receptors and of cytotoxic activity was measured in non-stimulated NK cells, whereas the intracellular expression of IL-4, IL-10, IL-13, IL-12, IFN?, TNF and VEGF, was assessed in non-stimulated peripheral blood mononuclear cells subsets using flow cytometry. Circulating soluble HLA-G was also determined by ELISA. The intracellular cytokines tested were significantly higher in NK cell subsets from severely preeclamptic women compared with the control group. On the other hand, the percentage of NK cells expressing NKG2A or NKG2C and the cytotoxic activity of NK cells were significantly higher in severely preeclamptic women. Furthermore, there was a significant correlation between urine protein concentration and soluble human leukocyte antigen G (soluble HLA-G) in serum. We conclude that patients with early-onset severe preeclampsia without HELLP syndrome have increased NK cell function related to cytokine production, cytotoxicity and expression of lectin-like receptors such as NKG2. PMID:23415844

  8. 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. PMID:24315655

  9. Postpartum evaluation and long term implications.

    PubMed

    Firoz, Tabassum; Melnik, Tanya

    2011-08-01

    Hypertension, proteinuria and biochemical changes caused by pre-eclampsia may persist for several weeks and even months postpartum. Hypertension and pre-eclampsia may even develop for the first time postpartum. Care in the six weeks postpartum should include management of hypertension and screening for secondary causes of hypertension including renal disease if abnormalities persist beyond six weeks. Optimal postpartum monitoring for patients with preeclampsia has not been determined, and care needs to be individualized. The postpartum period also provides a window of opportunity for planning for the next pregnancy in addition to discussing long term implications of pre-eclampsia. Increased risk for the development of premature cardiovascular disease is the most significant long term implication of pre-eclampsia. Pre-eclampsia and cardiovascular disease share a common disease pathophysiology. Women who develop pre-eclampsia have pre-existing metabolic abnormalities or may develop them later in life. Women with early onset pre-eclampsia are at the highest risk of ischemic heart disease. Women with a history of pre-eclampsia should adopt a heart healthy lifestyle and should be screened and treated for traditional cardiovascular risk factors according to locally accepted guidelines. PMID:21536498

  10. 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...

  11. 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...

  12. Average Age of First-Time Moms in U.S. Still Rising: CDC

    MedlinePLUS

    ... Ricans (24.1 years), blacks (24.2) and Mexican Americans (23.7), Mathews said. Dr. Jennifer Wu, ... pre-eclampsia and other complications, including passing on genetic defects." The full report is published in the ...

  13. Rare Nervous System Disorder Can Put Pregnancy At Risk

    MedlinePLUS

    ... a rate similar to that in the general population, according to the study published online Nov. 18 ... compared with about 3 percent in the general population. The risk of pre-eclampsia was even higher ...

  14. 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...

  15. 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...

  16. A Comparative Study of Serum Level of Vascular Cell Adhesion Molecule-1 (sVCAM-1), Intercellular Adhesion Molecule-1(ICAM-1) and High Sensitive C - reactive protein (hs-CRP) in Normal and Pre-eclamptic Pregnancies

    PubMed Central

    Farzadnia, Mehdi; Ayatollahi, Hossein; Hasan-zade, Maliheh; Rahimi, Hamid Reza

    2013-01-01

    Objective(s): Pre-eclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Endothelial dysfunction is thought to be a central pathogenic feature in pre-eclampsia on the basis of elevated adhesion molecules. The aim of this study was to determine the level of plasma serum level of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1(ICAM-1), high sensitive C- reactive protein (hs-CRP) in pre-eclampsia and to compare hs-CRP levels between normal pregnant women, mild and severe pre-eclampsia. Materials and Methods : A cross-sectional study was conducted to determine the plasma concentrations of sVCAM-1, ICAM-1 and hs-CRP in peripheral blood obtained from normal pregnant women (n=40), mild pre-eclampsia (n=37) and severe pre-eclampsia (n=38). Concentrations of soluble adhesion molecule was determined with enzyme linked immunosorbent assay (ELISA). Results: There were significant difference in the means serum hs-CRP between normal pregnant women and mild pre-eclamptic women (P<0.05). Serum concentration of hs-CRP, sVCAM-1(ng.ml) and sICAM-1(ng.ml) were significantly higher in severe pre-eclampsia (P<0.05) than normal pregnancy. There were also significant differences in hs-CRP, s ICAM- 1 and in sVCAM- 1 levels between mild and severe pre-eclampsia (P<0.05). There was no difference in the mean plasma log sVCAM-1, sICAM-1 between normal pregnant women and mild pre-eclamptic women. Conclusion: We have determined the serum concentration of soluble adhesion molecule ICAM-1, VCAM-1 and hsCRP in normal pregnancy and pre-eclampsia. Adhesion molecule is elevated in severe pre-eclampsia compared with normal pregnancy, hsCRP are elevated in severe preeclampsia compared with mild preeclampsia and normal pregnancy and may be useful in predicting the severity of pre-eclampsia. PMID:23826490

  17. Estrogen Receptor Alpha (ESR1) Gene Polymorphisms in Pre-eclamptic Saudi Patients

    PubMed Central

    El-Beshbishy, Hesham A.; Tawfeek, Manal A.; Al-Azhary, Nevin M.; Mariah, Reham A.; Habib, Fawzia A.; Aljayar, Lamya; Alahmadi, Abrar F.

    2015-01-01

    Objectives: Pre-eclampsia causes maternal mortality worldwide. Estrogen receptor alpha (ESR1) gene polymorphisms were responsible for cardiovascular diseases. This case control study was conducted to investigate whether 2 polymorphic genes of ESR1 are associated with pre-eclampsia among Saudi women in Madina city, Saudi Arabia. Methods: Blood samples from 97 pre-eclamptic and 94 healthy pregnant women were analyzed using restriction fragment length polymorphism-polymerase chain reaction method. All the subjects were recruited randomly from outpatient clinics of Madina Maternity Children Hospital (MMCH), Madina, Saudi Arabia, between Dec. 2012 and Jan. 2014. Results: There was no association between pre-eclampsia and PvuII and XbaI ESR1 gene polymorphisms individually. TT/AA and TT/AG genotype combination existed significantly in pre-eclamptic patients compared to control. The frequency of PvuII and XbaI combined TT/AA genotypes between pre-eclamptic women was 36.1% vs 9.6%, however, frequency of PvuII and XbaI combined TT/AG genotypes between pre-eclamptic women was 3.1% vs 17%, compared to control. The homozygous T-A haplotype carriers showed high pre-eclampsia risk, independent of pregnancy, BMI and smoking status (adjusted odds ratio (OR): 3.26, 95% confidence interval (CI):1.71-9.21). The heterozygous T-A haplotype carriers did not differ from that of non-carriers (adjusted OR: 1.12, 95% CI: 0.47-2.75). No association was observed between pre-eclampsia and T-G, C-G and C-A haplotype of PvuII and XbaIESR1 gene polymorphisms. Conclusions: T-A haplotype of homozygous associated with pre eclampsia not heterozygous carriers of ESR 1 PvuII and XbaI gene polymorphisms elicited high risk of pre-eclampsia. GG genotype of XbaI polymorphism decreased pre-eclampsia risk. Further studies using larger sample size are recommended to investigate the ESR 1 gene polymorphisms associated with pre-eclampsia. PMID:26430422

  18. Increased microvascular vasodilation and cardiovascular risk following a pre-eclamptic pregnancy.

    PubMed

    Murphy, Malia S Q; Vignarajah, Meera; Smith, Graeme N

    2014-11-01

    Women who develop pre-eclampsia are at high-risk for premature cardiovascular disease and death. The aim of this study was to assess microvascular function and cardiovascular risk in the early postpartum period for women who did/did not have a pregnancy complicated by pre-eclampsia. Peripheral microvascular function was assessed in women in the third trimester of uncomplicated pregnancies, with re-evaluation at 2 and 6 months postpartum. The effect of pre-eclampsia on postpartum microvascular function was assessed 2 and 6 months after delivery. Never-pregnant, naturally cycling women served for comparison. Cutaneous microvascular reactivity to acetylcholine and sodium nitroprusside, delivered locally by iontophoresis, was measured by laser Doppler flowmetry. 30-year and lifetime risk estimates for cardiovascular disease were established. Acetylcholine-mediated vasodilation was enhanced by normotensive pregnancy, and declined to nonpregnant levels by 6 months postpartum. Acetylcholine-mediated vasodilation remained high in pre-eclamptic subjects from 2 to 6 months postpartum compared to normotensive and never-pregnant controls. Pre-eclamptic subjects exhibited elevated 30-year and lifetime risk at 6 months postpartum. This study provides in vivo evidence of microvascular and cardiovascular risk implications of pre-eclampsia as early as 6 months postpartum, and suggests that the development of pre-eclampsia may be used to identify women at risk and eligible for risk screening and intervention. PMID:25428950

  19. Aortic stiffness in normal and hypertensive pregnancy.

    PubMed

    Avni, B; Frenkel, G; Shahar, L; Golik, A; Sherman, D; Dishy, V

    2010-02-01

    The objective of this study was to examine whether aortic stiffness, as assessed by pulse wave analysis, could reliably discriminate between normal and hypertensive pregnancies. One hundred pregnant women were studied: five with severe pre-eclampsia, 27 with gestational hypertension, 14 with chronic hypertension and 54 with normal pregnancy. Central hemodynamic parameters were obtained by an applanation tonometry and included central aortic systolic blood pressure (CSBP), central aortic diastolic blood pressure (CDBP), augmentation pressure (AP), augmentation index (AIx), AIx corrected to a heart rate of 75 (AIx@75) and time to reflection (Tr). All measures of aortic stiffness, including AP, AIx and AIx@75 were significantly higher in women with gestational hypertension and pre-eclampsia compared with normal pregnancies and women with chronic hypertension (p < 0.05 for all comparisons). There were no significant differences between normal pregnancies and women with chronic hypertension (p > 0.05 for all comparisons). Tr was significantly shorter in women with pre-eclampsia and gestational hypertension compared with normal pregnancies (p < 0.05). Aortic stiffness, as assessed by pulse wave analysis, is significantly increased in women with pre-eclampsia and gestational hypertension but not in treated women with chronic hypertension. Pulse wave analysis has a potential as a screening tool in women at high risk for pre-eclampsia. The final role of this method should be determined in prospective studies. PMID:20001391

  20. Preeclampsia and Eclampsia

    MedlinePLUS

    ... 1998). Does gestational hypertension become pre-eclampsia? British Journal of Obstetrics and Gynaecology , 105, 11771184. [top] What causes it? Last Reviewed: 06/18/2013 Related A-Z Topics High-Risk Pregnancy Obesity and Overweight Pregnancy All related topics NICHD News ...

  1. (Epi)genetics of pregnancy-associated diseases

    PubMed Central

    van Dijk, Marie; Oudejans, Cees

    2013-01-01

    This review describes the current knowledge regarding genetics and epigenetics of pregnancy-associated diseases with placental origin. We discuss the effect on genetic linkage analyses when the fetal genotype determines the maternal phenotype. Secondly, the genes identified by genome-wide linkage studies to be associated with pre-eclampsia (ACVR2A, STOX1) and the HELLP-syndrome (LINC-HELLP) are discussed regarding their potential functions in the etiology of disease. Furthermore, susceptibility genes identified by candidate gene approaches (e.g., CORIN) are described. Next, we focus on the additional challenges that come when epigenetics also play a role in disease inheritance. We discuss the maternal transmission of the chromosome 10q22 pre-eclampsia linkage region containing the STOX1 gene and provide further evidence for the role of epigenetics in pre-eclampsia based on the cdkn1c mouse model of pre-eclampsia. Finally, we provide recommendations to unravel the genetics of pregnancy-associated diseases, specifically regarding clear definitions of patient groups and sufficient patient numbers, and the potential usefulness of (epi)genetic data in early non-invasive biomarker development. PMID:24058367

  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 pregnancy and have a potential therapeutic role in pre-eclampsia treatment. PMID:26685104

  3. Statistical analysis of the maternal death rate at the Ebonyi State University Teaching Hospital, Abakaliki, for the year ending 31 December 2007

    PubMed Central

    2009-01-01

    ABSTRACT Background The maternal mortality rate in developing countries, such as Nigeria, remains relatively high, with the causes being multidimensional. The unbooked primigravidae with severe pre-eclampsia/eclampsia constitute a high risk group. Method The data from the case notes of all the maternal deaths that occurred at the Ebonyi State University Teaching Hospital, Abakaliki, between 1 January and 31 December 2007 form the basis of this study. The case notes relating to all such deaths were stored in the office of the Head of the Department of Obstetrics and Gynaecology when the deaths occurred. Information was extracted from the case files at the end of 2007. Data relating to the total number of deliveries were obtained from the registers kept in the labour and isolation wards. Results Of the 45 maternal deaths recorded, 40 (88.9%) were found to have occurred among the unbooked and 5 (11%) among the booked mothers, constituting a maternal mortality ratio (MMR) of 23 121.4 and 339.7 per 100 000 deliveries respectively. The combined mortality ratio was 2 735.6 per 100 000 deliveries. Fifteen (37.5%) unbooked primigravidae were found to have died of severe pre-eclampsia/eclampsia. A total of 1 645 mothers were noted to have delivered babies, of whom 1 472(89.5%) were booked, and 173 (10.5%) unbooked, with the hospital. Conclusion Severe pre-eclampsia/eclampsia, haemorrhaging and sepsis were the major causes of death. A high maternal mortality rate was found to be common among the unbooked primigravidae, who are known usually to present late with pre-eclampsia/eclampsia. More research into the causes and management of pre-eclampsia/eclampsia is needed to reduce the high maternal death rate associated with it. The lack of antenatal care is also a high risk factor for maternal death.

  4. A Study on Atherogenic Indices of Pregnancy Induced Hypertension Patients as Compared to Normal Pregnant Women

    PubMed Central

    Pathak, Mauchumi Saikia; Paul, Anindita

    2015-01-01

    Introduction Pregnancy induced hypertension (PIH) includes Gestational hypertension, Pre-eclampsia and Eclampsia and is one of the most common obstetric complication. Worldwide about 76,000 pregnant women die each year from pre-eclampsia and related hypertensive disorders. The aetiology of Pre-eclampsia is unknown but it is thought to be related to abnormal development of placenta. Several studies have shown the presence of reduced endothelial function in pre-eclamptic pregnancy. Endothelial dysfunction is also a feature of atherosclerosis. Aim To assess fasting lipid profile and atherogenic indices in women diagnosed with pre-eclampsia as well as in women with normal pregnancy and to correlate the findings of pre-eclamptic women with that of normal pregnant women, in an attempt to utilize the data for the development of a new clinical approach for early recognition and prevention of risk of future cardiovascular diseases in women with PIH. Materials and Methods This case-control study was conducted on 50 pre-eclampsia patients who were in third trimester of pregnancy (Case group). A control group of 50 age and gestational age matched normal pregnant women was taken. Strict inclusion and exclusion criteria were followed. Fasting Lipid profile parameters were assessed and used to calculate the atherogenic indices namely Atherogenic index of plasma (AIP), Cardiac risk ratio (CRR) and Atherogenic coefficient (AC). Statistical Analysis was done by using students t-test. Mann-Whitney U-test was used wherever applicable and correlations between the variables were estimated by Pearsons correlation coefficients. Results There was an extremely significant (p<0.0001) increase in Atherogenic indices (AIP, CRR and AC) in case group as compared to the control group. A positive and significant correlation of systolic blood pressure with AIP (r=0.3583), CRR (r=0.3137), AC (r=0.3193) was found in cases. There was a positive and significant correlation between gestational age and atherogenic indices in the case group. Conclusion Women with pre-eclampsia present abnormalities in lipid profile and these lipids turn out to be a risk factor for cardiovascular complications. Evaluation of the atherogenic indices during pregnancy may help prevent this risk. PMID:26393117

  5. 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

  6. Systemic and uteroplacental reninangiotensin system in normal and pre-eclamptic pregnancies

    PubMed Central

    Anton, Lauren

    2009-01-01

    Pregnancy is characterized by an increase in many of the different components of the circulating reninangiotensin system [RAS]. However, the physiological mechanisms of stimulated RAS activity during pregnancy are unknown. Even less understood is how this system may be altered in pre-eclampsia, a hypertensive disorder of pregnancy. Additional studies have shown the presence of a local tissue specific RAS in the uteroplacental unit of normal and pre-eclamptic pregnancies. Differences in normal pregnant and pre-eclamptic RAS component regulation may provide insight into the mechanisms responsible for the clinical pathological features of pre-eclampsia. Specifically, this review summarizes the key findings in the circulating and uteroplacental RAS in normal and pre-eclamptic pregnancies. PMID:19124433

  7. 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

  8. 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. PMID:22007763

  9. Urine protein concentration estimation for biomarker discovery.

    PubMed

    Mistry, Hiten D; Bramham, Kate; Weston, Andrew J; Ward, Malcolm A; Thompson, Andrew J; Chappell, Lucy C

    2013-10-01

    Recent advances have been made in the study of urinary proteomics as a diagnostic tool for renal disease and pre-eclampsia which requires accurate measurement of urinary protein. We compared different protein assays (Bicinchoninic acid (BCA), Lowry and Bradford) against the 'gold standard' amino-acid assay in urine from 43 women (8 non-pregnant, 34 pregnant, including 8 with pre-eclampsia). BCA assay was superior to both Lowry and Bradford assays (Bland Altman bias: 0.08) compared to amino-acid assay, which performed particularly poorly at higher protein concentrations. These data highlight the need to use amino-acid or BCA assays for unprocessed urine protein estimation. PMID:26103798

  10. Moving beyond silos: How do we provide distributed personalized medicine to pregnant women everywhere at scale? Insights from PRE-EMPT.

    PubMed

    von Dadelszen, Peter; Magee, Laura A; Payne, Beth A; Dunsmuir, Dustin T; Drebit, Sharla; Dumont, Guy A; Miller, Suellen; Norman, Jane; Pyne-Mercier, Lee; Shennan, Andrew H; Donnay, France; Bhutta, Zulfiqar A; Ansermino, J Mark

    2015-10-01

    While we believe that pre-eclampsia matters-because it remains a leading cause of maternal and perinatal morbidity and mortality worldwide-we are convinced that the time has come to look beyond single clinical entities (e.g. pre-eclampsia, postpartum hemorrhage, obstetric sepsis) and to look for an integrated approach that will provide evidence-based personalized care to women wherever they encounter the health system. Accurate outcome prediction models are a powerful way to identify individuals at incrementally increased (and decreased) risks associated with a given condition. Integrating models with decision algorithms into mobile health (mHealth) applications could support community and first level facility healthcare providers to identify those women, fetuses, and newborns most at need of facility-based care, and to initiate lifesaving interventions in their communities prior to transportation. In our opinion, this offers the greatest opportunity to provide distributed individualized care at scale, and soon. PMID:26433496

  11. 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

  12. Leptin receptor gene polymorphisms in severely pre-eclamptic women.

    PubMed

    Rig, Jnos; Szendei, Gyrgy; Rosta, Klra; Fekete, Andrea; Bgi, Krisztina; Molvarec, Attila; Rnai, Zsolt; Vr, Agota

    2006-09-01

    Variants of the leptin receptor gene (LEPR) may modulate the effect of elevated serum leptin levels in pre-eclampsia. The aim of our study was to evaluate the LEPR gene polymorphisms Lys109Arg (A109G) and Gln223Arg (A223G) in severely pre-eclamptic women. In a case-control study, we analyzed blood samples from 124 severely pre-eclamptic patients and 107 healthy control women by the polymerase chain reaction-restriction fragment length polymorphism method. The Pearson chi2 test was used to estimate odds ratios (OR) and 95% confidence intervals (CI). The association was adjusted for maternal age, pre-pregnancy body mass index and primiparity with logistic regression analysis. Pregnant women with the LEPR 223G allele (223A/G or 223G/G genotype) had almost double the risk of developing severe pre-eclampsia compared with patients with the 223A/A genotype (adjusted OR = 1.92, 95% CI: 1.07-3.41). Genotype variants of LEPR A109G alone did not affect the risk of severe pre-eclampsia. Haplotype estimation of A109G and A223G polymorphisms of the LEPR gene revealed that the G-A haplotype versus other pooled haplotypes was significantly less common in the pre-eclamptic group (p < 0.01), while the G-G haplotype versus others was overrepresented among severely pre-eclamptic patients (p < 0.01), compared with controls. In conclusion, our data indicate that LEPR A223G polymorphism may individually modify the risk of severe pre-eclampsia. PMID:17071538

  13. Electronic readout enzyme-linked immunosorbent assay with organic field-effect transistors as a preeclampsia prognostic.

    PubMed

    Hammock, Mallory L; Knopfmacher, Oren; Ng, Tse Nga; Tok, Jeffrey B-H; Bao, Zhenan

    2014-09-17

    Organic field-effect transistor (OFET) sensors can meet the need for portable and real-time diagnostics. An electronicreadout enzyme-linked immunosorbent assay using OFETs for the detection of a panel of three biomarkers in complex media to create a pre-eclampsia prognostic is demonstrated, along with biodetection utilizing a fully inkjet-printed and flexible OFET to underscore our ability to produce disposable devices. PMID:25047764

  14. [Maternal refusal to consent to a cesarean delivery, stillbirth].

    PubMed

    Defline, A; Obadia, M; El Djerbi, A; Plevy, P; Lepercq, J

    2014-01-01

    The doctor-lawyer perspective that we discuss is a maternal refusal to consent to a cesarean delivery for a fetal indication in June 2011. Despite repeated information of the risks during a three-week hospitalization for pre-eclampsia, after being assured of the proper understanding of the seriousness of the situation by the patient and spouse, and after consideration to transfer to another hospital, the reiterated refusal led to a late fetal extraction resulting in term stillbirth. PMID:23972774

  15. Thrombophilia and Pregnancy Complications.

    PubMed

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

    2015-01-01

    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. PMID:26633369

  16. Thrombophilia and Pregnancy Complications

    PubMed Central

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

    2015-01-01

    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. PMID:26633369

  17. Oocyte donation is an independent risk factor for pregnancy complications: the implications for women of advanced age.

    PubMed

    Younis, Johnny S; Laufer, Neri

    2015-02-01

    Maternal age at first pregnancy and age-related infertility are steadily increasing, and the demand for assisted reproductive technologies (ART) to treat age-related infertility is also on the rise. The latest registry findings from Europe and the United States show that the meager results of ART in women above 43 years of age have not improved much over the past 10 years. The latest evidence shows that the demand for oocyte donation (OD) is steadily increasing. Contrary to previous belief-attributing increased perinatal complications in OD recipients to advanced maternal age and multifetal pregnancy-accumulating evidence from the past few years suggests that OD itself is a significant and independent risk factor for pregnancy complications, mostly for pre-eclampsia. The increased rate of chronic maternal disease and medical complications in pregnancy observed in advanced maternal age, coupled with the growing demand for OD, with its independent association with pre-eclampsia, create an urgent need to adopt a clear policy taking these risks into account. We present recent evidence showing that OD is an independent risk factor for pre-eclampsia and suggest recommendations for women approaching OD treatment in advanced age. PMID:25646636

  18. Gene expression profiling of pre-eclamptic placentae by RNA sequencing.

    PubMed

    Kaartokallio, Tea; Cervera, Alejandra; Kyllnen, Anjuska; Laivuori, Krista

    2015-01-01

    Pre-eclampsia is a common and complex pregnancy disorder that often involves impaired placental development. In order to identify altered gene expression in pre-eclamptic placenta, we sequenced placental transcriptomes of nine pre-eclamptic and nine healthy pregnant women in pools of three. The differential gene expression was tested both by including all the pools in the analysis and by excluding some of the pools based on phenotypic characteristics. From these analyses, we identified altogether 53 differently expressed genes, a subset of which was validated by qPCR in 20 cases and 19 controls. Furthermore, we conducted pathway and functional analyses which revealed disturbed vascular function and immunological balance in pre-eclamptic placenta. Some of the genes identified in our study have been reported by numerous microarray studies (BHLHE40, FSTL3, HK2, HTRA4, LEP, PVRL4, SASH1, SIGLEC6), but many have been implicated in only few studies or have not previously been linked to pre-eclampsia (ARMS2, BTNL9, CCSAP, DIO2, FER1L4, HPSE, LOC100129345, LYN, MYO7B, NCMAP, NDRG1, NRIP1, PLIN2, SBSPON, SERPINB9, SH3BP5, TET3, TPBG, ZNF175). Several of the molecules produced by these genes may have a role in the pathogenesis of pre-eclampsia, and some could qualify as biomarkers for prediction or detection of this pregnancy complication. PMID:26388242

  19. Pregnancy complications in polycystic ovary syndrome patients.

    PubMed

    Katulski, Krzysztof; Czyzyk, Adam; Podfigurna-Stopa, Agnieszka; Genazzani, Andrea R; Meczekalski, Blazej

    2015-02-01

    Infertility is a widely disputed problem affecting patients suffering from polycystic ovary syndrome (PCOS). As a serious dysfunction, it frequently occurs in PCOS patients. It is, therefore, important to devote more attention to pregnancy in PCOS sufferers. According to various data, the risk of miscarriage in PCOS women is three times higher than the risk of miscarriage in healthy women. Unfortunately, the risk of most frequent pregnancy pathologies is also higher for PCOS patients, as gestational diabetes (GD), pregnancy-induced hypertension and pre-eclampsia, and small for gestational age (SGA) children. Impaired glucose tolerance and GD in pregnant PCOS patients occur more frequently than in healthy women. A quadruple increase in the risk of pregnancy-induced hypertension linked to arterial wall stiffness has also been observed in PCOS patients. The risk of pre-eclampsia, the most severe of all complications, is also four times higher in those suffering from PCOS. Pre-eclampsia is also more frequent in patients presenting additional risk factors accompanying PCOS, such as obesity or GD. At that point, it should be mentioned that PCOS patients are under 2.5 higher risk of giving birth to SGA children than healthy women. It appears that SGA can be linked to insulin resistance and insulin-dependent growth dysfunction. Therefore, PCOS pregnant women are patients of special obstetrical care. PMID:25356655

  20. Gene expression profiling of pre-eclamptic placentae by RNA sequencing

    PubMed Central

    Kaartokallio, Tea; Cervera, Alejandra; Kyllnen, Anjuska; Laivuori, Krista; Laivuori, Hannele; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli

    2015-01-01

    Pre-eclampsia is a common and complex pregnancy disorder that often involves impaired placental development. In order to identify altered gene expression in pre-eclamptic placenta, we sequenced placental transcriptomes of nine pre-eclamptic and nine healthy pregnant women in pools of three. The differential gene expression was tested both by including all the pools in the analysis and by excluding some of the pools based on phenotypic characteristics. From these analyses, we identified altogether 53 differently expressed genes, a subset of which was validated by qPCR in 20 cases and 19 controls. Furthermore, we conducted pathway and functional analyses which revealed disturbed vascular function and immunological balance in pre-eclamptic placenta. Some of the genes identified in our study have been reported by numerous microarray studies (BHLHE40, FSTL3, HK2, HTRA4, LEP, PVRL4, SASH1, SIGLEC6), but many have been implicated in only few studies or have not previously been linked to pre-eclampsia (ARMS2, BTNL9, CCSAP, DIO2, FER1L4, HPSE, LOC100129345, LYN, MYO7B, NCMAP, NDRG1, NRIP1, PLIN2, SBSPON, SERPINB9, SH3BP5, TET3, TPBG, ZNF175). Several of the molecules produced by these genes may have a role in the pathogenesis of pre-eclampsia, and some could qualify as biomarkers for prediction or detection of this pregnancy complication. PMID:26388242

  1. Influence of mineral and vitamin supplements on pregnancy outcome.

    PubMed

    Hovdenak, Nils; Haram, Kjell

    2012-10-01

    The literature was searched for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcome. Maternal iron (Fe) deficiency has a direct impact on neonatal Fe stores and birth weight, and may cause cognitive and behavioural problems in childhood. Fe supplementation is recommended to low-income pregnant women, to pregnant women in developing countries, and in documented deficiency, but overtreatment should be avoided. Calcium (Ca) deficiency is associated with pre-eclampsia and intra-uterine growth restriction. Supplementation may reduce both the risk of low birth weight and the severity of pre-eclampsia. Gestational magnesium (Mg) deficiency may cause hematological and teratogenic damage. A Cochrane review showed a significant low birth weight risk reduction in Mg supplemented individuals. Intake of cereal-based diets rich in phytate, high intakes of supplemental Fe, or any gastrointestinal disease, may interfere with zinc (Zn) absorption. Zn deficiency in pregnant animals may limit fetal growth. Supplemental Zn may be prudent for women with poor gastrointestinal function, and in Zn deficient women, increasing birth weight and head circumference, but no evidence was found for beneficial effects of general Zn supplementation during pregnancy. Selenium (Se) is an antioxidant supporting humoral and cell-mediated immunity. Low Se status is associated with recurrent abortion, pre-eclampsia and IUGR, and although beneficial effects are suggested there is no evidence-based recommendation for supplementation. An average of 20-30% of pregnant women suffer from any vitamin deficiency, and without prophylaxis, about 75% of these would show a deficit of at least one vitamin. Vitamin B6 deficiency is associated with pre-eclampsia, gestational carbohydrate intolerance, hyperemesis gravidarum, and neurologic disease of infants. About 25% of pregnant women in India are folate deficient. Folate deficiency may lead to congenital malformations (neural tube damage, orofacial clefts, cardiac anomalies), anaemia and spontaneous abortions, and pre-eclampsia, IUGR and abruption placentae. Pregestational supplementation of folate prevents neural tube defects. A daily supplemental dose of 400 μg/day of folate is recommended when planning pregnancy. In developing countries diets are generally low in animal products and consequently in vitamin B12 content. An insufficient supply may cause reduced fetal growth. In vegetarian women, supplementation of vitamin B12 may be needed. Vitamin A deficiency is prevalent in the developing world, impairing Fe status and resistance to infections. The recommended upper limit for retinol supplements is 3000 IU/day. Vitamin A supplementation enhances birth weight and growth in infants born to HIV-infected women. Overdosing should be avoided. Low concentrations of vitamin C seem to increase the development of pre-eclampsia, and supplementation may be beneficial. Supplementation with vitamin D in the third trimester in vitamin D deficient women seems to be beneficial. The use of vitamins E, although generally considered "healthy", may be harmful to the pregnancy outcome by disrupting a physiologic oxidative gestational state and is consequently not recommended to prevent pre-eclampsia. Further studies on specific substances are needed as the basis for stratified, placebo-controlled analyses. PMID:22771225

  2. 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, Jrgen

    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 (-0.05pre-eclampsia hemo concentration and increased fibrinogen turnover due to enhanced coagulation activation are weighty co factors of pv but were associated with lower pv in patients with pre-eclampsia. However, coincidental increased RBC aggregation and hemo concentration may potentially derogate blood flow in the materno-fetal unit that is commonly traceable using vessel duplex ultra sound in pre-eclampsia. PMID:19433886

  3. [Massive proteinuria and HELLP syndrome].

    PubMed

    Toblli, J E; Engel, H J; Podzun, I; Gonzlez, G F

    1992-01-01

    HELLP syndrome continues to be a clinical entity of difficult diagnosis. Weinstein first defined it in 1982 giving the practicing obstetrician a sequence of useful initials (H = hemolysis; EL = elevated liver enzymes; LP = low platelets). Since then a lot has been written and it has become clear that the syndrome is a form of severe preeclampsia. The American College of Obstetrics and Gynecology does not include HELLP in the description of severe pre-eclampsia as such but does accept each of its components as being part of severe pre-eclampsia. The case presented deals with a 33 year old white female, admitted at 27 weeks gestation with nausea, epigastric pain resembling acute abdomen, nose bleeding and mild hypertension. The analysis revealed an abnormal liver profile with elevated GOT, GPT and LDH, heavy proteinuria (14.4 g/day), decreased platelet count (92000/mm3) and elevated total bilirubin. Pregnancy was terminated by cesarean section 24 hours after admission because the patient's condition was deteriorating. Obviously in pre-eclampsia/eclampsia there is a systematic injury to all tissues. Proof of this is the hypertension as a consequence of vascular spasm and proteinuria due to glomerular injury. In HELLP the sequence of events is probably altered; hepatic injury precedes vascular and renal injury of conventional preeclampsia. The syndrome results from many clinical and pathological symptoms derived from endothelial microvascular injury which determine a rapid platelet activation causing vascular spasm, platelet aggregation and further endothelial injury through a feedback mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1308908

  4. A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications.

    PubMed

    Slatter, Tania L; Hung, Natalie Gly; Clow, William M; Royds, Janice A; Devenish, Celia J; Hung, Noelyn A

    2015-10-01

    Viral infections are known to adversely affect pregnancy, but scant attention has been given to human papilloma virus (HPV) infection. We aimed to determine the molecular and histopathological features of placental HPV infection, in association with pregnancy complications including fetal growth restriction, pre-maturity, pre-eclampsia, and diabetes. Three hundred and thirty-nine placentae were selected based on the presence or absence of pregnancy complications. Five independent methods were used to identify HPV in the placenta, namely, immunohistochemistry for L1 viral capsid, in situ hybridization to high-risk HPV DNA, PCR, western blotting, and transmission electron microscopy. Pregnancy complications and uterine cervical smear screening results were correlated with placental HPV histopathology. In this study, which was deliberately biased towards complications, HPV was found in the decidua of 75% of placentae (253/339) and was statistically associated with histological acute chorioamnionitis (P<0.05). In 14% (35/253) of the HPV positive cases, HPV L1 immunoreactivity also occurred in the villous trophoblast where it was associated with a lymphohistiocytic villitis (HPV-LHV), and was exclusively of high-risk HPV type. HPV-LHV significantly associated with fetal growth restriction, preterm delivery, and pre-eclampsia (all P<0.05). All cases of pre-eclampsia (20/20) in our cohort had high-risk placental HPV. A further 55 cases (22%, 55/253) of HPV positive placentae had minimal villous trophoblast HPV L1 immunoreactivity, but a sclerosing pauci-immune villitis, statistically associated with diabetes (49.1%, 27/55, P<0.05). For women with placental HPV, 33% (69/207) had an HPV-related positive smear result before pregnancy compared with (9.4% 8/85) of women with HPV-negative placentae (P=0.0001). Our findings support further investigations to determine if vaccination of women and men will improve pregnancy outcomes. PMID:26293778

  5. Increased planned delivery contributes to declining rates of pregnancy hypertension in Australia: a population-based record linkage study

    PubMed Central

    Roberts, Christine L; Algert, Charles S; Morris, Jonathan M; Ford, Jane B

    2015-01-01

    Objective Since the 1990s, pregnancy hypertension rates have declined in some countries, but not all. Increasing rates of early planned delivery (before the due date) have been hypothesised as the reason for the decline. The aim of this study was to explore whether early planned delivery can partly explain the declining pregnancy hypertension rates in Australia. Design Population-based record linkage study utilising linked birth and hospital records. Setting and participants A cohort of 1?076?122 deliveries in New South Wales, Australia, 20012012. Outcome measures Pregnancy hypertension (including gestational hypertension, pre-eclampsia and eclampsia) was the main outcome; pre-eclampsia was a secondary outcome. Results From 2001 to 2012, pregnancy hypertension rates declined by 22%, from 9.9% to 7.7%, and pre-eclampsia by 27%, from 3.3% to 2.4% (trend p<0.0001). At the same time, planned deliveries increased: prelabour caesarean section by 43% (12.918.4%) and labour inductions by 10% (24.827.2%). Many maternal risk factors for pregnancy hypertension significantly increased (p<0.01) over the study period including nulliparity, age ?35?years, diabetes, overweight and obesity, and use of assisted reproductive technologies; some risk factors decreased including multifetal pregnancies, age <20?years, autoimmune diseases and previous pregnancy hypertension. Given these changes in risk factors, the pregnancy hypertension rate was predicted to increase to 10.5%. Examination of annual gestational age distributions showed that pregnancy hypertension rates actually declined from 38?weeks gestation and were steepest from 41?weeks; at least 36% of the decrease could be attributed to planned deliveries. The risk factors for pregnancy hypertension were also risk factors for planned delivery. Conclusions It appears that an unanticipated consequence of increasing early planned deliveries is a decline in the incidence of pregnancy hypertension. Women with risk factors for hypertension were relatively more likely to be selected for early delivery. PMID:26438140

  6. Inflammatory Bowel Disease and Risk of Adverse Pregnancy Outcomes

    PubMed Central

    Boyd, Heather A.; Basit, Saima; Harpse, Maria C.; Wohlfahrt, Jan; Jess, Tine

    2015-01-01

    Background and Objectives Existing data on pregnancy complications in inflammatory bowel disease (IBD) are inconsistent. To address these inconsistencies, we investigated potential associations between IBD, IBD-related medication use during pregnancy, and pregnancy loss, pre-eclampsia, preterm delivery, Apgar score, and congenital abnormalities. Methods We conducted a cohort study in >85,000 Danish National Birth Cohort women who were pregnant in the period 1996-2002 and had information on IBD, IBD-related medication use (systemic or local corticosteroids, 5-aminosalicylates), pregnancy outcomes and potential confounders. We evaluated associations between IBD and adverse pregnancy/birth outcomes using Cox regression and log-linear binomial regression. Results IBD was strongly and significantly associated with severe pre-eclampsia, preterm premature rupture of membranes and medically indicated preterm delivery in women using systemic corticosteroids during pregnancy (hazard ratios [HRs] >7). IBD was also associated with premature preterm rupture of membranes in women using local corticosteroid medications (HR 3.30, 95% confidence interval [CI] 1.33-8.20) and with medically indicated preterm delivery (HR 1.91, 95% CI 0.99-3.68) in non-medicated women. Furthermore, IBD was associated with low 5-minute Apgar score in term infants (risk ratio [RR] 2.19, 95% CI 1.03-4.66). Finally, Crohns disease (but not ulcerative colitis) was associated with major congenital abnormalities in the offspring (RR 1.85, 95% CI 1.06-3.21). No child with a congenital abnormality born to a woman with IBD was exposed to systemic corticosteroids in utero. Conclusion Women with IBD are at increased risk of severe pre-eclampsia, medically indicated preterm delivery, preterm premature rupture of membranes, and delivering infants with low Apgar score and major congenital malformations. These associations are only partly explained by severe disease as reflected by systemic corticosteroid use. PMID:26083614

  7. The 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is not associated with HELLP syndrome.

    PubMed

    Muetze, Sabine; Eggermann, Thomas; Leeners, Brigitte; Birke, Cornelia; Kuse, Sabine; Ortlepp, Jan Rudolf; Rudnik-Schoeneborn, Sabine; Zerres, Klaus; Rath, Werner

    2009-02-01

    Plasminogen activator inhibitor-1 (PAI-1) is a major inhibitor of fibrinolysis, and a single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been identified. Subjects homozygous for the 4G allele have the highest PAI-levels due to increased PAI-1 gene transcription. Pre-eclampsia, and one of its most severe forms, the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, are characterized by increased placental thrombosis based on a procoagulatory state in the mother. Several studies have investigated the role of the PAI-1 4G/5G polymorphism in pre-eclampsia, but no study has focused especially on HELLP syndrome. Therefore we aimed to assess the association between HELLP syndrome and the 4G/5G polymorphism in the PAI-1 gene. Genotyping of the PAI-1 4G/5G promoter polymorphism was performed in 102 Caucasian women with HELLP syndrome and 102 Caucasian women with uncomplicated pregnancies. The 4G/4G genotype was more frequent in women with HELLP syndrome than in controls (35.3% vs. 22.5%, respectively) but this difference was not significantly different (P = 0.129). The frequency of the 4G allele was 0.588 in patients and 0.515 in controls. These data suggest that women carrying a 4G/4G genotype of the PAI-1 gene are not at increased risk for developing HELLP syndrome and are thus in line with the majority of previous studies on the association between the PAI-1 4G/5G polymorphism and pre-eclampsia. PMID:18058192

  8. Previous miscarriage and the subsequent risk of preterm birth in Scotland, 19802008: a historical cohort study

    PubMed Central

    Oliver-Williams, C; Fleming, M; Wood, AM; Smith, GCS

    2015-01-01

    Objective To determine whether the relationship between previous miscarriage and risk of preterm birth changed over the period 19802008, and to determine whether the pattern varied according to the cause of the preterm birth. Design Linked birth databases. Setting All Scottish NHS hospitals. Population A total of 732719 nulliparous women with a first live birth between 1980 and 2008. Methods Risk was estimated using logistic regression. Main outcome measures Preterm birth, subdivided by cause (spontaneous, induced with a diagnosis of pre-eclampsia, or induced without a diagnosis of pre-eclampsia) and severity [extreme (2428weeks of gestation), moderate (2932weeks of gestation), and mild (3336weeks of gestation)]. Results Consistent with previous studies, previous miscarriage was associated with an increased risk of all-cause preterm birth (adjusted odds ratio, aOR1.26; 95%confidence interval, 95%CI 1.221.29). This arose from associations with all subtypes. The strongest association was found with extreme preterm birth (aOR1.73; 95%CI 1.571.90). Risk increased with the number of miscarriages. Women with three or more miscarriages had the greatest risk of all-cause preterm birth (aOR2.14; 95%CI 1.932.38), and the strongest association was with extreme preterm birth (aOR3.87; 95%CI 2.855.26). The strength of the association between miscarriage and preterm birth decreased from 1980 to 2008. This was because of weakening associations with spontaneous preterm birth and induced preterm birth without a diagnosis of pre-eclampsia. Conclusions The association between a prior history of miscarriage and the risk of preterm birth declined in Scotland over the period 19802008. We speculate that changes in the methods of managing incomplete termination of pregnancy might explain the trend, through reduced cervical damage. PMID:25626593

  9. 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 programme for Research and Technological development of the EU. http://www.fp7-improved.eu/ PMID:24314209

  10. Endoglin: a critical mediator of cardiovascular health

    PubMed Central

    Kapur, Navin K; Morine, Kevin J; Letarte, Michelle

    2013-01-01

    Endoglin (CD105) is a type III auxiliary receptor for the transforming growth factor beta (TGF?) superfamily. Several lines of evidence suggest that endoglin plays a critical role in maintaining cardiovascular homeostasis. Seemingly disparate disease conditions, including hereditary hemorrhagic telangiectasia, pre-eclampsia, and cardiac fibrosis, have now been associated with endoglin. Given the central role of the TGF? superfamily in multiple disease conditions, this review provides a detailed update on endoglin as an evolving therapeutic target in the management of cardiovascular disease. PMID:23662065

  11. [History of the Rostock University Gynecology Clinic 1887-1997: what remains?].

