Sample records for pre-eclampsia

  1. Pre-eclampsia: an update.

    PubMed

    von Dadelszen, Peter; Magee, Laura A

    2014-08-01

    Pre-eclampsia remains the second leading direct cause of maternal death, >99 % of which occurs in less developed countries. Over 90 percent of the observed reduction in pre-eclampsia-related maternal deaths in the UK (1952-2008) occurred with antenatal surveillance and timed delivery. In this review, we discuss the pathogenesis, diagnostic criteria, disease prediction models, prevention and management of pre-eclampsia. The Pre-eclampsia Integrated Estimate of RiSk (PIERS) models and markers of angiogenic imbalance identify women at incremental risk for severe pre-eclampsia complications. For women at high risk of developing pre-eclampsia, low doses of aspirin (especially if started <17 weeks) and calcium are evidence-based preventative strategies; heparin is less so. Severe hypertension must be treated and the Control of Hypertension In Pregnancy (CHIPS) Trial (reporting: 2014) will guide non-severe hypertension management. Magnesium sulfate prevents and treats eclampsia; there is insufficient evidence to support alternative regimens. Pre-eclampsia predicts later cardiovascular disease; however, at this time we do not know what to do about it. PMID:24915961

  2. Maternal pathophysiology in pre-eclampsia

    Microsoft Academic Search

    Louise Kenny; Philip N. Baker

    1999-01-01

    Pre-eclampsia is a common condition, unique to pregnancy, and almost unique among medical conditions in that we have, at best, only a patchy knowledge of the underlying aetiology and pathophysiology. In this chapter, established and new hypotheses will be discussed and the recent supporting evidence for each will be reviewed. The principal systems affected by pre-eclampsia, namely the cardiovascular, coagulation,

  3. Fluid management in pre-eclampsia

    Microsoft Academic Search

    T. Engelhardt; F. M. MacLennan

    1999-01-01

    We review the evidence base for fluid management in pre-eclampsia. Current understanding of the relevant pathophysiology and the possible impact of styles of fluid management on maternal and fetal outcome are presented. There is little evidence upon which to base the management of fluid balance in pre-eclampsia. Reports are conflicting and no large prospective outcome studies of fluid management have

  4. Pre-eclampsia and HELLP syndrome

    Microsoft Academic Search

    Sonji D Clarke; Catherine Nelson-Piercy

    2005-01-01

    Pre-eclampsia remains one of the main direct causes of maternal death, as reported in the Confidential Enquiry into Maternal Deaths in the United Kingdom. Many of those deaths feature elements of substandard care. This article discusses the definitions of hypertension and the current thinking on the pathophysiology of pre-eclampsia and also discusses the relevant risk factors: general, familial, obstetric and

  5. Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia

    Microsoft Academic Search

    S Sohda; T Arinami; H Hamada; N Yamada; H Hamaguchi; T Kubo

    1997-01-01

    A common missense mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, a C to T substitution at nucleotide 677, is responsible for reduced MTHFR activity and associated with modestly increased plasma homocysteine concentrations. Since underlying maternal vascular disease increases the risk of pre-eclampsia, we had the working hypothesis that pre-eclampsia patients would have an increased T677 allele frequency compared with controls.

  6. Early platelet consumption in pre-eclampsia

    Microsoft Academic Search

    C W G REDMAN; J Bonnar; L Beilin

    1978-01-01

    One hundred and thirty-one women with chronic hypertension were studied serially during pregnancy to determine the sequence of events in the development of superimposed pre-eclampsia and to discover the time of onset. Twenty-seven women developed a sustained rise in plasma urate concentrations, which began at about 28 weeks' gestation and which is characteristic of pre-eclampsia. The mean platelet count was

  7. Pre-eclampsia and the anaesthetist

    Microsoft Academic Search

    Andrew H. Shennan

    2007-01-01

    Pre-eclampsia remains a significant problem in modern obstetrics, contributing to 1 in 4 very low birth weight babies. Between 2–4% of women will develop pre-eclampsia. Maternal and fetal morbidity and mortality remain a significant problem. Increasing understanding of the underlying pathophysiology has resulted in a more scientific approach to prophylaxis and prevention. Larger data sets are now being analysed, and

  8. Predictors of pre-eclampsia in women at high risk

    Microsoft Academic Search

    Steve Caritis; Baha Sibai; John Hauth; Marshall Lindheimer; Peter VanDorsten; Mark Klebanoff; Elizabeth Thom; Mark Landon; Richard Paul; Menachem Miodovnik; Paul Meis; Gary Thurnau; Mitchell Dombrowski; Donald McNellis; James Roberts

    1998-01-01

    Objective: We assessed several variables as predictors for pre-eclampsia risk in a group of women at high risk. Study Design: We studied 2503 women with either diabetes mellitus, chronic hypertension, multifetal gestation, or pre-eclampsia in a previous pregnancy who participated in a multicenter study comparing aspirin and placebo in preventing pre-eclampsia. We evaluated multiple variables for predicting pre-eclampsia risk with

  9. Lipids and the pathogenesis of pre-eclampsia

    Microsoft Academic Search

    N. Sattar; I. A. Greer

    1999-01-01

    This review summarizes evidence for the involvement of lipids in the pathophysiology of pre-eclampsia. The following areas are addressed: lipids and lipoprotein subfractions in pre-eclampsia set against a background of the lipid pattern seen in normal pregnancy; the potential mechanism(s) for such changes in pre-eclampsia; and potential links of the atherogenic lipid profile in pre-eclampsia to oxidative pathways, endothelial dysfunction

  10. The pathogenesis of pre-eclampsia

    Microsoft Academic Search

    C. W. G Redman; I. L Sargent

    2001-01-01

    Syncytiotrophoblast normally sheds redundant placental debris into the maternal circulation, a process, which depends on apoptosis. It is renewed from the underlying mononuclear cytotrophoblast. We propose that the continual clearance of this debris from the maternal circulation causes a systemic inflammatory response that is present in all pregnant women in the third trimester. Pre-eclampsia occurs when the systemic inflammatory response

  11. Genetic control of severe pre-eclampsia

    Microsoft Academic Search

    D W Cooper; W A Liston

    1979-01-01

    A genetic analysis has been made of published and new data on the familial occurrence of severe pre-eclampsia in primigravid women. This has shown that the condition may be largely a Mendelian recessive one. Bcause the condition occurs only in pregnancy, and because susceptible women cannot otherwise be identified, it is difficult to decide whether the genotype of the parent

  12. Pre-eclampsia and HELLP syndrome

    Microsoft Academic Search

    Sonji D. Clarke; Catherine Nelson-Piercy

    2008-01-01

    Pre-eclampsia, eclampsia and HELLP syndrome are discussed in this article. The most recent theory on the pathophysiology of these conditions, the various risk factors and how knowledge of these may help in the management of these conditions are also discussed. Current measures used for prophylaxis in the form of low-dose aspirin, and low molecular weight heparin (LMWH) are discussed, together

  13. Mechanisms of Disease: pre-eclampsia

    Microsoft Academic Search

    Norberto Perico; Giuseppe Remuzzi; Marina Noris

    2005-01-01

    Pre-eclampsia, a syndrome of pregnant women, is one of the leading causes of maternal and fetal morbidity and mortality. Despite active research, the etiology of this disorder remains an enigma. Recent work has, however, provided promising explanations for the causation of the disorder and some of its phenotypes. Evidence indicates that the symptoms of hypertension and proteinuria, upon which the

  14. Pre-eclampsia and the anaesthetist

    Microsoft Academic Search

    Andrew H. Shennan; Kate E. Duhig

    2010-01-01

    Pre-eclampsia remains a significant problem in modern obstetrics occurring in 2–4% of women. The disease is still responsible for 60,000 maternal deaths worldwide annually. An increased understanding of the underlying pathophysiology has resulted in a more scientific approach to prophylaxis and prevention, yet the underlying disease mechanisms are not fully understood.The role of combining good prediction with prevention has yet

  15. Recent Insights into the Pathogenesis of Pre-eclampsia

    Microsoft Academic Search

    J. M. Roberts; K. Y. Lain

    2002-01-01

    Pre-eclampsia is more than pregnancy induced hypertension. The emerging view described in this presentation is that pre-eclampsia is secondary to the interactions of reduced placental perfusion with diverse maternal factors that alter endothelial function. The maternal contribution is from factors that antedate pregnancy and are influenced by the usual metabolic adaptations of pregnancy. The endothelium and other targets for the

  16. Working conditions and prevalence of pre-eclampsia, Norway 1989

    Microsoft Academic Search

    E. Wergeland; K. Strand

    1997-01-01

    Objective: To study the associations between working conditions and pre-eclampsia. Methods: A cross-sectional study based on questionnaires to all parturients was conducted in Norway from 16 October 1989 to 26 November 1989, with an 87.2% response rate. Of the 5388 responders with singleton pregnancies, 3321 continued in paid work beyond the 3rd month of pregnancy. Pre-eclampsia was recorded if the

  17. 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

  18. 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

  19. Placental Superoxide is Increased in Pre-eclampsia

    Microsoft Academic Search

    J. M. Sikkema; B. B. van Rijn; A. Franx; H. W. Bruinse; R. de Roos; E. S. G. Stroes; E. E. van Faassen

    2001-01-01

    One of the current hypotheses on the pathophysiology of pre-eclampsia (PE) states that the placenta secretes one or more cytotoxic factors resulting in maternal endothelial dysfunction. Among the candidate factors are the products of increased oxidative stress. Although there is circumstantial evidence of such an increase, direct evidence is still lacking. Electron paramagnetic spin trap resonance (EPR), the most direct

  20. Immunoregulation in normal pregnancy and pre-eclampsia: an overview

    Microsoft Academic Search

    Ian L Sargent; Angela M Borzychowski; Chris WG Redman

    2006-01-01

    Pre-eclampsia is a major disorder of human pregnancy, which may have an immunological basis. It is a disease of two stages. The first stage concerns the relative failure of early trophoblast invasion and remodelling of the spiral arteries, leading to a poor blood supply to the placenta, exposing it to oxidative stress. The inadequate trophoblast invasion may result from decreased

  1. Prediction and diagnosis of pre-eclampsia; the scientific basis.

    PubMed

    Poston, Lucilla

    2013-04-01

    The accurate prediction of women at risk of pre-eclampsia, and certain diagnosis are central to optimal management and treatment. Prediction has improved, particularly through measurement of angiogenic/antiangiogenic factors but sensitivity and specificity remains suboptimal, and the heterogeneity of underlying clinical risk confounds generalisability of a single early pregnancy test for all women. The 'omics' methodologies offer the potential for discovery of novel biomarkers and proteomics, metabolomics and transcriptomic approaches are beginning to identify multiple new candidates for evaluation. However, once pregnancy is established the potential for modification of established pathological processes, increasingly identifiable by accurate biomarkers, remains an unanswered and possibly unattainable challenge. The potential for more accurate pre-conceptional identification of risk, and subsequent modification of risk, presents an increasingly attractive alternative to prevention of pre-eclampsia. Advances have certainly been made in diagnosis; the measurement of PlGF in women with suspected pre-eclampsia is likely to become an integral component of clinical care, improving detection and management of pre-eclampsia. PMID:26105837

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

    Microsoft Academic Search

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

    2010-01-01

    Autism spectrum disorders (ASD) are primarily inherited, but perinatal or other environmental factors may also be important.\\u000a In an analysis of 87,677 births from 1996 through 2002, insured by the South Carolina Medicaid program, birth weight was significantly\\u000a inversely associated with the odds of ASD (OR = 0.78, p = .001 for each additional kilogram). Maternal pre-eclampsia\\/eclampsia was significantly associated with greater odds of

  3. Preventing pre-eclampsia - are dietary factors the key?

    PubMed

    Dodd, Jodie M; O'Brien, Cecelia; Grivell, Rosalie M

    2014-01-01

    Pre-eclampsia is a common pregnancy related condition, which contributes significantly both to maternal and perinatal morbidity and mortality. The precise pathophysiology of pre-eclampsia is uncertain, and the development of effective preventive strategies remains elusive. Schoenaker and colleagues conducted a systematic review and meta-analysis of observational studies reporting dietary intake and dietary patterns. The findings indicated that women with a low dietary calcium intake were more likely to be diagnosed with gestational hypertension, while there was a suggestion (although not statistically significant) of a beneficial effect of a diet rich in fruits and vegetables on risk of pre-eclampsia. This is in contrast to the findings of systematic reviews and meta-analyses of randomised trials in pregnancy evaluating calcium supplementation and anti-oxidant vitamin C and E supplementation. The validity of any systematic review is reliant on both the underlying methodology and the quality of each of the included studies; the review by Schoenaker and colleagues is limited by the observational nature of the included studies.Please see related article: http://www.biomedcentral.com/1741-7015/12/157/abstract. PMID:25286368

  4. Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data

    Microsoft Academic Search

    Lisa M. Askie; Lelia Duley; David J. Henderson-Smart; Lesley A. Stewart

    2007-01-01

    Summary Background Pre-eclampsia is a major cause of mortality and morbidity during pregnancy and childbirth. Antiplatelet agents, especially low-dose aspirin, might prevent or delay pre-eclampsia, and thereby improve outcome. Our aim was to assess the use of antiplatelet agents for the primary prevention of pre-eclampsia, and to explore which women are likely to benefit most. Methods We did a meta-analysis

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

    PubMed

    Lavallee, Layla

    2015-07-01

    Pre-eclampsia is a complex and unpredictable disorder that may occur during pregnancy. Its presentation ranges from mild to severe, and the condition may lead to the death of the mother and/or the baby in extreme cases. The earlier the disorder is detected and managed, the better the outcome. This article provides an outline of the disorder and its management, within the framework of UK and international guidelines. A series of suggested activities encourages the reader to reflect on the information provided within the context of their practice. PMID:26153971

  6. Placental mitochondria as a source of oxidative stress in pre-eclampsia

    Microsoft Academic Search

    Y. Wang; S. W. Walsh

    1998-01-01

    Pre-eclampsia is a hypertensive disorder of human pregnancy that is a leading cause of premature delivery and fetal growth retardation. It is characterized by hypertension, reduced uteroplacental blood flow, proteinuria and oedema. Pre-eclampsia is associated with increased lipid peroxidation in the maternal circulation and in the placenta. Mitochondria are sources of oxygen radicals and are enriched with polyunsaturated fatty acids

  7. Could uric acid have a pathogenic role in pre-eclampsia?

    Microsoft Academic Search

    Annabel C. Martin; Mark A. Brown

    2010-01-01

    Interest has been renewed over the role of uric acid in the pathogenesis of hypertension, endothelial dysfunction and renal dysfunction, which are all features of pre-eclampsia. Uric acid is not a consistent predictive factor for the development of pre-eclampsia but its levels generally increase once the disease manifests, and plasma levels of uric acid approximately correlate with disease severity. Hyperuricemia

  8. Pre-eclampsia: evidence of altered ventricular repolarization by standard ECG parameters and QT dispersion.

    PubMed

    Raffaelli, Ricciarda; Prioli, Maria Antonia; Parissone, Francesca; Prati, Daniele; Carli, Michela; Bergamini, Corinna; Cacici, Giuseppe; Balestreri, Debora; Vassanelli, Corrado; Franchi, Massimo

    2014-11-01

    Pre-eclampsia complicates approximately 6-8% of all pregnancies. Epidemiologic studies have demonstrated a relationship between pre-eclampsia and cardiac morbidity and mortality later in life, but the effect of pre-eclampsia on electrical cardiac activity during the acute phase has not yet been understood. The aim of this study was to investigate ECG alterations during pre-eclampsia. Prepartum ECGs of 76 consecutive pre-eclamptic women were compared with those of 76 healthy pregnant women. All of the routine ECG parameters were considered, and ventricular repolarization was assessed by QT interval and QT dispersion (QTd). Pregnancies complicated by pre-eclampsia showed a significant alteration of ventricular repolarization compared with the control group. Among ECG parameters, QT and QTc intervals and QTd were more prolonged in pre-eclamptic women. Multivariate analysis also showed that pre-eclampsia was the only independent determinant of QTd. In conclusion, pre-eclampsia has a significant effect on ventricular repolarization. This alteration could, in part, explain the increased cardiovascular risk of women with a history of pre-eclampsia. Further studies are necessary to confirm the relationship between ventricular repolarization abnormalities and increased cardiovascular risk later in life. PMID:24965173

  9. Does Nitric Oxide Play a Role in the Aetiology of Pre-eclampsia?

    Microsoft Academic Search

    L. M. Postovit; M. A. Adams; C. H. Graham

    2001-01-01

    Although progress has been made toward our understanding of the pathophysiology of pre-eclampsia, the precise aetiology of this disease still remains an enigma. One of the hallmarks of pre-eclampsia is a failure of the extravillous cytotrophoblast cells to invade and remodel the uterine spiral arterioles during the first trimester of pregnancy. Moreover, studies suggest that the cause of this disorder

  10. Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review

    Microsoft Academic Search

    Shakila Thangaratinam; Arri Coomarasamy; Fidelma O'Mahony; Steve Sharp; Javier Zamora; Khalid S Khan; Khaled MK Ismail

    2009-01-01

    BACKGROUND: Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies. METHODS: We

  11. Recent advances in the diagnosis and management of pre-eclampsia.

    PubMed

    Duhig, Kate E; Shennan, Andrew H

    2015-01-01

    Pre-eclampsia complicates around 5% of pregnancies and hypertensive disorders of pregnancy are responsible for over 60,000 maternal deaths worldwide annually. Pre-eclampsia is characterized by hypertension and features of multiple organ disease. Diagnosis remains a challenge as clinical presentation is highly variable and even with severe disease a woman can be asymptomatic. Pre-eclampsia is characterized by abnormal placentation with subsequent maternal inflammatory and vascular response. Improved understanding of the underlying pathophysiology relating to the role of angiogenic factors, has emerged and placed intense interest on their role in prognostic modelling or diagnosis of pre-eclampsia. This article summarizes new developments in diagnosis with a focus on angiogenic biomarkers for prediction of disease onset, and recent advances in management strategies for patients with pre-eclampsia. PMID:25750742

  12. Advances in the pathophysiology of pre-eclampsia and related podocyte injury

    PubMed Central

    Craici, Iasmina M.; Wagner, Steven J.; Weissgerber, Tracey L.; Grande, Joseph P.; Garovic, Vesna D.

    2014-01-01

    Pre-eclampsia is a pregnancy-specific hypertensive disorder that may lead to serious maternal and fetal complications. It is a multisystem disease that is commonly, but not always, accompanied by proteinuria. Its cause(s) remain unknown, and delivery remains the only definitive treatment. It is increasingly recognized that many pathophysiological processes contribute to this syndrome, with different signaling pathways converging at the point of systemic endothelial dysfunction, hypertension, and proteinuria. Different animal models of pre-eclampsia have proven utility for specific aspects of pre-eclampsia research, and offer insights into pathophysiology and treatment possibilities. Therapeutic interventions that specifically target these pathways may optimize pre-eclampsia management and may improve fetal and maternal outcomes. In addition, recent findings regarding placental, endothelial, and podocyte pathophysiology in pre-eclampsia provide unique and exciting possibilities for improved diagnostic accuracy. Emerging evidence suggests that testing for urinary podocytes or their markers may facilitate the prediction and diagnosis of pre-eclampsia. In this review, we explore recent research regarding placental, endothelial, and podocyte pathophysiology. We further discuss new signaling and genetic pathways that may contribute to pre-eclampsia pathophysiology, emerging screening and diagnostic strategies, and potential targeted interventions. PMID:24573315

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

    PubMed

    Williams, Paula Juliet; Morgan, Linda

    2012-01-01

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

  14. Role of kinins in mediating vascular function in healthy pregnancy and pre-eclampsia 

    E-print Network

    Moyes, Amie Jane

    2010-01-01

    Pre-eclampsia is a pregnancy-related disorder characterised by high blood pressure, proteinuria and oedema. The aetiology of the disease is unclear but evidence suggests that endothelial dysfunction is central to the ...

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

    PubMed

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

    2014-01-01

    Pre-eclampsia is the main cause of maternal and fetal death and disability worldwide. Its incidence in the Islamic Republic of Iran is 5%-12%. Air pollution has been reported to be one of the causative factors, and this case-control study determined its effect on pre-eclampsia in 195 pregnant women (65 with pre-eclampsia and 130 without) admitted to hospitals in Tehran. Women were divided into high and low exposure groups according to the mean density of exposure to pollutants during pregnancy. There was no statistically significant relationship between exposure to air pollutants including CO, particulate matter, SO2, NO2 and O3 and pre-eclampsia. The combined effect was also not significant. Air pollution is one of the problems of modern society and its avoidance is almost impossible for pregnant women. This study should reduce concern about pregnant women living in polluted cities. PMID:24995762

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

    Microsoft Academic Search

    M P Moore; C W Redman

    1983-01-01

    Twenty four women with severe pre-eclampsia diagnosed before 34 weeks' gestation were compared with 48 randomly selected controls matched for age and parity. Subjects were studied in the puerperium using a questionnaire, clinical examination, and review of case records. A history of infertility, headaches (particularly migraine), pre-eclampsia in a previous pregnancy, or a raised serum alpha-fetoprotein concentration at the time

  17. Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review

    Microsoft Academic Search

    Lelia Duley; David Henderson; Marian Knight; James King; Epidemiology Unit

    2001-01-01

    Objective To assess the effectiveness and safety of antiplatelet drugs for prevention of pre›eclampsia and its consequences. Design Systematic review. Data sources Register of trials maintained by Cochrane Pregnancy and Childbirth Group, Cochrane Controlled Trials Register, and Embase. Included studies Randomised trials involving women at risk of pre›eclampsia, and its complications, allocated to antiplatelet drug(s) versus placebo or no antiplatelet

  18. Pregnant women with chronic hypertension and superimposed pre-eclampsia have high cerebral perfusion pressure

    Microsoft Academic Search

    Michael A Belfort; Cathy Tooke-Miller; John C Allen; Michael A Varner; Charlotta Grunewald; Henry Nisell; J. Alan Herd

    2001-01-01

    Objective To determine any differences in cerebral perfusion pressure in patients with chronic hypertension compared with those with chronic hypertension and superimposed pre-eclampsia.Design A prospective observational study.Setting University hospital clinic and labour and delivery suite.Participants Fifteen women with chronic hypertension and 15 with superimposed pre-eclampsia.Methods Transcranial Doppler ultrasound was used to measure blood velocity in the middle cerebral arteries of

  19. Pre-eclampsia in pregnancy and subsequent risk for breast cancer

    Microsoft Academic Search

    L J Vatten; P R Romundstad; D Trichopoulos; R Skjærven

    2002-01-01

    Women who experience pre-eclampsia or hypertension during pregnancy may have a reduced risk for breast cancer later in life. The evidence is based on case–control studies, and here we report the results of a cohort study exploring the link between pre-eclampsia and gestational hypertension diagnosed in the first pregnancy and subsequent risk for breast cancer. We combined information from the

  20. AT1-receptor autoantibodies and uteroplacental RAS in pregnancy and pre-eclampsia

    Microsoft Academic Search

    Florian Herse; Lydia Hering; Dominik N. Müller; Friedrich C. Luft; Ralf Dechend

    2008-01-01

    Pre-eclampsia is a common, pregnancy-induced disorder, consisting of hypertension and proteinuria. The condition is one of\\u000a the leading causes for maternal and perinatal morbidity and mortality. Nonetheless, the underlying molecular mechanisms remain\\u000a unclear. Immunological mechanisms and the renin–angiotensin system have been implicated in the development of pre-eclampsia.\\u000a Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) have been identified

  1. Inspiratory flow limitation during sleep in pre-eclampsia: comparison with normal pregnant and nonpregnant women

    Microsoft Academic Search

    G. Connolly; A. R. A. Razak; A. Hayanga; A. Russell; P. McKenna; W. T. McNicholas

    2001-01-01

    Inspiratory flow limitation during sleep in pre-eclampsia: comparison with normal pregnant and nonpregnant women. G. Connolly, A.R.A. Razak, A. Hayanga, A. Russell, P. McKenna, W.T. McNicholas. #ERS Journals Ltd 2001. ABSTRACT: Self-reported snoring is common in pregnancy, particularly in females with pre-eclampsia. The prevalence of inspiratory flow limitation during sleep in pre- eclamptic females was objectively assessed and compared with

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

    PubMed Central

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

    2012-01-01

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

  3. 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.

  4. An evaluation of serum magnesium status in pre-eclampsia compared to the normal pregnancy.

    PubMed

    Jafrin, W; Mia, A R; Chakraborty, P K; Hoque, M R; Paul, U K; Shaha, K R; Akhter, S; Roy, A S

    2014-10-01

    Pre-eclampsia is a disease which causes significant maternal and fetal morbidity and mortality, especially in the developing countries. Despite numerous studies, the etiology of pre-eclampsia has not yet been fully elucidated. Although several evidences indicate that various elements such as serum Magnesium, Calcium etc. might play an important role in pre-eclampsia. The present study prospectively determines and evaluate whether maternal serum levels of magnesium has any association with pre-eclampsia or not. It was a cross sectional study carried out in the Department of Biochemistry, Mymensingh Medical College from July 2009 to June 2010. A total of 108 subjects were selected with the duration of pregnancy from 28th week of gestation to term of which 42 were normal pregnant women (as control) and 66 were pre-eclamptic (34 with mild and 32 with severe preeclampsia) admitted in the Obstetrics and Gynaecology department of Mymensingh medical college hospital. Serum Magnesium level was determined in the laboratory by colorimetric method using recommended commercial kit. Student's unpaired t-test was used to see the statistical significance of the difference between the mean values of the estimated parameters. The mean serum levels of Magnesium in normal pregnant group was 1.91±0.08mg/dl, mild pre-eclamptic group was 1.8±0.11mg/dl,and in severe pre-eclamptic group was 1.75±0.10mg/dl. The mean serum Magnesium of women with mild pre-eclampsia as well as severe pre-eclampsia was significantly (p<0.001) decreased in comparison to that of the control. A significant (p<0.05) decrease in serum magnesium was also found in subject with severe pre-eclamptic compared to that of the mild pre-eclamptic. So, these results indicate that reduction in serum levels of magnesium during pregnancy might be a possible contributor in the etiology of pre-eclampsia and supplementation of this element as diet or drugs may be of value to prevent pre-eclampsia. PMID:25481580

  5. Trophoblast Deportation in Human Pregnancy—its Relevance for Pre-eclampsia

    Microsoft Academic Search

    M Johansen; C. W. G Redman; T Wilkins; I. L Sargent

    1999-01-01

    The maternal syndrome of pre-eclampsia is thought to result from endothelial cell damage caused by a circulating factor derived from the placenta. This study investigates the hypothesis that trophoblast deportation may be part of the process by which this factor enters the maternal circulation. The nature and incidence of trophoblast deportation was studied in uterine vein and peripheral blood taken

  6. Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast

    Microsoft Academic Search

    Raymond W Redline; Patricia Patterson

    1995-01-01

    Pre-eclampsia\\/toxemia (PET) is an idiopathic hypertensive disorder of pregnancy elicited in susceptible mothers by exposure to placental trophoblast. Three facts regarding the placenta in PET are known: an association with large placentas (excessive trophoblast), a tendency for superficial implantation, and inappropriate trophoblastic immaturity, as assessed by ultrastructural and biochemical criteria. A unitary hypothesis is that PET is related to a

  7. Telomere aggregate formation in placenta specimens of pregnancies complicated with pre-eclampsia

    Microsoft Academic Search

    Rivka Sukenik-Halevy; Moshe Fejgin; Devora Kidron; Lilach Goldberg-Bittman; Reuven Sharony; Tal Biron-Shental; Yona Kitay-Cohen; Aliza Amiel

    2009-01-01

    Telomeres are specific repetitive DNA sequences that cap and stabilize the ends of chromosomes. Functional telomeres are essential for the normal segregation and maintenance of chromosomes during mitotic and meiotic division. Pre-eclampsia, a pregnancy-specific syndrome of increased blood pressure accompanied by proteinuria, is often associated with growth deficiency in the fetus. Oxidative stress is a major component in the pathophysiology

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

    PubMed

    Ahmed, Asif; Ramma, Wenda

    2015-03-01

    Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the 'two-stage model' of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the 'accelerator'. The 'braking system' includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-?-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. PMID:25303561

  9. The effect of leisure time physical activity on the risk of pre-eclampsia and gestational hypertension

    Microsoft Academic Search

    S Marcoux; J Brisson; J Fabia

    1989-01-01

    STUDY OBJECTIVE: To assess the relation between leisure time physical activity (LTPA) during the first 20 weeks of pregnancy and the risk of developing pre-eclampsia and gestational hypertension. DESIGN: Case-control study carried out over a 28 month period with retrospective data collection. SETTING: Six hospitals in Quebec City and four hospitals in Montreal. PARTICIPANTS: 172 women with pre-eclampsia, 254 with

  10. Maternal and perinatal outcome of temporizing management in 254 consecutive patients with severe pre-eclampsia remote from term

    Microsoft Academic Search

    Willy Visser; Henk C. S. Wallenburg

    1995-01-01

    Objective: To assess maternal and perinatal outcomes of expectant management with plasma volume expansion and pharmacologic vasodilatation in patients with severe pre-eclampsia remote from term. Study design\\/it: All women with severe pre-eclampsia between 20 and 32 weeks' gestation, not in labor and with a live, single fetus admitted to the University Hospital Rotterdam from 1985 to 1993 were managed with

  11. Elevated C-reactive protein and pro-inflammatory cytokines in Andean women with pre-eclampsia

    Microsoft Academic Search

    E. Teran; C. Escudero; W. Moya; M. Flores; P. Vallance; P. Lopez-Jaramillo

    2001-01-01

    Objective: To investigate the concentration of markers of inflammation in non-pregnant women, women with normal pregnancy and women with pre-eclampsia. Methods: Pregnant women (n=26), women with pre-eclampsia (n=25) and non-pregnant normotensive women (n=21) were included in the study. C-reactive protein was measured by latex-enhanced immunoturbidimetric assay, serum tumor necrosis factor-alpha (TNF-?) and interleukin-6 (IL-6) by high sensitivity ELISA. Kruskal–Wallis non-parametric

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

    Microsoft Academic Search

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

    2008-01-01

    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

  13. 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

  14. Trophoblast calcyclin is elevated in placental tissue from patients with early pre-eclampsia.

    PubMed

    Schol, P B B; Güzel, C; Steegers, E A P; de Krijger, R R; Luider, T M

    2014-01-01

    The aetiology of pre-eclampsia is thought to originate from aberrant spiral artery remodelling and invasion evoking cellular oxidative stress. Previously, we discovered differentially expressed proteins in trophoblast cells of pre-eclamptic pregnancies. One of these proteins is calcyclin (S100A6); a Ca(2+)-binding protein associated with cellular stress response. By immunohistochemistry on formalin-fixed paraffin-embedded placental tissue, calcyclin expression was compared between women with early pre-eclampsia (n=72) and non-hypertensive control patients (n=66) (?(2), p=0.006) blindly by two observers. Significantly more intense staining was seen in trophoblast cells of pre-eclamptic pregnancies compared to control placentas suggesting that trophoblast calcyclin is elevated in early pregnancy. PMID:26104246

  15. Emerging technologies for the identification of therapeutic targets for the management of pre-eclampsia.

    PubMed

    Pritlove, D C; Tan, B K; de Wit, N C J; Vatish, M

    2004-12-01

    Pre-eclampsia is a common and serious complication of pregnancy characterised by hypertension and proteinuria. Genetic and environmental factors influence the occurrence and progression of the disease. Emerging experimental systems and increasingly specific analytical methods for the study of differences between normal and pre-eclamptic placentae are close to identifying specific indicators of disease, which may allow early diagnosis and intervention and reveal targets against which therapeutic agents can be developed. PMID:15584857

  16. Pregnancies complicated by retained placenta: Sex ratio and relation to pre-eclampsia

    Microsoft Academic Search

    T. Y. Khong; A. Staples; A. S. L. Chan; R. J. Keane; C. S. Wilkinson

    1998-01-01

    Pre-eclampsia and placenta accreta have opposite histological features of placentation. This study set out to test the hypotheses that the sex ratios in these two pregnancy complications are opposite and that these conditions are mutually exclusive. A population-based database covering all deliveries in South Australia between 1986 and 1995 and the hospital-based obstetric database of the Adelaide Women's and Children's

  17. Platelet sodium\\/hydrogen ion exchange in normal pregnancy and non-proteinuric pre-eclampsia

    Microsoft Academic Search

    D Graham; JCP Kingdom; J McDonald; DL Davies; CJ Kenyon

    1997-01-01

    In non-pregnant individuals, abnormalities in cation transport in vascular tissues have been linked to essential hypertension. In the present study, we consider whether Na+\\/H+ exchange (NHE) is affected in non-proteinuric pre-eclampsia (NPP). Platelet NHE characteristics and plasma cholesterol were measured in a cross-sectional study of normal primigravidae at 14 ± 0.5 (n = 9), 29 ± 0.7 (n = 7),

  18. Urinary excretion of 6-keto prostaglandin F 1? in pre-eclampsia

    Microsoft Academic Search

    M. Yamaguchi; N. Mori

    1988-01-01

    In order to investigate whether urinary excretion of prostaglandins (PG) is involved in the pathophysiology of pre-eclampsia, urinary immunoreactive 6-keto PGF1a and TXB2 were measured in normal and preeclamptic women by radio-immunoassay after extraction with Bond Elut column. Urinary levels of 6-keto PGF1a and TXB2 were expressed as ratio of urinary concentration of prostaglandin vs. creatinine (pg prostaglandin\\/mg creatinine; pg\\/mg

  19. Analytical approaches to detect maternal\\/fetal genotype incompatibilities that increase risk of pre-eclampsia

    Microsoft Academic Search

    Neeta Parimi; Gerard Tromp; Helena Kuivaniemi; Jyh Kae Nien; Ricardo Gomez; Roberto Romero; Katrina AB Goddard

    2008-01-01

    BACKGROUND: In utero interactions between incompatible maternal and fetal genotypes are a potential mechanism for the onset or progression of pregnancy related diseases such as pre-eclampsia (PE). However, the optimal analytical approach and study design for evaluating incompatible maternal\\/offspring genotype combinations is unclear. METHODS: Using simulation, we estimated the type I error and power of incompatible maternal\\/offspring genotype models for

  20. Adrenomedullin and atrial natriuretic peptide concentrations in normal pregnancy and pre-eclampsia

    Microsoft Academic Search

    Takashi Minegishi; Manabu Nakamura; Kazuko Abe; Mari Tano; Akihiko Andoh; Mitsunori Yoshida; Tsuyoshi Takagi; Toshio Nishikimi; Masayasu Kojima; Kenji Kangawa

    1999-01-01

    3To whom correspondence should be addressed Adrenomedullin (AM) is a peptide that elicits a long-lasting vasorelaxant activity, while atrial natriuretic peptide (ANP) has also been shown to be a potent vasodilatory agent. To clarify the possible role of AM and ANP in the physiology of pregnancy and pathophysiology of pre-eclampsia, we measured plasma concentrations of these peptides in non-pregnant women,

  1. Pathophysiology of pre-eclampsia: Update on the role of nitric oxide

    Microsoft Academic Search

    Maki Kashiwagi; Roland Zimmermann; Ernst Beinder

    2003-01-01

    Women with chronic hypertension and pregnancy-induced hypertension are at substantial risk for developing preeclampsia\\/ eclampsia,\\u000a a disease with high fetomaternal morbidity and mortality. However, the etiology of this disease is still unknown. In this\\u000a article, recent concepts on the pathophysiology of pre-eclampsia, with special attention to the role of nitric oxide, are\\u000a reviewed.

