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1

Pre-eclampsia: pathophysiology, diagnosis, and management  

PubMed Central

The incidence of pre-eclampsia ranges from 3% to 7% for nulliparas and 1% to 3% for multiparas. Pre-eclampsia is a major cause of maternal mortality and morbidity, preterm birth, perinatal death, and intrauterine growth restriction. Unfortunately, the pathophysiology of this multisystem disorder, characterized by abnormal vascular response to placentation, is still unclear. Despite great polymorphism of the disease, the criteria for pre-eclampsia have not changed over the past decade (systolic blood pressure >140 mmHg or diastolic blood pressure ?90 mmHg and 24-hour proteinuria ?0.3 g). Clinical features and laboratory abnormalities define and determine the severity of pre-eclampsia. Delivery is the only curative treatment for pre-eclampsia. Multidisciplinary management, involving an obstetrician, anesthetist, and pediatrician, is carried out with consideration of the maternal risks due to continued pregnancy and the fetal risks associated with induced preterm delivery. Screening women at high risk and preventing recurrences are key issues in the management of pre-eclampsia. PMID:21822394

Uzan, Jennifer; Carbonnel, Marie; Piconne, Olivier; Asmar, Roland; Ayoubi, Jean-Marc

2011-01-01

2

Neurokinin B and pre-eclampsia: a decade of discovery  

PubMed Central

At the start of the last decade, we provided evidence that levels of the peptide neurokinin B were highly elevated in pre-eclampsia. We hypothesized that elevated levels of neurokinin B may be an indicator of pre-eclampsia and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms. At the time of the original hypothesis many questions remained outstanding. These included - Does neurokinin B have any diagnostic value in the detection and diagnosis of pre-eclampsia? - What is the cause of the elevated levels of neurokinin B during pre-eclampsia? - What is the physiological significance of neurokinin B in the placenta? This review discusses the answers to these questions taking into account the subsequent developments of the past ten years and analyzing the plethora of discoveries that have arisen from those initial observations. PMID:20074343

2010-01-01

3

Does consanguinity affect the severity of pre-eclampsia?  

Microsoft Academic Search

To determine whether consanguinity is more likely to be associated with severe forms of pre-eclampsia\\/eclampsia. Presuming a pure genetic contribution, we speculated that consanguineous marriages would increase the occurrence of severe forms of pre-eclampsia\\/eclampsia, through an expected increased chance for homozygosity to the putative gene. The study is a clinical case series on pre-eclamptic\\/eclamptic primiparae delivered at Princess Badea Teaching

Francis L. Badria; Z. O. Amarin

2003-01-01

4

Diagnosis and management of pre-eclampsia: an update  

PubMed Central

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

Turner, Judi A

2010-01-01

5

Effect of Low-Dose Aspirin or Calcium Supplementation on the incidence of Pre-eclampsia  

E-print Network

Effect of Low-Dose Aspirin or Calcium Supplementation on the incidence of Pre-eclampsia among the incidence of pre-eclampsia. This study was designed to evaluate the effects of low-dose aspirin or calcium or obstetric complications. Women were divided into three equivalent groups. Group 1 received 75 mg of Aspirin

6

Recent advances in the diagnosis and management of pre-eclampsia  

PubMed Central

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.

Duhig, Kate E.

2015-01-01

7

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

PubMed Central

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

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

2014-01-01

8

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

PubMed

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

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

2015-02-01

9

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

E-print Network

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 ...

Moyes, Amie Jane

2010-01-01

10

Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study  

PubMed Central

Objective The objective of this study was to compare international trends in pre-eclampsia rates and in overall pregnancy hypertension rates (including gestational hypertension, pre-eclampsia and eclampsia). Design Population data (from birth and/or hospital records) on all women giving birth were available from Australia (two states), Canada (Alberta), Denmark, Norway, Scotland, Sweden and the USA (Massachusetts) for a minimum of 6?years from 1997 to 2007. All countries used the 10th revision of the International Classification of Diseases, except Massachusetts which used the 9th revision. There were no major changes to the diagnostic criteria or methods of data collection in any country during the study period. Population characteristics as well as rates of pregnancy hypertension and pre-eclampsia were compared. Results Absolute rates varied across the populations as follows: pregnancy hypertension (3.6% to 9.1%), pre-eclampsia (1.4% to 4.0%) and early-onset pre-eclampsia (0.3% to 0.7%). Pregnancy hypertension and/or pre-eclampsia rates declined over time in most populations. This was unexpected given that factors associated with pregnancy hypertension such as pre-pregnancy obesity and maternal age are generally increasing. However, there was also a downward shift in gestational age with fewer pregnancies reaching 40?weeks. Conclusion The rate of pregnancy hypertension and pre-eclampsia decreased in northern Europe and Australia from 1997 to 2007, but increased in Massachusetts. The use of a different International Classification of Diseases coding version in Massachusetts may contribute to the difference in trend. Elective delivery prior to the due date is the most likely explanation for the decrease observed in Europe and Australia. Also, the use of interventions that reduce the risk of pregnancy hypertension and/or progression to pre-eclampsia (low-dose aspirin, calcium supplementation and early delivery for mild hypertension) may have contributed to the decline. PMID:22021762

Ford, Jane B; Algert, Charles S; Antonsen, Sussie; Chalmers, James; Cnattingius, Sven; Gokhale, Manjusha; Kotelchuck, Milton; Melve, Kari K; Langridge, Amanda; Morris, Carole; Morris, Jonathan M; Nassar, Natasha; Norman, Jane E; Norrie, John; Sørensen, Henrik Toft; Walker, Robin; Weir, Christopher J

2011-01-01

11

Activin signalling and pre-eclampsia: from genetic risk to pre-symptomatic biomarker.  

PubMed

Pre-eclampsia is a multi-system condition in pregnancy that is characterised by the onset of hypertension and proteinuria in women after the 20th week and it remains a leading cause of maternal and fetal mortality. Despite this the causative molecular basis of pre-eclampsia remains poorly understood. As a result, an intensive research effort has focused on understanding the molecular mechanisms involved in pre-eclampsia and using this information to identify new pre-symptomatic bio-markers of the condition. Activin A and its receptor, ACVR2A, have been extensively studied in this regard. Activin A is a member of the transforming growth factor (TGF)-? superfamily that has a wide range of biological functions depending on the cellular context. Recent work has shown that polymorphisms in ACVR2A may be a genetic risk factor for pre-eclampsia. Furthermore, both placenta and serum levels of Activin A are significantly increased in pre-eclampsia suggesting that Activin A may be a possible biomarker for the condition. Here we review the latest advances in this field and link these with new molecular data that suggest that the oxidative stress and pro-inflammatory cytokine production seen in pre-eclampsia may result in increased placental Activin A secretion in an attempt to maintain placental function. PMID:25510903

Williamson, Rachel D; O'Keeffe, Gerard W; Kenny, Louise C

2015-02-01

12

Development of Purtscher-like retinopathy after pre-eclampsia combined with acute pancreatitis  

PubMed Central

Visual disturbances are common among women with pre-eclampsia. The obstetricians should have an understanding of the various conditions associated with visual impairments. We report a case of Purtscher-like retinopathy developed after pre-eclampsia combined with acute pancreatitis. A 33-year-old primigravida with twin pregnancy was admitted to the department of obstetrics and gynecology for preterm labor and pre-eclampsia at 36+4 weeks gestation. After a cesarean section, she complained of abdominal pain and visual acuity loss. She was diagnosed with Purtscher-like retinopathy combined with acute pancreatitis after ophthalmologic examination and an abdominal computed tomography scan. Purtscher-like retinopathy, most often observed after trauma, is very rare in pre-eclampsia. In addition, while visual disturbances from other conditions are transient, it can result in persistent visual impairments. Thus, when a patient with pre-eclampsia complains of visual problems for a long period of time, obstetricians should consider an ophthalmologic evaluation and treatments during the earliest stage of the disease. PMID:24328012

Jeon, Sun Young; Seol, Hyun Joo; Hur, Yun Jung

2013-01-01

13

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

PubMed Central

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

Williams, Paula J.; Broughton Pipkin, Fiona

2011-01-01

14

Association between risk for pre-eclampsia and HLA DR4  

SciTech Connect

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.

Not Available

1990-03-17

15

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

PubMed Central

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

Gandhi, Sangeetha; Rao, Vishwas

2014-01-01

16

Blood group AB and factor V Leiden as risk factors for pre-eclampsia: A population-based nested case-control study  

Microsoft Academic Search

IntroductionPre-eclampsia is an important cause of maternal morbidity and mortality. Its etiology is still unknown. Clinical symptoms correlate with activation of coagulation and inherited thrombophilia has been associated with pre-eclampsia. ABO blood group has been associated with thrombotic disorders and pre-eclampsia.We assessed ABO blood group, seven thrombophilia associated polymorphisms, and anti-beta2-glycoprotein I antibodies as risk factors for pre-eclampsia.

Leena M Hiltunen; Hannele Laivuori; Anna Rautanen; Risto Kaaja; Juha Kere; Tom Krusius; Mikko Paunio; Vesa Rasi

2009-01-01

17

Pregnancy-Onset Habitual Snoring, Gestational Hypertension, and Pre-eclampsia: Prospective Cohort Study  

PubMed Central

Objective This study aimed to prospectively examine the impact of chronic vs. pregnancy-onset habitual snoring on gestational hypertension, pre-eclampsia, and gestational diabetes. Study Design Third trimester pregnant women were recruited from a large, tertiary medical center, between March 2007 and December 2010 and screened for the presence and duration of habitual snoring, as a known marker for sleep-disordered breathing. Clinical diagnoses of gestational hypertension, pre-eclampsia, and gestational diabetes were obtained. Results Of 1,719 pregnant women, 34% reported snoring, with 25% reporting pregnancy-onset snoring. After adjusting for confounders pregnancy-onset, but not chronic snoring, was independently associated with gestational hypertension (odds ratio 2.36, 95%CI 1.48–3.77, p<0.001) and pre-eclampsia (odds ratio 1.59, 95%CI 1.06–2.37 p=0.024) but not gestational diabetes. Conclusion New-onset snoring during pregnancy is a strong risk factor for gestational hypertension and pre-eclampsia. In view of the significant morbidity and healthcare costs associated with hypertensive diseases of pregnancy, simple screening of pregnant women may have clinical utility. Trial registration: Clinical Trials NCT01030003 PMID:22999158

O’BRIEN, Louise M.; BULLOUGH, Alexandra S.; OWUSU, Jocelynn T.; TREMBLAY, Kimberley A.; BRINCAT, Cynthia A.; CHAMES, Mark C.; KALBFLEISCH, John D.; CHERVIN, Ronald D.

2012-01-01

18

Studies suggest an association between maternal periodontal disease and pre-eclampsia  

Microsoft Academic Search

In this systematic review, several types of infections are identified and investigated: urinary tract infection, periodontal disease, Chlamydia pneumoniae infection, HIV infection, malaria and other persistent bacterial and viral infections. Separate analyses were conducted for each of them. This summary review will only focus on the link between pre-eclampsia and periodontitis, which was just a part of the original systematic

Jean-Noel Vergnes

2008-01-01

19

Association between the Presence of Autoantibodies against Adrenoreceptors and Severe Pre-Eclampsia: A Pilot Study  

PubMed Central

Background Pre-eclampsia is the leading cause of maternal and neonatal morbidity and mortality with incompletely understood etiopathogenesis. The purpose of the current study is to determine whether there is a relationship between the presence of autoantibodies against ?1, ?2 and ?1 adrenoreceptors and severe pre-eclampsia. Methodology/Principal Findings Synthetic peptides corresponding to amino acid sequences of the second extracellular loops of ?1, ?2 and ?1 adrenoreceptors were synthesized as antigens to test 34 patients with severe pre-eclampsia, 36 normal pregnancy women and 40 non-pregnant controls for the presence of autoantibodies using enzyme-linked immunosorbent assay. The respective frequencies of autoantibodies against ?1, ?2 and ?1 adrenoreceptors were 50.0% (17/34), 52.9% (18/34) and 55.9% (19/34) in patients with severe pre-eclampsia, 19.4% (7/36) (p?=?0.011), 19.4% (7/36) (p?=?0.006) and 17.6% (6/36) (p?=?0.001) in normal pregnancy women and 10% (4/40), 7.5% (3/40) and 10% (4/40) (p<0.001) in non-pregnant controls. Titers of these autoantibodies were also significantly increased in patients with severe pre-eclampsia. By logistic regression analysis, the presence of these three autoantibodies significantly increased the risk of neonatal death (odds ratio, 13.5; 95% confidence interval, 1.3–141.3; p?=?0.030) and long-term neonatal hospitalization (odds ratio, 5.0; 95% confidence interval, 1.3–19.1; p?=?0.018). The risk of hypertension and fetal distress were also associated with the presence of these three autoantibodies. Conclusions/Significance This novel pilot study demonstrated for the first time that the presence of autoantibodies against ?1, ?2 and ?1 adrenoreceptors are increased in patients with severe pre-eclampsia. Pregnant women who are positive for the three autoantibodies are at increased risks of neonatal mortality and morbidity. We posit that these autoantibodies may be involved in the pathogenesis of severe pre-eclampsia. PMID:23483958

Liu, Hao; Hou, Dongyan; Zhu, Lei; Zhang, Zhenyu; Zhang, Lin

2013-01-01

20

Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries  

PubMed Central

Objective To assess disparities in pre-eclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries. Design Cross-country comparative study of linked population-based databases. Setting Provincial or regional obstetric delivery data from Australia, Canada, Spain and the USA and national data from Denmark and Sweden. Population All immigrant and non-immigrant women delivering in the six industrialised countries within the most recent 10-year period available to each participating centre (1995–2010). Methods Data was collected using standardised definitions of the outcomes and maternal regions of birth. Pooled data were analysed with multilevel models. Within-country analyses used stratified logistic regression to obtain odds ratios (OR) with 95% confidence intervals (95% CI). Main outcome measures Pre-eclampsia, eclampsia and pre-eclampsia with prolonged hospitalisation (cases per 1000 deliveries). Results There were 9 028 802 deliveries (3 031 399 to immigrant women). Compared with immigrants from Western Europe, immigrants from Sub-Saharan Africa and Latin America & the Caribbean were at higher risk of pre-eclampsia (OR: 1.72; 95% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native-born women, European and East Asian immigrants were at lower risk in most industrialised countries. Spain exhibited the largest disparities and Australia the smallest. Conclusion Immigrant women from Sub-Saharan Africa and Latin America & the Caribbean require increased surveillance due to a consistently high risk of pre-eclampsia and eclampsia. PMID:24758368

Urquia, ML; Glazier, RH; Gagnon, AJ; Mortensen, LH; Nybo Andersen, A-M; Janevic, T; Guendelman, S; Thornton, D; Bolumar, F; Río Sánchez, I; Small, R; Davey, M-A; Hjern, A

2014-01-01

21

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

PubMed Central

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

Ahmed, Asif; Ramma, Wenda

2015-01-01

22

Development of mHealth applications for pre-eclampsia triage.  

PubMed

The development of mobile applications for the diagnosis and management of pregnant women with pre-eclampsia is described. These applications are designed for use by community-based health care providers (c-HCPs) in health facilities and during home visits to collect symptoms and perform clinical measurements (including pulse oximeter readings). The clinical data collected in women with pre-eclampsia are used as the inputs to a predictive model providing a risk score for the development of adverse outcomes. Based on this risk, the applications provide recommendations on treatment, referral, and reassessment. c-HCPs can access patient records across multiple visits, using multiple devices that are synchronized using a secure Research Electronic Data Capture server. A unique feature of these applications is the ability to measure oxygen saturation with a pulse oximeter connected to a smartphone (Phone Oximeter). The mobile health application development process, including challenges encountered and solutions are described. PMID:25375683

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

2014-11-01

23

Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia  

Microsoft Academic Search

OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and

L Morgan; S Crawshaw; P N Baker; J F Brookfield; F Broughton Pipkin; N Kalsheker

1998-01-01

24

Clinical management of established pre-eclampsia and gestational hypertension: an anaesthetist’s perspective  

Microsoft Academic Search

Expert and aggressive pre-operative preparation of the woman with severe pre-eclampsia will ultimately determine her intraoperative outcome. Such considerations as the effect of endotracheal manipulation on intracranial pressure, of thrombocytopenia on the potential to produce a compressive epidural haematoma following epidural or combined spinal–epidural neuraxial block and of adequacy of invasive monitoring for Caesarean section loom large in the eyes

Stephen P. Gatt

1999-01-01

25

A criteria-based audit of the management of severe pre-eclampsia in Kampala, Uganda  

Microsoft Academic Search

Objective: To improve the quality of clinical care for women with severe pre-eclampsia. Methods: A criteria-based audit was conducted in a large government hospital in Uganda. Management practices were evaluated against standards developed by an expert panel by retrospectively evaluating 43 case files. Results of the audit were presented, and recommendations developed and implemented. A re-audit was conducted 6 months

G. Alia; S. Ononge; E. O. Otolorin; F. M. Mirembe

2005-01-01

26

Comparative Proteomics Analysis Suggests that Placental Mitochondria are Involved in the Development of Pre-Eclampsia  

PubMed Central

Introduction Pre-eclampsia (PE), a severe pregnancy-specific disease characterized by the new onset of hypertension, proteinuria, edema, and a series of other systematic disorders, is a state of widespread mitochondrial dysfunction of the placenta. Methods We compared the morphology of mitochondria in pre-eclamptic and normotensive placentae using electron microscopy. To reveal the systematic protein expression changes of placental mitochondria that might explain the pathogenesis of PE, we performed iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on differentially expressed placental mitochondria proteins from 4 normotensive and 4 pre-eclamptic pregnancies. Bioinformatics analysis was used to find the relative processes that these differentially expressed proteins were involved in. Three differentially expressed proteins were chosen to confirm by Western blotting and immunohistochemistry. Results Morphological data demonstrated degenerative and apoptotic changes in the mitochondria of pre-eclamptic placentae. We found four proteins were upregulated and 22 proteins were downregulated in pre-eclamptic placentae compared with normotensive placentae. Bioinformatics analysis showed that these proteins were involved in many critical processes in the development of pre-eclampsia such as apoptosis, fatty acid oxidation, the respiratory chain, reactive oxygen species generation, the tricarboxylic acid cycle and oxidative stress. Conclusions This preliminary work provides a better understanding of the proteomic alterations of mitochondria from pre-eclamptic placentae and may aid in our understanding of the importance of mitochondria in the development of pre-eclampsia. PMID:23671712

Zhao, Chun; Guo, Xirong; Shen, Rong; Ding, Hongjuan

2013-01-01

27

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

PubMed

Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 ?g/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0·039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial. PMID:24708917

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

2014-07-14

28

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

PubMed Central

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

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

2014-01-01

29

Can first trimester placental protein-13 and pregnancy-associated plasma protein-A predict pre-eclampsia in Turkish women?  