    PubMed

    Schwarz, R

    1998-01-01

    110 years after the opening of the Department of Obstetrics and Gynaecology, which is still functioning, a historical review about those scientific facts published during these years and continuing to do so up to now is presented. Scientific highlights in obstetrics and gynaecology created in Rostock are the publication by Friedrich Schatz on intrauterine tocography, the anatomic description of the menstrual cycle by Robert Schrder, and the studies by Helmut Kyank on the physiology and pathophysiology of pregnancy, especially pre-eclampsia and eclampsia. PMID:9885356

  12. Maternal morbidity and preterm birth in 22 low- and middle-income countries: a secondary analysis of the WHO Global Survey dataset

    PubMed Central

    2014-01-01

    Background Preterm birth (PTB) (<37weeks) complicates approximately 15 million deliveries annually, 60% occurring in low- and middle-income countries (LMICs). Several maternal morbidities increase the risk of spontaneous (spPTB) and provider-initiated (piPTB) preterm birth, but there is little data from LMICs. Method We used the WHO Global Survey to analyze data from 172,461 singleton deliveries in 145 facilities across 22 LMICs. PTB and six maternal morbidities (height <145cm, malaria, HIV/AIDS, pyelonephritis/UTI, diabetes and pre-eclampsia) were investigated. We described associated characteristics and developed multilevel models for the risk of spPTB/piPTB associated with maternal morbidities. Adverse perinatal outcomes (Apgar <7 at 5 minutes, NICU admission, stillbirth, early neonatal death and low birthweight) were determined. Results 8.2% of deliveries were PTB; one-quarter of these were piPTB. 14.2% of piPTBs were not medically indicated. Maternal height <145cm (AOR 1.30, 95% CI 1.101.52), pyelonephritis/UTI (AOR 1.16, 95% CI 1.011.33), pre-gestational diabetes (AOR 1.41, 95% CI 1.091.82) and pre-eclampsia (AOR 1.25, 95% CI 1.051.49) increased odds of spPTB, as did malaria in Africa (AOR 1.67, 95%CI 1.32-2.11) but not HIV/AIDS (AOR 1.17, 95% CI 0.79-1.73). Odds of piPTB were higher with maternal height <145cm (AOR 1.47, 95% CI 1.23-1.77), pre-gestational diabetes (AOR 2.51, 95% CI 1.81-3.47) and pre-eclampsia (AOR 8.17, 95% CI 6.80-9.83). Conclusions Maternal height <145cm, diabetes and pre-eclampsia significantly increased odds of spPTB and piPTB, while pyelonephritis/UTI and malaria increased odds of spPTB only. Strategies to reduce PTB and associated newborn morbidity/mortality in LMICs must prioritize antenatal screening/treatment of these common conditions and reducing non-medically indicated piPTBs where appropriate. PMID:24484741

  13. Levels of Serum Calcium and Magnesium in Pre-eclamptic and Normal Pregnancy: A Study from Coastal India

    PubMed Central

    Rajesh, Aparna; Rao, Kavyarashmi; Devi, Ullal Harshini; Shetty, Harish; Kumari, Sucheta; Shetty, Prasanna Kumar

    2014-01-01

    Background: Pre-eclampsia is one of the major causes of maternal and fetal morbidity and mortality. Though the aetiology is obscure, recent studies indicate that serum levels of calcium and magnesium may have a role in pre-eclampsia. Aim: The aim of this study was to find out the relationship of serum levels of calcium and magnesium in pre-eclamptic pregnancies compared to normal pregnancies in women from southern coastal India. Settings and Design: This study was done in a medical college hospital in southern coastal India. Materials and Methods: The blood samples from 60 pre-eclamptic women and an equal number of controls were analysed for calcium and magnesium levels. Data on Body Mass Index, maternal and gestational ages, serum calcium and magnesium were compared between the two groups. Outcome of pregnancy was analysed in both the groups and compared. Statistical Analysis: Data was expressed as Mean Standard Deviation. Data analysis was done by SPSS version 20. Comparison of serum levels of the elements between the two groups was performed by Independent t-test and Chi-square test and P-value of < 0.05 was considered as statistically significant. Results: The serum calcium concentration was significantly lower in the pre-eclamptic group compared to normotensives (7.84 0.87 mg/dl Vs 8.97 0.69 mg/dl, p<0.001) whereas the levels of serum magnesium showed a marginal difference in both the groups. (1.43 0.55 mg/dl Vs, 1.57 0.72 mg/dl P 0.257) The study also showed that pre-eclamptic women were older, their BMI was higher and birth weight of babies lower compared to normotensives. Conclusion: According to the results of our research, intake of supplements, mainly calcium may help in the reduction of incidence of pre-eclampsia especially in a population of a developing country like ours where the nutrition is poor. Not many studies have been done in developing countries to assess the role of these elements in pre-eclampsia. The actual role of magnesium and calcium supplements needs further investigation. PMID:25177604

  14. 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

  15. Primary antiphospholipid syndrome in monozygotic twins.

    PubMed

    Ravindran, V; Rajendran, S; Elias, G

    2013-01-01

    Monozygotic twins, 27 years old, with primary anti-phospholipid syndrome have been described. The first of the twins had obstetric morbidities (one miscarriage at 12 weeks and premature birth of a growth-restricted fetus at 27 weeks secondary to pre-eclampsia) and the second had venous thrombosis. Lupus anticoagulant was present in both and anti-cardiolipin antibodies were present in high titres when re-tested at appropriate intervals. Development of clinical features of APS in monozygotic twins points to an underlying genetic basis in the pathogenesis of anti-phospholipid syndrome. PMID:23154322

  16. Anaesthesia for lower-segment caesarean section: Changing perspectives

    PubMed Central

    Yeoh, Sean Brian; Leong, Sng Ban; Heng, Alex Sia Tiong

    2010-01-01

    The number of caesarean sections has increased over the last two decades, especially in the developed countries. Hence, it has increasingly become a greater challenge to provide care for the parturient, but this has given obstetric anaesthetists a greater opportunity to contribute to obstetric services. While caesarean deliveries were historically performed using general anaesthesia, there is a recent significant move towards regional anaesthesia. Unique problems that patients with obesity and pre-eclampsia present will be discussed in the present article. New medications and devices now used in obstetric anaesthesia will change the practice and perspectives of our clinical practice. PMID:21189878

  17. Late postpartum eclampsia complicated with posterior reversible encephalopathy syndrome: a case report and a literature review

    PubMed Central

    Zhang, Lihong; Wang, Yacong; Shi, Liang; Cao, Jianhui

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare but serious clinical-neuroradiological entity characterized by headache, vomiting, visual disturbances, altered mental status, seizures, and unconsciousness associated with the characteristic imaging findings including sub-cortical vasogenic edema at the bilateral parietal and occipital lobes. We describe a case of 28-year-old PRES patient secondary to delayed maternal postpartum eclampsia. This patient was not initially diagnosed with pre-eclampsia and PRES. The diagnosis was established after magnetic resonance imaging. After treatment this patients PRES resolved. Early diagnosis and treatment are the keys to reverse PRES. A literature review for PRES is provided in this report. PMID:26807372

  18. Managing pregnancy in inflammatory rheumatological diseases

    PubMed Central

    2011-01-01

    Historically, pregnancy in women with many inflammatory rheumatic diseases was not considered safe and was discouraged. Combined care allows these pregnancies to be managed optimally, with the majority of outcomes being favorable. Disease activity at the time of conception and anti-phospholipid antibodies are responsible for most complications. Disease flares, pre-eclampsia, and thrombosis are the main maternal complications, whereas fetal loss and intrauterine growth restriction are the main fetal complications. Antirheumatic drugs used during pregnancy and lactation to control disease activity are corticosteroids, hydroxychloroquine, sulphasalzine, and azathioprine. Vaginal delivery is possible in most circumstances, with cesarean section being reserved for complications. PMID:21371350

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

    PubMed

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

    2015-12-01

    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. PMID:26614540

  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. PMID:7625306

  1. Effect of lycopene in prevention of preeclampsia in high risk pregnant women

    PubMed Central

    Antartani, Ramalingappa; Ashok, Kiran

    2011-01-01

    Objective To evaluate the effect of pre-natal supplementation of antioxidant Lycopene in prevention of pre-eclampsia in the high risk pregnant women. We also assessed the effect of lycopene supplementation on intra-uterine growth restriction and the perinatal outcome in women at high risk of developing pre-eclampsia. Materials and Methods A total of 54 women between 14–28 weeks of pregnancy who were at high risk of developing pre-eclampsia were considered for the study. Inclusion criteria were women with a previous history of preeclampsia, a growth-retarded fetus, perinatal death, multifetal gestation and chronic hypertension. Of the total of 54 women, 30 women were randomized to receive Lycopene in a dose of 2 mg twice daily starting from the date of entry and were instructed to continue the drug regularly until delivery. The other 24 women were randomized to the control group and they did not take lycopene. The controls were matched to cases with respect to the risk factors for the development of preeclampsia. Both groups were followed at monthly intervals. In addition, a Doppler assessment for evidence of intrauterine growth retardation was done at around 28 wks of gestation. Data regarding development of preeclampsia, period of gestation during delivery, mode of delivery, fetal weight and perinatal outcome were recorded and subjected to statistical analysis. Results Of the 30 women randomized to receive the drug, ten women were lost to follow-up. Thus only 20 women in the treatment group completed the study. All the 24 women in the control group completed the study. Lycopene was not found to decrease the incidence of pre-eclampsia in high risk women. Women in the lycopene supplementation group had significantly lesser incidence of growth restricted babies and had a significantly better perinatal outcome compared to women in the placebo group. Conclusion Lycopene supplementation does not decrease the incidence of preeclampsia in high risk women. However lycopene supplementation does seem to help in reducing the incidence of intra-uterine growth restriction. PMID:24591955

  2. Successful angioplasty during pregnancy for renal artery stenosis.

    PubMed

    Margueritte, Franois; Velasco, Stephane; Pourrat, Olivier; Pierre, Fabrice

    2016-03-01

    Renal artery stenosis can be diagnosed during pregnancy and treated at the same time. A 30-year-old woman had a sudden, severe but asymptomatic hypertensive crisis at 21 weeks of gestation. The diagnosis of renal artery stenosis suspected on Doppler ultrasonography was confirmed and treated by renal angioplasty, which reduced her blood pressure. At 27 weeks of gestation, her blood pressure increased again, associated with significant proteinuria, suggesting pre-eclampsia. A cesarean section was performed giving birth to a healthy 940-g child. Renal artery stenosis should be considered when sudden and early-onset hypertension appears during pregnancy. PMID:26818942

  3. Postpartum hemolytic uremic syndrome in a 17-year-old Filipina primigravid.

    PubMed

    Anacleto, Francisco E; Cifra, Christina L; Elises, Joel S

    2003-12-01

    A 17-year-old Filipina primigravid developed acute renal failure secondary to hemolytic uremic syndrome (HUS) after undergoing emergency cesarean section for severe pre-eclampsia and abruptio placenta. She underwent hemodialysis with concurrent infusions of fresh-frozen plasma and packed red cells for 5 weeks. Renal biopsy revealed findings consistent with HUS with glomerular crescents. She received three doses of pulse methylprednisolone followed by oral prednisone. Renal function improved 5 weeks after the onset of HUS. The pathogenesis, differential diagnosis, and treatment options of postpartum HUS are discussed. PMID:14564496

  4. 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. PMID:25457861

  5. 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. PMID:26094567

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

    PubMed Central

    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. PMID:26828433

  7. Treatment of poor placentation and the prevention of associated adverse outcomes what does the future hold?

    PubMed Central

    Spencer, RN; Carr, DJ; David, AL

    2014-01-01

    ABSTRACT Poor placentation, which manifests as pre-eclampsia and fetal growth restriction, is a major pregnancy complication. The underlying cause is a deficiency in normal trophoblast invasion of the spiral arteries, associated with placental inflammation, oxidative stress, and an antiangiogenic state. Peripartum therapies, such as prenatal maternal corticosteroids and magnesium sulphate, can prevent some of the adverse neonatal outcomes, but there is currently no treatment for poor placentation itself. Instead, management relies on identifying the consequences of poor placentation in the mother and fetus, with iatrogenic preterm delivery to minimise mortality and morbidity. Several promising therapies are currently under development to treat poor placentation, to improve fetal growth, and to prevent adverse neonatal outcomes. Interventions such as maternal nitric oxide donors, sildenafil citrate, vascular endothelial growth factor gene therapy, hydrogen sulphide donors, and statins address the underlying pathology, while maternal melatonin administration may provide fetal neuroprotection. In the future, these may provide a range of synergistic therapies for pre-eclampsia and fetal growth restriction, depending on the severity and gestation of onset. PMID:24799349

  8. 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

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

    PubMed

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

    2015-07-01

    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

  10. 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. PMID:26828433

  11. 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. PMID:25879992

  12. 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. PMID:25704354

  13. 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 [RR 0.70; 95 % CI 0.56-0.88] and risk of pre-term birth [RR 0.88, 95 % CI 0.78-0.99]. Recommendations for LiST for reduction in maternal mortality were based on risk reduction in gestational hypertensive related severe morbidity/mortality [RR 0.80; 95% CI 0.70-0.91] and that for neonatal mortality were based on risk reduction in all-cause neonatal mortality [RR 0.70; 95% CI 0.56-0.88]. Conclusion Calcium supplementation during pregnancy is associated with a reduction in risk of gestational hypertension, pre-eclampsia neonatal mortality and pre-term birth in developing countries. PMID:21501435

  14. The risk of adverse pregnancy outcomes in women who are overweight or obese

    PubMed Central

    2010-01-01

    Background The prevalence of obesity amongst women bearing children in Australia is rising and has important implications for obstetric care. The aim of this study was to assess the prevalence and impact of mothers being overweight and obese in early to mid-pregnancy on maternal, peripartum and neonatal outcomes. Methods A secondary analysis was performed on data collected from nulliparous women with a singleton pregnancy enrolled in the Australian Collaborative Trial of Supplements with antioxidants Vitamin C and Vitamin E to pregnant women for the prevention of pre-eclampsia (ACTS). Women were categorized into three groups according to their body mass index (BMI): normal (BMI 18.5-24.9 kg/m2); overweight (BMI 25-29.9 kg/m2) and; obese (BMI 30-34.9 kg/m2). Obstetric and perinatal outcomes were compared by univariate and multivariate analyses. Results Of the 1661 women included, 43% were overweight or obese. Obese women were at increased risk of pre-eclampsia (relative risk (RR) 2.99 [95% confidence intervals (CI) 1.88, 4.73], p < 0.0001) and gestational diabetes (RR 2.10 [95%CI 1.17, 3.79], p = 0.01) compared with women with a normal BMI. Obese and overweight women were more likely to be induced and require a caesarean section compared with women of normal BMI (induction - RR 1.33 [95%CI 1.13, 1.57], p = 0.001 and 1.78 [95%CI 1.51, 2.09], p < 0.0001, caesarean section - RR 1.42 [95%CI 1.18, 1.70], p = 0.0002 and 1.63 [95%CI 1.34, 1.99], p < 0.0001). Babies of women who were obese were more likely to be large for gestational age (LFGA) (RR 2.08 [95%CI 1.47, 2.93], p < 0.0001) and macrosomic (RR 4.54 [95%CI 2.01, 10.24], p = 0.0003) compared with those of women with a normal BMI. Conclusion The rate of overweight and obesity is increasing amongst the Australian obstetric population. Women who are overweight and obese have an increased risk of adverse pregnancy outcomes. In particular, obese women are at increased risk of gestational diabetes, pregnancy induced hypertension and pre-eclampsia. Effective preventative strategies are urgently needed. Trial Registration Current Controlled Trials ISRCTN00416244 PMID:20849609

  15. 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 NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes. Trial registration Italian trial: ClinicalTrials.gov Identifier: NCT01244347. Dutch trial: Dutch Trial Register ID: NTR3161. PMID:24884885

  16. Global approach to perinatal medicine: functional genomics and proteomics.

    PubMed

    Kralj, Marijeta; Kraljevi?, Sandra; Sedi?, Mirela; Kurjak, Asim; Paveli?, Kresimir

    2005-01-01

    Functional genomics (transcriptomics and proteomics) is a global, systematic and comprehensive approach to the identification and description of the processes and pathways involved in normal and abnormal physiological states. The functional genomics methods most applied today are DNA microarrays and proteomics methods, primarily two-dimensional gel electrophoresis coupled with mass spectrometry. To date, interesting research has been carried out, representing milestones for future implementation of functional genomics/proteomics in perinatal medicine. For instance, possible biomarkers of pre-eclampsia, preterm labor and gestational trophoblastic diseases have been discovered. Further systematic examination of differentially regulated genes and proteins in maternal and fetal tissues and fluids will be required. However, high-throughput technologies reflect biological fluctuations and methodological errors. Large amounts of such different data challenge the performance and capacity of the statistical tools and software available at present. Further major developments in this field are pending and the intellectual investment will certainly result in clinical advances. PMID:15841607

  17. Extracellular vesicles and reproductionpromotion of successful pregnancy

    PubMed Central

    Tannetta, Dionne; Dragovic, Rebecca; Alyahyaei, Zahraa; Southcombe, Jennifer

    2014-01-01

    Extracellular vesicles (EVs) are membrane-bound complexes secreted from cells under both physiological and pathological conditions. They contain proteins, nucleic acids and lipids and act as messengers for cellcell communication and signalling, particularly between immune cells. EV research is a rapidly evolving and expanding field, and it appears that all biological fluids contain very large numbers of EVs; they are produced from all cells that have been studied to date, and are known to have roles in several reproductive processes. This review analyses the evidence for the role of EVs throughout human reproduction, starting with the paternal and maternal gametes, followed by the establishment and continuation of successful pregnancies, with specific focus, where possible, on the interaction of EVs with the maternal immune system. Importantly, variations within the EV populations are identified in various reproductive disorders, such as pre-term labour and pre-eclampsia. PMID:24954226

  18. Iontophoresis of vasoactive drugs. Effect on peripheral blood flow during pregnancy.

    PubMed

    Eneroth-Grimfors, E; Lindblad, L E; Westgren, M; Etzell, B M; Bevegård, S

    1991-01-01

    The aim of this study was to evaluate whether iontophoretic administration of the vasoactive agents noradrenaline (NA) and angiotensin (AII) combined with measurement of skin blood flow with a laser Doppler technique could serve as a predictive method for pre-eclampsia. Nine healthy non-pregnant women, 9 healthy pregnant women and 9 pre-eclamptic patients were investigated. A significant reduction of skin blood flow was induced by NA in all three groups and by AII in the non-pregnant group. There was no significant difference between healthy pregnant and pre-eclamptic patients in the degree of reduction of blood flow with respect to NA and AII administration. PMID:1858491

  19. Successful pregnancy with autoimmune cirrhosis.

    PubMed

    Braga, António; Braga, Jorge

    2016-01-01

    Pregnancy with liver cirrhosis is a rare and dangerous event that exposes mother and fetus to potentially lethal risks. During pregnancy, hepatic decompensation could suffice and the development of hepatic failure and encephalopathy could occur. The incidence of obstetric complications is also increased with a high rate of pre-eclampsia, postpartum bleeding, preterm delivery and stillbirth. We report a case of a 27-year-old woman with autoimmune hepatitis and liver cirrhosis complicated by splenomegaly, oesophageal varices and severe thrombocytopaenia. During pregnancy, close clinical and analytical surveillance was performed. She was medicated with corticosteroids, azathioprine and propranolol. At the 25th week of gestation, an upper gastrointestinal endoscopy was performed to control oesophageal varices. This patient had an uneventful pregnancy until 37 weeks. At 37th week of gestation, after spontaneous rupture of membranes, signs of acute fetal distress were observed, and an urgent caesarean was performed. Good neonatal and maternal outcomes were achieved. PMID:26825934

  20. Inherited and acquired thrombophilia: pregnancy outcome and treatment.

    PubMed

    De Santis, Marco; Cavaliere, A F; Straface, G; Di Gianantonio, E; Caruso, A

    2006-08-01

    Maternal thrombophilias increases the risk of an adverse pregnancy outcome. An extensive literature review highlights the role of inherited and acquired thrombophilic disorders in spontaneous abortion, both early and late, recurrent or isolate, in intrauterine growth retardation, in placenta abruption, in pre-eclampsia and in venous thromboembolism. We have particularly focused attention on the following factors: antithrombin III (ATIII), proteins C (PC) and S (PS) deficiencies, genetic mutations particularly factor V Leiden (FVL), prothrombin gene G20210A (PTM) and the thermolabile variant of the methylene tetrahydrofolate reductase C677T (MTHFR) gene, lupus anticoagulant (LAC) and anticardiolipin antibodies, VIIIc factor, hyperhomocysteinemia and acquired activated protein C resistance. Appropriate treatment can improve pregnancy outcome without teratogenic effects. PMID:16797917

  1. Successful Pregnancy Following Assisted Reproduction in Woman With Systemic Lupus Erythematosus and Hypertension

    PubMed Central

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

    2015-01-01

    Abstract 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. PMID:26376400

  2. Annexin A2 autoantibodies in thrombosis and autoimmune diseases.

    PubMed

    Caas, Felipe; Simonin, Laurent; Couturaud, Francis; Renaudineau, Yves

    2015-02-01

    Antiphospholipid syndrome (APS) is an autoimmune disease characterized by arterial, venous or small-vessel thrombotic events, and recurrent miscarriages or fetal loss. APS diagnosis is based on the repeated detection of anti-phospholipid (PL) antibodies (Ab), typically associated with anti-?2 glycoprotein I (?2GPI)-Ab. Recent studies suggest that anti-?2GPI Ab activity involves a protein complex including ?2GPI and annexin A2 (ANXA2). Anti-ANXA2 Ab recognizes this complex, and these Ab can effectively promote thrombosis by inhibiting plasmin generation, and by activating endothelial cells. Therefore, anti-ANXA2 Ab represent a new biomarker, which can be detected in up to 25% of APS patients. Moreover, anti-ANXA2 Ab have been detected, in thrombotic associated diseases including pre-eclampsia, in other autoimmune diseases, and in cancer. PMID:25533130

  3. 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

  4. Hypertension in women

    PubMed Central

    Hage, Fadi G; Mansur, Sulaf J; Xing, Dongqi; Oparil, Suzanne

    2013-01-01

    Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestational hypertension, pre-eclampsia or eclampsia). Randomized controlled trials show that antihypertensive therapy provides similar reductions in major cardiovascular events in men and women. Therefore, gender should not influence decisions on selection of blood pressure lowering therapies, except for consideration of gender-specific side effects or contraindications for use in women who are or may become pregnant. This article reviews the prevalence, awareness, treatment, and control of hypertension in women, as well as recent guidelines for management of hypertension in women. PMID:25028640

  5. Infertility today: the management of female medical causes.

    PubMed

    Tinneberg, Hans-Rudolf; Gasbarrini, Antonio

    2013-12-01

    It has to be suspected that some environmentally hazardous substances have genotoxic properties, revealing their reproductive toxicity at a later stage only. Cancer, including childhood cancer, is more common than usually expected. Undesirable side effects of surgery, chemotherapy, and/or radiation can be premature ovarian failure or even premature menopause. In cases of autoimmune disease, autoantibodies can directly affect maturation of oocytes in the follicle, fertilization, and implantation. Spontaneous abortions are more common in patients with autoimmune disease. Thrombophilia is known to display a higher rate of spontaneous abortions as well as pre-eclampsia and intrauterine growth retardation. Infections are a common threat to pregnancy. Metabolic syndrome is increasingly frequent in western countries and often associated with hyperandrogenemia and polycystic disease. Women with inflammatory bowel disease such as Crohn disease or ulcerative colitis usually have no problems conceiving. In conclusion, even though infertility is a multifactorial disease, various medical and non-medical conditions can be attributed to it. PMID:24140222

  6. Endoplasmic reticulum stress is induced in the human placenta during labour

    PubMed Central

    Veerbeek, J.H.W.; Tissot Van Patot, M.C.; Burton, G.J.; Yung, H.W.

    2015-01-01

    Placental endoplasmic reticulum (ER) stress has been postulated in the pathophysiology of pre-eclampsia (PE) and intrauterine growth restriction (IUGR), but its activation remains elusive. Oxidative stress induced by ischaemia/hypoxia-reoxygenation activates ER stress invitro. Here, we explored whether exposure to labour represents an invivo model for the study of acute placental ER stress. ER stress markers, GRP78, P-eIF2? and XBP-1, were significantly higher in laboured placentas than in Caesarean-delivered controls localised mainly in the syncytiotrophoblast. The similarities to changes observed in PE/IUGR placentas suggest exposure to labour can be used to investigate induction of ER stress in pathological placentas. PMID:25434970

  7. Thyroid dysfunction during pregnancy and in postpartum period: treatment and latest recommendations.

    PubMed

    Vandana; Kumar, Amit; Khatuja, Ritu; Mehta, Sumita

    2014-05-01

    Thyroid dysfunction is the second most common endocrine disorder, only after diabetes mellitus, affecting females in reproductive age group. Pregnancy is associated with profound repercussions on the thyroid status of a lady. Thyroid dysfunctions such as hypothyroidism, thyrotoxicosis and thyroid nodules may develop during pregnancy leading to abortion, placental abruptions, pre-eclampsia, preterm delivery and reduced intellectual function in the offspring. Thus, maintenance of euthyroid state is of utmost important for maternal and fetal well being during pregnancy as well as after. The Endocrine Society has issued latest guidelines regarding the diagnosis and management of thyroid dysfunction related to pregnancy. All the clinicians should be well aware of the latest recommendations regarding management of thyroid dysfunction in pregnancy and in postpartum phase and practice them accordingly. PMID:24510157

  8. Keap1-Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring.

    PubMed

    Chapple, Sarah J; Puszyk, William M; Mann, Giovanni E

    2015-11-01

    Intrauterine exposure to gestational diabetes, pre-eclampsia or intrauterine growth restriction alters the redox status of the developing fetus. Such pregnancy-related diseases in most cases do not have a readily identifiable genetic cause, and epigenetic 'priming' mechanisms in utero may predispose both mother and child to later-life onset of cardiovascular and metabolic diseases. The concept of 'fetal programing' or 'developmental priming' and its association with an increased risk of disease in childhood or adulthood has been reviewed extensively. This review focuses on adaptive changes in the in utero redox environment during normal pregnancy and the consequences of alterations in redox control associated with pregnancies characterized by oxidative stress. We evaluate the evidence that the Keap1-Nrf2 pathway is important for protecting the fetus against adverse conditions in utero and may itself be subject to epigenetic priming, potentially contributing to an increased risk of vascular disease and insulin resistance in later life. PMID:26279476

  9. Asymptomatic spontaneous complete uterine rupture in a term pregnancy after uterine packing during previous caesarean section: a case report.

    PubMed

    Zhang, J; Chen, S F; Luo, Y E

    2014-01-01

    Uterine rupture is a life-threatening obstetrical complication with significant neonatal and maternal morbidity. The authors report a 36-year-old woman with a history of previous caesarean section because of pre-eclampsia and antepartum haemorrhage at 31 gestational weeks during her first pregnancy. Postpartum haemorrhage occurred and the uterine cavity was packed with gauze for reducing blood loss. After two years, she underwent elective, repeat caesarean section at 38+1 gestational weeks with no abdominal pain or vaginal bleeding. During the operation, a six- to seven-cm-long defect was found in the lower uterine segment, with complete separation of the uterine scar and disruption of the visceral peritoneum. A live baby was delivered. The postoperative course was uneventful. Uterine dehiscence and rupture should be suspected in the presence of risk factors such as previous caesarean section, especially uterine packing involved. Spontaneous silent rupture can occur in women without any alarming symptoms. PMID:25864270

  10. Villitis of unknown aetiology: Clinical implications in preterm population.

    PubMed

    Iskender, C; Zergeroglu, S; Kaymak, O; Çelen, S; Danisman, N

    2016-02-01

    Villitis of unknown aetiology (VUE) is a chronic inflammatory process of chorionic villi which is reported to occur in up to 15% of term placentas. The present study aimed to investigate the association between VUE and perinatal complications in a population who delivered before term. Patients with VUE had a significantly higher rate of intrauterine growth restriction than the control group (47.1% vs. 20.6%, p < 0.01). In addition patients with VUE had a higher rate of deliveries due to absent diastolic flow on umbilical artery doppler than the control group (17.6% vs. 4.4%, p: 0.03). The rate of spontaneous preterm birth or pre-eclampsia was similar in patients with VUE and control groups. The present study provides some evidence that VUE is associated with abnormal perinatal outcomes in pregnant women who give birth before term. PMID:26431437

  11. Prehospital and emergency department delivery: a review of eight years experience.

    PubMed

    Brunette, D D; Sterner, S P

    1989-10-01

    We reviewed the medical records of all patients who delivered in the prehospital or emergency department setting from 1980 through 1987 at Hennepin County Medical Center. There were 80 deliveries. Twelve women had no prenatal care; the remaining 68 women had an average of seven prenatal visits. There were seven perinatal infant deaths, and an additional seven infants had morbidity subsequent to delivery. Twenty infants required some degree of resuscitation at the time of delivery, including 19 endotracheal intubations. Complications during delivery were numerous and included nuchal cord, breech presentation, shoulder dystocia, postpartum hemorrhage, pre-eclampsia, prolapsed cord, and meconium staining. Prehospital and ED delivery were associated with a high rate of maternal and infant complications. PMID:2802289

  12. Development of prenatal screening-A historical overview.

    PubMed

    Cuckle, Howard; Maymon, Ron

    2016-02-01

    The first prenatal screening test to be introduced was based on a single maternal serum marker of neural tube defects. Since then various prenatal screening concepts have been developed, the most successful being Down syndrome risk estimation using multiple serum and ultrasound markers. Today a completely new approach to aneuploidy screening is available based on maternal plasma cell-free DNA testing. This has the potential to markedly improve screening performance but routine testing is currently too expensive in a public health setting. However, it can be cost-effective when used in combination with existing multi-maker tests. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia that can be prevented using soluble low-dose aspirin treatment started before 16 weeks of gestation. Prenatal screening for cardiac abnormalities, fragile X syndrome and recessive genetic disorders is underutilized and public health planners should considered a more widespread application of available methods. PMID:26764253

  13. Endogenous digitalis

    PubMed Central

    Bagrov, Alexei Y; Shapiro, Joseph I

    2008-01-01

    SUMMARY Endogenous digitalis-like factors, also called cardiotonic steroids, have been thought for nearly half a century to have important roles in health and disease. The endogenous cardiotonic steroids ouabain and marinobufagenin have been identified in humans, and an effector mechanism has been delineated by which these hormones signal through the sodium/potassium-transporting ATPase. These findings have increased interest in this field substantially. Although cardiotonic steroids were first considered important in the regulation of renal sodium transport and arterial pressure, subsequent work has implicated these hormones in the control of cell growth, apoptosis and fibrosis, among other processes. This Review focuses on the role of endogenous cardiotonic steroids in the pathophysiology of essential hypertension, congestive heart failure, end-stage renal disease and pre-eclampsia. We also discuss potential therapeutic strategies that have emerged as a result of the increased understanding of the regulation and actions of cardiotonic steroids. PMID:18542120

  14. Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox signaling and function in health and disease☆

    PubMed Central

    Chapple, Sarah J.; Cheng, Xinghua; Mann, Giovanni E.

    2013-01-01

    4-hydroxynonenal (HNE) is a lipid hydroperoxide end product formed from the oxidation of n-6 polyunsaturated fatty acids. The relative abundance of HNE within the vasculature is dependent not only on the rate of lipid peroxidation and HNE synthesis but also on the removal of HNE adducts by phase II metabolic pathways such as glutathione-S-transferases. Depending on its relative concentration, HNE can induce a range of hormetic effects in vascular endothelial and smooth muscle cells, including kinase activation, proliferation, induction of phase II enzymes and in high doses inactivation of enzymatic processes and apoptosis. HNE also plays an important role in the pathogenesis of vascular diseases such as atherosclerosis, diabetes, neurodegenerative disorders and in utero diseases such as pre-eclampsia. This review examines the known production, metabolism and consequences of HNE synthesis within vascular endothelial and smooth muscle cells, highlighting alterations in mitochondrial and endoplasmic reticulum function and their association with various vascular pathologies. PMID:24024167

  15. Idiopathic intracranial hypertension presenting as postpartum headache.

    PubMed

    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

  16. What are the roles of macrophages and monocytes in human pregnancy?

    PubMed

    Tang, Mao-Xing; Hu, Xiao-Hui; Liu, Zhao-Zhao; Kwak-Kim, Joanne; Liao, Ai-Hua

    2015-11-01

    During pregnancy, the maternal immune system is challenged by the semi-allogeneic fetus, which leads to systemic and local immunity. Systemic immunity, including enhanced innate immunity with increased activation of monocytes, is induced by various placental factors. Maternal immune adaptations are most evident at the feto-maternal interface, where macrophages are enriched and communicate with various decidual leukocytes. These cells are not only contributing to the protection of the growing fetus from microorganisms, but also aiding placental development by promoting trophoblast invasion and spiral artery remodeling, and the parturition process. Thus, monocytes and macrophages concurrently play important roles throughout the trimesters. Dysregulation of these cells may thus lead to pregnancy complications, such as pre-eclampsia and preterm labor. In this review, monocytes and macrophage subsets and their roles in normal and pathological pregnancies are reviewed. PMID:26340023

  17. The obstetric management of sickle cell disease.

    PubMed

    Howard, Jo; Oteng-Ntim, Eugene

    2012-02-01

    Sickle cell disease (SCD) is the most common inherited disease worldwide and is associated with anaemia and intermittent severe pain. Pregnant women who are affected have increased maternal and fetal mortality and morbidity. In view of this obstetricians should have an awareness of this condition and its complications, and pregnancies in women with SCD should be managed by a multidisciplinary team with experience of high risk pregnancies. Ideally women should be seen preconceptually for optimisation of their SCD and partner screening. Antenatal care should include regular outpatient visits with regular monitoring for pre-eclampsia and of fetal growth. Blood transfusion should be used for the treatment of acute anaemia, acute chest syndrome or acute stroke but there is not sufficient evidence currently to recommend its use prophylactically. There is an increased prevalence of sickle crisis during pregnancy and patients should be monitored carefully throughout this time. PMID:22113135

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

    PubMed

    de Macedo, Jos 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. PMID:26376400

  19. The Role of Decidual Macrophages During Normal and Pathological Pregnancy.

    PubMed

    Ning, Fen; Liu, Huishu; Lash, Gendie E

    2016-03-01

    Macrophages perform many specific functions including host defense, homeostasis, angiogenesis, and tissue development. Macrophages are the second most abundant leukocyte population in the non-pregnant endometrium and pregnant decidua and likely play a central role in the establishment and maintenance of normal pregnancy. Importantly, aberrantly activated uterine macrophages can affect trophoblast function and placental development, which may result in various adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth restriction or demise. Only by fully understanding the roles of macrophage in pregnancy will we be able to develop interventions for the treatment of these various pregnancy complications. This review discusses the general origin and classification of monocytes and macrophages and focuses on the phenotype and functional roles of decidual macrophage at the maternal-fetal interface in normal pregnancy, as well as discussing the potential contribution of the abnormal state of these cells to various aspects of pregnancy pathologies. PMID:26750089

  20. Antenatal tests of fetal wellbeing.

    PubMed

    Everett, Thomas R; Peebles, Donald M

    2015-06-01

    In current obstetric practice, there is frequently a need to assess fetal wellbeing. This is particularly so in those fetuses at risk, including the small-for-gestational-age fetus or the fetus of a mother who presents with reduced fetal movements or who has an obstetric complication such as pre-eclampsia. It is important that the clinician is able to assess fetal wellbeing in such cases, especially in preterm gestations, when inappropriate delivery could have serious adverse consequences. In this paper, we review the current evidence for the use and the limitations of widely used methods of antenatal monitoring including the use of cardiotocography, biophysical profile, and ultrasound-derived parameters including umbilical artery, middle cerebral artery, and ductus venosus Doppler flow. PMID:25936927

  1. A second delivery after heart transplantation a case study

    PubMed Central

    Kalinka, Jaros?aw; Szubert, Maria; Zdziennicki, Andrzej; Chojnowski, Krzysztof; Maciejewski, Marek; Piestrzeniewicz, Katarzyna; Dro?d?, Jaros?aw

    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

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

    PubMed

    elebi, N; Ktk, M S; Ta?, M; Soylu, E; Etz, 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. PMID:23441802

  3. Corin in Natriuretic Peptide Processing and Hypertension

    PubMed Central

    Zhou, Yiqing; Wu, Qingyu

    2014-01-01

    Corin is a serine protease originally isolated from the heart. Functional studies show that corin is the long-sought enzyme responsible for activating cardiac natriuretic peptides. In mice, lack of corin prevents the natriuretic peptide processing, causing salt-sensitive hypertension. In humans, corin variants and mutations that reduce corin activity have been identified in patients with hypertension and heart failure. Decreased plasma levels of corin antigen and activity have been reported in patients with heart failure and coronary artery disease. Low levels of urinary corin also have been found in patients with chronic kidney disease. Most recent studies show that corin also acts in the uterus to promote spiral artery remodeling and prevent pregnancy-induced hypertension. Here we review the role of corin in natriuretic peptide processing and cardiovascular diseases such as hypertension, heart disease, pre-eclampsia, and chronic kidney disease. PMID:24407448

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

    PubMed

    English, Nicola; Rao, Jegajeeva

    2015-01-01

    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. PMID:25878236

  5. Posterior reversible encephalopathy syndrome following an inadvertent dural puncture during an emergency laparotomy for ischemic colitis a case report

    PubMed Central

    Shah, Reena; Kubisz-Pudelko, Agnieszka; Reid, Jeremy

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome characterized by various symptoms of neurological disease. It has commonly been reported in association with acute hypertension, pre-eclampsia, eclampsia, sepsis, and exposure to immunosuppressants. Here, we report on a normotensive woman who developed a severe frontal headache, visual disturbances, and hypertension 3 days after undergoing an emergency laparotomy for ischemic colitis during which she suffered an inadvertent dural puncture. Neuro-imaging revealed features consistent with PRES. The patient went on to make a good recovery, being discharged 21 days postoperatively, with only minor visual disturbances and memory problems. This case highlights the importance of awareness of PRES to all specialties. On reviewing the literature, we feel that PRES may be a potential differential diagnosis to post-procedural neurological symptoms in those patients undergoing routine procedures such as spinal anesthetics or lumbar punctures. PMID:24600245

  6. A Short History of Sonography in Obstetrics and Gynaecology

    PubMed Central

    Campbell, S.