  2. Magnesium Sulphate Therapy in Women with Pre-Eclampsia and Eclampsia in Kuwait

    Microsoft Academic Search

    A. E. Omu; J. Al-Harmi; H. L. Vedi; L. Mlechkova; A. F. Sayed; N. S. Al-Ragum

    2008-01-01

    Objective: To evaluate the outcome of the use of MgSO4 therapy in women with severe pre-eclampsia in Kuwait from January 2002 to December 2004. Subjects and Methods: The study involved 450 women managed at the Maternity Hospital in Kuwait with a blood pressure of 160\\/110 mm Hg and proteinuria of >0.3–5 g\\/24 h. A loading dose of 4 g MgSO4

  3. 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

  4. Predictive value of plasma haematocrit level in early diagnosis of pre-eclampsia.

    PubMed

    Golboni, F; Heydarpour, S; Taghizadeh, Z; Kazemnezhad, A

    2011-10-01

    While pre-eclampsia is the most common complication of pregnancy, a definitive screening test for early diagnosis is still elusive. In this study, haematocrit value was assessed as a screening test for pre-eclampsia in 660 women at 24-28 weeks of pregnancy attending a hospital in Tehran, Islamic Republic of Iran. Mean haematocrit values were significantly higher in pre-eclamptic than non-pre-eclamptic women: 37.7% (SD 2.0%) and 35.9% (SD 1.7%) respectively. The receiver operating characteristics curve showed that the most appropriate cut-off point for the haematocrit test in this sample of women was 38%; at this value the sensitivity was 58.6% and specificity was 88.9%; positive and negative predictive values were 33.7% and 95.7% respectively. The haematocrit, done as a routine screening test for anaemia at 24-28 weeks of pregnancy, may also be useful as a screening test for early diagnosis of pre-eclampsia. PMID:22256407

  5. 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

  6. Poor periodontal health as a risk factor for development of pre-eclampsia in pregnant women

    PubMed Central

    Varshney, Shailesh; Gautam, Akansha

    2014-01-01

    Aims: Periodontal disease has been considered a systemic exposure implicated in a higher risk of adverse pregnancy outcomes. The aim of the present study was to determine whether maternal oral health is associated with an increased risk of pre-eclampsia. Subjects and Methods: A case-control study was conducted which included 40 pregnant women patients admitted to the Department of Obstetrics and Gynecology, J.N. Medical College, A.M.U, Aligarh. Pre-eclampsia was defined as classic triad of hypertension, proteinuria and symptoms such as swelling/edema esp. in hands and face, headache, visual changes etc., A periodontal examination was done during 48 h after child delivery. Maternal oral status was evaluated using gingival index by Loe and Silness, oral hygiene index (simplified) by greene and vermillion and periodontal pockets and clinical attachment level (CAL). Statistical Analysis: Null hypothesis that no difference exist between the two groups (pre-eclamptic and non-pre-eclamptic Group) was calculated using paired t-test, Chi-square and Mann-Whitney U statistical tests using SPSS 11.5 (Statistical Package for Social sciences, Chicago). P < 0.05 was considered to be statistically significant. Results: The amount of gingival inflammation, oral hygiene levels, pocket depth and CALs as measured by their respective indices were higher in the pre-eclamptic group when compared to non-pre-eclamptic group. Furthermore CAL was significantly increased in the test group. This study showed that pre-eclamptic cases were more likely to develop periodontal disease (P < 0.05). 30% of the test group and 65% of the case group had periodontal disease (P < 0.05) which had shown that pre-eclamptic cases were 4.33 times more likely to have periodontal disease (odds ratio = 4.33). Conclusions: Maternal oral status was determined to be associated with an increased risk of pre-eclampsia. PMID:25024545

  7. Human cytotrophoblast differentiation/invasion is abnormal in pre-eclampsia.

    PubMed Central

    Lim, K. H.; Zhou, Y.; Janatpour, M.; McMaster, M.; Bass, K.; Chun, S. H.; Fisher, S. J.

    1997-01-01

    During human placental development, cytotrophoblast stem cells differentiate and invade the uterus. Simultaneously, the cells modulate their expression of several classes of stage-specific antigens that mark transitions in the differentiation process and play a role in either uterine invasion (integrin cell-extracellular matrix receptors and matrix metalloproteinase-9) or immune interactions (HLA-G). The pregnancy disease pre-eclampsia is associated with shallow cytotrophoblast invasion. Previously we showed, by immunofluorescence localization on placental tissue, that in pre-eclampsia invasive cytotrophoblasts fail to properly modulate their integrin repertoire. This finding suggests possible abnormalities in the differentiation pathway that leads to uterine invasion. Here we used a culture system that supports this differentiation process to compare the differentiative and invasive potential of cytotrophoblasts obtained from control (n = 8, 22 to 38 weeks) and pre-eclamptic (n = 9, 24 to 38 weeks) placentas. In culture, the cells from pre-eclamptic placentas failed to properly modulate alpha1 integrin and matrix metalloproteinase-9 expression at the protein and mRNA levels. Their invasive potential was also greatly reduced. Likewise, the cells failed to up-regulate HLA-G protein and mRNA expression. These results suggest that defective cytotrophoblast differentiation/invasion can have significant consequences to the outcome of human pregnancy (ie, development of pre-eclampsia) and that, by the time delivery becomes necessary, the defect is not reversed by removing the cells from the maternal environment. Images Figure 1 Figure 2 Figure 5 Figure 6 Figure 9 PMID:9403732

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

    PubMed Central

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

    2014-01-01

    Background Epidemiological data link low dietary calcium with pre-eclampsia. Current recommendations are for 1.5–2 g/day calcium supplementation for low-intake pregnant women, based on randomised controlled trials of ?1 g/day calcium supplementation from 20 weeks of gestation. This is problematic logistically in low-resource settings; excessive calcium may be harmful; and 20 weeks 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, <1 g/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] 0.28–0.52), as well as for subgroups: LDC alone (four trials, 980 women, RR 0.36; 95% CI 0.23–0.57]); LDC plus linoleic acid (two trials, 134 women, RR 0.23; 95% CI 0.09–0.60); LDC plus vitamin D (two trials, 1060 women, RR 0.49; 0.31–0.78) and a trend for LDC plus antioxidants (one trial, 60 women, RR 0.24; 95% CI 0.06–1.01). Overall results were consistent with the single quality trial of LDC alone (171 women, RR 0.30; 95% CI 0.06–1.38). LDC plus antioxidants commencing at 8–12 weeks tended to reduce miscarriage (one trial, 60 women, RR 0.06; 95% CI 0.00–1.04). 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. Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler at 11-14 weeks of gestation

    Microsoft Academic Search

    A. M. Martin; R. Bindra; P. Curcio; S. Cicero; K. H. Nicolaides

    2001-01-01

    Objective To examine the value of uterine artery Doppler at 11-14 weeks of gestation in the identification of women at risk of developing pre-eclampsia and fetal growth restriction. Methods Uterine artery Doppler was carried out at 11- 14 weeks in 3324 consecutive singleton pregnancies attend- ing for routine care in three London hospitals. The right and left uterine arteries were

  10. A genome-wide scan reveals a maternal susceptibility locus for pre-eclampsia on chromosome 2p13

    Microsoft Academic Search

    R. Arngrimsson; Sigrún Sigur; Michael L. Frigge; I. Bjarnadóttir; Thorlákur Jónsson; Hreinn Stefánsson; Ásdís Baldursdóttir; Anna S. Einarsdóttir; Birgir Palsson; Steinunn Snorradóttir; A. M. A. Lachmeijer; Augustine Kong; Birkir Thor Bragason; Jeffrey R. Gulcher; Reynir Tómas Geirsson; Kári Stefánsson

    1999-01-01

    Pre-eclampsia is a common and serious disease and a major cause of maternal and infant mortality. Antenatal care systems world-wide screen for signs of the disease such as hypertension and proteinuria. Unlike most other human disorders it impacts two individuals, the mother and the child, both of whom can be severely affected. The pathophysiology of the disorder is incom- pletely

  11. Severe pre-eclampsia and eclampsia: a broad overview with discussion of the nursing care required for the eclamptic patient

    Microsoft Academic Search

    D. Burnett

    1997-01-01

    Severe pre-eclampsia and eclampsia are conditions which are rarely seen in A & E departments today. Although the percentage of patients suffering from these conditions in extremely small, the author has been involved in the care and treatment of two patients with this severe complication of pregnancy.A lack of clear guidelines on this subject was the motivation which prompted further

  12. Factors associated with persistent hypertension after puerperium among women with pre-eclampsia/eclampsia in Mulago hospital, Uganda

    PubMed Central

    2010-01-01

    Background Women with severe pre-eclampsia/eclampsia are at risk of developing chronic hypertension in future. Chronic hypertension may manifest initially as persistent hypertension at the end of the puerperium. The objective was to determine the incidence and maternal biochemical, hematological and socio-demographic risk factors for persistent hypertension in patients with pre-eclampsia/eclampsia. Methods This was a prospective cohort study conducted from November 2008 to May 2009 at Mulago hospital labor ward and postnatal clinic. Participants were 200 women managed for pre-eclampsia/eclampsia and followed up to the end of the puerperium. Data was collected through using pre-coded interviewer-administered questionnaires, checking medical records and laboratory investigations. STATA (release 9) software was used for data analysis. At bivariate analysis, the relative risk of persistent hypertension was estimated at the 95% confidence level. Using multivariate logistic regression analysis, factors that were independently associated with persistent hypertension were evaluated. Results Fifty four (27.7%) out of the total 195 women had persistent hypertension after puerperium. Serum creatinine and the age of the patient were the only factors associated with persistence of hypertension after puerperium. Conclusion Nearly every one in four mothers with pre-eclampsia/eclampsia are at risk of persistent hypertension after the puerperium. Serum creatinine, serum uric acid and participants' age were the only factors independently associated with persistence of hypertension after the puerperium. PMID:20222993

  13. Uteroplacental blood flow in pre-eclampsia measurements with /sup 113 m/In and a computer-linked gamma camera

    SciTech Connect

    Lunell, N.O.; Nylund, L.E.; Lewander, R.; Sarby, B.

    1982-01-01

    Uteroplacental blood flow was measured with a computer-linked gamma camera after intravenous injection of 1 mCi /sup 113/In. Results of the measurements from 32 pre-eclamptic pregnancies and 37 normal controls are compared. The uteroplacental blood flow was measured as an index calculated from the rise time and maximum activity of the isotope accumulation curve. The uteroplacental blood flow was reduced with 50% in pre-eclampsia. In severe pre-eclampsia it was more compromised than in mild pre-eclampsia. A diminished uteroplacental blood flow was found in pre-eclampsia even in the absence of intrauterine growth retardation. The maternal placental circulation in the supine position was reduced with one third compared to that in the left lateral recumbent position.

  14. Increased Superoxide Generation is Associated with Decreased Superoxide Dismutase Activity and mRNA Expression in Placental Trophoblast Cells in Pre-eclampsia

    Microsoft Academic Search

    Y Wang; S. W Walsh

    2001-01-01

    Pre-eclampsia is a multi-system disorder unique to human pregnancy. Although the aetiology of pre-eclampsia is still unknown, increased placental oxidative stress contributes to the pathophysiology of this pregnancy disorder. The goal of this study was to determine if placental trophoblast cells generate superoxide, and if there was a difference in superoxide generation and superoxide dismutase (SOD) activity between trophoblast cells

  15. Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

    Microsoft Academic Search

    Jane Weiler; Stephen Tong; Kirsten R. Palmer

    2011-01-01

    BackgroundBoth pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not

  16. Microarray analysis of differentially expressed genes in placental tissue of pre-eclampsia: up-regulation of obesity-related genes

    Microsoft Academic Search

    T. Reimer; D. Koczan; B. Gerber; D. Richter; H. J. Thiesen; K. Friese

    2002-01-01

    Susceptibility genes present in both mother and fetus most likely contribute to the risk of pre-eclampsia. Placental biopsies were therefore investigated by high-density DNA microarray analysis to determine genes differentially regulated within chorionic villous tissue in pre-eclampsia and normal pregnancy. The pooled RNAs of pre-eclamptic and normotensive subjects were hybridized to the HuGeneFL array representing sequences from ~5600 full-length human

  17. [Characterization of the epithelial sodium channel in human pre-eclampsia syncytiotrophoblast].

    PubMed

    del Monaco, Silvana; Assef, Yanina; Damiano, Alicia; Zotta, Elsa; Ibarra, Cristina; Kotsias, Basilio A

    2006-01-01

    The syncytiotrophoblast (SCT), a multinucleated epithelium forming the outer layer of chorionic villi, acts in human placenta as a transporting barrier regulating the transference of nutrients, solutes and water between maternal and fetal blood. Electrolyte homeostasis and extracellular fluid volume are maintained primarily by regulated Na+ transport. The present study was conducted to analyze the presence of the epithelial Na channel (ENaC) in placental tissue from normal and pre-eclamptic women and in BeWo cell, a model of a human SCT. Changes in the expression of these proteins during sodium transport across the placenta may be related to the pathogeny of pre-eclampsia. The role that ENaC and Na+ transport deregulation play on human placental tissues still remains unknown although in aldosterone-responsive epithelial cells (kidney, colon), abnormalities upregulating its activity lead to increased Na+ uptake and hypertension (i.e. Liddle's syndrome) whereas a diminished channel activity can result in the pseudohypoaldosteronisn syndrome with salt loss and hypotension. Our results show that ENaC is expressed in the apical membrane of normal syncytiotrophoblast. The amplified fragment of alpha-ENaC was cloned and sequenced having a 100% identity with the sequence of (alpha-ENaC obtained from GenBank (SCNN1A, accession number Z92981). We found that the transcription of the alpha-ENaC mRNA was not detectable in preeclamptic placentas and the protein was not observed with immunohistochemistry staining, probably indicating a low protein expression level. In BeWo cells ENac was found and its expression is regulated by aldosterone, vasopressin, progesterone and estradiol. With patch clamp techniques we studied the currents trough ENaO channels in Bewo cells. We observed currents that were blocked by 10 microM amiloride in cells incubated in 100 nM aldosterone for 12 hs. The amplitude of this current was 20-fold the basal current, a reversal potential of 3 mV and a conductance of 127 +/- 26 pS/pF with pulses between -60 and -140 mV. These characteristics are similar to those reported in ENaC channels in several tissues. Although their roles in placenta are still poorly understood, the differences in the expression of ENaC in pre-eclamptic placentas may have consequences for ion transport and these data could lead to future studies concerning the mechanism involved in the pathophysiology of pre-eclampsia. PMID:16555725

  18. Differential Levels of Interleukin 6 in Maternal and Cord Sera and Placenta in Women with Pre-Eclampsia

    Microsoft Academic Search

    Saed Al-Othman; Alexander E. Omu; F. M. E. Diejomaoh; Magda Al-Yatama; Fawzia Al-Qattan

    2001-01-01

    Background: Interleukin 6 (IL-6) is a T helper 2 cytokine with a variety of properties including pro-inflammatory characteristics. It has, therefore, been implicated in the pathophysiology of abnormal pregnancies. Objective: To investigate the association between IL-6 and pre-eclampsia by estimating the differential levels of IL-6 in maternal and cord serum and supernatant of homogenized placental tissue. Methods: 50 primigravidae with

  19. Developmental regulation of circulating insulin-like growth factor-binding proteins in normal pregnancies and in pre-eclampsia

    Microsoft Academic Search

    Moira S. Lewitt; Fergus P. Scott; Nicole M. Clarke; Robert C. Baxter

    1995-01-01

    The insulin-like growth factors (IGFs) and their binding properties (IGFBPs) are believed to play important roles in the growth and development of the human fetus. They have been implicated in the pathophysiology of pre-eclampsia. In this study we have characterized the developmental regulation, in normal and pre-eclamptic pregnancies, of IGFs and IGFBPs in maternal serum, neonatal serum and amniotic fluid.

  20. Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis

    Microsoft Academic Search

    Jeltsje S Cnossen; Karlijn C Vollebregt; Nynke de Vrieze; Gerben ter Riet; Ben W J Mol; Arie Franx; Khalid S Khan; Joris A M van der Post

    2008-01-01

    Objective To determine the accuracy of using systolic and diastolic blood pressure, mean arterial pressure, and increase of blood pressure to predict pre-eclampsia.Design Systematic review with meta-analysis of data on test accuracy.Data sources Medline, Embase, Cochrane Library, Medion, checking reference lists of included articles and reviews, contact with authors.Review methods Without language restrictions, two reviewers independently selected the articles in

  1. Intravenous nicardipine for severe hypertension in pre-eclampsia – effects of an acute treatment on mother and foetus

    Microsoft Academic Search

    A. G. M. Aya; R. Mangin; M. Hoffet; J.-J. Eledjam

    1999-01-01

    Objectives: To assess the efficacy in lowering blood pressure, and the safety for mother and foetus of an acute nicardipine therapy\\u000a in severe pre-eclampsia.¶Design: Prospective clinical study.¶Setting: One university hospital obstetric unit.¶Patients: Twenty consecutive adult pre-eclamptic patients with severe hypertension.¶Intervention: Nicardipine, 1 ?g\\/kg per min, was given intravenously to lower the mean arterial pressure (MAP) by at least 15 %.

  2. Evolutionary adaptations to pre-eclampsia/eclampsia in humans: low fecundability rate, loss of oestrus, prohibitions of incest and systematic polyandry.

    PubMed

    Robillard, Pierre-Yves; Dekker, Gustaaf A; Hulsey, Thomas C

    2002-02-01

    Gestational-hypertension/pre-eclampsia occurs in approximately 10% of human pregnancies. This persistent complication of pregnancy has been reported to occur more frequently in couples conceiving very shortly after the beginning of their sexual relationship and/or after a change in paternity. Primipaternity may be the leading cause of pre-eclampsia in women under 30 years of age when genetic susceptibility to cardio-vascular disease has not yet been expressed, especially in women before their twenties, who for the last 40,000 years have perhaps comprised the age group when the majority of parturients classified as Homo sapiens sapiens initiated their reproductive life. In terms of evolution, the prevalence of pre-eclampsia represents a distinct reproductive disadvantage in humans as compared with other mammals. Indeed, pre-eclampsia is a consequence of the defect of the normal human-specific deep endovascular invasion of the trophoblast. The large size of the human fetal brain imposing this deep trophoblastic invasion induced the need for major immunogenetic compromises in terms of paternal-maternal tissue tolerance. The price that mankind has had to pay to adapt to the pre-eclampsia risk is a low fecundability rate and therefore loss of oestrus, possibly a step in the deviation between apes and hominids. Further, pre-eclampsia risk may be a contributing factor leading to the rejection of systematic polyandry in human societies and have influenced prohibition of incest. PMID:11900595

  3. Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study

    PubMed Central

    2009-01-01

    Objective To determine if pre-eclampsia is associated with reduced thyroid function during and after pregnancy. Design Nested case-control study during pregnancy and population based follow-up study after pregnancy. Setting Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous women in the United States during 1992-5, and a Norwegian population based study (Nord-Trondelag Health Study or HUNT-2) during 1995-7 with linkage to the medical birth registry of Norway. Participants All 141 women (cases) in the Calcium for Pre-eclampsia Prevention trial with serum measurements before 21 weeks’ gestation (baseline) and after onset of pre-eclampsia (before delivery), 141 normotensive controls with serum measurements at similar gestational ages, and 7121 women in the Nord-Trondelag Health Study whose first birth had occurred in 1967 or later and in whom serum levels of thyroid stimulating hormone had been subsequently measured. Main outcome measures Thyroid function tests and human chorionic gonadotrophin and soluble fms-like tyrosine kinase 1 concentrations in the Calcium for Pre-eclampsia Prevention cohort and odds ratios for levels of thyroid stimulating hormone above the reference range, according to pre-eclampsia status in singleton pregnancies before the Nord-Trondelag Health Study. Results In predelivery specimens of the Calcium for Pre-eclampsia Prevention cohort after the onset of pre-eclampsia, thyroid stimulating hormone levels increased 2.42 times above baseline compared with a 1.48 times increase in controls. The ratio of the predelivery to baseline ratio of cases to that of the controls was 1.64 (95% confidence interval 1.29 to 2.08). Free triiodothyronine decreased more in the women with pre-eclampsia than in the controls (case ratio to control ratio 0.96, 95% confidence interval 0.92 to 0.99). The predelivery specimens but not baseline samples from women with pre-eclampsia were significantly more likely than those from controls to have concentrations of thyroid stimulating hormone above the reference range (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4). Both in women who developed pre-eclampsia and in normotensive controls the increase in thyroid stimulating hormone concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1 (P for trend 0.002 and <0.001, respectively). In the Nord-Trondelag Health Study, women with a history of pre-eclampsia in their first pregnancy were more likely than other women (adjusted odds ratio 1.7, 95% confidence interval 1.1 to 2.5) to have concentrations of thyroid stimulating hormone above the reference range (>3.5 mIU/l). In particular, they were more likely to have high concentrations of thyroid stimulating hormone without thyroid peroxidase antibodies (adjusted odds ratio 2.6, 95% confidence interval 1.3 to 5.0), suggesting hypothyroid function in the absence of an autoimmune process. This association was especially strong (5.8, 1.3 to 25.5) if pre-eclampsia had occurred in both the first and the second pregnancies. Conclusion Increased serum concentration of soluble fms-like tyrosine kinase 1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy. Pre-eclampsia may also predispose to reduced thyroid function in later years. PMID:19920004

  4. Pre-eclampsia has an adverse impact on maternal and fetal health.

    PubMed

    Lin, Saunders; Leonard, Dean; Co, Mary A M; Mukhopadhyay, Dhriti; Giri, Badri; Perger, Lena; Beeram, Madhava R; Kuehl, Thomas J; Uddin, Mohammad N

    2015-04-01

    Pre-eclampsia (preE) is a multifaceted complication found uniquely in the pregnant patient and one that has puzzled scientists for years. PreE is not a single disorder, but a complex syndrome that is produced by various pathophysiological triggers and mechanisms affecting about 5% of obstetrical patients. PreE is a major cause of premature delivery and maternal and fetal morbidity and mortality. PreE is characterized by de novo development of hypertension and proteinuria after 20 weeks of gestation and affects nearly every organ system, with the most severe consequences being eclampsia, pulmonary edema, intrauterine growth restriction, and thrombocytopenia. PreE alters the intrauterine environment by modulating the pattern of hormonal signals and activating the detrimental cellular signaling that has been transported to the fetus. The fetus has to adapt to this intrauterine environment with detrimental signals. The adaptive changes increase the risk of disease later in life. This review defines the predisposition and causes of preE and the cellular signaling detrimental to maternal health during preE. Moreover, the risk factors for diseases that are transmitted to the offspring have been addressed in this review. The detrimental signaling molecules that have been overexpressed in preE patients raises the possibility that those signals could be therapeutically blocked one day. PMID:25468481

  5. Relationship between Periodontitis and Pre-Eclampsia: A Meta-Analysis

    PubMed Central

    Sgolastra, Fabrizio; Petrucci, Ambra; Severino, Marco; Gatto, Roberto; Monaco, Annalisa

    2013-01-01

    Background Studies have suggested controversial results regarding a possible association between pre-eclampsia (PE) and periodontal disease (PD) and no meta-analysis has been performed to clarify this issue. Methods A literature search of electronic databases was performed for articles published through March 24, 2013, followed by a manual search of several dental and medical journals. The meta-analysis was conducted according to the recommendations of the Cochrane Collaboration and PRISMA. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed with the ?2-based Cochran Q test and I2 statistic. The level of significance was set at P<0.05. Results Fifteen studies were included, including three cohort and 12 case-control studies. A positive association was found between PE and PD (OR 2.17, 95% CI 1.38–3.41, P?=?0.0008). However, a high and significant heterogeneity was found (?2?=?62.42, P<0.00001, I2?=?75%). In most cases, subgroup analysis had low power to detect significant differences between PE and non-PE groups. Conclusion Based on the findings of the meta-analysis, PD appears to be a possible risk factor for PE. However, given the important differences in the definitions and diagnoses of PD and PE among the studies, as well as their lack of good methodological quality, future trials are needed to confirm the results of the present meta-analysis. PMID:23990948

  6. Short-term couplings of the cardiovascular system in pregnant women suffering from pre-eclampsia.

    PubMed

    Riedl, Maik; Suhrbier, Alexander; Stepan, Holger; Kurths, Jürgen; Wessel, Niels

    2010-05-13

    Pre-eclampsia (PE), a serious pregnancy-specific disorder, causes significant neonatal and maternal morbidity and mortality. Recent studies showed that cardiovascular variability parameters as well as the baroreflex sensitivity remarkably improve its early diagnosis. For a better understanding of the dynamical changes caused by PE, in this study the coupling between respiration, systolic and diastolic blood pressure, and heart rate is investigated. Thirteen datasets of healthy pregnant women and 10 of subjects suffering from PE are included. Nonlinear additive autoregressive models with external input are used for a model-based coupling analysis following the idea of Granger causality. To overcome the problem of misdetections of standard methods in systems with a dominant driver, a heuristic ensemble approach is used here. A coupling is assumed to be real when existent in more than 80 per cent of the ensemble members, and otherwise denoted as artefacts. As the main result, we found that the coupling structure between heart rate, systolic blood pressure, diastolic blood pressure and respiration for healthy subjects and PE patients is the same and reliable. As a pathological mechanism, however, a significant increased respiratory influence on the diastolic blood pressure could be found for PE patients (p=0.003). Moreover, the nonlinear form of the respiratory influence on the heart rate is significantly different between the two groups (p=0.002). Interestingly, the influence of systolic blood pressure on the heart rate is not selected, which indicates that the baroreflex sensitivity estimation strongly demands the consideration of causal relationships between heart rate, blood pressure and respiration. Finally, our results point to a potential role of respiration for understanding the pathogenesis of PE. PMID:20368244

  7. 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

  8. Prevention and management of severe pre-eclampsia/eclampsia in Afghanistan

    PubMed Central

    2013-01-01

    Background An evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care (EmONC) in Afghanistan have the capacity to manage severe PE/E cases. Methods A further analysis was conducted of the 2009–10 Afghanistan EmONC Needs Assessment. Assessors observed equipment and supplies available, and services provided at 78 of the 127 facilities offering comprehensive EmONC services and interviewed 224 providers. The providers also completed a written case scenario on severe PE/E. Descriptive statistics were used to summarize facility and provider characteristics. Student t-test, one-way ANOVA, and chi-square tests were performed to determine whether there were significant differences between facility types, doctors and midwives, and trained and untrained providers. Results The median number of severe PE/E cases in the past year was just 5 (range 0–42) at comprehensive health centers (CHCs) and district hospitals, compared with 44 (range 0–130) at provincial hospitals and 108 (range 32–540) at regional and specialized hospitals (p?

  9. 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

  10. Nitration of p38 MAPK in the placenta: association of nitration with reduced catalytic activity of p38 MAPK in pre-eclampsia

    Microsoft Academic Search

    R. P. Webster; D. Brockman; L. Myatt

    2006-01-01

    Peroxynitrite, a potent pro-oxidant formed from the interaction of superoxide and nitric oxide, has been widely reported to be nitrating tyrosine residues in proteins resulting in the formation of nitrotyrosine. Biological nitration of tyrosine, a footprint of oxidative injury, has been found to occur in various pathological states including pre-eclampsia, a leading cause of maternal mor- tality and increased perinatal

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

    PubMed

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

    2015-06-01

    One of the most frequent causes of maternal and perinatal morbidity is represented by hypertensive disorders during pregnancy. Women at high risk must be subjected to a more intensive antenatal surveillance and prophylactic treatments. Many genetic risk factors, clinical features and biomarkers have been proposed but none of these seems able to prevent pre-eclampsia onset. English literature review of manuscripts focused on calcium intake and hypertensive disorders during pregnancy was performed. We performed a critical analysis of evidences about maternal calcium metabolism pattern in pregnancy analyzing all possible bias affecting studies. Calcium supplementation seems to give beneficial effects on women with low calcium intake. Some evidence reported that calcium supplementation may drastically reduce the percentage of pre-eclampsia onset consequently improving the neonatal outcome. Starting from this evidence, it is intuitive that investigations on maternal calcium metabolism pattern in first trimester of pregnancy could represent a low cost, large scale tool to screen pregnant women and to identify those at increased risk of pre-eclampsia onset. We propose a biochemical screening of maternal calcium metabolism pattern in first trimester of pregnancy to discriminate patients who potentially may benefit from calcium supplementation. In a second step we propose to randomly allocate the sub-cohort of patients with calcium metabolism disorders in a treatment group (calcium supplementation) or in a control group (placebo) to define if calcium supplementation may represent a dietary mean to reduce pre-eclampsia onset and to improve pregnancy outcome. PMID:25153423

  12. 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

  13. Phase I pilot clinical trial of antenatal maternally administered melatonin to decrease the level of oxidative stress in human pregnancies affected by pre-eclampsia (PAMPR): study protocol

    PubMed Central

    Hobson, Sebastian R; Lim, Rebecca; Gardiner, Elizabeth E; Alers, Nicole O; Wallace, Euan M

    2013-01-01

    Introduction Pre-eclampsia is a common pregnancy condition affecting between 3% and 7% of women. Unfortunately, the exact pathophysiology of the disease is unknown and as such there are no effective treatments that exist notwithstanding prompt delivery of the fetus and culprit placenta. As many cases of pre-eclampsia occur in preterm pregnancies, it remains a significant cause of maternal and perinatal morbidity and mortality. Recently, in vitro and animal studies have highlighted the potential role of antioxidants in mitigating the effects of the disease. Melatonin is a naturally occurring antioxidant hormone and provides an excellent safety profile combined with ease of oral administration. We present the protocol for a phase I pilot clinical trial investigating the efficacy and side effects of maternal treatment with oral melatonin in pregnancies affected by preterm pre-eclampsia. Methods and analysis We propose undertaking a single-arm open label clinical trial recruiting 20 women with preterm pre-eclampsia (24+0–35+6 weeks). We will take baseline measurements of maternal and fetal well-being, levels of oxidative stress, ultrasound Doppler studies and other biomarkers of pre-eclampsia. Women will then be given oral melatonin (10?mg) three times daily until delivery. The primary outcome will be time interval between diagnosis and delivery compared to historical controls. Secondary outcomes will compare the baseline measurements previously mentioned with twice-weekly measurements during treatment and then 6?weeks postpartum. Ethics and dissemination Ethical approval has been obtained from Monash Health Human Research Ethics Committee B (HREC 13076B). Data will be presented at international conferences and published in peer-reviewed journals. Trial registration number ACTRN12613000476730 (ANZCTR). PMID:24056493

  14. Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity

    PubMed Central

    Yong, Hannah E. J.; Murthi, Padma; Borg, Anthony; Kalionis, Bill; Moses, Eric K.; Brennecke, Shaun P.; Keogh, Rosemary J.

    2014-01-01

    Introduction Pre-eclampsia (PE) has a familial association, with daughters of women who had PE during pregnancy having more than twice the risk of developing PE themselves. Through genome-wide linkage and genetic association studies in PE-affected families and large population samples, we previously identified the following as positional candidate maternal susceptibility genes for PE; ACVR1, INHA, INHBB, ERAP1, ERAP2, LNPEP,COL4A1 and COL4A2. The aims of this study were to determine mRNA expression levels of previously identified candidate maternal pre-eclampsia susceptibility genes from normotensive and severe PE (SPE) pregnancies and correlate mRNA expression levels with the clinical severity of SPE. Methods Third trimester decidual tissues were collected from both normotensive (n=21) and SPE pregnancies (n=24) and mRNA expression levels were determined by real-time PCR. Gene expression was then correlated with several parameters of clinical severity in SPE. Statistical significance was determined by Mann-Whitney U test and Spearman's Correlation. Results The data demonstrate significantly increased decidual mRNA expression levels of ACVR1, INHBB, ERAP1, ERAP2, LNPEP, COL4A1 and COL4A2 in SPE (p<0.05). Increased mRNA expression levels of several genes – INHA, INHBB, COL4A1 and COL4A2 were correlated with earlier onset of PE and earlier delivery of the fetus (p<0.05). Conclusion These results suggest altered expression of maternal susceptibility genes may play roles in PE development and the course of disease severity. PMID:24331737

  15. Folic Acid and Homocyst(e)ine Metabolic Defects and the Risk of Placental Abruption, Pre-eclampsia and Spontaneous Pregnancy Loss: A Systematic Review

    Microsoft Academic Search

    J. G Ray; C. A Laskin

    1999-01-01

    Placental infarction or abruption, recurrent pregnancy loss and pre-eclampsia are thought to arise due to defects within the placental vascular bed. Deficiencies of vitamin B12 and folate, or other abnormalities within the methionine-homocyst(e)ine pathway have been implicated in the development of such placental diseases. We conducted a systematic literature review to quantify the risk of placental disease in the presence

  16. Monitoring Severe Pre-Eclampsia and Eclampsia Treatment in Resource Poor Countries: Skilled Birth Attendant Perception of a New Treatment and Monitoring Chart (LIVKAN Chart)

    Microsoft Academic Search

    Charles A. AmehChristine; Christine I. Ekechi; Jamilu Tukur

    The lack of easy to use protocols and monitoring charts in the management of pre-eclampsia\\/eclampsia contribute to substandard\\u000a care of women in resource poor settings. A treatment monitoring tool (LIVKAN chart) has been developed to improve the quality\\u000a of care for these women. Based on feedback from skilled birth attendants (SBAs), a two page document which provides a visual\\u000a record

  17. Uterine Artery Doppler Flow and Uteroplacental Vascular Pathology in Normal Pregnancies and Pregnancies Complicated by Pre-eclampsia and Small for Gestational Age Fetuses

    Microsoft Academic Search

    M. W. Aardema; H. Oosterhof; A. Timmer; I. van Rooy; J. G. Aarnoudse

    2001-01-01

    This study was conducted to investigate the association between uterine artery Doppler flow patterns and uteroplacental vascular pathology in normal and complicated pregnancies in view of the recently described concept of heterogeneous causes of hypertensive pregnancy complications. Forty-three women whose pregnancies were complicated by pre-eclampsia, the HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) syndrome and\\/or small for gestational age (SGA)

  18. Increased adrenomedullin protein content and mRNA expression in human fetal membranes but not placental tissue in pre-eclampsia

    Microsoft Academic Search

    A. Al-Ghafra; N. M. Gude; S. P. Brennecke; R. G. King

    2006-01-01

    The relationship between Pre-eclampsia (PE) and placental production of Adrenomedullin (AdM) is not completely understood. This study measured placental and fetal membrane AdM protein concentrations by specific radioimmunoassay and mRNA expression by Northern blot analysis in samples obtained at either term or preterm gestation from women either in labour or not in labour. Samples were obtained from women with normotensive

  19. Augmented PLA 2Activity in Pre-eclamptic Decidual Tissue—A Key Player in the Pathophysiology of ‘Acute Atherosis’ in Pre-eclampsia?