PubMed

The aim of study was to evaluate placental protein-13 (PP-13) and pregnancy-associated plasma protein-A (PAPP-A) in first trimester maternal serum, for predicting pre-eclampsia. A prospective case-control study included 30 pre-eclampsia patients and 90 control pregnant women. Pre-eclampsia patients were divided into two subgroups: early- and late-onset (9 vs 21), and PP-13 and PAPP-A levels were compared between the groups and the comparison of risks for pre-eclampsia were calculated. Results showed that there was a significant inverse correlation between PAPP-A and late pre-eclampsia (p = 0.003), with a cut-off value of 0.805 (ROC analysis area under curve = 0.751). There was a significant reverse correlation between PAPP-A and early pre-eclampsia (p = 0.02). There was no significant relationship between PP-13 and early pre-eclampsia, nor with late pre-eclampsia (p = 0.7, p = 0.6, respectively). It was concluded that neither of these markers can serve as a sufficient and reliable screening test of pre-eclampsia because of inadequate sensitivity in the Turkish pregnant population. PMID:24786703

Ceylan, N; Ozaksit, G; Unlu, B S; Yildiz, Y; Yilmaz, S; Agaca, F

2014-08-01

30

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

PubMed Central

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

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

1997-01-01

31

Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia  

Microsoft Academic Search

Elevated circulating levels of the tachykinin, neurokinin B (NKB), have been observed in women with pre-eclampsia during the third trimester of pregnancy. Currently, the molecular mechanisms responsible for these increased levels remain unknown. To understand the molecular regulation, we have compared the differences in gene expression of the tachykinins and their receptors in control and pre-eclamptic placentae and the responses

N. M. Page; J. Dakour; D. W. Morrish

2006-01-01

32

Pre-Eclampsia and Risk of Cardiovascular Disease and Cancer in Later Life: Systematic Review and Meta-Analysis  

Microsoft Academic Search

Objective: To quantify the risk of future cardiovascular diseases, cancer, and mortality after pre-eclampsia. Design: Systematic review and meta-analysis. Data sources: Embase and Medline without language restrictions, including papers published between 1960 and December 2006, and hand searching of reference lists of relevant articles and reviews for additional reports. Review methods: Prospective and retrospective cohort studies were included, providing a

Leanne Bellamy; Juan-Pablo Casas; Aroon D. Hingorani; David J. Williams; Magee; von Dadelszen

2007-01-01

33

Localization of Hyaluronan with a Hyaluronan-Specific Hyaluronic Acid Binding Protein in the Placenta in Pre-Eclampsia  

Microsoft Academic Search

Hyaluronan (HA), a high molecular weight polysaccharide, is a major component of connective tissue and is thus present in the extracellular matrix of most tissues. Increased serum concentrations have been reported in association with pre-eclampsia and liver malfunction, amongst other disorders. We have performed histochemical investigations with a HA-specific hyaluronic acid binding protein in placentas from uncomplicated pregnancies and from

D. Matejevic; H. Neudeck; R. Graf; T. Müller; J. Dietl

2001-01-01

34

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

PubMed

T helper 17 (TH17) cells have been identified as a new lineage of helper T cells and have been shown to be important in host defense against extracellular infectious agents, autoimmune disease and chronic inflammatory diseases. Recently, TH17 cells have also been shown to participate in successful pregnancy, as well as in the pathogenesis of diseases of pregnancy, such as recurrent spontaneous abortion (RSA) and pre-eclampsia (PE). Here, we review our current knowledge of TH17 cells in human RSA and PE. We also discuss how the local uterine microenvironment affects the differentiation of TH17 cells and the mechanisms that regulate TH17 cells during pregnancy. Research into TH17 cells will not only advance our understanding of TH17-related pregnancy complications, but will also facilitate the design of novel therapies for reproductive diseases. PMID:25027967

Fu, Binqing; Tian, Zhigang; Wei, Haiming

2014-11-01

35

TH17 cells in human recurrent pregnancy loss and pre-eclampsia  

PubMed Central

T helper 17 (TH17) cells have been identified as a new lineage of helper T cells and have been shown to be important in host defense against extracellular infectious agents, autoimmune disease and chronic inflammatory diseases. Recently, TH17 cells have also been shown to participate in successful pregnancy, as well as in the pathogenesis of diseases of pregnancy, such as recurrent spontaneous abortion (RSA) and pre-eclampsia (PE). Here, we review our current knowledge of TH17 cells in human RSA and PE. We also discuss how the local uterine microenvironment affects the differentiation of TH17 cells and the mechanisms that regulate TH17 cells during pregnancy. Research into TH17 cells will not only advance our understanding of TH17-related pregnancy complications, but will also facilitate the design of novel therapies for reproductive diseases. PMID:25027967

Fu, Binqing; Tian, Zhigang; Wei, Haiming

2014-01-01

36

Association of Plasminogen Activator Inhibitor-Type 1 (-675 4G/5G) Polymorphism with Pre-Eclampsia: Systematic Review  

PubMed Central

Background and Aims Excessive generation of plasminogen activator inhibitor-type 1 (PAI-1) is implicated in the pathogenesis of pre-eclampsia and related conditions. The PAI-1 (?675 4G/5G) promoter polymorphism (rs1799889) affects transcriptional activity and is a putative genetic risk factor for pre-eclampsia. The aim of this study was identify, appraise and synthesise the available evidence for the association of the PAI-1 (?675 4G/5G) polymorphism with pre-eclampsia. Methods Systematic review and random effects meta-analysis of genetic association studies. Results We found 12 eligible genetic association studies in which a total of 1511 women with pre-eclampsia, eclampsia or HELLP syndrome and 3492 controls participated. The studies were generally small (median number of cases 102, range 24 to 403) and underpowered to detect plausible association sizes. Meta-analysis of all of the studies detected statistically significant gene-disease associations in the recessive [pooled odds ratio 1.28 (95% confidence interval 1.09, 1.50); population attributable risk 7.7%] and dominant [pooled odds ratio 1.21 (95% confidence interval 1.01, 1.44); population attributable risk 13.7%] models. We did not find evidence of statistical heterogeneity, funnel plot asymmetry or small study bias. Conclusions These data suggest that the fibrinolytic pathway regulated by the PAI-1 gene may contribute to the pathogenesis of pre-eclampsia and related conditions. This association, if confirmed in larger genetic association studies, may inform research efforts to develop novel interventions or help to prioritise therapeutic targets that merit evaluation in randomised clinical trials. PMID:23457639

Morgan, Jessie A.; Bombell, Sarah; McGuire, William

2013-01-01

37

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

PubMed Central

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 which the accuracy of blood pressure measurement during pregnancy was evaluated to predict pre-eclampsia. Data were extracted on study characteristics, quality, and results to construct 2×2 tables. Summary receiver operating characteristic curves and likelihood ratios were generated for the various levels and their thresholds. Results 34 studies, testing 60?599 women (3341 cases of pre-eclampsia), were included. In women at low risk for pre-eclampsia, the areas under the summary receiver operating characteristic curves for blood pressure measurement in the second trimester were 0.68 (95% confidence interval 0.64 to 0.72) for systolic blood pressure, 0.66 (0.59 to 0.72) for diastolic blood pressure, and 0.76 (0.70 to 0.82) for mean arterial pressure. Findings for the first trimester showed a similar pattern. Second trimester mean arterial pressure of 90 mm Hg or more showed a positive likelihood ratio of 3.5 (95% confidence interval 2.0 to 5.0) and a negative likelihood ratio of 0.46 (0.16 to 0.75). In women deemed to be at high risk, a diastolic blood pressure of 75 mm Hg or more at 13 to 20 weeks’ gestation best predicted pre-eclampsia: positive likelihood ratio 2.8 (1.8 to 3.6), negative likelihood ratio 0.39 (0.18 to 0.71). Additional subgroup analyses did not show improved predictive accuracy. Conclusion When blood pressure is measured in the first or second trimester of pregnancy, the mean arterial pressure is a better predictor for pre-eclampsia than systolic blood pressure, diastolic blood pressure, or an increase of blood pressure. PMID:18480117

2008-01-01

38

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

PubMed

The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification. PMID:25602073

Elliot, Michael G; Crespi, Bernard J

2015-03-01

39

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

Microsoft Academic Search

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

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

40

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

PubMed Central

Abstract Aims: Storkhead box 1 (STOX1) is a winged-helix transcription factor that is implicated in the genetic forms of a high-prevalence human gestational disease, pre-eclampsia. STOX1 overexpression confers pre-eclampsia-like transcriptomic features to trophoblastic cell lines and pre-eclampsia symptoms to pregnant mice. The aim of this work was to evaluate the impact of STOX1 on free radical equilibrium and mitochondrial function, both in vitro and in vivo. Results: Transcriptome analysis of STOX1-transgenic versus nontransgenic placentas at 16.5 days of gestation revealed alterations of mitochondria-related pathways. Placentas overexpressing STOX1 displayed altered mitochondrial mass and were severely biased toward protein nitration, indicating nitroso-redox imbalance in vivo. Trophoblast cells overexpressing STOX1 displayed an increased mitochondrial activity at 20% O2 and in hypoxia, despite reduction of the mitochondrial mass in the former. STOX1 overexpression is, therefore, associated with hyperactive mitochondria, resulting in increased free radical production. Moreover, nitric oxide (NO) production pathways were activated, resulting in peroxynitrite formation. At low oxygen pressure, STOX1 overexpression switched the free radical balance from reactive oxygen species (ROS) to reactive nitrogen species (RNS) in the placenta as well as in a trophoblast cell line. Innovation: In pre-eclamptic placentas, NO interacts with ROS and generates peroxynitrite and nitrated proteins as end products. This process will deprive the maternal organism of NO, a crucial vasodilator molecule. Conclusion: Our data posit STOX1 as a genetic switch in the ROS/RNS balance and suggest an explanation for elevated blood pressure in pre-eclampsia. Antioxid. Redox Signal. 21, 819–834. PMID:24738702

Doridot, Ludivine; Châtre, Laurent; Ducat, Aurélien; Vilotte, Jean-Luc; Lombès, Anne; Méhats, Céline; Barbaux, Sandrine; Calicchio, Rosamaria

2014-01-01

41

Greater pressor reactivity in women with pre-eclampsia is not related to specific psychological or emotional stressors.  

PubMed

To investigate whether emotional or psychosocial factors could be significantly related with the development of pre-eclampsia, 15 pregnant women with early diagnosis of pre-eclampsia and 15 normotensive pregnant controls of comparable age (23-37 yr.), gestational age (10-37 wk.), parity (70% primiparous), amount of instruction, and marital status underwent a blood pressure monitoring during a specific psychological assessment based on a semistructured interview followed by the administration of three different questionnaires: the Symptom Checklist 90-Revised, the Perceived Stress Questionnaire-Recent, and the Questionnaire about Social Relationships. Systolic and diastolic blood pressure and heart rate were measured at 2-min. intervals by an automatic device both during the interview and the questionnaires' administration. Both systolic and diastolic responses were significantly increased in both groups during the interview (deltaSBP = 15 vs. 10%; deltaDBP=28 vs. 15.8%), whereas no differences were observed in blood pressure while answering questionnaires. Conversely, differences in questionnaire responses between groups were not statistically significant. Present results confirm a greater pressor reactivity in these women with pre-eclampsia but does not specifically support that this was related to psychological or emotional stress. PMID:21117466

Rossi, Nicolino C F; Montebarocci, Ornella; Surcinelli, Paola; Baldaro, Bruno; Immordino, Vincenzo; Borghi, Claudio

2010-10-01

42

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

PubMed

Seasonal patterns influencing maternal health have been documented globally and are of particular importance for women in developing countries who disproportionately suffer from anemia, pre-eclampsia and eclampsia. This paper adopts a realist systematic approach to investigate the maternal outcome of anemia and eclampsia in relation to seasonality. A review of 23 published studies shows a statistically significant link between these maternal disorders and seasonality in developing countries in Sub-Saharan Africa and Central and South Asia. Anemia and eclampsia tend to decrease during the dry season, only to increase with greater rainfall, low and cold temperatures. Numerous studies suggest that the seasonality of anemia and eclampsia is associated with changes in malaria transmission. This was observed during the rainy season, suggesting a potential seasonal relationship with malaria as a driver of these disorders in Sub-Saharan Africa. Anemia and eclampsia were principally exacerbated among primigravidae and young women. Food insecurity, access to antenatal care, poverty, and environmental factors may also play a crucial role in the predisposition to these disorders. More research is required to identify the seasonal link between malaria and eclampsia particularly as climate change may exacerbate the rate of the disorders in tropical and sub-tropical areas. PMID:25555235

Hlimi, Tina

2015-01-01

43

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

NASA Astrophysics Data System (ADS)

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

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

2007-03-01

44

Genome-wide hypermethylation coupled with promoter hypomethylation in the chorioamniotic membranes of early onset pre-eclampsia.  

PubMed

Pre-eclampsia is the leading cause of fetal and maternal morbidity and mortality. Early onset pre-eclampsia (EOPE) is a disorder that has severe maternal and fetal outcomes, whilst its etiology is poorly understood. We hypothesize that epigenetics plays an important role to mediate the development of EOPE and conducted a case-control study to compare the genome-wide methylome difference between chorioamniotic membranes from 30 EOPE and 17 full-term pregnancies using the Infinium Human Methylation 450 BeadChip arrays. Bioinformatics analysis tested differential methylation (DM) at CpG site level, gene level, and pathway and network level. A striking genome-wide hypermethylation pattern coupled with hypomethylation in promoters was observed. Out of 385 184 CpG sites, 9995 showed DM (2.6%). Of those DM sites, 91.9% showed hypermethylation (9186 of 9995). Over 900 genes had DM associated with promoters. Promoter-based DM analysis revealed that genes in canonical cancer-related pathways such as Rac, Ras, PI3K/Akt, NF?B and ErBB4 were enriched, and represented biological functional alterations that involve cell cycle, apoptosis, cancer signaling and inflammation. A group of genes previously found to be up-regulated in pre-eclampsia, including GRB2, ATF3, NFKB2, as well as genes in proteasome subunits (PSMA1, PMSE1, PSMD1 and PMSD8), harbored hypomethylated promoters. Contrarily, a cluster of microRNAs, including mir-519a1, mir-301a, mir-487a, mir-185, mir-329, mir-194, mir-376a1, mir-486 and mir-744 were all hypermethylated in their promoters in the EOPE samples. These findings collectively reveal new avenues of research regarding the vast epigenetic modifications in EOPE. PMID:24944161

Ching, Travers; Song, Min-Ae; Tiirikainen, Maarit; Molnar, Janos; Berry, Marla; Towner, Dena; Garmire, Lana X

2014-09-01

45

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

PubMed Central

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?

2013-01-01

46

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

PubMed Central

Objective To investigate the incidence of retinal vein occlusion (RVO) in pregnant women and in the subpopulation of pregnant women with pre-eclampsia/eclampsia compared to that in the age-matched general female population to determine if there is increased risk of RVO in pregnancy. Design Nationwide population-based retrospective study using data entered into the Korean national health claims database from 2007 to 2011. Setting and Participants Of the incident RVO cases in the database, RVO cases that occurred during the pregnancy-associated period, which spanned a 52-week period from 40-weeks-before to 12-weeks-after childbirth, were identified. Of these cases, the presence of pre-eclampsia/eclampsia was determined. Main Outcome and Measure The standardized incidence ratios (SIRs) of RVO in the general pregnant population and in the pregnant population with pre-eclampsia/eclampsia were determined with respect to the age-matched general female population. Results Pregnancy-related RVO was identified in 33 cases from the 1.8 million women who experience childbirth during the study period, while the expected number of cases calculated by the direct standardization to the age-matched general population was 113. Of the 33 patients, 12 patients (36.4%) had pre-eclampsia or eclampsia. The SIR for the general pregnant population in reference to the age-matched general female population was 0.29 (95% CI, 0.20–0.41). In contrast, the SIR for the pregnant population with pre-eclampsia/eclampsia in reference to the age-matched general female population and the age-matched general pregnant population was 67.50 (95% CI, 34.88–117.92) and 246.50 (95% CI, 127.37–430.59), respectively. Conclusions and Relevance The results suggest that pre-eclampsia/eclampsia is a risk factor for RVO, while pregnancy itself may not be a risk factor for RVO. PMID:25774513

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

2015-01-01

47

Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia  

PubMed Central

Pre-eclampsia is a serious complication of pregnancy that can affect both maternal and fetal outcomes. Early-onset pre-eclampsia (EOPET) is a severe form of pre-eclampsia that is associated with altered physiological characteristics and gene expression in the placenta. DNA methylation is a relatively stable epigenetic modification to DNA that can reflect gene expression, and can provide insight into the mechanisms underlying such expression changes. This case–control study focused on DNA methylation and gene expression of whole chorionic villi samples from 20 EOPET placentas and 20 gestational age-matched controls from pre-term births. DNA methylation was also assessed in placentas affected by late-onset pre-eclampsia (LOPET) and normotensive intrauterine growth restriction (nIUGR). The Illumina HumanMethylation450 BeadChip was used to assess DNA methylation at >480 000 cytosine-guanine dinucleotide (CpG) sites. The Illumina HT-12v4 Expression BeadChip was used to assess gene expression of >45 000 transcripts in a subset of cases and controls. DNA methylation analysis by pyrosequencing was used to follow-up the initial findings in four genes with a larger cohort of cases and controls, including nIUGR and LOPET placentas. Bioinformatic analysis was used to identify overrepresentation of gene ontology categories and transcription factor binding motifs. We identified 38 840 CpG sites with significant (false discovery rate <0.01) DNA methylation alterations in EOPET, of which 282 had >12.5% methylation difference compared with the controls. Significant sites were enriched at the enhancers and low CpG density regions of the associated genes and the majority (74.5%) of these sites were hypomethylated in EOPET. EOPET, but not associated clinical features, such as intrauterine growth restriction (IUGR), presented a distinct DNA methylation profile. CpG sites from four genes relevant to pre-eclampsia (INHBA, BHLHE40, SLC2A1 and ADAM12) showed different extent of changes in LOPET and nIUGR. Genome-wide expression in a subset of samples showed that some of the gene expression changes were negatively correlated with DNA methylation changes, particularly for genes that are responsible for angiogenesis (such as EPAS1 and FLT1). Results could be confounded by altered cell populations in abnormal placentas. Larger sample sizes are needed to fully address the possibility of sub-profiles of methylation within the EOPET cohort. Based on DNA methylation profiling, we conclude that there are widespread DNA methylation alterations in EOPET that may be associated with changes in placental function. This property may provide a useful tool for early screening of such placentas. This study identifies DNA methylation changes at many loci previously reported to have altered gene expression in EOPET placentas, as well as in novel biologically relevant genes we confirmed to be differentially expressed. These results may be useful for DNA- methylation-based non-invasive prenatal diagnosis of at-risk pregnancies. PMID:23770704

Blair, John D.; Yuen, Ryan K.C.; Lim, Brendan K.; McFadden, Deborah E.; von Dadelszen, Peter; Robinson, Wendy P.

2013-01-01

48

Catalase activity, serum trace element and heavy metal concentrations, and vitamin A, D and E levels in pre-eclampsia.  

PubMed

Catalase (antioxidant enzyme) activity in erythrocytes and serum levels of trace elements (copper, iron, zinc), heavy metals (cadmium, cobalt) and vitamins A (retinol), D (cholecalciferol) and E (alpha-tocopherol) were measured in 145 subjects comprising 47 pre-eclamptic pregnant women (PE), 48 healthy pregnant women (HP) and 50 healthy non-pregnant controls (NP). Catalase, vitamins A, D and E and levels of cobalt were significantly lower in the PE group compared with the HP and NP groups, whereas levels of copper, iron and cadmium were significantly higher in the PE group than in the HP and NP groups. Levels of zinc were significantly lower in both the PE and HP groups compared with the NP group. This assessment of oxidant/antioxidant imbalance in pregnant women could be useful in the early identification of pre-eclampsia and antioxidant supplementation in the early weeks of gestation might be useful. PMID:19094444

Kolusari, A; Kurdoglu, M; Yildizhan, R; Adali, E; Edirne, T; Cebi, A; Demir, H; Yoruk, I H

2008-01-01

49

Distress conditions during pregnancy may lead to pre-eclampsia by increasing cortisol levels and altering lymphocyte sensitivity to glucocorticoids.  

PubMed

Psychological stress may affect up to 18% of all pregnant women, altering the function of both neuroendocrine and immune systems. Distress conditions may directly change the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased cortisol levels and associated changes in cellular immunity. Psychological events such as high stress levels, anxiety or depression may directly or indirectly affect pregnancy and may thus lead to pre-eclampsia (PE). Here, we suggest that distress conditions during pregnancy may lead the development of PE by enhancing in vivo cortisol levels. High cortisol levels are associated with hypertension and endothelial dysfunction, features often observed in patients with PE. Lymphocytes from patients with high cortisol levels may have a reduced sensitivity to the synthetic glucocorticoid dexamethasone (DEX). Stress-related steroid resistance may disrupt the HPA axis, leading to post-natal detrimental effects such as increased allostatic load, increased pro-inflammatory cytokine levels and even depression in the offspring. PMID:21550175

Vianna, Priscila; Bauer, Moisés E; Dornfeld, Dinara; Chies, José Artur Bogo

2011-08-01

50

Salinity in Drinking Water and the Risk of (Pre)Eclampsia and Gestational Hypertension in Coastal Bangladesh: A Case-Control Study  

PubMed Central

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

Khan, Aneire Ehmar; Scheelbeek, Pauline Franka Denise; Shilpi, Asma Begum; Chan, Queenie; Mojumder, Sontosh Kumar; Rahman, Atiq; Haines, Andy; Vineis, Paolo

2014-01-01

51

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

PubMed Central

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

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

2013-01-01

52

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

PubMed Central

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

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

53

Matrix Metalloproteinase 1 in Pre-eclampsia and Fetal Growth Restriction: Reduced Gene Expression in Decidual Tissue and Protein Expression in Extravillous Trophoblasts  

Microsoft Academic Search

Superficial invasion of extravillous trophoblasts (EVTs) and impaired spiral artery remodelling are characterizing phenomena in pregnancies complicated by pre-eclampsia (PE) and fetal growth restriction (FGR). However, the underlying causes remain unclear. In this study, gene expression in decidua basalis tissue from pregnancies complicated with PE and\\/or FGR (n = 18) and normal pregnancies (n = 17) was assessed by Affymetrix HG Focus microarray to

I. A. Lian; J. H. Toft; G. D. Olsen; M. Langaas; L. Bjørge; I. P. Eide; P. E. Børdahl; R. Austgulen

2010-01-01

54

Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach  

Microsoft Academic Search

Pre-eclampsia\\/eclampsia (PE\\/E) is a common and serious disorder of human pregnancy that is associated with substantial mater- nal and perinatal morbidity and mortality. The suspected aetiology of PE\\/E is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. By assuming that the underlying liability towards PE\\/E suscepti- bility is inherently quantitative, any PE\\/E susceptibility gene

M. P. Johnson; E. Fitzpatrick; T. D. Dyer; J. B. M. Jowett; S. P. Brennecke; J. Blangero; E. K. Moses

2006-01-01

55

Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease  

PubMed Central

Abstract Pre-eclampsia is a leading cause of maternal and foetal morbidity and mortality worldwide. Insufficient uteroplacental oxygenation is believed to be responsible for the disease. However, what molecular events involve in hypoxic responses and how they affect placental development remain unclear. Recently, miRNAs have emerged as a new class of molecules in response to hypoxia. We show here that the expression of microRNA-210 (mir-210) is up-regulated in patients with pre-eclampsia, as well as in trophoblast cells cultured under hypoxic conditions. Ectopic expression of mir-210 inhibited the migration and invasion capability of trophoblast cells. Ephrin-A3 and Homeobox-A9, which related with cell migration and vascular remodelling, were then experimentally validated as the functional targets of mir-210 both in vivo and in vitro. Using luciferase reporter, chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) experiments, we finally identified a new transcriptional mechanism that the overexpression of mir-210 under hypoxia was regulated by NF-?B transcriptional factor p50, apart from the well-known HIF 1?. Taken together, our study implicates an important role for mir-210 in the molecular mechanism of pre-eclampsia. PMID:21388517

Zhang, Yi; Fei, Mingyu; Xue, Geng; Zhou, Qi; Jia, Yin; Li, Li; Xin, Hong; Sun, Shuhan

2012-01-01

56

Mesenchymal Stem Cells Ameliorate Th1-Induced Pre-Eclampsia-Like Symptoms in Mice via the Suppression of TNF-? Expression  

PubMed Central

Pre-eclampsia (PE) is thought to be a pregnancy-induced autoimmune disease. Despite several strategies carried out for targeting specific factors relevant to its pathogenesis, PE remains potentially fatal to some patients. Here, we reported a way to isolate mesenchymal stem cells (MSCs) from decidua. The MSCs not only exhibited differentiation and self-renewal capacities, they also possessed immunomodulatory functions and secreted some soluble mediators including IL-6, TGF-?, IDO, VEGF and COX-2. Most importantly, the MSCs were specifically provided with the ability to suppress T cells proliferation by IDO in response to inflammatory cytokine IFN-?. Moreover, we developed a Th1 cell-induced PE mouse model which displayed a high level of pathogenesis factor TNF-?. Strikingly, MSCs-based therapy significantly ameliorated both clinical and histopathological severity of PE symptoms including decreasing the blood pressure and proteinuria, suppressing glomerulonephritis, protecting the feto-placental development. The therapy also reversed abnormal TNF-? expression in uterine and splenic lymphocytes. These data suggest that MSCs may ameliorate Th1-induced PE-like symptoms in mice via the suppression of TNF-? and MSCs-based therapy may provide a potential novel method for PE. PMID:24558374

Liu, Liu; Zhao, Guangfeng; Fan, Hongye; Zhao, Xiaoyin; Li, Pengfei; Wang, Zhiqun; Hu, Yali; Hou, Yayi

2014-01-01

57

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

PubMed Central

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

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

2013-01-01

58

Early onset pre-eclampsia is associated with altered DNA methylation of cortisol-signalling and steroidogenic genes in the placenta.  