    2013-01-01

    The history of sonography in Obstetrics and Gynaecology dates from the classic 1958 Lancet paper of Ian Donald and his team from Glasgow. Fifty years on it is impossible to conceive of practising Obstetrics and Gynaecology without one of the many forms of ultrasound available today. Technological developments such as solid state circuitry, real time imaging, colour and power Doppler, transvaginal sonography and 3/4D imaging have been seized by clinical researchers to enhance the investigation and management of patients in areas as diverse as assessment of fetal growth and wellbeing, screening for fetal anomalies, prediction of pre-eclampsia and preterm birth, detection of ectopic gestation, evaluation of pelvic masses, screening for ovarian cancer and fertility management. Ultrasound guided procedures are now essential components of fetal therapy and IVF treatment. This concise history is written by someone who has witnessed each of these advances throughout the ultrasound era and is able to give perspective to these momentous happenings. PMID:24753947

  7. 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).

  8. Neurokinin B induces oedema formation in mouse lung via tachykinin receptor-independent mechanisms

    PubMed Central

    Grant, Andrew D; Akhtar, Roksana; Gerard, Norma P; Brain, Susan D

    2002-01-01

    The tachykinin neurokinin B (NKB) has been implicated in the hypertension that characterises pre-eclampsia, a condition where tissue oedema is also observed. The ability of NKB, administered intradermally or intravenously, to induce oedema formation (assessed as plasma extravasation) was examined by extravascular accumulation of intravenously injected 125I-albumin in wild-type and tachykinin NK1 receptor knockout mice. Intradermal NKB (30-300 pmol) caused dose-dependent plasma extravasation in wild-type (P < 0.05) but not NK1 knockout mice, indicating an essential role for the NK1 receptor in mediating NKB-induced skin oedema. Intravenous administration of NKB to wild-type mice produced plasma extravasation in skin, uterus, liver (P < 0.05) and particularly in the lung (P < 0.01). Surprisingly, the same doses of NKB led to plasma extravasation in the lung and liver of NK1 knockout mice. By comparison, the tachykinin substance P induced only minimal plasma extravasation in the lungs of wild-type mice. The plasma extravasation produced by NKB in the lungs of NK1 receptor knockout mice was unaffected by treatment with the NK2 receptor antagonist SR48968 (3 mg kg?1), by the NK3 receptor antagonists SR142801 (3 mg kg?1) and SB-222200 (5 mg kg?1) or by the cyclo-oxygenase (COX) inhibitor indomethacin (20 mg kg?1). L-Nitro-arginine methyl ester (15 mg kg?1), an inhibitor of endothelial nitric oxide synthase (eNOS), produced only a partial inhibition. We conclude that NKB is a potent stimulator of plasma extravasation through two distinct pathways: via activation of NK1 receptors, and via a novel neurokinin receptor-independent pathway specific to NKB that operates in the mouse lung. These findings are in keeping with a role for NKB in mediating plasma extravasation in diseases such as pre-eclampsia. PMID:12231654

  9. Selenium supplementation protects trophoblast cells from oxidative stress.

    PubMed

    Watson, M; van Leer, L; Vanderlelie, J J; Perkins, A V

    2012-12-01

    Oxidative stress is a key feature in the pathogenesis of pre-eclampsia and antioxidants have been proposed as a potential therapy in the treatment of this important complication of pregnancy. In this report selenium supplementation was used to up-regulate the antioxidant enzymes glutathione peroxidase and thioredoxin reductase and the protective effect that this had on cellular metabolism during oxidative stress was examined. Bewo and Jeg-3 trophoblast cells were supplemented with organic and inorganic forms of selenium and 3 forms of peroxide in a range of doses were utilised to generate oxidative stress. Thioredoxin reductase and glutathione peroxidase activity were maximally expressed after supplementation with 100 nM NaSe and 500 nM SeMethionine. Application of H?O? in the range of 200-400 ?M for 24h resulted in significant (p<0.001) inhibition of cellular activity, an effect negated by Se supplementation. Tert-butyl H?O? and cumene H?O? concentrations between 30 and 50 uM similarly inhibited cellular activity and this could be significantly (p<0.001) reversed by Se supplementation. Auranofin, a specific inhibitor of thioredoxin reductase and glutathione peroxidase was used to prove that the protective effect generated by Se supplementation was due to up regulation of these enzymes. These studies provide direct evidence that selenium supplementation can up-regulate endogenous antioxidant systems and protects trophoblast cells from oxidative stress. This may inform the development of future therapies for pre-eclampsia and emphasises the importance of selenium adequacy during pregnancy. PMID:23063346

  10. Clinical cardiovascular risk during young adulthood in offspring of hypertensive pregnancies: insights from a 20-year prospective follow-up birth cohort

    PubMed Central

    Davis, Esther F; Lewandowski, Adam J; Aye, Christina; Williamson, Wilby; Boardman, Henry; Huang, Rae-Chi; Mori, Trevor A; Newnham, John; Beilin, Lawrence J; Leeson, Paul

    2015-01-01

    Objectives Offspring of hypertensive pregnancies have increased cardiovascular risk factors during childhood. We hypothesised that offspring of hypertensive pregnancies would demonstrate increased clinical levels of hypertension by young adult life, which would be proportional to the severity of the pregnancy complication. Design Prospective birth cohort study Setting Tertiary obstetric hospital. Participants 2868 young adult offspring of women enrolled during pregnancy into the Western Australia Pregnancy Cohort (Raine) Study. Main outcome measures Cardiovascular risk, including incidence of hypertension and metabolic disease, in those born to hypertensive compared to normotensive pregnancies. Results Young adult offspring of hypertensive pregnancies were 2.5 times (95% CI 1.32 to 4.56, p=0.004) more likely to have global lifetime risk (QRISK) scores above the 75th centile. Thirty per cent of 20 year olds with hypertensive blood pressures were born following a hypertensive pregnancy. Pre-eclampsia or hypertension resulting in preterm birth associated with a threefold (95% CI 1.3 to 7.0, p=0.01) greater risk of being hypertensive by age 20 years, with no differences in body mass index. Whereas pregnancy-induced hypertension associated with a smaller 3±1 mm Hg blood pressure rise (p=0.001) and a twofold (95% CI 1.5 to 2.8, p=0.001) greater risk of being obese or overweight. Risk factor associations were consistent throughout early life and independent of other birth-factors. Conclusions Incidence of offspring hypertension was significantly increased in those whose mothers had a more complicated pregnancy history, including preterm birth and pre-eclampsia. PMID:26105032

  11. Pregnancy in renal transplantation: Recipient and donor aspects in the Arab world

    PubMed Central

    Kukla, Aleksandra; Issa, Naim; Ibrahim, Hassan N.

    2012-01-01

    Objective There are many kidney transplant recipients and living donors of reproductive age, and the prevalence of pregnancies in kidney transplant recipients can reach 55% in the Middle Eastern countries. Living kidney donation is predominant in this region. As the risks and outcomes of pregnancy should be a part of counselling for both recipients and donors, we reviewed available reports on maternal and foetal outcomes in these particular populations. Methods Information was obtained from retrospective analyses of a large database, and from single-centre reports indexed in PubMed on pregnancy in donors and kidney transplant recipients. The keywords used for the search included fertility, kidney disease, pregnancy, maternal/foetal outcomes, kidney transplant recipient, immunosuppression side-effects, living donor and Arab countries. Results Pregnancies in kidney transplant recipients are most successful in those with adequate kidney function and controlled comorbidities. Similarly to other regions, pregnant recipients in the Middle East had a higher risk of pre-eclampsia (26%) and gestational diabetes (7%) than in the general population. Caesarean section was quite common, with an incidence rate of 61%, and the incidence of pre-term birth reached 46%. Conclusions Most living donors can have successful pregnancies and should not be routinely discouraged. Women who had pregnancies before and after donation were more likely to have adverse maternal outcomes (gestational diabetes, hypertension, proteinuria, and pre-eclampsia) in the latter, but no adverse foetal outcomes were found after donation. The evaluation before donation should include a gestational history and counselling about the potential risks. PMID:26558022

  12. Gestational and Pregestational Diabetes Mellitus in Omani Women

    PubMed Central

    Abu-Heija, Adel T.; Al-Bash, Majeda; Mathew, Mariam

    2015-01-01

    Objectives: The aim of this study was to assess the prevalence of gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM) among pregnant women in Oman and compare their obstetric and perinatal outcomes. Methods: This retrospective study assessed the obstetric and perinatal outcomes of pregnant Omani women with GDM or PGDM who delivered at the Sultan Qaboos University Hospital in Muscat, Oman, between January 2009 and December 2010. Results: There were a total of 5,811 deliveries during the study period. Of the 5,811 women who gave birth, 639 women were found to have diabetes mellitus (11.0%). A total of 581 of the diabetic women had GDM (90.9%) and only 58 (9.1%) had PGDM. Women with PGDM had a significantly higher incidence of pre-eclampsia (P = 0.022), preterm deliveries (P <0.001) and Caesarean sections (P <0.001). Neonatal complications, such as respiratory distress syndrome (RDS), neonatal hypoglycaemia, neonatal jaundice and subsequent admission to a neonatal intensive care unit (NICU) were significantly higher for neonates born to mothers with PGDM compared to those born to mothers with GDM (P <0.001). The corrected perinatal mortality rates for women with PGDM and GDM were 34.5 and 13.7 per 1,000 live births, respectively. Conclusion: In this Omani cohort, women with PGDM were at higher risk of developing obstetric and perinatal complications such as pre-eclampsia, preterm delivery and Caesarean delivery compared to women with GDM. In addition, neonates who had mothers with PGDM had higher rates of RDS, neonatal hypoglycaemia, neonatal jaundice and admission to the NICU. PMID:26629376

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

    PubMed

    Hyvnen-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). PMID:6323054

  14. Prenatal and Neonatal Risk Factors for Sleep Disordered Breathing in School-Aged Children Born Preterm

    PubMed Central

    Hibbs, Anna Maria; Johnson, Nathan L; Rosen, Carol L; Kirchner, H Lester; Martin, Richard; Storfer-Isser, Amy; Redline, Susan

    2009-01-01

    Objectives Previously published data from the Cleveland Childrens Sleep and Health Study (CCSHS) demonstrated that preterm infants are especially vulnerable both to sleep disordered breathing (SDB) and its neurocognitive sequelae at age 811 years. In this analysis, we aimed to identify the components of the neonatal medical history associated with childhood SDB among children born prematurely. Study design This analysis focuses on the 383 children in the population-based CCSHS cohort who were born <37 weeks gestational age and who had technically acceptable sleep studies performed at ages 811 years (92% of all preterm children). Logistic regression was used to evaluate the associations between candidate perinatal and neonatal risk factors and the presence of childhood SDB by sleep study. Results Twenty-eight preterm children (7.3%) met the definition for SDB at age 811 years. Having a single mother and mild maternal pre-eclampsia were strongly associated with SDB in unadjusted and race-adjusted models. Unadjusted analyses also identified xanthine use and CPR and/or intubation in the delivery room as potential risk-factors for SDB. We did not find a significant link between traditional markers of severity of neonatal illness -- such as gestational age, birth weight, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), or duration of ventilation -- and childhood SDB at school age. Conclusions These results represent a first step in identifying prenatal and neonatal characteristics which place preterm infants at higher risk for childhood SDB. The strong association between mild pre-eclampsia and childhood SDB underscores the importance of research aimed at understanding in utero risk factors for neurorespiratory development. PMID:18534222

  15. Impact of Janani Suraksha Yojana on institutional delivery rate and maternal morbidity and mortality: an observational study in India.

    PubMed

    Gupta, Sanjeev K; Pal, Dinesh K; Tiwari, Rajesh; Garg, Rajesh; Shrivastava, Ashish K; Sarawagi, Radha; Patil, Rajkumar; Agarwal, Lokesh; Gupta, Prashant; Lahariya, Chandrakant

    2012-12-01

    The Government of India initiated a cash incentive scheme--Janani Suraksha Yojana (JSY)--to promote institutional deliveries with an aim to reduce maternal mortality ratio (MMR). An observational study was conducted in a tertiary-care hospital of Madhya Pradesh, India, before and after implementation of JSY, with a sample of women presenting for institutional delivery. The objectives of this study were to: (i) determine the total number of institutional deliveries before and after implementation of JSY, (ii) determine the MMR, and (iii) compare factors associated with maternal mortality and morbidity. The data were analyzed for two years before implementation of JSY (2003-2005) and compared with two years following implementation of JSY (2005-2007). Overall, institutional deliveries increased by 42.6% after implementation, including those among rural, illiterate and primary-literate persons of lower socioeconomic strata. The main causes of maternal mortality were eclampsia, pre-eclampsia and severe anaemia both before and after implementation of JSY. Anaemia was the most common morbidity factor observed in this study. Among those who had institutional deliveries, there were significant increases in cases of eclampsia, pre-eclampsia, polyhydramnios, oligohydramnios, antepartum haemorrhage (APH), postpartum haemorrhage (PPH), and malaria after implementation of JSY. The scheme appeared to increase institutional delivery by at-risk mothers, which has the potential to reduce maternal morbidity and mortality, improve child survival, and ensure equity in maternal healthcare in India. The lessons from this study and other available sources should be utilized to improve the performance and implementation of JSY scheme in India. PMID:23304913

  16. Pregnancies in liver and kidney transplant recipients: a review of the current literature and recommendation.

    PubMed

    Blume, C; Pischke, S; von Versen-Hynck, F; Gnter, H H; Gross, M M

    2014-11-01

    In this article, we focus on the biggest groups of organ transplant recipients, patients with a kidney or liver graft. Among these patients, about one sixth included women of childbearing potential. Therefore, the wish of getting pregnant is frequent in these peculiar patients, and careful planning and management of the pregnancies requires the expertise of obstetricians, midwives and transplant experts. Altogether, the outcome of the pregnancies in these women is acceptable. About 75% off all pregnancies ended successfully with live births, and this is comparable if not superior to pregnancies in healthy women. This success might be caused not only by the special and intensive care provided to these high-risk pregnancies by the transplant centres but also by the low rate of unplanned pregnancies. The risk of rejections and organ loss after delivery is about 10%, and it is slightly enhanced in liver transplant recipients (LTRs) in comparison to kidney graft recipients (KTRs) but the number of organ losses in direct association with a pregnancy is rare. However, there is not only a higher frequency of pregnancy-associated disorders such as pre-eclampsia and preterm delivery but also an acceleration of hypertension, new-onset diabetes mellitus and newly arising infections also favoured by the maintained immunosuppressive therapy. This implies a specialized 'control system' for these pregnant women that comprises ultrasound and Doppler investigation for risk assessment, infection screening, suitable therapy and the choice of non-teratogenic immunosuppressives. Antihypertensive treatment must be well balanced and adjusted to the possible growth-retarding effect on the foetus as well as on the co-morbidity of the mother. Finally, supplementation of vitamin D and iron is much more important in these transplanted women than in healthy pregnant women as vitamin D deficiency and anaemia are discussed to have an impact on pre-eclampsia and preterm delivery. These claims are widely discussed. Furthermore, the current literature is systematically reviewed by Scopus analysis. PMID:25194281

  17. Does high-density lipoprotein protect vascular function in healthy pregnancy?

    PubMed

    Sulaiman, Wan N Wan; Caslake, Muriel J; Delles, Christian; Karlsson, Helen; Mulder, Monique T; Graham, Delyth; Freeman, Dilys J

    2016-04-01

    The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur. PMID:26888561

  18. The use of oral hypoglycaemic agents in pregnancy.

    PubMed

    Holt, R I G; Lambert, K D

    2014-03-01

    While insulin has been the treatment of choice when lifestyle measures do not maintain glycaemic control during pregnancy, recent studies have suggested that certain oral hypoglycaemic agents may be safe and acceptable alternatives. With the exception of metformin and glibenclamide (glyburide), there are insufficient data to recommend treatment with any other oral hypoglycaemic agent during pregnancy. There are no serious safety concerns with metformin, despite it crossing the placenta. When used in the first trimester, there is no increase in congenital abnormalities and there appears to be a reduction in miscarriage, pre-eclampsia and subsequent gestational diabetes. Studies of the use of metformin in gestational diabetes show at least equivalent neonatal outcomes, while reporting reductions in neonatal hypoglycaemia, maternal hypoglycaemia and weight gain and improved treatment satisfaction. Glibenclamide effectively lowers blood glucose in women with gestational diabetes, possibly with a lower treatment failure rate than metformin. Although generally well tolerated, some studies have reported higher rates of pre-eclampsia, neonatal jaundice, longer stay in the neonatal care unit, macrosomia and neonatal hypoglycaemia. There is a paucity of long-term follow-up data on children exposed to oral agents in utero. The American College of Obstetrics and Gynecology and the UK National Institute of Health and Care Excellence (NICE) have recommended that either metformin or glibenclamide can be used to treat gestational diabetes. Metformin is also recommended for use in the pre-conception period by NICE. By contrast, the American Diabetes Association recommends that both drugs should only be used during pregnancy in the context of clinical trials. PMID:24528229

  19. Decidual natural killer cells regulate vessel stability: implications for impaired spiral artery remodelling.

    PubMed

    Fraser, Rupsha; Whitley, Guy St J; Thilaganathan, Baskaran; Cartwright, Judith E

    2015-08-01

    Decidual NK (dNK) cells are present during uterine spiral artery remodelling, an event that is crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Spiral artery remodelling is impaired in the pregnancy complication pre-eclampsia. Although dNK cells are known to play active roles at the maternal-fetal interface, little is known about their effect on endothelial integrity, an important component of vessel stability. We present a study in which we have modelled dNK-endothelium interactions, using first-trimester dNK cells isolated from both normal pregnancies and those with impaired spiral artery remodelling. dNK cells were isolated from first-trimester pregnancies, screened by uterine artery Doppler ultrasound to determine resistance indices (RI) that relate to the extent of spiral artery remodelling. dNK culture supernatant from normal-RI pregnancies (but not high-RI pregnancies) destabilised endothelial tube-like structures in Matrigel, and normal-RI dNK cells induced endothelial intercellular adhesion molecule-1 and tumour necrosis factor-? expression to a greater extent than high-RI dNK cells. We have established a functional role for dNK cells in the disruption of endothelial structures and have suggested how impairment of this process may be contributing to the reduced vessel remodelling in pregnancies with a high uterine artery resistance index. These findings have implications for our understanding of the pathology of pre-eclampsia and other pregnancy disorders where remodelling is impaired. PMID:26004035

  20. Decidual natural killer cells regulate vessel stability: implications for impaired spiral artery remodelling

    PubMed Central

    Fraser, Rupsha; Whitley, Guy St.J.; Thilaganathan, Baskaran; Cartwright, Judith E.

    2015-01-01

    Decidual NK (dNK) cells are present during uterine spiral artery remodelling, an event that is crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Spiral artery remodelling is impaired in the pregnancy complication pre-eclampsia. Although dNK cells are known to play active roles at the maternalfetal interface, little is known about their effect on endothelial integrity, an important component of vessel stability. We present a study in which we have modelled dNKendothelium interactions, using first-trimester dNK cells isolated from both normal pregnancies and those with impaired spiral artery remodelling. dNK cells were isolated from first-trimester pregnancies, screened by uterine artery Doppler ultrasound to determine resistance indices (RI) that relate to the extent of spiral artery remodelling. dNK culture supernatant from normal-RI pregnancies (but not high-RI pregnancies) destabilised endothelial tube-like structures in Matrigel, and normal-RI dNK cells induced endothelial intercellular adhesion molecule-1 and tumour necrosis factor-? expression to a greater extent than high-RI dNK cells. We have established a functional role for dNK cells in the disruption of endothelial structures and have suggested how impairment of this process may be contributing to the reduced vessel remodelling in pregnancies with a high uterine artery resistance index. These findings have implications for our understanding of the pathology of pre-eclampsia and other pregnancy disorders where remodelling is impaired. PMID:26004035

  1. Pulse Wave Analysis in Normal Pregnancy: A Prospective Longitudinal Study

    PubMed Central

    Khalil, Asma; Jauniaux, Eric; Cooper, Derek; Harrington, Kevin

    2009-01-01

    Background Outside pregnancy, arterial pulse wave analysis provides valuable information in hypertension and vascular disease. Studies in pregnancy using this technique show that vascular stiffness is raised in women with established pre-eclampsia. We aimed to establish normal ranges for parameters of pulse wave analysis in normal pregnancy and to compare different ethnic groups. Methodology/Principal Findings This prospective study was conducted at The Homerton University Hospital, London between January 2006 and March 2007. Using applanation tonometry, the radial artery pulse waveform was recorded and the aortic waveform derived. Augmentation pressure (AP) and Augmentation Index at heart rate 75/min (AIx-75), measures of arterial stiffness, were calculated. We recruited 665 women with singleton pregnancies. Women who developed pre-eclampsia (n?=?24, 3.6%) or gestational hypertension (n?=?36, 5.4%) were excluded. We also excluded 47 women with other pregnancy complications or incomplete follow-up, leaving 541 healthy normotensive pregnant women for subsequent analysis. In the overall group of 541 women, there were no significant changes in AP or AIx-75 as pregnancy progressed. In 45 women followed longitudinally, AP and AIx-75 fell significantly from the first to the second trimester, then rose again in the third (P<0.001). The two main ethnic groups represented were Caucasian (n?=?229) and Afrocaribbean (n?=?216). There were no significant differences in AP or AIx-75 in any trimester between these two ethnic groups. Conclusions This study is the largest to date of pulse wave analysis in normal pregnancy, the first to report on a subset of women studied longitudinally, and the first to investigate the effect of ethnicity. These data provide the foundation for further investigation into the potential role of this technique in vascular disorders in pregnancy. PMID:19578538

  2. Impaired decidual natural killer cell regulation of vascular remodelling in early human pregnancies with high uterine artery resistance

    PubMed Central

    Fraser, Rupsha; Whitley, Guy StJ; Johnstone, Alan P; Host, Amanda J; Sebire, Neil J; Thilaganathan, Baskaran; Cartwright, Judith E

    2012-01-01

    During human pregnancy, natural killer (NK) cells accumulate in the maternal decidua, but their specific roles remain to be determined. Decidual NK (dNK) cells are present during trophoblast invasion and uterine spiral artery remodelling. These events are crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Remodelling of spiral arteries is impaired in the dangerous pregnancy complication pre-eclampsia. We studied dNK cells isolated from pregnancies at 914 weeks' gestation, screened by uterine artery Doppler ultrasound to determine resistance indices which relate to the extent of spiral artery remodelling. dNK cells were able to promote the invasive behaviour of fetal trophoblast cells, partly through HGF. Cells isolated from pregnancies with higher resistance indices were less able to do this and secreted fewer pro-invasive factors. dNK cells from pregnancies with normal resistance indices could induce apoptotic changes in vascular smooth muscle and endothelial cells in vitro, events of importance in vessel remodelling, partly through Fas signalling. dNK cells isolated from high resistance index pregnancies failed to induce vascular apoptosis and secreted fewer pro-apoptotic factors. We have modelled the cellular interactions at the maternal-fetal interface and provide the first demonstration of a functional role for dNK cells in influencing vascular cells. A potential mechanism contributing to impaired vessel remodelling in pregnancies with a higher uterine artery resistance is presented. These findings may be informative in determining the cellular interactions contributing to the pathology of pregnancy disorders where remodelling is impaired, such as pre-eclampsia. Copyright 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:22653829

  3. Cluster-Randomized Non-Inferiority Trial to Compare Supplement Consumption and Adherence to Different Dosing Regimens for Antenatal Calcium and Iron-Folic Acid Supplementation to Prevent Preeclampsia and Anaemia: Rationale and Design of the Micronutrient Initiative Study

    PubMed Central

    Dickin, Katherine L; Chapleau, Gina M.; Martin, Stephanie L.; Chang, Christopher; Mwanga, Erick O.; Kungu, Jacqueline K.; Stoltzfus, Rebecca J.

    2015-01-01

    Background: To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca) intake, the World Health Organisation (WHO) recommends routine Ca supplementation during antenatal care (ANC). WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA) supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose) regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients. Design and methods: This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill) and IFA (60 mg Fe + 400 g folic acid) taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill) with IFA taken as above. Measurements: Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Statistical analyses: Unit of randomization is the healthcare facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering. Expected public health impact: If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources. Significance for public health Pre-eclampsia is a leading cause of maternal mortality. Based on clinical evidence of significant reduction in risk of pre-eclampsia, the WHO recommends including calcium (Ca) supplementation in antenatal care services in settings with inadequate dietary Ca intakes. A high daily amount of Ca administered in a complex dosing regimen is recommended to maximize efficacy and bioavailability. Factors such as client adherence, motivation, cost and logistical complexities may undermine effectiveness when implemented in public health programs. This cluster-randomized trial will compare Ca supplement consumption between higher and lower-dose regimens delivered through antenatal care in Kenya, integrated with iron-folic acid supplementation. If a lower-dose regimen improves adherence, womens Ca supplement consumption may be comparable to that achieved under a complex, higher-dose regimen. Evidence gained from this trial will guide public health planning for antenatal calcium supplementation programs to maximize benefits through reducing logistical, cost and adherence barriers. PMID:26751372

  4. Different intensities of glycaemic control for pregnant women with pre-existing diabetes

    PubMed Central

    Middleton, Philippa; Crowther, Caroline A; Simmonds, Lucy

    2014-01-01

    Background The optimal glycaemic control target in pregnant women with pre-existing diabetes is unclear, although there is a clear link between high glucose concentrations and adverse birth outcomes. Objectives To assess the effects of different intensities of glycaemic control in pregnant women with pre-existing type 1 or type 2 diabetes. Search methods We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (30 April 2012). Selection criteria We included randomised controlled trials comparing different glycaemic control targets in pregnant women with pre-existing diabetes. Data collection and analysis Two review authors assessed trial eligibility and risk of bias, and extracted data. Main results We included three trials all in women with type 1 diabetes (223 women and babies), and all with a high risk of bias. Two trials compared very tight (3.33 to 5.0 mmol/L fasting blood glucose (FBG)) with tight-moderate (4.45 to 6.38) glycaemic control targets, with one trial of 22 babies reporting no perinatal deaths or serious perinatal morbidity. In the same trial, there were two birth defects in the very tight and none in the tight-moderate group with no significant differences in caesarean section between groups (risk ratio 0.92, 95% confidence interval (CI) 0.49 to 1.73). In these two trials glycaemic control was not significantly different between the very tight and tight-moderate groups by the third trimester, although one trial of 22 women found significantly less maternal hypoglycaemia in the tight-moderate group. In a trial of 60 women and babies comparing tight ( 5.6 mmol/L FBG); moderate (5.6 to 6.7); and loose (6.7 to 8.9) glycaemic control targets, there were two neonatal deaths in the loose and none in the tight or moderate groups. There were significantly fewer women with pre-eclampsia, fewer caesareans and fewer birthweights greater than 90th centile in the combined tight-moderate compared with the loose group. Authors conclusions In a very limited body of evidence, few differences in outcomes were seen between very tight and tight-moderate glycaemic control targets in pregnant women with pre-existing type 1 diabetes, including actual glycaemic control achieved. There is evidence of harm (increased pre-eclampsia, caesareans and birthweights greater than 90th centile) for loose control (FBG above 7 mmol/L). Future trials comparing interventions, rather than glycaemic control targets, may be more feasible particularly for pregnant women with type 2 diabetes. PMID:22895976

  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. PMID:26880019

  6. Lipotoxicity in obese pregnancy and its potential role in adverse pregnancy outcome and obesity in the offspring

    PubMed Central

    Jarvie, Eleanor; Hauguel-de-Mouzon, Sylvie; Nelson, ScottM.; Sattar, Naveed; Catalano, PatrickM.; Freeman, DilysJ.

    2010-01-01

    Increasing maternal obesity is a challenge that has an impact on all aspects of female reproduction. Lean and obese pregnant women gain similar fat mass, but lean women store fat in the lower-body compartment and obese women in central compartments. In the non-pregnant, central storage of fat is associated with adipocyte hypertrophy and represents a failure to adequately store excess fatty acids, resulting in metabolic dysregulation and ectopic fat accumulation (lipotoxicity). Obese pregnancy is associated with exaggerated metabolic adaptation, endothelial dysfunction and increased risk of adverse pregnancy outcome. We hypothesize that the preferential storage of fat in central rather than safer lower-body depots in obese pregnancy leads to lipotoxicity. The combination of excess fatty acids and oxidative stress leads to the production of oxidized lipids, which can be cytotoxic and influence gene expression by acting as ligands for nuclear receptors. Lipid excess and oxidative stress provoke endothelial dysfunction. Oxidized lipids can inhibit trophoblast invasion and influence placental development, lipid metabolism and transport and can also affect fetal developmental pathways. As lipotoxicity has the capability of influencing both maternal endothelial function and placental function, it may link maternal obesity and placentally related adverse pregnancy outcomes such as miscarriage and pre-eclampsia. The combination of excess/altered lipid nutrient supply, suboptimal in utero metabolic environment and alterations in placental gene expression, inflammation and metabolism may also induce obesity in the offspring. PMID:20443782

  7. A step-by-step diagnosis of exclusion in a twin pregnancy with acute respiratory failure due to non-fatal amniotic fluid embolism: a case report

    PubMed Central

    Papaioannou, Vasilios E; Dragoumanis, Christos; Theodorou, Vassiliki; Konstantonis, Dimitrios; Pneumatikos, Ioannis

    2008-01-01

    Introduction Respiratory failure may develop during the later stages of pregnancy and is usually associated with tocolysis or other co-existing conditions such as pneumonia, sepsis, pre-eclampsia or amniotic fluid embolism syndrome. Case presentation We present the case of a 34-year-old healthy woman with a twin pregnancy at 31 weeks and 6 days who experienced acute respiratory failure, a few hours after administration of tocolysis (ritodrine), due to preterm premature rupture of the membranes. Her chest discomfort was significantly ameliorated after the ritodrine infusion was stopped and a Cesarean section was performed 48 hours later under spinal anesthesia; however, 2 hours after surgery she developed severe hypoxemia, hypotension, fever and mild coagulopathy. The patient was intubated and transferred to the intensive care unit where she made a quick and uneventful recovery within 3 days. As there was no evidence for drug- or infection-related thromboembolic or myocardial causes of respiratory failure, we conclude that our patient experienced a rare type of non-fatal amniotic fluid embolism. Conclusion In spite of the lack of solid scientific support for our diagnosis, we conclude that our patient suffered an uncommon type of amniotic fluid embolism syndrome and we believe that this report highlights the need for extreme vigilance and a high index of suspicion for such a diagnosis in any pregnant individual. PMID:18505548

  8. Living kidney donation: outcomes, ethics, and uncertainty.

    PubMed

    Reese, Peter P; Boudville, Neil; Garg, Amit X

    2015-05-16

    Since the first living-donor kidney transplantation in 1954, more than half a million living kidney donations have occurred and research has advanced knowledge about long-term donor outcomes. Donors in developed countries have a similar life expectancy and quality of life as healthy non-donors. Living kidney donation is associated with an increased risk of end-stage renal disease, although this outcome is uncommon (<05% increase in incidence at 15 years). Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. Many donors incur financial expenses due to factors such as lost wages, need for sick days, and travel expenses. Yet, most donors have no regrets about donation. Living kidney donation is practised ethically when informed consent incorporates information about risks, uncertainty about outcomes is acknowledged when it exists, and a donor's risks are proportional to benefits for the donor and recipient. Future research should determine whether outcomes are similar for donors from developing countries and donors with pre-existing conditions such as obesity. PMID:26090646

  9. 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. PMID:12633732

  10. Pregnancy-induced hypertension and congenital hearing loss.

    PubMed

    Wells, M D

    1991-07-01

    It has been suggested that pregnancy-induced hypertension (PIH--pre-eclampsia or toxaemia of pregnancy) may cause sensorineural hearing loss (SNHL) in the offspring. To establish the validity of this concept a clinical survey of the prevalence of congenital hearing loss in relation to PIH in the South East Kent Health District in the United Kingdom over a period of 4 years was undertaken. Description of the temporal bones in a case of PIH is presented. The total number of live births in this period was 12,927, out of which 512 mothers (3.9%) were diagnosed as having PIH. To date 17 cases of bilateral SNHL have been diagnosed in this period (excluding known syndromes, conductive hearing loss and unilateral SNHL). One of the mothers of these children had PIH. It is possible that otologists, in the absence of any obvious cause, have attributed the cause of bilateral SNHL to PIH. Histopathological findings in temporal bones from a 29-week fetus, whose cause of death was severe maternal hypertension, showed massive haemorrhages in the inner ear and middle ear and internal auditory meatus, a frequent finding in temporal bones obtained at autopsy from fetuses and neonates who were born prematurely. This study suggests that PIH per se is unlikely to cause SNHL in the newborn. PMID:1917337

  11. Endothelial progenitor cells, late stent thrombosis and delayed re-endothelialisation.

    PubMed

    Khurana, Rohit; Mayr, Manuel; Hill, Jonathan M

    2008-01-01

    A decade ago, the description of a primitive novel cell type capable of differentiating into cells expressing a mature endothelial cell -phenotype and their capacity to incorporate into regions of active angiogenesis, witnessed the emergence of endothelial progenitor cell (EPC) biology1. The development and maturation of this new concept in vascular biology has resulted in numerous studies describing the role of EPCs in a myriad of disease states where abnormalities of the vasculature have been implicated. Thus, from pre-eclampsia to pulmonary hypertension, erythropoietin administration to erectile dysfunction and cancer to coronary disease the discovery of EPCs has added greatly to the understanding of basic pathophysiology. However, it is in the study of coronary artery -disease where this paradigm shift has had greatest impact, not only regarding basic disease mechanisms, but in the rapid translation of these findings into a clinical context. The purpose of this review is to outline the current understanding of the EPC phenotypes and their relationship with risk factors for coronary disease. In addition, the potential problems of EPC dysfunction and its impact on percutaneous intervention will be appraised together with both pharmacological and stent based strategies to augment EPC -number and function. PMID:19736097

  12. Pregnancy complications of the antiphospholipid syndrome.

    PubMed

    Tincani, A; Balestrieri, G; Danieli, E; Faden, D; Lojacono, A; Acaia, B; Trespidi, L; Ventura, D; Meroni, P L

    2003-02-01

    Starting from their first description, antiphospholipid antibodies (aPL) were associated with repeated miscarriages and fetal losses. Other complications of pregnancy like preterm birth,with pre-eclampsia or severe placental insufficiency were also frequently reported and are included in the current classification criteria of the antiphospholipid syndrome (APS). The titre, the isotype of the antibodies or their antigen specificity may be important in the risk level determination. Some of the difference in the reported results can be explained by the poor standardization achieved in aPL testing or by the not univocal classification of pregnancy complications. The pathogenesis of pregnancy failures is linked to the thrombophilic effect of aPL but also to different mechanisms including a direct effect of antibodies on the throphoblast differentiation and invasion. The study of experimental animal models provided sound evidence of the pathogenic role of aPL both in lupus prone and naive mice. The definition of APS as a condition linked to high obstetric risk and the application of an effective therapy have completely changed the prognosis of pregnancy in these patients. In fact, despite the high number of complications and preterm delivery, today a successful outcome can be achieved in the large majority of the cases. PMID:12765468

  13. 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 Tanahashis 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

  14. Biological functions of thyroid hormone in placenta.

    PubMed

    Chen, Cheng-Yi; Chen, Chie-Pein; Lin, Kwang-Huei

    2015-01-01

    The thyroid hormone, 3,3,5-triiodo-L-thyronine (T3), modulates several physiological processes, including cellular growth, differentiation, metabolism, inflammation and proliferation, via interactions with thyroid hormone response elements (TREs) in the regulatory regions of target genes. Infection and inflammation are critical processes in placental development and pregnancy-related diseases. In particular, infection is the leading cause of neonatal mortality and morbidity worldwide. However, to date, no successful approach has been developed for the effective diagnosis of infection in preterm infants. Pre-eclampsia (PE) is a serious disorder that adversely affects ~5% of human pregnancies. Recent studies identified a multiprotein complex, the inflammasome, including the Nod-like receptor (NLR) family of cytosolic pattern recognition receptors, the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, which plays a vital role in the placenta. The thyroid hormone modulates inflammation processes and is additionally implicated in placental development and disease. Therefore, elucidation of thyroid hormone receptor-regulated inflammation-related molecules, and their underlying mechanisms in placenta, should facilitate the identification of novel predictive and therapeutic targets for placental disorders. This review provides a detailed summary of current knowledge with respect to identification of useful biomarkers and their physiological significance in placenta. PMID:25690032

  15. Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

    PubMed Central

    Swellam, Menha; Samy, Nervana; Abdl Wahab, Susan; Ibrahim, Mohamed Saeed

    2009-01-01

    Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations. Materials and methods: We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays. Results: Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P < 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy nonpregnant vs PE or normotensive pregnant vs PE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity. Conclusions: Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE. PMID:19597295

  16. Stress Questionnaires and Stress Biomarkers during Pregnancy

    PubMed Central

    Savitz, David A.; Dole, Nancy; Herring, Amy H.; Thorp, John M.