    Microsoft Academic Search

    T. Ranheim; B. Halvorsen

    2003-01-01

    Decidual acute atherosis is associated with pre-eclampsia, but the underlying mechanism is still unclear. We have previously demonstrated elevated level of the oxidative stress marker 8-isoprostaglandin F2?(8-isoprostane) and lipids in pre-eclamptic decidual tissue. Arachidonic acid (AA) in tissue phospholipids is a source for 8-isoprostane generation, and 8-isoprostane is liberated from tissue phospholipids by phospholipase A2(PLA2). The aims of this study

  20. Three mechanisms in the pathogenesis of pre-eclampsia suggested by over-represented transcription factor-binding sites detected with comparative promoter analysis

    Microsoft Academic Search

    B. Vasarhelyi; Á. Cseh; I. Kocsis; A. Treszl; B. Györffy; J. Rigó Jr

    2006-01-01

    Microarray studies generating lists of genes with altered expression in placentas from pregnancies complicated with pre-eclampsia (PE) have so far been published in several different studies. Working under the assumption that altered gene expression in PE may be the result of altered expression of regulatory transcription factors (TFs), we looked for over-represented TF-binding sites (TFBSs)—which indicate the involvement of TFs

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

    PubMed Central

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

    2013-01-01

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

  2. Pre-eclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles.

    PubMed Central

    Arkwright, P D; Rademacher, T W; Dwek, R A; Redman, C W

    1993-01-01

    Pre-eclampsia is a placental disorder, but until now, biochemical details of dysfunction have been lacking. During an analysis of the oligosaccharide content of syncytiotrophoblast microvesicles purified from the placental chorionic villi of 10 primigravid women with proteinuric pre-eclampsia, we found an excess of glycogen breakdown products. Further investigation revealed a 10-fold increase in glycogen content (223 +/- 117 micrograms glycogen/mg protein), when compared with controls matched for gestational age at delivery (23 +/- 18 micrograms glycogen/mg protein) (P < 0.01). This was confirmed by examination of electron micrographs of chorionic villous tissue stained for glycogen. The increase in glycogen content was associated with 16 times more glycogen synthase (1,323 +/- 1,013 relative to 83 +/- 96 pmol glucose/mg protein per min) (P < 0.001), and a threefold increase in glycogen phosphorylase activity (2,280 +/- 1,360 relative to 700 +/- 540 pmol glucose/mg protein per min; P < 0.05). Similar changes in glycogen metabolism were found in trophoblast microvesicles derived from hydatidiform moles. Glycogen accumulation in villous syncytiotrophoblast may be a metabolic marker of immaturity of this cell which is unable to divide. The implications of these findings with regard to the pathogenesis of pre-eclampsia are discussed. Images PMID:8514882

  3. Innate and Adaptive Immune Interactions at the Fetal–Maternal Interface in Healthy Human Pregnancy and Pre-Eclampsia

    PubMed Central

    Hsu, Peter; Nanan, Ralph Kay Heinrich

    2014-01-01

    Maternal immune tolerance of the fetus is indispensable for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal–maternal interface – the decidua, the site of implantation, and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, pre-eclampsia. Within the innate immune system, decidual NK cells and antigen presenting cells (including dendritic cells and macrophages) make up a large proportion of the decidual leukocyte population, and are thought to modulate vascular remodeling and trophoblast invasion. On the other hand, within the adaptive immune system, Foxp3+ regulatory T cells are crucial for ensuring immune tolerance toward the semi-allogeneic fetus. Additionally, another population of CD4+HLA-G+ suppressor T cells has also been identified as a potential player in the maintenance of immune tolerance. More recently, studies are beginning to unravel the potential interactions between the innate and the adaptive immune system within the decidua, that are required to maintain a healthy pregnancy. In this review, we discuss the recent advances exploring the complex crosstalk between the innate and the adaptive immune system during human pregnancy. PMID:24734032

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

    PubMed Central

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

    2014-01-01

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

  5. Up-Regulated Expression and Aberrant DNA Methylation of LEP and SH3PXD2A in Pre-Eclampsia

    PubMed Central

    Li, Xiaotian; Li, Qiaoli; Xu, Jiawei; Zhang, Junyu; Liu, Yun; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

    2013-01-01

    The primary mechanism underlying pre-eclampsia (PE) remains one of the most burning problems in the obstetrics and gynecology. In this study, we performed an expression profiling screen and detected 1312 genes that were differentially expressed (p<0.05 and fold change >1.5) in PE placentas, including LEP and SH3PXD2A. After validating the microarray results, we conducted the quantitative methylation analysis of LEP and SH3PXD2A in preeclamptic (n?=?16) versus normal placentas (n?=?16). Our results showed that many CpG sites close to the transcriptional start site (TSS) of LEP gene were hypomethylated in placentas from pregnancies with PE compared with those of in controls, including the TSS position (p?=?0.001), the binding sites of Sp1 (p?=?1.57×10?4), LP1 (p?=?0.023) and CEBP? (p?=?0.031). Luciferase reporter analysis confirmed the aberrant methylation of LEP promoter and CEBP? co-transfection had a role in the regulation of gene expression. Our results indicated the aberrant LEP promoter methylation was involved in the development of PE. We did not find a significant methylation differences between groups in the promoter region of SH3PXD2A, however, a CGI region in the gene body (CGI34) presented a higher methylation in preeclamptic placentas (p?=?1.57×10?4), which might promote the efficiency of gene transcription. We speculated that SH3PXD2A may take part in the pathogenesis of PE through its role in the regulation of trophoblast cell invasion in the period of placenta formation. PMID:23544093

  6. Reduced placental taurine transporter (TauT) activity in pregnancies complicated by pre-eclampsia and maternal obesity.

    PubMed

    Desforges, Michelle; Ditchfield, Andrea; Hirst, Chloe R; Pegorie, Claire; Martyn-Smith, Kathryn; Sibley, Colin P; Greenwood, Susan L

    2013-01-01

    Taurine is an important nutrient in intrauterine life, being required for fetal organ development and cellular renewal of syncytiotrophoblast (STB), the nutrient transport epithelium of the placenta. As taurine is conditionally essential in human pregnancy, the fetal and placental demand for taurine is met by uptake from maternal blood into STB through the activity of TauT. Pre-eclampsia (PE) and maternal obesity are serious complications of pregnancy, associated with fetal growth restriction (FGR) and abnormal renewal of STB, and maternal obesity is a major risk factor for PE. Here we test the hypothesis that STB TauT activity is reduced in maternal obesity and PE compared to normal pregnancy.STB TauT activity, measured in fragments of placental tissue, was negatively related to maternal BMI over the range 18-46 kg/m(2) in both the first trimester (7-12 weeks gestation) and at term (p < 0.01; linear regression). Neither TauT activity nor expression in the first trimester differed to normal pregnancy at term. STB TauT activity was significantly lower in PE than normal pregnancy (p < 0.01). Neuropeptide Y (NPY), a protein kinase C (PKC) activator which is elevated in PE and obesity, reduced STB TauT activity by 20% (50 pM-50 nM: 2 h) (p < 0.03). Activation of PKC by phorbol 12-myristate-13-acetate (1 ?M) reduced TauT activity by 18% (p < 0.05). As TauT activity is inhibited by phosphorylation, we propose that NPY activates PKC in the STB which phosphorylates TauT in PE and maternal obesity.Reduced TauT activity could contribute to dysregulated renewal of STB and FGR that are common to PE and maternal obesity. PMID:23392873

  7. Recombinant Vascular Endothelial Growth Factor 121 Attenuates Autoantibody-Induced Features of Pre-eclampsia in Pregnant Mice

    PubMed Central

    Siddiqui, Athar H.; Irani, Roxanna A.; Zhang, Yujin; Dai, Yingbo; Blackwell, Sean C.; Ramin, Susan M.; Kellems, Rodney E.; Xia, Yang

    2012-01-01

    BACKGROUND Pre-eclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by excessive production of a soluble form of the vascular endothelial growth factor (VEGF) receptor-1, termed soluble fms-like tyrosine kinase-1 (sFlt-1). This placental-derived factor is believed to be a key contributor to the clinical features of PE. Women with PE are also characterized by the presence of autoantibodies, termed angiotensin type 1 receptor activating autoantibody (AT1-AA), that activate the major angiotensin receptor, AT1. These autoantibodies cause clinical features of PE and elevated sFlt-1 when injected into pregnant mice. The research reported here used this autoantibody-injection model of PE to assess the therapeutic potential of recombinant VEGF121, a relatively stable form of the natural ligand. METHODS Immunoglobulin G (IgG) from women with PE was injected into pregnant mice with or without continuous infusion of recombinant VEGF121. Injected mice were monitored for symptoms of PE. RESULTS As a result of infusion of recombinant VEGF121 autoantibody-induced hypertension (systolic blood pressure) was reduced from 159 ± 5 to 124 ± 5 mm Hg, proteinuria from 111 ± 16 to 40 ± 5 mg protein/mg creatinine and blood urea nitrogen levels from 31 ± 1 mg/ dl to 18 ± 2 mg/dl, P < 0.05. Histological analysis revealed that autoantibody-induced glomerular damage including the narrowing of Bowman’s space and occlusion of capillary loop spaces was largely prevented by VEGF121 infusion. Finally, impaired placental angiogenesis resulting from AT1-AA injection was significantly improved by VEGF121 infusion. CONCLUSIONS The infusion of recombinant VEGF121 significantly attenuated autoantibody-induced features of PE. PMID:21183928

  8. Maternal and fetal single nucleotide polymorphisms in the epoxide hydrolase and gluthatione S-transferase P1 genes are not associated with pre-eclampsia in the Coloured population of the Western Cape, South Africa.

    PubMed

    Gebhardt, G S; Peters, W H M; Hillermann, R; Odendaal, H J; Carelse-Tofa, K; Raijmakers, M T M; Steegers, E A P

    2004-11-01

    Oxidative stress is thought to play an important role in the pathophysiology of pre-eclampsia. A defect in certain enzymes responsible for detoxification may cause prolonged exposure to reactive by-products and contribute to maternal endothelial as well as placental damage. Two polymorphisms affecting the function of the biotransformation enzymes epoxide hydrolase and glutathione S-transferase P1 were shown previously to be associated with pre-eclampsia in a Dutch population. The aim of this study was to determine if these two polymorphisms (maternal or fetal) contribute to pre-eclampsia in an anthropologically distinct population (the Western Cape region of South Africa) with a high incidence of the disease. Genomic DNA of mother - infant pairs with severe pre-eclampsia (n = 144), a population control group (n = 156) and control mother - infant pairs with uncomplicated pregnancy outcome (n = 45) were analysed for the EPHX and GSTP1 polymorphisms by polymerase chain reaction amplification and restriction enzyme digestion. Each polymorphism had a similar distribution in case and control subjects (mother and infant). The Val105/Val105 genotype of GSTP1 occurred at a higher frequency than reported for other populations. Neither maternal nor fetal EPHX Tyr113His and GSTP1 Ile105Val polymorphisms appear to contribute significantly to the pathophysiology of pre-eclampsia in the Coloured population of the Western Cape region of South Africa. PMID:16147638

  9. 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

  10. Pre-eclampsia but not pregnancy-induced hypertension is a risk factor for diabetic nephropathy in type 1 diabetic women

    Microsoft Academic Search

    D. Gordin; V. Hiilesmaa; J. Fagerudd; M. Rönnback; C. Forsblom; R. Kaaja; K. Teramo; P.-H. Groop

    2007-01-01

    Aims\\/hypothesis  Our aim was to study whether pre-eclampsia and pregnancy-induced hypertension are predictors of diabetic nephropathy in type\\u000a 1 diabetic women.\\u000a \\u000a \\u000a \\u000a Materials and methods  A total of 203 type 1 diabetic women, who were pregnant between 1988 and 1996 and followed at the Department of Obstetrics\\u000a and Gynaecology in Helsinki, were re-assessed after an average of 11 years within the nationwide, multi-centre Finnish

  11. 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 ?, ? and ? 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 ?, ? and ? 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

  12. Factors Regulating Trophoblast Migration and Invasiveness: Possible Derangements Contributing to Pre-eclampsia and Fetal Injury 1 1 Studies from the authors’ laboratory summarized in this article were supported by the Canadian Institutes of Health Research Grant MOP36446

    Microsoft Academic Search

    P. K. Lala; C. Chakraborty

    2003-01-01

    Impaired trophoblast invasiveness and spiral arterial remodelling, which results in poor placental perfusion during early pregnancy, is believed to cause fetal injury and growth retardation, and also endothelial cell activation\\/dysfunction in a susceptible mother, leading to clinical manifestations of pre-eclampsia. This article briefly reviews the regulatory roles of certain locally active factors in trophoblast migration and invasiveness. This background is

  13. Genome-wide association study of pre-eclampsia detects novel maternal single nucleotide polymorphisms and copy-number variants in subsets of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study cohort.

    PubMed

    Zhao, Linlu; Bracken, Michael B; DeWan, Andrew T

    2013-07-01

    A genome-wide association study was undertaken to identify maternal single nucleotide polymorphisms (SNPs) and copy-number variants (CNVs) associated with pre-eclampsia. Case-control analysis was performed on 1070 Afro-Caribbean (n = 21 cases and 1049 controls) and 723 Hispanic (n = 62 cases and 661 controls) mothers and 1257 mothers of European ancestry (n = 50 cases and 1207 controls) from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. European ancestry subjects were genotyped on Illumina Human610-Quad and Afro-Caribbean and Hispanic subjects were genotyped on Illumina Human1M-Duo BeadChip microarrays. Genome-wide SNP data were analyzed using PLINK. CNVs were called using three detection algorithms (GNOSIS, PennCNV, and QuantiSNP), merged using CNVision, and then screened using stringent criteria. SNP and CNV findings were compared to those of the Study of Pregnancy Hypertension in Iowa (SOPHIA), an independent pre-eclampsia case-control dataset of Caucasian mothers (n = 177 cases and 116 controls). A list of top SNPs were identified for each of the HAPO ethnic groups, but none reached Bonferroni-corrected significance. Novel candidate CNVs showing enrichment among pre-eclampsia cases were also identified in each of the three ethnic groups. Several variants were suggestively replicated in SOPHIA. The discovered SNPs and copy-number variable regions present interesting candidate genetic variants for pre-eclampsia that warrant further replication and investigation. PMID:23551011

  14. The Magpie Trial follow up study: outcome after discharge from hospital for women and children recruited to a trial comparing magnesium sulphate with placebo for pre-eclampsia [ISRCTN86938761

    Microsoft Academic Search

    2004-01-01

    BACKGROUND: The Magpie Trial compared magnesium sulphate with placebo for women with pre-eclampsia. 10,141 women were recruited, 8804 before delivery. Overall, 9024 children were included in the analysis of outcome at discharge from hospital. Magnesium sulphate more than halved the risk of eclampsia, and probably reduced the risk of maternal death. There did not appear to be any substantive harmful

  15. Susceptibility to pre-eclampsia in Finnish women is associated with R485K polymorphism in the factor V gene, not with Leiden mutation.

    PubMed

    Faisel, Fareeza; Romppanen, Eeva-Liisa; Hiltunen, Mikko; Helisalmi, Seppo; Laasanen, Jaana; Punnonen, Kari; Salonen, Jukka T; Heinonen, Seppo

    2004-03-01

    This study determines whether genetic variability in the gene-encoding factor V contributes to differences in pre-eclampsia susceptibility. Allele and genotype frequencies of three single-nucleotide polymorphisms (SNPs) in the factor V gene leading to nonsynonymous changes (M385T in exon 8, and R485K and R506Q (Leiden mutation) in exon 10) were studied in 133 Caucasian women with pre-eclampsia and 112 healthy controls. Single-point analysis was expanded to haplotype analysis, and haplotype frequencies were estimated using an expectation-maximization algorithm. Comparison of single-point allele and genotype distributions of SNPs in exons 8 and 10 of the factor V gene revealed statistically significant differences in R485K allele (P=0.003) and genotype (P=0.03) frequencies between the patients and the control subjects. The A allele of SNP R485K was over-represented among the patients (12%) vs the control subjects (4%), at an odds ratio (OR) of 2.8 (95% confidence interval (CI) 1.2-6.2) for combined A genotypes (GA+AA vs GG). Allele and genotype differences between the patients and control subjects as regards M385T and Leiden mutation were not significant. In haplotype estimation analysis, there was a significantly elevated frequency of haplotype T-A-G encoding the M385-K485-R506 variant in the pre-eclamptic group vs the control group (P=0.01), at an OR of 2.6 (95% CI 1.2-5.5). We conclude that the T-A-G haplotype was more frequent among the patient group than in the control group, and genetic variations in the factor V gene other than the Leiden mutation may play a role in disease susceptibility. PMID:14673478

  16. Presence of auto-antibody against two placental proteins, annexin A1 and vitamin D binding protein, in sera of women with pre-eclampsia.

    PubMed

    Behrouz, Gharesi-Fard; Farzaneh, Ghaderi-shabankareh; Leila, Jafarzadeh; Jaleh, Zolghadri; Eskandar, Kamali-Sarvestani

    2013-09-01

    Pre-eclampsia (PE) is one of the most complex and life-threatening pregnancy disorders. PE is characterized by maternal hypertension and proteinuria. There is much evidence to support an immunological etiology for PE and auto-immunity is considered a predisposing factor for PE. The aim of the present study was the investigation of placental proteins as targets for auto-antibodies in PE patients. 2D-PAGE technique was used for separation of the total human placental proteins. After separation, protein spots were transferred to the PVDF membranes and blotted with sera from 20 PE patients and compared with membranes blotted with 20 sera from normal women. MALDI TOF/TOF mass spectrometry technique was used for identification of differentially blotted spots. Moreover, the results of mass analysis were confirmed using western blot with commercial mAbs and RT-PCR technique. The results indicated that two placental proteins, annexin A1 and vitamin D binding protein (DBP), might be targeted by PE sera. The expression of annexin A1 and DBP was also confirmed at RNA level using the RT-PCR technique. Furthermore, the mass results were confirmed by western blotting with commercial mAbs against two targeted proteins. The data of the present study suggest two new placental proteins, annexin A1 and DBP, as placental immune targets. Considering the relation among vitamin D deficiency, increased risk of PE, and the role of annexin A1 in the resolution of inflammation, production of antibody against annexin A1 and DBP may be considered a new auto-immune hypothesis in pre-eclampsia that calls for further investigation in future work. PMID:23830177

  17. Differential activation of placental unfolded protein response pathways implies heterogeneity in causation of early- and late-onset pre-eclampsia.

    PubMed

    Yung, Hong Wa; Atkinson, Daniel; Campion-Smith, Tim; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J

    2014-10-01

    Based on gestational age at diagnosis and/or delivery, pre-eclampsia (PE) is commonly divided into early-onset (<34 weeks) and late-onset (?34 weeks) forms. Recently, the distinction between 'placental' and 'maternal' causation has been proposed, with 'placental' cases being more frequently associated with early-onset and intrauterine growth restriction. To test whether molecular placental pathology varies according to clinical presentation, we investigated stress-signalling pathways, including unfolded protein response (UPR) pathways, MAPK stress pathways, heat-shock proteins and AMPK? in placentae delivered by caesarean section for clinical indications at different gestational ages. Controls included second-trimester, pre-term and normal-term placentae. BeWo cells were used to investigate how these pathways react to different severities of hypoxia-reoxygenation (H/R) and pro-inflammatory cytokines. Activation of placental UPR and stress-response pathways, including P-IRE1?, ATF6, XBP-1, GRP78 and GRP94, P-p38/p38 and HSP70, was higher in early-onset PE than in both late-onset PE and normotensive controls (NTCs), with a clear inflection around 34 weeks. Placentae from ? 34 weeks PE and NTC were indistinguishable. Levels of UPR signalling were similar between second-trimester and term controls, but were significantly higher in pre-term 'controls' delivered vaginally for chorioamnionitis and other conditions. Severe H/R (1/20% O2 ) induced equivalent activation of UPR pathways, including P-eIF2?, ATF6, P-IRE1?, GRP78 and GRP94, in BeWo cells. By contrast, the pro-inflammatory cytokines TNF? and IL-1? induced only mild activation of P-eIF2? and GRP78. AKT, a central regulator of cell proliferation, was reduced in the < 34 weeks PE placentae and severe H/R-treated cells, but not in other conditions. These findings provide the first molecular evidence that placental stress may contribute to the pathophysiology of early-onset pre-eclampsia, whereas that is unlikely to be the case in the late-onset form of the syndrome. PMID:24931423

  18. Differential activation of placental unfolded protein response pathways implies heterogeneity in causation of early- and late-onset pre-eclampsia

    PubMed Central

    Yung, Hong Wa; Atkinson, Daniel; Campion-Smith, Tim; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J

    2014-01-01

    Based on gestational age at diagnosis and/or delivery, pre-eclampsia (PE) is commonly divided into early-onset (<34 weeks) and late-onset (?34 weeks) forms. Recently, the distinction between ‘placental’ and ‘maternal’ causation has been proposed, with ‘placental’ cases being more frequently associated with early-onset and intrauterine growth restriction. To test whether molecular placental pathology varies according to clinical presentation, we investigated stress-signalling pathways, including unfolded protein response (UPR) pathways, MAPK stress pathways, heat-shock proteins and AMPK? in placentae delivered by caesarean section for clinical indications at different gestational ages. Controls included second-trimester, pre-term and normal-term placentae. BeWo cells were used to investigate how these pathways react to different severities of hypoxia–reoxygenation (H/R) and pro-inflammatory cytokines. Activation of placental UPR and stress-response pathways, including P-IRE1?, ATF6, XBP-1, GRP78 and GRP94, P-p38/p38 and HSP70, was higher in early-onset PE than in both late-onset PE and normotensive controls (NTCs), with a clear inflection around 34 weeks. Placentae from ? 34 weeks PE and NTC were indistinguishable. Levels of UPR signalling were similar between second-trimester and term controls, but were significantly higher in pre-term ‘controls’ delivered vaginally for chorioamnionitis and other conditions. Severe H/R (1/20% O2) induced equivalent activation of UPR pathways, including P-eIF2?, ATF6, P-IRE1?, GRP78 and GRP94, in BeWo cells. By contrast, the pro-inflammatory cytokines TNF? and IL-1? induced only mild activation of P-eIF2? and GRP78. AKT, a central regulator of cell proliferation, was reduced in the < 34 weeks PE placentae and severe H/R-treated cells, but not in other conditions. These findings provide the first molecular evidence that placental stress may contribute to the pathophysiology of early-onset pre-eclampsia, whereas that is unlikely to be the case in the late-onset form of the syndrome. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:24931423

  19. Non-synonymous sequence variants within the oxygen-dependent degradation domain of the HIF1A gene are not associated with pre-eclampsia in the Finnish population

    Microsoft Academic Search

    Sanna Heino; Milja Kaare; Sture Andersson; Hannele Laivuori

    2008-01-01

    BACKGROUND: Reduced placental perfusion predisposes to the maternal syndrome pre-eclampsia characterized by systemically reduced perfusion. Considerable data support the role of angiogenic factors in the development of the maternal syndrome. Hypoxia-inducible factor (HIF-1) mediates the cellular responses to hypoxia e.g. by promoting angiogenesis. METHODS: Here we studied whether two single nucleotide sequence variants, c.1744 C>T that changes residue 582 of

  20. Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia

    Microsoft Academic Search

    Yoshiki Kudo; C. A. R. Boyd; I. L. Sargent; C. W. G. Redman

    2003-01-01

    The fundamental process of placental trophoblast cell fusion (syncytiotrophoblast formation or syncytialisation) which is a characteristic of this tissue is poorly understood. Pre-eclampsia is associated with placental hypoxia and suppressed syncytiotrophoblast formation. We therefore have studied the effect of low-oxygen tensions on the rate of cell fusion, relative abundance of mRNAs encoding syncytin and its receptor, amino acid transport system

  1. 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

  2. The effects of S-nitrosoglutathione and S-nitroso-N-acetyl-D, L-penicillamine in a rat model of pre-eclampsia

    PubMed Central

    Brown, Caneta; McFarlane-Anderson, Norma; Alexander-Lindo, Ruby; Bishop, Karen; Dasgupta, Tara; McGrowder, Donovan

    2013-01-01

    Background: Pre-eclampsia (PE) complicates approximately 5-7% of all pregnancies. This study investigates the effects of S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) on the classical features of PE. Materials and Methods: On day 14 of gestation, female Sprague-Dawley rats were separated into five groups and treated intravenously for 7 days as follows: (i) 0.3 mL 0.9% saline (control, n = 11); (ii) 50 mg/kg Body Weight (BW) N-nitro-L-arginine methyl ester (L-NAME) in 0.3 mL saline (n = 10); (iii) 50 mg/kg BW L-NAME and 8 mg/kg BW GSNO in 0.15 mL saline (n = 6); (iv) 50 mg/kg BW L-NAME in 0.15 mL saline and 8 mg/kg BW SNAP in 0.15 mL DMSO (n = 9); and (v) 0.15 mL DMSO and 0.15 mL saline (SNAP control, n = 7). Blood pressures were measured on day 14 through day 20, a 4-h urine sample was taken on day 20, and animals were sacrificed on day 21. Pups were counted and weighed individually. Results: SNAP and GSNO significantly decreased systolic, diastolic, and mean arterial pressures in PE-induced rats from day 14 through day 20 (P < 0.05). Pup weights in SNAP and GSNO groups were higher than in L-NAME group but lower than in controls (P ? 0.001). SNAP and GSNO partially reversed growth retardation. Conclusion: Elevated blood pressure, proteinuria, and intrauterine growth restriction associated with PE were induced in Sprague-Dawley rats using L-NAME. These were partially reversed with the use of GSNO and SNAP. The mechanism of action of these S-nitrosothiols (RSNOs) should be further explored. PMID:24082727

  3. Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia.

    PubMed

    Kudo, Yoshiki; Boyd, C A R; Sargent, I L; Redman, C W G

    2003-05-20

    The fundamental process of placental trophoblast cell fusion (syncytiotrophoblast formation or syncytialisation) which is a characteristic of this tissue is poorly understood. Pre-eclampsia is associated with placental hypoxia and suppressed syncytiotrophoblast formation. We therefore have studied the effect of low-oxygen tensions on the rate of cell fusion, relative abundance of mRNAs encoding syncytin and its receptor, amino acid transport system B(0), which are thought to be involved in trophoblast cell fusion (as well as the activity of amino acid transport through this system) in a cell model of syncytialisation (BeWo cells following forskolin treatment). Forskolin-induced cell fusion (determined by a quantitative flow cytometry assay) was reversibly suppressed in 2% oxygen compared to 20% oxygen. This was associated with suppressed secretion of human chorionic gonadotropin. Forskolin stimulated relatively less syncytin mRNA (determined by reverse transcription-polymerase chain reaction) in 2% than in 20% oxygen and there was no stimulation after 48 h in 2% oxygen. There was a spontaneous, time-dependent increase of amino acid transporter B(0) mRNA in vehicle, which was suppressed by 2% oxygen and by forskolin treatment in 20% oxygen. Forskolin-induced changes in amino acid transport system B(0) function were not seen in cells cultured for 48 h in 2% oxygen. These observations suggest that under conditions of low ambient oxygen, dysregulation of expression of syncytin and of its receptor may suppress the normal process of cell fusion necessary for syncytiotrophoblast formation and contributes to syncytiotrophoblast abnormalities characteristic of pre-eclampsia. PMID:12757936

  4. The maternal HLA-G 1597?C null mutation is associated with increased risk of pre-eclampsia and reduced HLA-G expression during pregnancy in African-American women

    PubMed Central

    Loisel, Dagan A.; Billstrand, Christine; Murray, Kathleen; Patterson, Kristen; Chaiworapongsa, Tinnakorn; Romero, Roberto; Ober, Carole

    2013-01-01

    The non-classical major histocompatibility complex molecule, human leukocyte antigen (HLA)-G, is thought to contribute to maternal immune tolerance and successful placentation during pregnancy. Genetic polymorphisms in HLA-G are known to influence expression levels as well as the relative expression of individual protein isoforms. As diminished or aberrant HLA-G expression patterns may contribute to the development of certain pregnancy complications, we sought to investigate the association between functional HLA-G polymorphisms and the risk of pre-eclampsia (PE) in African-American women. The association between maternal and fetal genotype at six HLA-G polymorphisms and risk of PE was assessed in 372 pregnancies (314 normotensive; 58 pre-eclamptic). We observed an elevated risk of PE (P = 0.00027) in pregnancies where the mother carried the 1597?C allele, a null allele that abolishes expression of full-length HLA-G isoforms. Furthermore, the frequency of the maternal 1597?C allele was highest in the subset of pre-eclamptic pregnancies that were delivered preterm, suggesting an association between the null allele and the severity of PE. We then replicated the association between higher maternal 1597?C allele frequency and increased severity of PE (P = 0.038) in an independent sample of 533 African-American women. Finally, to investigate the mechanistic basis of this association, we measured circulating soluble HLA-G (sHLA-G) concentrations in maternal serum collected during pregnancy in 51 healthy, normotensive African-American control women and found significantly lower levels in women carrying the 1597?C allele (P = 0.012). These results demonstrate that maternal HLA-G genotype is significantly associated with risk of PE in African-American women and is predictive of circulating sHLA-G levels during pregnancy. PMID:23002110

  5. Pre-Eclampsia: Clinical Manifestations and Molecular Mechanisms

    Microsoft Academic Search

    Suzanne Baumwell; S. Ananth Karumanchi

    2007-01-01

    Preeclampsia affects 3–5% of pregnancies and can have a significant impact on health for both mother and fetus. Risk factors include maternal co-morbidities such as obesity and chronic hypertension, paternal factors, and genetic factors. New hypertension and proteinuria during the second half of pregnancy are key diagnostic criteria, but the clinical features and associated prognostic implications are somewhat heterogeneous and

  6. Nerve growth factor, birth outcome and pre-eclampsia

    Microsoft Academic Search

    Anitha Kilari; Savita Mehendale; Hemlata Pisal; Tushar Panchanadikar; Anvita Kale; Sadhana Joshi

    2011-01-01

    The present study compares nerve growth factor (NGF) levels between preeclamptic (PE) (n=86) and normotensive (NT) women (n=105) and their associations with blood pressure and infant size. Maternal plasma NGF levels were reduced (p<0.05) in the PE group as compared to the NT group. Furthermore, NGF levels were reduced in PE mothers delivering low birth weight babies (LBW) as compared

  7. Plasminogen activator inhibitor-1 polymorphism in women with pre-eclampsia.

    PubMed

    Häkli, Tanja; Romppanen, Eeva-Liisa; Hiltunen, Mikko; Helisalmi, Seppo; Punnonen, Kari; Heinonen, Seppo

    2003-01-01

    We determined whether or not genetic variability in the promoter region of the gene encoding plasminogen activator inhibitor-1 (PAI1) contributes to individual differences in susceptibility to the development of preeclampsia. The study involved 133 preeclamptic and 115 healthy control pregnant women who were genotyped for a single-nucleotide insertion/deletion polymorphism (4G/5G) at position -675 in the PAI1 gene promoter. Furthermore, the frequencies of the alleles in the general middle-aged population are presented for comparison. Chi-square analysis was used to assess genotype and allele frequency differences between preeclamptic women and controls. A similar allelic distribution of PAI1 4G/5G polymorphism was observed in the two groups, with the frequency of the variant 4G allele being 50.4% in the preeclampsia group and 54.3% in the control group (p = 0.377; OR = 0.85, 95% CI = 0.60-1.22). Accordingly, the genotype distribution of the PAI1 4G/5G polymorphism in the preeclamptic and control groups was found to be similar (p = 0.68). Overall, this genotype data on fertile women is almost identical to that in the general middle-aged Finnish population. The 4G/5G polymorphism of the PAI1 gene promoter is unlikely to be a major genetic predisposing factor as regards preeclampsia in subjects from eastern Finland. These results are not suggestive of an important contribution of the PAI1 genotype on preeclampsia across populations. PMID:14642005

  8. Oxygen and Placental Development During the First Trimester: Implications for the Pathophysiology of Pre-eclampsia

    Microsoft Academic Search

    I. Caniggia; J. Winter; S. J. Lye; M. Post

    2000-01-01

    During early pregnancy, placentation occurs in a relatively hypoxic environment which is essential for appropriate embryonic development. Intervillous blood flow increases at around 10–12 weeks of gestation and results in exposure of the trophoblast to increased oxygen tension (Po2). Prior to this time, low oxygen appears to prevent trophoblast differentiation towards an invasive phenotype. In other mammalian systems, oxygen tension

  9. Proteome Analysis of Human Placentae: Pre-eclampsia Versus Normal Pregnancy

    Microsoft Academic Search

    K. Mine; A. Katayama; T. Matsumura; T. Nishino; Y. Kuwabara; G. Ishikawa; T. Murata; R. Sawa; Y. Otsubo; S. Shin; T. Takeshita

    2007-01-01

    Although placental proteins play multiple roles in fetal and placental development and in the maintenance of pregnancy, many remain inadequately characterized. In the present study, we comprehensively analyzed these proteins by using a proteomic approach. Samples were denatured with guanidine hydrochloride, which was found to be superior to the commonly used urea for the present purpose, and subjected to 2-dimensional

  10. Recent developments in the pathophysiology and management of pre-eclampsia

    Microsoft Academic Search

    M. C. MUSHAMBI; A. W. HALLIGAN; K. WILLIAMSON

    Fits occurring in pregnant women were recognized and recorded as early as the 4th century BC by Hippocrates (94). The condition was termed eclampsia—a Greek word which translates literally as 'shine forth'—implying a sudden development. Little was known about eclampsia until 1843, when Lever of Guy's Hospital found that many of the women who had fits also had albumin in

  11. Lipoprotein (a) levels in normal pregnancy and in pregnancy complicated with pre-eclampsia

    Microsoft Academic Search

    Naveed Sattar; Peter Clark; Ian A Greer; James Shepherd; Chris J Packard

    2000-01-01

    Lipoprotein (a) (Lp(a)) is recognised as a risk factor for arterial and venous thrombosis, a property which may relate to its structural similarity to plasminogen. Pregnancy is associated with a hypofibrinolytic state. Elevated Lp(a) may influence fibrinolysis and have an unfavourable role in pregnancy outcome. In this study alterations in plasma Lp(a) concentrations during normal pregnancy was examined, in a

  12. 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 signalling—ACVR1, ACVR1C, ACVR2A, INHA, INHBB; structural components—COL4A1, COL4A2 and M1 family aminopeptidases—ERAP1, 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

  13. The Proteomic Analysis of Human Placenta with Pre-eclampsia and Normal Pregnancy.

    PubMed

    Yang, Jeong In; Kong, Tae Wook; Kim, Haeng Soo; Kim, Ho Yeon

    2015-06-01

    Preeclampsia is one of the most important and complexed disorders for women's health. Searching for novel proteins as biomarkers to reveal pathogenesis, proteomic approaches using 2DE has become a valuable tool to understanding of preeclampsia. To analyze the proteomic profiling of preclamptic placenta compared to that of normal pregnancy for better understanding of pathogenesis in preeclampsia, placentas from each group were handled by use of proteomics approach using 2DE combined with MALDI-TOF-MS. The 20 spots of showing differences were analysed and identified. Among differentially expressed protein spots Hsp 27 and Hsp 70 were selected for validation using Western blot analysis. In preeclamptic placenta 9 differentially expressed proteins were down-regulated with Hsp 70, serum albumin crystal structure chain A, lamin B2, cytokeratin 18, actin cytoplasmic, alpha fibrinogen precursor, septin 2, dihydrolipoamide branched chain transacylase E2 and firbrinogen beta chain. The 11 up-regulated proteins were fibrinogen gamma, cardiac muscle alpha actin proprotein, cytokeratin 8, calumenin, fibrinogen fragment D, F-actin capping protein alpha-1 subunit, Hsp 27, Hsp 40, annexin A4, enoyl-CoA delta isomerase and programmed cell death protein 6. The western blot analysis for validation also showed significant up-regulation of Hsp 27 and down-regulation of Hsp 70 in the placental tissues with preeclmaptic pregnancies. This proteomic profiling of placenta using 2DE in preeclampsia successfully identifies various proteins involved in apoptosis, mitochondrial dysfunction, as well as three Hsps with altered expression, which might play a important role for the understanding of pathogenesis in preeclampsia. PMID:26028931

  14. 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)

  15. Prolactin fragmentation by trophoblastic matrix metalloproteinases as a possible contributor to peripartum cardiomyopathy and pre-eclampsia

    Microsoft Academic Search

    Anne Q. Reuwer; Paul J. H. M. Reuwer; Joris A. van der Post; Maarten J. Cramer; John J. P. Kastelein; Marcel Th. B. Twickler

    2010-01-01

    Although peripartum cardiomyopathy (PPCM) is a rare disease, it has very serious consequences for both mother and child. No single cause has been held responsible for the pathogenesis. Recent studies have indicated that increased proteolytic cathepsin D activity in cardiomyocytes results in 16 kDa prolactin fragments with anti-angiogenic and apoptotic properties, which may contribute to the development of PPCM. In

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

    E-print Network

    Charnock-Jones, D. Stephen

    2015-07-14

    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... in the placenta but once placentation is complete there is little angiogenesis in the decidua. A distinction needs to be made between angiogenesis (the growth of new blood vessels from pre-existing vessels) and vascular remodelling which clearly occurs...