PubMed

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

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

2013-01-01

59

Risk Factors of Pre-Eclampsia/Eclampsia and Its Adverse Outcomes in Low- and Middle-Income Countries: A WHO Secondary Analysis  

PubMed Central

Background Pre-eclampsia has an immense adverse impact on maternal and perinatal health especially in low- and middle-income settings. We aimed to estimate the associations between pre-eclampsia/eclampsia and its risk factors, and adverse maternal and perinatal outcomes. Methods We performed a secondary analysis of the WHO Global Survey on Maternal and Perinatal Health. The survey was a multi-country, facility-based cross-sectional study. A global sample consisting of 24 countries from three regions and 373 health facilities was obtained via a stratified multi-stage cluster sampling design. Maternal and offspring data were extracted from records using standardized questionnaires. Multi-level logistic regression modelling was conducted with random effects at the individual, facility and country levels. Results Data for 276,388 mothers and their infants was analysed. The prevalence of pre-eclampsia/eclampsia in the study population was 10,754 (4%). At the individual level, sociodemographic characteristics of maternal age ?30 years and low educational attainment were significantly associated with higher risk of pre-eclampsia/eclampsia. As for clinical and obstetric variables, high body mass index (BMI), nulliparity (AOR: 2.04; 95%CI 1.92–2.16), absence of antenatal care (AOR: 1.41; 95%CI 1.26–1.57), chronic hypertension (AOR: 7.75; 95%CI 6.77–8.87), gestational diabetes (AOR: 2.00; 95%CI 1.63–2.45), cardiac or renal disease (AOR: 2.38; 95%CI 1.86–3.05), pyelonephritis or urinary tract infection (AOR: 1.13; 95%CI 1.03–1.24) and severe anemia (AOR: 2.98; 95%CI 2.47–3.61) were found to be significant risk factors, while having >8 visits of antenatal care was protective (AOR: 0.90; 95%CI 0.83–0.98). Pre-eclampsia/eclampsia was found to be a significant risk factor for maternal death, perinatal death, preterm birth and low birthweight. Conclusion Chronic hypertension, obesity and severe anemia were the highest risk factors of preeclampsia/eclampsia. Implementation of effective interventions prioritizing risk factors, provision of quality health services during pre-pregnancy and during pregnancy for joint efforts in the areas of maternal health are recommended. PMID:24657964

Bilano, Ver Luanni; Ota, Erika; Ganchimeg, Togoobaatar; Mori, Rintaro; Souza, João Paulo

2014-01-01

60

Association of Lipid Profile and Uric Acid with Pre-eclampsia of Third Trimester in Nullipara Women  

PubMed Central

Background: Pre-eclampsia (PE) affects approximately 3% of all pregnancies worldwide, with onset of symptoms in the late second or third trimester, commonly after 32nd week. It is common in nulliparous women. To avoid complications it is necessary to diagnose it in advance, but the available tools are unable to clinch the diagnosis of preeclampsia effectively in majority. Aim: To find out an association of lipid profile and uric acid with PE in nullipara pregnant women in third trimester. Materials and Methods: One hundred nulliparous pregnant women in their third trimester of 18-35 years were divided into; 50 pre-eclamptics of study group and 50 non pre-eclamptic in control group; further subdivided according to age, 18-26 and 27-35 yrs. Diagnosis was confirmed as per the standard criteria. Lipid profile and uric acid levels were estimated by Vitros 250 dry chemistry analyser. Data was analysed statistically by student t-test at p<0.01 level of significance. Results: TC, LDL-c and VLDL-c levels in the study group as a whole and in the patients between 18-26 years were significant; HDL-c levels in the patients between 27-35 years were significant while TG and uric acid levels in all the three study groups were significant. Conclusion: Total cholesterol, LDL-c, VLDL-c, triglycerides (TGs) and uric acid levels were raised in preeclampsia and statistically significant; while HDL-c levels were raised in these patients but statistically non-significant, it can be concluded that there exists an association in lipid profile and uric acid with PE therefore dyslipidemia and raised uric acid levels are the features of PE in nullipara pregnant women in their third trimester. PMID:25177559

Gupta, Bharat Kumar; Vishnu, Abhishek; Mamtatyagi; Shiprasolanki; Kiran, Jas

2014-01-01

61

Paternal contribution of HLA-G*0106 significantly increases risk for pre-eclampsia in multigravid pregnancies.  

PubMed

Pre-eclampsia (PE) is a leading cause of maternal and fetal mortality and morbidity. Structural or functional alterations of human leukocyte antigen (HLA)-G present at the maternal-fetal interface may predispose women to PE. We tested the HLA-G gene for association with PE in a case-control study of 83 PE and 240 normotensive Malay women. HLA-G was amplified in a single-tube multiplex-PCR reaction and genotyped for 18 single nucleotide polymorphisms (SNPs) by multiplex-minisequencing. Case-control comparisons were performed, and associations with disease were expressed as odds ratios (ORs). Risk for PE was significantly associated with fetal allele G*0106 only in multigravid pregnancies (P = 0.002, OR = 5.0, 95% CI = 1.8-13.8). Among multigravid pregnancies, the frequency of PE babies heterozygous or homozygous for G*0106 was also significantly higher compared with normal control babies (P = 0.002, OR = 5.4, 95% CI = 1.9-15.4). Multivariate analyses with adjustment for factors associated with PE revealed similar results (P = 0.003, OR = 10.1, 95% CI = 2.2-46.8). Additionally, a significantly higher frequency of fetal-maternal G*0106 genotype mismatch was observed in PE compared with normal multigravid pregnancies (P = 0.001, OR = 9.6, 95% CI = 2.4-38.7). Thus, paternal HLA-G G*0106 contribution significantly increases risk for PE in multigravidas who do not carry this allele, potentially mediated by a gradual maternal alloimmune response to repeated exposure to the paternal HLA-G variant. PMID:18353802

Tan, Chia Yee; Ho, Julia F V; Chong, Yap Seng; Loganath, Annamalai; Chan, Yiong Huak; Ravichandran, Jeganathan; Lee, Caroline G; Chong, Samuel S

2008-05-01

62

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

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

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

2013-01-01

63

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

PubMed Central

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

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

2015-01-01

64

Characterisation of Syncytiotrophoblast Vesicles in Normal Pregnancy and Pre-Eclampsia: Expression of Flt-1 and Endoglin  

PubMed Central

Background The placental syncytiotrophoblast releases micro and nanovesicles (STBM), into the maternal circulation in normal pregnancy and in increased amounts in pre-eclampsia (PE), which have proinflammatory and antiangiogenic activity and are implicated in PE pathophysiology. Better characterisation of STBM is essential to understand their role in PE. Methods and Results STBM prepared by placental lobe dual perfusion (pSTBM) and mechanical disruption (mSTBM) were analysed by four colour flow cytometry (4CFC), nanoparticle tracking analysis (NTA) and Western blotting to determine vesicle size, purity and Flt-1 and endoglin (Eng) expression. Biological activity of STBM associated Flt-1 and endoglin was assessed by the ability of VEGF, PlGF and TGF? to bind to mSTBM and inhibit mSTBM induced endothelial monolayer disruption. STBM content was consistently high (?87–95%) across the different preparations. However, surface antigen intensities differed, with significantly lower placental alkaline phosphatase (P<0.05) and Eng (P<0.05) expression on mSTBM, and Flt-1 (P<0.05) expression on pSTBM. For PE placenta derived preparations, pSTBM contained lower Eng positive STBM (P<0.05) and mSTBM Eng expression was increased (P<0.05). Western blotting revealed increased Flt-1/sFlt-1 (P<0.02) and decreased placental alkaline phosphatase (P?=?0.0002) content of PE placenta pSTBM. Using NTA, perfused PE placentas released significantly larger MV (P<0.001). Finally, VEGF, PlGF and TGF? bound to mSTBM at physiologically relevant concentrations and inhibited mSTBM induced endothelial disruption (P<0.05-P<0.001). Conclusions This study has found differences in physical and antigenic characteristics of normal and PE placenta STBM preparations produced by placental perfusion or mechanical disruption. We have also demonstrated that large quantities of biologically active STBM associated endoglin and Flt-1/sFlt-1 could contribute to the increased circulating levels measured in PE patients and add to the perturbation of the maternal vascular endothelium, normally attributed to non-membrane bound sFlt-1 and sEndoglin. PMID:23437230

Tannetta, Dionne S.; Dragovic, Rebecca A.; Gardiner, Chris; Redman, Christopher W.; Sargent, Ian L.

2013-01-01

65

Maternal Circulating Levels of Activin A, Inhibin A, sFlt-1 and Endoglin at Parturition in Normal Pregnancy and Pre-Eclampsia  

PubMed Central

Background Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1), endoglin (sEng) and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies. Methodology To assess the effects of labour, samples were taken from 10 normal pregnant (NP) and 10 pre-eclamptic (PE) women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively. Results The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase. Conclusion Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum. PMID:19412349

Reddy, Aparna; Suri, Sangeeta; Sargent, Ian L.; Redman, Christopher W. G.; Muttukrishna, Shanthi

2009-01-01

66

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

Microsoft Academic Search

BACKGROUND: Few empirical studies of research utilisation have been conducted in low and middle income countries. This paper explores how research information, in particular findings from randomised controlled trials and systematic reviews, informed policy making and clinical guideline development for the use of magnesium sulphate in the treatment of eclampsia and pre-eclampsia in South Africa. METHODS: A qualitative case-study approach

Karen Daniels; Simon Lewin

2008-01-01

67

A follow-up linkage study of Finnish pre-eclampsia families identifies a new fetal susceptibility locus on chromosome 18.  

PubMed

Pre-eclampsia is a common vascular disorder of pregnancy. It originates in the placenta and targets the maternal endothelium. According to epidemiological research, >50% of the liability to this disorder can be accounted for by genetic factors. Both maternal and fetal genes contribute to the risk, but especially the fetal genetic risk profile is still poorly understood. We have previously detected linkage signals in multiplex Finnish families on chromosomes 2p25, 4q32, and 9p13 using maternal phenotypes. We performed a linkage analysis using updated maternal phenotypes and an unprecedented linkage analysis using fetal phenotypes. Markers genotyped were available from 237 individuals in 15 Finnish families, including 72 affected mothers and 49 affected fetuses. The MERLIN software was used for sample and marker quality control and linkage analysis. The results were compared against the original ones obtained by using the GENEHUNTER 2.1 software. The previous identification of the maternal susceptibility locus to a genetic location at 21.70 cM near marker D2S168 on chromosome 2 was confirmed by using both maternal and fetal phenotypes (maternal non-parametric linkage (NPL) score 3.79, P=0.00008, LOD (logarithm (base 10) of odds)=2.20 and fetal NPL score 2.95, P=0.002, LOD=1.71). As a novel finding, we present a suggestive linkage to chromosome 18 at 86.80 cM near marker D18S64 (NPL score 2.51, P=0.006, LOD=1.20) using the fetal phenotype. We propose that chromosome 18 may harbor a new fetal susceptibility locus for pre-eclampsia. PMID:23386034

Majander, Kerttu K; Villa, Pia M; Kivinen, Katja; Kere, Juha; Laivuori, Hannele

2013-09-01

68

An integrative review of the side effects related to the use of magnesium sulfate for pre-eclampsia and eclampsia management  

PubMed Central

Background Pre-eclampsia/eclampsia is one of the most common causes of maternal and perinatal morbidity and mortality in low and middle income countries. Magnesium sulfate is the drug of choice for prevention of seizures as part of comprehensive management of the disease. Despite the compelling evidence for the effectiveness of magnesium sulfate, concern has been expressed about its safety and potential for toxicity, particularly among providers in low- and middle-income countries. The purpose of this review was to determine whether the literature published in these global settings supports the concerns about the safety of use of magnesium sulfate. Methods An integrative review of the literature was conducted to document the known incidences of severe adverse reactions to magnesium sulphate, and specific outcomes of interest related to its use. All types of prospective clinical studies were included if magnesium sulfate was used to manage pre-eclampsia or eclampsia, the study was conducted in a low- or middle-income country, and the study included the recording of the incidence of any adverse side effect resulting from magnesium sulfate use. Results A total of 24 studies that compared a magnesium sulfate regimen against other drug regimens and examined side effects among 34 subject groups were included. The overall rate of absent patellar reflex among all 9556 aggregated women was 1.6%, with a range of 0-57%. The overall rate of respiratory depression in 25 subject groups in which this outcome was reported was 1.3%, with a range of 0–8.2%. Delay in repeat administration of magnesium sulfate occurred in 3.6% of cases, with a range of 0-65%. Calcium gluconate was administered at an overall rate of less than 0.2%. There was only one maternal death that was attributed by the study authors to the use of magnesium sulfate among the 9556 women in the 24 studies. Conclusion Concerns about safety and toxicity from the use of magnesium sulfate should be mitigated by findings from this integrative review, which indicates a low incidence of the most severe side effects, documented in studies that used a wide variety of standard and modified drug regimens. Adverse effects of concern to providers occur infrequently, and when they occurred, a delay of repeat administration was generally sufficient to mitigate the effect. Early screening and diagnosis of the disease, appropriate treatment with proven drugs, and reasonable vigilance for women under treatment should be adopted as global policy and practice. PMID:23383864

2013-01-01

69

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

PubMed Central

Genome-wide scans in Icelandic, Australian/New Zealand and Finnish pedigrees have provided evidence for maternal susceptibility loci for pre-eclampsia on chromosome 2, although at different positions (Iceland: 2p13 and 2q23, Australia/New Zealand: 2p11–12 and 2q22, Finland: 2p25). In this project, a large population-based (n=65?000) nested case–control study was performed in Norway to further explore the association between positional candidate genes on chromosome 2q and pre-eclampsia, using single-nucleotide polymorphisms (SNPs). DNA samples from 1139 cases (women with one or more pre-eclamptic pregnancies) and 2269 controls (women with normal pregnancies) were genotyped using the Applied Biosystems SNPlex high-throughput genotyping assay. In total, 71 SNPs within positional candidate genes at 2q22–23 locus on chromosome 2 were genotyped in each individual. Genotype data were statistically analysed with the sequential oligogenic linkage analysis routines (SOLAR) computer package. Nominal evidence of association was found for six SNPs (rs1014064, rs17742134, rs1424941, rs2161983, rs3768687 and rs3764955) within the activin receptor type 2 gene (ACVR2A) (all P-values <0.05). The non-independence of statistical tests due to linkage disequilibrium between SNPs at a false discovery rate of 5% identifies our four best SNPs (rs1424941, rs1014064, rs2161983 and rs3768687) to remain statistically significant. The fact that populations with different ancestors (Iceland/Norway–Australia/New Zealand) demonstrate a common maternal pre-eclampsia susceptibility locus on chromosome 2q22–23, may suggest a general role of this locus, and possibly the ACVR2A gene, in pre-eclampsia pathogenesis. PMID:18781190

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

2009-01-01

70

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

PubMed

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

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

2015-02-01

71

HIF1A and MIF as potential predictive mRNA biomarkers of pre-eclampsia: a longitudinal prospective study in high risk population.  

PubMed

Abstract Background: Pre-eclampsia (PE) is a hypertensive multisystem disorder, causing significant fetal-maternal mortality and morbidity worldwide. This study aims to define possible longitudinal predictive mRNA markers involved in the main pathogenic pathways of PE: inflammation [macrophage migration inhibitory factor (MIF)], hypoxia and oxidative stress [hypoxia inducible factor 1-? subunit (HIF1A) and ?-site APP-cleaving enzyme-2 (BACE2)] and endothelial dysfunction [endoglin (ENG), fms-related tyrosine kinase-1 (FLT1) and vascular endothelial growth factor (VEGF)]. Methods: Peripheral blood was collected from 33 singleton pregnancies characterized by a high cardiovascular profile risk sampled consecutively at 6-16; 17-23; 24-30; 31-34; ?35 weeks followed by the Obstetrics and Gynecology Unit of the San Raffaele Hospital in Milan. A real-time quantitative PCR reaction was performed on plasma RNA. Results: Of the 33 women enrolled, nine developed PE. Until 23 weeks HIF1A was significantly higher in women who later developed PE compared to women who did not (p=0.049 and p=0.012 in the first and second blood collection). In the third time interval MIF (p=0.0005), FLT1 (p=0.024), ENG (p=0.0034) and BACE2 (p=0.044) appeared to be significantly increased while HIF1A was elevated even from 24 week onwards but not reaching the statistical significance. In the fourth time interval ENG mRNA still remained increased (p=0.037). Conclusions: HIF1A, marker of hypoxia and oxidative stress, and MIF, marker of inflammation, seemed to be the most promising RNA markers, suggesting that hypoxia, principally, and inflammation may play an important role in PE pathogenesis. PMID:25460285

Galbiati, Silvia; Inversetti, Annalisa; Causarano, Vincenza; Stenirri, Stefania; Soriani, Nadia; Ambrosi, Alessandro; Valsecchi, Luca; Candiani, Massimo; Cremonesi, Laura; Ferrari, Maurizio; Smid, Maddalena

2014-12-01

72

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

PubMed Central

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

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

2013-01-01

73

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

PubMed Central

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

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

2014-01-01

74

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

PubMed Central

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

Daniels, Karen; Lewin, Simon

2008-01-01

75

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

PubMed Central

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

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

2009-01-01

76

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

PubMed Central

Background Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. Methods and Findings From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735–0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658–0.768). A predicted probability ?25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. Conclusions The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care. Please see later in the article for the Editors' Summary PMID:24465185

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

2014-01-01

77

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

PubMed

The SERPINE1 -675 4G/5G promoter region insertion/deletion polymorphism (rs1799889) has been implicated in the pathogenesis of pre-eclampsia (PE), but the genetic association has been inconsistently replicated. To derive a more precise estimate of the association, a systematic review and meta-analysis was conducted. This study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed (MEDLINE), Scopus and HuGE Literature Finder literature databases were systematically searched for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the allelic comparison (4G versus 5G) and genotypic comparisons following the co-dominant (4G/4G versus 5G/5G and 4G/5G versus 5G/5G), dominant (4G/4G+4G/5G versus 5G/5G) and recessive (4G/4G versus 4G/5G+5G/5G) genetic models. Between-study heterogeneity was quantified by I(2) statistics and publication bias was appraised with funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. Meta-analysis of 11 studies involving 1297 PE cases and 1791 controls found a significant association between the SERPINE1 -675 4G/5G polymorphism and PE for the recessive genetic model (OR = 1.36, 95% CI: 1.13-1.64, P = 0.001), a robust finding according to sensitivity analysis. A low level of between-study heterogeneity was detected (I(2) = 20%) in this comparison, which may be explained by ethnic differences. Funnel plot inspection did not reveal evidence of publication bias. In conclusion, this study provides a comprehensive examination of the available literature on the association between SERPINE1 -675 4G/5G and PE. Meta-analysis results support this polymorphism as a likely susceptibility variant for PE. PMID:23180602

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

2013-03-01

78

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

PubMed Central

Background/Objective Pre-eclampsia or Eclampsia (PE or E) accounts for 25% of cases of maternal mortality worldwide. There is some evidence of a link to dietary factors, but few studies have explored this association in developing countries, where the majority of the burden falls. We examined the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E in Indian women. Methods Cross-sectional data from India’s third National Family Health Survey (NFHS-3, 2005-06) was used for this study. Self-reported symptoms suggestive of PE or E during pregnancy were obtained from 39,657 women aged 15-49 years who had had a live birth in the five years preceding the survey. Multivariable logistic regression analysis was used to estimate the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of PE or E after adjusting for maternal, health and lifestyle factors, and socio-demographic characteristics of the mother. Results In their most recent pregnancy, 1.2% (n=456) of the study sample experienced symptoms suggestive of PE or E. Mothers who consumed an adequately diversified diet were 34% less likely (OR: 0.66; 95% CI: 0.51-0.87) to report PE or E symptoms than mothers with inadequately diversified dietary intake. The likelihood of reporting PE or E symptoms was also 36% lower (OR: 0.64; 95% CI: 0.47-0.88) among those mothers who consumed iron and folic acid supplementation for at least 90 days during their last pregnancy. As a sensitivity analysis, we stratified our models sequentially by education, wealth, antenatal care visits, birth interval, and parity. Our results remained largely unchanged: both adequately diversified dietary intake and iron and folic acid supplementation during pregnancy were associated with a reduced occurrence of PE or E symptoms. Conclusion Having a adequately diversified dietary intake and iron and folic acid supplementation in pregnancy was associated with a reduced occurrence of symptoms suggestive of PE or E in Indian women. PMID:25785774

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

2015-01-01

79

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

PubMed

Placental development is known for its resemblance with tumor development, such as in the expression of oncogenes (c-myc) and telomerase (hTERT). The expression of c-myc and hTERT is up-regulated during early pregnancy and gestational trophoblastic diseases (GTDs). To determine the role of DNA methylation [via methylation-sensitive high resolution melting (MS-HRM)] and histone modifications [via chromatin immunoprecipitation (ChIP assay)] in regulating the differential expression of c-myc and hTERT during normal gestation and their dysregulation during placental disorders, we obtained placental samples from 135 pregnant women, in five groups: normal first, second and third trimester (n = 30 each), pre-eclamptic pregnancy (n = 30) and molar pregnancy (n = 15). Two placental cell lines (JEG-3 and HTR-8/SVneo) and isolated first-trimester cytotrophoblasts were also studied. Quantitative RT-PCR revealed decreased mRNA expression levels of c-myc and hTERT, which were associated with a higher level of H3K9me3 (1.5-fold, P < 0.05) and H3K27me3 (1.9-fold, P < 0.05), respectively, in third-trimester placental villi versus first-trimester villi. A significantly lower level of H3K27me3 in molar placenta was associated with a higher mRNA expression of c-myc and hTERT. The development of pre-eclampsia (PE) was associated with increased methylation (P < 0.001) and H3K27me3 (P < 0.01) at the c-myc promoter and reduced H3K9me3 (P < 0.01) and H3K27me3 (P < 0.05) at the hTERT promoter. Further, mRNA expression of c-myc and hTERT was strongly correlated in molar villi (r = 0.88, P < 0.01) and JEG-3 cells (r = 0.99, P < 0.02). Moreover, on the basis of methylation data, we demonstrate the potential of c-myc as a fetal DNA epigenetic marker for pre-eclamptic pregnancies. Thus we suggest a role for epigenetic mechanisms in regulating differential expression of c-myc and hTERT during placental development and use of the c-myc promoter region as a potential fetal DNA marker in the case of PE. PMID:25024139

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

2014-10-01

80

Pre-eclampsia - The "uterine reinnervation" view.  