    2009-01-01

    Abstract Objective Both self-reported indicators of stress and hormones such as cortisol and corticotrophin-releasing hormone (CRH) have been examined in relation to preterm birth. Although these hormones have been interpreted as biomarkers of stress, it is unclear whether psychosocial measures are empirically associated with biomarkers of stress in pregnant women. Methods We analyzed data from 1,587 North Carolina pregnant women enrolled in the Pregnancy, Infection, and Nutrition study during 20002004 who provided at least one saliva sample for cortisol measurement or blood samples for CRH at 1419 and 2429 weeks' gestation. Cortisol measures were limited to those taken between 8 and 10 a.m. Perceived stress, state-trait anxiety, coping style, life events, social support, and pregnancy-specific anxiety were measured by questionnaires and interviews. Spearman correlations and multiple regressions were used to describe the relationship among the measures of stress. Results No correlations larger than r?=?0.15 were seen between reported psychosocial measures and cortisol or CRH. Women with demographic characteristics associated with poor pregnancy outcomes (unmarried, African-American, young, low pre-pregnancy body mass index) reported higher levels of stress but did not consistently have higher levels of stress hormones. Pre-eclampsia was associated with higher CRH, but not with higher cortisol. Conclusions The relationship between measurements of reported stress and biomarkers is not straightforward in large epidemiological studies of pregnancy. For online Supplementary Material, see www.liebertonline.com. PMID:19757520

  17. Blood Pressure in Third Trimester of Pregnancy.

    PubMed

    Sufrin, S; Nessa, A; Islam, M T; Khatun, A A; Husain, M F; Khatun, N; Wahed, F; Das, R K; Zannat, M R

    2016-01-01

    Pregnancy is a great stressful physiological condition in women during their reproductive period. During pregnancy several hemodynamic, biochemical and hematological modifications occur as a part of the physiological adaptation of the body. Changes in blood pressure occur in third trimester of pregnancy, which may be associated with increased maternal and infant mortality and morbidity. This cross-sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, from July 2013 to June 2014. Study subjects were selected by following purposive sampling procedure and the protocol of this study was approved by Institutional Ethics Committee (IEC) of Mymensingh. This study enrolled 100 pregnant women of third trimester of pregnancy and 100 aged matched non-pregnant women from Mymensingh district. Mean systolic blood pressure in study group were 124.8±14.51mm of Hg and in control group were 106.50±10.67mm of Hg, which was statistically increased. Diastolic blood pressure in study group was 83.00±13.37mm of Hg and in control group 71.05±7.12mm of Hg, which was also statistically significant. The changes in blood pressure in third trimester of pregnancy is the major concern of developing the risk of pre-eclampsia & eclampsia, and increased prevalence of IUGR, pre-maturity and perinatal mortality. This study reveals significant changes of blood pressure during third trimester of pregnancy. PMID:26931243

  18. Urinary tract infection (UTI) in newborns: risk factors, identification and prevention of consequences.

    PubMed

    Milas, Vesna; Puselji?, Silvija; Stimac, Maja; Dobri?, Hana; Luki?, Gordana

    2013-09-01

    The aim of the study is identification of urinary tract infections (UTI) and urinary tract anomalies (UTA) already in the perinatal period. The authors attempted to prevent serious consequences of the above conditions in the examined children. Family history data, certain conditions in pregnancy and appertaining symptoms in children were elaborated to specify selective distinctive criteria for children at risk. Newborns (1200) were selected for potential existence of a UTI. All the examined newborns underwent a urinalysis. Those with significant bacteriuria were taken urine specimens, C-reactive protein (RVP), Complete Blood Count (CBC) and bilirubin. The newborns with a UTI and a suspected UTA were sent to ultrasound examination, direct radio nuclide cystography and Tc99m MAG3 dynamic scanning. The frequency of a UTI in the perinatal period amounted to 4.5%. A UTA was found in 29.6% of the examinees. The infection was more likely to appear among newborns with a UTA in their families, a UTI, pre-eclampsia and a febrile infection in mother, intrauterine growth retardation, premature rupture of membranes (RVP), umbilical cord strangulation, jaundice, cyanosis, breathing difficulties, seizures and asphyxia. PMID:24308231

  19. Regulation of MT1-MMP/MMP-2/TIMP-2 axis in human placenta

    PubMed Central

    Vincent, Zo L; Mitchell, Murray D; Ponnampalam, Anna P

    2015-01-01

    Matrix metalloproteinases (MMPs) and specific endogenous tissue inhibitors of metalloproteinases (TIMPs) mediate rupture of the fetal membranes in both physiological and pathological conditions. MMPs and TIMPs are subject to regulation by DNA methylation in human malignancies and pre-eclampsia. To determine if membrane type 1 MMP (MT1-MMP), MMP2, and TIMP2 are regulated by DNA methylation in human placentas, we employed an in vitro model where human placental tissues were collected at term gestation and cultured with methylation inhibiting agent 5-AZA-2?-deoxycytidine (AZA) and lipopolysaccharide. The results suggest that DNA methylation is not directly involved in the regulation of MT1-MMP in placental tissue; however, remodeling of chromatin by a pharmacologic agent such as AZA potentiates an infection-related increase in MT1-MMP. MT1-MMP is a powerful activator of MMP2 and this action, coupled with either no change or a decrease in TIMP2 concentrations, favors a gelatinolytic state leading to extracellular matrix degradation, which could predispose fetal membranes to rupture prematurely during inflammation. PMID:26491367

  20. Utility of proteomics in obstetric disorders: a review

    PubMed Central

    Hernndez-Nez, Jnathan; Valds-Yong, Magel

    2015-01-01

    The study of proteomics could explain many aspects of obstetric disorders. We undertook this review with the aim of assessing the utility of proteomics in the specialty of obstetrics. We searched the electronic databases of MEDLINE, EBSCOhost, BVS Bireme, and SciELO, using various search terms with the assistance of a librarian. We considered cohort studies, case-control studies, case series, and systematic review articles published until October 2014 in the English or Spanish language, and evaluated their quality and the internal validity of the evidence provided. Two reviewers extracted the data independently, then both researchers simultaneously revised the data later, to arrive at a consensus. The search retrieved 1,158 papers, of which 965 were excluded for being duplicates, not relevant, or unrelated studies. A further 86 papers were excluded for being guidelines, protocols, or case reports, along with another 64 that did not contain relevant information, leaving 43 studies for inclusion. Many of these studies showed the utility of proteomic techniques for prediction, pathophysiology, diagnosis, management, monitoring, and prognosis of pre-eclampsia, perinatal infection, premature rupture of membranes, preterm birth, intrauterine growth restriction, and ectopic pregnancy. Proteomic techniques have enormous clinical significance and constitute an invaluable weapon in the management of obstetric disorders that increase maternal and perinatal morbidity and mortality. PMID:25926758

  1. IFPA Award in Placentology Lecture: Biology of the placental syncytiotrophoblast--myths and facts.

    PubMed

    Huppertz, B

    2010-03-01

    About 15 years ago apoptosis was attributed a role in the development of the human placenta. Since then an increasing number of publications has shown that programmed cell death plays an essential role in placental growth and differentiation, especially in the villous trophoblast. During the last ten years a concept was established linking the progress of apoptosis to differentiation of cytotrophoblasts and syncytiotrophoblast. Thus, development and maintenance of the syncytiotrophoblast depends on the precise orchestration of different processes and stages of the apoptosis cascade. This review focuses on the maintenance and growth of the syncytiotrophoblast as well as the deportation of trophoblast material into the maternal circulation. Nuclear morphology is related to transcriptional activity, RNA protection and storage strategies are discussed and the differences between syncytial expression rates of RNA and protein are highlighted. Moreover, deportation of trophoblast fragments is related to the relevant morphological structures (syncytial knots) and to their effects on the maternal system. Finally, different modes of release of trophoblast fragments such as apoptotic, aponecrotic and necrotic are discussed as being responsible for the maternal inflammatory response during pre-eclampsia. PMID:20042237

  2. Pregnancy Outcomes in Women with Chronic Kidney Disease: A Systematic Review

    PubMed Central

    Reitsma, Angela; Dominic, Arunmozhi; McDonald, Sarah; Thabane, Lehana; Akl, Elie A.; Hladunewich, Michelle; Akbari, Ayub; Joseph, Geena; Sia, Winnie; Iansavichus, Arthur V.; Garg, Amit X.

    2011-01-01

    Summary Background and objectives Pregnant women with chronic kidney disease (CKD) are at risk of adverse maternal and fetal outcomes. We conducted a systematic review of observational studies that described this risk. Design, setting, participants, & measurements We searched several databases from their date of inception through June 2010 for eligible articles published in any language. We included any study that reported maternal or fetal outcomes in at least five pregnant women in each group with or without CKD. We excluded pregnant women with a history of transplantation or maintenance dialysis. Results We identified 13 studies. Adverse maternal events including gestational hypertension, pre-eclampsia, eclampsia, and maternal mortality were reported in 12 studies. There were 312 adverse maternal events among 2682 pregnancies in women with CKD (weighted average of 11.5%) compared with 500 events in 26,149 pregnancies in normal healthy women (weighted average of 2%). One or more adverse fetal outcomes such as premature births, intrauterine growth restriction, small for gestational age, neonatal mortality, stillbirths, and low birth weight were reported in nine of the included studies. Overall, the risk of developing an adverse fetal outcome was at least two times higher among women with CKD compared with those without. Conclusions This review summarizes current available evidence to guide physicians in their decision-making, advice, and care for pregnant women with CKD. Additional studies are needed to better characterize the risks. PMID:21940842

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

    PubMed Central

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

    2015-01-01

    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. PMID:25954092

  4. Low birth weight incidence in Lundu, Sarawak.

    PubMed

    Yadav, H

    1994-06-01

    The overall mean birth weight of the total deliveries (1986-1988) in Lundu Hospital was 2.96 kg. The mean birth weight for the male babies was 2.94 kg. The Chinese babies had a significantly higher mean birth weight (3.12 kg) than the other ethnic groups (p < 0.05). The overall incidence of low birth weight (LBW) in this study was 11.84 per cent. The Chinese again had a lower incidence of LBW of 6.73 per cent compared to Ibans who had the highest incidence of LBW, 13.59 per cent, with the Bidayuhs 12.97 per cent and Malays, 12.45 per cent. It was also noticed that of the 14.9 per cent preterm deliveries, 37.5 per cent were LBW. The very young mothers (15-19 years) and older mothers (> 40 years) seem to have a higher incidence of LBW. Mothers who had medical conditions like anaemia, hypertension, pre-eclampsia also had a higher incidence of LBW when compared to mothers who did not have a medical condition. Special emphasis should be given to mothers who have medical conditions, and to very young and very old mothers during antenatal care, to prevent incidence of LBW. PMID:8090096

  5. New insights into the function of Cullin 3 in trophoblast invasion and migration.

    PubMed

    Zhang, Qian; Yu, Song; Huang, Xing; Tan, Yi; Zhu, Cheng; Wang, Yan-Ling; Wang, Haibin; Lin, Hai-Yan; Fu, Jiejun; Wang, Hongmei

    2015-08-01

    Cullin 3 (CUL3), a scaffold protein, assembles a large number of ubiquitin ligase complexes, similar to Skp1-Cullin 1-F-box protein complex. Several genetic models have shown that CUL3 is crucial for early embryonic development. Nevertheless, the role of CUL3 in human trophoblast function remains unclear. In this study, immunostaining revealed that CUL3 was strongly expressed in the villous cytotrophoblasts, the trophoblast column, and the invasive extravillous trophoblasts. Silencing CUL3 significantly inhibited the outgrowth of villous explant ex vivo and decreased invasion and migration of trophoblast HTR8/SVneo cells. Furthermore, CUL3 siRNA decreased pro-MMP9 activity and increased the levels of TIMP1 and 2. We also found that the level of CUL3 in the placental villi from pre-eclamptic patients was significantly lower as compared to that from their gestational age-matched controls. Moreover, in the lentiviral-mediated placenta-specific CUL3 knockdown mice, lack of CUL3 resulted in less invasive trophoblast cells in the maternal decidua. Taken together, these results suggest an essential role for CUL3 in the invasion and migration of trophoblast cells, and dysregulation of its expression may be associated with the onset of pre-eclampsia. PMID:26021998

  6. Impact of dose-finding studies on administration of oxytocin during caesarean section in the UK.

    PubMed

    West, R; West, S; Simons, R; McGlennan, A

    2013-10-01

    Debate continues over the dose and methods of administration of oxytocin for the prevention of haemorrhage during caesarean section. We surveyed 206 lead obstetric anaesthetists in the UK to determine standard practice in their unit as well as any differences in practice for high-risk cases. There were 150 responses (72.9% response rate). A total of 149 units use oxytocin. The majority use an initial 5-IU dose, whilst a small proportion (8; 5.3%) administer a dose < 5 IU for elective caesarean section. The administration of a 10-IU dose has ceased altogether. There is a broad range of administration methods, particularly with infusions. Forty (26.8%) respondents give a different oxytocin regimen following caesarean section in patients with severe pre-eclampsia, 72 (48.3%) in those with cardiac disease of New York Heart Association class 1-2, and 100 (66.7%) with class 3-4. In conclusion, there is a trend towards the use of lower doses of oxytocin in caesarean section, but there are still wide variations in detail. We suggest that there is a need for a national protocol to standardise oxytocin administration. PMID:23944710

  7. New frontiers in heart hypertrophy during pregnancy

    PubMed Central

    Li, Jingyuan; Umar, Soban; Amjedi, Marjan; Iorga, Andrea; Sharma, Salil; Nadadur, Rangarajan D; Regitz-Zagrosek, Vera; Eghbali, Mansoureh

    2012-01-01

    During Pregnancy, heart develops physiological left ventricular hypertrophy as a result of the natural volume overload. Previously we have characterized the molecular and functional signature of heart hypertrophy during pregnancy. Cardiac hypertrophy during pregnancy is a complex process that involves many changes including in the signalling pathways, composition of extracellular matrix as well as the levels of sex hormones. This review summarises the recent advances and the new frontiers in the context of heart hypertrophy during pregnancy. In particular we focus on structural and extracellular matrix remodelling as well as signalling pathways in pregnancy-induced physiological heart hypertrophy. Emerging evidence shows that various microRNAs modulate key components of hypertrophy, therefore the role of microRNAs in the regulation of gene expression in pregnancy induced hypertrophy is also discussed. We also review the role of ubiquitin proteasome system, the major machinery for the degradation of damaged and misfolded proteins, in heart hypertrophy. The role of sex hormones in particular estrogen in cardiac remodeling during pregnancy is also discussed. We also review pregnancy-induced cardiovascular complications such as peripartum cardiomyopathy and pre-eclampsia and how the knowledge from the animal studies may help us to develop new therapeutic strategies for better treatment of cardiovascular diseases during pregnancy. Special emphasis has to be given to the guidelines on disease management in pregnancy. PMID:22937489

  8. The nuclear bile acid receptor FXR controls the liver derived tumor suppressor histidine-rich glycoprotein.

    PubMed

    Deuschle, Ulrich; Birkel, Manfred; Hambruch, Eva; Hornberger, Martin; Kinzel, Olaf; Perovi?-Ottstadt, Sanja; Schulz, Andreas; Hahn, Ulrike; Burnet, Michael; Kremoser, Claus

    2015-06-01

    The nuclear bile acid receptor Farnesoid X receptor (FXR) is strongly expressed in liver and intestine, controls bile acid and lipid homeostasis and exerts tumor-protective functions in liver and intestine. Histidine-rich glycoprotein (HRG) is an abundant plasma protein produced by the liver with the proposed function as a pattern recognition molecule involved in the clearance of immune complexes, necrotic cells and pathogens, the modulation of angiogenesis, the normalization of deranged endothelial vessel structure in tumors and tumor suppression. FXR recognition sequences were identified within a human HRG promoter fragment that mediated FXR/FXR-agonist dependent reporter gene activity in vitro. We show that HRG is a novel transcriptional target gene of FXR in human hepatoma cells, human upcyte primary hepatocytes and 3D human liver microtissues in vitro and in mouse liver in vivo. Prolonged administration of the potent nonsteroidal FXR agonist PX20606 increases HRG levels in mouse plasma. Finally, daily oral administration of this FXR agonist for seven days resulted in a significant increase of HRG levels in the plasma of healthy human male volunteers during a clinical Phase I safety study. HRG might serve as a surrogate marker indicative of liver-specific FXR activation in future human clinical studies. Furthermore, potent FXR agonists might be beneficial in serious health conditions where HRG is reduced, for example, in hepatocellular carcinoma but also other solid cancers, liver failure, sepsis and pre-eclampsia. PMID:25363753

  9. The role of macrophages in utero-placental interactions during normal and pathological pregnancy.

    PubMed

    Renaud, Stephen J; Graham, Charles H

    2008-01-01

    The intimate association between maternal and placental tissues elicits an interesting immunological paradox. Placental tissue contains paternal antigens, but under normal circumstances the semi-allogeneic fetus and placenta are not attacked by the maternal immune system. Interestingly, this tolerance to fetal antigens occurs in the presence of a large number of maternal leukocytes, almost all of which are members of the innate immune system. Macrophages are one of the most abundant leukocytes in the decidua and their numbers remain constant throughout gestation. They are recruited to the decidua by both stromal cells and trophoblast cells, where they adopt a specialized phenotype that may assist in various aspects of decidual homeostasis, placental development, and tolerance to the semi-allogeneic trophoblast. Aberrant behavior of these macrophages can affect trophoblast function and placental development, potentially leading to a spectrum of adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth restriction or demise. This review will focus on the phenotype and putative functions of decidual macrophages in normal pregnancy, and how abnormal activation of these cells can affect various aspects of placental development. PMID:18716937

  10. 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. PMID:21929634

  11. 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. PMID:23445841

  12. Micronutrients and pregnancy; effect of supplementation on pregnancy and pregnancy outcomes: a systematic review

    PubMed Central

    2013-01-01

    Introduction Every year more than 20 million infants are born with low birth weight worldwide. About 3.6 million infants die during the neonatal period. More than one third of child deaths are thought to be attributable to maternal and child under nutrition. Objectives To systematically review the effect of supplementing various combinations and types of micronutrients on the course and outcomes of pregnancy. Methods Electronic search of Medline, Pub Med, Health Internetwork access to Research Initiative, and Google Scholar databases was conducted. Outcomes of interest were birth weight, low birth weight, small size for gestational age, prenatal mortality and neonatal mortality. After exclusion of irrelevant /incomplete ones, 17 out of 115 articles were considered for the final analysis. Findings Majority of the articles reviewed favored the supplementation of micronutrients to pregnant mother. Some studies suggested calcium supplementation is associated with a significant protective benefit in the prevention of pre-eclampsia. The remaining articles reviewed, showed significant benefit of Multiple Micronutrients supplementation during pregnancy in reducing low birth weight, small for Gestational Age births as compared to the usual iron-folate supplements. Conclusions Supplying micronutrients, mainly multiple micronutrients have beneficial effect in reducing the risk of low birth weight and other complications. Further studies at various combination and doses of micronutrient supplements are recommended. PMID:23368953

  13. Magnesium in disease

    PubMed Central

    Wanner, Christoph

    2012-01-01

    Although the following text will focus on magnesium in disease, its role in healthy subjects during physical exercise when used as a supplement to enhance performance is also noteworthy. Low serum magnesium levels are associated with metabolic syndrome, Type 2 diabetes mellitus (T2DM) and hypertension; consequently, some individuals benefit from magnesium supplementation: increasing magnesium consumption appears to prevent high blood pressure, and higher serum magnesium levels are associated with a lower risk of developing a metabolic syndrome. There are, however, conflicting study results regarding magnesium administration with myocardial infarction with and without reperfusion therapy. There was a long controversy as to whether or not magnesium should be given as a first-line medication. As the most recent trials have not shown any difference in outcome, intravenous magnesium cannot be recommended in patients with myocardial infarction today. However, magnesium has its indication in patients with torsade de pointes and has been given successfully to patients with digoxin-induced arrhythmia or life-threatening ventricular arrhythmias. Magnesium sulphate as an intravenous infusion also has an important established therapeutic role in pregnant women with pre-eclampsia as it decreases the risk of eclamptic seizures by half compared with placebo. PMID:26069818

  14. 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. PMID:24996894

  15. Diffuse multifocal chorangiomatosis of the placenta with multiple intestinal stenosis of the fetus: combination of rare causes for nonimmune hydrops fetalis.

    PubMed

    Chopra, Anita; Iyer, Venkateswaran K; Thapar, Rajeev; Singh, Neeta

    2006-10-01

    Non-immune causes of hydrops fetalis are rare but frequently fatal. Identification of the cause for hydrops fetalis is essential to institute therapy. Chorangiomatosis and intestinal stenosis have not been previously reported as aetiological factors for the development of hydrops. We report a fetus born with hydrops associated with both of these conditions. A 1575 gms preterm neonate was born to a multigravida at 31 weeks of gestation. Emergency caesarean section was performed after detection of hydrops by prenatal ultrasonography. Baby had generalized edema at birth and died after 3 days due to progressive heart failure. At autopsy there was generalized edema and effusions. There were multiple stenotic segments in the intestine. Placenta showed numerous chorangiomas varying from 0.2 to 3 cm in diameter, hence diagnosed as diffuse multifocal chorangiomatosis. Examination of the placenta at neonatal autopsy is an essential part of assessment for hydrops fetalis. Chorangiomatosis is a rare and under reported condition which can cause prematurity, intrauterine growth retardation, pre-eclampsia and rarely hydrops fetalis. PMID:17183871

  16. 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. PMID:21115197

  17. 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. PMID:27017177

  18. Antiphospholipid Syndrome during pregnancy: the state of the art

    PubMed Central

    Di Prima, Fosca A. F.; Valenti, Oriana; Hyseni, Entela; Giorgio, Elsa; Faraci, Marianna; Renda, Eliana; De Domenico, Roberta; Monte, Santo

    2011-01-01

    Obstetric complications are the hallmark of antiphospholipid syndrome. Recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, pre-eclampsia/eclampsia, HELLP syndrome, arterial or venous thrombosis and placental insufficiency are the most severe APS-related complication for pregnant women. Antiphospholipid antibodies promote activation of endothelial cells, monocytes and platelets, causing an overproduction of tissue factor and thromboxane A2. Complement activation might have a central pathogenetic role. These factors, associated with the typical changes in the hemostatic system during normal pregnancy, result in a hypercoagulable state. This is responsible of thrombosis that is presumed to provoke many of the pregnancy complications associated with APS. Obstetric care is based on combined medical-obstetric high-risk management and treatment with the association between aspirin and heparin. This review aims to deter- mine the current state of the art of APS by investigating the knowledge achievements of recent years, to provide the most appropriate diagnostic and therapeutic management for pregnant women suffering from this syndrome. PMID:22439075

  19. Autonomic denervation: A new aetiological framework for clinical obstetrics and gynaecology.

    PubMed

    Quinn, M J

    2016-04-01

    The hypothesis is that many clinical conditions in obstetrics and gynaecology result from the diverse and varying consequences of injuries to pelvic autonomic nerves. These injuries result from difficult first labours, persistent physical efforts during defaecation, and, medical and surgical techniques for evacuation of the uterus. The neuro-immunohistochemical "signatures" of these injuries are variations of the Dixon-Robertson-Brosens (DRB) lesion in preeclampsia, where there is hyperplasia of the tunica intima and media of arterioles with narrowing of the lumen of the vessel. In stage IV, nulliparous "endometriosis" (and other gynaecological conditions) there are circumferential layers of abnormal nerves around a narrowed arteriole, whereas in early-onset preeclampsia (and other obstetric conditions) there are similar histological findings in uterine arterioles but there is no sign of injured nerves. During pregnancy there is elongation of blood vessels but no elongation of injured nerves leading to relative denervation of the myometrium. These lesions are detectable in most of the "great" obstetric syndromes, and, across the spectrum of gynaecological syndromes. They provide a coherent explanation of the natural history and clinical presentations of many of these syndromes. Clinical features vary with the site, nature and extent of the injury; a minor injury may enable pregnancy though it is complicated by late-onset pre-eclampsia whereas a more extensive injury may prevent pregnancy and present with chronic pelvic pain with, or without, endometriosis. PMID:26968908

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

    PubMed

    Weinert, Letcia 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. PMID:24748216

  1. Co-evolution of NK receptors and HLA ligands in humans is driven by reproduction.

    PubMed

    Moffett, Ashley; Colucci, Francesco

    2015-09-01

    Allogeneic individuals co-exist during pregnancy in eutherian mammals. Maternal and fetal cells intermingle at the site of placental attachment in the uterus, where the arteries are remodeled to supply the fetus with oxygen and nutrients. This access by placental cells to the maternal supply line determines the growth and birth weight of the baby and is subject to stabilizing selection. Invading placental trophoblast cells express human leukocyte antigen class I ligands (HLA-E, HLA-G, and HLA-C) for receptors on maternal uterine natural killer (NK) and myelomonocytic cells, CD94/NKG2, leukocyte immunoglobulin-like receptor (LILR), and killer immunoglobulin receptor (KIR). Of these, only the KIR/HLA-C system is highly polymorphic. Different combinations of maternal KIR and fetal HLA-C variants are correlated with low birth weight and pre-eclampsia or high birth weight and obstructed labor, the two extremes of the obstetric dilemma. This situation has arisen because of the evolution of bipedalism and subsequently, in the last million years, larger brains. At this point, the human system began to reach a balance between KIR A and KIR B haplotypes and C1 and C2 epitopes of HLA-C alleles that reflects a functional compromise between the competing demands of immunity and reproduction. PMID:26284484

  2. Amniotic fluid phospholipid profile determined by two-dimensional thin-layer chromatography as index of fetal lung maturation.

    PubMed Central

    Whittle, M J; Wilson, A I; Whitfield, C R; Paton, R D; Logan, R W

    1981-01-01

    A phospholipid profile, the main features of which were the lecithin/sphingomyelin (L/S) ratio and the presence or absence of phosphatidylglycerol (PG), was determined in amniotic fluid from 188 patients. There was a mature profile (L/S ratio of at least 2 . 0 and detectable PG) in 145 patients, including seven insulin-dependent diabetics, and noe of their babies developed respiratory distress syndrome (RDS). The L/S ratio was less than 2 . 0 and PG absent in 12 patients, nine of whose babies developed RDS, whereas only three small babies (delivered between 28 and 35 weeks because of fulminant pre-eclampsia or severe abruptio placentae) out of 31 developed RDS when the L/S ratio was less than 2 . 0 but PG was present. When amniotic fluid was collected from the vagina only one out of 69 babies developed RDS when PG was present (regardless of the L/S ratio), while all of seven babies developed RDS when PG was absent. It is concluded that the amniotic fluid phospholipid profile, particularly the presence or absence of PG, gives an accurate assessment of fetal lung maturation. The profile may prove a useful adjunct to the management of high-risk pregnancies, especially after premature membrane rupture and perhaps also when the mother is diabetic. PMID:6780058

  3. The placenta: a multifaceted, transient organ.

    PubMed

    Burton, Graham J; Fowden, Abigail L

    2015-03-01

    The placenta is arguably the most important organ of the body, but paradoxically the most poorly understood. During its transient existence, it performs actions that are later taken on by diverse separate organs, including the lungs, liver, gut, kidneys and endocrine glands. Its principal function is to supply the fetus, and in particular, the fetal brain, with oxygen and nutrients. The placenta is structurally adapted to achieve this, possessing a large surface area for exchange and a thin interhaemal membrane separating the maternal and fetal circulations. In addition, it adopts other strategies that are key to facilitating transfer, including remodelling of the maternal uterine arteries that supply the placenta to ensure optimal perfusion. Furthermore, placental hormones have profound effects on maternal metabolism, initially building up her energy reserves and then releasing these to support fetal growth in later pregnancy and lactation post-natally. Bipedalism has posed unique haemodynamic challenges to the placental circulation, as pressure applied to the vena cava by the pregnant uterus may compromise venous return to the heart. These challenges, along with the immune interactions involved in maternal arterial remodelling, may explain complications of pregnancy that are almost unique to the human, including pre-eclampsia. Such complications may represent a trade-off against the provision for a large fetal brain. PMID:25602070

  4. Large-for-dates babies at the age of four years: health, handicap and developmental status.

    PubMed

    Ounsted, M K; Moar, V A; Scott, A

    1983-12-01

    236 Average-for-dates (AFD) and 212 large-for-dates (LFD) children were personally examined at birth, and seen thereafter at regular intervals up to 4 yr, when a thorough assessment was made. No differences were found in the prevalence of handicap, health problems, speech and hearing defects, impaired vision or squint; and abnormalities of gross and fine-motor movements were equally low in both groups. At 4 yr the mean scores for five sectors of development were slightly higher in the LFD group, and the difference in total scores was significant; but when adjustment was made for sex and social class the difference became insignificant. Within group analyses of 16 variables and their effects on developmental scores showed no associations in either group according to maternal weight, height and siblings birthweight; hypertension, pre-eclampsia or bleeding during pregnancy; asphyxia or injury at birth. Within each group the net effect of eight factors was assessed; adjustment being made for the other seven variables. In the AFD group significant differences in total scores were found according to sex, social class, smoking, and method of infant feeding. In the LFD group social class and method of delivery made a significant contribution to total scores. PMID:6667653

  5. Non?cardiac complications during pregnancy in women with isolated congenital pulmonary valvar stenosis

    PubMed Central

    Drenthen, W; Pieper, P G; Roos?Hesselink, J W; Schmidt, A C M; Mulder, B J M; van Dijk, A P J; Vliegen, H W; Sollie, K M; Voors, A A; Ebels, T; van Veldhuisen, D J

    2006-01-01

    Background Information on the outcome of pregnancy in patients with pulmonary valvar stenosis is scarce, mostly limited to cardiac complications observed during pregnancy. Objectives To investigate the magnitude and determinants of non?cardiac and fetal risks during pregnancy of women with isolated pulmonary valvar stenosis. Methods Using the nationwide registry (CONgenital CORvitia), 106 women with (un?)corrected pulmonary valvar stenosis receiving care in six tertiary medical centres in The Netherlands were included. A total of 51 women had 108 pregnancies, including 21 (19%) miscarriages and 6 elective abortions. Results In the 81 completed (>20?weeks of gestation) pregnancies, we observed a high number of hypertension?related disorders (n?=?12, 15%, including pre?eclampsia (n?=?4) and eclampsia (n?=?2)), premature deliveries (n?=?14, 17%, including one twin) and thromboembolic events (n?=?3, 3.7%). Furthermore, recurrence of congenital heart defects in the offspring was detected in three children (3.7%, pulmonary valvar stenosis (n?=?2) and complete transposition of the great arteries in combination with anencephaly). In addition to the intrauterine fetal demise of the transposition child, three other children died shortly after birth owing to immaturity, hydrocephalus combined with prematurity and meningitis (overall offspring mortality, 4.8%). Conclusion In this largest report on pregnancy in women with (un?) corrected isolated pulmonary valvar stenosis, an excessive number of (serious) non?cardiac complications and mortality were observed in the offspring. PMID:16818485

  6. Pregnancy Weight Gain Limitation by a Supervised Nutritional Program Influences Placental NF-?B/IKK Complex Expression and Oxidative Stress

    PubMed Central

    Zern, Hugo Mendieta; Flores, Alejandro Parada; Chvez, Araceli Amaya; Alans, Adriana Garduo; Ferreyra, Mara del Carmen Coln; Bentez, Jonnathan Guadalupe Santilln; Castaeda, Violeta Sara Morales; Garca, Ma. Victoria Domnguez

    2013-01-01

    Objective Nuclear factor kappa B (NF-?B) 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-?B, 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-?B 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-?B 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-?B/IKK complex expression and oxidative stress reactions in the placenta. PMID:23772281

  7. Fetalmaternal interface impedance parallels local NADPH oxidase related superoxide production

    PubMed Central

    Guedes-Martins, L.; Silva, E.; Gaio, A.R.; Saraiva, J.; Soares, A.I.; Afonso, J.; Macedo, F.; Almeida, H.

    2015-01-01

    Blood flow assessment employing Doppler techniques is a useful procedure in pregnancy evaluation, as it may predict pregnancy disorders coursing with increased uterine vascular impedance, as pre-eclampsia. While the local causes are unknown, emphasis has been put on reactive oxygen species (ROS) excessive production. As NADPH oxidase (NOX) is a ROS generator, it is hypothesized that combining Doppler assessment with NOX activity might provide useful knowledge on placental bed disorders underlying mechanisms. A prospective longitudinal study was performed in 19 normal course, singleton pregnancies. Fetal aortic isthmus (AoI) and maternal uterine arteries (UtA) pulsatility index (PI) were recorded at two time points: 2022 and 4041 weeks, just before elective Cesarean section. In addition, placenta and placental bed biopsies were performed immediately after fetal extraction. NOX activity was evaluated using a dihydroethidium-based fluorescence method and associations to PI values were studied with Spearman correlations. A clustering of pregnancies coursing with higher and lower PI values was shown, which correlated strongly with placental bed NOX activity, but less consistently with placental tissue. The study provides evidence favoring that placental bed NOX activity parallels UtA PI enhancement and suggests that an excess in oxidation underlies the development of pregnancy disorders coursing with enhanced UtA impedance. PMID:25912167

  8. Clinical profile and predisposing factors of cerebral palsy.

    PubMed

    Anwar, S; Chowdhury, J; Khatun, M; Mollah, A H; Begum, H A; Rahman, Z; Nahar, N

    2006-07-01

    This was an analysis of one hundred ten children with cerebral palsy (CP) attending at the Child Development & Neurology Care Center of Dhaka Medical College Hospital during January 2002 to December 2003. These children were observed to study their clinical profile, etiological factors and associated problems. The mean age of these children was 2.9 +/- 2.9 years, mostly being males (n=79, 71.8%). Most of the families of these children belonged to poorer socioeconomic strata. Spastic diplegia constituted the predominant group (34.5 per cent), followed by spastic quadriplegia (25.5 per cent). Dyskinetic CP was present in 15.5 percent of the cases. Hypotonic CP constituted a significant proportion of cases. Delayed Motor Function was observed in all 110 cases, delayed speech was complained in 67.3% cases and impaired hearing was identified in 26.8% CP children. Mothers of 43.6% CP cases reported that they had prolonged labour during delivery and almost one third (29.1%) had suffered from pre-eclampsia or eclampsia. Majority (53.6%) of the CP cases were reported to have had perinatal asphyxia. Comprehensive assessment and early management of these problems are emphasized, which can minimize the extent of disabilities. By proper perinatal care, CP can be prevented. PMID:16878093

  9. Posterior reversible encephalopathy syndrome in a woman with focal segmental glomerulosclerosis

    PubMed Central

    Chowdhary, Mudit; Kabbani, Ahmad A; Tobey, Devon; Hope, Thomas D

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare syndrome characterized by reversible vasogenic edema in the posterior hemispheres. PRES is most often attributed to primary hypertension, pre-eclampsia, and neurotoxicity secondary to immunosuppressants such as cyclosporine. Renal disease is an infrequent cause of PRES with a majority of cases occurring in adults with complete renal failure or in pediatric cases with underlying renal parenchymal disease and concurrent immunosuppressive therapy. Typical symptoms include seizure, headache, altered mental status, and visual disturbances. PRES is rarely associated with cerebral hemorrhage, and even less so with subarachnoid bleeds. Herein we report on a 25-year-old female with focal segmental glomerulosclerosis who developed PRES. The patients presentation was more severe as she presented with seizure, nephrotic syndrome, and subarachnoid hemorrhage. Computed tomography and magnetic resonance imaging with concurrent symptoms led us to the final diagnosis. The patient was treated with antihypertensives, diuretics, and corticosteroids and follow-up imaging revealed resolution of PRES. Our case illustrates that underlying kidney disease even without immunosuppressive agents should be added to the list of possible causes for PRES. Symptoms are reversible with treatment of underlying cause or offending agent. PMID:25960654

  10. 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

  11. Maternal and fetal outcomes after introduction of magnesium sulphate for treatment of preeclampsia and eclampsia in selected secondary facilities: a low-cost intervention.

    PubMed

    Tukur, Jamilu; Ahonsi, Babatunde; Ishaku, Salisu Mohammed; Araoyinbo, Idowu; Okereke, Ekechi; Babatunde, Ayodeji Oginni

    2013-09-01

    The aim of this study was to evaluate whether a new low-cost strategy for the introduction of magnesium sulphate (MgSO4) for preeclampsia and eclampsia in low-resource areas will result in improved maternal and perinatal outcomes. Doctors and midwives from ten hospitals in Kano, Nigeria, were trained on the use of MgSO4. The trained health workers later conducted step-down training at their health facilities. MgSO4, treatment protocol, patella hammer, and calcium gluconate were then supplied to the hospitals. Data was collected through structured data forms. The data was analyzed using SPSS software. From February 2008 to January 2009, 1,045 patients with severe preeclampsia and eclampsia were treated. The case fatality rate for severe preeclampsia and eclampsia fell from 20.9 % (95 % CI 18.7-23.2) to 2.3 % (95 % CI 1.5-3.5). The perinatal mortality rate was 12.3 % as compared to 35.3 % in a center using diazepam. Introduction of MgSO4 in low-resource settings led to improved maternal and fetal outcomes in patients presenting with severe pre-eclampsia and eclampsia. Training of health workers on updated evidence-based interventions and providing an enabling environment for their practice are important components to the attainment of the Millennium Development Goals (MDG) in developing countries. PMID:22956402

  12. Immunofluorescence confocal laser scanning microscopy and immuno-electron microscopic identification of keratins in human materno-foetal interaction zone.