  17. Characterisation of tone oscillations in placental and myometrial arteries from normal pregnancies and those complicated by pre-eclampsia and growth restriction.

    PubMed

    Sweeney, M; Wareing, M; Mills, T A; Baker, P N; Taggart, M J

    2008-04-01

    Agonist-induced tone oscillations (rhythmic contractions and relaxations) occur in vascular beds to allow acute regulation of volume flow and thus the delivery of oxygen and nutrients to the tissue. Mechanisms responsible for the control of human placental vasomotor tone and blood flow are poorly characterized. This study aimed to characterise thromboxane-induced tone oscillations in human placental and myometrial arteries. Chorionic plate and myometrial arteries obtained from biopsies at term were mounted for isometric tension measurement. Tone oscillations were observed in chorionic arteries only when exposed to sub-maximal (<1 microM) concentrations of U46619. Slow (mean+/-SEM) frequency (2.6+/-0.5 per hour), large amplitude (39+/-7% of peak contraction) tone oscillations were elicited by 0.03 microM U46619 (n=18). In the presence of the nitric oxide synthase (NOS) inhibitor l-NNA (100 microM) the amplitude was significantly reduced (40+/-13% to 18+/-8%, P<0.05, n=6), frequency was unaltered and the bradykinin-dependent vasodilator response was reduced (68+/-13% to 40+/-19%, P<0.05, n=6). Myometrial arteries exposed to 1 microM U46619 developed tone oscillations within 10 min, which increased in amplitude over 30min occurring at relatively constant frequency. The mean amplitude of oscillations at 30 min (31+/-7%, n=16) was similar to that in chorionic arteries but the occurrence more frequent (42.8+/-9.7 per hour, P<0.001). Inhibition of NOS did not alter tone oscillations in myometrial arteries. Tone oscillations in chorionic arteries from pre-eclamptic and growth restricted (FGR) pregnancies were reduced in amplitude whereas those in myometrial arteries had increased frequency. Inhibition of NOS further reduced oscillation amplitude in chorionic arteries from FGR pregnancies. The alterations may contribute to the vasculopathology of these conditions, or, may represent compensatory mechanisms to maintain a matching of materno-placental blood flow. PMID:18336903

  18. New scope in angiogenesis: role of vascular endothelial growth factor (VEGF), NO, lipid peroxidation, and vitamin E in the pathophysiology of pre-eclampsia among Egyptian females 1 1 Abbreviations: VEGF (vascular endothelial growth factor), PE (pre-eclampsia), NO (nitric oxide), MDA (malondialdehyde), EPH (edema proteinurea hypertension), HPLC (high performance liquid chromatography)

    Microsoft Academic Search

    Eman M El-Salahy; Maha I Ahmed; Amina El-Gharieb; Hassan Tawfik

    2001-01-01

    Objectives: The purpose of this study was to investigate the role of VEGF, NO, MDA, and Vitamin E in the pathophysiology of preeclampsia (PE) among Egyptian women.Patients and Methods: Our study included 20 pregnant women with mild PE, 40 pregnant women with severe PE, 20 normal control women and 20 normal control pregnant women. Plasma from all women were subjected

  19. Prenatal Depression and Adverse Birth Outcomes: An Updated Systematic Review

    E-print Network

    Accortt, EE; Cheadle, ACD; Dunkel Schetter, C

    2015-01-01

    pregnancies, hypertension, pre-eclampsia, maternal weightdisorders i.e. pre-eclampsia or chronic hypertension, hearteclampsia, vaginal bleeding and multiple deliveries No stars Behavioral: smoking, alcohol Socio-demographic: education, marital status Medical: pre-

  20. The Regional Expression of Insulin-like Growth Factor II (IGF-II) and Insulin-like Growth Factor Binding Protein1 (IGFBP-1) in the Placentae of Women with Pre-eclampsia

    Microsoft Academic Search

    R. J. Gratton; H. Asano; V. K. M. Han

    2002-01-01

    Insulin-like growth factors and their binding proteins regulate cellular proliferation, differentiation and function, and play an important role in placental development. IGF-II and IGFBP-1 are abundantly expressed by cells at the maternal-fetal interface and mediate cell-to-cell communication between trophoblasts and decidua. Placentae of pre-eclamptic pregnancies show villous cytotrophoblast proliferation, increased syncytial sprout formation and impaired trophoblast invasion. We hypothesized that

  1. 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

  2. A Framework for the Application of Decision Trees to the Analysis of SNPs Data

    E-print Network

    Krasnogor, Natalio

    specific diseases. One of these diseases which is still under extensive analysis is pre-eclampsia data related to cases of pre-eclampsia. The results show the validity of this methodology to detect to genetic causes, there is one called pre-eclampsia (PE) which is currently under genetic analysis for any

  3. Transmission line models to simulate the impedance of the uterine vasculature during the ovarian cycle and pregnancy

    E-print Network

    Chesler, Naomi C.

    adequately with pregnancy is a hallmark of pre-eclampsia [8­11]. Increases in uterine vascular compliance with pre- eclampsia, which contributes to insufficient uterine perfusion [14,15], but the consequences of pre-eclampsia for uterine artery compliance changes during pregnancy are not known. Further- more

  4. New Queen's research may lead to healthier pregnancies

    E-print Network

    Abolmaesumi, Purang

    inflammation during pregnancy, a condition that can cause serious diseases like pre-eclampsia and can lead. Many of these growth-restricted babies are born to women suffering from pre-eclampsia, a disease often, there are currently no effective treatments to prevent fetal growth restriction or pre-eclampsia as doctors do

  5. Pathophysiology of the Clinical Manifestations of Preeclampsia

    Microsoft Academic Search

    Michelle Hladunewich; S. Ananth Karumanchi; Richard Lafayette

    2007-01-01

    ive to 7% of all pregnancies are complicated by pre- eclampsia. Proteinuria and hypertension dominate the clinical picture, because the chief target organ is the kidney (glomerular endotheliosis). The pathogenesis of pre- eclampsia is complex; numerous genetic, immunologic, and environmental factors interact. It has been suggested that pre- eclampsia is a two-stage disease (1). The first stage is asymp- tomatic,

  6. UNIVERSITY OF GLOBAL HEALTH

    E-print Network

    MacMillan, Andrew

    Teachers' Day 2 Pre-eclampsia may be caused by the fetus not the placenta 3 Nine surprising facts about 3.internationalmidwives.org/assets/ uploads/documents/CoreDocuments/ CD2008_001%20V2014%20ENG% #12;. Pre-eclampsia may be caused by the fetus

  7. Neutrophil Activation Induced by Placental Factors in Normal and Pre-eclamptic Pregnancies In Vitro

    Microsoft Academic Search

    Y. Wang; Y. Gu; L. Philibert; M. J. Lucas

    2001-01-01

    Increased neutrophil activation has been demonstrated in women with pre-eclampsia. Activated neutrophils may play a significant role in the vascular endothelial pathophysiology in this disorder of pregnancy. How neutrophils become activated in pre-eclampsia is unknown. It has been proposed that activating factors could be produced and released by the placenta. To test if placental factors could stimulate neutrophil activation and

  8. Flt1, pregnancy, and malaria: Evolution of a complex interaction

    E-print Network

    Haig, David

    pregnancy outcomes such as fetal growth restriction, stillbirth, pre- mature delivery, and possibly pre- eclampsia (2­4). Women develop antibodies against placental parasites during their first affected pregnancy

  9. Differential Localization of Superoxide Dismutase Isoforms in Placental Villous Tissue of Normotensive, Pre-eclamptic, and Intrauterine Growth-restricted Pregnancies

    Microsoft Academic Search

    Leslie Myatt; Annie L. W. Eis; Diane E. Brockman; Wilhelm Kossenjans; Ian A. Greer; Fiona Lyall

    1997-01-01

    Several isoforms of superoxide dismutase (SOD), including copper\\/zinc (cytosolic) and manganese (mitochondrial), exist. In the human placenta, SOD may prevent excessive superoxide accumulation and any potential deleterious oxidative effects. In pre-eclampsia, increased levels of lipid peroxide and decreased SOD activity have been described in the placenta. Oxidative stress such as occurs in pre-eclampsia can alter expression of SOD isoforms. The

  10. Lipid peroxidation and antioxidants in normal and pre-eclamptic pregnancies

    Microsoft Academic Search

    A.-K. Poranena; U. Ekblad; P. Uotila; M. Ahotupa

    1996-01-01

    Lipid peroxidation has been suggested as a pathogenetic factor of pre-eclampsia. In this study we measured lipid peroxidation products and the counteracting antioxidant functions in maternal serum and placental tissue in normal pregnancy and pre-eclampsia. Placentae and maternal serum from 15 normal and 15 pre-eclamptic pregnancies were collected. Lipid peroxidation was measured as peroxidation potential, thiobarbituric acid reacting substances (TBARS)

  11. Placental cell turnover in health and disease

    Microsoft Academic Search

    Alexander Heazell; Lynda Harris; Karen Forbes; Ian Crocker

    2006-01-01

    Pre-eclampsia (PE) and intra-uterine growth restriction (IUGR) cause significant maternal and perinatal morbidity and mortality. Placental dysfunction is central to the development of both conditions. Although the pathophysiology of these conditions is unknown, there is common placental pathology with an increase in apoptotic cell death seen within the trophoblast. In addition, in pre-eclampsia, apoptotic fragments of syncytiotrophoblast have been detected

  12. Hypertension in pregnancy

    Microsoft Academic Search

    R. A. Duckett; L. Kenny; P. N. Baker

    2001-01-01

    Hypertension is associated with between 6–8% of pregnancies and has serious repercussions for both fetal and maternal well being. Hypertension may predate or develop during pregnancy. Pre-eclampsia, arguably the most important cause of hypertension in pregnancy, has a complex aetiology and pathophysiology. Pre-eclampsia is associated with a defect in placentation which may be secondary to abnormal genetic and immunological factors.

  13. The treatment of hypertension in pregnancy

    Microsoft Academic Search

    Bobby Krishnachetty; Felicity Plaat

    2011-01-01

    Hypertension is the commonest medical condition encountered in pregnancy and pre-eclampsia\\/eclampsia is the second leading cause of maternal mortality in the UK. The precise cause of pre-eclampsia is unknown but the pathophysiology involves abnormal placentation with an exaggerated inflammatory response causing a multisystem disorder. The very presence of rising blood pressure in a pregnant woman should alert the clinician to

  14. Intrauterine expression of parathyroid hormone-related protein in normal and pre-eclamptic pregnancies

    Microsoft Academic Search

    N. E. Curtis; R. G. King; J. M. Moseley; P. W. M. Ho; G. E. Rice; M. E. Wlodekd

    1998-01-01

    Maternal hypertension, vasoconstriction and placental insufficiency are features of pre-eclampsia. Alterations in calcium homeostasis and in the production of calciotropic hormones and vasoactive agents have also been described in association with pre-eclampsia. Parathyroid hormone-related protein (PTHrP) is abundantly expressed in intrauterine tissues during normal pregnancy and has roles in fetal growth and calcium homeostasis, placental calcium transport and vascular tone

  15. Placental Overexpression of Transforming Growth Factor-?3 in the HELLP Syndrome

    Microsoft Academic Search

    M. Emanuelli; S. R. Giannubilo; B. Landi; D. Sartini; F. Pierella; A. Corradetti; A. L. Tranquilli

    2008-01-01

    Objective: To evaluate the placental expression of transforming growth factor-?3 (TGF-?3) in patients with HELLP syndrome and pre-eclampsia compared to controls, and its correlation to Doppler velocimetry analysis of the utero-placental blood flow. Study Design: Real-time PCR analysis was performed, after cesarean section, in placental samples from 10 women affected by HELLP syndrome, 10 women with pre-eclampsia and 10 controls.

  16. Genomewide Oligonucleotide Microarray Analysis on Placentae of Pre-Eclamptic Pregnancies

    Microsoft Academic Search

    Rongrong Zhou; Qianyong Zhu; Yahui Wang; Yonghong Ren; Liang Zhang; Yuxiang Zhou

    2006-01-01

    Objective: Human placentae from normal and pre-eclamptic pregnancies were evaluated for possible changes in gene expression by microarray analysis to uncover new clues for the research of the etiology of pre-eclampsia. Methods: Placentae from five normal pregnancies and five pregnancies complicated by pre-eclampsia were collected. mRNA levels of five pre-eclamptic placentae were examined using genome-wide 70-mer oligonucleotide microarrays (CapitalBio, Beijing,

  17. 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

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

    PubMed Central

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

    2014-01-01

    Abstract 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. The hypertensive disorders of pregnancy (29.3).

    PubMed

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

    2015-07-01

    Hypertensive disorders are the most common medical complication of pregnancy. As such, a large part of antenatal care is dedicated to the detection of pre-eclampsia, the most dangerous of the hypertensive disorders. The highlights of this chapter include progress in the use of out-of-office blood pressure measurement as an adjunct to office blood pressure measurement, pre-eclampsia defined as proteinuria or relevant end-organ dysfunction, antihypertensive therapy for severe and non-severe hypertension and post-partum follow-up to mitigate the increased cardiovascular risk associated with any of the hypertensive disorders of pregnancy. PMID:26141795

  20. Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy.

    PubMed

    Cui, Yujie; Wang, Wei; Dong, Ningzheng; Lou, Jinglei; Srinivasan, Dinesh Kumar; Cheng, Weiwei; Huang, Xiaoyi; Liu, Meng; Fang, Chaodong; Peng, Jianhao; Chen, Shenghan; Wu, Shannon; Liu, Zhenzhen; Dong, Liang; Zhou, Yiqing; Wu, Qingyu

    2012-04-12

    In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia. PMID:22437503

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

    PubMed Central

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

    2014-01-01

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

  2. Nitrotyrosine Immunostaining Correlates with Increased Extracellular Matrix: Evidence of Postplacental Hypoxia

    Microsoft Academic Search

    J. Stanek; A. L. W. Eis; L. Myatt

    2001-01-01

    Nitrotyrosine residues (NT), an index of oxidative stress arising from peroxynitrite formation and action, are found in placental vasculature of pregnancies complicated by pre-eclampsia (PE) or pregestational insulin-dependent diabetes mellitus (IDDM). This study correlates conventional placental pathology with NT immunostaining in 20 cases of perinatal mortality (13 stillbirths and seven cases of neonatal mortality) associated with PE, IDDM, amniotic fluid

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

    PubMed

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

    2014-02-01

    Pre-eclampsia is a devastating multi system syndrome and a major cause of maternal, fetal, neonatal morbidity and mortality. Pre-eclampsia is associated with oxidative stress in the maternal circulation. To have an insight on the effect of pre-eclampsia/eclampsia on the neonates, the study was made to explore the oxidative status by quantification of byproducts generated during protein oxidation and oxidative DNA damage and deficient antioxidant activity in umbilical cord blood of pre-eclamptic/eclamptic mothers during fetal circulation. Umbilical cord blood during delivery from neonates born to 19 pre-eclamptic mothers, 14 eclamptic mothers and 18 normotensive mothers (uncomplicated pregnancy) as control cases was collected. 8-OHdG (8-hydroxy-2-deoxyguanosine), protein carbonyl, nitrite, catalase, non-enzymatic antioxidants (vitamin A, E, C), total antioxidant status and iron status were determined. Significant elevation in the levels of 8-OHdG, protein carbonyl, nitrite and iron along with decreased levels of catalase, vitamin A, E, C, total antioxidant status were observed in the umbilical cord blood of pre-eclamptic and eclamptic pregnancies. These parameters might be influential variables for the risk of free radical damage in infants born to pre-eclamptic/eclamptic pregnancies. Increased oxidative stress causes oxidation of DNA and protein which alters antioxidant function. Excess iron level and decreased unsaturated iron binding capacity may be the important factor associated with oxidative stress and contribute in the pathogenesis of pre-eclampsia/eclampsia which is reflected in fetal circulation. PMID:24296128

  4. Breathing during sleep: Studies related to upper airway calibre in pregnancy 

    E-print Network

    Izci, Bilgay

    2007-01-01

    in the nonpregnant women (p = 0.01) but similar in women with pre-eclampsia and pregnant women (p > 0.3). When seated, pregnant women had wider UAs than nonpregnant women (p < 0.02). There was a non-significant trend for pregnant women to have narrower airways than...

  5. Clinical details, cytogenic studies,and cellular physiology of a 69, XXX fetus, with comments on the biological effect of triploidy in man

    Microsoft Academic Search

    C M Gosden; M O Wright; W G Paterson; K A Grant

    1976-01-01

    A triploid fetus, 69, XXX, aborted spontaneously at 26 weeks' gestation. It had multiple abnormalities including syndactyly of the hands and feet single palmar creases, hypoplasia of the adrenals and ovaries, hypertrophy of thigh muscles, and abnormalities of the brain. The placenta was large and showed hydatidiform degeneration. The pregnancy had been complicated by acute dyspnoea, pre-eclampsia, and postpartum haemorrhage.

  6. Overview of randomised trials of diuretics in pregnancy

    Microsoft Academic Search

    R Collins; S Yusuf; R Peto

    1985-01-01

    Over the past 20 years at least 11 randomised trials of the prevention with diuretics of pre-eclampsia and its sequelae have been undertaken. Nine of these were reviewed. Reliable data from the remaining two were not available. The nine reviewed had investigated a total of nearly 7000 people. Significant evidence of prevention of \\

  7. Vitamin C as an antioxidant supplement in women's health: a myth in need of urgent burial

    Microsoft Academic Search

    Vikram Sinai Talaulikar; Isaac T. Manyonda

    2011-01-01

    Epidemiological data suggest that diets rich in antioxidants protect against diseases associated with free radical damage, including cancer, cardiovascular disease and diabetes. Early observations also suggested that vitamin supplements with antioxidant properties, like vitamins C and E, could also prevent or ameliorate pre-eclampsia, but most large randomized clinical trials have failed to show any benefit. Vitamin C given orally, even

  8. Mechanisms of renal damage owing to infection

    Microsoft Academic Search

    Timo Jahnukainen; Ming Chen; Gianni Celsi

    2005-01-01

    Urinary tract infection (UTI) is a common bacterial illness in children. It is known to be associated with an increased risk of permanent renal cell damage and scarring which may lead to generation of pathological conditions such as hypertension, pre-eclampsia during pregnancy, renal insufficiency, and end-stage kidney disease. The pathophysiology of renal scarring is still obscure, which makes the prevention

  9. Rho A\\/Rho kinase: human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction

    Microsoft Academic Search

    Anne M Friel; Donal J Sexton; Michael W O'Reilly; Terry J Smith; John J Morrison

    2006-01-01

    Pre eclampsia represents a state of increased or prolonged vasoconstriction, partially linked to the potent vasocontractile effect of isoprostanes. The process of Rho A-mediated calcium sensitisation is inherent to a state of prolonged contractility in many smooth muscle types. The aim of this study was (1) to investigate mRNA expression levels of Rho A and Rho kinase isoforms (I and

  10. Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a challenging clinical dilemma

    Microsoft Academic Search

    A. Mak; B. P. L. Chan; I. B. Yeh; R. C. M. Ho; M. L. Boey; P. H. Feng; D. R. Koh; B. K. C. Ong

    2008-01-01

    Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly recognized and reported in the literature. While the condition has been well described in patients with acute hypertension, pre-eclampsia, eclampsia, post-transplantation and chemotherapy, RPLS has been increasingly identified in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Though experience in the diagnosis and management of RPLS in patients with SLE

  11. Modern management of eclampsia

    Microsoft Academic Search

    Osama Salha; James J Walker

    1999-01-01

    Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains an important cause of maternal mortality and morbidity. Despite being recognised since antiquity, consistent management practices are still lacking. Given that the aim of good care is to prevent seizures, it is disappointing that in the majority of cases the first eclamptic convulsion occurs after admission to hospital. This

  12. Defective implantation and placentation: laying the blueprint for pregnancy complications

    Microsoft Academic Search

    Errol R Norwitz

    2006-01-01

    Normal implantation and placentation is critical for pregnancy success. Many pregnancy-related complications that present late in gestation (such as pre-eclampsia and preterm labour) appear to have their origins early in pregnancy with abnormalities in implantation and placental development. Implantation is characterized by invasion of the maternal tissues of the uterus by fetal trophoblast, and the degree to which trophoblast invades

  13. ‘Cor placentale’: placental intervillus\\/intravillus blood flow mismatch is the pathophysiological mechanism in severe intrauterine growth restriction due to uteroplacental disease

    Microsoft Academic Search

    N. J. Sebire; D. Talbert

    2001-01-01

    The underlying pathophysiology in most cases of severe intrauterine growth restriction and pre-eclampsia is thought to be abnormal and inadequate conversion of the branches of the uterine arteries into low resistance uteroplacental vessels, due to poor extravillous trophoblastic invasion, leading to reduced intervillous blood flow. Since, in most vascular beds the main site of flow resistance is at the level

  14. Evidence of Placental Translation Inhibition and Endoplasmic Reticulum Stress in the Etiology of Human Intrauterine Growth Restriction

    Microsoft Academic Search

    Hong-wa Yung; Stefania Calabrese; Debby Hynx; Brian A. Hemmings; Irene Cetin; D. Stephen Charnock-Jones; Graham J. Burton

    2008-01-01

    Unexplained intrauterine growth restriction of the fetus (IUGR) results from impaired placental develop- ment, frequently associated with maternal malperfu- sion. Some cases are complicated further by pre- eclampsia (PEIUGR). Here, we provide the first evidence that placental protein synthesis inhibition and endoplasmic reticulum (ER) stress play key roles in IUGR pathophysiology. Increased phosphorylation of eukaryotic initiation factor 2 suggests suppres-

  15. A novel in vitro co-culture system for the study of maternal decidual endothelial cell–trophoblast interactions in human pregnancy

    Microsoft Academic Search

    Eileen D. M. Gallery; Suzanne Campbell; Biljana Ilkovski; Michael J. Sinosich; Christopher Jackson

    2001-01-01

    Investigation of the pathophysiology of pre-eclampsia (characterised by insufficient invasion of the intrauterine vasculature by cytotrophoblasts) has been hampered by the absence of a suitable animal model, and ethical constraints in clinical studies. We have developed a novel in vitro human cell co-culture system allowing direct assessment of cytotrophoblast invasion of a decidual endothelial cell monolayer from the abluminal side,

  16. Review: The effects of oxygen on normal and pre-eclamptic placental tissue – insights from metabolomics

    Microsoft Academic Search

    A. E. P. Heazell; M. Brown; S. A. Worton; W. B. Dunn

    2011-01-01

    Placental dysfunction is central to many complications of human pregnancy including pre-eclampsia (PE), intra-uterine growth restriction (IUGR) and stillbirth. The precise molecular pathophysiology of placental dysfunction in these conditions is not known, although oxidative and nitrative stresses have been implicated. Metabolites are low molecular weight chemicals which play an important role in biological function, primarily through metabolism and regulation of

  17. Hypertension in pregnancy

    Microsoft Academic Search

    Richard Hayman

    2004-01-01

    A diagnosis of hypertension may be made in 5–8% of all pregnancies. Pre-eclampsia, a disease associated with defective placentation, is arguably the most important cause of maternal and fetal morbidity and mortality associated with a rise in maternal blood pressure. This clinical syndrome has a complex aetiology and pathophysiology, and is possibly the result of an as yet unidentified circulating

  18. Formation of Syncytial Knots is Increased by Hyperoxia, Hypoxia and Reactive Oxygen Species

    Microsoft Academic Search

    A. E. P. Heazell; S. J. Moll; C. J. P. Jones; P. N. Baker; I. P. Crocker

    2007-01-01

    The syncytiotrophoblast contains aggregates of nuclei termed syncytial knots. Increased numbers of syncytial knots have been reported in placentae of pregnancies complicated by pre-eclampsia and fetal growth restriction (FGR). As oxidative stress has been implicated in the pathophysiology of these disorders, we hypothesised that the formation of syncytial knots may be induced by exposure to hypoxia, hyperoxia or reactive oxygen

  19. Circulating biomarkers of oxidative stress in complicated pregnancies

    Microsoft Academic Search

    Hilmi Orhan; Lütfü Önderoglu; Aykan Yücel; Gönül Sahin

    2003-01-01

    Increased lipid peroxidation (LPO) and reduced antioxidant activity may contribute to the development of complications in pregnancy. The present study discusses the possibility of LPO and antioxidant activity in both maternal and umbilical cord blood as an indicator of oxygen radical activity. For this aim, pregnancies with hypertension and pre-eclampsia, diabetes mellitus (insulin dependent diabetes mellitus and gestational diabetes mellitus),

  20. Classification of hypertension in pregnancy

    Microsoft Academic Search

    Mark A. Brown; Michael de Swiet

    1999-01-01

    In many ways there should be no need to classify hypertensive disorders in clinical practice. The very presence of rising blood pressure should alert the clinician to seek evidence for the development of pre-eclampsia and whether there are any emerging abnormalities of fetal growth and\\/or maternal renal, cerebral, hepatic or coagulation functions which may necessitate specific treatment, including delivery. While

  1. Defective implantation and placentation: laying the blueprint for pregnancy complications

    Microsoft Academic Search

    Errol R Norwitz

    2007-01-01

    Normal implantation and placentation is critical for pregnancy success. Many pregnancy-related complications that present late in gestation (such as pre-eclampsia and preterm labour) appear to have their origins early in pregnancy with abnormalities in implantation and placental development. Implantation is characterized by invasion of the maternal tissues of the uterus by fetal trophoblast, and the degree to which trophoblast invades

  2. Gestational vascular complications

    Microsoft Academic Search

    Arnon Samueloff

    2003-01-01

    Severe pregnancy complications, primarily severe pre-eclampsia, placental abruption, intrauterine growth restriction (IUGR) and intrauterine fetal death (IUFD) occur in about 1–5% of gestations. This rate is even higher in special medical situations. These pregnancy complications have been shown to increase maternal and fetal morbidity and mortality considerably. Severe pregnancy complications have also been shown to be associated with deficient uteroplacental

  3. The Human First Trimester Gestational Sac Limits Rather than Facilitates Oxygen Transfer to the Foetus—A Review

    Microsoft Academic Search

    E. Jauniaux; B. Gulbis; G. J. Burton

    2003-01-01

    Oxygen (O2) free radicals are a potential teratologic threat to the foetal tissues and are known to be involved in the pathophysiology of common human pregnancy disorders such as miscarriage and pre-eclampsia. During the first two months of human gestation, the placenta surrounds the whole gestational sac, the villi contain only a few capillaries located mainly within the centre of

  4. Vascular endothelial growth factor, epidermal growth factor and fibroblast growth factor-4 and -10 stimulate trophoblast plasminogen activator system and metalloproteinase-9

    Microsoft Academic Search

    E. Y. Anteby; C. Greenfield; S. Natanson-Yaron; D. Goldman-Wohl; Y. Hamani; V. Khudyak; I. Ariel; S. Yagel

    2004-01-01

    Trophoblast invasion, accompanied by degradation of extracellular matrix, is crucial to normal pregnancy development, whereas shallow placental invasion and implantation likely plays a role in the subsequent development of pre-eclampsia. The growth factors vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and fibroblast growth factor (FGF) are placental growth factors that activate degradation of extracellular matrix. We determined the

  5. Gestational diabetes: what’s new?

    Microsoft Academic Search

    Helen R Murphy

    There is consensus that maternal hyperglycaemia is associated with increased risk of adverse perinatal outcome, in particular caesarean section delivery, infant birth weight that is large for gestational age, increased infant fat mass, pre-eclampsia and premature delivery. However, there is widespread controversy and lack of uniformity regarding the classification, diagnosis and treatment of specific levels of hyperglycaemia during pregnancy. This

  6. Obstetric outcome in women with polycystic ovarian syndrome

    Microsoft Academic Search

    A. Tiitinen; V. Hiilesmaa; M. Halttunen; L. Suhonen

    2001-01-01

    Women with polycystic ovarian syndrome (PCOS) often have insulin resistance and hyperinsulinaemia and may therefore be at an increased risk for gestational diabetes mellitus (GDM). Hyperinsulinaemia may also be associated with pre-eclampsia. Information concerning outcome of pregnancies in PCOS women is scanty and somewhat controversial. Therefore, 99 pregnancies were retrospectively evaluated in women with PCOS and the findings were compared

  7. Extracellular control of TGF? signalling in vascular development and disease

    Microsoft Academic Search

    Peter ten Dijke; Helen M. Arthur

    2007-01-01

    The intracellular mechanism of transforming growth factor-? (TGF?) signalling via kinase receptors and SMAD effectors is firmly established, but recent studies of human cardiovascular syndromes such as Marfan syndrome and pre-eclampsia have refocused attention on the importance of regulating the availability of active extracellular TGF?. It seems that elastic extracellular matrix (ECM) components have a crucial role in controlling TGF?

  8. Multiple concomitant cranial nerve palsies secondary to preeclampsia.

    PubMed

    Gilca, Marina; Luneau, Katie

    2015-06-01

    A 32-year-old primigravid woman developed pre-eclampsia after delivery of twins along with left fifth, sixth, and seventh cranial neuropathies. She also had evidence of hepatic and renal involvement. Results of patient evaluation were otherwise unremarkable, and the palsies completely resolved over 3 months after treatment with valacyclovir and systemic corticosteroids. PMID:25768245

  9. Linkage Disequilibrium Between Human Leukocyte Antigen (HLA) Class II and HLA-G—Possible Implications for Human Reproduction and Autoimmune Disease

    Microsoft Academic Search

    Thomas Vauvert F. Hviid; Ole B. Christiansen

    2005-01-01

    A line of investigation indicates that one or several genes in the human major histocompatibility complex (MHC) influences reproductive success. Studies have revealed associations between human leukocyte antigen (HLA) class II genes and risk of recurrent spontaneous abortion (RSA) and pre-eclampsia. However, these genes are not expressed at the feto-maternal interface. Furthermore, associations between polymorphisms in the nonclassical HLA class

  10. Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes

    Microsoft Academic Search

    Leon Bernal-Mizrachi; Wenche Jy; Christian Fierro; Rick Macdonough; Hermes A. Velazques; Joshua Purow; Joaquin J. Jimenez; Lawrence L. Horstman; Alexandre Ferreira; Eduardo de Marchena; Yeon S. Ahn

    2004-01-01

    Background: Endothelial Microparticles (EMP) are small fragments of endothelial cell membrane shed during apoptosis or activation. Our group has previously reported elevations of EMP in patients with coronary artery disease (CAD), thrombotic thrombocytopenic purpura (TTP), pre-eclampsia, multiple sclerosis (MS), and severe hypertension (HTN). In the present study, we evaluate the possible relationship between EMP levels and the angiographic severity and

  11. [Hypertension in pregnancy].