PubMed

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

Quinn, M J

2014-11-01

81

Pre-Eclampsia, Birth Weight, and Autism Spectrum Disorders  

ERIC Educational Resources Information Center

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

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

2010-01-01

82

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

ERIC Educational Resources Information Center

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

Mann, Joshua R.; McDermott, Suzanne

2011-01-01

83

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

PubMed

39 year old woman, pregnant for 31+5 weeks, who came to our intensive care unit (ICU) referred from the emergency department of the hospital, having swollen ankles, headache and fatigue at moderate effort. We proceeded to take blood pressure (158/96mmHg) and assess lower limb edema. The fetal heart rate monitoring was normal. Knowledgeable and user of healthy guidelines during her pregnancy, she did not follow any treatment. Single mother, she worried about her fetus (achieved through in vitro fertilization), her mother offered to help for any mishap. We developed an Individualized Care Plan. For data collection we used: Rating 14 Virginia Henderson Needs and diagnostic taxonomy NANDA, NOC, NIC. Nursing diagnoses of "fluid volume excess" and "risk of impaired maternal-fetal dyad" were detected, as well as potential complications such as eclampsia and fetal prematurity. Our overall objectives (NOC) were to integrate the woman in the process she faced and that she knew how to recognize the risk factors inherent in her illness. Nursing interventions (NIC) contemplated the awareness and treatment of her illness and the creation of new healthy habits. The work of nursing Maternal ICU allowed women to help maintain maximum maternal and fetal well-being by satisfying any of her needs. Mishandling of the situation leads into a framework of high morbidity and mortality in our units. PMID:25600462

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

2015-01-01

84

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

PubMed Central

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

Seyhan, Tülay Özkan; Bezen, Olgaç; Sungur, Mukadder Orhan; Kalelio?lu, ?brahim; Karadeniz, Meltem; Koltka, Kemalettin

2014-01-01

85

Pregnancy in the Setting of Asymptomatic Non-Cirrhotic Chronic Portal Vein Thrombosis Complicated by Pre-Eclampsia  

PubMed Central

Portal vein thrombosis (PVT) can be chronic or acute in nature; it is characterized by a thrombus formation in the main portal vein and/or its right or left branches. Herein, we present a 36-year-old woman with asymptomatic noncirrhotic chronic PVT who developed preeclampsia in the later stage of pregnancy. This report will emphasize the clinical differential diagnosis, outcome, and management of pregnancies complicated by noncirrhotic PVT. PMID:23781362

Üstüner, I??k; Akdo?an, Remzi Adnan; Güven, Emine Seda Güvenda?; ?ahin, Figen K?r; ?entürk, ?enol; Akdo?an, Elif; Ta?ç?, Filiz

2013-01-01

86

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia  

E-print Network

) Maternal KIR in combination with paternal HLA-C2 regulate human birth weight. J Immunol 192(11):5069-5073. 34. Xiong S, et al. (2013) Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation. J Clin Invest 123(10):4264-4272. 35. Abi...

Nakimuli, Annettee; Chazara, Olympe; Hiby, Susan E.; Farrell, Lydia; Tukwasibwe, Stephen; Jayaraman, Jyothi; Traherne, James A.; Trowsdale, John; Colucci, Francesco; Lougee, Emma; Vaughan, Robert W.; Elliott, Alison M.; Byamugisha, Josaphat; Kaleebu, Pontiano; Mirembe, Florence; Nemat-Gorgani, Neda; Parham, Peter; Norman, Paul J.; Moffett, Ashley

2015-01-05

87

Distress conditions during pregnancy may lead to pre-eclampsia by increasing cortisol levels and altering lymphocyte sensitivity to glucocorticoids  

Microsoft Academic Search

Psychological stress may affect up to 18% of all pregnant women, altering the function of both neuroendocrine and immune systems. Distress conditions may directly change the hypothalamic–pituitary–adrenal (HPA) axis, leading to increased cortisol levels and associated changes in cellular immunity. Psychological events such as high stress levels, anxiety or depression may directly or indirectly affect pregnancy and may thus lead

Priscila Vianna; Moisés E. Bauer; Dinara Dornfeld; José Artur Bogo Chies

2011-01-01

88

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

PubMed

Ruptured subcapsular hematoma of the liver (RSHL) can mimic ruptured interstitial pregnancy because each of these conditions occasionally presents at the same gestational period and both do manifest hemodynamic instability. The similarities between the two conditions pose a diagnostic challenge, especially in an unbooked patient. We report a case of an unbooked primigravida, at 21 weeks of gestation, who arrived at a regional hospital with evidence of intra-abdominal bleeding and hypovolemic shock. She was diagnosed as potentially having a ruptured interstitial pregnancy. During the ensuing emergency laparotomy, RSHL was discovered, the area around the ruptured liver capsule was packed with large abdominal swabs, and the patient recovered. This case report illustrates the need to consider RSHL in patients presenting with features of ruptured interstitial pregnancy, as this will assist in the planning of intraoperative care. We also describe abdominal packing and highlight the need for this essential surgical intervention to be taught to doctors practising in low-resource settings. PMID:25666012

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

2015-01-01

89

Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia  

PubMed Central

During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK cells are functionally and phenotypically distinct from PB NK and are implicated in regulation of trophoblast transformation of the uterine spiral arteries, which if inadequately performed, can result in pregnancy disorders. Here, we have used uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure of the extent of transformation of the spiral arteries to identify pregnancies with a high RI, indicative of impaired spiral artery remodeling. We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI. We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the decidua was examined by receptor blocking in trophoblast coculture and altered dNK expression of the cytokines CXCL10 and TNF-?, which regulate trophoblast behavior. These results indicate that dNK cells from high RI pregnancies may display altered interactions with trophoblast via decreased expression of HLA-binding cell-surface receptors, impacting on successful transformation of the uterus for pregnancy. PMID:25381387

Wallace, Alison E.; Whitley, Guy S.; Thilaganathan, Baskaran; Cartwright, Judith E.

2015-01-01

90

National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark: a role for hyperemesis, gestational hypertension and pre-eclampsia?  

Microsoft Academic Search

Objectives:While reproductive factors might plausibly be involved in the aetiology of rheumatoid arthritis (RA), the female predominance remains unexplained. A study was undertaken to address the possible impact of live births, pregnancy losses and pregnancy complications on the subsequent risk of RA in a nationwide cohort study.Methods:National register data were used to link reproductive histories and later RA hospitalisations in

K T Jørgensen; B V Pedersen; S Jacobsen; R J Biggar; M Frisch

2010-01-01

91

Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia.  

PubMed

During pregnancy, a specialized type of NK cell accumulates in the lining of the uterus (decidua) and interacts with semiallogeneic fetal trophoblast cells. dNK cells are functionally and phenotypically distinct from PB NK and are implicated in regulation of trophoblast transformation of the uterine spiral arteries, which if inadequately performed, can result in pregnancy disorders. Here, we have used uterine artery Doppler RI in the first trimester of pregnancy as a proxy measure of the extent of transformation of the spiral arteries to identify pregnancies with a high RI, indicative of impaired spiral artery remodeling. We have used flow cytometry to examine dNK cells isolated from these pregnancies compared with those from pregnancies with a normal RI. We report a reduction in the proportion of dNK cells from high RI pregnancies expressing KIR2DL/S1,3,5 and LILRB1, receptors for HLA-C and HLA-G on trophoblast. Decreased LILRB1 expression in the decidua was examined by receptor blocking in trophoblast coculture and altered dNK expression of the cytokines CXCL10 and TNF-?, which regulate trophoblast behavior. These results indicate that dNK cells from high RI pregnancies may display altered interactions with trophoblast via decreased expression of HLA-binding cell-surface receptors, impacting on successful transformation of the uterus for pregnancy. PMID:25381387

Wallace, Alison E; Whitley, Guy S; Thilaganathan, Baskaran; Cartwright, Judith E

2015-01-01

92

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

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

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

93

The first trimester: prediction and prevention of the great obstetrical syndromes.  

PubMed

A number of groups are currently examining the potential of screening for pre-eclampsia and gestational diabetes at 12 weeks' gestation. This can be performed at the time of combined first-trimester screening for aneuploidy using a similar method of regression analysis to combine multiple demographic and investigative factors. At present, research into the prediction of pre-eclampsia is more robust and is associated with the potential for therapeutic intervention that can reduce the prevalence of early-onset pre-eclampsia and improve maternal and neonatal outcomes. PMID:25482532

Sweeting, Arianne; Park, Felicity; Hyett, Jon

2015-02-01

94

32 CFR 732.16 - Emergency care requirements.  

Code of Federal Regulations, 2010 CFR

...Premature or term labor with delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy with cardiovascular instability. (7) Premature rupture of membrames with prolapse of the umbilical cord....

2010-07-01

95

P-16  

Microsoft Academic Search

BACKGROUND: Pre-eclampsia affects 2-10% of all pregnancies and is a major cause of maternal and fetal morbidity and mortality. As compared with the general population, IVF pregnancies are associated with a 2.7-fold risk of pre- eclampsia. An advanced age and associated subfertility in the IVF group reflects a general decrease in ovarian reserve, which itself has been linked to cardiovascular

G. H. Woldringh; M. H. A. Frunt; J. A. M. Kremer; M. E. A. Spaanderman

2006-01-01

96

Proteases and their inhibitors are indicative in gestational disease  

Microsoft Academic Search

Objective: To assess whether various proteolytic factors which are involved in trophoblast invasion show different concentrations in plasma and placenta of patients with HELLP syndrome, pre-\\/eclampsia and highly pathological Doppler flow measurements but without additional complications (hpD). Design: Case control and observational study; 18 women with HELLP syndrome, 21 with pre-\\/eclampsia, 13 with hpD, as well as healthy pregnant women

M. Kolben; A. Lopens; J. Bläser; K. Ulm; M. Schmitt; K. T. M. Schneider; H. Tschesche

1996-01-01

97

Hypertensive Disorders of Pregnancy: A Systematic Review of International Clinical Practice Guidelines  

PubMed Central

Background Clinical practice guidelines (CPGs) are developed to assist health care providers in decision-making. We systematically reviewed existing CPGs on the HDPs (hypertensive disorders of pregnancy) to inform clinical practice. Methodology & Principal Findings MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessments, and Database of Abstracts of Reviews of Effects (Ovid interface), Grey Matters, Google Scholar, and personal records were searched for CPGs on the HDPs (Jan/03 to Nov/13) in English, French, Dutch, or German. Of 13 CPGs identified, three were multinational and three developed for community/midwifery use. Length varied from 3–1188 pages and three guidelines did not formulate recommendations. Eight different grading systems were identified for assessing evidence quality and recommendation strength. No guideline scored ?80% on every domain of the AGREE II, a tool for assessing guideline methodological quality; two CPGs did so for 5/6 domains. Consistency was seen for (i) definitions of hypertension, proteinuria, chronic and gestational hypertension; (ii) pre-eclampsia prevention for women at increased risk: calcium when intake is low and low-dose aspirin, but not vitamins C and E or diuretics; (iii) antihypertensive treatment of severe hypertension; (iv) MgSO4 for eclampsia and severe pre-eclampsia; (v) antenatal corticosteroids at <34 wks when delivery is probable within 7 days; (vi) delivery for women with severe pre-eclampsia pre-viability or pre-eclampsia at term; and (vii) active management of the third stage of labour with oxytocin. Notable inconsistencies were in: (i) definitions of pre-eclampsia and severe pre-eclampsia; (ii) target BP for non-severe hypertension; (iii) timing of delivery for women with pre-eclampsia and severe pre-eclampsia; (iv) MgSO4 for non-severe pre-eclampsia, and (v) postpartum maternal monitoring. Conclusions Existing international HDP CPGs have areas of consistency with which clinicians and researchers can work to develop auditable standards, and areas of inconsistency that should be addressed by future research. PMID:25436639

Gillon, Tessa E. R.; Pels, Anouk; von Dadelszen, Peter; MacDonell, Karen; Magee, Laura A.

2014-01-01

98

Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy  

PubMed Central

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

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

2012-01-01

99

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

PubMed

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

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

2014-11-01

100

The pathophysiology of preeclampsia involves altered levels of angiogenic factors promoted by hypoxia and autoantibody-mediated mechanisms.  

PubMed

Pre-eclampsia is a syndrome characterized by inadequate placentation, which is due to deficient trophoblastic invasion of the uterine spiral arteries. This deficiency can lead to placental hypoxia, secretion of proinflammatory cytokines, and release of angiogenic and antiangiogenic factors. Hypoxic conditions in the placenta can promote oxidative stress and the production of angiogenic factors that are antagonized by soluble receptors, which are also elevated in this syndrome. In addition to these factors, the development of hypertension in women with pre-eclampsia may be associated with the renin-angiotensin system and endothelial dysfunction. The presence of antiangiotensin II type 1 receptor autoantibodies is relevant in pre-eclampsia because it has been related to the secretion of antiangiogenic factors through cytokine pathways, indicating that autoimmune mechanisms may participate in the pathophysiology of this syndrome. PMID:22649072

Laresgoiti-Servitje, Estibalitz; Gomez-Lopez, Nardhy

2012-08-01

101

Characterization of a TGF?-responsive Human Trophoblast-derived Cell Line  

Microsoft Academic Search

The placenta is formed by developing trophoblast cells to facilitate fluid, gas and nutrient exchange with the mother. Inappropriate trophoblast responsiveness can lead to life threatening complications during pregnancy including intrauterine growth retardation, pre-eclampsia, spontaneous abortion and malignancy that could lead to fetal loss. Transforming growth factor beta (TGF?) is a multifunctional cytokine required for embryonic development and is an

A. N. Smith; Q. L. Carter; D. A. Kniss; T. L. Brown

2001-01-01

102

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

PubMed Central

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.

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

2014-01-01

103

Recruiting American Indian Women for a Genetic Epidemiology Study  

Microsoft Academic Search

Due to previous negative experiences, some American Indian communities are distrustful of research in general and genetic research in particular. The Turtle Mountain Community College was awarded a National Institutes of Health (NIH) grant with 3 aims: (1) to study possible genetic influences on pre-eclampsia, (2) to encourage tribal college students to consider biomedical careers and (3) to develop the

M. Nadeau; L. Best

2010-01-01

104

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

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.

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

1976-01-01

105

Interventions for leg edema and varicosities in pregnancy  

Microsoft Academic Search

Leg oedema from venous insufficiency is not dangerous but it can cause women symptoms such as pain, feelings of heaviness, night cramps and paraesthesiae. Leg oedema can be a sign of pre-eclampsia when associated with raised blood pressure or proteinuria. The objective of this review was to assess the effects of treatment to relieve the symptoms associated with varicosity in

Anthony Akinloye Bamigboye; George Justus Hofmeyr

2006-01-01

106

Hypertension in pregnancy: natural history and treatment options.  

PubMed

Hypertensive disorders of pregnancy affect approximately 5-10 % of all maternities and are major contributors of maternal and neonatal morbidity and mortality worldwide. This group of disorders encompasses chronic hypertension, as well as conditions that arise de novo in pregnancy: gestational hypertension and pre-eclampsia. The latter group is thought to be part of the same continuum but with arbitrary division. Research into the aetiology of hypertension in pregnancy have largely been focused on pre-eclampsia, with a majority of studies exploring either pregnancy-associated factors such as placental-derived or immunologic responses to pregnancy tissue, or maternal constitutional factors such as cardiovascular health and endothelial dysfunction. The evidence base for the pathophysiology and progression of hypertensive disorders in pregnancy, particularly pre-eclampsia, is reviewed. Clinical algorithms and pharmacological agents for the management of hypertension in pregnancy are summarised, with a brief focus on post-partum considerations and long-term health implications. Novel therapeutic options for the management of pre-eclampsia are also explored. PMID:25833457

Foo, L; Tay, J; Lees, C C; McEniery, C M; Wilkinson, I B

2015-05-01

107

Angiogenesis, proteases and angiogenic factors during the inception of pregnancy. Crucial contributors or trivial bystanders?  

Microsoft Academic Search

Vascularised, receptive endometrium is essential for implantation and for the success of the embryo-maternal interaction. Disturbances in vascular development may play an important role in frequently occurring pathologies during pregnancy, such as early pregnancy wastage, pre-eclampsia and intrauterine growth restriction. Adaptation to implantation starts during the menstrual cycle by stromal decidualisation and the induction of angiogenesis, the formation of new

Geertruida Maria Plaisier

2008-01-01

108

Comp. by:dshanthi Date:1/8/05 Time:15:46:44 Stage:First Proof File Path:// spsind002s/serials/PRODENV/000000~1/001BFD~1/S00000~1/00D23E~1/000000~3/  

E-print Network

, but not in the fetus. Severe complications of pre- eclampsia can include acute renal failure, cerebral edema, cerebral* *Renal, Molecular, and Vascular Medicine Division, Departments of Medicine Obstetrics and Gynecology by the new onset of hypertension and protein- uria after 20 weeks of gestation (Roberts, 2000; Roberts

Haig, David

109

Obesity in pregnancy: a major healthcare issue  

Microsoft Academic Search

The prevalence of maternal obesity is rising, up to 20% in some antenatal clinics, in line with the prevalence of obesity in the general population. Maternal obesity poses significant risks for all aspects of pregnancy. There are risks to the mother with increased maternal mortality, pre-eclampsia, diabetes and thromboembolic disorders. There is increased perinatal mortality, macrosomia and congenital malformation. The

Elly Tsoi; Humera Shaikh; Stephen Robinson; Tiong Ghee Teoh

2010-01-01

110

Name: prof. dr. A. Franx Faculty Medicine  

E-print Network

exhibit an excess of classic and novel cardiovascular risk factors and scores and are at increased risk of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review AJ. Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased

Utrecht, Universiteit

111

Sexually dimorphic effects of maternal asthma during pregnancy on placental glucocorticoid metabolism and fetal growth  

Microsoft Academic Search

Human pregnancy is associated with sexually dimorphic differences in mortality and morbidity of the fetus with the male fetus experiencing the poorest outcome following complications such as pre-eclampsia, pre-term delivery and infection. The physiological mechanisms that confer these differences have not been well characterised in the human. Work conducted on the effect of maternal asthma during pregnancy, combining data collected

Vicki L. Clifton

2005-01-01

112

Evolution, Medicine, and Public Health [2014] pp. 5153 doi:10.1093/emph/eou008  

E-print Network

Evolution, Medicine, and Public Health [2014] pp. 51­53 doi:10.1093/emph/eou008 Medical, ethical February 2014 K EYWORDS: evolutionary medicine; medical ethics; parent­offspring conflict Among the most for a broad swath of major medical conditions, including pre- eclampsia, gestational diabetes and intrauterine

Crespi, Bernard J.

113

Increased Placental Phospholipid Levels in Pre-Eclamptic Pregnancies  

PubMed Central

Physiological pregnancy is associated with an increase in lipids from the first to the third trimester. This is a highly regulated response to satisfy energy and membrane demands of the developing fetus. Pregnancy disorders, such as pre-eclampsia, are associated with a dysregulation of lipid metabolism manifesting in increased maternal plasma lipid levels. In fetal placental tissue, only scarce information on the lipid profile is available, and data for gestational diseases are lacking. In the present study, we investigated the placental lipid content in control versus pre-eclamptic samples, with the focus on tissue phospholipid levels and composition. We found an increase in total phospholipid content as well as changes in individual phospholipid classes in pre-eclamptic placental tissues compared to controls. These alterations could be a source of placental pathological changes in pre-eclampsia, such as lipid peroxide insult or dysregulation of lipid transport across the syncytiotrophoblast. PMID:23389044

Huang, Xiao; Jain, Arjun; Baumann, Marc; Körner, Meike; Surbek, Daniel; Bütikofer, Peter; Albrecht, Christiane

2013-01-01

114

The identification of high risk pregnancy: a new challenge in obstetrics.  