    PubMed

    Ahenkorah, J; Hottor, B; Byrne, S; Bosio, P; Ockleford, C D

    2009-04-01

    We show here that at least 5 keratin proteins are present in villous trophoblast and the same 5 in extravillous trophoblast. A further 14 tested were undetectable in these tissues. In contrast, 10 of the 19 keratins tested were present in amniotic epithelium. The marking of amniotic epithelium on the one hand, as distinct from villous and extravillous trophoblast on the other, can be achieved using 5 keratins (K4, 6, 13, 14 and 17) with a mixture of positive and negative discrimination that is expected, in combination, to be highly sensitive. All the specific keratins identified in trophoblast were apparently up-regulated on the pathway to extravillous trophoblast. Co-ordinated differentiation at the molecular expression level is indicated by this finding. The relevant keratins are K5, 7, 8, 18 and 19. Specific keratins have been identified that are down-regulated in villous trophoblast in pre-eclamptic pregnancy. This difference between healthy and pre-eclamptic chorionic villous trophoblast keratin expression was statistically significant in 4 out of the 5 keratins. This was not the case for the extravillous trophoblast at the immunofluorescence confocal level but significant differences were obtained using immunogold electron microscopy. We suggest that the villous trophoblast in pre-eclamptic placentae is cytoskeletally weaker with respect to the filaments made from these specific proteins and that this is one reason why, in pre-eclampsia, trophoblast is deported in greater quantity than in healthy placentae. PMID:18466353

  13. Correlation of pregnancy outcome with quadruple screening test at second trimester

    PubMed Central

    Yazdani, Shahla; Rouholahnejad, Rahele; Asnafi, Nesa; Sharbatdaran, Majid; Zakershob, Marziihe; Bouzari, Zinatossadat

    2015-01-01

    Background: Abnormal levels of the markers AFP, hCG, and uE3 could be useful in predicting adverse pregnancy outcomes. This study was designed to determine the correlation between second trimester maternal serum markers and adverse pregnancy outcome (APO). Methods: In this historical cohort study, we randomly followed 231 obstetric patients with quadruple screening test in 14-18 weeks of gestation from March 2012 to March 2013 in a medical laboratory in Babol, Iran. We measured maternal serum levels of alphafetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin-A. The risk of adverse pregnancy outcomes (APOs) were then compared between patients with negative and positive test results. We used Chi-square and Fisher-exact tests for qualitative variables and t-test for quantitative variables. Demographic differences between the two groups were minimized by applying logistic regression. Results: The risk of having an APO such as pre-eclampsia (p=0.008), fetal growth restriction (p=0.028) and premature rupture of membrane (p=0.040) increased significantly in patients with abnormal markers. Conclusion: Abnormal results of quadruple screening test could be associated with APO in women with normal appearing fetus. PMID:26913244

  14. The association between physical activity and maternal and neonatal outcomes: a prospective cohort.

    PubMed

    Currie, Lisa M; Woolcott, Christy G; Fell, Deshayne B; Armson, B Anthony; Dodds, Linda

    2014-10-01

    Some evidence, but not enough to be conclusive, suggests that physical activity in pregnancy reduces the risk of perinatal complications. Our objective was to examine if physical activity in the year before pregnancy and in the first half of pregnancy is associated with maternal and neonatal outcomes. Associations between physical activity and maternal and neonatal outcomes were examined in a prospective cohort (n = 1,749) in Halifax, Canada. The Kaiser Physical Activity Survey, completed at approximately 20 weeks' gestation, requested information regarding physical activity during the year before the pregnancy and the first 20 weeks of pregnancy. Outcomes were assessed by medical chart review. Multiple logistic regression was used to estimate odds ratios (OR) with 95 % confidence intervals (CI). Women with prepregnancy physical activity levels in the middle and highest tertiles were more likely to have high gestational weight gain relative to women in the lowest tertile [OR (CI): 1.40 (1.06-1.85) and 1.57 (1.18-2.09), respectively]. Higher physical activity in the first half of pregnancy decreased the odds of delivering a macrosomic infant (p trend = 0.005). Associations were not observed between total physical activity and gestational diabetes, gestational hypertension, pre-eclampsia, preterm birth, and low birth weight. Physical activity before, but not in the first half of pregnancy, is associated with high gestational weight gain. Physical activity in the first half of pregnancy may reduce the occurrence of macrosomia without affecting preterm birth or low birth weight. PMID:24347091

  15. Systematic Analysis of the Molecular Mechanism Underlying Decidualization Using a Text Mining Approach

    PubMed Central

    Liu, Ji-Long; Wang, Tong-Song

    2015-01-01

    Decidualization is a crucial process for successful embryo implantation and pregnancy in humans. Defects in decidualization during early pregnancy are associated with several pregnancy complications, such as pre-eclampsia, intrauterine growth restriction and recurrent pregnancy loss. However, the mechanism underlying decidualization remains poorly understood. In the present study, we performed a systematic analysis of decidualization-related genes using text mining. We identified 286 genes for humans and 287 genes for mice respectively, with an overlap of 111 genes shared by both species. Through enrichment test, we demonstrated that although divergence was observed, the majority of enriched gene ontology terms and pathways were shared by both species, suggesting that functional categories were more conserved than individual genes. We further constructed a decidualization-related protein-protein interaction network consisted of 344 nodes connected via 1,541 edges. We prioritized genes in this network and identified 12 genes that may be key regulators of decidualization. These findings would provide some clues for further research on the mechanism underlying decidualization. PMID:26222155

  16. Use of oral anti-diabetic agents in pregnancy: a pragmatic approach.

    PubMed

    Kalra, Bharti; Gupta, Yashdeep; Singla, Rajiv; Kalra, Sanjay

    2015-01-01

    Insulin is the gold standard for treatment of hyperglycemia during pregnancy, when lifestyle measures do not maintain glycemic control during pregnancy. However, recent studies have suggested that certain oral hypoglycemic agents (metformin and glyburide) may be safe and be acceptable alternatives. There are no serious safety concerns with metformin, despite it crossing the placenta. Neonatal outcomes are also comparable, with benefit of reductions in neonatal hypoglycemia, maternal hypoglycemia and weight gain, and improved treatment satisfaction. Glibenclamide is more effective in lowering blood glucose in women with gestational diabetes, and with a lower treatment failure rate than metformin. Although generally well-tolerated, some studies have reported higher rates of pre-eclampsia, neonatal jaundice, longer stay in the neonatal care unit, macrosomia, and neonatal hypoglycaemia. There is also paucity of long-term follow-up data on children exposed to oral agents in utero. This review aims to provide an evidence-based approach, concordant with basic and clinical pharmacological knowledge, which will help medical practitioners use oral anti-diabetic agents in a rational and pragmatic manner. Pubmed search was made using Medical Subject Headings (MESH) terms "Diabetes" and "Pregnancy" and "Glyburide"; "Diabetes" and "Pregnancy" and "Metformin". Limits were randomized controlled trials (RCTs) and meta-analysis. The expert reviews on the topic were also used for discussion. Additional information (studies/review) pertaining to discussion under sub-headings like safety during breastfeeding; placental transport; long-term safety data were searched (pubmed/cross-references/expert reviews). PMID:25709972

  17. Use of Oral Anti-Diabetic Agents in Pregnancy: A Pragmatic Approach

    PubMed Central

    Kalra, Bharti; Gupta, Yashdeep; Singla, Rajiv; Kalra, Sanjay

    2015-01-01

    Insulin is the gold standard for treatment of hyperglycemia during pregnancy, when lifestyle measures do not maintain glycemic control during pregnancy. However, recent studies have suggested that certain oral hypoglycemic agents (metformin and glyburide) may be safe and be acceptable alternatives. There are no serious safety concerns with metformin, despite it crossing the placenta. Neonatal outcomes are also comparable, with benefit of reductions in neonatal hypoglycemia, maternal hypoglycemia and weight gain, and improved treatment satisfaction. Glibenclamide is more effective in lowering blood glucose in women with gestational diabetes, and with a lower treatment failure rate than metformin. Although generally well-tolerated, some studies have reported higher rates of pre-eclampsia, neonatal jaundice, longer stay in the neonatal care unit, macrosomia, and neonatal hypoglycaemia. There is also paucity of long-term follow-up data on children exposed to oral agents in utero. This review aims to provide an evidence-based approach, concordant with basic and clinical pharmacological knowledge, which will help medical practitioners use oral anti-diabetic agents in a rational and pragmatic manner. Pubmed search was made using Medical Subject Headings (MESH) terms Diabetes and Pregnancy and Glyburide; Diabetes and Pregnancy and Metformin. Limits were randomized controlled trials (RCTs) and meta-analysis. The expert reviews on the topic were also used for discussion. Additional information (studies/review) pertaining to discussion under sub-headings like safety during breastfeeding; placental transport; long-term safety data were searched (pubmed/cross-references/expert reviews). PMID:25709972

  18. Overweight and Obesity before, during and after Pregnancy

    PubMed Central

    Stupin, J. H.; Arabin, B.

    2014-01-01

    Overweight and obesity before conception as well as excessive weight gain during pregnancy are associated with endocrinological changes of mother and fetus. Insulin resistance physiologically increases during pregnancy, additional obesity further increases insulin resistance. In combination with reduced insulin secretion this leads to gestational diabetes which may develop into type-2-diabetes. The adipose tissue produces TNF-alpha, interleukins and leptin and upregulates these adipokines. Insulin resistance and obesity induce inflammatory processes and vascular dysfunction, which explains the increased rate of pregnancy-related hypertension and pre-eclampsia in obese pregnant women. Between 14 and 28 gestational weeks, the fetal adipose tissue is generated and the number of fat lobules is determined. Thereafter, an increase in adipose tissue is arranged by an enlargement of the lobules (hypertrophy), or even an increase in the number of fat cells (hyperplasia). Human and animal studies have shown that maternal obesity “programmes” the offspring for further obesity and chronic disease. Pregnant women, midwives, physicians and health care politicians should be better informed about prevention, pathophysiological mechanisms, and the burden for society caused by obesity before, during and after pregnancy. PMID:25100878

  19. 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

  20. The placenta: a multifaceted, transient organ

    PubMed Central

    Burton, Graham J.; Fowden, Abigail L.

    2015-01-01

    The placenta is arguably the most important organ of the body, but paradoxically the most poorly understood. During its transient existence, it performs actions that are later taken on by diverse separate organs, including the lungs, liver, gut, kidneys and endocrine glands. Its principal function is to supply the fetus, and in particular, the fetal brain, with oxygen and nutrients. The placenta is structurally adapted to achieve this, possessing a large surface area for exchange and a thin interhaemal membrane separating the maternal and fetal circulations. In addition, it adopts other strategies that are key to facilitating transfer, including remodelling of the maternal uterine arteries that supply the placenta to ensure optimal perfusion. Furthermore, placental hormones have profound effects on maternal metabolism, initially building up her energy reserves and then releasing these to support fetal growth in later pregnancy and lactation post-natally. Bipedalism has posed unique haemodynamic challenges to the placental circulation, as pressure applied to the vena cava by the pregnant uterus may compromise venous return to the heart. These challenges, along with the immune interactions involved in maternal arterial remodelling, may explain complications of pregnancy that are almost unique to the human, including pre-eclampsia. Such complications may represent a trade-off against the provision for a large fetal brain. PMID:25602070

  1. Endothelial-Derived Hyperpolarization Factor (EDHF) Contributes to PlGF-Induced Dilation of Mesenteric Resistance Arteries from Pregnant Rats

    PubMed Central

    Mandal, Maurizio; Gokina, Natalia; Barron, Carolyn; Osol, George

    2011-01-01

    The aim of this study was to investigate the cellular mechanism involved in the potent vasodilatory action of PlGF on mesenteric resistance arteries from pregnant rats. PlGF (3 nM) induced a vasodilation of 64 3.8% that was completely abolished by endothelial denudation. Significant dilation (28 4.0%) remained, however, in the presence of nitric oxide synthase and cyclooxygenase inhibition, and was associated with significant reductions in vascular smooth muscle cell calcium. Absence of dilation in potassium-depolarizing solution (30 mM) confirmed its dependence on endothelial-derived hyperpolarization factor. Subsequent studies established that vasodilation was abolished by pharmacologic inhibition of SKCa (apamin) and BKCa (iberiotoxin) but not IKCa (tram-34) potassium channels. In summary, PlGF acts through the release of a combination of endothelium-derived relaxation factors. Based on the results of potassium channel blockade, we suggest that it induces endothelial hyperpolarization via SKCa channel activation; this, in turn, leads to the release of a diffusible mediator that activates vascular smooth muscle BKCa channels, hyperpolarization and vasodilation. This is the first study to identify the mechanism for PlGF/VEGFR-1 resistance artery dilation in the pregnant state, whose attenuation likely contributes to the systemic hypertension characteristic of pre-eclampsia. PMID:21985802

  2. Postnatal diagnosis of maternal congenital heart disease: missed opportunities.

    PubMed

    Vashisht, Ananya; Katakam, Narmada; Kausar, Samina; Patel, Neena; Stratton, Jane

    2015-01-01

    A 30-year-old primigravida with no known comorbidities presented to the emergency department at 29+6/40 gestation, with breathlessness. The initial diagnosis was pulmonary embolism, which was later revised following initial investigations and considered to be pre-eclampsia/HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome. Following caesarean section and delivery of a live baby, the patient had episodes of cyanotic hypoxia and was admitted to intensive care. A provisional diagnosis of idiopathic pulmonary hypertension was performed. Decompensation led to transfer to a specialist intensive care unit for extracorporeal membrane oxygenation, where a diagnosis of patent ductus arteriosus and Eisenmenger's syndrome was made. Heart disease is the leading indirect cause of maternal death, and Eisenmenger's syndrome in pregnancy carries a 50-65% mortality. A literature review demonstrated that this is the only reported case of a postnatal diagnosis of Eisenmenger's syndrome. We considered missed opportunities to make an earlier diagnosis, so that patients and doctors will benefit from the lessons we learnt. PMID:26370636

  3. Neighborhood conditions are associated with maternal health behaviors and pregnancy outcomes.

    PubMed

    Vinikoor-Imler, L C; Messer, L C; Evenson, K R; Laraia, B A

    2011-11-01

    Women residing in neighborhoods of low socioeconomic status are more likely to experience adverse reproductive outcomes; however, few studies explore which specific neighborhood features are associated with poor maternal health behaviors and pregnancy outcomes. Based upon our conceptual model, directly observed street-level data from four North Carolina US counties were used to create five neighborhood indices: physical incivilities (neighborhood degradation), social spaces (public space for socializing), walkability (walkable neighborhoods), borders (property boundaries), and arterial features (traffic safety). Singleton birth records (2001-2005) were obtained from the North Carolina State Center for Vital Statistics and maternal health behavior information (smoking, inadequate or excessive weight gain) and pregnancy outcomes (pregnancy-induced hypertension/pre-eclampsia, low birthweight, preterm birth) were abstracted. Race-stratified random effect models were used to estimate associations between neighborhood indices and women's reproductive behaviors and outcomes. In adjusted models, higher amounts of physical incivilities were positively associated with maternal smoking and inadequate weight gain, while walkability was associated with lower odds of these maternal health behaviors. Social spaces were also associated with inadequate weight gain during pregnancy. Among pregnancy outcomes, high levels of physical incivilities were consistently associated with all adverse pregnancy outcomes, and high levels of walkability were inversely associated with pregnancy-induced hypertension and preterm birth for Non-Hispanic white women only. None of the indices were associated with adverse birth outcomes for Non-Hispanic black women. In conclusion, certain neighborhood conditions were associated with maternal health behaviors and pregnancy outcomes. PMID:21920650

  4. Hypomagnesemic disorders.

    PubMed

    Dacey, M J

    2001-01-01

    Adequate magnesium stores are vitally important for life. Critically ill patients will almost always have diminished levels of circulating magnesium, and this predisposes them to a variety of adverse effects, some life threatening. The causes of hypomagnesemia are many and varied, but in the critically ill, losses from the kidneys, often secondary to medications and from the gastrointestinal (GI) tract, predominate. The measurement of magnesium is not straightforward, although many clinicians are now switching to the use of ionized magnesium from ion selective electrodes. The use of supplemental magnesium in acute flares of asthma has some support in medical literature, especially for those patients with severe disease who fail traditional therapy. Magnesium holds the preeminent position in the treatment of pre-eclampsia and eclampsia in the minds of most obstetricians, who have decades of experience showing it to be both effective and safe. Magnesium is clearly useful for certain types of ventricular tachycardia, and probably assists in the treatment of several types of supraventricular tachycardia. Its role in acute myocardial ischemia is less certain, although there is no benefit once reperfusion therapy has already been carried out. Finally, the role of magnesium in the treatment of acute cerebral insults is an exciting area of active investigation with initial studies suggesting much promise. PMID:11219227

  5. 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.

  6. PubMed Central

    Mnard, 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

  7. Utility of proteomics in obstetric disorders: a review.

    PubMed

    Hernndez-Nez, Jnathan; Valds-Yong, Magel

    2015-01-01

    The study of proteomics could explain many aspects of obstetric disorders. We undertook this review with the aim of assessing the utility of proteomics in the specialty of obstetrics. We searched the electronic databases of MEDLINE, EBSCOhost, BVS Bireme, and SciELO, using various search terms with the assistance of a librarian. We considered cohort studies, case-control studies, case series, and systematic review articles published until October 2014 in the English or Spanish language, and evaluated their quality and the internal validity of the evidence provided. Two reviewers extracted the data independently, then both researchers simultaneously revised the data later, to arrive at a consensus. The search retrieved 1,158 papers, of which 965 were excluded for being duplicates, not relevant, or unrelated studies. A further 86 papers were excluded for being guidelines, protocols, or case reports, along with another 64 that did not contain relevant information, leaving 43 studies for inclusion. Many of these studies showed the utility of proteomic techniques for prediction, pathophysiology, diagnosis, management, monitoring, and prognosis of pre-eclampsia, perinatal infection, premature rupture of membranes, preterm birth, intrauterine growth restriction, and ectopic pregnancy. Proteomic techniques have enormous clinical significance and constitute an invaluable weapon in the management of obstetric disorders that increase maternal and perinatal morbidity and mortality. PMID:25926758

  8. Pregnancy-related issues in women with systemic lupus erythematosus.

    PubMed

    Singh, Abha G; Chowdhary, Vaidehi R

    2015-02-01

    While fertility is preserved in females with systemic lupus erythematosus (SLE), it is well established that pregnancy in these patients is associated with adverse maternal and fetal outcomes, including pregnancy loss, pre-eclampsia, preterm delivery and intrauterine growth retardation, as well as neonatal mortality. Mechanisms underlying these adverse outcomes are poorly understood, and better understanding of these would allow development of targeted and personalized treatment strategies. Established risk factors for adverse pregnancy outcomes include active disease within 6 months prior to conception and during pregnancy, active nephritis, maternal hypertension, antiphospholipid antibodies and hypocomplementemia. While intensive monitoring is recommended, the comparative effectiveness of appropriate management strategies is unclear. While current strategies are able to achieve live births in 85-90% of pregnancies, certain aspects such as prevention of preterm birth, treatment of congenital heart block due to neonatal lupus and recurrent pregnancy loss despite best management, remains challenging. Pregnancy is also associated with an increased risk of flare of lupus, particularly in patients with active disease at time of conception or within 6 months prior to conception. Pregnant patients with SLE should be followed in a high-risk obstetric clinic, and care should be closely coordinated between the obstetrician and rheumatologist. PMID:25545844

  9. 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

  10. [Cerebral vasospasms with hemodynamic infarctions as a complication of HELLP syndrome].

    PubMed

    Harscher, S; Witte, O W; Mller, U; Bloos, G; Pfleiderer, S O R; Terborg, C

    2003-12-01

    Sinal thrombosis, intracerebral bleeding, cerebral edema, and cerebral vasospasm are typical neurological complications in pre- and eclampsia. Hemolysis, elevated liver enzyme, and low platelet (HELLP) syndrome is a rare, severe complication of pre-eclampsia. We present the case of a 33-year-old woman with HELLP syndrome. After a cesarean section, generalized epileptic seizure occurred and intubation was necessary due to sustained unconsciousness. Despite magnesium therapy, bilateral hemodynamic ischemic infarctions and narrowing of the circle of Willis were visible on MRI, and vasospasm of all large basal cerebral arteries was confirmed by cerebral angiography and transcranial Doppler sonography. During the following 2 weeks, the cerebral vasospasm resolved with application of high-dose methyl prednisolone and nimodipine. After extubation, the patient initially suffered from mild psychosyndrome and ataxia but recovered completely after 3 months. The HELLP syndrome may be complicated by cerebral vasospasm with subsequent hemodynamic strokes. Combined treatment with magnesium, corticosteroids, and nimodipine can be recommended. In our case, this regimen led to resolution of the cerebral vasospasm and complete clinical recovery. PMID:14647914

  11. Biological Functions of Thyroid Hormone in Placenta

    PubMed Central

    Chen, Cheng-Yi; Chen, Chie-Pein; Lin, Kwang-Huei

    2015-01-01

    The thyroid hormone, 3,3,5-triiodo-l-thyronine (T3), modulates several physiological processes, including cellular growth, differentiation, metabolism, inflammation and proliferation, via interactions with thyroid hormone response elements (TREs) in the regulatory regions of target genes. Infection and inflammation are critical processes in placental development and pregnancy-related diseases. In particular, infection is the leading cause of neonatal mortality and morbidity worldwide. However, to date, no successful approach has been developed for the effective diagnosis of infection in preterm infants. Pre-eclampsia (PE) is a serious disorder that adversely affects ~5% of human pregnancies. Recent studies identified a multiprotein complex, the inflammasome, including the Nod-like receptor (NLR) family of cytosolic pattern recognition receptors, the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, which plays a vital role in the placenta. The thyroid hormone modulates inflammation processes and is additionally implicated in placental development and disease. Therefore, elucidation of thyroid hormone receptor-regulated inflammation-related molecules, and their underlying mechanisms in placenta, should facilitate the identification of novel predictive and therapeutic targets for placental disorders. This review provides a detailed summary of current knowledge with respect to identification of useful biomarkers and their physiological significance in placenta. PMID:25690032

  12. 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; Knfler, Martin; Frhlich, Camilla; Pollheimer, Jrgen

    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. PMID:24695627

  13. Gestational Diabetes Mellitus.

    PubMed

    Spaight, Caroline; Gross, Justine; Horsch, Antje; Puder, Jardena Jacqueline

    2016-01-01

    Based on the Hyperglycemia and Adverse Pregnancy Outcome study, new universal screening recommendations and cut-offs for gestational diabetes mellitus (GDM) have been proposed. In addition to the immediate perinatal risk, GDM carries an increased risk of metabolic disease in the mother and child. Maternal obesity has even been shown to be associated with increased all-cause mortality in offspring. In addition to known risk factors, excessive gestational weight gain, increased fat consumption, a low vitamin D level, psychological stress and negative mood are risk factors for GDM. Regarding therapy, the US Preventive Task Force concluded in 2013 that GDM treatment significantly reduces the risks of pre-eclampsia, macrosomia and shoulder dystocia (relative risks of 0.62, 0.5 and 0.42, respectively). Although nutrition therapy represents a cornerstone in GDM management, the results of studies are not clear regarding which types of dietary advice are the most suitable. Most physical activity interventions improve glucose control and/or reduce insulin use. Recent studies have evaluated and provided more information about treatment with metformin or glyburide. Postpartum management is essential and should focus on long-term screening and diabetes prevention strategies. PMID:26824237

  14. [Premature newborn: a case presentation].

    PubMed

    Pastor Rodrguez, Jess David; Pastor Bravo, Mara Del Mar; Lpez Garca, Visitacin; Cotes Teruel, Mara Isabel; Mellado, Jess Eulogio; Crceles, Jos 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. PMID:20605104

  15. Pattern and factors affecting the outcome of pregnancy in hypertensive patients.

    PubMed Central

    Familoni, Oluranti B.; Adefuye, Peter O.; Olunuga, Taiwo O.

    2004-01-01

    The pattern and factors affecting the outcome of pregnancy in hypertensive patients at the Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria between January 1997 and December 2002 were studied. There were 2,393 deliveries, with 127 (5.3%) patients fulfilling the criteria for hypertensive disorder of pregnancy. 26.2% had de-novo (gestational) hypertension, 19.7% had pre-eclampsia (PET) superimposed on chronic hypertension and 54.1% had PET/eclampsia. All patients with prepregnancy chronic hypertension had superimposed PET or eclampsia in this study. The PET/eclampsia group had the worst maternal and fetal outcomes as demonstrated by maternal mortality (6.1%), fetal mortality (36.4%), fetal respiratory distress (66.7%) and abruptio (6.1%). They also had more target organ damage (18.2%). 50.8% of these were categorized as high risk. Furthermore, patients in the PET/eclampsia group tended to be illiterate, attended antenatal clinic (ANC) less regularly and had more maternal and fetal adverse outcomes. Twenty percent of the patients had poorly controlled blood pressures (BP) at discharge, and only one out of five of the chronic hypertensive patients attended the medical hypertension clinic on discharge. These poor outcomes further emphasize the need for patient education; regular antenatal clinic attendance; prompt treatment of elevated BP; compliance with postnatal clinic follow-up, including medical outpatient care in these patients. PMID:15622693

  16. 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. PMID:26016557

  17. Intravenous Infusion of Magnesium Sulphate During Subarachnoid Anaesthesia in Hip Surgery and Its Effect on Postoperative Analgesia: Our Experience

    PubMed Central

    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. PMID:23905078

  18. Pregnancy and autoimmune diseases.

    PubMed

    Gordon, Caroline

    2004-06-01

    Until about 15 years ago, the general advice to women with autoimmune rheumatic diseases, especially systemic lupus erythematosus, systemic sclerosis and vasculitic syndromes, was to avoid pregnancy as there was a high risk of maternal and fetal morbidity and mortality. However, it is now clear that these risks can be reduced in general by avoiding pregnancy when the diseases are active and continuing appropriate medication to reduce the chances of disease flare during pregnancy. This article will review the evidence for this advice and will also consider other issues that should be discussed with women before they attempt to become pregnant. This will include the influence of pregnancy on the individual autoimmune diseases, as well as the potential impact of the diseases and drug therapy on fertility and pregnancy outcomes. Anti-phospholipid antibody syndrome has emerged as a major cause of fetal loss, pre-eclampsia and premature birth. The clinical and laboratory diagnosis of this condition will not be covered, but the reader is referred to an excellent recent review. Much of the data on pregnancy and autoimmune rheumatic diseases come from retrospective analyses, but some prospective studies have been reported over the past 10 years. There have been very few meta-analyses or randomized clinical trials. PMID:15158746

  19. CUL1 promotes trophoblast cell invasion at the maternalfetal interface

    PubMed Central

    Zhang, Q; Chen, Q; Lu, X; Zhou, Z; Zhang, H; Lin, H-Y; Duan, E; Zhu, C; Tan, Y; Wang, H

    2013-01-01

    Human trophoblast progenitor cells differentiate via two distinct pathways, to become the highly invasive extravillous cytotrophoblast (CTB) cells (EVT) or fuse to form syncytiotrophoblast. Inadequate trophoblast differentiation results in poor placenta perfusion, or even complications such as pre-eclampsia (PE). Cullin1 (CUL1), a scaffold protein in cullin-based ubiquitin ligases, plays an important role in early embryonic development. However, the role of CUL1 in trophoblast differentiation during placenta development has not been examined. Here we show that CUL1 was expressed in CTB cells and EVT in the first trimester human placentas by immunohistochemistry. CUL1 siRNA significantly inhibited outgrowth of extravillous explants in vitro, as well as invasion and migration of HTR8/SVneo cells of EVT origin. This inhibition was accompanied by decreased gelatinolytic activities of matrix metalloproteinase (MMP)-9 and increased expression of tissue inhibitors of MMPs (TIMP-1 and -2). Consistently, exogenous CUL1 promoted invasion and migration of HTR8/SVneo cells. Notably, CUL1 was gradually decreased during trophoblast syncytialization and CUL1 siRNA significantly enhanced forskolin-induced fusion of choriocarcinoma BeWo cells. CUL1 protein levels in human pre-eclamptic placental villi were significantly lower as compared to their matched control placentas. Taken together, our results suggest that CUL1 promotes human trophoblast cell invasion and dysregulation of CUL1 expression may be associated with PE. PMID:23429288

  20. The role of visfatin (PBEF/Nampt) in pregnancy complications.

    PubMed

    Pavlová, Tereza; Novák, Jan; Bienertová-Vašků, Julie

    2015-11-01

    Visfatin (PBEF/Nampt) is an adipocytokine that exerts pleiotropic effects within the human body, particularly affecting its metabolism and immunity. Visfatin was originally identified as being secreted by peripheral blood lymphocytes acting as a pre-B-cell colony-enhancing factor (PBEF). However, it was subsequently reported to be expressed in almost every tissue of the human body, with visceral fat deposits being the main source of visfatin. In addition to its secreted form, visfatin may also be found intracellularly where it functions as a nicotinamide phosphoribosyltransferase (Nampt). Visfatin maternal plasma concentrations increase during pregnancy, suggesting its important role in this complicated process. Alterations in visfatin level also take place in patients during pregnancy complications. This review focuses on the ones that most commonly occur in connection with visfatin: preterm labor, pre-eclampsia and gestational diabetes mellitus. The review aims to provide a better understanding of the role of visfatin during pregnancy and the causes of its alteration in maternal plasma, highlighting the potential use of visfatin as a diagnostic marker of pregnancy complications in the future. PMID:26451650

  1. Cardiology for gynecologists--a minireview.

    PubMed

    Schenck-Gustafsson, Karin; Rees, Margaret

    2013-08-01

    Despite cardiovascular disease (CVD) being by far the most common cause of death in women worldwide, awareness is low. Myocardial infarction occurs 10 years later in women than in men. Symptoms may be atypical: dyspnea rather than chest pain. Also more women than men have myocardial infarction with normal coronary angiography, probably due to microvascular disease or coronary spasm. The prognosis of non-obstructive disease is now recognized to be the same than for obstructive disease. The conventional risk factors for CVD are the same for both genders but have a different impact for women. One example is psychosocial stress and angina pectoris can more often be induced by mental stress in women than in men. Also there are risk factors specific to women such as a history of pre-eclampsia, gestational hypertension or diabetes and polycystic ovary syndrome (PCOS). Furthermore atrial fibrillation increases the risk of stroke more in women than in men. However, 6 out of 10 deaths from CVD can be prevented by a healthy life style and dealing with preexisting risk factors. Hence it is important that gynecologists who start seeing women at an earlier age than cardiologists should be aware of cardiovascular disease. PMID:23727147

  2. Delivering obstetrical critical care in developing nations

    PubMed Central

    Bajwa, Sukhwinder Kaur; Bajwa, Sukhminder Jit Singh

    2012-01-01

    Obstetrical critical care has not been able to achieve the same level of peaks in developing nations like India, as in the western countries. Numerous factors, including clinical and economical, have played a major role in widening the gap of quality care delivery in severely ill obstetric patients, between the two extreme worlds. Moreover, this wide gap can be, to a large extent, attributable to the lower literacy rates, paucity of research in obstetrical critical care, poverty, lack of awareness, and the sociocultural and behavioral factors prevalent in these developing nations. The most common indication for Intensive Care Unit (ICU) admission of such patients throughout the world is hemorrhage, both antepartum and postpartum. Hypertensive disorders, pre-eclampsia, and its related complications are also major contributory factors for such admissions. The pattern of the disease necessitating such admissions influences maternal mortality to a great extent. The present article reviews the most common indications of obstetrical admissions to the ICU, the challenges and obstacles in the treatment of severely ill obstetric patients, their possible outcome in the developing nations, room for improvement, and the need for a change in the system for better delivery of critical care obstetrical services. PMID:22624100

  3. 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.

  4. 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 commenced antenatally (MD 8.10, 95% CI 6.23 to 9.97) and postnatally (MD 3.70, 95% CI 0.96 to 6.44). Authors’ conclusions There was no clear evidence of any effect of corticosteroids on substantive clinical outcomes. Those receiving steroids showed significantly greater improvement in platelet counts which was greater for those receiving dexamethasone than those receiving betamethasone. There is to date insufficient evidence of benefits in terms of substantive clinical outcomes to support the routine use of steroids for the management of HELLP. The use of corticosteroids may be justified in clinical situations in which increased rate of recovery in platelet count is considered clinically worthwhile. PMID:20824872

  5. Vitamin D supplementation for women during pregnancy

    PubMed Central

    De-Regil, Luz Maria; Palacios, Cristina; Ansary, Ali; Kulier, Regina; Pea-Rosas, Juan Pablo

    2013-01-01

    Background Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse gestational outcomes. Objectives To examine whether supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011), the International Clinical Trials Registry Platform (ICTRP) (31 October 2011), the Networked Digital Library of Theses and Dissertations (28 October 2011) and also contacted relevant organisations (8 April 2011). Selection criteria Randomised and quasi-randomised trials with randomisation at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy. Data collection and analysis Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy. Main results The search strategy identified 34 potentially eligible references. We included six trials assessing a total of 1023 women, excluded eight studies, and 10 studies are still ongoing. Five trials involving 623 women compared the effects of vitamin D alone versus no supplementation/placebo and one trial with 400 women compared the effects of vitamin D and calcium versus no supplementation. Only one trial with 400 women reported on pre-eclampsia: women who received 1200 IU vitamin D along with 375 mg of elemental calcium per day were as likely to develop pre-eclampsia as women who received no supplementation (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.33 to 1.35). Data from four trials involving 414 women consistently show that women who received vitamin D supplements had higher concentrations of vitamin D in serum at term than those women who received no intervention or a placebo; however the magnitude of the response was highly heterogenous. Data from three trials involving 463 women suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 grams than those women receiving no treatment or placebo; statistical significance was borderline (RR 0.48; 95% CI 0.23 to 1.01). In terms of other conditions, there were no significant differences in adverse side effects including nephritic syndrome (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women); stillbirths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) or neonatal deaths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) between women who received vitamin D supplements in comparison with women who received no treatment or placebo. No studies reported on preterm birth, maternal death, admission to neonatal intensive care unit/special nursery or Apgar scores. Authors' conclusions Vitamin D supplementation in a single or continued dose during pregnancy increases serum vitamin D concentrations as measured by 25-hydroxyvitamin D at term. The clinical significance of this finding and the potential use of this intervention as a part of routine antenatal care are yet to be determined as the number of high quality trials and outcomes reported is too limited to draw conclusions on its usefulness and safety. Further rigorous randomised trials are required to evaluate the role of vitamin D supplementation in pregnancy. PMID:22336854

  6. Inhibition of DDAH1, but not DDAH2, results in apoptosis of a human trophoblast cell line in response to TRAIL

    PubMed Central

    Lumicisi, B.A.; Cartwright, J.E.; Leslie, K.; Wallace, A.E.; Whitley, G.S.

    2015-01-01

    STUDY QUESTION Does inhibition of dimethylarginine dimethylaminohydrolase (DDAH) increase the sensitivity of trophoblasts to TRAIL-induced apoptosis? SUMMARY ANSWER Inhibition of DDAH1, but not DDAH2, increases the sensitivity of trophoblasts to TRAIL-induced apoptosis. WHAT IS KNOWN ALREADY Successful human pregnancy is dependent on adequate trophoblast invasion and remodelling of the maternal spiral arteries. Increased trophoblast apoptosis is seen in pregnancies complicated by pre-eclampsia. The mechanism underlying this increase is unknown. We have previously shown that nitric oxide (NO) is involved in regulating trophoblast motility and invasion, and have also demonstrated an important role for NO in regulating trophoblast sensitivity to apoptotic stimuli. DDAH is an enzyme that metabolizes asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis, previously shown to be elevated in the plasma of pre-eclamptic mothers. STUDY DESIGN, SIZE, DURATION This study used the human extravillous trophoblast-derived cell line SGHPL-4 cells. All experiments were performed at least three times. PARTICIPANTS/MATERIALS, SETTING, METHODS The effect of DDAH on trophoblast apoptosis was examined using siRNA and time-lapse microscopy. Changes in the expression of DDAH were followed by PCR and western blot analysis. Receptor expression was followed by flow cytometry. MAIN RESULTS AND THE ROLE OF CHANCE Inhibiting the expression of DDAH1, but not DDAH2, resulted in a significant increase in the sensitivity of the EVT cell line SGHPL-4 to tumour necrosis factor related apoptosis inducing ligand (TRAIL) induced apoptosis (P < 0.01). This response could be mimicked by the addition of Asymmetric Dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis and the substrate for both isoforms of DDAH. We further showed that this increased sensitivity to apoptosis is accompanied by a significant increase in the expression of TRAIL receptor 2 (TR2; P < 0.05) but not TRAIL receptor 1 (TR1). LIMITATIONS, REASONS FOR CAUTION This study was performed only in vitro using a well characterized trophoblast cell line, SGHPL-4, derived from first trimester extravillous trophoblasts. WIDER IMPLICATIONS OF THE FINDINGS This study provides new insight into the role of the DDAH/ADMA pathway in the regulation of trophoblast function. Both dysregulation of DDAH and the accumulation of ADMA have been associated with the development of pre-eclampsia. This is the first study to implicate the DDAH/ADMA pathway as a mechanism that might underlie the poor trophoblast invasion seen in this common pregnancy disorder. STUDY FUNDING/COMPETING INTEREST(S) B.A.L. was supported by a grant from Action Medical Research UK (SP4577). A.E.W. was supported by a grant from the Wellcome Trust (091550). There are no competing interests and the authors have no conflict interest to declare. PMID:26082478

  7. EFFECT OF HEME OXYGENASE-1 DEFICIENCY ON PLACENTAL DEVELOPMENT

    PubMed Central

    Zhao, Hui; Wong, Ronald J.; Kalish, Flora S.; Nayak, Nihar R.; Stevenson, David K.

    2009-01-01

    Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway and highly expressed in the placenta. Deficiencies in HO-1, the inducible isoform, have been associated with pregnancy disorders, such as recurrent miscarriages, intrauterine growth retardation, and pre-eclampsia. The aim of this study was to identify if a deficiency in HO-1 affects placental development using a mouse model. When HO-1 heterozygote (Het, HO-1+/?) mice were cross-bred, an extremely low birth rate in homozygote (Mut, HO-1?/?) offspring (2.4%) and small litter sizes were observed. Placentas and fetuses from Het cross-breedings were relatively smaller and weighed less than those from wild-type (WT) cross-breedings at E12.5 and E15.5. Furthermore, Het placentas had significantly less HO-1 mRNA and protein levels than WT placentas, but no significant differences in placental HO activity. Interestingly, HO-2, the constitutive HO isoform, as well as iNOS and eNOS expression were significantly upregulated in Het placentas. Histological examination showed that the junctional zone (JZ) of Het placentas were markedly thinner than those of WT placentas and appeared to be due to an increase in apoptosis. Immunohistochemistry revealed that HO-1-expressing cells were located primarily in the JZ of Het placentas, specifically in the spongiotrophoblast layer. In addition, diastolic blood pressures and plasma soluble VEGFR-1 (sFlt-1) levels were significantly elevated in pregnant Het mice. We conclude that a partial deficiency in HO-1 is associated with morphological changes in the placenta and elevations in maternal diastolic blood pressure and plasma sFlt-1 levels, despite a compensatory increase in HO-2 expression. PMID:19699520

  8. Oxfordshire Women and Their Children's Health (OxWATCH): protocol for a prospective cohort feasibility study

    PubMed Central

    Harrison, S; Petrovic, G; Chevassut, A; Brook, L; Higgins, N; Kenworthy, Y; Selwood, M; Snelgar, T; Arnold, L; Boardman, H; Heneghan, C; Leeson, P; Redman, C; Granne, I

    2015-01-01

    Introduction Some specific pregnancy disorders are known to be associated with increased incidence of long-term maternal ill health (eg, gestational diabetes with late onset type 2 diabetes; pre-eclampsia with arterial disease). To what degree these later health conditions are a consequence of the woman's constitution prior to pregnancy rather than pregnancy itself triggering changes in a woman's health is unknown. Additionally, there is little prospective evidence for the impact of pre-pregnancy risk factors on the outcome of pregnancy. To understand the importance of pre-pregnancy health requires the recruitment of women into a long-term cohort study before their first successful pregnancy. The aim of this feasibility study is to test recruitment procedures and acceptability of participation to inform the planning of a future large-scale cohort study. Methods The prospective cohort feasibility study will recruit nulliparous women aged 18–40 years. Women will be asked to complete a questionnaire to assess the acceptability of our recruitment and data collection procedures. Baseline biophysical, genetic, socioeconomic, behavioural and psychological assessments will be conducted and samples of blood, urine, saliva and DNA will be collected. Recruitment feasibility and retention rates will be assessed. Women who become pregnant will be recalled for pregnancy and postpregnancy assessments. Ethics and dissemination The study protocol was approved by South Central Portsmouth REC (Ref: 12/SC/0492). The findings from the study will be disseminated through peer reviewed journals, national and international conference presentations and public events. Trial registration number http://www.clinicaltrials.gov; NCT02419898. PMID:26553837

  9. Reducing the Decline in Physical Activity during Pregnancy: A Systematic Review of Behaviour Change Interventions

    PubMed Central

    Currie, Sinead; Sinclair, Marlene; Murphy, Marie H.; Madden, Elaine; Dunwoody, Lynn; Liddle, Dianne

    2013-01-01

    Purpose Physical activity (PA) typically declines throughout pregnancy. Low levels of PA are associated with excessive weight gain and subsequently increase risk of pre-eclampsia, gestational diabetes mellitus, hypertension disorders, delivery by caesarean section and stillbirth. Systematic reviews on PA during pregnancy have not explored the efficacy of behaviour change techniques or related theory in altering PA behaviour. This systematic review evaluated the content of PA interventions to reduce the decline of PA in pregnant women with a specific emphasis on the behaviour change techniques employed to elicit this change. Search and Review Methodology Literature searches were conducted in eight databases. Strict inclusion and exclusion criteria were employed. Two reviewers independently evaluated each intervention using the behaviour change techniques (BCT) taxonomy to identify the specific behaviour change techniques employed. Two reviewers independently assessed the risk of bias using the guidelines from the Cochrane Collaboration. Overall quality was determined using the GRADE approach. Findings A total of 1140 potentially eligible papers were identified from which 14 studies were selected for inclusion. Interventions included counselling (n?=?6), structured exercise (n?=?6) and education (n?=?2). Common behaviour change techniques employed in these studies were goal setting and planning, feedback, repetition and substitution, shaping knowledge and comparison of behaviours. Regular face-to-face meetings were also commonly employed. PA change over time in intervention groups ranged from increases of 28% to decreases of 25%. In 8 out of 10 studies, which provided adequate data, participants in the intervention group were more physically active post intervention than controls. Conclusions and Implications Physical activity interventions incorporating behaviour change techniques help reduce the decline in PA throughout pregnancy. Range of behaviour change techniques can be implemented to reduce this decline including goals and planning, shaping knowledge and comparison of outcomes. A lack of high quality interventions hampers conclusions of intervention effectiveness. PMID:23799096

  10. A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries

    PubMed Central

    Saleem, Sarah; Goudar, Shivaprasad S; Patel, Archana; Esamai, Fabian; Garces, Ana; Chomba, Elwyn; Althabe, Fernando; Moore, Janet; Kodkany, Bhalachandra; Pasha, Omrana; Belizan, Jose; Mayansyan, Albert; Derman, Richard J; Hibberd, Patricia L; Liechty, Edward A; Krebs, Nancy F; Hambidge, K Michael; Buekens, Pierre; Carlo, Waldemar A; Wright, Linda L; Koso-Thomas, Marion; Jobe, Alan H; Goldenberg, Robert L

    2014-01-01

    Abstract Objective To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths. Methods A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until sixweeks postpartum. Findings Between 2010 and 2012, 214?070 of 220?235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100?000 live births, ranging from 69 per 100?000 in Argentina to 316 per 100?000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive sixweeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.9711.27), as were perinatal deaths (RR: 4.30; 95%CI: 3.265.67) and 7-day (RR: 3.94; 95%CI: 2.745.65) and 28-day neonatal deaths (RR: 7.36; 95%CI: 5.549.77). Conclusion Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality. PMID:25177075

  11. Structure-function relations in the human placenta.

    PubMed

    Dockery, P; Bermingham, J; Jenkins, D

    2000-02-01

    The human haemochorial placenta is a complex and dynamic interface between embryonic and maternal tissues. A myriad array of compounds has been identified at this interface, some of which exert local effects which might be important in maintaining the integrity of the organ. These compounds are diverse in nature and function; they include enzymes, hormones and bioactive peptides. Successful nidation requires the synchronization of endometrial maturation and embryonic development. The complex nature of this interface requires the application of sound sampling strategies. The new stereological methods have thrown fresh light on the growth and development of the human placenta. These methods permit the objective, quantitative description of morphology by efficient design-based methods. This approach has permitted a better definition of the functional morphology of the placenta. Applications of these methodologies are providing a spatial and temporal framework on which to lay the new physiological and molecular information. Here we review the essential features of the stereological approach, identify useful structural quantities and provide some examples of their application. The problems associated with the quantification of immunocytochemistry are illustrated with the use of immunoreactivity to insulin-like growth factor I receptor in normal placentae and in pre-eclampsia. Although stereology can provide useful quantitative information about the structure of this dynamic tissue, other anatomical methods that could be applied to better define the relationships between structure and function will be discussed. These include confocal microscopy, to examine the dynamic physiological interactions of the different tissue compartments, and low-temperature electron microscopy techniques such as cryosubstitution, to allow better access to the biochemical information resident in the tissue. The complex and dynamic nature of the tissue requires a multidisciplinary approach; central to these investigations is a comprehensive understanding of its fine structure. PMID:10816128

  12. [The obstetrical outlook in uterine malformations].