    PubMed

    Lunati, Fabio; Dugnani, Maurizio; Campanini, Mauro

    2008-09-01

    In literature, there is not an unanimous agreement on the definition of hypertension in pregnancy. The most severe complications are pre-eclampsia and eclampsia which need an early diagnosis to be avoided. The problem of therapy is discussed: there is no evidence about the positive effect of a pharmacological treatment on the maternal and/or fetal clinical outcomes. In case of blood pressure < 180/110 mmHg, the alpha metil dopa is the first choice drug. Among calcium-antagonist drugs, the efficacy of nifedipine is proved; and in the pre-eclampsia, metil dopa, beta blockers and idralazine. Many questions are anyway still unsolved needing more studies. PMID:19044251

  12. [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

  13. The fgl2 prothrombinase\\/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction

    Microsoft Academic Search

    David A. Clark; Katharina Foerster; Laisum Fung; Wei He; Lydia Lee; Michael Mendicino; Udo R. Markert; Reginald M. Gorczynski; Philip A. Marsden; Gary A. Levy

    2004-01-01

    Increased fgl2 prothrombinase activity in maternal decidua and fetal trophoblasts may trigger abortions by proinflammatory cytokines induced by bacterial lipopolysaccharide (LPS) in mice and is implicated in human recurrent miscarriages and pre- eclampsia. Defining the physiological and pathological role of the fgl2\\/fibroleukin gene required an fgl2-knockout mouse and data on normal pattern of fgl2 expression during pregnancy. Expression of fgl2

  14. Effects of smoking during pregnancy

    Microsoft Academic Search

    Anne Castles; E. Kathleen Adams; Cathy L Melvin; Christopher Kelsch; Matthew L Boulton

    1999-01-01

    Background:The purpose of this study was to estimate, using meta-analysis, pooled odds ratios for the effects of smoking on five pregnancy complications: placenta previa, abruptio placenta, ectopic pregnancy, preterm premature rupture of the membrane (PPROM), and pre-eclampsia.Methods:Published articles were identified through computer search and literature review. Five criteria were applied to those studies initially identified to determine those eligible for

  15. Matrix-metalloproteinase Activity in First Trimester Placental Bed Biopsies in Further Complicated and Uncomplicated Pregnancies

    Microsoft Academic Search

    M. A. Huisman; A. Timmer; M. Zeinstra; E. K. Serlier; R. Hanemaaijer; H. v. Goor; J. J. H. M. Erwich

    2004-01-01

    Trophoblast invasion is partly regulated by matrix-metalloproteinases (MMPs). Aberrations in MMP-activity in early pregnancy are thought to play a role in the pathophysiology of pregnancy associated conditions like pre-eclampsia and intra-uterine growth restriction (IUGR). A direct relation however, has not been published. We tested the hypothesis that MMP activity in the decidua is compromised in the first trimester of pregnancies,

  16. Regulation of insulin-like growth factor-binding protein-3 ternary complex formation in pregnancy

    Microsoft Academic Search

    M S Lewitt; F P Scott; N M Clarke; T Wu; M J Sinosich; R C Baxter

    1998-01-01

    The IGFs are believed to be important in pregnancy and are implicated in the pathophysiology of pre-eclampsia. In adults the IGFs circulate primarily with IGF-binding protein-3 (IGFBP-3) and an acid-labile glycoprotein (ALS) in a 140 kDa complex which limits IGF bioavail- ability. Less than 10% of IGFBP-3 is in lower molecular weight forms. We have investigated the developmental regulation of

  17. Correlation between Soluble Endoglin, Vascular Endothelial Growth Factor Receptor1, and Adipocytokines in Preeclampsia

    Microsoft Academic Search

    Hisashi Masuyama; Hideki Nakatsukasa; Norio Takamoto; Yuji Hiramatsu

    Context: Recent reports have demonstrated that soluble endoglin (sEng), an antiangiogenic protein thought to impair TGF- binding to receptors, and soluble vascular endothelial growth factor receptor (sVEGFR)-1 play important roles in the pathophysiology of pre- eclampsia (PE). Moreover, insulin resistance, which is greatly influ- enced by adipocytokines, characterizes PE. Objectives: We examined possible links between sEng, VEGF, sVEGFR, and adipocytokines

  18. Oxidative DNA damage in placentas from normal and pre-eclamptic pregnancies

    Microsoft Academic Search

    Henryk Wiktor; Marta Kankofer; Ivo Schmerold; Agnes Dadak; Maciej Lopucki; Hans Niedermüller

    2004-01-01

    Placental oxidative stress was suggested to play a role in the pathogenesis of pre-eclampsia (PE). In this study, levels of 8-hydroxy-2?-deoxyguanosine (8-OH-dG), a well-established marker of oxidative DNA damage, were analysed in placental cellular DNA from normal (group NP) and pre-eclamptic (group PE) pregnancies as well as from PE pregnancies complicated by intrauterine growth restriction (group PE-IUGR). Placental samples obtained

  19. Possible involvement of inositol phosphoglycan-P in human parturition

    Microsoft Academic Search

    M. A. Paine; C. H. Rodeck; P. J. Williams; T. W. Rademacher

    2003-01-01

    Preterm labour is a major cause of neonatal morbidity and mortality but the pathophysiology that underlies preterm labour is unknown. Inositolphosphoglycans (IPGs) comprise a ubiquitous family of putative carbohydrate second messengers and they have been linked to the pathogenesis of various conditions, including diabetes and pre-eclampsia. Studying IPG-P levels in normal and pre-eclamptic pregnancies, we noticed a constant rise of

  20. Maternal Caffeine Intake, Blood Pressure, and the Risk of Hypertensive Complications During Pregnancy. The Generation R Study

    Microsoft Academic Search

    Rachel Bakker; Eric A. P. Steegers; Hein Raat; Albert Hofman; Vincent W. V. Jaddoe

    2011-01-01

    BackgroundCaffeine intake has been suggested to be associated with the risk of hypertension. Less is known about the associations of caffeine intake on maternal cardiovascular adaptations during pregnancy. We examined the associations of caffeine intake in different trimesters of pregnancy with repeatedly measured blood pressure and the risks of pregnancy-induced hypertension and pre-eclampsia in a population-based cohort of 7,890 pregnant

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

    Microsoft Academic Search

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

    2012-01-01

    The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is

  2. Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage\\/dysfunction and activation in pregnancy induced hypertension

    Microsoft Academic Search

    Sunil K Nadar; Eman Al Yemeni; Andrew D Blann; Gregory Y. H Lip

    2004-01-01

    Objective: Endothelial disturbance (whether activation, dysfunction or damage) is a likely pathogenic mechanism in pre-eclampsia and pregnancy-induced hypertension (PIH). We set out to determine which of three plasma markers of endothelial disturbance, indicating endothelial activation (E-selectin) or damage\\/dysfunction (von Willebrand factor (vWf), soluble thrombomodulin), would provide the best discriminator of PIH compared to normotensive pregnancy. Study design: Cross-sectional study of

  3. Increased biological oxidation and reduced anti-oxidant enzyme activity in pre-eclamptic placentae

    Microsoft Academic Search

    J. Vanderlelie; K. Venardos; V. L. Clifton; N. M. Gude; F. M. Clarke; A. V. Perkins

    2005-01-01

    Oxidative stress occurs when cellular levels of reactive oxygen species exceed anti-oxidant capabilities and has been implicated in the pathogenesis of pre-eclampsia. In this study we have examined the tissue levels of endogenous anti-oxidant proteins (superoxide dismutase, glutathione peroxidase, thioredoxin reductase and thioredoxin) and the level of lipid and protein oxidation in placental samples from normal and pre-eclamptic pregnancies. Pre-eclamptic

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

    Microsoft Academic Search

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

    1984-01-01

    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

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

    Microsoft Academic Search

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

    2011-01-01

    This 2006 study investigated ethnicity-related factors contributing to sub-standard maternity care and the effects on severe maternal morbidity among immigrant women in the Netherlands. In-depth interviews were carried out with 40 immigrant and 10 native Dutch women. The immigrant women reported that health care providers often paid insufficient attention to their pregnancy-related complaints, especially in cases of pre-eclampsia. They also

  6. Capgras' syndrome with organic disorders.

    PubMed Central

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

    1990-01-01

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

  7. Primary versus secondary antiphospholipid syndrome: Is this lupus or not?

    Microsoft Academic Search

    Jennifer M. Grossman

    2004-01-01

    Antiphospholipid syndrome is a hypercoaguable state characterized by recurrent venous and\\/or arterial thrombosis and\\/or pregnancy\\u000a complications of fetal loss, pre-eclampsia, or eclampsia in the presence of antiphospholipid antibodies. It was first described\\u000a in the setting of systemic lupus erythematosus and subsequently recognized to also exist as an independent condition and in\\u000a conjunction with a variety of other autoimmune, infectious, and

  8. Localization of Indoleamine 2,3Dioxygenase and 4-Hydroxynonenal in Normal and Pre-eclamptic Placentae

    Microsoft Academic Search

    D. I. S. Santoso; P. Rogers; E. M. Wallace; U. Manuelpillai; D. Walker; Sri Bekti Subakir

    2002-01-01

    This study was undertaken to compare placental levels of 2,3-Dioxygenase (IDO), a free radical scavenger, and 4-Hydroxynonenal (4-HNE), a major by-product of lipid peroxidation, in normal and pre-eclamptic pregnancies. Placentae were collected at caesarean section from women with a term, normal singleton pregnancy (37–40 weeks' gestation, n=10) and women with a term singleton pregnancy complicated by pre-eclampsia (n=10). IDO and

  9. Confidential enquiry into maternal deaths in The Netherlands 1983–1992

    Microsoft Academic Search

    Nico Schuitemaker; Jos van Roosmalen; Guus Dekker; Pieter van Dongen; Herman van Geijn; Jack Bennebroek Gravenhorst

    1998-01-01

    Objective: To determine the causes of maternal death in The Netherlands. Study design: Nationwide Confidential Enquiry into the Causes of Maternal Deaths during the period 1983–1992. Results: Of 192 direct and indirect maternal deaths, 154 (80%) were available for the Enquiry. The most frequent direct causes were (pre-)eclampsia, thrombo-embolism, obstetrical haemorrhage and sepsis. Cerebro- and cardiovascular disorders were the most

  10. Diagnosis of gestational diabetes: falling through the net

    E-print Network

    Meek, Claire L.; Lewis, Hannah B.; Patient, Charlotte; Murphy, Helen R.; Simmons, David

    2015-06-14

    . This article is published with open access at Springerlink.com Abstract Aims/hypothesis Gestational diabetesmellitus (GDM) is asso- ciated with increased risks to mother and child, but globally agreed diagnostic criteria remain elusive. Identification of women... or recog- nition in pregnancy [1, 2], is increasing in incidence in many populations worldwide as obesity becomes more prevalent [3]. Untreated GDM results in poor maternal and fetal out- comes: women with GDM are more likely to suffer pre- eclampsia...

  11. Extreme Hypertension, Eclampsia and Critical Care Seizures

    Microsoft Academic Search

    Errol Gordon; Michel T. Torbey

    \\u000a The association between seizures and blood pressure elevation remains a common medical emergency encountered in an ICU setting.\\u000a Syndromes such as pre-eclampsia or eclampsia, hypertensive encephalopathy, and posterior leukoencephalopathy commonly present\\u000a with seizures. The primary treatment goal is to reduce the arterial blood pressure. In most cases seizure control is thus\\u000a achieved, but unique medications, such as magnesium sulfate, may

  12. Pregnancy-induced hypertension and hyaline membrane disease

    Microsoft Academic Search

    M. A. Carvalho; A. Faúndes; L. C. Santos

    1997-01-01

    Objectives: (1) To determine whether the incidence of hyaline membrane disease (HMD) is different among premature babies of pre-eclamptic women and those of normotensive controls; (2) to determine the relative risk (RR) of HMD according to the severity of pre-eclampsia and gestational age. Methods: A retrospective and prospective cohort of 271 pre-eclamptic women and 271 normotensive controls, with gestational age

  13. Upregulation of Neutrophil Surface Adhesion Molecules in Infants of Pre-eclamptic Women

    Microsoft Academic Search

    Hemant Saini; Bhagya L Puppala; Denise Angst; Alice Gilman-Sachs; Michael Costello

    2004-01-01

    OBJECTIVE: To evaluate evidence of neutrophil activation in infants born to pre-eclamptic women and examine any association between degree of neutrophil activation and severity of pre-eclampsia.DESIGN: This study utilized quantitative flow cytometry to determine whether the expression of surface adhesion molecules: CD18, CD11a, CD11b, and CD11c on cord blood neutrophils using mean channel fluorescence values (MCF). A total of 20

  14. Platelet parameters in healthy and pathological pregnancy.

    PubMed

    Maconi, Mariacaterina; Cardaropoli, Simona; Cenci, A M

    2012-01-01

    Changes in platelet count (PLT) are very important during pregnancy. Many platelet disorders occur during pregnancy and a reduction in PLT is the most common hemostasis abnormality identified, and this has important implications for mother and foetus. Many of these disorders share clinical and laboratory features, making accurate diagnosis difficult. The aim of this study was to establish reference intervals of platelet parameters for some of the more important pathologies associated to pregnancy (pre-eclampsia, gestational diabetes, autoimmune disorders, viral infections) using the automated hematology analyzer Sysmex XE-2100 and to evaluate the difference between healthy and pathological pregnancy. We enrolled in our study 100 pregnant women in the third trimester of pregnancy. The parameters analyzed included PLT, platelet distribution width, and mean platelet volume (MPV). We found statistically significant difference in PLT in pre-eclampsia, autoimmune disorders, and viral infections. Our results demonstrated also a statistically significant difference in MPV in pre-eclampsia and gestational diabetes. Our results allow the clinicians to detect hematologic change by simple complete blood count useful for the management of the pathological pregnancies. In conclusion, the overall picture of platelet disorders is extremely variegated, leading to numerous diagnostic and therapeutic problems whose solutions require close collaboration between clinicians and laboratory specialists. PMID:24833533

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

    PubMed Central

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

    2015-01-01

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

  16. The visually-evoked cerebral blood flow response in women with a recent history of preeclampsia and/or eclampsia.

    PubMed

    Martens, E G H J; Peeters, L L H; Gommer, E D; Mess, W H; van de Vosse, F N; Passos, V Lima; Reulen, J P H

    2009-01-01

    Several studies provide evidence for altered cerebral hemodynamics during (pre)eclampsia. Whether (pre)eclampsia has a persistent negative impact on cerebral hemodynamics, possibly contributing to an elevated risk of premature stroke, is unknown. The aims of this study were (i) to refine and apply a control system-based method previously introduced by Rosengarten to quantify the visually-evoked blood flow response of the posterior cerebral artery (PCA); and (ii) to test the hypothesis with this method that cerebral hemodynamics in women with a recent history of (pre)eclampsia is abnormal relative to that in parous controls. Hereto, we recorded cerebral blood flow velocity (CBFV) in the PCA by transcranial Doppler (TCD) sonography during cyclic visual stimulation in 15 former preeclamptics, 13 former eclamptics and 13 controls. The typical CBFV response was fitted with the step response of a second-order-linear model enabling quantification by parameters K (gain), zeta (damping), omega (natural frequency), T(v) (rate time) and T(d) (time delay). The method refinement introduced here consisted of response filtering before quantification and of considering the individual instead of group-averaged response patterns. Application of this refinement reduced the fitting errors (1.4 +/- 1.2 vs. 3.2 +/- 1.8, p < 0.01). Intergroup differences in model parameters were not found. Although statistically not significant, a trend was observed that critical damping (zeta>1) occurred more frequently in the combined group of former patients than in the controls (7 of 28 vs.1 of 13, p = 0.16). Critical damping (zeta>1) reflects an abnormal response, which is either compensated for by a rise in rate time ("intermediate"; zeta>1; T(v) > 20) or remains uncompensated ("sluggish"; zeta>1; T(v) < 20). Critical damping increased significantly (p = 0.039) with (pre-)eclampsia-to-test-interval in the PE+E patients with abnormal responses (zeta>1), suggesting that (pre)eclampsia might induce diminishing cerebral hemodynamic function over time. Based on a system-analytical classification approach, the data of this study provide evidence for individual CBFV responses to be abnormal in former (pre)eclamptics compared with controls. Further study is needed to reveal how the abnormal CBFV response classification reflects cerebrovascular dysfunction. PMID:18845379

  17. Inflammatory Bowel Disease and Risk of Adverse Pregnancy Outcomes

    PubMed Central

    Boyd, Heather A.; Basit, Saima; Harpsøe, 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, Crohn’s 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

  18. Low levels of plasma protein S, protein C and coagulation factor XII during early pregnancy and adverse pregnancy outcome.

    PubMed

    Ebina, Y; Ieko, M; Naito, S; Kobashi, G; Deguchi, M; Minakami, H; Atsumi, T; Yamada, H

    2015-06-30

    It was the study objective to evaluate whether low levels of plasma protein S (PS) activity, free PS, protein C (PC) activity and coagulation factor XII (FXII) during early pregnancy are related to adverse pregnancy outcomes. Peripheral blood samples were obtained at 8-14 gestational weeks (GW) from a consecutive series of 1,220 women. The levels of plasma PS activity, free PS, PC activity, and FXII were measured. Cut-off values were defined as pre-eclampsia. FXII level of pre-eclampsia. In conclusion, women with low levels of plasma PS activity and free PS during early pregnancy might have increased risks of PIH, severe PIH or pre-eclampsia. Women with low FXII level might have an increased risk of PD at

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

    PubMed Central

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

    2007-01-01

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

  20. Role of antenatal care in toxemia of pregnancy in alexandria.

    PubMed

    Mohamed, Aida M; Kishk, Nahla A; Shokeir, Nagwa F; Kassem, Mohamed S

    2006-01-01

    Pre-eclampsia and eclampsia remain one of the major obstetrical problems in less developed countries. Proper antenatal care (ANC) with regular measurement of blood pressure remains the mainstay of screening for hypertension in pregnancy. The aim of the current study was to identify frequency and characteristics of women with toxemia of pregnancy, assess both the quantitative and qualitative adequacy of antenatal care among cases with toxemia of pregnancy and to evaluate the effect of antenatal care on maternal and perinatal outcome. A cross-sectional case series study design was utilized .The study population was all cases, with confirmed diagnosis of toxemia of pregnancy who were admitted to El-Shatby University hospital during the period from January to May 2005. A structured interviewing schedule was used to collect data on characteristics of cases, maternal and fetal outcome. Site, adequacy and quality of received antenatal care were assessed. Out of total cases (336), 14.29% were diagnosed as mild pre-eclampsia, 83.31% were found to have severe pre-eclampsia while 2.40% were suffering from eclampsia. The severity of the condition was significantly associated with older maternal age, multiple pregnancy, primigravity, nulliparity, low socioeconomic conditions, husband's smoking and excessive caffeine consumption. Three-quarters of eclampsia cases (75.0%) didn't receive antenatal care and 60.0% of severe pre-eclamptics received inadequate antenatal care. The mean percent score of quality care domains of antenatal care content for mild pre-eclamptics was 75.62 +/- 13.80%. This was significantly higher than that for those of severe (59.96 +/- 27.95%) or for eclampsia cases (48.75 +/- 20.04%) where X(2) of Kruskal-Wallis=8.316 (P<0.001). Adverse maternal and fetal outcome occurred in 79.4% of women and 72.3% of babies for those who received poor quality ANC. In conclusion, the complications of pre-eclampsia and eclampsia could be prevented by wide spread use of adequate antenatal care, education and training of primary medical care personnel, prompt diagnosis of high risk patients and timely referral to higher level health care. PMID:17382081

  1. 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

  2. Endothelin1 and leptin as markers of intrauterine growth restriction

    Microsoft Academic Search

    Mohamed Al-Shahat Nezar; Azza Mohammad Abd El-Baky; Othman Al-Said Soliman; Hesham Al-Said Abdel-Hady; Ayman Mohammad Hammad; Mohammad Saleh Al-Haggar

    2009-01-01

    Objective  To explore the role of endothelin-1 (ET-1) and leptin in intrauterine growth restriction (IUGR) among preeclamptic and non-pre-eclamptic\\u000a women.\\u000a \\u000a \\u000a \\u000a Methods  Forty three patients with a pregnancy complicated by IUGR, 23 cases with severe pre-eclampsia and 20 cases of non-pre-eclamptic\\u000a were enrolled. Control group comprised 15 cases with uncomplicated pregnancy. Blood samples from umbilical artery and maternal\\u000a venous blood were collected at

  3. Prevention of stillbirth

    E-print Network

    Smith, Gordon C. S.

    2015-01-01

    interventions The use of low dose aspirin in women deemed to be at high risk of pre-eclampsia has been shown to be associated with a modest reduction in the risk of stillbirth.4 Otherwise, there are no antenatal interventions which have been shown... to be effective. The meta-analysis of RCTs of aspirin does show that the intervention is not significantly associated with complications. Hence, it is reasonable to consider use of aspirin in women deemed to be at high risk. A recent RCT, the paper reporting...

  4. Purinergic signalling in the reproductive system in health and disease.

    PubMed

    Burnstock, Geoffrey

    2014-03-01

    There are multiple roles for purinergic signalling in both male and female reproductive organs. ATP, released as a cotransmitter with noradrenaline from sympathetic nerves, contracts smooth muscle via P2X1 receptors in vas deferens, seminal vesicles, prostate and uterus, as well as in blood vessels. Male infertility occurs in P2X1 receptor knockout mice. Both short- and long-term trophic purinergic signalling occurs in reproductive organs. Purinergic signalling is involved in hormone secretion, penile erection, sperm motility and capacitation, and mucous production. Changes in purinoceptor expression occur in pathophysiological conditions, including pre-eclampsia, cancer and pain. PMID:24271059

  5. Quantifying the causal strength of multivariate cardiovascular couplings with momentary information transfer.

    PubMed

    Runge, Jakob; Riedl, Maik; Müller, Andreas; Stepan, Holger; Kurths, Jürgen; Wessel, Niels

    2015-04-01

    This article studies a recently introduced information-theoretic approach to detect and quantify the causal couplings in a complex cardiovascular system. In the first step a causal algorithm detects the coupling delays and in the second step the causal strength of each coupling mechanism is quantified using the recently introduced momentary information transfer. As an example, the method is applied to time series of respiration, systolic and diastolic blood pressure, and heart rate of pregnant healthy women and women suffering from pre-eclampsia. A possible explanation for the influence of heart rate on systolic blood pressure is found and some differences between healthy women and patients are discussed. PMID:25799083

  6. [Periodontal diseases--a review on the association between maternal periodontitis and adverse pregnancy outcome].

    PubMed

    Manegold-Brauer, G; Hoesli, I; Brauer, H U; Beikler, T

    2014-12-01

    Several prospective clinical trials have indicated an association between maternal periodontal status and adverse pregnancy outcome, e.g., low birth weight, pre-term birth and pre-eclampsia. However, the translation of these findings into clinical care and decision making is still a matter of debate. Gynecologists and obstetricians are usually not very familiar with periodontal diseases and do not always consider this pathology in routine preconception counselling. This article outlines the clinical pictures of the most common periodontal diseases and thus helps the gynecologists to identify patients with periodontal diseases. PMID:25518830

  7. ENDOCRINOLOGY IN PREGNANCY: Influence of maternal vitamin D status on obstetric outcomes and the fetal skeleton.

    PubMed

    Moon, Rebecca J; Harvey, Nicholas C; Cooper, Cyrus

    2015-08-01

    Vitamin D status has been increasingly associated with wide-ranging clinical outcomes. There is now a wealth of observational studies reporting on its associations with obstetric complications, including pre-eclampsia, gestational diabetes and the mode and timing of delivery. The findings are inconsistent, and currently there is a lack of data from high-quality intervention studies to confirm a causal role for vitamin D in these outcomes. This is similarly true with regards to fetal development, including measures of fetal size and skeletal mineralisation. Overall, there is an indication of possible benefits of vitamin D supplementation during pregnancy for offspring birthweight, calcium concentrations and bone mass as well as for reduced maternal pre-eclampsia. However, for none of these outcomes is the current evidence base conclusive, and the available data justify the instatement of high-quality randomised placebo controlled trials in a range of populations and health care settings to establish the potential efficacy and safety of vitamin D supplementation to improve particular outcomes. PMID:25862787

  8. 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

  9. Circulating Angiogenic Factors in Gestational Proteinuria without Hypertension

    PubMed Central

    Holston, Alexander M.; Qian, Cong; F.Yu, Kai; H.Epstein, Franklin; Karumanchi, S. Ananth; Levine, Richard J.

    2009-01-01

    Objectives Our goal was to determine whether obstetrical outcomes and serum angiogenic factors are altered in women with gestational proteinuria without hypertension. Methods We performed a nested case-control study of 108 women with gestational proteinuria, comparing them to 1564 randomly selected normotensive women without proteinuria during pregnancy (controls) and to 319 women who developed pre-eclampsia. Results Women with gestational proteinuria had greater body-mass index and higher blood pressure at study enrollment. Adverse obstetrical outcomes were infrequent. Levels of PlGF were lower than controls beginning early in gestation. Compared to gestational-age matched controls, PlGF was reduced beginning 6 to 8 weeks before proteinuria. Although sFlt-1 and soluble endoglin concentrations were elevated 1 to 2 weeks before proteinuria, these elevations were modest and transient. After onset of proteinuria, angiogenic factor levels generally did not differ significantly from controls. Conclusion Gestational proteinuria in healthy nulliparous women appears to be a mild variant of pre-eclampsia. PMID:19168169

  10. Effects of low oxygen levels on the expression and function of transporter OCTN2 in BeWo cells.

    PubMed

    Rytting, Erik; Audus, Kenneth L

    2007-08-01

    Although hypoxia is normal in early pregnancy, low placental oxygen concentrations later in pregnancy are often linked to complications such as pre-eclampsia and intrauterine growth restriction. The effects of low oxygen levels on drug and nutrient uptake via the organic cation transporter OCTN2 has been studied in BeWo cells, an in-vitro model of human trophoblast. BeWo cells were cultured under 20% (control) or 2% O(2) (hypoxia) for 48 h before each experiment. In-vitro hypoxia was also simulated by the addition of CoCl(2) to the cell culture medium. RT-PCR indicated increased transcription of OCTN2 in BeWo cells cultured under hypoxia, but Western blots did not show a corresponding increase in the amount of OCTN2 protein in the hypoxic cells compared with control. Hypoxia resulted in significant reductions in OCTN2-mediated carnitine uptake. Decreased placental transport of carnitine may lead to symptoms of carnitine deficiency in infants from hypoxic pregnancies, whether caused by high altitude, pre-eclampsia or other factors. The OCTN1 substrate ergothioneine reversed the effects of hypoxia on carnitine transport, but identical concentrations of N-acetylcysteine, another water-soluble intracellular antioxidant, did not have the same effect. PMID:17725851

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

    PubMed

    An, Li-Bin; Li, Wen-Tao; Xie, Tie-Nan; Peng, Xin; Li, Bo; Xie, Shu-Hong; Xu, Jing; Zhou, Xiao-Hua; Guo, Shao-Ning

    2015-05-01

    Hypertensive disorders of pregnancy are closely related to maternal mortality and morbidity. Calcium supplementation during pregnancy seems to reduce the risk of hypertensive disorders. No systematic review on multicentre RCTs of calcium supplementation during pregnancy has been published. The purpose of this study was to report a quantitative systematic review of the effectiveness of calcium supplementation during pregnancy on reducing the risk of hypertensive disorders of pregnancy and related problems. Publications over the years of 1991-2012 were searched through PubMed, Science Direct, EMBASE, CINAHL and Web of Science. The literatures were selected of the multicentre RCTs on calcium supplementation during pregnancy in prevention of hypertensive disorders and related problems. Reference lists from the studies were also examined for additional references. Studies were critically appraised by three independent reviewers, and the Cochrane Handbook was used to assess the quality of those included trials. Four studies were included in this systematic review. All included studies were high quality, with low risk of bias. There was an observed risk reduction in hypertension in calcium group. However, there was no reduction in the risk of severe gestational hypertension, pre-eclampsia, severe pre-eclampsia, preterm birth and low birthweight. Calcium supplementation appears to reduce the risk of hypertension in pregnancy. PMID:26125571

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

    PubMed

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

    2011-01-01

    Hypertensive disorders in pregnancy (HDP) are the main complication and cause of maternal and perinatal death. Pre-eclampsia represents a 34%, according to the Secretaría de Salud de México. To offer the family physicians tools for the opportune detection and diagnosis of HDP a clinical guideline was developmented. Clinical questions were formulated and structured. A standardized sequence to search for Practice Guidelines, based on the key words: hypertensive disorders in pregnancy, pre-eclampsia. Tripdatabase, MDConsult, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, National Institute for Health and Clinical Excellence were used. In addition, Cochrane Library Plus, Science Direct and OVID were used. Most of the recommendations were taken from guidelines selected and supplemented with the remaining material. The information is expressed in levels of evidence and grade of recommendation according to the characteristics of the study design and type of publications. To reduce morbidity and mortality from HDP health professionals should identify risk factors; conduct a close monitoring and early diagnosis. It is essential to provide information to the pregnant patient on alarm data and behavior to follow. This clinical practice guide offers current evidence for screening and diagnosis of HDP in primary care. PMID:21703152

  14. Malignant hypertensive retinopathy as a presenting sign of an occult dead fetus.

    PubMed

    Araújo, Joana; Tavares-Ferreira, João; Penas, Susana; Figueira, Luís; Paiva, Flávio Prézia; Falcão-Reis, Fernando

    2015-01-01

    We report one case of malignant hypertensive retinopathy as a presenting sign of fetal death in utero. Ophthalmic examination (including intravenous fluorescein angiography and optical coherence tomography) and obstetric and systemic evaluation were performed, providing a multidisciplinary approach. A 33-year-old overweight woman (body mass index 47 kg/m(2)) with no systemic or ocular known disease was admitted to our emergency department with a one-week history of bilateral vision loss and no systemic complaints. On examination, best corrected visual acuity was 1/10 in the right eye and 1/10 in the left eye. Anterior segment examination of both eyes was unremarkable. Ophthalmoscopic fundus findings included bilateral optic disc edema, diffuse cotton wool spots, intraretinal exudates, retinal hemorrhages, and multiple serous retinal detachments involving both maculae. Physical examination revealed a blood pressure of 220/110 mmHg. Further systemic workup revealed a previously unknown 35-week pregnancy with a dead fetus. An emergency cesarean section was performed. Pre-eclampsia is a life-threatening disorder for both mother and fetus. This case highlights the need to rule out pre-eclampsia in all women of childbearing age presenting with ocular signs of malignant hypertension, even without external signs of pregnancy. PMID:26082609

  15. Malignant hypertensive retinopathy as a presenting sign of an occult dead fetus

    PubMed Central

    Araújo, Joana; Tavares-Ferreira, João; Penas, Susana; Figueira, Luís; Paiva, Flávio Prézia; Falcão-Reis, Fernando

    2015-01-01

    We report one case of malignant hypertensive retinopathy as a presenting sign of fetal death in utero. Ophthalmic examination (including intravenous fluorescein angiography and optical coherence tomography) and obstetric and systemic evaluation were performed, providing a multidisciplinary approach. A 33-year-old overweight woman (body mass index 47 kg/m2) with no systemic or ocular known disease was admitted to our emergency department with a one-week history of bilateral vision loss and no systemic complaints. On examination, best corrected visual acuity was 1/10 in the right eye and 1/10 in the left eye. Anterior segment examination of both eyes was unremarkable. Ophthalmoscopic fundus findings included bilateral optic disc edema, diffuse cotton wool spots, intraretinal exudates, retinal hemorrhages, and multiple serous retinal detachments involving both maculae. Physical examination revealed a blood pressure of 220/110 mmHg. Further systemic workup revealed a previously unknown 35-week pregnancy with a dead fetus. An emergency cesarean section was performed. Pre-eclampsia is a life-threatening disorder for both mother and fetus. This case highlights the need to rule out pre-eclampsia in all women of childbearing age presenting with ocular signs of malignant hypertension, even without external signs of pregnancy. PMID:26082609

  16. Helicobacter pylori and pregnancy-related disorders

    PubMed Central

    Cardaropoli, Simona; Rolfo, Alessandro; Todros, Tullia

    2014-01-01

    Helicobacter pylori (H. pylori) infection is investigated in gastric diseases even during pregnancy. In particular, this Gram-negative bacterium seems to be associated with hyperemesis gravidarum, a severe form of nausea and vomiting during pregnancy. During the last decade, the relationship among H. pylori and several extra-gastric diseases strongly emerged in literature. The correlation among H. pylori infection and pregnancy-related disorders was mainly focused on iron deficiency anemia, thrombocytopenia, fetal malformations, miscarriage, pre-eclampsia and fetal growth restriction. H. pylori infection may have a role in the pathogenesis of various pregnancy-related disorders through different mechanisms: depletion of micronutrients (iron and vitamin B12) in maternal anemia and fetal neural tube defects; local or systemic induction of pro-inflammatory cytokines release and oxidative stress in gastrointestinal disorders and pre-eclampsia; cross-reaction between specific anti-H. pylori antibodies and antigens localized in placental tissue and endothelial cells (pre-eclampsia, fetal growth restriction, miscarriage). Since H. pylori infection is most likely acquired before pregnancy, it is widely believed that hormonal and immunological changes occurring during pregnancy could activate latent H. pylori with a negative impact not only on maternal health (nutritional deficiency, organ injury, death), but also on the fetus (insufficient growth, malformation, death) and sometime consequences can be observed later in life. Another important issue addressed by investigators was to determine whether it is possible to transmit H. pylori infection from mother to child and whether maternal anti-H. pylori antibodies could prevent infant’s infection. Studies on novel diagnostic and therapeutic methods for H. pylori are no less important, since these are particularly sensitive topics in pregnancy conditions. It could be interesting to study the possible correlation between H. pylori infection and other pregnancy-related diseases of unknown etiology, such as gestational diabetes mellitus, obstetric cholestasis and spontaneous preterm delivery. Since H. pylori infection is treatable, the demonstration of its causative role in pregnancy-related disorders will have important social-economic implications. PMID:24574739

  17. 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

  18. Fatal outcome of posterior "reversible" encephalopathy syndrome in metastatic colorectal carcinoma after irinotecan and fluoropyrimidine chemotherapy regimen.