PubMed

Preterm delivery (PTD) and pre-eclampsia (PE) represent the main "obstetric syndromes," caused by multiple conditions, and characterized by complex pathogenesis. Nonetheless, recent evidences attest that deregulation of the immune system and exaggeration of inflammatory processes, taking place in the feto-placental unit, represent common central mechanisms occurring in both diseases. Tertiary prevention represents the only intervention to prevent PTD, but its incidence is still increasing. Advances in secondary prevention, focusing on risk factors and possible markers, are necessary. PMID:22348307

Torricelli, Michela; Voltolini, Chiara; De Bonis, Maria; Vellucci, Francesca Letizia; Conti, Nathalie; Severi, Filiberto Maria; Petraglia, Felice

2012-04-01

115

Maternal endothelial function and serum concentrations of placental growth factor and soluble endoglin in women with abnormal placentation  

Microsoft Academic Search

Objectives To determine whether maternal serum con- centrations of placental growth factor (PlGF) and soluble endoglin (sEng) are altered in women who subsequently develop pre-eclampsia (PE) or have small-for-gestational- age (SGA) infants, and whether these changes are associ- ated with maternal endothelial dysfunction. Methods Maternal serum PlGF and sEng were measured in two groups of pregnant women at 23-25 weeks'

M. D. Savvidou; M. Noori; J. M. Anderson; A. D. Hingorani; K. H. Nicolaides

2008-01-01

116

Regulation of Plasminogen Activator Inhibitor (PAI)-1 Expression in a Human Trophoblast Cell Line by Glucocorticoid (GC) and Transforming Growth Factor (TGF)-?  

Microsoft Academic Search

Plasminogen activator inhibitor (PAI)-1 plays a key role in the regulation of fibrinolysis and cellular invasion by virtue of suppression of plasminogen activator function. Excessive production of placental PAI-1 has been associated with aberrant periplacental fibrin deposition in pregnancies complicated by pre-eclampsia (PE) and intrauterine growth restriction (IUGR). In the current study we used HTR-8\\/SVneo cells and primary cultures of

Y. Ma; J. S. Ryu; A. Dulay; M. Segal; S. Guller

2002-01-01

117

Analysis of the Metabolic Footprint and Tissue Metabolome of Placental Villous Explants Cultured at Different Oxygen Tensions Reveals Novel Redox Biomarkers  

Microsoft Academic Search

Pre-eclampsia (PE) is a multi-system disorder of pregnancy hypothesised to arise from circulating factors derived from an unhealthy placenta. Some changes in placental phenotype seen in PE can be reproduced by culture in altered oxygen (O2) tension. Currently, these circulating factors are unidentified, partly due to the complexity of maternal plasma. Investigation of factors released from placental tissue provides a

A. E. P. Heazell; M. Brown; W. B. Dunn; S. A. Worton; I. P. Crocker; P. N. Baker; D. B. Kell

2008-01-01

118

Pregnancy outcomes after bariatric surgery: maternal, fetal, and infant implications  

Microsoft Academic Search

Obese women who become pregnant face many health risks, including gestational diabetes, pregnancy-induced hypertension, and pre-eclampsia. These women also have a greater incidence of preterm labor, cesarean sections, and perioperative morbidity. Infants born to obese women have increased rates of macrosomia and congenital anomalies, as well as life-long complications such as obesity and its associated morbidities. With the increase in

Adam Abodeely; G. Dean Roye; David T. Harrington; William G. Cioffi

2008-01-01

119

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

Microsoft Academic Search

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

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

2011-01-01

120

Reversible cerebral vasoconstriction syndrome: a rare cause of postpartum headache.  

PubMed

We describe two women presenting with severe postpartum headache associated with hypertension but with no other signs or investigation results to suggest pre-eclampsia. In one case, the headache was associated with atypical subarachnoid haemorrhage. The variable nature of the headache and the degree of associated hypertension raised the clinical suspicion of reversible cerebral vasoconstriction syndrome, confirmed on MR angiography. Both patients took nimodipine until the cerebral vasoconstriction had resolved radiologically. PMID:25573342

Wiles, Kate S; Nortley, Ross; Siddiqui, Ata; Holmes, Paul; Nelson-Piercy, Catherine

2015-04-01

121

Alternative management of placenta accreta  

Microsoft Academic Search

A 27-year-old lady presented at 32 weeks gestation complaining of shortness of breath, headache, palpitations and feeling\\u000a generally unwell for 1 day. Her current pregnancy was complicated by major placenta praevia. Because she developed worsening\\u000a symptoms of pre-eclampsia and raised blood pressure, a decision was made to deliver her by an elective Caesarean section.\\u000a The Caesarean section was complicated by

Joseph Mechery; David Burch

2006-01-01

122

Confidential enquiry into maternal deaths in The Netherlands 1983–1992  

Microsoft Academic Search

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

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

1998-01-01

123

Managing pregnancy in inflammatory rheumatological diseases  

Microsoft Academic Search

Historically, pregnancy in women with many inflammatory rheumatic diseases was not considered safe and was discouraged. Combined\\u000a care allows these pregnancies to be managed optimally, with the majority of outcomes being favorable. Disease activity at\\u000a the time of conception and anti-phospholipid antibodies are responsible for most complications. Disease flares, pre-eclampsia,\\u000a and thrombosis are the main maternal complications, whereas fetal loss

Varsha Jain; Caroline Gordon

2011-01-01

124

Growing evidence that several human cancers may originate in utero  

Microsoft Academic Search

Hormone-related cancers may originatein utero. Accumulating evidence is given by animal studies, descriptive epidemiologic data and analytic etiologic studies. Indicators of high levels of endogenous pregnancy hormones, like high birth weight and jaundice in the offspring, are associated with increased risk for breast, prostate, and non-seminoma testicular cancer. Indicators of low levels, like pre-eclampsia, are associated with decreased risk. These

Anders Ekbom

1998-01-01

125

Costs of maternal conditions attributable to smoking during pregnancy  

Microsoft Academic Search

Context: Despite known adverse health effects, many women continue to smoke during pregnancy. Public attention has now focused on the economic as well as health effects of this behavior.Objective: To estimate health care costs associated with smoking-attributable cases of placenta previa, abruptio placenta, ectopic pregnancy, preterm premature rupture of the membrane (PPROM), pre-eclampsia, and spontaneous abortion.Design: Pooled odds ratios were

E. Kathleen Adams; Cathy L. Melvin

1998-01-01

126

Validation of a solar powered blood pressure device, suitable for use in low resource settings  

Microsoft Academic Search

Hypertensive diseases in pregnancy are a significant cause of morbidity and mortality, particularly in low resource settings (LRS). Pre-eclampsia and eclampsia alone claim up to 50 000 women's lives globally each year, with an estimated fetal case death of 7–25% in African countries.1 Accurate and regular antenatal blood pressure (BP) monitoring is a cost effective means for early identification and

A de Greef; D Ashraf; L Saad; N L Hezelgrave; A H Shennan

2011-01-01

127

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

PubMed Central

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

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

2013-01-01

128

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

PubMed

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

Younis, Johnny S; Laufer, Neri

2015-02-01

129

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

PubMed Central

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

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

2015-01-01

130

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

PubMed

Plasma volume expansion of more than 1.5 l and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.e. pre-eclampsia commonly coincide with hemo concentration and over activation of blood coagulation both of which alter blood rheology. On the basis of 4,985 consecutively recorded singleton pregnancies values range of blood rheological parameters in women with normal and complicated outcome of pregnancy at the time of their delivery were compared. Plasma viscosity (pv) was determined using KSPV 1 Fresenius and RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. Seventy-nine point four percent (n=3,959) had normal pregnancy outcome and 1,026 with adverse outcome of pregnancy had pre-eclampsia (8.4%; n=423), had newborn with a birth-weight < 2,500 g (9.5%; n=473), had early-birth before week 37 (9.3%; n=464), and/or were diagnosed with intra uterine growth retardation (IUGR) (5.0%; n=250). In women with normal pregnancy outcome mean (+/-SD) of pv was 1.31+/-0.09 mPa s, of E0 was 21.6+/-5.3, and of E1 was 38.4+/-7.9 while in women with adverse outcome means for rheological parameters were statistically significantly different i.e. pv: 1.32+/-0.08 mPa s; p=0.006, E0: 22.1+/-5.5; p=0.002 and E1: 39.5+/-8.5; p=0.0006. Subgroup analysis revealed statistical significant lower pv in women who either had pre term delivery or a low birth-weight child (p<0.005) as compared to women who had normal pregnancy outcome while patients with pre-eclampsia had markedly higher low shear and stasis RBC aggregation (p<0.0001). None of the rheological results at term were correlated with either maternal age (r<0.04), BMI (r<0.09), maternal weight gain until delivery (r<0.04), or fetal outcome such as APGAR-score (r<0.09) art. pH in the umbilical cord (-0.05pre-eclampsia hemo concentration and increased fibrinogen turnover due to enhanced coagulation activation are weighty co factors of pv but were associated with lower pv in patients with pre-eclampsia. However, coincidental increased RBC aggregation and hemo concentration may potentially derogate blood flow in the materno-fetal unit that is commonly traceable using vessel duplex ultra sound in pre-eclampsia. PMID:19433886

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

2009-01-01

131

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

PubMed Central

Background 5% of first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROvED Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The key objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia. Methods/Design We report the design of a multicentre, phase IIa clinical study aiming to recruit 5000 low risk primiparous women to assess and refine innovative prototype tests based on emerging metabolomic and proteomic technologies. Participation involves maternal phlebotomy at 15 and 20 weeks’ gestation, with optional testing and biobanking at 11 and 34 weeks. Blood samples will be analysed using two innovative, proprietary prototype platforms; one metabolomic based and one proteomic based, both of which outperform current biomarker based screening tests at comparable gestations. Analytical and clinical data will be collated and analysed via the Copenhagen Trials Unit. Discussion The IMPROvED study is expected to refine proteomic and metabolomic panels, combined with clinical parameters, and evaluate clinical applicability as an early pregnancy predictive test for pre-eclampsia. If ‘at risk’ patients can be identified, this will allow stratified care with personalised fetal and maternal surveillance, early diagnosis, timely intervention, and significant health economic savings. The IMPROvED biobank will be accessible to the European scientific community for high quality research into the cause and prevention of adverse pregnancy outcome. Trial registration Trial registration number NCT01891240 The IMPROvED project is funded by the seventh framework programme for Research and Technological development of the EU. http://www.fp7-improved.eu/ PMID:24314209

2013-01-01

132

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

PubMed Central

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

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

1996-01-01

133

Managing pregnancy in inflammatory rheumatological diseases  

PubMed Central

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

2011-01-01

134

Endoglin: a critical mediator of cardiovascular health  

PubMed Central

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

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

2013-01-01

135

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

PubMed Central

Background Preterm birth (PTB) (<37weeks) complicates approximately 15 million deliveries annually, 60% occurring in low- and middle-income countries (LMICs). Several maternal morbidities increase the risk of spontaneous (spPTB) and provider-initiated (piPTB) preterm birth, but there is little data from LMICs. Method We used the WHO Global Survey to analyze data from 172,461 singleton deliveries in 145 facilities across 22 LMICs. PTB and six maternal morbidities (height <145 cm, malaria, HIV/AIDS, pyelonephritis/UTI, diabetes and pre-eclampsia) were investigated. We described associated characteristics and developed multilevel models for the risk of spPTB/piPTB associated with maternal morbidities. Adverse perinatal outcomes (Apgar <7 at 5 minutes, NICU admission, stillbirth, early neonatal death and low birthweight) were determined. Results 8.2% of deliveries were PTB; one-quarter of these were piPTB. 14.2% of piPTBs were not medically indicated. Maternal height <145 cm (AOR 1.30, 95% CI 1.10–1.52), pyelonephritis/UTI (AOR 1.16, 95% CI 1.01–1.33), pre-gestational diabetes (AOR 1.41, 95% CI 1.09–1.82) and pre-eclampsia (AOR 1.25, 95% CI 1.05–1.49) increased odds of spPTB, as did malaria in Africa (AOR 1.67, 95%CI 1.32-2.11) but not HIV/AIDS (AOR 1.17, 95% CI 0.79-1.73). Odds of piPTB were higher with maternal height <145 cm (AOR 1.47, 95% CI 1.23-1.77), pre-gestational diabetes (AOR 2.51, 95% CI 1.81-3.47) and pre-eclampsia (AOR 8.17, 95% CI 6.80-9.83). Conclusions Maternal height <145 cm, diabetes and pre-eclampsia significantly increased odds of spPTB and piPTB, while pyelonephritis/UTI and malaria increased odds of spPTB only. Strategies to reduce PTB and associated newborn morbidity/mortality in LMICs must prioritize antenatal screening/treatment of these common conditions and reducing non-medically indicated piPTBs where appropriate. PMID:24484741

2014-01-01

136

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

PubMed Central

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

Shahien, Radi; Bowirrat, Abdalla

2011-01-01

137

[Bacterial lipopolsaccharides in pathogenesis of gynecological diseases and obstetric complications].  

PubMed

Analysis of literature data and author studies on the role of lipopolysaccharides (endotoxin) of Gram negative bacteria in women genital tract pathology and obstetric complications is presented. The role of endogenous infection associated with altered microecology of intestinal tract and vaginal biotopes of women in the development of endotoxinemia is discussed. The participation of endotoxin in embryo resorption, delay of intrauterine development and antenatal death of fetus, premature birth, pre-eclampsia, placental dysfunction is examined. The level of endotoxinema and pro-inflammatory cytokines is a marker of chronic endogenous infectious-inflammatory disease of various parts of genital tract with damage of a network of female reproduction system organs. PMID:25286536

Bondarenko, K M; Bondarenko, V M

2014-01-01

138

Reducing morbidity and mortality among pregnant obese.  

PubMed

Obesity is increasing; in the UK, almost 20% of pregnant women have a body mass index (BMI) of ?30 kg/m(2). Obese mothers have increased risks of pregnancy complications including miscarriage, congenital anomaly, gestational diabetes, pre-eclampsia, macrosomia, induction of labour, caesarean section, anaesthetic and surgical complications, post-partum haemorrhage, infection and venous thromboembolism. Complications tend to be greater in those with the highest BMIs. In recent triennia, obesity (27-29%) was over-represented in maternal mortality figures. Strategies to reduce morbidity and mortality include calculating BMI at booking visit to identify obese mothers and plan their antenatal care and delivery. This should include nutritional and lifestyle advice, screening for gestational diabetes and pre-eclampsia, thromboembolism risk assessment, antenatal anaesthetic review if BMI is ? 40 kg/m(2), ensuring availability of robust theatre tables and other equipment and involving senior doctors, especially in the labour ward. Afterwards, continuing weight reduction should be encouraged to reduce future pregnancy and health risks. PMID:25457861

Harper, Ann

2015-04-01

139

The effect of Kraussianone-2 (Kr2), a natural pyrano-isoflavone from Eriosema kraussianum, in an L-NAME- induced pre-eclamptic rat model.  

PubMed

This study aimed to investigate the effects of Kraussianone-2 (Kr2), a pyrano-isoflavone isolated from the roots of Eriosema kraussianum N. E. Br. (Fabaceae) on various fetal and physiological parameters in pregnant, L-NAME treated Sprague-Dawley rats. Twenty-four pregnant Sprague-Dawley dams were divided into three groups (n?=?8), i.e. the control group (CON), the experimental control group (PRE), where the pre-eclampsia-like symptoms were induced using L-NAME, and the experimental group (EK2), where the pre-eclampsia-like symptoms were once again induced using L-NAME, however, these animals were treated with Kr2. On gestation day 20 the animals were sacrificed, at which time a laparotomy was performed and the number of live pups were counted and their corresponding birth and placental weights were recorded. Blood was also collected in heparin-coated tubes and the plasma samples were then analysed for specific variables using commercially available kits for rats. Kraussianone-2 administration decreased fetal mortality and demonstrated a trend toward increasing birth and placental weights in this model. Furthermore, Kr2 administration also reduced blood pressure amplification and decreased the plasma concentrations of two antiangiogenic factors, soluble fms-like tyrosine kinase1 (sFlt-1) and soluble endoglin (sEng). We speculate that Kr2, by improving uterine artery blood flow, results in improved fetal outcomes and decreased antiangiogenic factors in pregnant, L-NAME treated, Sprague-Dawley rats. PMID:22308016

Ramesar, S V; Drewes, S E; Gathiram, P; Moodley, J; Mackraj, I

2012-09-01

140

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

PubMed Central

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

Spencer, RN; Carr, DJ; David, AL

2014-01-01

141

Managing lupus patients during pregnancy  

PubMed Central

Systemic lupus erythematosus (SLE) is an autoimmune disease, primarily affecting young females. Pregnancy in a woman with SLE remains a high risk situation with higher maternal and fetal mortality and morbidity. Although live births are achieved in majority of the pregnancies, active disease and major organ involvement can negatively affect the outcomes. Higher risk of fetal loss, pre-term birth, intra-uterine growth restriction and neonatal lupus syndromes are major fetal issues. Mothers are faced with disease flares, pre-eclampsia and other complications. Disease flares during SLE pregnancy pose the unique issue of recognition and differentiation between physiologic changes and disease state. Similarly pre-eclampsia and lupus nephritis may lead to diagnostic confusion. Treatment choices during pregnancy are limited to a few safe drugs, further restricting the options. Refractory pregnancy loss associated with anti-phospholipid antibodies and complete heart block associated with anti-Ro antibodies remain unresolved issues. A multidisciplinary approach, with close monitoring, is essential for optimal outcomes. PMID:24238698

Lateef, Aisha; Petri, Michelle

2013-01-01

142

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

PubMed

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

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

2015-03-01

143

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

PubMed

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

Spencer, R N; Carr, D J; David, A L

2014-07-01

144

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

PubMed Central

Objective: To determine the prevalence of eclampsia in Qatar, the associated maternal and perinatal outcomes for the period from January 1991 to December 2009 and to define any possible preventive measures to this potentially fatal complication. Methods: A retrospective case review was performed of all women with eclampsia admitted to the Women's Hospital and Obstetrics and Gynecology department at Al Khor Hospital for the period from January 1991 to December 2009. Details were collected by reviewing the files of the patients from the medical records. Data were analyzed by either X2 analysis or the unpaired student “t” test as appropriate. Results: During the period of the study there were 224,809 births. Seventy women developed eclampsia (0.31/1000 deliveries), 44.3% of them were antepartum, 31.4% postpartum and 24.3% intrapartum eclampsia. 34.3% of patients presented with fits, 38.5% presented with pre-eclampsia (PE) and 20% presented with severe pre eclampsia; 18.5% were mild PE and another 27.2% were admitted with different complaints. Symptoms of impending eclampsia were seen in 22.9% of the PE patients. Thirty percent had no antenatal care (ANC). Antihypertensive therapy was given to 72% of cases. Antiepileptic therapy was administered to 48% of cases and 58.5% received magnesium sulfate. Eclampsia was associated with increased rate of cesarean section (CS) (64.2%). There was one maternal death, and the rate of major maternal complications was 20%. The perinatal mortality rate was 12.8%. Conclusion: The incidence of eclampsia in Qatar is 0.31 per 1000 deliveries. Although rare, this condition is associated with increased maternal morbidity and perinatal mortality. However our result is lower than reported worldwide. Improvement of obstetric care by having high index of suspicion even with apparently low risk patients, using magnesium sulfate prophylaxis for all cases of severe pre-eclampsia, in addition to community based approach to improve community health, education and prenatal care, all can be effective measures for the decrease incidence of this fatal condition although eclampsia cannot be entirely prevented. PMID:25003034

Sharara, Hussein Attia

2012-01-01

145

Availability of Treatment for Eclampsia in Public Health Institutions in Maharashtra, India  

PubMed Central

Severe pre-eclampsia and eclampsia are common causes of maternal deaths worldwide and more so in developing countries. Magnesium sulphate (MgSO4) is now the most-recommended drug of choice to treat these conditions. Despite favourable policies for the use of MgSO4 treatment in India, eclampsia continues to take a high toll. This study examined the availability and use of MgSO4 treatment in the public health system and poor women's recent experiences with eclampsia treatment in Maharashtra state. A mix of qualitative and quantative methods was used. A facility-based survey of all secondary and tertiary healthcare facilities (n=44) in 3 selected districts and interviews with public and contracted-in private sector obstetricians, health officials, and programme managers were conducted. A list of recently-delivering women from marginalized communities, with up to two livebirths, was drawn through a community-level survey in 272 villages covered by 60 subcentres selected at random. Mothers were selected for interviews, using maximum variation sampling, and interviews were conducted with 17% of the mothers who reported having experienced eclampsia; 61% of facilities had no stock of MgSO4, the stock-out position continuing from a period ranging from 3 months to 3 years while another 20% had some stock, although less than the expected minimum quantity. No treatment for eclampsia was provided in the recent 3 months at 73% facilities. Our survey of recently-delivering mothers recorded a history of eclampsia in 3.2% pregnancies/deliveries. Interviews with 10 such mothers revealed that treatment for eclampsia has been sought from public as well as private hospitals and from traditional healers. However, facilities where women have received medical treatment are exclusively in the private sector. Almost all public and private care providers were aware of MgSO4 as the gold standard to treat eclampsia; however, it is unclear if they knew of its use to treat severe pre-eclampsia. The private care providers routinely used MgSO4 for eclampsia treatment while the public care providers seemed hesitant to use it fearing risks of complications. We stress the need for improved inventory control practices to ensure sustained availability of supplies and building confidence of care providers in using MgSO4 treatment for severe pre-eclampsia and eclampsia in public facilities, in addition to teaching expectant mothers how to recognize symptoms of these conditions. PMID:23617209

Chaturvedi, Sarika; Randive, Bharat

2013-01-01

146

Helicobacter pylori and pregnancy-related disorders  

PubMed Central

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

Cardaropoli, Simona; Rolfo, Alessandro; Todros, Tullia

2014-01-01

147

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

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

2014-01-01

148

[Pregnancy and childbirth in adolescents under 16. Study of 150 cases in French Guyana].  