    PubMed

    Rudigoz, R C; Gaucherand, P; Dargent, D

    1989-01-01

    The authors start with an anatomical description which makes it possible to distinguish from one another septate, bicornuate unicornuate and pseudo-cornuate uteri. The diagnosis is often suggested by the clinical features and is made by using complementary examinations such as ultrasound, hysterography, hysteroscopy and laparoscopy. Although it is difficult to be sure of the incidence of the condition it is thought to be around 1%. In the 10 years from 1978 to 1987 the authors have studied 296 pregnancies occurring in 109 patients who were not operated on and 34 pregnancies occurring in 21 patients who had plastic operations on their uteri. They show that the condition has an effect at all stages of pregnancy and delivery and in the first category of patients (abortion in 38%, extra-uterine pregnancy in 8%, prematurity, pre-eclampsia and malpresentation in 28%, with a high rate for caesarean section in 37%). The prognosis was quite different in patients who had been operated on. The published literature confirms these findings. The authors discuss the different ways of carrying out surgical treatment (simple section or excision of the septum, or Bret-Palmer's plastic operation on the uterus with treatment of the associated vaginal abnormalities), plus the medical treatment (with rest and the use of vasodilatators and drugs for anti-platelet aggregation) to be used during the pregnancy. They conclude that it is necessary to make a diagnosis of what type of malformation is present, to decide which surgical procedures to carry out as this does improve the prognosis greatly. PMID:2723350

  13. Vitamin D3 alters Toll-like receptor 4 signaling in monocytes of pregnant women at risk for preeclampsia.

    PubMed

    Qian, Lei; Wang, Hongyou; Wu, Fenghui; Li, Ming; Chen, Wei; Lv, Lianzheng

    2015-01-01

    Vitamin D deficiency during pregnancy is thought to play a role in the development of preeclampsia; however, the underlying mechanism is not fully understood. In this study, a 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 a daily dose of 2000 IU vitamin D3 supplements (n=30) or receive placebo (n=30) between gestational weeks 20-32 for a total of 12 consecutive weeks. Because vitamin D3 supplementation can induce anti-inflammatory cytokine signaling, peripheral blood monocytes were investigated by flow cytometry for expression of toll-like receptor 4 (TLR4), an important mediator of innate immune response. The pro-inflammatory cytokines secretion of tumor necrosis factor (TNF)-?, interleukin (IL)-6, and IL-1 from monocytes, which are typically upregulated in preeclampsia, was also assessed. The incidence of preeclampsia was significantly lower in patients treated with vitamin D3 compared to the placebo group. Both the mean fluorescence intensity and the positive percentage of monocytes TLR4 in the vitamin D group were significantly lower compared to the placebo group, as well as the concentrations of secreted TNF-?, IL-6, and IL-1, while the concentration of IL-10 was higher. In the placebo group, the positive frequency of monocytes TLR4 was negatively correlated with the concentration of serum 25-hydroxyvitamin D in preeclampsia patients. Based on these results, we conclude that vitamin D3 supplementation for patients at risk of preeclampsia leads to a decrease in the expression of peripheral blood monocytes TLR4 and a subsequent decrease in pro-inflammatory cytokine secretion. Therefore, inhibiting the expression of monocytes TLR4 through vitamin D3 supplement may be a new approach to preeclampsia prevention. PMID:26770399

  14. Notch-dependent RBPJ? inhibits proliferation of human cytotrophoblasts and their differentiation into extravillous trophoblasts.

    PubMed

    Velicky, P; Haider, S; Otti, G R; Fiala, C; Pollheimer, J; Knfler, M

    2014-08-01

    Abnormal development of invasive trophoblasts has been implicated in the pathogenesis of human pregnancy diseases such as pre-eclampsia. However, critical signalling pathways controlling formation and differentiation of these cells have been poorly elucidated. Here, we provide evidence that the canonical Notch pathway, operating through Notch-dependent activation of its key regulatory transcription factor RBPJ?, controls proliferation and differentiation in villous explant cultures and primary trophoblasts of early pregnancy. Immunofluorescence of first trimester placental tissue revealed expression of RBPJ? and its co-activators, the MAML proteins, in nuclei of proliferative cell column trophoblasts (CCT) and differentiated, extravillous trophoblasts (EVTs). However, RBPJ? expression, transcript levels of the Notch target gene HES1 and activity of a Notch/RBPJ?-dependent luciferase reporter decreased during in vitro differentiation of primary cytotrophoblasts on fibronectin. Silencing of RBPJ? using silencing RNAs (siRNAs) increased proliferation of CCTs in floating villous explant cultures analysed by outgrowth and BrdU labelling. Similarly, down-regulation of the transcription factor enhanced BrdU incorporation in isolated primary cultures. However, motility of these cells was not affected. In addition, gene silencing of RBPJ? increased cyclin D1 expression in the two trophoblast model systems as well as markers of the differentiated, EVT, i.e. integrin ?1, ADAM12 and T-cell factor 4. In summary, the data suggest that Notch-dependent RBPJ? activity could be required for balanced rates of trophoblast proliferation and differentiation in human placental anchoring villi preventing exaggerated trophoblast overgrowth as well as premature formation of EVTs. PMID:24850908

  15. Effects of Lipopolysaccharide on Human First Trimester Villous Cytotrophoblast Cell Function In Vitro.

    PubMed

    Li, Liping; Tu, Jiaoqin; Jiang, Yao; Zhou, Jie; Yabe, Shinichiro; Schust, Danny J

    2016-02-01

    It has been shown that adverse obstetrical outcomes such as pre-eclampsia and intrauterine growth retardation correlate with maternal infection. In this study, we investigated mechanisms involved in infection-associated abnormalities in cytotrophoblast function. Primary human first trimester cytotrophoblast cells were isolated and treated with lipopolysaccharide (LPS). Levels of the cytokines and chemokines were measured and cytotrophoblast invasion was investigated. In addition, first trimester decidual macrophages were isolated and treated with the conditioned medium from LPS-treated cytotrophoblast cells, and macrophage migration was assessed. Coculturing decidual macrophages with cytotrophoblast cells was conducted to investigate macrophage costimulatory molecule and receptor expression and intracellular cytokine production. We found that LPS exposure increased cytotrophoblast production of pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, and chemokines IL-8, macrophage inflammatory protein (MIP)-1alpha, and CXCL12 in a dose-dependent manner. In addition, LPS decreased cytotrophoblast invasion, and its effect was Toll-like receptor 4 (TLR4)-dependent and partly TNF-alpha-dependent. Conditioned medium from LPS-stimulated cytotrophoblast cells increased decidual macrophage migration and this effect was partly TLR4-dependent. Furthermore, coculturing decidual macrophages with LPS-exposed cytotrophoblast cells up-regulated macrophage CD80 and CD86 expression and intracellular TNF-alpha and IL-12p40 production, while down-regulating macrophage CD206 and CD209 expression and intracellular IL-10 secretion. LPS-stimulated macrophages also inhibited cytotrophoblast invasion. In conclusion, our results indicate that LPS increases the production of a subset of proinflammatory cytokines and chemokines by human first trimester cytotrophoblast cells, decreases cytotrophoblast invasion, and alters the cross talk between cytotrophoblast cells and decidual macrophages. PMID:26700943

  16. Heme oxygenase and the immune system in normal and pathological pregnancies

    PubMed Central

    Ozen, Maide; Zhao, Hui; Lewis, David B.; Wong, Ronald J.; Stevenson, David K.

    2015-01-01

    Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity. PMID:25964759

  17. The Ubiquitin Ligase ASB4 Promotes Trophoblast Differentiation through the Degradation of ID2

    PubMed Central

    Townley-Tilson, W. H. Davin; Wu, Yaxu; Ferguson, James E.; Patterson, Cam

    2014-01-01

    Vascularization of the placenta is a critical developmental process that ensures fetal viability. Although the vascular health of the placenta affects both maternal and fetal well being, relatively little is known about the early stages of placental vascular development. The ubiquitin ligase Ankyrin repeat, SOCS box-containing 4 (ASB4) promotes embryonic stem cell differentiation to vascular lineages and is highly expressed early in placental development. The transcriptional regulator Inhibitor of DNA binding 2 (ID2) negatively regulates vascular differentiation during development and is a target of many ubiquitin ligases. Due to their overlapping spatiotemporal expression pattern in the placenta and contrasting effects on vascular differentiation, we investigated whether ASB4 regulates ID2 through its ligase activity in the placenta and whether this activity mediates vascular differentiation. In mouse placentas, ASB4 expression is restricted to a subset of cells that express both stem cell and endothelial markers. Placentas that lack Asb4 display immature vascular patterning and retain expression of placental progenitor markers, including ID2 expression. Using JAR placental cells, we determined that ASB4 ubiquitinates and represses ID2 expression in a proteasome-dependent fashion. Expression of ASB4 in JAR cells and primary isolated trophoblast stem cells promotes the expression of differentiation markers. In functional endothelial co-culture assays, JAR cells ectopically expressing ASB4 increased endothelial cell turnover and stabilized endothelial tube formation, both of which are hallmarks of vascular differentiation within the placenta. Co-transfection of a degradation-resistant Id2 mutant with Asb4 inhibits both differentiation and functional responses. Lastly, deletion of Asb4 in mice induces a pathology that phenocopies human pre-eclampsia, including hypertension and proteinuria in late-stage pregnant females. These results indicate that ASB4 mediates vascular differentiation in the placenta via its degradation of ID2. PMID:24586788

  18. [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. PMID:17321188

  19. 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. PMID:17196252

  20. Psychosocial deprivation in women with gestational diabetes mellitus is associated with poor fetomaternal prognoses: an observational study

    PubMed Central

    Cosson, Emmanuel; Bihan, Hlne; Reach, Grard; 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

  1. A systems biology perspective on sVEGFR1: its biological function, pathogenic role and therapeutic use

    PubMed Central

    Wu, Florence T H; Stefanini, Marianne O; Gabhann, Feilim Mac; Kontos, Christopher D; Annex, Brian H; Popel, Aleksander S

    2010-01-01

    Abstract Angiogenesis is the growth of new capillaries from pre-existent microvasculature. A wide range of pathological conditions, from atherosclerosis to cancer, can be attributed to either excessive or deficient angiogenesis. Central to the physiological regulation of angiogenesis is the vascular endothelial growth factor (VEGF) system – its ligands and receptors (VEGFRs) are thus prime molecular targets of pro-angiogenic and anti-angiogenic therapies. Of growing interest as a prognostic marker and therapeutic target in angiogenesis-dependent diseases is soluble VEGF receptor-1 (sVEGFR1, also known as sFlt-1) – a truncated version of the cell membrane-spanning VEGFR1. For instance, it is known that sVEGFR1 is involved in the endothelial dysfunction characterizing the pregnancy disorder of pre-eclampsia, and sVEGFR1’s therapeutic potential as an anti-angiogenic agent is being evaluated in pre-clinical models of cancer. This mini review begins with an examination of the protein domain structure and biomolecular interactions of sVEGFR1 in relation to the full-length VEGFR1. A synopsis of known and inferred physiological and pathological roles of sVEGFR1 is then given, with emphasis on the utility of computational systems biology models in deciphering the molecular mechanisms by which sVEGFR1’s purported biological functions occur. Finally, we present the need for a systems biology perspective in interpreting circulating VEGF and sVEGFR1 concentrations as surrogate markers of angiogenic status in angiogenesis-dependent diseases. PMID:19840194

  2. 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

  3. 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 ?M 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. PMID:24623739

  4. Lack of cardioprotection by single-dose magnesium prophylaxis on isoprenaline-induced myocardial infarction in adult Wistar rats

    PubMed Central

    Garson, Christie; Kelly-Laubscher, Roisin; Gwanyanya, Asfree; Blackhurst, Dee

    2015-01-01

    Summary Aim Magnesium (Mg2+) is effective in treating cardiovascular disorders such as arrhythmias and pre-eclampsia, but its role during myocardial infarction (MI) remains uncertain. In this study, we investigated the effects of Mg2+ pre-treatment on isoprenaline (ISO)-induced MI in vivo. Methods Rats divided into four groups were each pre-treated with either MgSO4 (270 mg/kg intraperitoneally) or an equivalent volume of physiological saline, prior to the ISO (67 mg/kg subcutaneously) or saline treatments. One day post-treatment, the electrocardiogram and left ventricular blood pressures were recorded. Infarcts were determined using 2,3,5-triphenyltetrazolium chloride staining, and serum markers of lipid peroxidation were measured with spectrophotometric assays. Results Mg2+ pre-treatment neither altered the ISO-induced infarct size compared with ISO treatment alone (p > 0.05), nor reversed the low-voltage electrocardiogram or the prominent Q waves induced by ISO, despite a trend to decreased Q waves. Similarly, Mg2+ did not prevent the ISO-induced decrease in peak left ventricular blood pressure or the decrease in minimal rate of pressure change. Mg2+ did not reverse the ISO-induced gain in heart weight or loss of body weight. Neither ISO nor Mg2+ altered the concentrations of lipid peroxidation markers 24 hours post MI induction. Conclusion Although Mg2+ had no detrimental effects on electrical or haemodynamic activity in ISO-induced MI, the lack of infarct prevention may detract from its utility in MI therapy. PMID:26212925

  5. Physical activity, sedentary behavior and risk of hypertensive disorders of pregnancy in Hispanic women

    PubMed Central

    Chasan-Taber, Lisa; Silveira, Marushka; Pekow, Penelope; Braun, Barry; Manson, JoAnn E.; Solomon, Caren G.; Markenson, Glenn

    2016-01-01

    Objective Prior studies of the association between physical activity and hypertensive disorders of pregnancy have been conflicting; the majority focused on leisure-time activity only, did not use physical activity questionnaires validated for pregnancy, and were conducted in primarily non-Hispanic white populations. Methods We prospectively evaluated this association among 1240 Hispanic women in Proyecto Buena Salud. The Pregnancy Physical Activity Questionnaire, validated for use in pregnancy, was used to assess pre- and early pregnancy sports/exercise, household/caregiving, occupational and transportation activity. Diagnoses of hypertensive disorders of pregnancy were based on medical record abstraction and confirmed by the study obstetrician. Results A total of 49 women (4.0%) were diagnosed with a hypertensive disorder of pregnancy, including 32 women (2.6%) with pre-eclampsia. In age-adjusted analyses, high levels of early pregnancy household/caregiving activity were associated with reduced risk of total hypertensive disorders (OR = 0.4, 95% CI 0.1–0.9) and preeclampsia (OR = 0.3, 95% CI 0.1–0.9) relative to low levels; however, these findings were no longer statistically significant in multivariable models. Pre-pregnancy activity and pattern of activity from pre- to early-pregnancy were not significantly associated with risk. Finally, sedentary behavior was not significantly associated with hypertensive disorders. Conclusion Findings from this prospective study of Hispanic women were consistent with those of prior prospective cohorts indicating that physical activity prior to and during early pregnancy does not significantly reduce risk of hypertensive disorders of pregnancy. PMID:25121645

  6. Three-Dimensional Segmented Poincar Plot Analyses SPPA3 Investigates Cardiovascular and Cardiorespiratory Couplings in Hypertensive Pregnancy Disorders

    PubMed Central

    Fischer, Claudia; Voss, Andreas

    2014-01-01

    Hypertensive pregnancy disorders affect 68% 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 Poincar 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. PMID:25429364

  7. 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. PMID:18309767

  8. Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells.

    PubMed

    Djurisic, S; Teiblum, S; Tolstrup, C K; Christiansen, O B; Hviid, T V F

    2015-03-01

    The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy complications, partly explained by HLA-G polymorphisms which are associated with differences in the alternative splicing pattern and of the stability of HLA-G mRNA. Of special importance is a 14 bp insertion/deletion polymorphism located in the 3'-untranslated region of the HLA-G gene. In the current study, we present novel evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, using a very accurate and sensitive Digital droplet PCR technique. Allelic imbalance in heterozygous samples was observed as differential expression levels of 14 bp insertion/deletion allele-specific mRNA transcripts, which was further associated with low levels of HLA-G surface expression on primary trophoblast cells. Full gene sequencing of HLA-G allowed us to study correlations between HLA-G extended haplotypes and single-nucleotide polymorphisms and HLA-G surface expression. We found that a 1:1 expression (allelic balance) of the 14 bp insertion/deletion mRNA alleles was associated with high surface expression of HLA-G and with a specific HLA-G extended haplotype. The 14 bp del/del genotype was associated with a significantly lower abundance of the G1 mRNA isoform, and a higher abundance of the G3 mRNA isoform. Overall, the present study provides original evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, which influences HLA-G surface expression on primary trophoblast cells, considered to be important in the pathogenesis of pre-eclampsia and other pregnancy complications. PMID:25425608

  9. Heme oxygenase and the immune system in normal and pathological pregnancies.

    PubMed

    Ozen, Maide; Zhao, Hui; Lewis, David B; Wong, Ronald J; Stevenson, David K

    2015-01-01

    Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity. PMID:25964759

  10. 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

  11. Adverse fetomaternal outcome among pregnant overweight women

    PubMed Central

    Awan, Shazia; Bibi, Seema; Makhdoom, Asadullah; Farooq, Sumaiya; SM, Tahir; Qazi, Roshan Ara

    2015-01-01

    Objective: To compare the adverse fetometernal out come in overweight and normal weight pregnant women. Methods: This comparative cohort study was conducted from 1st October 2010 to 30 September 2012. Total 200 gravid women 100 were overweight and 100 normal weight pregnant women with gestational age for 08-40 weeks were included. Women having BMI (25 29.9 Kg/m2) were measured overweight and included in group A and 100 women having normal BMI of 18.5 to 24.9 as controls were in-group B. Chi-square test was applied to compare the proportion of maternal and fetal outcomes. Significant P value of < 0.05 was considered. Results: The age range was between 30 to 45 years with mean age of 304.1 years in both groups. Overweight pregnant women had significantly high frequency of pre-eclampsia (27% versus 9% in controls), PIH (24% versus 8% in controls), gestational diabetes mellitus (22% versus 5% in controls), prolonged labour (4% versus 6% in controls), Caesarean section (44% versus 16% in controls), Wound infection (3% versus 2% in controls) and Postpartum Hemorrhage (5% versus 2% in controls). P-value < 0.001 was considered significance. Fetal complications in overweight pregnant women compared to controls i.e. Still birth (13% versus 2%), Early neonatal death (11% versus 1%), shoulder dystocia (5% versus 1%) and NICU admission (47% versus 10%). Results were statistically significant except shoulder dystocia. Conclusion: We conclude that the result of present study indicates obesity exerts deleterious effect, both on fetal and maternal outcome. PMID:26101496

  12. A rare presentation of aplasia cutis congenita after feto-reduction in a trichorionic-triamniotic pregnancy.

    PubMed

    Vettori, D J; Jairath, P

    2015-01-01

    Aplasia cutis congenita (ACC) is rare skin disorder of newborns that has been linked to both assisted reproductive technology (ART) and feto-reduction procedures. ACC is characterized by well-demarcated lesions that are devoid of all skin layers. Group-V ACC presents with a distinctive and symmetrical distribution pattern. It is thought to result from an insult to the fetus after concomitant twin demise and is almost exclusively reported in monochorionic gestations.A 41-year-old female with an in vitro fertilization (IVF) assisted tri-chorionic gestation subsequently underwent selective feto-reduction of Fetus C. The patient delivered two pre-term neonates secondary to pre-eclampsia. The initial exam of Twin B showed extensive, well-demarcated, symmetrical areas devoid of any skin over the anterior and lateral trunk, extending up the lateral thoracic walls. Chest and abdominal viscera were visible through a thin fibrous membrane. The skin defects were managed conservatively with twice-daily dressings of Aquaphor, and Vaseline gauze. The areas of aplasia slowly contracted, though residual scarring was noted. After four weeks in the NICU, most of the areas were healed.ACC in multi-fetal pregnancies is a rare, but well-described complication. This is, to our knowledge, the first reported case in a tri-chorionic IVF gestation after feto-reduction. With increased incidence of ART-associated pregnancies and the use of feto-reduction for higher order gestations, this may become more common. Neonates often require specialized intensive care. Conservative management usually will suffice, although surgical grafting may be required. Physicians should be aware of this condition and counsel their feto-reduction patients of the risk. PMID:26485557

  13. Lack of beneficial effects on the NO-donor, molsidomine, in the L-NAME-induced pre-eclamptic syndrome in pregnant rats.

    PubMed Central

    Richer, C.; Boulanger, H.; Es-Slami, S.; Giudicelli, J. F.

    1996-01-01

    1. In pregnant rats, chronic NO-synthase inhibition induces the development of a pre-eclamptic syndrome, characterized by an increase in maternal blood pressure, a loss of vascular refractoriness to pressor stimuli, a reduction in litter size and a decrease in pups (and maternal) weight. We investigated whether a NO-donor, molsidomine, administered during NO synthase inhibition, could restore a normal pregnancy. 2. Pregnant rats were given daily, starting from day 14 of gestation, saline (controls), or L-NAME (50 mg kg-1 d-1), or molsidomine (15 or 30 mg kg-1 d-1), or the L-NAME + molsidomine combinations. Maternal blood pressure and body weight, litter size, pups weight and vascular reactivity to pressor stimuli (angiotensin II, noradrenaline, electrical stimulation of the spinal cord) were investigated. 3. L-NAME alone, as compared to controls, increased maternal blood pressure, reduced litter size (-59%), increased foetal reabsorptions (+ 625%) and decreased foetal weight (-10%). Vascular reactivity to pressor stimuli was enhanced. 4. Molsidomine alone, as compared to controls, dose-dependently decreased maternal blood pressure but had no effect vascular reactivity and, whatever the dose, on foetal outcome. 5. The L-NAME-molsidomine combinations dose (of molsidomine)-dependently limited the rise in maternal blood pressure induced by L-NAME alone but unexpectedly, dose-dependently and significantly worsened pregnancy evolution, e.g., at 30 mg kg-1 d-1: litter size (-80%), foetal reabsorptions (+ 1025%), foetal weight (-24%). Vascular reactivity to pressor stimuli was paradoxically further enhanced. 6. Thus, in a chronic NO deprivation-induced model of pre-eclampsia in rats, molsidomine, possibly because of its hypotensive action, worsens the foetal outcome, which questions the usefulness of NO-donors in pre-eclamptic women. PMID:8982513

  14. Carotid angiodysplasia complicated by the use of anti-hypertensive drugs during pregnancy: a case report

    PubMed Central

    2011-01-01

    Introduction Hypertensive syndromes in pregnancy are one of the leading causes of obstetric admissions into intensive care units. They are related to changes in the central nervous system caused by a decrease in cerebral perfusion pressure, indicated by an increase in intracranial pressure. These changes in pressure usually result from acute injuries or a decrease in the mean arterial pressure due to iatrogenic action or shock. However, other vascular disorders may contribute to similar occurrences. Case presentation A 15-year-old girl was admitted to our hospital complaining of severe headaches since the eighth month of pregnancy, and presented with an arterial blood pressure of 180/120 mmHg. The diagnostic hypothesis was pre-eclampsia. Our patient's blood pressure levels remained elevated, and she was submitted to a cesarean section. After the procedure, she was referred to our infirmary, presenting with a blank distant look and with no interaction with the environment, dyslalia, and labial and upper and lower right limb paresis. She was confused and unable to speak, but responded to painful stimuli as she conveyed abdominal pain at superficial and deep palpation. The hypothesis of post-partum psychosis was suggested. She was then transferred to our intensive care unit, maintaining an impassive attitude in bed but reacting to external stimuli. Results of a computed tomography scan revealed ischemic infarction of the territory of her left middle cerebral artery. A selective cerebral arteriography showed bilateral occlusion of her internal carotid artery in the intracranial position, prebifurcation and angiodysplasia in the cervical segments of her internal carotid artery. Sixteen days after hospital admission, our patient died. Conclusion This data shows the need for careful monitoring of hypertensive syndromes in pregnancy cases, especially in cases with a history of chronic hypertension or with vascular alterations, It also highlights the need for constant supervision of blood pressure levels during the use of anti-hypertensive medications. PMID:21867546

  15. Comparison of obstetric outcome in pregnant women with and without microalbuminuria

    PubMed Central

    Singh, Harneet; Samal, Sunita; Mahapatro, Akshaya; Ghose, Seetesh

    2015-01-01

    Background: Maternal and neonatal outcome is an index of quality of health and life in human society. To predict serious outcomes in pregnancy various parameters are being researched so that pregnant women who are at risk are identified early and measures taken to ensure a good outcome of pregnancy. Studies have shown an association between microalbuminuria and adverse pregnancy outcome. This study was undertaken to compare obstetric outcome in pregnant women with and without microalbuminuria. Materials and Methods: A prospective cohort study was performed on 69 pregnant women between 20 and 28 weeks of gestation. Urine tests for albuminuria and creatinine measurements were performed in all women and the albumin to creatinine ratio was calculated. The women with microalbuminuria and those without microalbuminuria were monitored until the end of their pregnancy and compared for pregnancy outcome. Results: The age distribution in the two groups was found to be similar and comparable. Preterm labor was strongly associated with microalbuminuria group (P = 0.001**)strongly significant. Incidence of maternal complications were more with microalbuminuria group (P < 0.001**). Fetal complications were significantly more in terms of intrauterine growth restriction, prematurity, low birth weight, low Apgar score and more incidence of neonatal intensive care unit admission with microalbuminuria group (P = 0.010*)moderately significant. Conclusion: It was found that fetal complications were more associated with babies of pregnant women with microalbuminuria. Though maternal complications were more associated with microalbuminuria group, individual events like premature rupture of membrane, preterm premature rupture of membrane had no statistically significant association with microalbuminuria except preterm labor. However, occurrence of pre-eclampsia was more with microalbuminuria, though it didn’t carry any statistical significance. PMID:25810648

  16. Naturally Occurring Variation in Trophoblast Invasion as a Source of Novel (Epigenetic) Biomarkers

    PubMed Central

    van Dijk, Marie; Visser, Allerdien; Posthuma, Janny; Poutsma, Ankie; Oudejans, Cees B. M.

    2012-01-01

    During the first trimester of pregnancy fetal trophoblasts invade the maternal decidua, thereby remodeling the maternal spiral arteries. This process of trophoblast invasion is very similar to cancer cell invasion, with multiple signaling pathways shared between the two. Pregnancy-related diseases, e.g., pre-eclampsia, and cancer metastasis start with a decrease or increase in cellular invasion, respectively. Here, we investigate if first trimester placental explants can be used to identify epigenetic factors associated with changes in cellular invasion and their potential use as biomarkers. We show that the outgrowth potential of first trimester explants significantly correlates with promoter methylation of PRKCDBP and MMP2, two genes known to be differentially methylated in both placenta and cancer. The increase in methylation percentage of placental cells coincides with an increase in invasion potential. Subsequently, as a non-invasive marker must be detectable in blood, plasma samples of pregnant and non-pregnant women were analyzed. The MMP2 promoter showed high methylation levels in non-pregnant plasma samples, which decreased in pregnant plasma samples which also contain placental DNA. The decrease in methylated plasma DNA during pregnancy is most likely due to the fractional increase in unmethylated placental DNA. This suggests that the level of unmethylated DNA has the potential to be used as an invasion marker, where higher levels of unmethylated DNA indicate a lower invasion potential of trophoblasts. These proof of principle data provide evidence that human first trimester placental explants are an excellent ex vivo model system to identify (epigenetic) factors and thus potential biomarkers associated with changes in cellular invasion, e.g., to detect pregnancy-related diseases or cancer metastasis. To identify novel biomarkers the next step is to correlate naturally occurring variation in invasion potential to changes in (epigenetic) factors by genome-wide approaches such as massively parallel sequencing. PMID:22363344

  17. New-Onset Maternal Gestational Hypertension and Risk of Retinopathy of Prematurity

    PubMed Central

    Zayed, Mohamed A.; Uppal, Abhineet

    2010-01-01

    Purpose. To evaluate associations between conditions of maternal new-onset gestational hypertension (mHTN) and the features imparting risk of severe retinopathy of prematurity (ROP) in preterm infants. Methods. Hospital databases and charts of all preterm inborn infants at the University of North Carolina from 1996 to 2007 were retrospectively reviewed. The presence or absence of mHTN (e.g., pre-eclampsia) and infant factors (birthweight, gestational age, erythropoietin use, and zone and stage of ROP) were analyzed for independence of association. Results. Of the 5143 infants, 323 had ROP and 76 had mothers with mHTN. Infants with ROP were more likely to have mothers with mHTN and to be younger and smaller at birth. At initial examination, more infants of mothers with mHTN had vascularization into the lower zones than did infants of mothers without mHTN (P < 0.001). However, at the examination in which the most severe ROP was present, there was no association between mHTN and ROP stage (P = 0.2342). Analysis of stage and zone together showed that infants born to mothers with mHTN were more likely to have ROP at initial examination, after adjustment for gestational age, but not for birth weight. The use of erythropoietin was not associated with ROP zone or stage, even after adjustment for maternal condition, infant birth weight, or gestational age. Conclusions. Although larger avascular areas or higher severity scores were associated with mHTN after adjustment for gestational age at initial examination, no associations were found between mHTN and ROP severity score at the examination when ROP was most severe. There were no associations between ROP severity and treatment with erythropoietin. PMID:20463319

  18. Blood dendritic cells: "canary in the coal mine" to predict chronic inflammatory disease?

    PubMed

    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

  19. 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. PMID:20946275

  20. Obstetric Outcome in Early and Late Onset Gestational Diabetes Mellitus.

    PubMed

    Easmin, S; Chowdhury, T A; Islam, M R; Beg, A; Jahan, M K; Latif, T; Dhar, S; Alam, M N; Akhter, M

    2015-07-01

    Obstetric outcome in early onset and late onset GDM was compared in a prospective study conducted at the Department of Obstetrics & Gynecology in BIRDEM, Dhaka, Bangladesh. A total 120 pregnant women were recruited purposively for the study in which 60 were early onset GDM and 60 were late onset GDM during study period of January 2008 to December 2009. Patients were followed up in different periods of gestation, during delivery and early postpartum period & findings were compared between two groups. BMI & family history of diabetes were significantly higher in early GDM group (p<0.05). Evidence of increased glycaemia was observed in early GDM group & difference of glycaemic status was statistically significant (p<0.05). Insulin was needed in 85% of early onset GDM and 55% in late onset GDM. There was also significant difference (p<0.05). In this study, 23.3% of early onset GDM group developed pre-eclampsia while in late onset GDM it was 10% and was statistically significant (p<0.05). Regarding intrapartum & postpartum complications - perineal tear, PPH wound infection, puerperal sepsis were more in early onset than late onset GDM group with no significant difference. Regarding foetal outcome, 8.3% early GDM group delivered asphyxiated baby in comparison to 3.3% in late GDM group. Twenty percent (20%) of early onset GDM group had to admit their babies in neonatal unit while in late onset group it was 5%. There was significant difference between two groups (p<0.05). Neonatal hypoglycaemia was also statistically significantly (p<0.05) higher in early GDM group. Neonatal hyper-bilirubinaemia, RDS, perinatal death was more in early onset GDM subjects. Early onset GDM subjects are high risk subgroup & have significant deleterious effect on maternal and perinatal outcome than late GDM groups. PMID:26329938

  1. 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 transcriptionpolymerase chain reaction (qRTPCR). 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

  2. Heme oxygenase induction attenuates TNF-?-induced hypertension in pregnant rodents

    PubMed Central

    George, Eric M.; Stout, Jacob M.; Stec, David E.; Granger, Joey P.

    2015-01-01

    Pre-eclampsia is a hypertensive disorder of pregnancy initiated by placental insufficiency and chronic ischemia. In response, several pathways activated in the placenta are responsible for the maternal syndrome, including increased production of the anti-angiogenic protein, sFlt-1, and inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-?). Previous studies have demonstrated that heme oxygenase (HO) induction can block TNF-? pathways in vitro and attenuate placental ischemia-induced sFlt-1 in vivo. Here, we investigated whether HO-1 induction could attenuate TNF-?-induced hypertension in pregnant rats. In response to TNF-? infusion (100 ng/day i.p.), maternal mean arterial pressure (MAP) increased vs. control animals (104 3 vs. 119 3 mmHg). HO-1 induction had no effect in control animals, but significantly decreased MAP in TNF-?-infused animals (108 2 mmHg). Placental vascular endothelial growth factor (VEGF) was decreased in response to TNF-? infusion (92 4 vs. 76 2 pg/mg). Placental sFlt-1 was increased by TNF-? infusion (758 45 vs. 936 46 pg/mg, p < 0.05), which trended to normalization by HO-1 induction (779 98 pg/mg). In contrast, HO-1 induction had no significant effect on placental VEGF in TNF-?-infused animals. Taken together, these data suggest that one of the key mechanisms by which HO exerts cytoprotective actions in the placenta during inflammation due to chronic ischemia is through suppression of sFlt-1. Further work elucidating the bioactive metabolites of HO-1 in innate inflammatory responses to placental ischemia is warranted. PMID:26347650

  3. 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) PMID:1362187

  4. Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor.

    PubMed

    Evans, Jemma

    2016-03-01

    Human chorionic gonadotropin (hCG), as one of the first embryonic products, has been extensively investigated for its role in implantation and placental development. Discovery of an over-glycosylated form of this hormone, hyperglycosylated hCG (hCG-H), has provided an additional level of complexity in our understanding of the implantation and placentation process; the structure, activity and functional implications of alterations in hCG isoforms throughout pregnancy are still being characterized. HCG-H comprises up to 90% of total hCG measurable in serum and urine during the first 2-3 weeks of pregnancy when invasive trophoblast activity is high, dropping to negligible proportions, less than 5%, of total hCG at the end of the first trimester. Functionally, hCG-H promotes trophoblast invasion during early pregnancy and has potential roles in immune cell modulation and endothelial function within the uterus at the time of pregnancy initiation. Altered levels of hCG-H are characteristics of pregnancy complications of altered trophoblast function and inadequate placentation, such as pre-eclampsia, and also over-abundance of invasive cytotrophoblasts, such as Down's syndrome. Improving our basic knowledge of the functional role-specific hCG isoforms plays in the complex cascade of events involved in implantation and placental development, and determining dynamic changes in the structure and activity of hCG isoforms throughout gestation will facilitate evidence-based decisions in assisted reproduction/in vitro fertilization based on the potential of embryos to implant, provide biomarkers for diagnosis of pregnancy complications associated with altered placental development and enhance understanding of how hCG isoforms may influence receptivity of the endometrium. PMID:26676718

  5. Therapeutics and anaesthesia.

    PubMed

    Magee, Laura A; Lowe, S; Douglas, M J; Kathirgamanathan, A

    2011-08-01

    Many aspects of hypertension care outside pregnancy may be applied in pregnancy, but little information is available on which to base decision-making. It would seem reasonable to continue previous dietary salt restriction and physical activity in women with pre-existing (and controlled) hypertension, encourage a heart-healthy diet in all women with a hypertension disorder of pregnancy, and take patient preference into account when deciding on place of care. Although bed rest has become a key part of obstetric practice and for care of women with a hypertension disorder of pregnancy, in particular, the evidence is lacking to support this practice. This may also increase thromboembolic risk. Antihypertensive treatment is strongly advised for women with severe hypertension. The most common agents are parenteral labetalol, hydralazine, or oral nifedipine capsules. Clinicians should familiarise themselves with multiple agents. Until the role of antihypertensive treatment for non-severe hypertension in pregnancy is clarified by ongoing research, clinicians should explicitly state an individual patient's blood pressure goal, which could reasonably be anywhere between 130/80 and 155/105 mmHg. Labetalol and methyldopa are used most commonly. Breastfeeding should be encouraged. Many risk factors for hypertension (e.g. obesity), as well as hospitalisation and pre-eclampsia, all increase the thromboembolic risk for pregnant women, and care providers should consider thromboprophylaxis in the appropriate setting. Finally, anaesthetists play a critical role in the management of women with a hypertension disorder of pregnancy, and should be involved earlier rather than later in the course of their care. PMID:21478058

  6. 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

  7. 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

  8. Pattern of severe maternal morbidity in a tertiary hospital of Delhi, India: a pilot study.

    PubMed

    Chhabra, Pragti; Guleria, Kiran; Saini, Narinder Kumar; Anjur, Kannan Tupil; Vaid, Neelam Bala

    2008-10-01

    Severe maternal morbidity also known as 'near miss' may be a good indicator of the quality and effectiveness of obstetric care, as it may identify priorities in maternal care more rapidly than mortality alone. The objective of the study was to observe the pattern of severe maternal morbidity and its associated factors in a tertiary care hospital in Delhi. All patients admitted to the obstetrics and gynaecology department who fulfilled the definition of severe maternal morbidity conditions were included. A proforma was used to record sociodemographic, obstetric, antenatal care treatment and outcome details. A total of 63 women were included for analysis. The incidence of severe maternal morbidity was 3.3/100 deliveries. The mean age of the patients was 26.3 +/- 5 years. More than half (55.5%) were uneducated: almost one-third (32%) were from outside Delhi - the median distance travelled was 10 km. The majority were antenatal admissions (68.3%). The proportion of postdelivery or abortion cases were greater among women who came from outside Delhi. Only 38.1% were registered during the antenatal period. The diagnoses were: eclampsia/pre-eclampsia (35%); haemorrhage (35%); sepsis (13%); obstructed labour (9.5%) and other medical conditions (11%). Severe anaemia was observed in 22% of cases. Only 43.5% were normal vaginal deliveries and 54.5% were delivered by caesarean section or with the use of instruments; 61.3% were live births. Hysterectomy was performed in 14.8%: the proportion of hysterectomy was higher in obstructed labour. Severe maternal morbidity cases constitute a significant burden on health resources. PMID:18820181

  9. The role of arginine, homoarginine and nitric oxide in pregnancy.

    PubMed

    Khalil, Asma; Hardman, Lotte; O Brien, Pat

    2015-09-01

    Normal pregnancy leads to profound maternal hemodynamic changes, including increased blood volume and vasodilatation. Several vasodilator mediators are implicated, including prostaglandins, carbon monoxide and nitric oxide (NO). Pre-eclampsia (PE) affects 3-10 % of pregnancies and is associated with increased maternal and perinatal morbidity and mortality. Around 8 % of pregnancies are complicated by intra-uterine growth restriction (IUGR), also associated with increased perinatal mortality and morbidity. PE and IUGR often co-exist. NO is essential for the formation of healthy endothelium, and in pregnancy promotes endovascular invasion by the cytotrophoblast. As interstitial trophoblasts invade the maternal spiral arteries in the uterine wall, they produce NO which acts on artery walls to create a low-resistance, high-caliber uteroplacental unit. If this process fails, the result is a high-resistance uteroplacental circulation. The hypoperfused and ischemic placenta releases antiangiogenic factors which mediate generalized endothelial dysfunction, oxidative stress and inflammatory mediators. It is these mediators that are implicated in both the fetal and maternal syndromes of PE and IUGR. Studies of NO and its modulator amino acids, including the precursors arginine and homoarginine and the NO synthesis inhibitor asymmetric dimethylarginine (ADMA), have investigated their role in both normal and pathological pregnancies. Many studies of PE (and, to a lesser extent, IUGR) have investigated maternal circulating ADMA, arginine and homoarginine levels. This article reviews and discusses the role of these amino acids in pregnancy. The results have shed some light on their role in these pathologies, but some of the findings have been conflicting and more research is needed. Nevertheless, therapeutic interventions that manipulate these guanidine-amino acids and their interactions hold real promise for the management of pregnancies complicated by PE and/or IUGR, and the results of ongoing studies are eagerly awaited. PMID:26092522

  10. 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 can lead to adverse impacts on short-term survival as well as long-term health and development. 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 young children to help advance the global MNCH agenda. PMID:26166560

  11. 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 environmental factors for high-risk groups, and should consider this capacity in their usual practice. PMID:22224116

  12. Fetal cerebral hemodynamic in gestational diabetic versus normal pregnancies: a Doppler velocimetry of middle cerebral and umbilical arteries.