    PubMed

    Dedi? Plaveti?, Natalija; Rakuši?, Zoran; Ozreti?, David; Simeti?, Luka; Krpan, Ana Mišir; Bišof, Vesna

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity characterized by headaches, altered mental status, seizures, and visual disturbances. It can occur in many different clinical entities such as severe hypertension and pre-eclampsia, or due to cytotoxic or immunosuppressive therapies. The pathogenesis of PRES is unclear, with dysregulated cerebral auto-regulation and endothelial dysfunction as important mechanisms proposed. Endothelial dysfunction is important especially in cases associated with cytotoxic therapies. Herein, we describe a patient with PRES with fatal outcome, who presented 5 days after the infusion of cycle 1 of irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) regimen chemotherapy, without prior hypertension and other comorbidity, suggesting a link between PRES and FOLFIRI regimen. To our knowledge, this case report is the first describing PRES after FOLFIRI regimen, although others have described PRES after FOLFIRI with bevacizumab in colonic cancer patients. PMID:25142792

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

    PubMed

    Blickstein, Dorith; Hod, Moshe; Bar, Jacob

    2003-12-01

    The use of low-molecular-weight heparin has been expanded to prevent pregnancy complications such as pregnancy loss, intra-uterine growth restriction and severe early-onset pre-eclampsia in high-risk patients with evidence of acquired or congenital thrombophilia. Therefore, the number of patients with side effects from low-molecular-weight heparin is expected to increase. We describe two women with infiltrating patchy plaques that developed in reaction to low-molecular-weight heparin during pregnancy. In the first patient, a switch to other formulations of heparin and heparinoid failed; the second patient, however, did well when enoxaparin was replaced with dalteparin. This report confirms the risk of skin reactions to enoxaparin and dalteparin, and reports on a skin reaction associated with danaparoid sodium in a pregnant woman. PMID:14614358

  20. Adverse pregnancy outcome among teenagers: a reality?

    PubMed

    Chibber, R; Fouda, M; Al-Hijji, J; Al-Dossary, M; Sadeq, E H; Amen, A; Shishtawy, W; Tasneem, A

    2014-05-01

    The objective of this retrospective analysis was to evaluate maternal, fetal and neonatal outcomes in primi-adolescent pregnancies in Kuwait. Case records of primigravidae under 29 years of age, attending the antenatal clinic at our tertiary hospital, between January 2002 and December 2010, were analysed. The study group (up to 19 years of age at first pregnancy) consisted of 3,863 women and the control group (20-29 years of age at first pregnancy) comprised of 4,416 women. Maternal obstetric, fetal and neonatal complications were compared between the groups. Rates of ectopic pregnancy, pre-eclampsia, eclampsia, preterm labour, premature rupture of membrane and caesarean section were significantly higher among adolescents < 15 years of age; the risk then decreased steadily with age and became comparable with the control group after 16 years of age. PMID:24483162

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

    PubMed

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

    2014-02-01

    Women with persistently circulating antiphospholipid antibodies (aPL) have a higher incidence of recurrent abortions, fetal losses, pre-eclampsia, and placental insufficiency. Current treatment of patients with antiphospholipid syndrome (APS) during pregnancy with heparin and aspirin can act by preventing clot formation and improving live birth rates, but other obstetric morbidities remain high, especially in patients with a history of thrombotic events. In addition to the classical thrombotic placental events, other factors involving inflammation and complement activation seem to play a role in certain complications. In this article, we will review how medications interfere in the pathogenic mechanisms of APS, discuss the impact of current recommended treatment on pregnancy morbidity, and analyze new promising therapies. PMID:24390757

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

    PubMed

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

    2015-01-01

    Antiphospholipid syndrome (APS) comprises of a wide spectrum of clinical and obstetric manifestations linked to the presence of antiphospholipid antibodies (aPL). APS was described in the context of lupus, and later as an isolated syndrome or primary APS. The presence of aPL, especially the lupus anticoagulant test, is associated with adverse pregnancy outcomes, such as fetal death, recurrent early miscarriages, pre-eclampsia, and placental insufficiency, but does not seem to influence infertility. High quality scientific data to support these associations, however, are lacking, and controversies arise about the definition of positive aPL (low vs medium-high titers) or even the definition of the adverse events. This review discusses APS classification criteria and the current debate about it. PMID:25999948

  3. Annexin A2 autoantibodies in thrombosis and autoimmune diseases.

    PubMed

    Cañas, 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

  4. Coagulation and placenta-mediated complications.

    PubMed

    Greer, Ian A; Aharon, Anat; Brenner, Benjamin; Gris, Jean-Christophe

    2014-10-01

    Pregnancy is a physiological hypercoagulable state, preparing the mother for the hemostatic challenge of delivery. However, this is associated with an increased risk of venous thrombosis and placenta-mediated complications, which present major challenges for mother and fetus. Although these conditions are heterogeneous in their pathophysiology, hereditary and acquired thrombophilia has been associated with recurrent pregnancy loss and gestational vascular complications, such as early-onset pre-eclampsia and placental abruption. Prevention of such placenta-mediated complications, which collectively complicate up to 15% of pregnancies, is a major issue for women's health. Prospective interventional studies stratified by current knowledge of pathophysiological mechanisms related to placental and systemic hemostatic alterations will impact on the management of pregnancies at risk of these complications. PMID:25386350

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

    PubMed

    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 in vitro. Here, we explored whether exposure to labour represents an in vivo 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

  6. Extracellular vesicles and reproduction-promotion of successful pregnancy.

    PubMed

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

    2014-11-01

    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 cell-cell 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

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

    PubMed

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

    2015-04-01

    Maternal obesity is of major consequence, affecting every aspect of maternity care including both short- and long-term effects on the health of the offspring. Obese mothers are at a higher risk of developing gestational diabetes and pre-eclampsia, potentially exposing the foetus to an adverse intrauterine environment. Maternal obesity is linked to foetal macrosomia, resulting in increased neonatal and maternal morbidity. Foetal macrosomia is a result of a change in body composition in the neonate with an increase in both percentage fat and fat mass. Maternal obesity and gestational weight gain are associated with childhood obesity, and this effect extends into adulthood. Childhood obesity in turn increases chances of later life obesity, thus type 2 diabetes, and cardiovascular disease in the offspring. Further clinical trials of lifestyle and, potentially, pharmacological interventions in obese pregnant women are required to determine whether short- and long-term adverse effects for the mother and child can be reduced. PMID:25497183

  8. Assessment of Foetal DNA in Maternal Blood – A Useful Tool in the Hands of Prenatal Specialists

    PubMed Central

    Kagan, K. O.; Hoopmann, M.; Kozlowski, P.

    2012-01-01

    Over the last few years, first trimester screening between 11+ and 13+ weeks of gestation has become one of the most important ultrasound examinations in pregnancy, as it allows physicians to predict several pregnancy complications including pre-eclampsia or pre-term birth. Screening for trisomies 21/18 and 13 using maternal and gestational age, foetal nuchal translucency, and maternal serum biochemistry was formerly the main reason for first trimester screening. However, today this is only one part of the overall examination. In the near future, the analysis of foetal DNA obtained from maternal blood will be used to supplement first trimester screening for aneuploidy or even replace current screening methods. In this review we show how prenatal medicine specialists can use foetal DNA analysis. PMID:25258455

  9. Current trends in the treatment of polycystic ovary syndrome with desire for children.

    PubMed

    Sastre, Margalida E; Prat, Maria O; Checa, Miguel Angel; Carreras, Ramon C

    2009-04-01

    Polycystic ovary syndrome (PCOS), one of the most frequent endocrine diseases, affects approximately 5%-10% of women of childbearing age and constitutes the most common cause of female sterility regardless of the need or not for treatment, a change in lifestyle is essential for the treatment to work and ovulation to be restored. Obesity is the principal reason for modifying lifestyle since its reduction improves ovulation and the capacity for pregnancy and lowers the risk of miscarriage and later complications that may occur during pregnancy (gestational diabetes, pre-eclampsia, etc). When lifestyle modification is not sufficient, the first step in ovulation induction is clomiphene citrate. The second-step recommendation is either exogenous gonadotrophins or laparoscopic ovarian surgery. Recommended third-line treatment is in vitro fertilization. Metformin use in PCOS should be restricted to women with glucose intolerance. PMID:19536311

  10. Eosinophilic/T-cell Chorionic Vasculitis: Histological and Clinical Correlations.

    PubMed

    Cheek, Bradley; Heinrich, Stephen; Ward, Kenneth; Craver, Randall

    2015-04-01

    Eosinophilic T-cell chorionic vasculitis (E/TCV) is composed of eosinophils and T-lymphocytes originating within chorionic vessels, radiating toward the intervillous space and away from the amnion in a fashion different from the fetal vascular response seen in amnionitis. Clinical significance and risk factors are not well established. We report four pregnancies (five infants, one triplet was spared) with E/TCV, gestational ranging from 23 weeks to term. All had concurrent acute chorioamnionitis, three had the typical acute fetal inflammatory response. One had placental fetal obstructive vasculopathy and an upper extremity reduction defect (radio-ulnar synostosis), the mother had pre-eclampsia. A second case involved 2 of 3 23 week previable triplets. Our third case had a metatarsus varus resistant to casting, the mother had gestational diabetes. The last case was a normal infant. We review the literature, discuss the clinical findings and present the histologic characteristics of this infrequently recognized lesion. PMID:25338020

  11. Secondary headaches attributed to arterial hypertension

    PubMed Central

    Assarzadegan, Farhad; Hesami, Omid; Aryani, Omid; Mansouri, Behnam; Beladi moghadam, Nahid

    2013-01-01

    Mild (140 to 159/90 to 99 mmHg) or moderate (160 to 179/100 to 109 mmHg) chronic arterial hypertension does not appear to cause headache. Whether moderate hypertension predisposes patients to headache at all remains controversial, but there is little evidence that it does. Ambulatory blood pressure monitoring in patients with mild and moderate hypertension has shown no convincing relationship between blood pressure fluctuations over a 24-hour period and presence or absence of headache. However, headaches are associated to various disorders that lead to abrupt, severe, and paroxysmal elevations in blood pressure. In this paper, the secondary headaches attributed to acute crises of hypertension and the criteria for diagnosing each of them have been reviewed. These are headaches attributed to pheochromocytoma, hypertensive crisis without encephalopathy, hypertensive encephalopathy, pre-eclampsia, eclampsia, and acute pressure response to exogenous agents. PMID:24250915

  12. Hypertension in pregnancy. A study of 142 women presenting before 32 weeks' gestation.

    PubMed

    Horvath, J S; Korda, A; Child, A; Henderson-Smart, D; Phippard, A; Duggin, G G; Hall, B M; Tiller, D J

    1985-07-01

    This study evaluates the outcome of 142 consecutive pregnancies in women in whom hypertension was diagnosed before 32 weeks' gestation and who were managed by a team comprising obstetricians, physicians and perinatologists. Arterial pressure was lowered to 140/90 mmHg or lower with clonidine hydrochloride or methyldopa therapy to which, in most cases, a vasodilator, hydralazine or diazoxide was added. The outcome of patients who were managed by the multidisciplinary team from the clinical onset of their disease was compared to the outcome of those who were transferred after the onset of hypertension from other centres. A greater perinatal mortality rate was found among the infants of patients with pre-eclampsia and patients with essential hypertension in pregnancy when the mothers were referred late for management. Reasons for the difference in pregnancy outcome are not clear. Possible explanations are discussed which emphasize the need for further study to establish optimal management of this common complication of pregnancy. PMID:4010599

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

    PubMed Central

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

    2015-01-01

    Antiphospholipid syndrome (APS) comprises of a wide spectrum of clinical and obstetric manifestations linked to the presence of antiphospholipid antibodies (aPL). APS was described in the context of lupus, and later as an isolated syndrome or primary APS. The presence of aPL, especially the lupus anticoagulant test, is associated with adverse pregnancy outcomes, such as fetal death, recurrent early miscarriages, pre-eclampsia, and placental insufficiency, but does not seem to influence infertility. High quality scientific data to support these associations, however, are lacking, and controversies arise about the definition of positive aPL (low vs medium-high titers) or even the definition of the adverse events. This review discusses APS classification criteria and the current debate about it. PMID:25999948

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

    PubMed

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

    2013-05-01

    HELLP, a syndrome characterised by haemolysis, elevated liver enzymes and low platelets, a variant of pre-eclampsia/eclampsia, is a multisystemic disorder with an incidence of up to 0.9% in all pregnancies and occurs in about one-quarter of pre-eclamptic patients. Most obstetricians presume that HELLP derives from an autoimmune reaction, leading to a materno- fetal imbalance, with accompanying aggregation of platelets, endothelial malfunction along with inborn errors of fatty acid oxidative metabolism. HELLP is characterised by high mortality and morbidity rates, leading to possibly life-threatening complications regarding both the mother and the fetus. Delivery is indicated if HELLP syndrome occurs after 34 gestational weeks or the fetal and/or maternal conditions deteriorate. Vaginal delivery is preferable. Standard corticosteroid treatment is of uncertain clinical value in maternal HELLP syndrome. Future observations and research results may shed more light on improving our understanding of the aspects of HELLP syndrome. PMID:23654309

  15. Maternal deaths associated with eclampsia in South Africa: Lessons to learn from the confidential enquiries into maternal deaths, 2005 - 2007.

    PubMed

    Moodley, J

    2010-11-01

    Eclampsia is the commonest direct cause of maternal death in South Africa. The latest Saving Mothers Report (2005-2007) indicates that there were 622 maternal deaths due to hypertensive disorders of pregnancy. Of these, 334 (55.3%) were due to eclampsia; of the eclamptic deaths, 50 were over the age of 35 years and 83 were under 20 years old. Avoidable factors involved patient related factors (mainly delay in seeking help), administrative factors (mainly delay in transport) and health personnel issues (mainly due to delay in referring patients). The major causes of death were cerebrovascular accidents and cardiac failure. The majority of deaths due to cardiac failure were due to pulmonary oedema. To reduce deaths from eclampsia, more attention must be given to the detection of pre-eclampsia; the provision of information on the advantages of antenatal care to the population at large and training of health professions in the management of obstetric emergencies. PMID:21081020

  16. 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

  17. MFSD2a, the Syncytin-2 receptor, is important for trophoblast fusion.

    PubMed

    Toufaily, C; Vargas, A; Lemire, M; Lafond, J; Rassart, E; Barbeau, B

    2013-01-01

    The syncytiotrophoblast is formed at the placental periphery through cytotrophoblast fusion, which depends on Human Endogenous Retrovirus-encoded Envelope proteins Syncytin-1 and Syncytin-2. In the current study, the role of Major Facilitator Superfamily Domain Containing 2A (MFSD2a), the Syncytin-2 receptor, in trophoblast fusion and its expression in normal vs. pre-eclampsia placentas were studied. Forskolin-induced fusion of BeWo cells first parallelled an increase in MFSD2a expression. The MFSD2a signal localized in the cytoplasm and at the plasma membrane. Knockdown of MFSD2a expression confirmed its importance in BeWo fusion. Furthermore, reduced MFSD2a expression was noted in severe pre-eclamptic placentas. These data thus support the importance of MFSD2a in trophoblast fusion and placenta development. PMID:23177091

  18. Amniotic fluid alpha-fetoprotein is not a useful biological marker of pregnancy outcome.

    PubMed

    Verspyck, E; Degré, S; Hellot, M F; Descargues, G; Philippe, C; Labadie, G; Bénichou, J; Lemoine, J P; Marpeau, L

    1999-11-01

    The aim of our study was to determine if the amniotic fluid alpha-fetoprotein (AFP) level could be a useful predictive biochemical marker of pregnancy outcome. Amniotic fluid AFP measurement was prospectively carried out over a three-year period. After excluding factors susceptible to modifying AFP measurements, 587 subjects with gestational age between 14 and 20 weeks were selected to compare the amniotic fluid AFP mean levels depending on the occurrence of an adverse outcome. No significant associations between amniotic fluid AFP level and poor pregnancy outcome, i.e. pre-eclampsia, preterm delivery, premature rupture of fetal membranes, fetal growth retardation and placental abnormalities were observed. The routine measurement of amniotic fluid alpha-fetoprotein during an amniocentesis procedure was not considered useful in predicting pregnancy complications. PMID:10589054

  19. 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

  20. 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

  1. A cohort evaluation on arterial stiffness and hypertensive disorders in pregnancy

    PubMed Central

    2012-01-01

    Background Hypertensive disorders in pregnancy are associated with systemic endothelial dysfunction leading to impaired physiological vasodilation. Recent evidence has shown central aortic pressures obtained through pulse wave analysis, at less than 14 weeks of gestation, to be predictive of pre-eclampsia. In light of this, we aimed to evaluate the role of central aortic stiffness in the prediction and discrimination of hypertensive disorders in pregnancy. Methods A cohort study of women with viable, singleton pregnancies at less than 14 weeks of amenorrhoea, and without multiple pregnancies, autoimmune or renal disease, diagnosed with aneuploidy or fetal anomaly will be recruited from a single maternity hospital and followed up till delivery and puerperium. A targeted sample size of 1000 eligible pregnant women will be enrolled into the study from antenatal clinics. Main exposure under study is central aortic pulse pressure using radial pulse wave recording, and the outcomes under follow-up are gestational hypertension and pre-eclampsia. Other measures include lifestyle factors such as smoking, physical exercise, psychometric evaluations, vasoactive factors, uterine artery pulsatility index, height and weight measurements. These measures will be repeated over 4 antenatal visits at 11-14, 18-22, 28-32 and above 34 weeks of gestation. Double data entry will be performed on Microsoft Access, and analysis of data will include the use of random effect models and receiver operating characteristic curves on Stata 11.2. Discussion The proposed study design will enable a longitudinal evaluation of the central aortic pressure changes as a marker for vascular compliance during pregnancy. As measures are repeated over time, the timing and severity of changes are detectable, and findings may yield important information on how aberrant vascular responses occur and its role in the early detection and prediction of hypertensive disorders. PMID:23268774

  2. Inter-pregnancy weight change impacts placental weight and is associated with the risk of adverse pregnancy outcomes in the second pregnancy

    PubMed Central

    2014-01-01

    Background The inter-pregnancy period is considered a teachable moment when women are receptive to weight- management guidance aimed at optimising pregnancy outcome in subsequent pregnancies. In population based studies inter-pregnancy weight change is associated with several adverse pregnancy outcomes but the impact on placental size is unknown. Methods The association between inter-pregnancy weight change and the primary risk of adverse pregnancy outcomes in the second pregnancy was investigated in 12,740 women with first two consecutive deliveries at a single hospital using logistic regression. Results Compared with women who were weight stable, weight loss (>1BMI unit) between pregnancies was associated with an increased risk of spontaneous preterm delivery, low placental weight and small for gestational age (SGA) birth, while weight gain (>3BMI units) increased the risk of pre-eclampsia, gestational hypertension, emergency caesarean section, placental oversize and large for gestational age (LGA) birth at the second pregnancy. The relationship between weight gain and pre-eclampsia risk was evident in women who were overweight at first pregnancy only (BMI ?25 units), while that between weight loss and preterm delivery was confined to women with a healthy weight at first pregnancy (BMI <25 units). In contrast, the association between weight loss and SGA was independent of first pregnancy BMI. A higher percentage of women who were obese at first pregnancy were likely to experience a large weight gain (P

  3. 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).

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

    PubMed

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

    2002-09-15

    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 (125)I-albumin in wild-type and tachykinin NK(1) receptor knockout mice. Intradermal NKB (30-300 pmol) caused dose-dependent plasma extravasation in wild-type (P < 0.05) but not NK(1) knockout mice, indicating an essential role for the NK(1) 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 NK(1) 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 NK(1) receptor knockout mice was unaffected by treatment with the NK(2) receptor antagonist SR48968 (3 mg kg(-1)), by the NK(3) 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 NK(1) 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

  5. 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

  6. Impact of interventions to prevent and manage preeclampsia and eclampsia on stillbirths

    PubMed Central

    2011-01-01

    Background Pre-eclampsia and Eclampsia are relatively common complications of pregnancy, leading to considerable maternal and fetal mortality and morbidity. We sought to review the effect of aspirin, calcium supplementation, antihypertensive agents and magnesium sulphate on risk stillbirths. Methods A systematic literature search was conducted to identify studies evaluating the above interventions. We used a standardized abstraction and grading format and performed meta-analyses where data were available from more than one studies. The estimated effect on stillbirths was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules for multiple outcomes. For interventions with insufficient evidence for overall effect, a Delphi process was undertaken to estimate effectiveness. Results We identified 82 relevant studies. For aspirin, maganesium sulphate and use of antihypertensive we found an insignificant decrease in stillbirth and perinatal mortality. For calcium supplementation, there was a borderline significant reduction in stillbirths (RR 0.81, 95 % CI 0.63-1.03). We undertook a Delphi consultation among experts to assess the potential impact of a package of interventions for the management of pre-eclampsia and eclampsia (antihypertensive, magnesium sulphate and C-section if needed). The Delphi process suggested 20% reduction each in both antepartum and intrapartum stillbirths with the use of this package. Conclusions Despite promising benefits of calcium supplementation and aspirin use cases on maternal morbidity and eclampsia in high risk cases, further work is needed to ascertain their benefits in relation to stillbirths. The Delphi process undertaken for assessing potential impact of a package of interventions indicated that this could be associated with 20% reduction in stillbirths, for input into LiST. PMID:21501457

  7. 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

  8. Low-dose nitro-L-arginine administration in baboon (Papio hamadryas) pregnancy.

    PubMed

    Hennessy, A; Gillin, A G; Duggin, G G; Horvath, J S; Tiller, D J

    1999-11-01

    1. The purpose of the present study was to examine the effect of nitric oxide (NO) inhibition on mean arterial pressure (MAP), endothelin (ET) and the renin-aldosterone system in pregnancy in the non-human primate (baboon). 2. Twenty pregnant baboons (Papio hamadryas) were examined prospectively after the administration of an oral NO inhibitor in different phases of pregnancy. Haemodynamic responses to NO inhibition, evidence of pre-eclampsia and the renin-aldosterone system were examined under anaesthesia. 3. Oral NL-nitro-L-arginine (NOLA; 5 or 10 mg/kg) was given for 1 week in early (6-8 weeks gestation), middle (14-16 weeks gestation) and late (22-24 weeks gestation) pregnancy and while non-pregnant. Mean arterial pressure, heart rate, haematology, biochemistry, ET, plasma renin activity (PRA) and aldosterone were measured. Foetal effects of NOLA were also examined by ultrasound and neonatal measurements. 4. Nitric oxide inhibition led to an increase in MAP in non-pregnant animals (9 mmHg) and in middle and later pregnancy (6 and 7 mmHg, respectively). Mean arterial pressure in early pregnancy was not affected. A reduction in PRA occurred after NO inhibition in all stages of pregnancy. Significant proteinuria occurred only in late pregnancy. 5. Nitric oxide is involved in the maintenance of lower blood pressure in late pregnancy and inhibition leads to an increase in blood pressure and proteinuria in the baboon. Nitric oxide insufficiency may contribute to the clinical manifestations of human pre-eclampsia. Nitric oxide was not involved in the normal vasodilation of early primate pregnancy. PMID:10561803

  9. Number and distribution of myofibroblasts and ?-smooth muscle actin expression levels in fetal membranes with and without gestational complications.

    PubMed

    Ma, Xiaoyan; Yang, Fan; Yang, Shuli; Rasul, Azhar; Li, Ting; Liu, Lianlian; Kong, Min; Guo, Dongmei; Ma, Tonghui

    2015-08-01

    The permeability and tension of fetal membranes (FMs) is associated with extracellular matrix proteins produced largely by myofibroblasts (MFBBs). ??smooth muscle actin (??SMA) is involved in the contraction of MFBBs and has been implicated as a special biomarker of MFBBs in non?vessel FM. The present study demonstrated, by using immunohistochemistry, reverse?transcription polymerase chain reaction and western blotting, that MFBBs were mainly distributed in chorioamniotic mesoderm at 16?21 weeks and in chorionic mesoderm at 22?40 weeks, respectively, while overlapping with each other at 16?40 weeks. In addition, a quantity of MFBBs were identified in chorionic epithelia at 16?40 weeks. The MFBBs were distributed parallel to the FMs. The quantities of MFBBs and the expression levels of ??SMA were negatively associated with increasing gestational progress and of amniotic fluid indexes in full?term females (those from oligohydramnios were higher than polyhydramnios); however, the thickness of the FM's mesoderm remained unchanged. Of note, the number of MFBBs in early?onset severe pre?eclampsia (EOSP) was significantly decreased in comparison with that in EOSP controls and late?onset severe pre?eclampsia (LOSP), while that in LOSP was higher than that in LOSP controls. The present data indicated that the changes in the quantity and distribution of MFBBs in the FM affects the permeability and tension of the FM. In addition, the findings suggested that the expression levels of ??SMA in the FM also contributed to the properties of the FM. Simultaneously, the number and distribution of MFBBs and the expression levels of ??SMA in the FM may be involved in the mechanisms of development, apoptosis and trophoblast?MFBB transformation of the FM. PMID:25954927

  10. Acute Lung Injury Complicating Blood Transfusion in Post-Partum Hemorrhage: Incidence and Risk Factors

    PubMed Central

    Teofili, Luciana; Bianchi, Maria; Zanfini, Bruno A.; Catarci, Stefano; Sicuranza, Rossella; Spartano, Serena; Zini, Gina; Draisci, Gaetano

    2014-01-01

    Background We retrospectively investigated the incidence and risk factors for transfusion-related acute lung injury (TRALI) among patients transfused for post-partum hemorrhage (PPH). Methods We identified a series of 71 consecutive patients with PPH requiring the urgent transfusion of three or more red blood cell (RBC) units, with or without transfusion of fresh frozen plasma (FFP) and/or platelets (PLT). Clinical records were then retrieved and examined for respiratory distress events. According to the 2004 consensus definition, cases of new-onset hypoxemia, within 6 hours after transfusion, with bilateral pulmonary changes, in the absence of cardiogenic pulmonary edema were identified as TRALI. If an alternative risk factor for acute lung injury was present, possible TRALI was diagnosed. Results Thirteen cases of TRALI and 1 case of possible TRALI were identified (overall incidence 19.7%). At univariate analysis, patients with TRALI received higher number of RBC, PLT and FFP units and had a longer postpartum hospitalization. Among the diseases occurring in pregnancy- and various pre-existing comorbidities, only gestational hypertension and pre-eclampsia, significantly increased the risk to develop TRALI (p = 0.006). At multivariate analysis including both transfusion- and patient-related risk factors, pregnancy-related, hypertensive disorders were confirmed to be the only predictors for TRALI, with an odds ratio of 27.7 ( 95% CI 1.27–604.3, p=0.034). Conclusions Patients suffering from PPH represent a high-risk population for TRALI. The patients with gestational hypertension and pre-eclampsia, not receiving anti-hypertensive therapy, have the highest risk. Therefore, a careful monitoring of these patients after transfusions is recommended. PMID:25408855

  11. Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Objective To provide an accurate assessment of complications of pregnancy in women with chronic hypertension, including comparison with population pregnancy data (US) to inform pre-pregnancy and antenatal management strategies. Design Systematic review and meta-analysis. Data sources Embase, Medline, and Web of Science were searched without language restrictions, from first publication until June 2013; the bibliographies of relevant articles and reviews were hand searched for additional reports. Study selection Studies involving pregnant women with chronic hypertension, including retrospective and prospective cohorts, population studies, and appropriate arms of randomised controlled trials, were included. Data extraction Pooled incidence for each pregnancy outcome was reported and, for US studies, compared with US general population incidence from the National Vital Statistics Report (2006). Results 55 eligible studies were identified, encompassing 795?221 pregnancies. Women with chronic hypertension had high pooled incidences of superimposed pre-eclampsia (25.9%, 95% confidence interval 21.0% to 31.5 %), caesarean section (41.4%, 35.5% to 47.7%), preterm delivery <37 weeks’ gestation (28.1% (22.6 to 34.4%), birth weight <2500 g (16.9%, 13.1% to 21.5%), neonatal unit admission (20.5%, 15.7% to 26.4%), and perinatal death (4.0%, 2.9% to 5.4%). However, considerable heterogeneity existed in the reported incidence of all outcomes (?2=0.286-0.766), with a substantial range of incidences in individual studies around these averages; additional meta-regression did not identify any influential demographic factors. The incidences (the meta-analysis average from US studies) of adverse outcomes in women with chronic hypertension were compared with women from the US national population dataset and showed higher risks in those with chronic hypertension: relative risks were 7.7 (95% confidence interval 5.7 to 10.1) for superimposed pre-eclampsia compared with pre-eclampsia, 1.3 (1.1 to 1.5) for caesarean section, 2.7 (1.9 to 3.6) for preterm delivery <37 weeks’ gestation, 2.7 (1.9 to 3.8) for birth weight <2500 g, 3.2 (2.2 to 4.4) for neonatal unit admission, and 4.2 (2.7 to 6.5) for perinatal death. Conclusions This systematic review, reporting meta-analysed data from studies of pregnant women with chronic hypertension, shows that adverse outcomes of pregnancy are common and emphasises a need for heightened antenatal surveillance. A consistent strategy to study women with chronic hypertension is needed, as previous study designs have been diverse. These findings should inform counselling and contribute to optimisation of maternal health, drug treatment, and pre-pregnancy management in women affected by chronic hypertension. PMID:24735917

  12. Prevalence, Risk Factors and Outcomes of Velamentous and Marginal Cord Insertions: A Population-Based Study of 634,741 Pregnancies

    PubMed Central

    Ebbing, Cathrine; Kiserud, Torvid; Johnsen, Synnøve Lian; Albrechtsen, Susanne; Rasmussen, Svein

    2013-01-01

    Objectives To determine the prevalence of, and risk factors for anomalous insertions of the umbilical cord, and the risk for adverse outcomes of these pregnancies. Design Population-based registry study. Setting Medical Birth Registry of Norway 1999–2009. Population All births (gestational age >16 weeks to <45 weeks) in Norway (623,478 singletons and 11,263 pairs of twins). Methods Descriptive statistics and odds ratios (ORs) for risk factors and adverse outcomes based on logistic regressions adjusted for confounders. Main outcome measures Velamentous or marginal cord insertion. Abruption of the placenta, placenta praevia, pre-eclampsia, preterm birth, operative delivery, low Apgar score, transferral to neonatal intensive care unit (NICU), malformations, birthweight, and perinatal death. Results The prevalence of abnormal cord insertion was 7.8% (1.5% velamentous, 6.3% marginal) in singleton pregnancies and 16.9% (6% velamentous, 10.9% marginal) in twins. The two conditions shared risk factors; twin gestation and pregnancies conceived with the aid of assisted reproductive technology were the most important, while bleeding in pregnancy, advanced maternal age, maternal chronic disease, female foetus and previous pregnancy with anomalous cord insertion were other risk factors. Velamentous and marginal insertion was associated with an increased risk of adverse outcomes such as placenta praevia (OR?=?3.7, (95% CI?=?3.1–4.6)), and placental abruption (OR?=?2.6, (95% CI?=?2.1–3.2)). The risk of pre-eclampsia, preterm birth and delivery by acute caesarean was doubled, as was the risk of low Apgar score, transferral to NICU, low birthweight and malformations. For velamentous insertion the risk of perinatal death at term was tripled, OR?=?3.3 (95% CI?=?2.5–4.3). Conclusion The prevalence of velamentous and marginal insertions of the umbilical cord was 7.8% in singletons and 16.9% in twin gestations, with marginal insertion being more common than velamentous. The conditions were associated with common risk factors and an increased risk of adverse perinatal outcomes; these risks were greater for velamentous than for marginal insertion. PMID:23936197

  13. The herbal medicine Tokishakuyakusan increases fetal blood glucose concentrations and growth hormone levels and improves intrauterine growth retardation induced by N(omega)-nitro-L-arginine methyl ester.

    PubMed

    Takei, Hisato; Iizuka, Seiichi; Yamamoto, Masahiro; Takeda, Shuichi; Yamamoto, Masako; Arishima, Kazuyoshi

    2007-08-01

    N(omega)-Nitro-L-arginine methyl ester (L-NAME) induces a pre-eclampsia-like syndrome in pregnant rats. We have previously reported the anti-hypertensive effects of several Japanese traditional (Kampo) medicines in this model, and one of these, Tokishakuyakusan (TS), also improved intrauterine growth retardation (IUGR). In the present study, we characterized the effect of TS on IUGR. TS administration reversed the decrease in fetal body weight and fetal blood glucose concentration induced by the infusion of L-NAME. Growth hormone (GH) levels in the fetal blood, which were decreased by L-NAME infusion, were also significantly elevated by TS; however, levels of GH releasing hormone (GHRH) and insulin-like growth factor I (IGF-I) were unchanged and only slightly changed, respectively. Treatment with L-NAME with or without TS had no apparent effect on GH, GHRH, and IGF-I levels of dams. In an immunocytochemical study, the number of GH-positive cells in the fetal pituitary gland was significantly increased in TS-treated rats. These data suggest that enhanced proliferation of somatotrope cells of the pituitary gland and the resultant increase in GH secretion in the fetus may be involved in the improvement of IUGR by TS. PMID:17666866

  14. A role for mannose-binding lectin, a component of the innate immune system in preeclampsia

    PubMed Central

    Than, Nandor Gabor; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Tarca, Adi L.; Edwin, Samuel S.; Kim, Jung-Sun; Hassan, Sonia S.; Espinoza, Jimmy; Mittal, Pooja; Mazaki-Tovi, Shali; Friel, Lara; Gotsch, Francesca; Vaisbuch, Edi; Camacho, Natalia; Papp, Zoltan

    2008-01-01

    Problem Mannose-binding lectin (MBL) is a pattern-recognition receptor that activates complement and modulates inflammation. Homozygosity for the most common allele of the MBL2 gene associated with high MBL serum concentrations is more prevalent in patients with preeclampsia. The objective of this study was to determine maternal plasma MBL concentrations in normal pregnant women and patients with pre-eclampsia. Method of study This cross-sectional study included normal pregnant women (n=187) and patients with preeclampsia (n=99). Maternal plasma MBL concentrations were determined by ELISA. Results Women with preeclampsia had higher median maternal plasma MBL concentration than normal pregnant women. MBL concentration distribution curves were three-modal, the subintervals in normal pregnancy were low (<143.7), intermediate (143.7–1898.9) and high (>1898.9ng/ml). The proportion of normal pregnant women was larger in the low subinterval, while the proportion of patients with preeclampsia was larger in the high subinterval (p=0.02). Normal pregnant women in the high subinterval had a larger rate of placental underperfusion than those in the low and intermediate subintervals (P = 0.02). Conclusions Median maternal plasma MBL concentration is elevated in patients with preeclampsia and a larger proportion of these patients is in the high subinterval than normal pregnant women, suggesting that this innate immune system component is involved in the mechanisms of disease in preeclampsia. PMID:18727690

  15. Hemodynamic and neurohumoral profile in patients with different types of hypertension in pregnancy.

    PubMed

    Borghi, Claudio; Cicero, Arrigo Francesco Giuseppe; Degli Esposti, Daniela; Immordino, Vincenzo; Bacchelli, Stefano; Rizzo, Nicola; Santi, Francesca; Ambrosioni, Ettore

    2011-06-01

    Hypertension in pregnancy is a frequent disorder that includes a spectrum of conditions. We aimed at comparatively evaluating the hemodynamic, echocardiographic and biohumoral profile of a sample of pregnant Caucasian women with different form of pregnancy-related hypertension. We enrolled 39 non-hypertensive pregnant women (NP), 26 with Chronic HBP in pregnancy (CH), 24 with gestational hypertension (G-PIH), and 33 with pre-eclampsia. We recorded and compared blood pressure (BP), echocardiographic parameters, resting plasma renin activity (PRA) and plasma aldosterone (PA), Plasma levels of atrial (ANP) and brain natriuretic peptide (BNP). PE patients had a significantly higher BP than either G-PIH or NP patients. PE patients had also significantly lower cardiac output than NP, G-PIH and CH. In comparison to NP patients, the total peripheral vascular resistance was 61% higher in PE women and 38% higher in CH patients. All echographic parameters were significantly more altered in PE patients when compared with NP, in respect to any other form of hypertension. Either ANP (+35%) and BNP (+40%) were significantly higher in PE patients than in controls. The PRA was reduced in PE and CH patients when compared either with NP (-38 and -35%, respectively) or G-PIH (-47 and -43%, respectively). On the basis of our data, we can conclude that PE is the gestation associated hypertension with the largest anatomical, functional and biohumoral involvement, and so it has to be involved in a more intensive monitoring and evaluation. PMID:21116739

  16. [The course of pregnancy in congenital thyroid gland aplasia. Case report with special reference to maternal hypothyroidism].