PubMed

We studied 150 cases of adolescents under 16 having delivered at the maternity of Saint Laurent du Maroni hospital in French Guyana. These pregnancies were compared with those of 150 parturient women aged between 18 and 25. Significant differences were found between the two groups in terms of vaginal infectious diseases, premature birth rate and perinatal mortality. There was a significantly higher rate of assisted deliveries. These results are in concordance with the literature, except for the percentage of pre-eclampsia, which is not higher in our series. We point out the very high adolescent pregnancy prevalence in French Guyana and the need for setting up of a suitable prevention policy. PMID:9791577

Carles, G; Jacquelin, X; Raynal, P; Bertsch, M; Zoccarato, A M

1998-09-01

149

Corin in Natriuretic Peptide Processing and Hypertension  

PubMed Central

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

Zhou, Yiqing; Wu, Qingyu

2014-01-01

150

Recruiting American Indian Women for a Genetic Epidemiology Study  

PubMed Central

Due to previous negative experiences, some American Indian communities are distrustful of research in general and genetic research in particular. The Turtle Mountain Community College was awarded a National Institutes of Health (NIH) grant with 3 aims: (1) to study possible genetic influences on pre-eclampsia, (2) to encourage tribal college students to consider biomedical careers and (3) to develop the local research infrastructure. Retrospectively identified case (91) and control (188) participants were recruited into Phase I over a 3-year period and additional participants (71) were concurrently recruited from a prenatal clinic into a prospective case/control study, Phase II. This paper describes some of the challenges and solutions we encountered in the process of recruiting American Indian participants into a genetic epidemiologic study. PMID:20616521

Nadeau, M.; Best, L.

2010-01-01

151

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

PubMed

The autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by the dysregulation of the Fas apoptotic pathway. The Fas gene is expressed at the maternal-fetal interface and is involved in the regulation of immune response and implantation. Altered Fas expression may result in altered apoptosis and, ultimately, affect both the immune response and implantation; it is in fact associated with recurrent pregnancy loss, preterm premature rupture of membranes and pre-eclampsia. Currently, there are over 500 cases of ALPS reported worldwide from various racial and ethnic backgrounds. Up to date, the published work contains no specific reports on pregnancy outcome in women affected by ALPS. We present a case of full-term uneventful pregnancy in a patient affected by ALPS. A specific clinical follow-up in a pregnant woman with primary immunologic disease is suggested. PMID:25302402

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

2015-03-01

152

A short history of sonography in obstetrics and gynaecology.  

PubMed

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

Campbell, S

2013-01-01

153

Impact of maternal obesity on perinatal and childhood outcomes.  

PubMed

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

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

2015-04-01

154

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

PubMed

We present the case of a 33-year-old woman in her first pregnancy. She presented with pruritus at 34?weeks gestation. A diagnosis of intrahepatic cholestasis of pregnancy was made based on elevated bile acids and elevated liver transaminases. She re-presented 4?days later, jaundiced with abdominal pain and nausea, and was hypertensive. Her bilirubin was now elevated and her creatinine had doubled. The differential diagnosis-included pre-eclampsia and Hemolysis Elevated Liver enzymes Low Platelet count (HELLP) syndrome, and delivery was expedited. Postnatally, the patient became coagulopathic, though not thrombocytopaenic; she had persistent hypoglycaemia, hyponatraemia, developed acute pancreatitis and had profound ascites and peripheral oedema. Management was supportive with multidisciplinary care and over a period of 3?weeks she made a full clinical and biochemical recovery. PMID:25878236

English, Nicola; Rao, Jegajeeva

2015-01-01

155

Coagulation and placenta-mediated complications.  

PubMed

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

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

2014-10-01

156

[Anticoagulant prophylaxis in women affected by thrombophilia and previous obstetric complications].  

PubMed

Pregnancy is a condition of excessive clotting due to a decrease of some coagulation factors and a reduction of anticoagulant proteins, such as protein S. It is known that the causes of congenital or acquired thrombophilia may be associated with an increased risk of venous thromboembolism during pregnancy and/or obstetric complications, such early or late fetal loss, intrauterine fetal deaths, pre-eclampsia, fetal growth restriction. During pregnancy the use of a prophylaxis with antithrombotic drugs is considered at present a promising opportunity to significantly reduce the prevalence of thromboembolic complications, improving maternal and fetal outcomes. This article is a review to most recent evidence of pregnant anticoagulant prophylaxis in women with previous thromboembolic events. PMID:18854809

Grandone, E; Colaizzo, D; Vergura, P; Tiscia, G; Chinni, E; Tomaiuolo, M; Margaglione, M

2008-10-01

157

Triplet pregnancy with partial hydatiform mole.  

PubMed

Triplet pregnancy with a coexisting mole is extremely rare. A 26 years old primigravida with multiple gestation and severe pre-eclampsia at 32 weeks gestation was brought to Sri Ramachandra University casualty. In view of abnormal Doppler study with discordant twins emergency lower segment caesarean section was done six days later. Part of the placenta showed molar changes. Histopathology confirmed partial mole. Patient received three cycles of methotrexate in view of rising titres of betahCG. Three months after delivery both babies are alive and well and betahCG for the mother became normal. This pregnancy continued beyond 32 weeks gestational age with both babies being alive. Hence this case is being reported to highlight its rarity. PMID:21888177

Sundari, M Siva; Agarwal, Preet; Mohan, Jayanthi

2011-02-01

158

Complete hydatidiform mole with coexisting dichorionic diamniotic twins following testicular sperm extraction and intracytoplasmic sperm injection.  

PubMed

We present the first report of complete hydatidiform mole (HM) with coexisting dichorionic diamniotic twins. This pregnancy was achieved after testicular sperm extraction and intracytoplasmic sperm injection (ICSI) for azoospermia in the woman's husband. Standard in vitro fertilization may cause multisperm fertilization and increase triploid partial HM and complete HM, which arise from dispermic fertilization. In contrast, ICSI can avoid multisperm fertilization. In our case, paternal isodisomy in the molar tissue was confirmed by microsatellite analysis suggesting that it resulted from duplication of a haploid paternal genome following monospermic fertilization of an inactivated oocyte or from monospermic fertilization of an inactivated oocyte with a diploid sperm. Although the patient was eager to continue the pregnancy, the size of the HM component increased rapidly and termination of the pregnancy was required for pre-eclampsia-like symptoms at 15 weeks of gestation. After the operation, chemotherapy was initiated for persistent trophoblastic disease. PMID:18226144

Yamada, Takahiro; Matsuda, Takao; Kudo, Masataka; Yamada, Takashi; Moriwaki, Masashi; Nishi, Shinya; Ebina, Yasuhiko; Yamada, Hideto; Kato, Hidenori; Ito, Tomoo; Wake, Norio; Sakuragi, Noriaki; Minakami, Hisanori

2008-02-01

159

Reproductive & Cardiovascular Disease Research Group  

NSDL National Science Digital Library

The Reproductive & Cardiovascular Disease Research Group is "based in the Department of Biochemistry and Immunology at St. George's, University of London." The Group's "research interests include a number of areas concerned with reproductive and cardiovascular diseases such as trophoblast biology, nitric oxide and apoptosis, with particular emphasis on the role of these subjects in diseases of pregnancy such as pre-eclampsia." This website contains descriptions of protocols commonly utilized by the Research Group such as DNA laddering, Comet Assay, Immunoprecipitation, and Caspase Assay, to name a few. This site also contains informative sections concerning Nitric Oxide, Apoptosis, and Trophoblasts. The website includes a list of publications, and email addresses of group members as well.

Dash, Phil.

160

The platelet count and mean platelet volume.  

PubMed

The Coulter Model S-Plus Counter provides a measure of the platelet count and the mean platelet volume (MPV). An analysis of 5000 unselected blood specimens showed an inverse relationship between the number of circulating platelets and their MPV. In nearly 95% of normal adults the platelet count varied from 150 to 450 X 10(9)/l and the MPV from 7.0 to 10.5 fl. Thrombocytosis was found in iron deficiency anaemia, after trauma and acute blood loss and in rhematoid arthritis. Although there is a normal platelet distribution in pregnancy, patients with pre-eclampsia and uncomplicated hypertension in late pregnancy tended to have lower platelet counts and larger platelets than controls. A variable platelet pattern was found in infection, renal failure and treated malignant disease. PMID:7248189

Giles, C

1981-05-01

161

The risk of obstetrical syndromes after solid organ transplantation.  

PubMed

Pregnancy after solid organ transplantation is perfectly possible, but it is associated with an increased risk of major obstetrical complications including pre-eclampsia, foetal growth restriction and preterm birth. Following liver and kidney grafting, the risk of complications is higher especially after kidney transplant, reflecting pre-existing hypertensive and vascular disease. In these patients, prevention should start before the onset of pregnancy through normalisation of hypertensive and vascular conditions. Following heart and lung transplants, the risk of rejection during and after pregnancy remains significant and an adequate immunosuppression is imperative, especially after lung transplants because of their intrinsic high rate of rejection. A likely explanation for the higher risk of pregnancy complication is an alteration of the 'placental bed', the decidua and the inner myometrium underlying the placenta, a zone encompassing the full length of the spiral arteries supplying maternal blood to the placenta. Unfortunately, this zone has not been investigated in pregnancy after solid organ transplantation. PMID:25205234

Brosens, Ivo; Brosens, Jan J; Benagiano, Giuseppe

2014-11-01

162

Endoplasmic reticulum stress is induced in the human placenta during labour  

PubMed Central

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

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

2015-01-01

163

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

PubMed

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

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

2009-04-01

164

The role of hypoxia in mental development and in the treatment of mental disorders: a review.  

PubMed

The purpose of this review is to trace the trends in studying and applying hypoxia in the field of mental problems. A literature review was conducted using the PubMed database, with a time-frame extending to October 2010. According to the neurodevelopmental model of mental disorders, abnormalities in brain development during pre- and perinatal life lead to psychotic manifestation in adolescence or young adulthood. Studies show that hypoxia plays an important role in almost any risk factor related to brain development in early life: pre-eclampsia, infection/inflammation, hypoxia/ischemia, preterm birth, and asphyxia at birth. The cited data show trends in using hypoxia, especially in the form of intermittent hypoxic training, for the treatment and prevention of mental disorders, and trends in using it for increasing mental capacity in animals. PMID:21248426

Basovich, Simon N

2010-12-01

165

[Pregnancies in hemodialysis and in patients with end-stage chronic kidney disease : epidemiology, management and prognosis].  

PubMed

Pregnancy in patients presenting end-stage renal disease is rare and there are currently no recommendations for the management of these patients. In hemodialysis patients, reduced fertility and medical reluctance limit the frequency of pregnancies. Although the prognosis has significantly improved, a significant risk for unfavorable maternal (pre-eclampsia, eclampsia) and fetal (pre-term birth, intrauterine growth restriction, still death) outcome still remains. Increasing dialysis dose with the initiation of daily dialysis sessions, early adaptation of medications to limit teratogenicity and management of chronic kidney disease complications (anemia, hypertension) are required. A tight coordination between nephrologists and obstetricians remains the central pillar of the care. In peritoneal dialysis, pregnancy is also possible with modification of the exchange protocol and reducing volumes. PMID:25457994

Panaye, Marine; Jolivot, Anne; Lemoine, Sandrine; Guebre-Egziabher, Fitsum; Doret, Muriel; Morelon, Emmanuel; Juillard, Laurent

2014-12-01

166

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

PubMed Central

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

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

2012-01-01

167

A missed diagnosis or a masquerading disease: back to the basics  

PubMed Central

A 23-year-old gravid Ugandan female at 26 weeks was admitted to the maternity ward with sweats, abdominal pain, feeling of apprehension and palpitations. A diagnosis of pre-eclampsia was made and treatment with magnesium sulphate initiated. She was later transferred to intensive care unit for monitoring and control of blood pressure. Due to her labile blood pressures despite intravenous hydralazine and metoprolol, the pregnancy was terminated. However, she continued to have labile blood pressures. Better control of blood pressure was achieved on oral prazocin and nifedipine. The patient was then transferred to floor and discharged home a few days later. An abdominal computed-tomography scan showed a solid lobulated right paravertebral mass superio-medial to the right kidney. An open adrenelectomy was performed and antihypertensives discontinued. Histopathology revealed a benign pheochromocytoma. The mother had good post-operative outcome; however the premature baby died 2 days later in the special care unit. PMID:24009805

Lalitha, Rejani; Opio, Christopher Kenneth

2013-01-01

168

Use of fluorine-18-labelled deoxyglucose positron emission tomography with computed tomography to localize a paraganglioma in pregnancy.  

PubMed

A nine-weeks pregnant, 27-year-old female was admitted for hypertension with a blood pressure of 213/110 mm Hg, headaches, palpitations, and anxiety. There was no previous history of hypertension or pre-eclampsia. She had elevated urinary normetanephrine, plasma-free normetanephrine, and plasma-free metanephrine concentrations. Phenoxybenzamine and labetalol were initiated for presumed pheochromocytoma. At thirteen weeks of pregnancy, a noncontrast magnetic resonance imaging (MRI) of the abdomen failed to identify an adrenal or extra-adrenal mass. At 21-weeks gestation, an abdominal [18-F]-fluorodeoxyglucose positron emission tomography with computed tomography demonstrated an extra-adrenal lesion. The patient underwent a laparotomy during the second trimester with successful removal of a benign paraganglioma. PMID:21037527

Koroscil, Thomas M; McDonald, Stephen; Stutes, Shahan; Vila, Raul J

2010-12-01

169

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

PubMed

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

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

2014-10-22

170

Coagulation and Placenta-Mediated Complications  

PubMed Central

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

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

2014-01-01

171

The tryptophan utilization concept in pregnancy  

PubMed Central

The decrease in maternal plasma total (free + albumin-bound) tryptophan (Trp) during the third pregnancy trimester is attributed to induction of indoleamine 2,3-dioxygenase (IDO). When measured, free [Trp] is increased because of albumin depletion and non-esterified fatty acid elevation. The Trp depletion concept in pregnancy is therefore not supported because of incorrect interpretation of changes in Trp disposition and also for not addressing mouse strain differences in Trp-related responses and potential inhibition of Trp transport by the IDO inhibitor 1-methyl tryptophan. Application of the Trp utilization concept in pregnancy offers several physiological advantages favoring fetal development and successful outcome, namely provision of Trp for fetal protein synthesis and growth, serotonin for signaling pathways, kynurenic acid for neuroprotection, quinolinic acid for NAD+ synthesis, and other kynurenines for suppression of T cell responses. An excessive increase in Trp availability could compromise pregnancy by undermining T cell suppression, e.g., in pre-eclampsia. PMID:25105097

2014-01-01

172

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

PubMed

Acute kidney injury (AKI) is one of the most challenging and serious complications of pregnancy. We present our experience on the clinical profile and outcome of 57 patients with pregnancy-related AKI, of a total of 580 patients with AKI seen during the study period. This is a prospective single-center study in a civil hospital conducted from January to December 2010. The most common age group of the study patients was 20-25 years; 43.8% of the patients had received antenatal care. AKI was observed in the puerperium (n = 34), early pregnancy (n = 10) and late pregnancy (n = 13). The cause of AKI included puerperal sepsis (63.1%), pregnancy-induced hypertension (PIH) (33.33%), post-abortion (22.80%), ante-partum hemorrhage (APH) (14%) and post-partum hemorrhage (PPH) (8%). Complete, partial and no renal recovery was observed in 52.64%, 21.05% and 26.31% of the patients, respectively. Low platelet count and plasma fibrinogen and high bilirubin, D-dimer and activated partial thromboplast in time were observed more commonly in patients with partial recovery. Of the 57 patients, 50 received hemodialysis, three received peritoneal dialysis and seven patients were managed conservatively. A total of 13 patients developed cortical necrosis that was associated with sepsis in six, PPH and pre-eclampsia/eclampsia in three patients each and APH in one. Nine patients died, and the cause of death was septicemia in four, pre-eclampsia in three and APH and PPH in one patient each. In our study, puerperal sepsis was the most common etiological factor for pregnancy-related AKI. Prolonged oliguria or anuria were bad prognostic factors for renal recovery. Sepsis, thrombocytopenia, disseminated intra-vascular coagulation and liver involvement were associated with increased mortality. PMID:24969215

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

2014-07-01

173

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

SciTech Connect

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).

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

1984-04-01

174

Short-term suppression of the renin-angiotensin system in mice associated with hypertension during pregnancy.  

PubMed

Pregnancy-induced hypertension or pre-eclampsia is a major disorder that may result in serious complications for the mother and fetus. It is characterized from maternal hypertension in late pregnancy and peripheral tissue damage, including kidney, heart and placenta, and the fetus suffers from intrauterine growth retardation (IUGR) and high perinatal mortality. Recently, it has been postulated that angiotensin II (Ang II), a potent vasoconstrictor in the renin-angiotensin system (RAS), plays a pivotal role in the pathogenesis of pre-eclampsia; however, the beneficial effect of the suppression of RAS has not yet been fully elucidated. Previously, we generated a transgenic mouse model that developed pregnancy-associated hypertension (PAH) by the overproduction of Ang II in maternal circulation during late pregnancy. In addition, mice with PAH exhibited maternal and fetal abnormalities, such as proteinuria, cardiac hypertrophy, placental morphological changes and IUGR. In this study, in order to attenuate the activity of redundant RAS during the advanced stages of PAH, we administered olmesartan (Olm), an angiotensin receptor blocker, and captopril (Cp), an angiotensin converting enzyme inhibitor, from E17 to E19 days of gestation, and evaluated its effect on cardiac and placental abnormalities and fetal growth. Olm and Cp administration significantly lowered the blood pressure of mice with PAH, and placental histological change and severe IUGR were markedly ameliorated in both groups. On the contrary, Olm or Cp treatment had little effect on cardiac remodeling during the advanced stages of PAH. These findings highlight a variety of therapeutic actions of RAS repression on the progressive pathology of PAH in mice. PMID:22552605

Ishimaru, Tomohiro; Ishida, Junji; Nakamura, Shoko; Hashimoto, Misuzu; Matsukura, Tanomu; Nakamura, Ayumi; Kunita, Satoshi; Sugiyama, Fumihiro; Yagami, Ken-Ichi; Fukamizu, Akiyoshi

2012-07-01

175

Diagnosis and management of non-criteria obstetric antiphospholipid syndrome.  

PubMed

Accurate diagnosis of obstetric antiphospholipid syndrome (APS) is a prerequisite for optimal clinical management. The international consensus (revised Sapporo) criteria for obstetric APS do not include low positive anticardiolipin (aCL) and anti ?2 glycoprotein I (a?2GPI) antibodies (pre-eclampsia, placental abruption, late premature birth, or two or more unexplained in vitro fertilisation failures. In this review we examine the available evidence to address the question of whether patients who exhibit non-criteria clinical and/or laboratory manifestations should be included within the spectrum of obstetric APS. Prospective and retrospective cohort studies of women with pregnancy morbidity, particularly recurrent pregnancy loss, suggest that elimination of aCL and/or IgM a?2GPI, or low positive positive aCL or a?2GPI from APS laboratory diagnostic criteria may result in missing the diagnosis in a sizeable number of women who could be regarded to have obstetric APS. Such prospective and retrospective studies also suggest that women with non-criteria obstetric APS may benefit from standard treatment for obstetric APS with low-molecular-weight heparin plus low-dose aspirin, with good pregnancy outcomes. Thus, non-criteria manifestations of obstetric APS may be clinically relevant, and merit investigation of therapeutic approaches. Women with obstetric APS appear to be at a higher risk than other women of pre-eclampsia, placenta-mediated complications and neonatal mortality, and also at increased long-term risk of thrombotic events. The applicability of these observations to outcomes in women with non-criteria obstetric APS remains to be determined. PMID:25318976

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

2015-01-01

176

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

PubMed Central

Objectives Previously published data from the Cleveland Children’s Sleep and Health Study (CCSHS) demonstrated that preterm infants are especially vulnerable both to sleep disordered breathing (SDB) and its neurocognitive sequelae at age 8–11 years. In this analysis, we aimed to identify the components of the neonatal medical history associated with childhood SDB among children born prematurely. Study design This analysis focuses on the 383 children in the population-based CCSHS cohort who were born <37 weeks gestational age and who had technically acceptable sleep studies performed at ages 8–11 years (92% of all preterm children). Logistic regression was used to evaluate the associations between candidate perinatal and neonatal risk factors and the presence of childhood SDB by sleep study. Results Twenty-eight preterm children (7.3%) met the definition for SDB at age 8–11 years. Having a single mother and mild maternal pre-eclampsia were strongly associated with SDB in unadjusted and race-adjusted models. Unadjusted analyses also identified xanthine use and CPR and/or intubation in the delivery room as potential risk-factors for SDB. We did not find a significant link between traditional markers of severity of neonatal illness -- such as gestational age, birth weight, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), or duration of ventilation -- and childhood SDB at school age. Conclusions These results represent a first step in identifying prenatal and neonatal characteristics which place preterm infants at higher risk for childhood SDB. The strong association between mild pre-eclampsia and childhood SDB underscores the importance of research aimed at understanding in utero risk factors for neurorespiratory development. PMID:18534222

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

2009-01-01

177

Hypertension in pregnancy: changes in activin A maternal serum concentration.  