    PubMed

    Shabani Zanjani, Mansoureh; Nasirzadeh, Roya; Fereshtehnejad, Seyed-Mohammad; Yoonesi Asl, Ladan; Alemzadeh, Seyed-Amir Pooya; Askari, Sareh

    2014-03-01

    Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancies. Evaluating other conditions, including intra uterine growth restriction and pre-eclampsia, some studies have shown significant changes in blood flow velocity of fetal middle cerebral artery (MCA). Our study is one of the few that has aimed to assess the effects of GDM on Doppler parameters of the fetal MCA and umbilical artery (UA) and to compare with normal pregnancies. This cross-sectional study was performed on 66 pregnant women, including 33 women with GDM and the others without it, in Akbar-Abadi University Hospital in Tehran, Iran during 2010-2011. Peak systolic and diastolic velocities, pulsatility index (PI), resistance index (RI) and systolic diastolic ratio (SD) were recorded in UA as well as both right and left fetal MCAs for every recruited pregnant women by means of Doppler ultrasonography. The mean gestational age at the time of examination was 34.45 (SD = 2.62) weeks in GDM group. Although all of the measured Doppler parameters had higher values in GDM pregnancies, the differences were not significant between two groups of study; except for the left fetal MCA-PI, which was significantly higher in GDM group [2.07 (SD = 0.07) vs. 1.85 (SD = 0.74), P = 0.03]. Our results show that gestational diabetes may contribute to an elevated PI in the fetal MCA. Although there is not yet strong proof for the effect of GDM on the fetal brain hemodynamics, the significant higher MCA-PI warrants more attention towards better controlling of the hyperglycemia during pregnancy. PMID:23797352

  13. A Grhl2-dependent gene network controls trophoblast branching morphogenesis.

    PubMed

    Walentin, Katharina; Hinze, Christian; Werth, Max; Haase, Nadine; Varma, Saaket; Morell, Robert; Aue, Annekatrin; Ptschke, Elisabeth; Warburton, David; Qiu, Andong; Barasch, Jonathan; Purfrst, Bettina; Dieterich, Christoph; Popova, Elena; Bader, Michael; Dechend, Ralf; Staff, Anne Cathrine; Yurtdas, Zeliha Yesim; Kilic, Ergin; Schmidt-Ott, Kai M

    2015-03-15

    Healthy placental development is essential for reproductive success; failure of the feto-maternal interface results in pre-eclampsia and intrauterine growth retardation. We found that grainyhead-like 2 (GRHL2), a CP2-type transcription factor, is highly expressed in chorionic trophoblast cells, including basal chorionic trophoblast (BCT) cells located at the chorioallantoic interface in murine placentas. Placentas from Grhl2-deficient mouse embryos displayed defects in BCT cell polarity and basement membrane integrity at the chorioallantoic interface, as well as a severe disruption of labyrinth branching morphogenesis. Selective Grhl2 inactivation only in epiblast-derived cells rescued all placental defects but phenocopied intraembryonic defects observed in global Grhl2 deficiency, implying the importance of Grhl2 activity in trophectoderm-derived cells. ChIP-seq identified 5282 GRHL2 binding sites in placental tissue. By integrating these data with placental gene expression profiles, we identified direct and indirect Grhl2 targets and found a marked enrichment of GRHL2 binding adjacent to genes downregulated in Grhl2(-/-) placentas, which encoded known regulators of placental development and epithelial morphogenesis. These genes included that encoding the serine protease inhibitor Kunitz type 1 (Spint1), which regulates BCT cell integrity and labyrinth formation. In human placenta, we found that human orthologs of murine GRHL2 and its targets displayed co-regulation and were expressed in trophoblast cells in a similar domain as in mouse placenta. Our data indicate that a conserved Grhl2-coordinated gene network controls trophoblast branching morphogenesis, thereby facilitating development of the site of feto-maternal exchange. This might have implications for syndromes related to placental dysfunction. PMID:25758223

  14. Termination of pregnancy for maternal indications at the limits of fetal viability: a retrospective cohort study in the Dutch tertiary care centres

    PubMed Central

    van Eerden, L; Zeeman, G G; Page-Christiaens, G C M; Vandenbussche, F; Oei, S G; Scheepers, H C J; van Eyck, J; Middeldorp, J M; Pajkrt, E; Duvekot, J J; de Groot, C J M; Bolte, A C

    2014-01-01

    Objective Maternal morbidity, either pregnancy related or pre-existent, can become life threatening and of such severity as to warrant termination of pregnancy (TOP). In this situation, chances of fetal survival are usually poor, either because of low gestational age and/or because of the fetal effects of the maternal condition. Examples include severe growth restriction in pre-eclampsia and intrauterine infection due to the very early preterm prelabour rupture of membranes. There are very few reports on the prevalence of TOP for maternal indication at the limits of fetal viability. We investigated the prevalence of and indications for TOP on maternal indication in the 10 tertiary care centres in the Netherlands during the past decade. Study design We conducted a retrospective review of the medical records of all women who underwent TOP for maternal indications between 22 and 27 completed weeks of gestation in all 10 tertiary care centres from 2000 to 2009. Results During the study period, there were 1?929?470 deliveries; 163?052 (8.4%) of these took place in one of the 10 tertiary care centres and 177 pregnancies were terminated for severe maternal disease, 131 for hypertensive disorders, 29 for intrauterine infection and 17 for other reasons. The mean gestational age at TOP was 171?days (243/7)10?days. No maternal deaths were recorded. The overall perinatal mortality was 99.4%. Conclusions Over a 10-year period, TOP for maternal indications was performed in 1 in 1000 deliveries in the 10 Dutch tertiary care centres. Hypertensive disorders comprised three-quarters of the cases. PMID:24939810

  15. The Quality of Clinical Maternal and Neonatal Healthcare – A Strategy for Identifying ‘Routine Care Signal Functions’

    PubMed Central

    Brenner, Stephan; De Allegri, Manuela; Gabrysch, Sabine; Chinkhumba, Jobiba; Sarker, Malabika; Muula, Adamson S.

    2015-01-01

    Background A variety of clinical process indicators exists to measure the quality of care provided by maternal and neonatal health (MNH) programs. To allow comparison across MNH programs in low- and middle-income countries (LMICs), a core set of essential process indicators is needed. Although such a core set is available for emergency obstetric care (EmOC), the ‘EmOC signal functions’, a similar approach is currently missing for MNH routine care evaluation. We describe a strategy for identifying core process indicators for routine care and illustrate their usefulness in a field example. Methods We first developed an indicator selection strategy by combining epidemiological and programmatic aspects relevant to MNH in LMICs. We then identified routine care process indicators meeting our selection criteria by reviewing existing quality of care assessment protocols. We grouped these indicators into three categories based on their main function in addressing risk factors of maternal or neonatal complications. We then tested this indicator set in a study assessing MNH quality of clinical care in 33 health facilities in Malawi. Results Our strategy identified 51 routine care processes: 23 related to initial patient risk assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical performance assessment a total of 82 cases were observed. Birth attendants’ adherence to clinical standards was lowest in relation to risk monitoring processes. In relation to major complications, routine care processes addressing fetal and newborn distress were performed relatively consistently, but there were major gaps in the performance of routine care processes addressing bleeding, infection, and pre-eclampsia risks. Conclusion The identified set of process indicators could identify major gaps in the quality of obstetric and neonatal care provided during the intra- and immediate postpartum period. We hope our suggested indicators for essential routine care processes will contribute to streamlining MNH program evaluations in LMICs. PMID:25875252

  16. Effects of an aquatic physical exercise program on glycemic control and perinatal outcomes of gestational diabetes: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Gestational diabetes mellitus (GDM) is increasing worldwide and has been associated with adverse perinatal outcomes and high risk for chronic disease both for the mother and for the child. Physical exercise is feasible for diabetic pregnant women and contributes to better glycemic control and to a decrease in adverse perinatal outcomes. However, there are no randomized controlled trials (RCT) assessing the effects of aquatic physical exercise on GDM control and adverse maternal and fetal outcomes. Methods/Design An RCT will be conducted at Instituto de Medicina Integral Prof Fernando Figueira (IMIP), Brazil. A total of 72 pregnant women will be studied; 36 gestational diabetics will undergo an aquatic physical exercise program in a thermal pool, 3 times per week over 2 months. The primary endpoint will be glucose level control and use of insulin; secondary endpoints will be the following maternal and fetal outcomes: weight gain during pregnancy, blood pressure, pre-eclampsia diagnosis, intrauterus growth restriction, preterm birth, Cesarean section, macrosomia and maternal or neonatal intensive care admission. Endpoints between intervention and control group will analyzed by t test for unpaired data and χ2 test, and the level of significance will set at <0.05. Discussion The physical proprieties of water make aquatic exercises ideal for pregnant women. An aquatic physical exercise program developed for GDM women will be trialed in a thermal pool and under the supervision of physiotherapist to ensure compliance. It is expected that this study will provide evidence as to the effect of aquatic physical exercise on GDM control. Trial registration ClinicalTrial.gov, NCT01940003. PMID:24245914

  17. Tissue-Specific Education of Decidual NK Cells

    PubMed Central

    Xiong, Shiqiu; Kennedy, Philippa R.; Gardner, Lucy; Farrell, Lydia E.; Chazara, Olympe; Ivarsson, Martin A.; Hiby, Susan E.; Colucci, Francesco; Moffett, Ashley

    2015-01-01

    During human pregnancy, fetal trophoblast cells invade the decidua and remodel maternal spiral arteries to establish adequate nutrition during gestation. Tissue NK cells in the decidua (dNK) express inhibitory NK receptors (iNKR) that recognize allogeneic HLA-C molecules on trophoblast. Where this results in excessive dNK inhibition, the risk of pre-eclampsia or growth restriction is increased. However, the role of maternal, selfHLA-C in regulating dNK responsiveness is unknown. We investigated how the expression and function of five iNKR in dNK is influenced by maternal HLA-C. In dNK isolated from women who have HLA-C alleles that carry a C2 epitope, there is decreased expression frequency of the cognate receptor, KIR2DL1. In contrast, women with HLA-C alleles bearing a C1 epitope have increased frequency of the corresponding receptor, KIR2DL3. Maternal HLA-C had no significant effect on KIR2DL1 or KIR2DL3 in peripheral blood NK cells (pbNK). This resulted in a very different KIR repertoire for dNK capable of binding C1 or C2 epitopes compared with pbNK. We also show that, although maternal KIR2DL1 binding to C2 epitope educates dNK cells to acquire functional competence, the effects of other iNKR on dNK responsiveness are quite different from those in pbNK. This provides a basis for understanding how dNK responses to allogeneic trophoblast affect the outcome of pregnancy. Our findings suggest that the mechanisms that determine the repertoire of iNKR and the effect of self-MHC on NK education may differ in tissue NK cells compared with pbNK. PMID:26320253

  18. 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

  19. Lack of exercise is a major cause of chronic diseases.

    PubMed

    Booth, Frank W; Roberts, Christian K; Laye, Matthew J

    2012-04-01

    Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause versus treatment; physical activity and inactivity mechanisms differ; gene-environment interaction (including aerobic training adaptations, personalized medicine, and co-twin physical activity); and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, nonalcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, pre-eclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life. PMID:23798298

  20. [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. PMID:24075628

  1. Adverse Obstetric and Perinatal Outcomes following Treatment of Adolescent and Young Adult Cancer: A Population-Based Cohort Study

    PubMed Central

    Haggar, Fatima A.; Pereira, Gavin; Preen, David; Holman, C. D'Arcy; Einarsdottir, Kristjana

    2014-01-01

    Objective To investigate obstetric and perinatal outcomes among female survivors of adolescent and young adult (AYA) cancers and their offspring. Methods Using multivariate analysis of statewide linked data, outcomes of all first completed pregnancies (n?=?1894) in female survivors of AYA cancer diagnosed in Western Australia during the period 19822007 were compared with those among females with no cancer history. Comparison pregnancies were matched by maternal age-group, parity and year of delivery. Results Compared with the non-cancer group, female survivors of AYA cancer had an increased risk of threatened abortion (adjusted relative risk 2.09, 95% confidence interval 1.512.74), gestational diabetes (2.65, 2.083.57), pre-eclampsia (1.32, 1.041.87), post-partum hemorrhage (2.83, 1.924.67), cesarean delivery (2.62, 2.223.04), and maternal postpartum hospitalization>5 days (3.01, 1.725.58), but no excess risk of threatened preterm delivery, antepartum hemorrhage, premature rupture of membranes, failure of labor to progress or retained placenta. Their offspring had an increased risk of premature birth (<37 weeks: 1.68, 1.212.08), low birth weight (<2500 g: 1.51, 1.232.12), fetal growth restriction (3.27, 2.454.56), and neonatal distress indicated by low Apgar score (<7) at 1 minute (2.83, 2.283.56), need for resuscitation (1.66, 1.272.19) or special care nursery admission (1.44, 1.131.78). Congenital abnormalities and perinatal deaths (intrauterine or ?7 days of birth) were not increased among offspring of survivors. Conclusion Female survivors of AYA cancer have moderate excess risks of adverse obstetric and perinatal outcomes arising from subsequent pregnancies that may require additional surveillance or intervention. PMID:25485774

  2. Vitamin D3 alters Toll-like receptor 4 signaling in monocytes of pregnant women at risk for preeclampsia

    PubMed Central

    Qian, Lei; Wang, Hongyou; Wu, Fenghui; Li, Ming; Chen, Wei; LV, Lianzheng

    2015-01-01

    Vitamin D deficiency during pregnancy is thought to play a role in the development of preeclampsia; however, the underlying mechanism is not fully understood. In this study, a 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 a daily dose of 2000 IU vitamin D3 supplements (n=30) or receive placebo (n=30) between gestational weeks 20-32 for a total of 12 consecutive weeks. Because vitamin D3 supplementation can induce anti-inflammatory cytokine signaling, peripheral blood monocytes were investigated by flow cytometry for expression of toll-like receptor 4 (TLR4), an important mediator of innate immune response. The pro-inflammatory cytokines secretion of tumor necrosis factor (TNF)-?, interleukin (IL)-6, and IL-1 from monocytes, which are typically upregulated in preeclampsia, was also assessed. The incidence of preeclampsia was significantly lower in patients treated with vitamin D3 compared to the placebo group. Both the mean fluorescence intensity and the positive percentage of monocytes TLR4 in the vitamin D group were significantly lower compared to the placebo group, as well as the concentrations of secreted TNF-?, IL-6, and IL-1, while the concentration of IL-10 was higher. In the placebo group, the positive frequency of monocytes TLR4 was negatively correlated with the concentration of serum 25-hydroxyvitamin D in preeclampsia patients. Based on these results, we conclude that vitamin D3 supplementation for patients at risk of preeclampsia leads to a decrease in the expression of peripheral blood monocytes TLR4 and a subsequent decrease in pro-inflammatory cytokine secretion. Therefore, inhibiting the expression of monocytes TLR4 through vitamin D3 supplement may be a new approach to preeclampsia prevention. PMID:26770399

  3. 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.

  4. Abnormal pressure-wave reflection in pregnant women with chronic hypertension: association with maternal and fetal outcomes.

    PubMed

    Tomimatsu, Takuji; Fujime, Mika; Kanayama, Tomoko; Mimura, Kazuya; Koyama, Shinsuke; Kanagawa, Takeshi; Endo, Masayuki; Shimoya, Koichiro; Kimura, Tadashi

    2014-11-01

    The current study tested the hypothesis that abnormal pressure-wave reflection may have an important role in identifying pregnant women with chronic hypertension who might develop pre-eclampsia (PE) and/or fetal growth restriction. Pulse-wave analyses were performed to assess maternal arterial stiffness during 26-32 weeks of gestation in 41 women with chronic hypertension. We measured the central systolic pressure (CSP) and augmentation index (AIx) noninvasively using pulse waveforms of the radial artery with an automated applanation tonometric system. In a multiple regression analysis that included AIx-75 (AIx at a heart rate of 75 beats per minute), brachial systolic pressure, maternal height, smoking status, gestational age at testing and the presence of antihypertensive treatment at testing as independent determinants, AIx-75 was the only significant determinant of birth weight, whereas the brachial systolic pressure was not. In pregnant women with chronic hypertension who subsequently developed both superimposed PE and fetal growth restriction, CSP, AIx, AIx-75, and the brachial systolic and pulse pressures were all significantly higher than those who did not develop superimposed PE nor small for gestational age. In contrast, AIx-75 was the only significantly elevated hemodynamic parameter in patients who developed fetal growth restriction but not superimposed PE. In addition, CSP was the only significantly elevated hemodynamic parameter in patients who developed superimposed PE but not fetal growth restriction. Abnormal pressure-wave reflection during 26-32 weeks of gestation showed a stronger correlation with birth weight than conventional brachial blood pressure. Our findings might provide new insight into the pathophysiology of fetal growth restriction as well as superimposed PE in pregnancies complicated with chronic hypertension. PMID:24965168

  5. Safety of pertussis vaccination in pregnant women in UK: observational study

    PubMed Central

    King, Bridget; Bryan, Phil

    2014-01-01

    Objective To examine the safety of pertussis vaccination in pregnancy. Design Observational cohort study. Setting The UK Clinical Practice Research Datalink. Participants 20?074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group. Main outcome measure Adverse events identified from clinical diagnoses during pregnancy, with additional data from the matched child record identified through mother-child linkage. The primary event of interest was stillbirth (intrauterine death after 24 weeks gestation). Results There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 0.69, 95% confidence interval 0.23 to 1.62) or later in pregnancy (0.85, 0.44 to 1.61) compared with historical national rates. Compared with a matched historical cohort of unvaccinated pregnant women, there was no evidence that vaccination accelerated the time to delivery (hazard ratio 1.00, 0.97 to 1.02). Furthermore, there was no evidence of an increased risk of stillbirth, maternal or neonatal death, pre-eclampsia or eclampsia, haemorrhage, fetal distress, uterine rupture, placenta or vasa praevia, caesarean delivery, low birth weight, or neonatal renal failure, all serious events that can occur naturally in pregnancy. Conclusion In women given pertussis vaccination in the third trimester, there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy. In particular, there was no evidence of an increased risk of stillbirth. Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates, these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making. PMID:25015137

  6. Interventions to reduce or prevent obesity in pregnant women: a systematic review.

    PubMed Central

    Thangaratinam, S; Rogozińska, E; Jolly, K; Glinkowski, S; Duda, W; Borowiack, E; Roseboom, T; Tomlinson, J; Walczak, J; Kunz, R; Mol, B W; Coomarasamy, A; Khan, K S

    2012-01-01

    BACKGROUND Around 50% of women of childbearing age are either overweight [body mass index (BMI) 25-29.9 kg/m(2)] or obese (BMI ≥ 30 kg/m(2)). The antenatal period provides an opportunity to manage weight in pregnancy. This has the potential to reduce maternal and fetal complications associated with excess weight gain and obesity. OBJECTIVES To evaluate the effectiveness of dietary and lifestyle interventions in reducing or preventing obesity in pregnancy and to assess the beneficial and adverse effects of the interventions on obstetric, fetal and neonatal outcomes. DATA SOURCES Major electronic databases including MEDLINE, EMBASE, BIOSIS and Science Citation Index were searched (1950 until March 2011) to identify relevant citations. Language restrictions were not applied. REVIEW METHODS Systematic reviews of the effectiveness and harm of the interventions were carried out using a methodology in line with current recommendations. Studies that evaluated any dietary, physical activity or mixed approach intervention with the potential to influence weight change in pregnancy were included. The quality of the studies was assessed using accepted contemporary standards. Results were summarised as pooled relative risks (RRs) with 95% confidence intervals (CIs) for dichotomous data. Continuous data were summarised as mean difference (MD) with standard deviation. The quality of the overall evidence synthesised for each outcome was summarised using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology and reported graphically as a two-dimensional chart. RESULTS A total of 88 studies (40 randomised and 48 non-randomised and observational studies, involving 182,139 women) evaluated the effect of weight management interventions in pregnancy on maternal and fetal outcomes. Twenty-six studies involving 468,858 women reported the adverse effect of the interventions. Meta-analysis of 30 RCTs (4503 women) showed a reduction in weight gain in the intervention group of 0.97 kg compared with the control group (95% CI -1.60 kg to -0.34 kg; p = 0.003). Weight management interventions overall in pregnancy resulted in a significant reduction in the incidence of pre-eclampsia (RR 0.74, 95% CI 0.59 to 0.92; p = 0.008) and shoulder dystocia (RR 0.39, 95% CI 0.22 to 0.70; p = 0.02). Dietary interventions in pregnancy resulted in a significant decrease in the risk of pre-eclampsia (RR 0.67, 95% CI 0.53 to 0.85; p = 0.0009), gestational hypertension (RR 0.30, 95% CI 0.10 to 0.88; p = 0.03) and preterm birth (RR 0.68, 95% CI 0.48 to 0.96; p = 0.03) and showed a trend in reducing the incidence of gestational diabetes (RR 0.52, 95% CI 0.27 to 1.03). There were no differences in the incidence of small-for-gestational-age infants between the groups (RR 0.99, 95% CI 0.76 to 1.29). There were no significant maternal or fetal adverse effects observed for the interventions in the included trials. The overall strength of evidence for weight gain in pregnancy and birthweight was moderate for all interventions considered together. There was high-quality evidence for small-for-gestational-age infants as an outcome. The quality of evidence for all interventions on pregnancy outcomes was very low to moderate. The quality of evidence for all adverse outcomes was very low. LIMITATIONS The included studies varied in the reporting of population, intensity, type and frequency of intervention and patient complience, limiting the interpretation of the findings. There was significant heterogeneity for the beneficial effect of diet on gestational weight gain. CONCLUSIONS Interventions in pregnancy to manage weight result in a significant reduction in weight gain in pregnancy (evidence quality was moderate). Dietary interventions are the most effective type of intervention in pregnancy in reducing gestational weight gain and the risks of pre-eclampsia, gestational hypertension and shoulder dystocia. There is no evidence of harm as a result of the dietary and physical activity-based interventions in pregnancy. Individual patient data meta-analysis is needed to provide robust evidence on the differential effect of intervention in various groups based on BMI, age, parity, socioeconomic status and medical conditions in pregnancy. PMID:22814301

  7. Glucocorticoid Metabolism in Hypertensive Disorders of Pregnancy: Analysis of Plasma and Urinary Cortisol and Cortisone

    PubMed Central

    Kosicka, Katarzyna; Siemi?tkowska, Anna; Krzy?cin, Mariola; Br?borowicz, Grzegorz H.; Resztak, Matylda; Majchrzak-Celi?ska, Aleksandra; Chuchracki, Marek; G?wka, Franciszek K.

    2015-01-01

    Objectives The aim of the study was to analyze the plasma and urinary cortisol (F) and cortisone (E) levels in normotensive and hypertensive pregnant women. The parameters known to reflect the function of 11?-hydroxysteroid dehydrogenase type 2 (11?-HSD2) were calculated to verify the changes in glucocorticoid balance over the course of gestational hypertension (GH) and pre-eclampsia (PE). Materials and Methods This retrospective case-control study included women in the third trimester of pregnancy, diagnosed with: GH (n = 29), PE (n = 26), or chronic hypertension (CH; n = 22). Normotensive women in their third trimester of pregnancy were also included (controls; n = 43). The plasma and urinary F and E levels were measured with the HPLC-FLD method. The 11?-HSD2 function was estimated by calculating the following ratios: plasma F/E and urinary free F to urinary free E (UFF/UFE). A statistical analysis was performed based on case-control structure. Results and Discussion PE was characterized by lower plasma F levels (639.0 nmol/L), UFF/Cr levels (3.80 ?g/mmol) and F/E ratio (3.46) compared with that of the controls (811.7 nmol/L, 6.28 ?g/mmol and 5.19, respectively) with marked abnormalities observed in the changes of F/E and UFF/UFE ratios with advancing gestation. GH patients showed significant disparities in the urinary steroid profile with lower UFF/UFE ratio (0.330 vs. 0.401) compared with the normotensive controls and abnormal changes in the UFF/UFE throughout pregnancy. The observed tendency towards lower F/E and UFF/UFE ratios in PE and GH patients may reflect more intensive F metabolism over the course of those disorders. In the normal pregnancy group, the plasma F/E and UFF/UFE ratios tended to present inverse correlations with advancing gestation. This trend was much less marked in PE and GH patients, suggesting that the abnormalities in 11?-HSD2 functions progressed with the GA. The birth weights of neonates born from pre-eclamptic pregnancies were lower than those from uncomplicated pregnancies, although only when the babies were born prematurely. Children born at term to normotensive mothers or mothers suffering from PE had comparable birth weights. PMID:26637176

  8. Leptin receptor (LEPR) SNP polymorphisms in HELLP syndrome patients determined by quantitative real-time PCR and melting curve analysis

    PubMed Central

    2010-01-01

    Background Several studies have shown overexpression of leptin in microarray experiments in pre-eclampsia (PE) and in hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. We decided to study four leptin receptor (LEPR) SNP polymorphisms in HELLP syndrome patients by using quantitative real-time PCR and melting curve analysis. Methods DNA was isolated from blood samples from 83 normotensive pregnant women and 75 HELLP syndrome patients. Four SNPs, LEPR c.326A>G (K109), LEPR c.668A>G (Q223R), LEPR c.1968G>C (K656N) and LEPR c.3024A>G (S1008) were determined by quantitative real-time PCR and melting curve analysis. Investigators were blinded to clinical outcomes. Results LEPR c.326A>G, LEPR c.668A>G, LEPR c.1968G>C and LEPR c.3024A>G allele, genotype and haplotype polymorphisms were not different in HELLP syndrome patients and normotensive healthy pregnants. There were strong linkage disequilibrium (LD) between loci c.326A>G and c.6687A>G (D' = 0.974), and c.668A>G and c.1968G>C (D' = 0.934), and c.326A>G and c.1968G>C (D' = 0.885), and c.1968G>C and c.3024A>G (D' = 1.0). However, linkages of c.3024A>G with c.668A>G (D' = 0.111) and c.326A>G (D' = 0.398) were weak. The Hardy-Weinberg equilibrium was observed for all polymorphisms. However the LEPR c.326A>G AG genotype was twice more frequent and the (AG AG GG AG) haplotype was three times more frequent in HELLP syndrome patients. The introduced quantitative real-time PCR combined with melting curve analysis is a fast and reliable method for the determination of LEPR SNPs. Conclusion Although certain LEPR haplotypes are more frequent in HELLP syndrome, we conclude that there is no compelling evidence that the four studied LEPR SNP polymorphisms associated with the development of HELLP syndrome. PMID:20149225

  9. SFlt-1 Elevates Blood Pressure by Augmenting Endothelin-1-Mediated Vasoconstriction in Mice

    PubMed Central

    Hassani Lahsinoui, Hajar; Vogt, Liffert; van der Post, Joris; Peters, Stephan; Afink, Gijs; Ris-Stalpers, Carrie; van den Born, Bert-Jan

    2014-01-01

    Objective Scavenging of vascular endothelial growth factor (VEGF) elevates blood pressure (BP) in patients receiving anti-angiogenic therapy. Similarly, inhibition of circulation VEGF by its soluble receptor fms-like tyrosine kinase-1 (sFlt-1) underlies BP elevation in pre-eclampsia. Both phenotypes are characterized by augmented production of endothelin-1 (ET-1), suggesting a role for ET-1 in anti-angiogenic hypertension. We aimed to assess the effect of VEGF inhibition on ET-1-induced contractility and downstream ET-1 signaling. Approach and Results Male C57BL/6N mice were treated with either sFlt-1 or vehicle and BP was assessed via tail-cuff. Mean arterial pressure of sFlt-1-treated mice markedly increased compared to vehicle-treated controls (N = 11–12, p<0.05). After sacrifice, carotid and mesenteric arteries were isolated for isometric tension measurements. ET-1-induced contractions were similar in mesenteric arteries of vehicle and sFlt-1-treated mice, but augmented in carotid segments of sFlt-1-treated mice compared to controls (N = 9–10, p<0.05). The increased contraction in carotid segments could be completely abrogated by the cyclooxygenase (COX) inhibitor indomethacin (N = 9–10, p<0.05), indicating heightened prostaglandin-mediated vasoconstriction. This was associated with a shift towards procontractile ETB signaling in sFlt-1-treated mice, possibly explaining the increased ET-1-induced prostaglandin-mediated vasoconstriction. In line with the ex vivo findings, sFlt-1-induced BP elevation could be prevented in vivo by oral treatment with either a high-dose of the COX inhibitor aspirin (N = 7) or with picotamide (N = 9), a dual thromboxane A2 synthase inhibitor and receptor antagonist. Conclusions VEGF inhibition augments the pressor response to ET-1. The cyclooxygenase-thromboxane signaling route downstream of ET-1 might be a possible target to prevent BP elevation during VEGF inhibition. PMID:24632840

  10. Improved quality of management of eclampsia patients through criteria based audit at Muhimbili National Hospital, Dar es Salaam, Tanzania. Bridging the quality gap

    PubMed Central

    2012-01-01

    Background Criteria-based audits (CBA) have been used to improve clinical management in developed countries, but have only recently been introduced in the developing world. This study discusses the use of a CBA to improve quality of care among eclampsia patients admitted at a University teaching hospital in Dar es Salaam Tanzania. Objective The prevalence of eclampsia in MNH is high (?6%) with the majority of cases arriving after start of convulsions. In 20042005 the case-fatality rate in eclampsia was 5.1% of all pregnant women admitted for delivery (MNH obstetric data base). A criteria-based audit (CBA) was used to evaluate the quality of care for eclamptic mothers admitted at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania after implementation of recommendations of a previous audit. Methods A CBA of eclampsia cases was conducted at MNH. Management practices were evaluated using evidence-based criteria for appropriate care. The Ministry of Health (MOH) guidelines, local management guidelines, the WHO manual supplemented by the WHO Reproductive Health Library, standard textbooks, the Cochrane database and reviews in peer reviewed journals were adopted. At the initial audit in 2006, 389 case notes were assessed and compared with the standards, gaps were identified, recommendations made followed by implementation. A re-audit of 88 cases was conducted in 2009 and compared with the initial audit. Results There was significant improvement in quality of patient management and outcome between the initial and re-audit: Review of management plan by senior staff (76% vs. 99%; P=0.001), urine for albumin test (61% vs. 99%; P=0.001), proper use of partogram to monitor labour (75% vs. 95%; P=0.003), treatment with steroids for lung maturity (2.0% vs. 24%; P=0.001), Caesarean section within 2 hours of decision (33% vs. 61%; P=0.005), full blood count (28% vs. 93%; P=0.001), serum urea and creatinine (44% vs. 86%; P=0.001), liver enzymes (4.0% vs. 86%; P=0.001), and specialist review within 2 hours of admission (25% vs. 39%; P=0.018). However, there was no significant change in terms of delivery within 24 hours of admission (69% vs. 63%; P=0.33). There was significant reduction of maternal deaths (7.7% vs. 0%; P=0.001). Conclusion CBA is applicable in low resource setting and can help to improve quality of care in obstetrics including management of pre-eclampsia and eclampsia. PMID:23170817

  11. Lupus nephritis is associated with poor pregnancy outcomes in pregnant SLE patients in Cape Town: a retrospective analysis

    PubMed Central

    Mbuli, Lindisa; Mapiye, Darlington; Okpechi, Ikechi

    2015-01-01

    Introduction Systemic lupus erythematosus (SLE) is a multi-system auto-immune disease common in females of child-bearing age. The effect of pregnancy on SLE and vice versa have not been well characterised in Africans. The aim of this study is to describe the pregnancy outcomes of patients with SLE presenting to the maternity department of Groote Schuur Hospital, Cape Town. Methods This study was designed as a retrospective review of records of pregnant women known with SLE and followed-up at the maternity section of Groote Schuur Hospital. The duration of survey was from the 1st January 2003 to 31st December 2013. Results There were 61 pregnancies reviewed in 49 patients; 80.3% of the pregnancies were in patients of mixed ancestry and the rest (19.7%) in black African patients. The mean age at presentation of the current pregnancy was 27.2±5.0 years. Mean gestational age at presentation and delivery was 13.0 ± 6.0 weeks and 28.9 ± 9.8 weeks respectively and 47.5% of the pregnancies were in patients with lupus nephritis (LN). Thirty nine (63.9%) pregnancies reached the third trimester and 11.5% of all pregnancies ended in the first trimester. There was a lower number of live births to mothers of African ancestry than to those of mixed ancestry (p=0.001). In 55.7% of the pregnancies, no flare was reported while a renal flare was reported in 23%. Pregnancies in patients with LN had higher frequencies of flares (58.6% vs 31.3%; p=0.032), pre-eclampsia (34.5% vs 12.5%; p=0.041), longer stay in hospital (12.0 ± 9.1 days vs 6.1 ± 5.1 days; p=0.004) and low birth weight babies (1.94 ± 1.02 kg vs 2.55±0.95 kg; p=0.046) than in patients without LN. Only 36 (59%) of the neonates were discharged home alive and of these 2 (5.6%) were to mothers of black African ancestry (p=0.001). Conclusion Increased lupus activity in pregnant SLE patients may account for the increased deaths of neonates born to SLE mothers. Patients of black African descent and those with LN tend to have a poorer outcome. A multi-disciplinary approach to the management of SLE patients (of child-bearing age or pregnant) needs to be further assessed for better outcomes.

  12. Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older.

    PubMed

    Sauer, M V; Paulson, R J; Lobo, R A

    1996-11-01

    We analysed the results of oocyte donation to women of advanced reproductive age (> or = 45 years old) and followed their pregnancies through to delivery in order to assess obstetrical outcomes. Patients (n = 162) aged 45-59 years (mean +/- SD; 47.3 +/- 3.4 years) underwent 218 consecutive attempts to achieve pregnancy. Oocytes (16.2 +/- 7.2 per retrieval) were provided by donors < or = 35 years old. Cleaving embryos (8.2 +/- 4.8 zygotes/couple) were transferred transcervically (4.5 +/- 1.1 per embryo transfer) to recipients prescribed oral micronized oestradiol and intramuscular progesterone. Following oocyte aspiration there were six instances of non-fertilization (2.8%) and 212 embryo transfers. A total of 103 pregnancies was established for an overall pregnancy rate (PR) of 48.6%, which included 17 preclinical pregnancies, 12 spontaneous abortions, and 74 delivered pregnancies (clinical PR 40.6%; delivered PR 34.9%). Multiple gestations were frequent (n = 29; 39.2% of pregnancies) and included 20 twins, seven triplets, and two quadruplets. Two of the triplet and both of the quadruplet pregnancies underwent selective reduction to twins. Antenatal complications occurred in 28 women (37.8% of deliveries) and included preterm labour (n = 9), gestational hypertension (n = 8), gestational diabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia (n = 2), HELLP syndrome (n = 2), and fetal growth retardation (n = 2). 48 (64.8%) deliveries were by Caesarean section. The gestational age at delivery for singletons was 38.3 +/- 1.3 weeks (range 35-41 weeks), with birth weight 3218 +/- 513 g (range 1870-4775 g); twins 35.9 +/- 2.0 weeks (range 32-39 weeks), birth weight 2558 +/- 497 g (range 1700-3450 g); and triplets 33.5 +/- 0.7 weeks (range 32-34 weeks), birth weight 1775 +/- 190 g (range 1550-2100 g). Neonatal complications (4.6% of babies born) included growth retardation (n = 2), trisomy 21 (n = 1), ventricular septal defect (n = 1), and small bowel obstruction (n = 1). There were no maternal or neonatal deaths. We conclude that oocyte donation to women of advanced reproductive age is highly successful in establishing pregnancy. However, despite careful antenatal screening, obstetrical complications are common, often secondary to multiple gestation. PMID:8981151

  13. Oxidative stress markers in hypertensive states of pregnancy: preterm and term disease

    PubMed Central

    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-existing cardiovascular risk. PMID:25202276

  14. 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 exploration of which complications are specifically prevented by low-molecular-weight heparin. Systematic review registration PROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249 PMID:24969227

  15. 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 outcomes after 12 weeks of pregnancy. Trial registration number NCT00198068. PMID:26835148

  16. 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 blood residue area and volume compared to the non-structured controls of the same material. In addition, blood clotting area is reduced >5x using whole blood directly from the patient. In this study, biocompatible SH surfaces are achieved using commodity shrink-wrap film and are scaled up for R2R manufacturing. The purely structural modification negates complex and expensive post processing, and SH features are achieved in commercially-available and FDA-approved plastics.