    PubMed

    Bolz, M; Nagel, H

    1994-01-01

    A report is given on a 28 years old women with congenital aplasia of the thyroid gland. She was substituted with thyroxine (300 micrograms per day). Her first pregnancy was complicated by gestational hypertension and pre-eclampsia. Delivery was by forceps. During the first trimester of her second pregnancy, bleedings occurred. The thyroid-stimulating hormone level (TSH-level) was increased (18.3 microU/ml). The patient did not show clinical signs of manifested hypothyroidism. The thyroxine dosis was increased. Bleedings disappeared. Labour was terminated and induced. Labour intra partum was hypoactive. The delivery was again by forceps. The newborn did not show any signals of hypothyroidism. Dysfunction of thyroid gland is associated with reduced fertility. Hypothyroidism in pregnancy is associated with an adverse outcome in fetal health as well as an increase in obstetric complications. Thyroid hormones play a vital role in fetal development and maturation of brain. Women with a hypothyroidism have a lower rate of pregnancy and a higher rate of spontaneous miscarriages compared to a normal population. Recognition and treatment of thyroid disorders in reproductive age occur before conception. Iodoprophylaxis is necessary for prevention of congenital hypothyroidism (cretinism). Iodoprophylaxis is necessary to prevent endemic goiter in pregnancy. Euthyroid goiter is an indication for a combined treatment with jodid and levothyroxine. Treatment should be individualized. Assessment of efficacy of treatment is based on measurement of TSH- and free thyroid hormone (fT4)-levels. PMID:7975962

  17. 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 (<0·5% 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

  18. Hyperhomocysteinemia and pregnancy--review of our present understanding and therapeutic implications.

    PubMed

    Aubard, Y; Darodes, N; Cantaloube, M

    2000-12-01

    Homocysteine results from the transmethylation of methionine. Its metabolism depends primarily on three enzymes and several vitamin cofactors. Genetic abnormality in these enzymes or deficiency of these vitamins lead to hyperhomocysteinemia (HHCh). HHCh is usually biologically defined by a fasting value >15 micromol/l. HHCh belongs among the congenital hypercoagulable states and is a long-known vascular disease risk factor. The discovery that HHCh may also be responsible for several pregnancy complications has only recently been made. Studies in this area are still scarce and report on limited numbers of patients. It nevertheless appears clear that HHCh is associated with the syndromes of repeated miscarriage, pre-eclampsia, placenta abruptio, thromboembolic events, neural tube defects, and perhaps with fetal death-in-utero and intra-uterine growth retardation. Supplementation with vitamin B9 can reduce plasma HC levels, and is thus recommended in patients with HHCh. The prevention of thromboembolic events during pregnancy by anticoagulant treatment is also desirable in these patients. PMID:11074137

  19. [Hyperhomocysteinemia and pregnancy complications].

    PubMed

    Sztenc, S?awomir

    2004-04-01

    Homocysteine (Hcy) is a sulfur-containing amino acid produced when methionine is demethylated. The majority of Hcy undergoes transsulfuration to cysteine by cystathionine beta-synthase (CBS), of which vitamin B6 (pyridoxine) is an essential cofactor. The remainder of Hcy is remethylated by methionine synthase (MS), of which vitamin B12 (cobalamin) is an essential cofactor along with methylenetetrahydrofolate (MTHF). MTHF is generated by the enzyme MTHFR-reductase (MTHFR). High levels of Hcy can result from a variety of aquired factors (deficiency of vitamins B6, B12 and folic acid, high meat diet, smoking and others) or genetic (abnormalities of methionine--homocysteine metabolism). Hyperhomocysteinemia is associated with premature atherosclerosis and venous thromboembolism; so called "cholesterol of XXI. age". Results of many studies suggest that hyperhomocysteinemia, homozygous state for MTHFR gene mutation, folate deficiency are probably risk factors for recurrent fetal loss, intrauterine fetal death, thrombo-embolic disease in pregnancy, neural tube defects and congenital cardiac malformation at infants and other placental diseases (pre-eclampsia, placental abruption and intrauterine growth restriction IUGR). Those irregularities are very interesting and important for obstetricians and gynecologists. The plasma homocysteine values can be modulated by vitamins, vitamin B6 and folic acid in particular. The potential for research and possible prevention in this area is immense. PMID:15181872

  20. [Hyperhomocysteinemia and pregnancy: a dangerous association].

    PubMed

    Aubard, Y; Darodes, N; Cantaloube, M; Aubard, V; Diallo, D; Teissier, M P

    2000-06-01

    Homocysteine results from the demethylation of the essential amino acid methionine. Its metabolism depends primarily on three enzymes and several vitamin cofactors (vit. B6, B9 and B12). Genetic abnormality in these enzymes or deficiency of these vitamins lead to Hyperhomocysteinemia. Hyperhomocysteinemia belongs among the congenital thrombophilies and is a long-known vascular disease risk factor. The discovery that hyperhomocysteinemia may also be responsible for several pregnancy complications has only recently been made. Studies in this area are still scarce and report on limited numbers of patients. It nevertheless appears clear that HHCh is associated with the syndromes of repeated miscarriage, pre-eclampsia, placenta abruptio, thromboembolic events, neural tube defects, and perhaps with fetal death-in-utero and intra-uterine growth retardation. Supplementation with vitamin B9 can reduce plasma HC levels, and is thus recommended in patients with HHCh. The prevention of thromboembolic events during pregnancy by anticoagulant treatment is also desirable in these patients. PMID:10844324

  1. 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

  2. Placental nitric oxide metabolism.

    PubMed

    Sooranna, S R; Morris, N H; Steer, P J

    1995-01-01

    There is increasing evidence that nitric oxide (NO) has a role in pregnancy. NO is synthesized from L-arginine by NO synthase (NOS), which can exist either as a calcium-dependent or a calcium-independent isoform of the enzyme. Both isoforms are present in placental villi and the authors have measured NOS activities in tissues from early and term normal, pre-eclamptic and growth-retarded pregnancies. Higher activities were seen in first trimester placental villi than at term. An impairment of NO metabolism occurred in placental villi from pre-eclamptic and growth-retarded pregnancies. Smoking also results in decreased NOS activities in the placental villi, suggesting that problems attributed to smoking during pregnancy could be linked to NO metabolism. Polyamines arginine and citrulline (all of which are important metabolites in the NO pathway) were also measured in placental villous tissues. The data presented in this review article are from work carried out in the authors' laboratories and suggest that alterations in the placental arginine-NO pathway may not only play a role in the physiological changes of advancing gestation but may also contribute to the pathophysiology of pre-eclampsia and fetal growth retardation. PMID:8743159

  3. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study.

    PubMed

    Kabbali, Nadia; Tachfouti, Nabil; Arrayhani, Mohammed; Harandou, Mustapha; Tagnaouti, Mounia; Bentata, Yassamine; Laouad, Inass; Ramdani, Benyounes; Bayahia, Rabia; Oualim, Zouhair; Houssaini, Tarik Sqalli

    2015-01-01

    Acute kidney injury (AKI) is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%). Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases), hemorrhagic shock (six cases) and septic events (five cases). We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6%) cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care. PMID:26022044

  4. The rise in caesarean birth rate in Sagamu, Nigeria: reflection of changes in obstetric practice.

    PubMed

    Oladapo, O T; Sotunsa, J O; Sule-Odu, A O

    2004-06-01

    A retrospective and comparative study of women delivered by caesarean section over two different 3-year periods was conducted at Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria. The caesarean section rate (CSR) increased from 10.3% in 1989-1991 to 23.1% in 2000-2003. The most frequent indication in both periods was different: prolonged/obstructed labour (20.0%) in 1989-1991 and antepartum haemorrhage (14.9%) in 2000-2003. Malpresentation, antepartum haemorrhage and pre-eclampsia/eclampsia were responsible for 51.7% of the difference in the CSR recorded between both periods. The CSR rose from 13.3% to 25.0% while the instrumental vaginal delivery (IVD) rate decreased significantly by 11.4% among the nulliparous women between the periods. Increase in CSR can be attributed mainly to reduction in IVD rate and alteration in the management of labour complications and induction policy. Strategies to reduce the CSR should cut across all indications and focus on encouraging instrumental vaginal deliveries, especially among nulliparous women. PMID:15203575

  5. HLA-G Expression Pattern: Reliable Assessment for Pregnancy Outcome Prediction

    PubMed Central

    Mosaferi, Elnaz; Majidi, Jafar; Mohammadian, Mojdeh; Babaloo, Zohreh; Monfaredan, Amir; Baradaran, Behzad

    2013-01-01

    Because mothers and fathers are more or less dissimilar at multiple HLA loci, mother considers her fetus as a semi-allograft. Mother's immune system may recognize paternal HLA as foreign antigen and may develop anti-paternal HLA antibodies and cytotoxic T lymphocyte. There are some mechanisms that modulate maternal immune responses during pregnancy, in order to make uterus an immune privileged site. This immunosuppression is believed to be mediated, at least partly, by HLA-G, non-classical class I human leukocyte antigen (HLA) molecule that is strongly expressed in cytotrophoblast and placenta. The major HLA-G function is its ability to inhibit T and B lymphocytes, NK cells and antigen-presenting cells (APC).Since HLA-G is expressed strongly at the maternofetal interface and has an essential role in immunosuppression, HLA-G polymorphism and altered expression of HLA-G seems to be associated with some complications of pregnancy, such as pre-eclampsia, recurrent misscariage and failure in IVF.This perspective discusses recent findings about HLA-G genetics, function, expression and polymorphism; and focus on HLA-G role in the etiology of recurrent miscarriage. PMID:24312875

  6. [Placental 3D Doppler angiography: current and upcoming applications].

    PubMed

    Duan, J; Perdriolle-Galet, E; Chabot-Lecoanet, A-C; Callec, R; Beaumont, M; Chavatte-Palmer, P; Tsatsaris, V; Morel, O

    2015-02-01

    The placental dysfunction, which seems to be caused by a defect of trophoblastic invasion and impaired uterine vascular remodeling since the first trimester, is responsible in a non-exclusive way for the chronic placental hypoxia, resulting secondarily in the intra-uterine growth restriction (IUGR) and/or pre-eclampsia (PE). The quality of utero-placental vasculature is essential for a proper fetal development and a successful progress of pregnancy. However, the in vivo assessment of placental vascularization with non-invasive methods is complicated by the small size of placental terminal vessel and its complex architecture. Moreover, imaging with contrast agent is not recommended to pregnant women. Until recently, the fetal and maternal vascularization could only be evaluated through pulse Doppler of uterine arteries during pregnancy, which has little clinical value for utero-placental vascularization defects assessment. Recently, a non-invasive study, without use of contrast agent for vasculature evaluation of an organ of interest has become possible by the development of 3D Doppler angiography technique. The objective of this review was to make an inventory of its current and future applications for utero-placental vasculature quantification. The main findings of the literature on the assessment of utero-placental vascularization in physiological situation and major placental vascular dysfunction pathologies such as PE and IUGR were widely discussed. PMID:25307617

  7. New horizons in platelets flow cytometry.

    PubMed

    Saboor, Muhammad; Moinuddin, Moinuddin; Ilyas, Samina

    2013-03-01

    Platelet flow cytometry is an emerging tool in diagnostic and therapeutic hematology. It is eminently suited to study the expression of platelet surface receptors both qualitatively as well as quantitatively. It can serve as a useful marker for the documentation of in vivo platelet activation, and thus, fore-warn the risk of thromboembolism in patients with diabetes mellitus, coronary syndromes, peripheral vascular diseases, and pre-eclampsia. This technique can also be extended to study and compare the effect of various antiplatelet drugs on the level of activation of platelets and to establish any dose-effect relationship of these drugs. Topographical localization of platelet granules and study of platelet-platelet and platelet-leukocyte interaction is also possible by this procedure. All these parameters serve as pointers towards the presence of activated platelets in the circulation with its thromboembolic consequences. This is a simple reliable and cost effective technique which has a wide application in the diagnosis of various inherited and acquired platelet disorders. Study of platelet cluster of differentiation (CD) markers in various inherited disorders i.e. Bernard Soulier's disease, von Willebrand disease, Glanzman's disease, and Grey platelet syndrome may help categories the molecular lesions in these oft under-studied disorders. PMID:23983579

  8. New Horizons in Platelets Flow Cytometry

    PubMed Central

    Saboor, Muhammad; Moinuddin, Moinuddin; Ilyas, Samina

    2013-01-01

    Platelet flow cytometry is an emerging tool in diagnostic and therapeutic hematology. It is eminently suited to study the expression of platelet surface receptors both qualitatively as well as quantitatively. It can serve as a useful marker for the documentation of in vivo platelet activation, and thus, fore-warn the risk of thromboembolism in patients with diabetes mellitus, coronary syndromes, peripheral vascular diseases, and pre-eclampsia. This technique can also be extended to study and compare the effect of various antiplatelet drugs on the level of activation of platelets and to establish any dose-effect relationship of these drugs. Topographical localization of platelet granules and study of platelet-platelet and platelet-leukocyte interaction is also possible by this procedure. All these parameters serve as pointers towards the presence of activated platelets in the circulation with its thromboembolic consequences. This is a simple reliable and cost effective technique which has a wide application in the diagnosis of various inherited and acquired platelet disorders. Study of platelet cluster of differentiation (CD) markers in various inherited disorders i.e. Bernard Soulier’s disease, von Willebrand disease, Glanzman’s disease, and Grey platelet syndrome may help categories the molecular lesions in these oft under-studied disorders. PMID:23983579

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

    PubMed Central

    Zerón, Hugo Mendieta; Flores, Alejandro Parada; Chávez, Araceli Amaya; Alanís, Adriana Garduño; Ferreyra, María del Carmen Colín; Benítez, Jonnathan Guadalupe Santillán; Castañeda, Violeta Saraí Morales; García, Ma. Victoria Domínguez

    2013-01-01

    Objective Nuclear factor kappa B (NF-?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

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

    PubMed

    Gundling, William E; Wildman, Derek E

    2015-03-01

    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. A new possible function for placental pericytes.

    PubMed

    Jones, Carolyn J P; Desoye, Gernot

    2011-01-01

    The pericyte is a multifunctional cell closely associated with endothelial cells and may play a role in angiogenesis and vessel stabilisation. Re-examination of over 1,100 micrographs from archival material used to investigate ultrastructural changes in placental development and pathology has identified previously undescribed structures associated with the pericyte of the human placental terminal villus. These structures take the form of outgrowths from the main body of the cell, with a narrow neck rich in cytoplasmic filaments, terminating in swollen tips which appear to bleb off the pericyte and form electron lucent stromal vesicles. Semi-quantitative analysis indicated that these features are present in some placentae from normal, term pregnancies but are increasingly found where capillaries show abnormalities such as a failure to form sinusoids, as in pregnancies complicated by diabetes, postmaturity, rhesus incompatibility and pre-eclampsia. This blebbing is compared with similar phenomena associated with apoptosis and zeiosis and it is suggested that it may contribute to fluid homeostasis where normal mechanisms are impaired by thickening or damage to endothelial cells. PMID:21196697

  12. 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

  13. Long-term medical risks to the living kidney donor.

    PubMed

    Lam, Ngan N; Lentine, Krista L; Levey, Andrew S; Kasiske, Bertram L; Garg, Amit X

    2015-07-01

    Living kidney donation benefits recipients and society but carries short-term and long-term risks for the donor. This Review summarizes the studies that underlie our current understanding of these risks in the first decade after donation, with a view to improving the informed consent process. Two studies report a higher risk of end-stage renal disease (ESRD) among donors than among healthy nondonors; however, the absolute 15-year incidence of ESRD is <1%. All-cause mortality and the risk of cardiovascular events are similar among donors and healthy nondonors, although one study provides evidence for a 5% increase in all-cause mortality after 25 years that is attributable to donation. Some evidence suggests that the 20-year incidence of gout is slightly higher among donors than among healthy nondonors. The risks of gestational hypertension or pre-eclampsia seem to be 6% higher in pregnancies among donors than in pregnancies among healthy nondonors. The incidences of acute kidney injury, kidney stones that require surgical intervention, gastrointestinal bleeding and fractures seem no higher among donors than among healthy nondonors, although some of these conclusions are based on a small number of events. Future studies must clarify the lifetime incidence of long-term outcomes, particularly in relation to a donor's age, race, and history of comorbidities. PMID:25941060

  14. ?-thalassemia-associated hydrops fetalis: A rare cause of thyrotoxic cardiomyopathy.

    PubMed

    Tumian, Nor Rafeah; Wong, Ming; Wong, Chieh Lee

    2015-06-01

    ?°-thalassemia is a well-known cause of hydrops fetalis in South-East Asia and can be detected in utero. We report a very rare case of thyrotoxic cardiomyopathy associated with hyperplacentosis secondary to ?°-thalassemia-associated hydrops fetalis. A 22-year-old primigravida with microcytic anemia presented at 27 weeks' gestation with pre-eclampsia, hyperthyroidism and cardiac failure. Serum ?-human chorionic gonadotrophin was markedly elevated and abdominal ultrasound revealed severe hydropic features and enlarged placenta. Serum ?-human chorionic gonadotrophin, cardiac function and thyroid function tests normalized after she delivered a macerated stillbirth. Histopathology of the placenta showed hyperplacentosis. Blood DNA analysis revealed that both patient and husband have the ?°-thalassemia trait. This case illustrates a very atypical presentation of ?°-thalassemia-associated hydrops fetalis and the importance of early prenatal diagnosis of ?-thalassemia in women of relevant ethnic origin with microcytic anemia so that appropriate genetic counseling can be provided to reduce maternal morbidity and the incidence of hydrops fetalis. PMID:25510540

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

    PubMed

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

    2015-06-01

    Approximately 15% of expected births worldwide will result in life-threatening complications during pregnancy, delivery, or the postpartum period. Providers skilled in emergency obstetric and newborn care (EmONC) services are essential, particularly in countries with a high burden of maternal and newborn mortality. Jhpiego and its consortia partners have implemented three global programs to build provider capacity to provide comprehensive EmONC services to women and newborns in these resource-poor settings. Providers have been educated to deliver high-impact maternal and newborn health interventions, such as prevention and treatment of postpartum hemorrhage and pre-eclampsia/eclampsia and management of birth asphyxia, within the broader context of quality health services. This article describes Jhpiego's programming efforts within the framework of the basic and expanded signal functions that serve as indicators of high-quality basic and emergency care services. Lessons learned include the importance of health facility strengthening, competency-based provider education, global leadership, and strong government ownership and coordination as essential precursors to scale-up of high impact evidence-based maternal and newborn interventions in low-resource settings. PMID:26115858

  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. Uterine artery embolization for uterine arteriovenous malformation in five women desiring fertility: pregnancy outcomes.

    PubMed

    Vilos, Angelos G; Vilos, George A; Hollett-Caines, Jackie; Rajakumar, Chandrew; Garvin, Greg; Kozak, Roman

    2015-07-01

    Uterine arteriovenous malformations (AVM) are rare and can be classified as either congenital or acquired. Acquired AVMs may result from trauma, uterine instrumentation, infection or gestational trophoblastic disease. The majority of acquired AVMs are encountered in women of reproductive age with a history of at least one pregnancy. Traditional therapies of AVMs include medical management of symptomatic bleeding, blood transfusions, uterine artery embolization (UAE) or hysterectomy. In this retrospective case series, we report our experience with AVM and UAE in five symptomatic women of reproductive age who wished to preserve fertility. Patients were 18-32 years old, and had 1-3 previous pregnancies prior to initial presentation. All patients were followed until their deliveries. All five patients delivered live births. Three of the five patients required two embolization procedures and one of these women required a subsequent hysterectomy. Two deliveries were at term and had normal weight babies and normal placenta. One woman had cerclage placed and developed chorioamnionitis at 34 weeks but had a normal placenta. Two pregnancies were induced <37 weeks for pre-eclampsia/b intrauterine growth restriction ± abnormal umbilical artery dopplers. The low birthweight were both <2000 g. Both placentas showed accelerated maturity and infarcts. All estimated blood losses were recorded as <500 cc. In conclusion, UAE may not be as effective at managing AVM as previously thought and should be questioned as an initial therapy in symptomatic women of reproductive age desiring fertility preservation. PMID:25954037

  18. 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

  19. 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

  20. Outcomes of Spontaneous and Assisted Pregnancies in Turner Syndrome: The NIH Experience

    PubMed Central

    Hadnott, Tracy N; Gould, Harley N; Gharib, Ahmed M; Bondy, Carolyn A

    2011-01-01

    Objective To assess fetal and maternal outcomes of pregnancies in women with Turner syndrome (TS). Design Retrospective case series. Setting Clinical research center. Patients 276 adults with cytogenetically-proven TS participating in an intramural natural history protocol Interventions None. Main Outcome Measures Menstrual and obstetric histories, 50-cell karyotypes, and cardiovascular evaluation including aortic diameter measurements. Results Our cohort included five women with spontaneous pregnancies and five with pregnancies using assisted reproduction (ART). All five women with spontaneous pregnancies had spontaneous puberty, despite 45,X in ?90% of their 50-cell karyotype. Participants had a total of 13 pregnancies and 14 live births. One child had cerebral palsy; the others were chromosomally and developmentally normal. Delivery was by Cesarean section in 4/7 spontaneous and 6/6 ART-related pregnancies. One mother experienced pre-eclampsia in an ART-related twin pregnancy requiring preterm delivery; she has marked but stable aortic dilation years later. Conclusions Approximately 2% of our study cohort experienced spontaneous pregnancies despite high grade X monosomy, and a similar number achieved pregnancy via oocyte donation and ART. The potential for life-threatening cardiovascular complications warrants comprehensive screening prior to conception, single embryo transfer, and caution regarding unintentional pregnancies for TS women. PMID:21496813

  1. Effect of Treatment of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

    PubMed Central

    Poolsup, Nalinee; Suksomboon, Naeti; Amin, Muhammad

    2014-01-01

    Objective To assess the efficacy and safety of treating pregnant women with gestational diabetes mellitus in comparison to usual antenatal care. Methods A systematic review and meta-analysis was conducted by including randomized controlled trials comparing any form of therapeutic intervention in comparison to usual antenatal care. A literature search was conducted using electronic databases together with a hand search of relevant journals and conference proceedings. Results Ten studies involving 3,881 patients contributed to meta-analysis. Our results indicated that gestational diabetes mellitus treatment significantly reduced the risk for macrosomia (RR, 0.47; 95% CI, 0.38–0.57), large for gestational age births (RR, 0.55; 95% CI, 0.45–0.67), shoulder dystocia (RR, 0.42; 95% CI, 0.23–0.77) and gestational hypertension (RR, 0.68; 95% CI, 0.53–0.87) without causing any significant increase in the risk for small for gestational age babies. However, no significant difference was observed between the two groups regarding perinatal/neonatal mortality, neonatal hypoglycemia, birth trauma, preterm births, pre-eclampsia, caesarean section and labor induction. Conclusion Treating GDM reduces risk for many important adverse pregnancy outcomes and its association with any harm seems unlikely. PMID:24658089

  2. 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.

  3. How does variability of immune system genes affect placentation?

    PubMed

    Colucci, F; Boulenouar, S; Kieckbusch, J; Moffett, A

    2011-08-01

    Formation of the placenta is a crucial step in mammalian pregnancy. Apart from its function in ensuring an optimal supply of nutrients and oxygen to the fetus, the placenta is also the interface at which allo-recognition of invading trophoblast cells by the maternal immune system can potentially occur. We summarise here the "state of the art" on how variability of immune system genes that code for major histocompatibility complex (MHC) molecules and natural killer receptors (NKR) may impact on human placentation. MHC and NKR are the most polymorphic human genes. Our recent reports point out that specific combinations of fetal MHC and maternal NKR genes in humans correlate with the risk of pre-eclampsia, recurrent miscarriage (RM) and fetal growth restriction (FGR). Research in this field is still at an early stage and future studies in mouse and humans will be needed before the results can be translated to clinical applications. We discuss our recent work, as well as the opportunities offered by mouse genetics, to understand the cellular and molecular mechanisms underlying immune interactions at the maternal-fetal interface. PMID:21665273

  4. How does variability of immune system genes affect placentation?

    PubMed Central

    Colucci, F.; Boulenouar, S.; Kieckbusch, J.; Moffett, A.

    2011-01-01

    Formation of the placenta is a crucial step in mammalian pregnancy. Apart from its function in ensuring an optimal supply of nutrients and oxygen to the fetus, the placenta is also the interface at which allo-recognition of invading trophoblast cells by the maternal immune system can potentially occur. We summarise here the “state of the art” on how variability of immune system genes that code for major histocompatibility complex (MHC) molecules and natural killer receptors (NKR) may impact on human placentation. MHC and NKR are the most polymorphic human genes. Our recent reports point out that specific combinations of fetal MHC and maternal NKR genes in humans correlate with the risk of pre-eclampsia, recurrent miscarriage (RM) and fetal growth restriction (FGR). Research in this field is still at an early stage and future studies in mouse and humans will be needed before the results can be translated to clinical applications. We discuss our recent work, as well as the opportunities offered by mouse genetics, to understand the cellular and molecular mechanisms underlying immune interactions at the maternal-fetal interface. PMID:21665273

  5. 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

  6. The proprotein convertase furin is required for trophoblast syncytialization.

    PubMed

    Zhou, Z; Zhang, Q; Lu, X; Wang, R; Wang, H; Wang, Y-L; Zhu, C; Lin, H-Y; Wang, H

    2013-01-01

    The multinucleated syncytial trophoblast, which forms the outermost layer of the placenta and serves multiple functions, is differentiated from and maintained by cytotrophoblast cell fusion. Deficiencies in syncytial trophoblast differentiation or maintenance likely contribute to intrauterine growth restriction and pre-eclampsia, two common gestational diseases. The cellular and molecular mechanisms governing trophoblast syncytialization are poorly understood. We report here that the proprotein convertase furin is highly expressed in syncytial trophoblast in the first trimester human placentas, and expression of furin in the syncytiotrophoblast is significantly lower in the placentas from pre-eclamptic patients as compared with their gestational age-matched control placentas. Using multiple experimental models including induced fusion of choriocarcinoma BeWo cells and spontaneous fusion of primary cultured cytotrophoblast cells or placental explants, we demonstrate that cytotrophoblast cell fusion and syncytialization are accompanied by furin expression. Furin-specific siRNAs or inhibitors inhibit cell fusion in BeWo cells, as well as trophoblast syncytialization in human placental explants. Furthermore, type 1 IGF receptor (IGF1R) is indicated in this study as a substrate of furin, and processing of IGF1R by furin is an essential mechanism for syncytialization. Finally, using lentivirus-mediated RNAi targeting to mouse trophectoderm, we demonstrate that furin function is required for the development of syncytiotrophoblast structure in the labyrinth layer, as well as for normal embryonic development. PMID:23598405

  7. CUL1 promotes trophoblast cell invasion at the maternal-fetal interface.

    PubMed

    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

  8. The proprotein convertase furin is required for trophoblast syncytialization

    PubMed Central

    Zhou, Z; Zhang, Q; Lu, X; Wang, R; Wang, H; Wang, Y-L; Zhu, C; Lin, H-Y; Wang, H

    2013-01-01

    The multinucleated syncytial trophoblast, which forms the outermost layer of the placenta and serves multiple functions, is differentiated from and maintained by cytotrophoblast cell fusion. Deficiencies in syncytial trophoblast differentiation or maintenance likely contribute to intrauterine growth restriction and pre-eclampsia, two common gestational diseases. The cellular and molecular mechanisms governing trophoblast syncytialization are poorly understood. We report here that the proprotein convertase furin is highly expressed in syncytial trophoblast in the first trimester human placentas, and expression of furin in the syncytiotrophoblast is significantly lower in the placentas from pre-eclamptic patients as compared with their gestational age-matched control placentas. Using multiple experimental models including induced fusion of choriocarcinoma BeWo cells and spontaneous fusion of primary cultured cytotrophoblast cells or placental explants, we demonstrate that cytotrophoblast cell fusion and syncytialization are accompanied by furin expression. Furin-specific siRNAs or inhibitors inhibit cell fusion in BeWo cells, as well as trophoblast syncytialization in human placental explants. Furthermore, type 1 IGF receptor (IGF1R) is indicated in this study as a substrate of furin, and processing of IGF1R by furin is an essential mechanism for syncytialization. Finally, using lentivirus-mediated RNAi targeting to mouse trophectoderm, we demonstrate that furin function is required for the development of syncytiotrophoblast structure in the labyrinth layer, as well as for normal embryonic development. PMID:23598405

  9. 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

  10. Ischemic Stroke during Pregnancy and Puerperium

    PubMed Central

    Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Padovani, Alessandro; Pezzini, Alessandro

    2011-01-01

    Ischemic stroke during pregnancy and puerperium represents a rare occurrence but it could be a serious and stressful event for mothers, infants, and also families. Whenever it does occur, many concerns arise about the safety of the mother and the fetus in relation to common diagnostic tests and therapies leading to a more conservative approach. The physiological adaptations in the cardiovascular system and in the coagulability that accompany the pregnant state, which are more significant around delivery and in the postpartum period, likely contribute to increasing the risk of an ischemic stroke. Most of the causes of an ischemic stroke in the young may also occur in pregnant patients. Despite this, there are specific conditions related to pregnancy which may be considered when assessing this particular group of patients such as pre-eclampsia-eclampsia, choriocarcinoma, peripartum cardiomiopathy, amniotic fluid embolization, and postpartum cerebral angiopathy. This article will consider several questions related to pregnancy-associated ischemic stroke, dwelling on epidemiological and specific etiological aspects, diagnostic issue concerning the use of neuroimaging, and the related potential risks to the embryo and fetus. Therapeutic issues surrounding the use of anticoagulant and antiplatelets agents will be discussed along with the few available reports regarding the use of thrombolytic therapy during pregnancy. PMID:21331336

  11. Clomipramine concentration and withdrawal symptoms in 10 neonates

    PubMed Central

    ter Horst, Peter G J; van der Linde, Susanne; Smit, Jan Pieter; den Boon, Jan; van Lingen, Richard A; Jansman, Frank G A; De Jong-van den Berg, Lolkje T W; Wilffert, Bob

    2012-01-01

    AIM After in utero exposure to tricyclic antidepressants, neonatal withdrawal symptoms have been reported with an estimated incidence between 20 and 50%; however, few data are available for clomipramine. This could also be the case for neonatal pharmacokinetic clomipramine parameters and so this study was set up. METHODS Babies exposed to clomipramine in utero were included in an observational study, approved by the local ethics committee, after written informed consent. Withdrawal symptoms were scored at 12, 24 and 48 h after birth using the Finnegan score. Plasma concentrations were determined using an in-house-developed, validated liquid chromatography with mass detection (LC-MSMS) method at 0, 12, 24 and 48 h after birth. RESULTS We found that three of 11 pregnancies were complicated with pre-eclampsia. Ten neonates were observed for clomipramine withdrawal symptoms. The observed withdrawal symptoms were too short a period of sleep after feeding (6), poor feeding (3), mild to severe tremors (6), hyperactive Moro reflex (3) and respiratory rate >60 breaths min?1. Serious withdrawal reactions, such as tachycardia and cyanosis, were seen. We calculated a half-life value of 42 ± 16 h for clomipramine in neonates. Only a weak correlation was found between withdrawal reactions and clomipramine plasma concentration or desmethylclomipramine plasma concentration. CONCLUSIONS In neonates, clomipramine is eliminated with a half-life value of 42 h, compared with 20 h in adults. In two of 10 neonates, tachycardia and cyanosis were seen as serious withdrawal symptoms after maternal use of clomipramine. PMID:21801198

  12. Posterior reversible encephalopathy syndrome in obstetric patients. Report of three cases with literature review.

    PubMed

    Altinkaya, S O; Nergiz, S; Küçük, M; Yüksel, H; Dayanir, Y

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a serious clinico-neuroradiological maternal complication in pregnancy. Although it has various etiologies such as hypertensive encephalopathy, renal failure, autoimmune disorders, sepsis, multiple organ failure, and treatment with immunosuppressant or cytotoxic agents, pregnancy and postpartum complicated by hypertensive disorders more frequently lead to this condition. PRES is clinically characterized by headache, confusion, seizures, vomiting, and visual disturbances with radiographic vasogenic edema especially affecting symmetrical parietal and occipital lobes. The underlying pathophysiology is still a matter of debate. Prompt recognition and early intervention greatly improve the prognosis, so that obstetricians should be well aware of this rare entity. Timely imaging is of crucial importance especially in patients with an uncertain diagnosis for determining the appropriate treatment and preventing the possible development of neurologic deficits. In the present report, three cases of PRES are presented with clinical and radiological findings in pregnancies complicated by severe pre-eclampsia and eclampsia. The latest literature in the field is also carefully reviewed. PMID:25551975

  13. Modulation of the L-arginine/nitric oxide signalling pathway in vascular endothelial cells.

    PubMed

    Wyatt, Amanda W; Steinert, Joern R; Mann, Giovanni E

    2004-01-01

    Nitric oxide (NO) is synthesized from L-arginine, and in endothelial cells influx of L-arginine is mediated predominantly via Na+-independent cationic amino acid transporters. Constitutive, Ca2+-calmodulin-sensitive eNOS (endothelial nitric oxide synthase) metabolizes L-arginine to NO and L-citrulline. eNOS is present in membrane caveolae and the cytosol and requires tetrahydrobiopterin, NADPH, FAD and FMN as additional cofactors for its activity. Supply of L-arginine for NO synthesis appears to be derived from a membrane-associated compartment distinct from the bulk intracellular amino acid pool, e.g. near invaginations of the plasma membrane referred to as 'lipid rafts' or caveolae. Co-localization of eNOS and the cationic amino acid transport system y+ in caveolae in part explains the 'arginine paradox', related to the phenomenon that in certain disease states eNOS requires an extracellular supply of L-arginine despite having sufficient intracellular L-arginine concentrations. Vasoactive agonists normally elevate [Ca2+]i (intracellular calcium concentration) in endothelial cells, thus stimulating NO production, whereas fluid shear stress, 17beta-oestradiol and insulin cause phosphorylation of the serine/threonine protein kinase Akt/protein kinase B in a phosphoinositide 3-kinase-dependent manner and activation of eNOS at basal [Ca2+]i levels. Adenosine causes an acute activation of p42/p44 mitogen-activated protein kinase and NO release, with membrane hyperpolarization leading to increased system y+ activity in fetal endothelial cells. In addition to acute stimulatory actions of D-glucose and insulin on L-arginine transport and NO synthesis, gestational diabetes, intrauterine growth retardation and pre-eclampsia induce phenotypic changes in the fetal vasculature, resulting in alterations in the L-arginine/NO signalling pathway and regulation of [Ca2+]i. These alterations may have significant implications for long-term programming of the fetal cardiovascular system. PMID:15777019

  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. Multiple assessment techniques evaluate antepartum fetal risks.