PubMed

Human placenta is the major source of activin A in maternal circulation. The aim of the present study was to evaluate maternal activin A serum concentration in pregnant women with chronic hypertension (n = 14), pregnancy-induced hypertension (n = 10) or pre-eclampsia (n = 16). In the group of pregnant women with chronic hypertension and of healthy pregnant women (n = 10) activin A was measured in samples collected longitudinally throughout gestation. Using a specific two-site enzyme-linked immunosorbent assay, it has been possible to measure maternal serum activin A concentration. In addition, the effect of recombinant human activin A administration on mean arterial pressure and heart rate in female rats have been also investigated. Mean +/- SEM of maternal serum activin A concentration in pre-eclamptic women (57.4 +/- 28.3 ng/ml), was significantly higher than in women with pregnancy-induced hypertension (14.8 +/- 10.5 ng/ml), chronic hypertension (10.3 +/- 5.4 ng/ml) or healthy control women (9.2 +/- 9.4 ng/ml) (P < 0.01). Serum activin A levels evaluated 2 weeks after anti-hypertensive treatment were not significantly different in pre-eclamptic women. Moreover, when exogenous recombinant human activin A was administered in female rats arterial pressure or frequency of heart rate did not change. The present study showed that maternal serum activin A concentration is abnormally high in patients with pre-eclampsia. Thus, since the patients with chronic hypertension or pregnancy-induced hypertension have activin A concentration in the normal range of values, activin A may be a prognostic marker of hypertension in pregnancy. PMID:7479615

Petraglia, F; Aguzzoli, L; Gallinelli, A; Florio, P; Zonca, M; Benedetto, C; Woodruff, K

1995-07-01

178

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

PubMed

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

Blume, C; Pischke, S; von Versen-Höynck, F; Günter, H H; Gross, M M

2014-11-01

179

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

PubMed Central

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

2014-01-01

180

Altered placental expression of PAPPA2 does not affect birth weight in mice  

PubMed Central

Background Pregnancy-associated plasma protein A2 (PAPPA2) is an insulin-like growth factor binding protein (IGFBP) protease expressed in the placenta and upregulated in pregnancies complicated by pre-eclampsia. The mechanism linking PAPPA2 expression and pre-eclampsia and the consequences of altered PAPPA2 expression remain unknown. We previously identified PAPPA2 as a candidate gene for a quantitative trait locus (QTL) affecting growth in mice and in the present study examined whether this QTL affects placental PAPPA2 expression and, in turn, placental or embryonic growth. Methods Using a line of mice that are genetically homogenous apart from a 1 megabase QTL region containing the PAPPA2 gene, we bred mice homozygous for alternate QTL genotypes and collected and weighed placentae and embryos at E12.5. We used quantitative RT-PCR to measure the mRNA levels of PAPPA2, as well as mRNA levels of IGFBP-5 (PAPPA2's substrate), and PAPPA (a closely related IGFBP protease) to examine potential feedback and compensation effects. Western blotting was used to quantify PAPPA2 protein. Birth weight was measured in pregnancies allowed to proceed to parturition. Results PAPPA2 mRNA and protein expression levels in the placenta differed by a factor of 2.5 between genotypes, but we did not find a significant difference between genotypes in embryonic PAPPA2 mRNA levels. Placental IGFBP-5 and PAPPA mRNA expression levels were not altered in response to PAPPA2 levels, and we could not detect IGFBP-5 protein in the placenta by Western blotting. The observed difference in placental PAPPA2 expression had no significant effect on placental or embryonic mass at mid-gestation, birth weight or litter size. Conclusions Despite a significant difference between genotypes in placental PAPPA2 expression similar in magnitude to the difference between pre-eclamptic and normal placentae previously reported, we observed no difference in embryonic, placental or birth weight. Our results suggest that elevated PAPPA2 levels are a consequence, rather than a cause, of pregnancy complications. PMID:20642865

2010-01-01

181

Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence  

PubMed Central

Objective To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. Design Systematic review and meta-analysis. Data sources Major databases from inception to January 2012 without language restrictions. Study selection Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. Data synthesis Results summarised as relative risks for dichotomous data and mean differences for continuous data. Results We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference ?50 g, ?100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference ?60 g, ?120 to ?10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. Conclusions Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes. PMID:22596383

2012-01-01

182

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

PubMed

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

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

2013-09-01

183

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

PubMed

This study investigates the effects of anticoagulant therapy on pregnancy outcomes in 204 patients with thrombophilia and previous poor obstetric outcomes. Patients with poor obstetric history (pre-eclampsia, intrauterine growth retardation, fetal death, placental abruption, recurrent pregnancy loss) and having hereditary thrombophilia were included in this study. Poor obstetric outcomes were observed more frequently in patients who had not taken anticogulant therapy compared with treated group. Live birth rate, gestational age at birth and Apgar scores were significantly higher in the treated group when compared with the untreated group. There were no significant differences in terms of birthweight, mode of delivery and admission rates to the neonatal intensive care unit (NICU). Low-molecular-weight heparin (LMWH) plus acetylsalicylic acid (ASA) had higher gestational age at birth, Apgar scores, live birth rate and a lower abortion rates when compared with controls; in contrast, no significant difference was observed in terms of birthweight, mode of delivery, obstetric complications and admission rates to NICU. There were no significant differences between control group and both LMWH only and ASA only groups in terms of gestational age at birth, Apgar scores, birthweight, mode of delivery, obstetric complications and admission rates to NICU. Only LMWH group had higher live birth rate as compared with control group. The use of only ASA did not seem to affect the perinatal complication rates and outcomes. In conclusion, anticoagulant therapy with both LMWH and ASA seems to provide better obstetric outcomes in pregnant women with thrombophilia and previous poor obstetric outcomes. PMID:25268607

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

2015-04-01

184

Magnesium Metabolism and its Disorders  

PubMed Central

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

Swaminathan, R

2003-01-01

185

The etiology of preeclampsia: the role of the father.  

PubMed

Preeclampsia is often considered as simply a maternal disease with variable degrees of fetal involvement. More and more the unique immunogenetic maternal-paternal relationship is appreciated, and also the specific 'genetic conflict' that is characteristic of haemochorial placentation. From that perspective, pre-eclampsia can be seen as a disease of an individual couple with primarily maternal and fetal manifestations. The maternal and fetal genomes perform different roles during development. Heritable paternal, rather than maternal, imprinting of the genome is necessary for normal trophoblast development. Large population studies have estimated that 35% of the variance in susceptibility to preeclampsia is attributable to maternal genetic effects; 20% to fetal genetic effects (with similar contributions of both parents), 13% to the couple effect, less than 1% to the shared sibling environment and 32% to unmeasured factors. Not one of these large population studies focussed on the paternal contribution to preeclampsia, which is demonstrated by (1) the effect of the length of the sexual relationship; (2) the concept of primipaternity versus primigravidity; and (3) the existence of the so-called 'dangerous' father, as demonstrated in various large population studies. It is currently unknown how the father exerts this effect. Possible mechanisms include seminal cytokine levels and their effect on maternal immune deviation, specific paternal HLA characteristics and specific paternal single nucleotide polymorphisms (SNPs), in particular in the paternally expressed genes affecting placentation. Several large cohort studies, including the large international SCOPE consortium, have identified paternal SNPs with strong associations with preeclampsia. PMID:21529966

Dekker, Gus; Robillard, Pierre Yves; Roberts, Claire

2011-05-01

186

Future directions of clinical laboratory evaluation of pregnancy  

PubMed Central

In recent years, our understanding of how the immune system interacts with the developing fetus and placenta has greatly expanded. There are many laboratories that provide tests for diagnosis of pregnancy outcome in women who have recurrent pregnancy loss (RPL) or pre-eclampsia. These tests are based on the premise that immune response to the fetus is equivalent to the adaptive immune response to a transplant. New understanding leads to the concept that the activated innate response is vital for pregnancy and this can result in more effective testing and treatment to prevent an abnormal pregnancy in the future. We describe here only three such areas for future testing: one area involves sperm and semen and factors necessary for successful fertilization; another area would determine conditions for production of growth factors necessary for implantation in the uterus; finally, the last area would be to determine conditions necessary for the vascularization of the placenta and growing fetus by activated natural killer (NK) cells (combinations of killer cell immunoglobulin-like receptor (KIR) family genes with HLA-C haplotypes) that lead to capability of secreting angiogenic growth factors. These areas are novel but understanding their role in pregnancy can lead to insight into how to maintain and treat pregnancies with complicating factors. PMID:25042633

Beaman, Kenneth D; Jaiswal, Mukesh K; Dambaeva, Svetlana; Gilman-Sachs, Alice

2014-01-01

187

Perinatal outcomes of women with a prior history of unexplained recurrent miscarriage.  

PubMed

Abstract Objective: We sought to determine subsequent pregnancy outcomes in a cohort of women with a history of unexplained recurrent miscarriage (RM) who were not receiving medical treatment. Study design: This was a prospective cohort study, of women with a history of three unexplained consecutive first trimester losses, who were recruited and followed in their subsequent pregnancy. Control patients were healthy pregnant patients with no previous adverse perinatal outcome. Results: A total of 42 patients with a history of unexplained RM were recruited to the study. About nine (21.4%) experienced a further first trimester miscarriage, one case of ectopic and one case of partial molar pregnancy. About 74% (23/31) of the RM cohort had a vaginal delivery. There was one case of severe pre-eclampsia. The RM group delivered at a mean gestational age of 38?+?2 weeks and with a mean birthweight of 3.23?kg. None of the neonates were under the 10th centile for gestational age. Overall, there was no significant difference in pregnancy outcomes between the two cohorts. Conclusion: Our study confirms the reassuring prognosis for achieving a live birth in the unexplained RM population with a very low incidence of adverse events with the majority delivering appropriately grown fetuses at term. PMID:24824106

Dempsey, Mark A; Flood, Karen; Burke, Naomi; Fletcher, Patricia; Kirkham, Colin; Geary, Michael P; Malone, Fergal D

2014-06-01

188

[Prolactin and its cleaved 16 kDa fragment].  

PubMed

Prolactin, owing to its origins, actions and molecular forms, is an ubiquitous and pleiotropic hormone. Indeed prolactin, initially thought to be essentially synthesized in the hypophysis, is also produced by several tissues in mammals. It is involved in more than 300 different biological activities, such as reproduction, developmental immunity and behaviour. It is also described under several molecular forms resulting from co- or post-translational modifications and enzymatic cleavage. Among these, the 16 kDa form, derived from native prolactin, has received particular attention because of its inhibitory effect on angiogenesis. Recent results have suggested an important role of tissue enzymes in the production of this form in several tissues (retina, myocardium and mammary gland). The cleavage leading to the production of 16 kDa prolactin may occur outside the cells, in the interstitial medium and therefore in the vicinity of blood capillaries. This process implies tissue-specific mechanisms of regulation. A better knowledge of the location of the cleavage and of the regulation of these activities of the cleaving enzymes is now essential for controlling the processes. This knowledge will allow a better understanding of the relationships between some pathologies (cardiomyopathy, pre-eclampsia, retinopathy) and modification of the production of the anti-angiogenic form of prolactin. PMID:21187043

Lkhider, Mustapha; Seddiki, Touria; Ollivier-Bousquet, Michèle

2010-12-01

189

Effect of subacute exposure to lead and estrogen on immature pre-weaning rat leukocytes  

SciTech Connect

Lead is an environmental pollutant known to cause damage to human health, affecting specially the central nervous system, reproductive organs, the immune system and kidney. From the perspective or reproduction, lead affects both men and women. Reported effects in women include infertility, miscarriage, pre-eclampsia, pregnancy hypertension and premature delivery. In experimental animals, lead affects female reproductive organs through different mechanisms. The heavy metal may interact at the enzyme level. It may interfere with the action of reproductive hormones at the target organ, modifying the activity of estrogen receptors in the pregnant uterus and inhibiting responses where estrogens play a role. Lead may induce imprinting mechanism, causing persistent changes in uterine estrogen receptors and ovary LH receptors following perinatal exposure. Finally, it may interfere at the level of hypothalamus-pituitary, decreasing pituitary response to growth hormone releasing factor, affecting levels of FSH and LH and increasing blood levels of glucocorticoids, which modify the action of estrogens in the uterus. This study examines the mechanisms of lead-induced interference with female reproductive and immune functions. 33 refs., 2 figs., 2 tabs.

Villagra, R.; Tchernitchin, N.N.; Tchernitchin, A.N. [Univ. of Chile Medical School, Santiago (Chile)] [Univ. of Chile Medical School, Santiago (Chile)

1997-02-01

190

Unexplored territories in the nonsurgical patient: a look at pregnancy.  

PubMed

Venous thromboembolism (VTE) remains the most common cause of maternal death during pregnancy and the puerperium. The risk is increased in women older than 35 years and those with obesity, previous VTE, operative delivery, and underlying thrombophilia. Anticoagulant therapy is indicated for short-term treatment of VTE and as thromboprophylaxis in high-risk patients. Warfarin is contraindicated during the first trimester because of fetotoxicity; unfractionated heparin (UFH) is associated with practical disadvantages and a risk of heparin-induced thrombocytopoenia (HIT) and osteoporosis with long-term use. Low-molecular-weight heparins (LMWHs) are convenient to use, do not cross the placenta, carry a lower risk of HIT and osteoporosis, and have been shown to be safe and effective during treatment of approximately 500 pregnant women. LMHWs are increasingly replacing UFH as the anticoagulant of choice during pregnancy; further studies are required to determine optimal therapeutic and thromboprophylactic doses. Women with inherited or acquired thrombophilia are at increased risk of severe pregnancy complications, including recurrent miscarriage, pre-eclampsia, fetal growth restriction, abruptio placentae, and stillbirth; uteroplacental microvascular thrombosis caused by thrombophilia appears to be the pathophysiologic link. LMWHs have been shown to improve pregnancy outcome in women with a history of obstetric complications and confirmed thrombophilia. PMID:11449342

Eldor, A

2001-04-01

191

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

PubMed

The neuropeptide oxytocin was first noted for its capacity to promote uterine contractions and facilitate delivery in mammals. The study of oxytocin has grown to include awareness that this peptide is a neuromodulator with broad effects throughout the body. Accumulating evidence suggests that oxytocin is a powerful signal to the foetus, helping to prepare the offspring for the extrauterine environment. Concurrently, the use of exogenous oxytocin or other drugs to manipulate labour has become common practice. The use of oxytocin to expedite labour and minimise blood loss improves both infant and maternal survival under some conditions. However, further investigations are needed to assess the developmental consequences of changes in oxytocin, such as those associated with pre-eclampsia or obstetric manipulations associated with birth. This review focuses on the role of endogenous and exogenous oxytocin as a neurochemical signal to the foetal nervous system. We also examine the possible developmental consequences, including those associated with autism spectrum disorder, that arise from exogenous oxytocin supplementation during labour. PMID:25059673

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

2014-10-01

192

Elevated Risk of Adverse Obstetric Outcomes in Pregnant Women With Depression  

PubMed Central

Objective In this study, we evaluated the association between patient depression ratings at an initial obstetrics visit and adverse birth outcomes in African-American women. Study Design We conducted a retrospective cohort study of 261 pregnant, African American women who were screened with the Edinburgh Postnatal Depression Scale (EPDS) at their initial prenatal visit. Medical records were reviewed to assess pregnancy and neonatal outcomes, specifically pre-eclampsia, preterm birth, intrauterine growth retardation and low birth weight. Results Using multivariable logistic regression models, an EPDS score ? 10 was associated with increased risk for preeclampsia, preterm birth and low birth weight. An EPDS score ? 10 was associated with increased risk for intrauterine growth retardation but after controlling for behavioral risk factors this association was no longer significant. Conclusion A positive, patient-rated depression screening at the initial obstetrics visit depression is associated with increased risk for multiple adverse birth outcomes. Given the retrospective study design and small sample size, this finding should be confirmed in a prospective cohort study. PMID:23934018

KIM, Deborah R.; SOCKOL, Laura E.; SAMMEL, Mary; KELLY, Caroline; MOSELEY, Marian; EPPERSON, C. Neill

2013-01-01

193

DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.  

PubMed

Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia. PMID:24996894

Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

2014-09-01

194

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

PubMed

A woman developed Marburg haemorrhagic fever in the Netherlands, most likely as a consequence of being exposed to virus-infected bats in the python cave in Maramagambo Forest during a visit to Uganda. The clinical syndrome was dominated by acute liver failure with secondary coagulopathy, followed by a severe systemic inflammatory response, multiorgan failure, and fatal cerebral oedema. A high blood viral load persisted during the course of the disease. The initial systemic inflammatory response coincided with peaks in interferon-? and tumour necrosis factor-? concentrations in the blood. A terminal rise in interleukin-6, placental growth factor (PlGF), and soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) seemed to suggest an advanced pathophysiological stage of Marburg haemorrhagic fever associated with vascular endothelial dysfunction and fatal cerebral oedema. The excess of circulating sVEGF-R1 and the high sVEGF-R1:PlGF ratio shortly before death resemble pathophysiological changes thought to play a causative part in pre-eclampsia. Aggressive critical-care treatment with renal replacement therapy and use of the molecular absorbent recirculation system appeared able to stabilise--at least temporarily--the patient's condition. PMID:22394985

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

2012-08-01

195

Safety of protease inhibitors in HIV-infected pregnant women  

PubMed Central

The dire conditions of the human immunodeficiency virus/acquired immune deficiency syndrome epidemic and the immense benefits of antiretroviral prophylaxis in prevention of mother-to-child transmission far outweigh the potential for adverse effects and undeniably justify the rapid and widespread use of this therapy, despite incomplete safety data. Highly active antiretroviral therapy has now become standard care, and more than half the validated regimens include protease inhibitors. This paper reviews current knowledge of the safety of these drugs during pregnancy, in terms of maternal and fetal outcomes. Transfer of protease inhibitors across the placenta is known to be minimal, and current data about birth defects and fetal malignancies are reassuring. Maternal liver function and glucose metabolism should be monitored in women treated with protease inhibitor-based regimens, but concerns about the development of maternal resistance, should treatment be discontinued, have been shown to be groundless. Neonates should be screened for hematologic abnormalities, although these are rarely severe or permanent and are not usually related to the protease inhibitor component of the antiretroviral combination. Current findings concerning pre-eclampsia and growth restriction are discordant, and further research is needed to address the question of placental vascular complications. The increased risk of preterm birth attributed to protease inhibitors should be interpreted with caution considering the discrepant results and the multitude of confounding factors often overlooked. Although data are thus far reassuring, further research is needed to shed light on unresolved controversies about the safety of protease inhibitors during pregnancy. PMID:24101883

Chougrani, Imène; Luton, Dominique; Matheron, Sophie; Mandelbrot, Laurent; Azria, Elie

2013-01-01

196

Placental dysfunction in obese women and antenatal surveillance strategies.  

PubMed

This review is aimed at discussing placental dysfunction in obesity and its clinical implication in pregnancy as well as an antenatal surveillance strategy for these women. Maternal obesity is associated with adverse perinatal outcome. Obesity is an independent risk factor for fetal hyperinsulinaemia, birthweight and newborn adiposity. Maternal obesity is associated with childhood obesity and obesity in adult life. Obesity induces a low-grade inflammatory response in placenta, which results in short- and long-term programming of obesity in fetal life. Preconception and antenatal counselling on obstetrics risk in pregnancy, on diet and lifestyle in pregnancy and on gestational weight gain is associated with a better outcome. Fetal growth velocity is closely associated with maternal weight and gestational weight gain. Careful monitoring of gestational weight gain and fetal growth, and screening and management of obstetrical complications such as gestational diabetes and pre-eclampsia, improves perinatal outcome. The use of metformin in non-diabetic obese women is under investigation; further evidence is required before recommending it. PMID:25457859

Jeve, Yadava B; Konje, Justin C; Doshani, Anjum

2015-04-01

197

Clinical effectiveness of garlic (Allium sativum).  

PubMed

The objective of this review is to update and assess the clinical evidence based on rigorous trials of the effectiveness of garlic (A. sativum). Systematic searches were carried out in Medline, Embase, Amed, the Cochrane Database of Systematic Reviews, Natural Standard, and the Natural Medicines Comprehensive Database (search date December 2006). Our own files, the bibliographies of relevant papers and the contents pages of all issues of the review journal FACT were searched for further studies. No language restrictions were imposed. To be included, trials were required to state that they were randomized and double blind. Systematic reviews and meta-analyses of garlic were included if based on the results of randomized, double-blind trials. The literature searches identified six relevant systematic reviews and meta-analysis and double-blind randomized trials (RCT) that were published subsequently. These relate to cancer, common cold, hypercholesterolemia, hypertension, peripheral arterial disease and pre-eclampsia. The evidence based on rigorous clinical trials of garlic is not convincing. For hypercholesterolemia, the reported effects are small and may therefore not be of clinical relevance. For reducing blood pressure, few studies are available and the reported effects are too small to be clinically meaningful. For all other conditions not enough data are available for clinical recommendations. PMID:17918163

Pittler, Max H; Ernst, Edzard

2007-11-01

198

The placenta: a multifaceted, transient organ.  

PubMed

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

Burton, Graham J; Fowden, Abigail L

2015-03-01

199

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

PubMed Central

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

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

1981-01-01

200

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

PubMed

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

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

2015-06-01

201

Pregnancy and liver transplantation.  

PubMed

Since the first pregnancy in a transplant recipient in 1958, pregnancy in recipients of solid organ transplants has become increasingly common. Although previously considered a hazardous event, data collected over the last 50 years demonstrate that despite an increased risk of maternal and fetal complications, pregnancy in transplant recipients can have a successful outcome. As of 2006, there were over 3000 female liver transplant recipients of childbearing age in the USA. Two hundred and two pregnancies and 205 outcomes were reported in 121 liver transplant recipients in the National Transplantation Pregnancy Registry. Children born to female liver recipients have a greater risk of prematurity and low birth weight than the general population, but no malformation patterns have been observed. Mothers are more likely to experience pregnancy-induced hypertension, pre-eclampsia and caesarian section, but overall mortality is not worse. Rates of acute rejection and graft loss are similar to nonpregnant liver recipients. The optimal timing of conception post-transplant is controversial, but current recommendations suggest waiting for at least 1 year after transplantation. Choice of contraception is also debatable, although barrier methods have traditionally been preferred. Many medications used for post-transplant immunosuppression have potential effects during pregnancy and breast-feeding. The risks and benefits of each medication should be reviewed with patients contemplating pregnancy, and regimens should be tailored accordingly. PMID:18822076

Surti, Bijal; Tan, Jennifer; Saab, Sammy

2008-11-01

202

Pregnancy: occupational aspects of management: concise guidance.  