  17. STRIDER: Sildenafil therapy in dismal prognosis early-onset intrauterine growth restriction a protocol for a systematic review with individual participant data and aggregate data meta-analysis and trial sequential analysis

    PubMed Central

    2014-01-01

    Background In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis. The first aim of this review is to assess whether sildenafil benefits or harms these babies. The second aim is to analyse if these effects are modified in a clinically meaningful way by factors related to the women or the trial protocol. Methods/Design The STRIDER (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction) Individual Participant Data (IPD) Study Group will conduct a prospective IPD and aggregate data systematic review with meta-analysis and trial sequential analysis. The STRIDER IPD Study Group started trial planning and funding applications in 2012. Three trials will be launched in 2014, recruiting for three years. Further trials are planned to commence in 2015. The primary outcome for babies is being alive at term gestation without evidence of serious adverse neonatal outcome. The latter is defined as severe central nervous system injury (severe intraventricular haemorrhage (grade 3 and 4) or cystic periventricular leukomalacia, demonstrated by ultrasound and/or magnetic resonance imaging) or other severe morbidity (bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, or necrotising enterocolitis requiring surgery). The secondary outcomes are improved fetal growth velocity assessed by ultrasound abdominal circumference measurements, gestational age and birth weight (centile) at delivery, and age-adequate performance on the two-year Bayley scales of infant and toddler development-III (composite cognitive score and composite motor score). Subgroup and sensitivity analyses in the IPD meta-analysis include assessment of the influence of several patient characteristics: an abnormal or normal serum level of placental growth factor, absent/reversed umbilical arterial end diastolic flow at commencement of treatment, and other patient characteristics available at baseline such as gestational age and estimated fetal weight. The secondary outcomes for mothers include co-incidence and severity of the maternal syndrome of pre-eclampsia, mortality, and other serious adverse events. Discussion Trials are expected to start in 20132014 and end in 20162017. Data analyses of individual trials are expected to finish in 2019. Given the pre-planned and agreed IPD protocol, these results should be available in 2020. PMID:24618418

  18. 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 infant mortality it is necessary to know more about the nature, etiology, and prevention of LBW in developing countries. PMID:3886185

  19. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    SciTech Connect

    Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.; Issitt, Theo; Ulyatt, Clare; Walker, John H.; Homer-Vanniasinkam, Shervanthi; Ponnambalam, Sreenivasan

    2012-11-01

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black-Right-Pointing-Pointer Endothelial VEGFR levels are modulated during this response. Black-Right-Pointing-Pointer The cell regulates VEGF-A bioavailability and cell survival. Black-Right-Pointing-Pointer This may partly underlie endothelial dysfunction seen in many pathologies.

  20. The effect of mode of delivery on neonatal mortality in very low birthweight infants born in Victoria, Australia: Caesarean section is associated with increased survival in breech-presenting, but not vertex-presenting, infants.

    PubMed

    Jonas, H A; Lumley, J M

    1997-04-01

    To determine whether the improved survival of very low birthweight (VLBW) infants (< 1500 g) born in Australia can be attributed to currently high rates of Caesarean section, we examined the associations between neonatal mortality and Caesarean section in singleton liveborn VLBW infants (500-1499 g) born during 1986-93 in Victoria, Australia, using data from the Victorian Perinatal Collection Unit. The infants included in this study had completed > 23 weeks of gestation, had no life-threatening malformations and had not been delivered by a repeat Caesarean without a trial of labour (n = 2763). For infants weighing 500-749 g, 750-999 g, 1000-1249 g and 1250-1499 g, the neonatal mortality rates were 56.1%, 25.7%, 13.0% and 4.3% respectively, and the Caesarean section rates were 33.1%, 42.3%, 54.8% and 55.8%. Nearly half of these births (n = 1269) were associated with one or more obstetric indications for Caesarean section (non-breech malpresentation, fetal distress, prolapsed cord, placenta praevia, pre-eclampsia and hypertension). Overall, the odds ratio (OR) for neonatal death associated with Caesarean section was 0.92 [95% confidence interval 0.60-1.41], after adjustment for gestational age, birthweight, year of birth, type of hospital, presence or absence of labour, presentation and obstetric indications for Caesarean section. However, when the vertex-presenting (n = 1702) and breech-presenting (n = 746) infants were considered separately, the adjusted ORs for neonatal death were 1.98 [0.96-4.10] and 0.52 [0.29-0.96] respectively. For those infants without obstetric indications for Caesarean section, the adjusted ORs for neonatal death in vertex-presenting (n = 950) and breech-presenting (n = 446) infants were 3.80 [1.11-13.0] and 0.47 [0.23-0.6]. These recent population-based data support the view that Caesarean section does not enhance the neonatal survival of VLBW babies when obstetric complications are absent. PMID:9131710

  1. Maternal morbidity and perinatal outcome in preterm premature rupture of membranes before 37 weeks gestation

    PubMed Central

    Dars, Saira; Malik, Safia; Samreen, Irum; Kazi, Roshan Ara

    2014-01-01

    OBJECTIVE: To assess the maternal morbidity and perinatal outcome in pre-term pre mature rupture of membranes between 24 to 37 weeks gestation. METHODS: This observational study was carried out in Gynaecology & Obstetrics Unit I, at University Hospital Hyderabad, from October 2010 to October 2011. It included one hundred patients admitted through the outpatient department, as well as from casualty department of University Hospital Hyderabad. Detailed Clinical examination of the patient was done. Systemic review was also done to see any co-morbidity. All patients had laboratory investigations. Inclusion criteria were all patients gestational age between 24 to 37 weeks with preterm premature rupture of membrane (PPROM) confirmed by ultrasound and clinical examination regardless of their age. Exclusion criteria were patients with congenital anomalies, multiple pregnancy, pre-eclampsia & eclampsia, diabetes mellitus, polyhydramnios1 intrauterine growth restriction and placenta abruption. Data was collected using a proforma. Detailed workup including history, general physical examination, abdomen and pelvic examination and relevant specific investigations were noted. RESULTS: Out of 100 patients included in this study Primigravida were 17% and multigravida 83%. There was wide variation of age ranging from a minimum of 20to >40 years. The mean age was 30+ 3.1 years. Mostly patients belonged to the poor class in 72% cases followed by middle class in 21% and upper class 7%. Analysis shows that out of 100 mothers 26% had PROM of <24 hrs duration and 74% had >24 hrs of duration. Maternal outcome in 16 cases of Preterm Premature Rupture of Membrane findings revealed septicemia in 12% cases and Chorioamnionitis in 12% cases. Fetal outcome in 27 cases of preterm premature rupture of membrane revealed prematurity in 5% cases, fetal distress in 4% cases, cord compression in 5% cases, necrotizing enterocolitis in 2% cases, hypoxia in 9% cases and pulmonary hypoplasia in 2% cases. CONCLUSION: Low socioeconomic status is associated with increased neonatal morbidity due to fetal distress, cord compression, necrotizing enterocolitis, hypoxia and pulmonary hypoplasia at the time of delivery. An appropriate and accurate diagnosis of PROM is critical to optimize pregnancy outcome. It is suggested that the timely diagnosis and management of preterm PROM will allow obstetric care providers to optimize perinatal outcome and minimize neonatal morbidity. PMID:24948992

  2. The relationship between Caesarean section and neonatal mortality in very-low-birthweight infants born in Washington State, USA.

    PubMed

    Jonas, H A; Khalid, N; Schwartz, S M

    1999-04-01

    We examined the associations between Caesarean section and neonatal mortality in singleton liveborn very-low-birthweight (VLBW) infants (500-1499 g) born during 1984-95 in Washington State, USA, using data from the Washington State birth certificate files. The infants included in this study had no life-threatening congenital malformations and had not been delivered by a repeat Caesarean without a trial of labour (n = 5182). For infants weighing 500-749, 750-999, 1000-1249 and 1250-1499 g, the neonatal mortality rates were 57.8%, 18.6%, 9.7% and 4.7%, respectively, and the Caesarean section rates were 28.4%, 47.8%, 48.0% and 44.6%. The adjusted odds ratios (ORs) for neonatal death associated with Caesarean section were 0.55 [95% confidence interval 0.38, 0.78] for the 500-749 g infants (n = 1059), and 1.15 [0.91, 1.45] for the larger (750-1499 g) infants, after adjustment for birth year, type of hospital, birthweight, presence or absence of labour, breech/malpresentation, and other obstetric indications for Caesarean section (prolapsed cord, placenta praevia, eclampsia, pre-eclampsia and chronic hypertension). However, when the larger (750-1499 g) vertex-presenting (n = 3248) and breech/malpresenting (n = 809) infants were considered separately, the adjusted ORs were 1.42 [1.05, 1.91] and 0.37 [0.23, 0.58] respectively. In contrast, among infants weighing 500-749 g, the ORs were not modified by presentation. The results were similar when we restricted analyses to infants without the above obstetric indications for Caesarean section. Because such an observational study is liable to unmeasurable biases and incomplete reporting of obstetric complications, these OR estimates may be subject to residual confounding. In their present state, these recent population-based data support the view that Caesarean sections do not enhance the neonatal survival of larger (> 750 g) VLBW babies when obstetric complications are absent. The possibility of a protective effect of Caesarean section on the survival of breech/malpresenting infants and infants weighing 500-749 g deserves further studies. PMID:10214608

  3. Maternal obesity is associated with a reduction in placental taurine transporter activity

    PubMed Central

    Ditchfield, A M; Desforges, M; Mills, T A; Glazier, J D; Wareing, M; Mynett, K; Sibley, C P; Greenwood, S L

    2015-01-01

    Background/Objectives: Maternal obesity increases the risk of poor pregnancy outcome including stillbirth, pre-eclampsia, fetal growth restriction and fetal overgrowth. These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta. Taurine, a β-amino acid with antioxidant and cytoprotective properties, has a role in syncytiotrophoblast development and function and is required for fetal growth and organ development. Taurine is conditionally essential in pregnancy and fetal tissues depend on uptake of taurine from maternal blood. We tested the hypothesis that taurine uptake into placental syncytiotrophoblast by the taurine transporter protein (TauT) is lower in obese women (body mass index (BMI)⩾30 kg m−2) than in women of ideal weight (BMI 18.5–24.9 kg m−2) and explored potential regulatory factors. Subjects/Methods: Placentas were collected from term (37–42-week gestation), uncomplicated, singleton pregnancies from women with BMI 19–49 kg m−2. TauT activity was measured as the Na+-dependent uptake of 3H-taurine into placental villous fragments. TauT expression in membrane-enriched placental samples was investigated by western blot. In vitro studies using placental villous explants examined whether leptin or IL-6, adipokines/cytokines that are elevated in maternal obesity, regulates TauT activity. Results: Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19–49 kg m−2; P<0.05; n=61). There was no difference in TauT expression between placentas of ideal weight and obese class III (BMI⩾40) subjects. Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity. Conclusions: Placental TauT activity at term is negatively related to maternal BMI. We propose that the reduction in placental TauT activity in maternal obesity could lower syncytiotrophoblast taurine concentration, compromise placental development and function, and reduce the driving force for taurine efflux to the fetus, thereby increasing the risk of poor pregnancy outcome. PMID:25547282

  4. The association of maternal ACE A11860G with small for gestational age babies is modulated by the environment and by fetal sex: a multicentre prospective casecontrol study

    PubMed Central

    Zhou, Ang; Dekker, Gustaaf A.; Lumbers, Eugenie R.; Leemaqz, Shalem Y.; Thompson, Steven D.; Heinemann, Gary; McCowan, Lesley M.E.; Roberts, Claire T.

    2013-01-01

    We aimed to determine whether the ACE A11860G genotype is associated with small for gestational age babies (SGA) and to determine whether the association is affected by environmental factors and fetal sex. Overall, 3234 healthy nulliparous women with singleton pregnancies, their partners and babies were prospectively recruited in Adelaide, Australia and Auckland, New Zealand. Data analyses were confined to 2121 Caucasian parentinfant trios, among which 216 were pregnancies with SGA infants and 1185 were uncomplicated pregnancies. Women with the ACE A11860G GG genotype in the combined and Adelaide cohorts had increased risk for SGA [odds ratios (OR) 1.5, 95% confidence interval (CI) 1.12.1 and OR 2.0, 95% CI 1.33.3, respectively) and delivered lighter babies (P = 0.02; P = 0.007, respectively) compared with those with AA/AG genotypes. The maternal ACE A11860G GG genotype was associated with higher maternal plasma ACE concentration at 15 weeks' gestation than AA/AG genotypes (P < 0.001). When the Adelaide cohort was stratified by maternal socio-economic index (SEI) and pre-pregnancy green leafy vegetable intake, the ACE A11860G GG genotype was only associated with an increased risk for SGA (OR 4.9, 95% CI 1.813.4 and OR 3.3, 95% CI 1.67.0, respectively) and a reduction in customized birthweight centile (P = 0.006 and P = 0.03) if superimposed on maternal SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day. Furthermore, the associations of maternal ACE A11860G with customized birthweight centile observed among Adelaide women with SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day were female specific. The current study identified a novel association of maternal ACE A11860G with SGA. More interestingly, this association was modified by environmental factors and fetal sex, suggesting ACE A11860Genvironmentfetal sex interactions. Trial Registry Name: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, SGA babies and spontaneous preterm birth. URL: http://www.anzctr.org.au. Registration number: ACTRN12607000551493. PMID:23615722

  5. Nitric oxide-mediated changes in vascular reactivity in pregnancy in spontaneously hypertensive rats.

    PubMed

    Chu, Z M; Beilin, L J

    1993-11-01

    1. To examine the mechanisms which may account for pregnancy-induced vasodilatation in spontaneously hypertensive rats (SHR), we have investigated the changes in vascular reactivity and the effects of endothelial nitric oxide (NO) inhibition in the in situ blood-perfused, mesenteric resistance vessels of 18-20 day pregnant SHR. The effects of NG-nitro-L-arginine (L-NOARG) were compared in pregnant and nonpregnant SHR and gestation matched normotensive Wistar-Kyoto (WKY) rats. 2. Intra-arterial mean blood pressures (MBP) were similar in pregnant and nonpregnant SHR. Basal perfusion pressures (BPP) were decreased in pregnant compared with nonpregnant SHR. Pregnant WKY had lower MBP and BPP than either pregnant or nonpregnant SHR. 3. Vasoconstrictor responses to electrical stimulation (ES) and intra-arterial noradrenaline (NA) were decreased in pregnant compared with nonpregnant SHR. These responses were still greater in pregnant SHR when compared with pregnant WKY. Vascular reactivity to angiotensin II (AII) in pregnant SHR was reduced to a similar level to that in pregnant WKY. 4. L-NOARG (5 mg kg-1, i.v.), an inhibitor of nitric oxide synthase, increased MBP and BPP in all groups. After L-NOARG, BPP were equalized between pregnant and nonpregnant SHR. Pregnant WKY still showed lower MBP and BPP than SHR groups. 5. L-NOARG potentiated vascular responses to ES, NA and AII in all groups. The blunted vascular responses to NA and ES were normalized and the reactivity to AII was only partially reversed in pregnant SHR compared with nonpregnant SHR. Pregnant WKY still had much lower vascular responses to ES and NA than either pregnant or nonpregnant SHR. L-NOARG enhanced vascular responses to All to a greater extent in pregnant SHR than in pregnant WKY.6. These results demonstrate that blunted responses to NA and ES were NO-dependent, while diminished reactivity to AII was only partially dependent on NO in the in situ blood perfused mesenteric resistance vessels of pregnant SHR.7. The present results in pregnant SHR differ from our previous finding with pregnant normotensive WKY, in which blunted responses to NA, but not to ES, were equalized by L-NOARG. Pregnancy induced vasodilatation in hypertensive rats appears to be more dependent on endothelial NO than in normotensive WKY. A defect of the endothelial NO generating pathway which promotes vasodilatation in pregnancy may contribute to the predisposition of women with essential hypertension to develop pre-eclampsia. PMID:8298807

  6. Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development

    PubMed Central

    Moslehi, R; Signore, C; Tamura, D; Mills, JL; DiGiovanna, JJ; Tucker, MA; Troendle, J; Ueda, T; Boyle, J; Khan, SG; Oh, K-S; Goldstein, AM; Kraemer, KH

    2012-01-01

    The effects of DNA repair and transcription gene abnormalities in human pre-natal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10?6) recessive disorder caused by mutations in genes involved in nucleotide excision repair (NER) pathway and in transcription. Based on our novel clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD-affected offspring (n = 24) with respect to abnormalities during their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (n = 18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD-affected pregnancies. Small for gestational age (SGA) <10th percentile [Relative risk (RR) = 9.3, 95% CI = 1.460.5, p = 0.02], SGA <3rd percentile (RR = 7.2, 95% CI = 1.148.1, p = 0.04), and neonatal intensive care unit (NICU) hospitalization (RR = 6.4, 95% CI = 1.429.5, p = 0.02) occurred more frequently among TTD-affected neonates compared with their unaffected siblings. Compared with reference values from general obstetrical population, pregnancies that resulted in TTD-affected infants were significantly more likely to be complicated by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (RR = 35.7, 95% CI = 7.692.5, p = 0.0002), elevated mid-trimester maternal serum human chorionic gonadotropin (hCG) levels (RR = 14.3, 95% CI = 7.016.6, p < 0.0001), SGA <3rd percentile (RR = 13.9, 95% CI = 7.421.1, p < 0.0001), pre-term delivery (<32 weeks) (RR = 12.0, 95% CI = 4.921.6, p < 0.0001), pre-eclampsia (RR = 4.0, 95% CI = 1.67.4, p = 0.006), and decreased fetal movement (RR = 3.3, 95% CI = 1.65.2, p = 0.0018). Abnormal placental development is an underlying mechanism that may explain the constellation of observed complications in our study. Thus, we hypothesize that TTD DNA repair and transcription genes play an important role in normal human placental development. PMID:20002457

  7. The role of cytokines as inflammatory mediators in preeclampsia

    PubMed Central

    Udenze, Ifeoma; Amadi, Casimir; Awolola, Nicholas; Makwe, Christian Chigozie

    2015-01-01

    Introduction This study is to determine the concentrations of IL-6, TNF ?, and C reactive protein (CRP) in women with severe preeclampsia, and compare with those of gestational age- matched normotensive pregnant women and to correlate CRP levels with markers of organ damage in women with preeclampsia. Methods This was a case control study of fifty women with severe preeclampsia and fifty gestational age matched pregnant women with normal blood pressure. The women were drawn from The Antenatal Clinic of The Lagos University Teaching Hospital. Severe pre eclampsia was defined as systolic blood pressure ?160 mmHg and/or diastolic blood pressure ?110mmHg and ?2+ of proteinuria. After obtaining an informed consent, each participant completed a structured questionnaire. The questionnaire sought information on socio-demographic and clinical data. From each participant, mid-stream urine was collected for urinalysis and culture, and blood sample was collected for biochemical analysis. Comparisons of continuous variables and categorical variables were done using the Student's t test and Chi square test respectively. Correlation analysis was used to determine the associations between variables. Statistical significance was set at P Results The women were similar in their socio demographic characteristics. There was a statistically significant difference in the systolic blood pressure (p < 0.0001), diastolic blood pressure ( p < 0.0001), uric acid ( p < 0.0001), AST ( p < 0.0001), ALP ( p < 0.0001), creatinine ( p < 0.0013), GGT ( p < 0.005), IL 6 ( p < 0.021), CRP ( p < 0.0002), and TNF ? ( p < 0.023), between the group with severe preeclampsia and the group with normal blood pressure. This study also reports a significant association between CRP and systolic blood pressure, diastolic blood pressure, uric acid AST and ALP (p Conclusion The inflammatory cytokines, IL6, TNF ? and CRP are elevated in severe preeclampsia and may mediate some of the clinical manifestations of the disorder. A role may exist for anti inflammatory agents in the management of women with preeclampsia. PMID:26113950

  8. Study on the Expressions of PHD and HIF in Placentas from Normal Pregnant Women and Patients with Preeclampsia

    PubMed Central

    Liu, Wei; Wang, Shu-Jun; Lin, Qi-De

    2014-01-01

    Objective: To investigate the relationship between oxygen sensitivity of trophoblast and hypoxia in preeclamptic placenta by the study on the expressions of hypoxia-inducible factor prolyl 4-hydroxylase (PHD) and hypoxia-inducible factor (HIF) in placentas from normal pregnant women and patients with pre-eclampsia. Methods: Subjects were chosen from the in-patients or the out-patients from May 2003 to May 2004. They were divided into 5 groups: early pregnancy group (EP), 13 cases; middle pregnancy group (MP), 9 cases; late pregnancy group (LP, or control group), 12 cases; preeclampsia (PE) group, 20 cases; gestational hypertension group (GH), 10 cases. The mRNA expressions of PHD-1 and -2 and -3 in placentas from all the subjects were assessed by in situ hybridization and Real-time PCR. The expressions of HIF-1α and -2α in placentas from different groups were assessed by immunohistochemistry and western blot. Results: PHD-1,-2 and -3 mRNA were mainly expressed in cytoplasm of trophoblast, especially strongly expressed in extravillous trophoblast. During the progress of pregnancy, the expression of PHD-1 increased significantly (R=0.616, P<0.001). The PHD-1mRNA expression in placentas from PE group decreased significantly compared with that from control group, P<0.05. A significant direct correlation between the PHD-1 mRNA expression in placentas from PE group and their placenta weight was found (R=0.457, P<0.05). The HIF-2α, not the HIF-1α expression, from PE group was significantly higher than that from control group, P<0.01; The HIF-2α expression in trophoblast from PE was inversely correlated to the date of the onset of the disease (R=-0.730, P<0.01). Conclusions: PHD-1 played an important role in hypoxic response pathway of trophoblast through modulating the level of HIF-2α. The overly activated hypoxic response pathway of trophoblast in preeclamptic placenta, which is manifested as the result of HIF-2α over-expression, is the key point to hypoxic dysfunction of trophoblast. PMID:24644426

  9. Is teenage pregnancy an obstetric risk in a welfare society? A population-based study in Finland, from 2006 to 2011

    PubMed Central

    Leppälahti, Suvi; Gissler, Mika; Mentula, Maarit; Heikinheimo, Oskari

    2013-01-01

    Objective To assess obstetric outcomes in teenage pregnancies in a country with a low teenage delivery rate and comprehensive high-quality prenatal care. Design Retrospective population-based register study. Setting Finland. Participants All nulliparous teenagers (13–15 years (n=84), 16–17 years (n=1234), 18–19 years (n=5987)) and controls (25-year-old to 29-year-old women (n=51 142)) with singleton deliveries in 2006–2011. Main outcome measures Risk of adverse obstetric outcomes adjusted for demographic factors and clinically relevant pregnancy complications, with main focus on maternal pregnancy complications. Results Teenage mothers were more likely than controls to live in rural areas (16% (n=1168) vs 11.8% (n=6035)), smoke (36.4% (n=2661) vs 7% (n=3580)) and misuse alcohol or drugs (1.1% (n=82) vs 0.2% (n=96); p<0.001 for all). Teenagers made a good mean number of antenatal clinic visits (16.4 vs 16.5), but were more likely to have attended fewer than half of the recommended visits (3% (n=210) vs 1.4% (n=716)). Teenagers faced increased risks of several obstetric complications, for example, anaemia (adjusted OR 1.8, 95% CI 1.6 to 2.1), proteinuria (1.8, 1.2 to 2.6), urinary tract infection (UTI; 2.9, 1.8 to 4.8), pyelonephritis (6.3, 3.8 to 10.4) and eclampsia (3.2, 1.4 to 7.3), the risks increasing with descending age for most outcomes. Elevated risks of pre-eclampsia (3.7, 1.5 to 9.0) and preterm delivery (2.5, 1.2 to 5.3) were also found among 13-year-olds to 15-year-olds. However, teenage mothers were more likely to have vaginal delivery (1.9, 1.7 to 2.0) without complications. Inadequate prenatal care among teenagers was a risk factor of eclampsia (12.6, 2.6 to 62.6), UTI (5.8, 1.7 to 19.7) and adverse neonatal outcomes. Conclusions Pregnant teenagers tended to be socioeconomically disadvantaged versus controls and faced higher risks of various pregnancy complications. Special attention should be paid to enrolling teenagers into adequate prenatal care in early pregnancy. PMID:23959755

  10. 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 should be sufficient to correct deficiency. PMID:22742603

  11. Placental endoplasmic reticulum stress negatively regulates transcription of placental growth factor via ATF4 and ATF6?: 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, ATF6? and ATF6? 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 ATF6?, but not ATF6?, modulate PlGF transcription. To conclude, ATF4 and ATF6? 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 intervention for these pregnancy complications. 2015 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:26648175

  12. The Effect of pH and Ion Channel Modulators on Human Placental Arteries

    PubMed Central

    Ali, Tayyba Y; Broughton Pipkin, Fiona; Khan, Raheela N

    2014-01-01

    Chorionic plate arteries (CPA) are located at the maternofetal interface where they are able to respond to local metabolic changes. Unlike many other types of vasculature, the placenta lacks nervous control and requires autoregulation for controlling blood flow. The placental circulation, which is of low-resistance, may become hypoxic easily leading to fetal acidosis and fetal distress however the role of the ion channels in these circumstances is not well-understood. Active potassium channel conductances that are subject to local physicochemical modulation may serve as pathways through which such signals are transduced. The aim of this study was to investigate the modulation of CPA by pH and the channels implicated in these responses using wire myography. CPA were isolated from healthy placentae and pre-contracted with U46619 before testing the effects of extracellular pH using 1 M lactic acid over the pH range 7.4 - 6.4 in the presence of a variety of ion channel modulators. A change from pH 7.4 to 7.2 produced a 293% (n?=?9) relaxation of CPA which increased to 614% at the lowest pH of 6.4. In vessels isolated from placentae of women with pre-eclampsia (n?=?6), pH responses were attenuated. L-methionine increased the relaxation to 677% (n?=?6; p<0.001) at pH 6.4. Similarly the TASK 1/3 blocker zinc chloride (1 mM) gave a maximum relaxation of 725% (n?=?8; p<0.01) which compared with the relaxation produced by the TREK-1 opener riluzole (755%; n?=?6). Several other modulators induced no significant changes in vascular responses. Our study confirmed expression of several ion channel subtypes in CPA with our results indicating that extracellular pH within the physiological range has an important role in controlling vasodilatation in the human term placenta. PMID:25490401

  13. The effects of vitamin D3 on lipogenesis in the liver and adipose tissue of pregnant rats.

    PubMed

    Kang, Eun-Jin; Lee, Jae-Eon; An, Sung-Min; Lee, Jae Ho; Kwon, Hyeog Soong; Kim, Byoung Chul; Kim, Seon Jong; Kim, Joo Man; Hwang, Dae Youn; Jung, Young-Jin; Yang, Seung Yun; Kim, Seung Chul; An, Beum-Soo

    2015-10-01

    Obesity is a worldwide individual and public health issue, and contributes to the development of numerous chronic diseases. In particular, maternal obesity has harmful effects on both the mother and child during and after pregnancy. The digestion and metabolism of food are controlled by endocrine factors, including insulin, glucagon and estrogen. These hormonal factors are differentially regulated during pregnancy due to the specialized hormonal environment during this period. In the present study, we examined the effects of 1,25-dihydroxyvitaminD3(VD3), an active hormonal form of nutritional vitaminD3, on lipid metabolism in pregnant rats. The body weight of rats treated with VD3 was significantly reduced compared to that of the rats in the control group. In addition, histological analysis demonstrated that the amount of fat stored in adipocytes was reduced by treatment with VD3. To determine the role of VD3 in lipid metabolism, the expression levels of lipid metabolism?associated genes were measured in the rat adipose tissue and liver. VD3 negatively regulated the expression of various lipogenic genes, including fatty acid synthase(FAS), stearoyl-CoA desaturase1(SCD1) and acetyl-CoA carboxylase1(ACC1), in both the adipose tissue and liver. However, the regulators of lipogenic enzymes such as, sterol regulatory element-binding protein-1c(SREBP-1c), peroxisome proliferator-activated receptor-?(PPAR-?) and insulin-induced gene2(INSIG2) were differentially regulated by VD3 in a tissue?specific manner. On the whole, these findings suggest that VD3 regulates lipid metabolism and deposition in the liver and adipose tissue, and thereby reduces fat in pregnant animals, as well as body weight. Our results suggest that the alteration of lipogenesis through the administration of VD3 may help to reduce excessive weight gain during pregnancy and prevent obesity?related pregnancy complications such as pre-eclampsia, gestational diabetes, hypertension and issues with labor. PMID:26239543

  14. 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 pregnant mothers, were stabilised and transported to hospital by the new emergency ambulance service. 293 resuscitation attempts were documented in personal logbooks. A sustainable system for better managing emergencies has been established and is helping to negate the main obstacle impeding progress: the country's lack of available trained medical and nursing staff. However, insufficient attention was paid to improving staff morale and accommodation representing significant failings of the programme. PMID:20718979

  15. Maternal mortality in health institutions with emergency obstetric care facilities in Enugu State, Nigeria.

    PubMed

    Onah, H E; Okaro, J M; Umeh, U; Chigbu, C O

    2005-08-01

    In order to assess the current level of maternal mortality in health institutions with comprehensive emergency obstetric care in Enugu State, South Eastern Nigeria, a retrospective analysis of maternal deaths for the years 1999-2003 was carried out to establish the maternal mortality ratios in the eligible health institutions. Each maternal death was studied in detail to establish the socio-demographic characteristics of the women who died; their referral sources, type of delay (if any), medical causes of death and their preventability. In-depth interviews of the service providers were carried out to throw more light on the maternal mortality situation in the state. Five out of seven eligible health institutions were studied. Within the 5-year period (1999-2003), there were 141 maternal deaths and 18,257 live births giving a maternal mortality ratio of 772 maternal deaths per 100,000. The folders of 89 out of the 141 women who died were retrieved. Of these 89 maternal deaths, 51.7% of them were unemployed, 52.4% were referred from private hospitals; type 3 delay was the commonest type of delay encountered in the care of the women. Referral delay was the main cause of delay accounting for 46.4% of all cases of type 3 delay. The leading causes of maternal deaths among the women were obstetric haemorrhage (19.1%), sepsis (18.0%), prolonged obstructed labour/ruptured uterus (16.9%) and pre-eclampsia/eclampsia (16.9%). The in-depth interviews corroborated the high maternal mortality ratio recorded and the type 3 delays in tackling obstetric emergencies. It also showed some discrepancies between reality and the health providers' perception of the magnitude of maternal mortality situation in the state. It was concluded that in health institutions in Enugu State with comprehensive emergency obstetric care facilities, the maternal mortality ratio remains high due to type 3 delays. Most of the referrals come from private hospitals, hence the need to retrain the private practitioners in emergency obstetric care. PMID:16234142

  16. 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 symptoms, an association possibly mediated by other factors such as fetal/neonatal condition. Conclusions Despite the absence of robust evidence regarding the relationship between severe maternal morbidity and PTSD/PTSD symptoms, it is crucially important that clinicians and policy makers are aware of a potential higher risk of PTSD among women who experience severe morbidity. Further studies are now needed to confirm this risk as well as to understand underlying mechanisms in order to minimise the longer term psychiatric impact of severe maternal morbidity. PMID:23140343

  17. 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 on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed. Conclusion Although the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs. PMID:19426469

  18. Vitamin D supplementation in pregnancy: a systematic review.

    PubMed Central

    Harvey, Nicholas C; Holroyd, Christopher; Ntani, Georgia; Javaid, Kassim; Cooper, Philip; Moon, Rebecca; Cole, Zoe; Tinati, Tannaze; Godfrey, Keith; Dennison, Elaine; Bishop, Nicholas J; Baird, Janis; Cooper, Cyrus

    2014-01-01

    BACKGROUND: It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved. OBJECTIVES: To answer the following questions: (1) What are the clinical criteria for vitamin D deficiency in pregnant women? (2) What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)D? (3) Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)? (4) What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy? (5) Is supplementation with vitamin D in pregnancy likely to be cost-effective? METHODS: We performed a systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases [including Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR) and the Health Technology Assessment (HTA) database] were searched from inception up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary. Abstracts were reviewed by two reviewers. INCLUSION AND EXCLUSION CRITERIA: SUBJECTS: pregnant women or pregnant women and their offspring. EXPOSURE: either assessment of vitamin D status [dietary intake, sunlight exposure, circulating 25(OH)D concentration] or supplementation of participants with vitamin D or food containing vitamin D (e.g. oily fish). OUTCOMES: offspring - birthweight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes mellitus, low birthweight, serum calcium concentration, blood pressure and rickets; mother - pre-eclampsia, gestational diabetes mellitus, risk of caesarean section and bacterial vaginosis. RESULTS: Seventy-six studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence. The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes. For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)D and (1) offspring birthweight in meta-analysis of three observational studies using log-transformed 25(OH)D concentrations after adjustment for potential confounding factors [pooled regression coefficient 5.63 g/10% change maternal 25(OH)D, 95% confidence interval (CI) 1.11 to 10.16 g], but not in those four studies using natural units, or across intervention studies; (2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of six intervention studies (all found to be at high risk of bias; mean difference 0.05 mmol/l, 95% CI 0.02 to 0.05 mmol/l); and (3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis. The evidence base was insufficient to reliably answer questions 4 and 5. LIMITATIONS: Study methodology varied widely in terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition. CONCLUSIONS: The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birthweight, bone mass) or risk of bias and low quality (calcium concentrations). High-quality randomised trials are now required. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001426. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID:25025896

  19. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians.

    PubMed

    Vayssière, C; Sentilhes, L; Ego, A; Bernard, C; Cambourieu, D; Flamant, C; Gascoin, G; Gaudineau, A; Grangé, G; Houfflin-Debarge, V; Langer, B; Malan, V; Marcorelles, P; Nizard, J; Perrotin, F; Salomon, L; Senat, M-V; Serry, A; Tessier, V; Truffert, P; Tsatsaris, V; Arnaud, C; Carbonne, B

    2015-10-01

    Small for gestational age (SGA) is defined by weight (in utero estimated fetal weight or birth weight) below the 10th percentile (professional consensus). Severe SGA is SGA below the third percentile (professional consensus). Fetal growth restriction (FGR) or intra-uterine growth restriction (IUGR) usually correspond with SGA associated with evidence indicating abnormal growth (with or without abnormal uterine and/or umbilical Doppler): arrest of growth or a shift in its rate measured longitudinally (at least two measurements, 3 weeks apart) (professional consensus). More rarely, they may correspond with inadequate growth, with weight near the 10th percentile without being SGA (LE2). Birthweight curves are not appropriate for the identification of SGA at early gestational ages because of the disorders associated with preterm delivery. In utero curves represent physiological growth more reliably (LE2). In diagnostic (or reference) ultrasound, the use of growth curves adjusted for maternal height and weight, parity and fetal sex is recommended (professional consensus). In screening, the use of adjusted curves must be assessed in pilot regions to determine the schedule for their subsequent introduction at national level. This choice is based on evidence of feasibility and the absence of any proven benefits for individualized curves for perinatal health in the general population (professional consensus). Children born with FGR or SGA have a higher risk of minor cognitive deficits, school problems and metabolic syndrome in adulthood. The role of preterm delivery in these complications is linked. The measurement of fundal height remains relevant to screening after 22 weeks of gestation (Grade C). The biometric ultrasound indicators recommended are: head circumference (HC), abdominal circumference (AC) and femur length (FL) (professional consensus). They allow calculation of estimated fetal weight (EFW), which, with AC, is the most relevant indicator for screening. Hadlock's EFW formula with three indicators (HC, AC and FL) should ideally be used (Grade B). The ultrasound report must specify the percentile of the EFW (Grade C). Verification of the date of conception is essential. It is based on the crown-rump length between 11 and 14 weeks of gestation (Grade A). The HC, AC and FL measurements must be related to the appropriate reference curves (professional consensus); those modelled from College Francais d'Echographie Fetale data are recommended because they are multicentere French curves (professional consensus). Whether or not a work-up should be performed and its content depend on the context (gestational age, severity of biometric abnormalities, other ultrasound data, parents' wishes, etc.) (professional consensus). Such a work-up only makes sense if it might modify pregnancy management and, in particular, if it has the potential to reduce perinatal and long-term morbidity and mortality (professional consensus). The use of umbilical artery Doppler velocimetry is associated with better newborn health status in populations at risk, especially in those with FGR (Grade A). This Doppler examination must be the first-line tool for surveillance of fetuses with SGA and FGR (professional consensus). A course of corticosteroids is recommended for women with an FGR fetus, and for whom delivery before 34 weeks of gestation is envisaged (Grade C). Magnesium sulphate should be prescribed for preterm deliveries before 32-33 weeks of gestation (Grade A). The same management should apply for preterm FGR deliveries (Grade C). In cases of FGR, fetal growth must be monitored at intervals of no less than 2 weeks, and ideally 3 weeks (professional consensus). Referral to a Level IIb or III maternity ward must be proposed in cases of EFW <1500g, potential birth before 32-34 weeks of gestation (absent or reversed umbilical end-diastolic flow, abnormal venous Doppler) or a fetal disease associated with any of these (professional consensus). Systematic caesarean deliveries for FGR are not recommended (Grade C). In cases of vaginal delivery, fetal heart rate must be monitored continuously during labour, and any delay before intervention must be faster than in low-risk situations (professional consensus). Regional anaesthesia is preferred in trials of vaginal delivery, as in planned caesareans. Morbidity and mortality are higher in SGA newborns than in normal-weight newborns of the same gestational age (LE3). The risk of neonatal mortality is two to four times higher in SGA newborns than in non-SGA preterm and full-term infants (LE2). Initial management of an SGA newborn includes combatting hypothermia by maintaining the heat chain (survival blanket), ventilation with a pressure-controlled insufflator, if necessary, and close monitoring of capillary blood glucose (professional consensus). Testing for antiphospholipids (anticardiolipin, circulating anticoagulant, anti-beta2-GP1) is recommended in women with previous severe FGR (below third percentile) that led to birth before 34 weeks of gestation (professional consensus). It is recommended that aspirin should be prescribed to women with a history of pre-eclampsia before 34 weeks of gestation, and/or FGR below the fifth percentile with a probable vascular origin (professional consensus). Aspirin must be taken in the evening or at least 8h after awakening (Grade B), before 16 weeks of gestation, at a dose of 100-160mg/day (Grade A). PMID:26207980

  20. 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.; Loubire, 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 (811 weeks; n = 18) and second (1216 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 (TR?1, TR?1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different cell isolates were unaffected by T3 so changes in cell numbers could not account for any observed effects. In the first trimester, T3 decreased VEGF-A secretion by total decidual cells (P < 0.05) and increased angiopoietin-2 secretion by stromal-depleted cells (P < 0.05) but in the second trimester total decidual cells showed only increased angiogenin secretion (P < 0.05). In the first trimester, T3 reduced IL-10 secretion by total decidual cells (P < 0.05), and reduced granulocyte macrophage colony stimulating factor (P < 0.01), IL-8 (P < 0.05), IL-10 (P < 0.01), IL-1? (P < 0.05) and monocyte chemotactic protein -1 (P < 0.001) secretion by macrophages, but increased tumour necrosis factor-? secretion by stromal-depleted cells (P < 0.05) and increased IL-6 by uNK cells (P < 0.05). In contrast, in the second trimester T3 increased IL-10 secretion by total decidual cells (P < 0.01) but did not affect cytokine secretion by uNK cells and macrophages. Conditioned media from first trimester T3-treated total decidual cells and macrophages did not alter EVT invasion compared with untreated controls. Thus, treatment of decidual cells with T3 resulted in changes in both angiogenic growth factor and cytokine secretion in a cell type-specific and gestational age-dependent manner, with first trimester decidual macrophages being the most responsive to T3 treatment, but these changes in decidual cell secretome did not affect EVT invasion in vitro. LIMITATIONS, REASONS FOR CAUTION Our results are based on in vitro findings and we cannot be certain if a similar response occurs in human pregnancy in vivo. WIDER IMPLICATIONS OF THE FINDINGS Optimal maternal thyroid hormone concentrations could play a critical role in maintaining a balanced inflammatory response in early pregnancy to prevent fetal immune rejection and promote normal placental dev