    PubMed

    Bobby, Paul

    2003-09-01

    As technology has advanced, the field of antepartum fetal evaluation has grown. As reviewed here, a variety of options are available for use in the complicated pregnancy, including application of fetal heart rate monitoring techniques, noninvasive assessment of amniotic fluid volume, sonographic evaluation of fetal behavior, and Doppler assessment of fetal blood flow. It remains unclear which test is the best for any particular situation. The NST is the simplest test to perform but has a higher false-positive rate than the biophysical profile or the CST. These two tests also appear to demonstrate superior sensitivity, at the expense of increased testing time and cost. The application of vibroacoustic stimulation improves the specificity of the NST, while the addition of a sonographic assessment of amniotic fluid volume increases sensitivity and creates an acceptable alternative as a primary test. The limited biophysical profile, with the NST component initially omitted, provides some savings in time and cost without apparent loss of sensitivity or specificity when compared with the full profile. Ultimately, while one particular technique of fetal assessment may never prove to be the best, certain techniques may have advantages over others in particular clinical situations. Umbilical artery Doppler velocimetry appears to be a useful adjunct to other forms of testing, especially in the pregnancy at risk for intrauterine growth restriction and pre-eclampsia. Recent data have shown the biophysical profile predicts the onset of amnionitis in the setting of preterm premature rupture of membranes (PROM). The sonographic assessment of amniotic fluid volume is particularly important in the serial evaluation of the pregnancy complicated by fetal growth restriction. As new technology leads to innovative forms of testing, it is expected that these new tests of fetal status will similarly add to, rather than replace, the existing items in our armamentarium. PMID:14508894

  16. 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

  17. 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

  18. VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: protective effects of a VEGF164b therapy

    PubMed Central

    2013-01-01

    Background Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165b (VEGF164b in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was determined to be disturbed in many pathologies such as cancer and pre-eclampsia. Results The aims of this study were to examine the role of this inhibitory VEGF by expressing this molecule in a model of intestinal inflammation, and to evaluate its expression as a potential new therapeutic approach for treating UC. A modified model of TNBS colitis was used to determine the effects of rVEGF164b expression on colon inflammation. Expansion of the vascular system was assessed by immunhistochemical methods and macro- and microscopic measurements of inflammation in the colon were measured. Leukocyte invasion of the tissue was measured by myeloperoxidase assay and identification and counting of lymphoid follicles. Both angio- and lymphangiogenesis were reduced by expression of rVEGF164b, which correlated with reduction in both gross and microscopic inflammatory scores. Leukocyte invasion of the tissue was also reduced by rVEGF164b expression. Conclusions This is the first report using an endogenous inhibitory VEGF-A isoform for therapy in a model of experimental colitis. Inhibitory VEGF molecules play an important role in maintenance of gut homeostasis and may be dysregulated in UC. The results of this study suggest that restoration of rVEGF164b expression has anti-inflammatory activity in a TNBS model and warrants further examination as a possible therapeutic for UC. PMID:24020796

  19. The GPR54-Kisspeptin complex in reproductive biology: neuroendocrine significance and implications for ovulation induction and contraception.

    PubMed

    Sills, Eric Scott; Walsh, Anthony P H

    2008-12-01

    KISS1 encodes the kisspeptin (KP) family of peptides which were originally characterised as potent antimetastatic agents in breast cancer and malignant melanoma cells. One member of this family of arginine-phenylalanine amide peptides, KP-54, was subsequently identified as the natural ligand for the G-protein coupled receptor-54 (GPR54). In addition to its importance as a metastatic suppressor, KP has been found to play a major neuroregulatory role in governing endogenous gonadotropin release by its modulation of the hypothalamic-pituitary-gonadal (HPG) axis. In humans, KISS1 mRNA has been localised to the hypothalamic anteroventral periventricular nucleus and arcuate nucleus. Although GPR54 is expressed in human pituitary cells, it is not presently known if gonadotrope cells themselves are targets for significant KP activity. It was recently shown that full disruption of the KP/GPR54 complex resulted in hypogonadotropic hypogonadism. Indeed, evidence now suggests that KP/GPR54 signalling during gestation is necessary for sexual differentiation and implicates activation of the KP/GPR54 complex as the single most important upstream event regulating GnRH release. Several compelling studies have placed KP as the leading candidate molecule responsible for initiating puberty, making this receptor-ligand complex of fundamental importance to the neuroendocrinology of reproduction. Here, we discuss key KP/GPR54 discovery events and present an evolution of KP biology in the context of recent animal and human experimental work. With evidence pointing to proper KP/GPR54 signalling as the principal trigger for activation of GnRH neurons and subsequent ovulation, elucidation of how this pathway is modulated is likely to bring novel pharmacologic strategies for fertility treatment (and contraception) within reach. Because the physiological significance KP is now acknowledged to extend well beyond cancer biology (and may also contribute to the pathophysiology of pre-eclampsia), KP represents an exciting research theme in human reproductive biology and neuroendocrinology. PMID:19112386

  20. 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

  1. [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

  2. 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 30±4.1 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.

  3. Risk factors for maternal mortality in the west of Iran: a nested case-control study

    PubMed Central

    Poorolajal, Jalal; Alafchi, Behnaz; Najafi Vosoogh, Roya; Hamzeh, Sahar; Ghahramani, Masoomeh

    2014-01-01

    OBJECTIVES: With a gradual decline in maternal mortality in recent years in Iran, this study was conducted to identify the remaining risk factors for maternal death. METHODS: This 8-year nested case-control study was conducted in Hamadan Province, in the west of Iran, from April 2006 to March 2014. It included 185 women (37 cases and 148 controls). All maternal deaths that occurred during the study period were considered cases. For every case, four women with a live birth were selected as controls from the same area and date. Conditional logistic regression analysis was performed and the odds ratio (OR) and its 95% confidence interval (CI) were obtained for each risk factor. RESULTS: The majority of cases were aged 20-34 years, died in hospital, and lived in urban areas. The most common causes of death were bleeding, systemic disease, infection, and pre-eclampsia. The OR estimate of maternal death was 8.48 (95% CI=1.26-56.99) for advanced maternal age (?35 years); 2.10 (95% CI=0.07-65.43) for underweight and 10.99 (95% CI=1.65-73.22) for overweight or obese women compared to those with normal weight; 1.56 (95% CI=1.08-2.25) for every unit increase in gravidity compared to those with one gravidity; 1.73 (95% CI=0.34-8.88) for preterm labors compared to term labors; and 17.54 (95% CI= 2.71-113.42) for women with systemic diseases. CONCLUSIONS: According to our results, advanced maternal age, abnormal body mass index, multiple gravidity, preterm labor, and systemic disease were the main risk factors for maternal death. However, more evidence based on large cohort studies in different settings is required to confirm our results. PMID:25381997

  4. Placental changes in pregnancy induced hypertension and its impacts on fetal outcome.

    PubMed

    Nahar, L; Nahar, K; Hossain, M I; Yasmin, H; Annur, B M

    2015-01-01

    A descriptive cross sectional study was carried out in the Gynae and Obstetrics & Pathology department of Mymensingh Medical College & Hospital (MMCH) to see the placental changes in normal & pregnancy induced hypertension (PIH) and its impacts on fetus for one year period. Total 80 placentas were collected, 40 from normal pregnant mothers having no hypertension and 40 from PIH group (one from gestational hypertension, 17 from pre-eclampsia and 22 from eclampsia. Macroscopic study of the placenta revealed placental weight, surface area and number of cotyledons were less in study group. Mean placental weight in study group was 419.50gm and in control group was 477.50 (p<0.001). Mean surface area in study group & control group were 232.29cm² and 304.80cm² respectively (p<0.001). Mean number of cotyledons were 15.39 and 17.40 in study & control group respectively (P<0.001) and lower diameter of umbilical cord (p<0.04667). But in the present study placental thickness was not significant (p<0.539). There was a single umbilical artery present in one patient in PIH group .In PIH group syncytial knots (95%), fibrinoid necrosis (80%), VSM (vasculosyncytial membrane) formation, sclerosis, chorangiosis and calcification were more marked. Infarction was present in placenta of PIH 34(85%) and in control group 8(20%). There was a tendency of lowering the weight of neonate 2.47kg in study group and 3.06kg in control group (p<0.001), number of asphyxiated babies and perinatal morbidity and mortality( still birth was 7.5 and neonatal death was 15%) were more marked in PIH group. In PIH group placental changes were related with fetal outcome. Common placental changes were significant in this study. PMID:25725662

  5. Study protocol: Cost effectiveness of two strategies to implement the NVOG guidelines on hypertension in pregnancy: An innovative strategy including a computerised decision support system compared to a common strategy of professional audit and feedback, a randomized controlled trial

    PubMed Central

    2010-01-01

    Background Hypertensive disease in pregnancy remains the leading cause of maternal mortality in the Netherlands. Seventeen percent of the clinical pregnancies are complicated by hypertension and 2% by preeclampsia. The Dutch Society of Obstetrics and Gynaecology (NVOG) has developed evidence-based guidelines on the management of hypertension in pregnancy and chronic hypertension. Previous studies showed a low adherence rate to other NVOG guidelines and a large variation in usual care in the different hospitals. An explanation is that the NVOG has no general strategy of practical implementation and evaluation of its guidelines. The development of an effective and cost effective implementation strategy to improve adherence to the guidelines on hypertension in pregnancy is needed. Methods/Design The objective of this study is to assess the cost effectiveness of an innovative implementation strategy of the NVOG guidelines on hypertension including a computerised decision support system (BOS) compared to a common strategy of professional audit and feedback. A cluster randomised controlled trial with an economic evaluation alongside will be performed. Both pregnant women who develop severe hypertension or pre-eclampsia and professionals involved in the care for these women will participate. The main outcome measures are a combined rate of major maternal complications and process indicators extracted from the guidelines. A total of 472 patients will be included in both groups. For analysis, descriptive as well as regression techniques will be used. A cost effectiveness and cost utility analysis will be performed according to the intention-to-treat principle and from a societal perspective. Cost effectiveness ratios will be calculated using bootstrapping techniques. PMID:20819222

  6. 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

  7. Transcriptional regulation of human thromboxane synthase gene expression

    SciTech Connect

    Lee, K.D.; Baek, S.J.; Fleischer, T [Univ. of Maryland Medical School, Baltimore, MD (United States)] [and others

    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.

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

    PubMed Central

    Cosson, Emmanuel; Bihan, Hélène; Reach, Gérard; Vittaz, Laurence; Carbillon, Lionel; Valensi, Paul

    2015-01-01

    Objective To evaluate the prognoses associated with psychosocial deprivation in women with gestational diabetes mellitus (GDM). Design Observational study considering the 1498 multiethnic women with GDM who gave birth between January 2009 and February 2012. Setting Four largest maternity units in the northeastern suburban area of Paris. Participants The 994 women who completed the Evaluation of Precarity and Inequalities in Health Examination Centers (EPICES) questionnaire. Main outcome measure Main complications of GDM (large infant for gestational age (LGA), shoulder dystocia, caesarean section, pre-eclampsia). Results Psychosocial deprivation (EPICES score ?30.17) affected 577 women (56%) and was positively associated with overweight/obesity, parity and non-European origin, and negatively associated with family history of diabetes, fruit and vegetable consumption and working status. The psychosocially deprived women were diagnosed with GDM earlier, received insulin treatment during pregnancy more often and were more likely to have LGA infants (15.1% vs 10.6%, OR=1.5 (95% CI 1.02 to 2.2), p<0.05) and shoulder dystocia (3.1% vs 1.2%, OR=2.7 (0.97 to 7.2), p<0.05). In addition to psychosocial deprivation, LGA was associated with greater parity, obesity, history of GDM, ethnicity, excessive gestational weight gain and insulin therapy. A multivariate analysis using these covariates revealed that the EPICES score was independently associated with LGA infants (per 10 units, OR=1.12 (1.03 to 1.20), p<0.01). Conclusions In our area, psychosocial deprivation is common in women with GDM and is associated with earlier GDM diagnoses and greater insulin treatment, an increased likelihood of shoulder dystocia and, independently of obesity, gestational weight gain and other confounders with LGA infants. PMID:25748416

  9. 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

  10. Study protocol. A prospective cohort study of unselected primiparous women: the pregnancy outcome prediction study

    PubMed Central

    Pasupathy, Dharmintra; Dacey, Alison; Cook, Emma; Charnock-Jones, D Stephen; White, Ian R; Smith, Gordon CS

    2008-01-01

    Background There have been dramatic changes in the approach to screening for aneuploidy over the last 20 years. However, the approach to screening for other complications of pregnancy such as intra-uterine growth restriction, pre-eclampsia and stillbirth remains largely unchanged. Randomised controlled trials of routine application of high tech screening methods to the general population have generally failed to show improvement in outcome. We have previously reviewed this and concluded it was due, in large part, to poor performance of screening tests. Here, we report a study design where the primary aim is to generate clinically useful methods to screen women to assess their risk of adverse pregnancy outcome. Methods/design We report the design of a prospective cohort study of unselected primiparous women recruited at the time of their first ultrasound scan. Participation involves serial phlebotomy and obstetric ultrasound at the dating ultrasound scan (typically 10–14 weeks), 20 weeks, 28 weeks and 36 weeks gestation. In addition, maternal demographic details are obtained; maternal and paternal height are measured and maternal weight is serially measured during the pregnancy; maternal, paternal and offspring DNA are collected; and, samples of placenta and membranes are collected at birth. Data will be analysed as a prospective cohort study, a case-cohort study, and a nested case-control study. Discussion The study is expected to provide a resource for the identification of novel biomarkers for adverse pregnancy outcome and to evaluate the performance of biomarkers and serial ultrasonography in providing clinically useful prediction of risk. PMID:19019223

  11. Three-Dimensional Segmented Poincaré 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 6–8% of gestations representing the most common complication of pregnancy for both mother and fetus. The aim of this study was to introduce a new three-dimensional coupling analysis methods – the three-dimensional segmented Poincaré plot analyses (SPPA3) – to establish an effective approach for the detection of hypertensive pregnancy disorders and especially pre-eclampsia (PE). A cubic box model representing the three-dimensional phase space is subdivided into 12?×?12?×?12 equal predefined cubelets according to the range of the SD of each investigated signal. Additionally, we investigated the influence of rotating the cloud of points and the size of the cubelets (adapted or predefined). All single probabilities of occurring points in a specific cubelet related to the total number of points are calculated. In this study, 10 healthy non-pregnant women, 66 healthy pregnant women, and 56 hypertensive pregnant women (chronic hypertension, pregnancy-induced hypertension, and PE) were investigated. From all subjects, 30?min of beat-to-beat intervals (BBI), respiration (RESP), non-invasive systolic (SBP), and diastolic blood pressure (DBP) were continuously recorded and analyzed. Non-rotated adapted SPPA3 discriminated best between hypertensive pregnancy disorders and PE concerning coupling analysis of two or three different systems (BBI, DBP, RESP and BBI, SBP, DBP) reaching an accuracy of up to 82.9%. This could be increased to an accuracy of up to 91.2% applying multivariate analysis differentiating between all pregnant women and PE. In conclusion, SPPA3 could be a useful method for enhanced risk stratification in pregnant women. PMID:25429364

  12. 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

  13. 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

  14. 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

  15. Cesarean Section Rates and Indications in Sub-Saharan Africa: A Multi-Country Study from Medecins sans Frontieres

    PubMed Central

    Chu, Kathryn; Cortier, Hilde; Maldonado, Fernando; Mashant, Tshiteng; Ford, Nathan; Trelles, Miguel

    2012-01-01

    Objectives The World Health Organization considers Cesarean section rates of 5–15% to be the optimal range for targeted provision of this life saving intervention. However, access to safe Cesarean section in resource-limited settings is much lower, estimated at 1–2% reported in sub-Saharan Africa. This study reports Cesarean sections rates and indications in Democratic Republic of Congo, Burundi, and Sierra Leone, and describe the main parameters associated with maternal and early neonatal mortality. Methods Women undergoing Cesarean section from August 1 2010 to January 31 2011 were included in this prospective study. Logistic regression was used to model determinants of maternal and early neonatal mortality. Results 1276 women underwent a Cesarean section, giving a frequency of 6.2% (range 4.1–16.8%). The most common indications were obstructed labor (399, 31%), poor presentation (233, 18%), previous Cesarean section (184, 14%), and fetal distress (128, 10%), uterine rupture (117, 9%) and antepartum hemorrhage (101, 8%). Parity >6 (adjusted odds ratio [aOR]?=?8.6, P?=?0.015), uterine rupture (aOR?=?20.5; P?=?.010), antepartum hemorrhage (aOR?=?13.1; P?=?.045), and pre-eclampsia/eclampsia (aOR?=?42.9; P?=?.017) were associated with maternal death. Uterine rupture (aOR?=?6.6, P<0.001), anterpartum hemorrhage (aOR?=?3.6, P<0.001), and cord prolapse (aOR?=?2.7, P?=?0.017) were associated with early neonatal death. Conclusions This study demonstrates that target Cesarean section rates can be achieved in sub-Saharan Africa. Identifying the common indications for Cesarean section and associations with mortality can target improvements in antenatal services and emergency obstetric care. PMID:22962616

  16. Normal Human Pregnancy Results in Maternal Immune Activation in the Periphery and at the Uteroplacental Interface

    PubMed Central

    Yesayan, Maria N.; Kahn, Daniel A.

    2014-01-01

    Pregnancy poses a unique challenge to the human immune system: the semi-allogeneic fetus must be protected from maternal immune attack while immunity towards pathogens is maintained. Breakdown in maternal-fetal tolerance can lead to pregnancy-specific diseases with potentially high degrees of morbidity and mortality for both the mother and her fetus. Various immune cell-types could mediate these functions, but a comprehensive evaluation of the peripheral and local maternal T cell and regulatory T cell compartments in normal human pregnancy is lacking. In this case-control study, we apply the Human Immunology Project Consortium proposed gating strategies to samples from healthy 3rd trimester human subjects compared with healthy non-pregnant controls. The proportions of HLA-DR+ and CD38+ effector- and effector memory CD8 T cells are significantly increased in the peripheral blood of pregnant women. Utilizing a novel technique that takes advantage of the standard protocol for intrauterine cleanup after cesarean section, we isolate lymphocytes resident at the uteroplacental interface (UPI). At the UPI, the CD4 and CD8 T cell compartments largely mirror the peripheral blood, except that the proportion of HLA-DR+ activated T regulatory cells is significantly increased in direct proportion to an observed increase in the number of activated CD8 T cells. We find that cryopreservation and delayed sample processing (>12 hours) decreases our ability to identify regulatory T cell subsets. Further, the Consortium proposed method for Treg identification underrepresents Resting and Cytokine Tregs compared with Activated Tregs, thus skewing the entire population. Better understanding of the changes in the immune system during pregnancy in the peripheral blood and at the uteroplacental interface are essential for progress in treatment of pregnancy diseases such as pre-eclampsia and recurrent miscarriage. PMID:24846312

  17. 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

  18. 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.

  19. Controlling the Immunological Crosstalk during Conception and Pregnancy: HLA-G in Reproduction

    PubMed Central

    Lynge Nilsson, Line; Djurisic, Snezana; Hviid, Thomas Vauvert F.

    2014-01-01

    In several years after its discovery in the placenta, the human leukocyte antigen (HLA) class Ib protein, HLA-G, was not given much attention, nor was it assigned great importance. As time has unraveled, HLA-G has proven to have distinctive functions and an unforeseen and possibly important role in reproduction. HLA-G is characterized mainly by its low polymorphism and restricted tissue distribution in non-pathological conditions. In fact, its expression pattern is primarily limited to extravillous cytotrophoblast cells at the maternal-fetal interface during pregnancy. Due to low polymorphism, almost the same protein is expressed by virtually all individuals. It is these unique features that make HLA-G differ from its highly polymorphic HLA class Ia counterparts, the HLA-A, -B, and -C molecules. Its function, seemingly diverse, is typically receptor-mediated, and involves interactions with a wide range of immune cells. As the expression of HLA-G primarily is limited to gestation, this has given rise to the hypothesis that HLA-G plays an important role in the immunological tolerance of the fetus by the mother. In keeping with this, it might not be surprising that polymorphisms in the HLA-G gene, and levels of HLA-G expression, have been linked to reproductive failure and pre-eclampsia. Based on recent studies, we speculate that HLA-G might be involved in mechanisms in reproductive immunology even before conception because HLA-G can be detected in the genital tract and in the blood of non-pregnant women, and is present in seminal fluid from men. In addition, HLA-G expression has been found in the pre-implanted embryo. Therefore, we propose that a combined contribution from the mother, the father, and the embryo/fetus is likely to be important. Furthermore, this review presents important aspects of HLA-G in relation to reproduction: from genetics to physiological effects, from pregnancy and pregnancy complications to a short discussion on future possible means of preventative measures and therapy. PMID:24860568

  20. Differential effects of complement activation products c3a and c5a on cardiovascular function in hypertensive pregnant rats.

    PubMed

    Lillegard, Kathryn E; Loeks-Johnson, Alex C; Opacich, Jonathan W; Peterson, Jenna M; Bauer, Ashley J; Elmquist, Barbara J; Regal, Ronald R; Gilbert, Jeffrey S; Regal, Jean F

    2014-11-01

    Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia-induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension. On gestational day (GD) 14, rats underwent sham surgery or vascular clip placement on ovarian arteries and abdominal aorta (RUPP). Rats were treated once daily with the C5a receptor antagonist (C5aRA), PMX51 (acetyl-F-[Orn-P-(D-Cha)-WR]), the C3a receptor antagonist (C3aRA), SB290157 (N(2)-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14-18. Both the C3aRA and C5aRA attenuated placental ischemia-induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia-induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia-induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia-induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti-inflammatory approach. PMID:25150279

  1. Role of D-dimer in determining coagulability status in pre-eclamptic and normotensive pregnant women.

    PubMed

    Rahman, R; Begum, K; Khondker, L; Majumder, N I; Nahar, K; Sultana, R; Siddika, A

    2015-01-01

    A cross sectional study was carried out from January 2007 to December 2008 in the department of Obstetrics and Gynaecology, Dhaka Medical College Hospital, Dhaka in collaboration with Department of Haematology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Pregnant women with pre-eclampsia attending at Out-patient Department (OPD) and admitted in In-patient Department of Obstetrics and Gynaecology Dhaka Medical College Hospital, Dhaka were selected as cases. Healthy and uncomplicated pregnant women admitted in the same hospital were taken as controls. The study showed that 26-30 years and 21-25 years age category was higher in the case and control groups and the mean age was significantly higher in case group compared to control group (p=0.025). The study showed that 44% of case group had a significantly high level of plasma D-dimer (>0.5?g/ml) as opposed to control group (8%) (p<0.001). Estimation of odds ratio demonstrates that pre-eclamptic women (case) had 9 times (95% of CI = 2.8 - 28.9) more risk of having plasma D-dimer >0.5?g/ml than that of normal pregnant women (control). The mean systolic and diastolic blood pressures in patients with plasma D-dimer >0.5?g/ml were considerably higher than those who had plasma D-dimer ?0.5?g/ml (p<0.001). The study showed that majority (81.8%) of pre-eclamptic women with plasma D-dimer >0.5?g/ml had systolic blood pressure ? 160 mm Hg compared to 46.4% of those who had plasma D-dimer ?0.5?g/ml (p=0.010). And ninety percent of pre-eclamptic women with plasma D-dimer >0.5?g/ml had exhibited severe proteinuria as opposed to 53.6% of those who had plasma D-dimer ?0.5?g/ml (p=0.017). The study concludes that plasma D-dimer level can easily be used in screening for the hypercoagulable state in pre-eclamptic patients which have preventive and therapeutic implications. PMID:25725677

  2. 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 ?-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

  3. Autoantibody-mediated angiotensin receptor activation contributes to preeclampsia through TNF-alpha signaling

    PubMed Central

    Irani, Roxanna A.; Zhang, Yujin; Zhou, Cissy Chenyi; Blackwell, Sean C.; Hicks, M. John; Ramin, Susan M.; Kellems, Rodney E.; Xia, Yang

    2012-01-01

    Preeclampsia is a prevalent life-threatening hypertensive disorder of pregnancy whose pathophysiology remains largely undefined. Recently, a circulating maternal autoantibody, the angiotensin II type I receptor agonistic autoantibody (AT1-AA), has emerged as a contributor to disease features. Increased circulating maternal tumor necrosis factor alpha (TNF-?) is also associated with the disease, however it is unknown if this factor directly contributes to preeclamptic symptoms. Here we report that this autoantibody increases the pro-inflammatory cytokine TNF-? in the circulation of AT1-AA-injected pregnant mice, but not in non-pregnant mice. Co-injection of AT1-AA with a TNF-? neutralizing antibody reduced cytokine availability in AT1-AA-injected pregnant mice. Moreover, TNF-? blockade in AT1-AA-injected pregnant mice significantly attenuated the key features of preeclampsia. Autoantibody-induced hypertension was reduced from 131±4 to 110±4 mmHg and proteinuria was reduced from 212±25 to 155±23 ?g albumin/mg creatinine (both P<0.05). Injection of PE-IgG increased the serum levels of circulating soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) (34.1±5.1, 2.4±0.3 ng/ml, respectively), and co-injection with the TNF-? blocker significantly reduced their levels (21.7±3.4, 1.2±0.4 ng/ml, respectively). Renal damage and placental abnormalities were also decreased by TNF-alpha blockade. Lastly, the elevated circulating TNF-? in preeclamptic patients is significantly correlated to the AT1-AA bioactivity in our patient cohort. Similarly, the autoantibody, through AT1 receptor mediated TNF-? induction, contributed to increased sFlt-1, sEng secretion and increased apoptosis in cultured human villous explants. Overall, AT1-AA is a novel candidate that induces TNF-?, a cytokine which may play an important pathogenic role in preeclampsia. Keywords: Basic Science; Experimental models; Pre-eclampsia/pregnancy; Angiotensin receptors; Inflammation. PMID:20351341

  4. Utero-placental Doppler ultrasound for improving pregnancy outcome

    PubMed Central

    Stampalija, Tamara; Gyte, Gillian ML; Alfirevic, Zarko

    2014-01-01

    Background Impaired placentation can cause some of the most important obstetrical complications such as pre-eclampsia and intrauterine growth restriction and has been linked to increased fetal morbidity and mortality. The failure to undergo physiological trophoblastic vascular changes is reflected by the high impedance to the blood flow at the level of the uterine arteries. Doppler ultrasound study of utero-placental blood vessels, using waveform indices or notching, may help to identify the ‘at-risk’ women in the first and second trimester of pregnancy, such that interventions might be used to reduce maternal and fetal morbidity and/or mortality. Objectives To assess the effects on pregnancy outcome, and obstetric practice, of routine utero-placental Doppler ultrasound in first and second trimester of pregnancy in pregnant women at high and low risk of hypertensive complications. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (June 2010) and the reference lists of identified studies. Selection criteria Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of utero-placental vessel waveforms in first and second trimester compared with no Doppler ultrasound. We have excluded studies where uterine vessels have been assessed together with fetal and umbilical vessels. Data collection and analysis Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We checked data entry. Main results We found two studies involving 4993 participants. The methodological quality of the trials was good. Both studies included women at low risk for hypertensive disorders, with Doppler ultrasound of the uterine arteries performed in the second trimester of pregnancy. In both studies, pathological finding of uterine arteries was followed by low-dose aspirin administration. We identified no difference in short-term maternal and fetal clinical outcomes. We identified no randomised studies assessing the utero-placental vessels in the first trimester or in women at high risk for hypertensive disorders. Authors’ conclusions Present evidence failed to show any benefit to either the baby or the mother when utero-placental Doppler ultrasound was used in the second trimester of pregnancy in women at low risk for hypertensive disorders. Nevertheless, this evidence cannot be considered conclusive with only two studies included. There were no randomised studies in the first trimester, or in women at high risk. More research is needed to investigate whether the use of utero-placental Doppler ultrasound may improve pregnancy outcome. PMID:20824875

  5. 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

  6. Birth-weight, insulin levels, and HOMA-IR in newborns at term

    PubMed Central

    2012-01-01

    Background Recent studies have demonstrated that low and high birth-weight at birth are risk factors of developing diabetes. The aim of this study was to determine if the abnormal birth-weight is related with hyperinsulinemia and elevated index of the Homeostasis Model assessment for Insulin Resistance (HOMA-IR) at birth, in at term newborns. Methods Newborns with gestational age between 38 and 41?weeks, products of normal pregnancies of healthy mothers aged 18 to 39?years, were eligible to participate. Small-for-gestational age (SGA) and large-for-gestational age (LGA) newborns were compared with appropriate-for-gestational (AGA) age newborns. Incomplete or unclear data about mother’s health status, diabetes, gestational diabetes, history of gestational diabetes, hypertension, pre-eclampsia, eclampsia, and other conditions that affect glucose metabolism were exclusion criteria. Hyperinsulinemia was defined by serum insulin levels ?13.0 ?U/mL and IR by HOMA-IR ?2.60. Multiple logistic regression analysis was used to determine the odds ratio (OR) that computes the association between birth-weight (independent variable) with hyperinsulinemia and HOMA-IR index (dependent variables). Results A total of 107 newborns were enrolled; 13, 22, and 72 with SGA, LGA, and AGA, respectively. Hyperinsulinemia was identified in 2 (15.4%), 6 (27.3%), and 5 (6.9%) with SGA, LGA, and AGA (p=0.03), whereas IR in 3 (23.1%), 8 (36.4%), and 10 (13.9%) newborns with SGA, LGA and AGA (p=0.06). The LGA showed a strong association with hyperinsulinemia (OR 5.02; CI 95%, 1.15-22.3; p=0.01) and HOMA-IR (OR 3.54; CI 95%, 1.03-12.16; p=0.02); although without statistical significance, the SGA showed a tendency of association with hyperinsulinemia (OR 2.43; CI 95%, 0.43-17.3 p=0.29) and HOMA-IR (OR 1.86; CI 95%, 0.33-9.37; p=0.41). Conclusions Our results suggest that LGA is associated with hyperinsulinemia and elevated HOMA-IR at birth whereas the SGA show a tendency of association. PMID:22770114

  7. 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

  8. Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial

    PubMed Central

    2014-01-01

    Objective To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women. Design Multicentre randomised trial. We utilised a central telephone randomisation server, with computer generated schedule, balanced variable blocks, and stratification for parity, body mass index (BMI) category, and hospital. Setting Three public maternity hospitals across South Australia. Participants 2212 women with a singleton pregnancy, between 10+0 and 20+0 weeks’ gestation, and BMI ?25. Interventions 1108 women were randomised to a comprehensive dietary and lifestyle intervention delivered by research staff; 1104 were randomised to standard care and received pregnancy care according to local guidelines, which did not include such information. Main outcome measures Incidence of infants born large for gestational age (birth weight ?90th centile for gestation and sex). Prespecified secondary outcomes included birth weight >4000 g, hypertension, pre-eclampsia, and gestational diabetes. Analyses used intention to treat principles. Results 2152 women and 2142 liveborn infants were included in the analyses. The risk of the infant being large for gestational age was not significantly different in the two groups (lifestyle advice 203/1075 (19%) v standard care 224/1067 (21%); adjusted relative risk 0.90, 95% confidence interval 0.77 to 1.07; P=0.24). Infants born to women after lifestyle advice were significantly less likely to have birth weight above 4000 g (lifestyle advice 164/1075 (15%) v standard care 201/1067 (19%); 0.82, 0.68 to 0.99; number needed to treat (NNT) 28, 15 to 263; P=0.04). There were no differences in maternal pregnancy and birth outcomes between the two treatment groups. Conclusions For women who were overweight or obese, the antenatal lifestyle advice used in this study did not reduce the risk delivering a baby weighing above the 90th centile for gestational age and sex or improve maternal pregnancy and birth outcomes. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426). PMID:24513442

  9. 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

  10. Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner

    PubMed Central

    Vasilopoulou, E.; Loubière, L.S.; Lash, G.E.; Ohizua, O.; McCabe, C.J.; Franklyn, J.A.; Kilby, M.D.; Chan, S.Y.

    2014-01-01

    STUDY QUESTION Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? SUMMARY ANSWER T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. WHAT IS KNOWN ALREADY Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. STUDY DESIGN, SIZE, DURATION This laboratory-based study used human decidua from first (8–11 weeks; n = 18) and second (12–16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10?) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel® was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (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