PubMed

Most pregnant women are exposed to some physical activity at work. This Concise Guidance is aimed at doctors advising healthy women with uncomplicated singleton pregnancies about the risks arising from five common workplace exposures (prolonged working hours, shift work, lifting, standing and heavy physical workload). The adverse outcomes considered are: miscarriage, preterm delivery, small for gestational age, low birth weight, pre-eclampsia and gestational hypertension. Systematic review of the literature indicates that these exposures are unlikely to carry much of an increased risk for any of the outcomes, since small apparent effects might be explicable in terms of chance, bias, or confounding, while larger and better studies yield lower estimated risks compared with smaller and weaker studies. In general, patients can be reassured that such work is associated with little, if any, adverse effect on pregnancy. Moreover, moderate physical exercise is thought to be healthy in pregnancy and most pregnant women undertake some physical work at home. The guidelines provide risk estimates and advice on counselling. PMID:23472500

Palmer, Keith T; Bonzini, Matteo; Bonde, Jens-Peter Ellekilde

2013-02-01

203

Sources and Determinants of Vitamin D Intake in Danish Pregnant Women  

PubMed Central

Vitamin D deficiency during pregnancy has been associated with the development of several adverse health outcomes, e.g., pre-eclampsia, gestational diabetes mellitus, preterm delivery, low birth weight, birth length, and bone mineral content. The aims of the present study were to estimate the intake and sources of vitamin D in Danish pregnant women and to examine potential determinants of vitamin D intake of the recommended level (10 µg per day). In 68,447 Danish pregnant women the mean ± SD for vitamin D intake was 9.23 ± 5.60 µg per day (diet: 3.56 ± 2.05 µg per day, supplements: 5.67 ± 5.20 µg per day). 67.6% of the women reported use of vitamin D supplements but only 36.9% reported use of vitamin D supplements of at least 10 µg. Supplements were the primary source of vitamin D for the two higher quartiles of total vitamin D intake, with diet being the primary source for the two lower quartiles. Determinants of sufficient total vitamin D intake were: high maternal age, nulliparity, non-smoking, and filling out of the Food Frequency Questionnaire (FFQ) during summer or fall. We propose that clinicians encourage vitamin D supplementation among pregnant women, with special focus on vulnerable groups such as the young, smokers and multiparous women, in order to improve maternal and fetal health both during and after pregnancy. PMID:22606369

Jensen, Camilla B.; Petersen, Sesilje B.; Granström, Charlotta; Maslova, Ekaterina; Mølgaard, Christian; Olsen, Sjurdur F.

2012-01-01

204

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

PubMed Central

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

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

2007-01-01

205

Overweight and Obesity before, during and after Pregnancy  

PubMed Central

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

Stupin, J. H.; Arabin, B.

2014-01-01

206

An assessment of stillbirths in a tertiary hospital in northern Nigeria.  

PubMed

Abstract Objective: This study was undertaken to determine the stillbirth rate and causes in Birnin Kudu, North-west, Nigeria. Method: This was a retrospective study. It involved 705 women who presented for delivery in Federal Medical Centre, Birnin Kudu and had stillbirths. The hospital maternity and theatre registers were used to identify the women who had stillbirth during the study period from 1 January 2008 to 31 December 2012. The data obtained were analyzed using SPSS version 16.0 statistical software. Significant association between socio-demographic/obstetrics factors and stillbirth were tested using the chi-square test and p?pre-eclampsia/eclampsia (13.33%). Conclusion: The stillbirth rate reported in this study was higher than those reported from other regions of Nigeria and obstructed labour was the common cause. PMID:25204335

Ugwa, Emmanuel A; Ashimi, Adewale

2014-09-26

207

Giant hemorrhagic adrenal pseudocyst in a primiparous pregnancy: report of a case.  

PubMed

Adrenal cysts are rare and are usually discovered incidentally during diagnostic imaging, surgery, or autopsy. Most cystic lesions of the adrenal gland are nonfunctioning and become symptomatic when complicated by rupture, hemorrhage, or infection. A 40-year-old woman presented with a history of gradual-onset pain in her left flank region at 20 weeks' gestation. Ultrasound showed a 20-cm cystic mass in her left abdominal cavity. Pertinent laboratory tests were within normal limits. The patient underwent exploratory laparotomy, which revealed a 20 × 15-cm left adrenal cyst; thus, we performed left adrenalectomy with complete excision of the cyst. Histological examination confirmed a hemorrhagic adrenal pseudocyst. The patient had an uneventful postoperative course, and subsequent routine obstetric ultrasound examinations showed normal fetal activity and development until the pregnancy terminated with a stillbirth caused by pre-eclampsia at 34 weeks' gestation. To the best of our knowledge, this is only the 12th reported case of adrenal pseudocyst discovered during pregnancy. We analyze the clinicopathologic findings and discuss the possible association of pregnancy, with special reference to etiopathogenesis, presentation, diagnosis, and treatment. PMID:21191710

Karaman, Kerem; Teke, Zafer; Dalgic, Tahsin; Ulas, Murat; Seven, M Canbek; Zulfikaroglu, Ebru; Sakaogullari, Zisan; Bostanci, E Birol

2011-01-01

208

HLA-G regulates the invasive properties of JEG-3 choriocarcinoma cells by controlling STAT3 activation.  

PubMed

The expression of human leucocyte antigen-G (HLA-G) in trophoblasts plays a crucial role in successful embryonic implantation, and reduced HLA-G expression might contribute to adverse obstetric outcomes. In this study, we silenced HLA-G expression using RNA interference in JEG-3 cells, resulting in a notably attenuated invasion capacity of the cells in a Transwell assay; however, no alterations in cell proliferation or apoptosis were observed. The down-regulation of HLA-G dampened the activation of signal transducer and activator of transcription 3 (STAT3), whereas the up-regulation of HLA-G promoted STAT3 activation and invasion in JEG-3 cells treated with human galectin-1. Most importantly, interleukin-6 (IL-6), but not galectin-1, was shown to rescue invasion deficiency in a dose-dependent manner. Thus, we demonstrate that HLA-G is able to regulate JEG-3 cell invasion by influencing STAT3 activation, which may underlie the implantation defects accompanying HLA-G hypo-expression in pre-eclampsia. PMID:24054889

Liu, X; Gu, W; Li, X

2013-11-01

209

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

PubMed

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

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

2004-12-01

210

Intravenous infusion of magnesium sulphate during subarachnoid anaesthesia in hip surgery and its effect on postoperative analgesia: our experience.  

PubMed

The treatment of degenerative hip joint disease involves modern operative techniques and the use of prosthetic devices individualized on each patient. Being a surgery of considerable importance, great attention is always given by the anaesthesiologist to postoperative analgesia. In general, our goal is to limit the doses of NSAIDs, known to be associated with haemostasis interference and alteration of gastrointestinal apparatus; component of our baseline analgesic protocols after arthroplasty is morphine given parenterally. In order to steadily improve analgesic techniques, which directly impact on patient outcome, we experimented the use of a continuous infusion of magnesium sulphate during subarachnoid anaesthesia. Magnesium sulphate is the drug of choice in case of eclampsia, and pre-eclampsia (for the risk of evolution in eclampsia). According to the most recent findings, this drug has also analgesic properties: its use as an adjunct to analgesia is based on a non-competitive antagonism towards the NMDA receptor and on the blocking of calcium channels: these properties prevent the mechanisms of central sensitization due to nociceptive stimulation of peripheral nerves. PMID:23905078

Pastore, A; Lanna, M; Lombardo, N; Policastro, C; Iacovazzo, C

2013-01-01

211

Clomipramine concentration and withdrawal symptoms in 10 neonates  

PubMed Central

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

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

212

Twin and singleton births in Ghana--a case-control study.  

PubMed

A retrospective study involving 623 twin and 1246 singleton births was conducted to compare the two groups with regard to selected maternal, fetal and labor and delivery characteristics and outcomes. Maternal age and parity were significantly higher for twins. The risks of preterm delivery, arrival in the labor ward in second stage of labor, cesarean births and postpartum haemorrhage were significantly higher in twin than in singleton births. In vaginal deliveries twin mothers were significantly less likely to have had episiotomies or perineal lacerations. There was no difference in the duration of the third stage of labor or in the incidence of retained placentae. Antepartum haemorrhage was a less likely indication for cesarean delivery among twins, while there was no significant difference in the likelihood of severe pre-eclampsia/eclampsia being an indication. Singleton babies were significantly heavier than twins. The incidences of malpresentation, low birth weight, stillbirths and of admission of live births to the neonatal intensive care unit were significantly higher in twins. There was no difference in the rate of instrumental vaginal delivery, or in the route of delivery of fetuses presenting by the breech. There is the need for detailed study of the incidences of antepartum haemorrhage and hypertensive diseases in twin and singleton pregnancies and of the factors determining the mode of delivery when such complications arise. Labor and delivery should also be examined to determine any differences between the two groups, especially in the first and second stages. PMID:12217231

Nkyekyer, Kobinah

2002-08-01

213

Kiss1 mutant placentas show normal structure and function in the mouse  

PubMed Central

Introduction Kisspeptins, encoded by the Kiss1 gene, are a set of related neuropeptides that are required for activation of the mammalian reproductive axis at puberty and to maintain fertility. In addition, kisspeptin signaling via the G-protein coupled receptor GPR54 (KISS1R) has been suggested to regulate human placental formation and correlations have been found between altered kisspeptin levels in the maternal blood and the development of pre-eclampsia. Methods We have used Kiss1 and Gpr54 mutant mice to investigate the role of kisspeptin signaling in the structure and function of the mouse placenta. Results Expression of Kiss1 and Gpr54 was confirmed in the mouse placenta but no differences in birth weight were found in mice that had been supported by a mutant placenta during fetal development. Stereological measurements found no differences between Kiss1 mutant and wild-type placentas. Measurement of amino-acid and glucose transport across the Kiss1 mutant placentas at E15.5 days did not reveal any functional defects. Discussion These data indicate that mouse placentas can develop a normal structure and function without kisspeptin signaling and can support normal fetal development and growth. PMID:25468546

Herreboudt, A.M.; Kyle, V.R.L.; Lawrence, J.; Doran, J.; Colledge, W.H.

2015-01-01

214

Onset of Maternal Arterial Blood Flow and Placental Oxidative Stress  

PubMed Central

The aim was to measure changes in the oxygen tension within the human placenta associated with onset of the maternal arterial circulation at the end of the first trimester of pregnancy, and the impact on placental tissues. Using a multiparameter probe we established that the oxygen tension rises steeply from <20 mmHg at 8 weeks of gestation to >50 mmHg at 12 weeks. This rise coincides with morphological changes in the uterine arteries that allow free flow of maternal blood into the placenta, and is associated with increases in the mRNA concentrations and activities of the antioxidant enzymes catalase, glutathione peroxidase, and manganese and copper/zinc superoxide dismutase within placental tissues. Between 8 to 9 weeks there is a sharp peak of expression of the inducible form of heat shock protein 70, formation of nitrotyrosine residues, and derangement of the mitochondrial cristae within the syncytiotrophoblast. We conclude that a burst of oxidative stress occurs in the normal placenta as the maternal circulation is established. We speculate that this may serve a physiological role in stimulating normal placental differentiation, but may also be a factor in the pathogenesis of pre-eclampsia and early pregnancy failure if antioxidant defenses are depleted. PMID:11106583

Jauniaux, Eric; Watson, Adrian L.; Hempstock, Joanne; Bao, Yi-Ping; Skepper, Jeremy N.; Burton, Graham J.

2000-01-01

215

Thrombophilia and Damage of Kidney During Pregnancy  

PubMed Central

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

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

2011-01-01

216

Can we safely recommend gestational weight gain below the 2009 guidelines in obese women? A systematic review and meta-analysis.  

PubMed

A systematic review was conducted to determine the risk of adverse pregnancy outcomes with gestational weight gain (GWG) below the 2009 Institute of Medicine guidelines compared with within the guidelines in obese women. MEDLINE, Embase, Cochrane Register, CINHAL and Web of Science were searched from 1 January 2009 to 31 July 2014. Quality was assessed using a modified Newcastle-Ottawa scale. Three primary outcomes were included: preterm birth, small for gestational age (SGA) and large for gestational age (LGA). Eighteen cohort studies were included. GWG below the guidelines had higher odds of preterm birth (adjusted odds ratio [AOR] 1.46; 95% confidence interval [CI] 1.07-2.00) and SGA (AOR 1.24; 95% CI 1.13-1.36) and lower odds of LGA (AOR 0.77; 95% CI 0.73-0.81) than GWG within the guidelines. Across the three obesity classes, the odds of SGA and LGA did not show any notable gradient and remained unexplored for preterm birth. Decreased odds were noted for macrosomia (AOR 0.64; 95% CI 0.54-0.77), gestational hypertension (AOR, 0.70; 95% CI 0.53-0.93), pre-eclampsia (AOR 0.90; 95% CI 0.82-0.99) and caesarean (AOR 0.87; 95% CI 0.82-0.92). GWG below the guidelines cannot be routinely recommended but might occasionally be individualized for certain women, with caution, taking into account other known risk factors. PMID:25598037

Kapadia, M Z; Park, C K; Beyene, J; Giglia, L; Maxwell, C; McDonald, S D

2015-03-01

217

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

PubMed

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

Huppertz, B

2010-03-01

218

Implications of the angiotensin converting enzyme gene insertion/deletion polymorphism in health and disease: a snapshot review  

PubMed Central

This review considers the 250+ papers concerning the association of the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (rs1799752) and various disease conditions published in 2009. The deletion allele occurs in approximately 55% of the population and is associated with increased activity of the ACE enzyme. It might be predicted that the D allele, therefore, might be associated with pathologies involving increased activity of the renin-angiotensin system. The D allele was seen to be associated with an increased risk of hypertension, pre-eclampsia, heart failure, cerebral infarct, diabetic nephropathy, encephalopathy, asthma, severe hypoglycaemia in diabetes, gastric cancer (in Caucasians) and poor prognosis following kidney transplant. On the positive side, the D allele appears to offer protection against schizophrenia and chronic periodontitis and confers greater up-per-body strength in old age. The I allele, meanwhile, offers improved endurance/athletic performance and aerobic capacity as determined by lung function tests, although it does increase the risk of oral squamous cell carcinoma and obstructive sleep apnoea in hypertensives. PMID:21537387

Gard, Paul R

2010-01-01

219

Biological Functions of Thyroid Hormone in Placenta  

PubMed Central

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

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

2015-01-01

220

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

PubMed

Research into the extra-skeletal functions of vitamin D has been expanding in recent years. During pregnancy, maternal vitamin D status may be of concern because of the key role of this vitamin in fetal skeletal development and due to the association between hypovitaminosis D and adverse maternal-fetal outcomes. Therefore, the objective of this manuscript was to review the maternal-fetal impact of gestational vitamin D deficiency and the benefits of vitamin D supplementation during pregnancy. A literature search was performed in PubMed and Embase employing the following keywords: vitamin D deficiency, pregnancy, 25-hydroxyvitamin D, and hypovitaminosis D. All relevant articles in English language published since 1980 were analysed by the two authors. Neonatal complications derived from vitamin D deficiency include low birth weight, growth restriction, and respiratory tract infection. In the mother, vitamin D deficiency has been associated with altered glucose homeostasis and increased incidence of gestational diabetes mellitus, pre-eclampsia, and bacterial vaginosis. However, the current state of the evidence is controversial for some other endpoints and the actual benefit of vitamin D supplementation in pregnancy remains unclear. Additional longitudinal studies may clarify the actual impact of vitamin D deficiency during pregnancy, and randomised trials are required to define the benefits of vitamin D supplementation in reducing the incidence of adverse outcomes in the mother and infant. PMID:24748216

Weinert, Letícia Schwerz; Silveiro, Sandra Pinho

2015-01-01

221

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

PubMed Central

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

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

2015-01-01

222

Placental Nkx2.5 and Target Gene Expression in Early-Onset and Severe Preeclampsia  

PubMed Central

Objective Preeclampsia (PE) affects 2–8% of pregnancies worldwide and is a significant source of maternal and neonatal morbidity and mortality. However, the mechanisms underlying PE are poorly understood and major questions regarding etiology and risk factors remain to be addressed. Our objective was to examine whether abnormal expression of the cardiovascular developmental transcription factor, Nkx2-5, was associated with early onset and severe pre-eclampsia (EOSPE). Methods Using qPCR and immunohistochemical assay, we examined expression of Nkx2-5 and target gene expression in EOSPE and control placental tissue. We tested resulting mechanistic hypotheses in cultured cells using shRNA knockdown, qPCR and western blot. Results Nkx2-5 is highly expressed in racially disparate fashion (Caucasians > African Americans) in a subset of early EOSPE placentae. Nkx2-5 mRNA expression is highly correlated (Caucasians > African Americans) to mRNA expression of the preeclampsia marker sFlt-1, and of the Nkx2-5 target and RNA splicing factor, Sam68. Knockdown of Sam68 expression in cultured cells significantly impacts sFlt-1 mRNA isoform generation in vitro, supporting a mechanistic hypothesis that Nkx2-5 impacts EOSPE severity in a subset of patients via upregulation of Sam68 to increase sFlt-1 expression. Expression of additional Nkx2-5 targets potentially regulating metabolic stress response is also elevated in racially disparate fashion in EOSPE. Conclusions Expression of Nkx2-5 and its target genes may directly influence the genesis and racially disparate severity, and define a mechanistically distinct subclass of EOSPE. PMID:24987805

Rivers, Elena R.; Horton, Anthony J.; Hawk, Angela F.; Favre, Elizabeth G.; Senf, Katherine M.; Nietert, Paul J.; Chang, Eugene Y.; Foley, Ann C.; Robinson, Christopher J.; Lee, Kyu-Ho

2014-01-01

223

What health professionals should know about the health effects of air pollution and climate change on children and pregnant mothers  

PubMed Central

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

Poursafa, Parinaz; Kelishadi, Roya

2011-01-01

224

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

PubMed Central

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

King, Bridget; Bryan, Phil

2014-01-01

225

Interventions for leg edema and varicosities in pregnancy. What evidence?  

PubMed

Leg oedema from venous insufficiency is not dangerous but it can cause women symptoms such as pain, feelings of heaviness, night cramps and paraesthesiae. Leg oedema can be a sign of pre-eclampsia when associated with raised blood pressure or proteinuria. The objective of this review was to assess the effects of treatment to relieve the symptoms associated with varicosity in pregnancy and to reduce leg oedema. We searched the Cochrane Pregnancy and Childbirth Group trials register in October 2004 for randomised trials of any form of treatment for varicosity and or leg oedema in pregnancy. Trial quality was assessed and data were extracted. Four trials of three different treatments were included. In one trial, women given rutoside capsules in the last 3 months of pregnancy noted an improvement in symptoms compared with placebo (relative risk 0.54 95% CI 0.32, 0.89). They had a decrease in ankle circumference at 36 weeks' gestation after 8 weeks of treatment, while women given placebo had a small increase. In one trial, women with ankle oedema had a small non-significant reduction in lower leg volume when treated with external pneumatic intermittent compression for 30 min. In another trial compression stockings prophylactically reduced the emergence of leg symptoms but not venous varicosities (relative risk 0.74 95% CI 0.59, 0.93). Lymphatic reflexology was studied in too few women to draw conclusions. In conclusions, rutosides appear to relieve symptoms of venous insufficiency in late pregnancy. However, it is not known if the drug is safe in pregnancy. External pneumatic compression appears to reduce ankle swelling and compression stockings reduce leg symptoms but not varicose veins. PMID:16678328

Bamigboye, Anthony Akinloye; Hofmeyr, George Justus

2006-11-01

226

A novel regulator of human villous trophoblast fusion: the Krüppel-like factor 6.  

PubMed

Cell-cell fusion is an essential event during life. Throughout human pregnancy, the syncytiotrophoblast (STB) layer of the placenta is formed by continuous fusion of the underlying villous cytotrophoblasts, thus maintaining placental functionality. Defects in this process are associated with pathologies like pre-eclampsia and intrauterine growth restriction. Krüppel-like factor 6 (KLF6) is a transcription factor highly expressed in human and murine placenta. However, KLF6 functions in trophoblast cells remain largely unexplored. The aim of this work was to address the role of KLF6 during STB formation. KLF6 knockdown through small interfering RNA experiments hindered cell-cell fusion revealed by immunofluorescence microscopy in human primary villous cytotrophoblast as well as in the human placental-derived BeWo cell line. Furthermore, KLF6 silencing led to a decrease in the expression of the fusogenic protein Syncytin-1 and the cell cycle regulator p21 CIP1/WAF1: measured by quantitative RT-PCR and western blot assays. On the contrary, transcript levels of genes that encode for proteins involved in STB formation such as Syncytin-1, Syncytin-2, Connexin-43 and Zonula Occludens-1 increased when KLF6 was overexpressed in differentiating villous cytotrophoblasts and in non-fusing placental-derived JEG-3 cells. Interestingly, the expression of two trophoblast biochemical differentiation markers, ?hCG and PSG3, were not reduced after KLF6 silencing in differentiating trophoblast cells. Present results support the notion that KLF6 is a relevant participant in cytotrophoblast fusion. PMID:25537765

Racca, Ana Cristina; Ridano, Magali Evelin; Camolotto, Soledad; Genti-Raimondi, Susana; Panzetta-Dutari, Graciela María

2015-04-01

227

Basic investigation of the lectin method for separation and recovery of nucleated red blood cells in maternal blood, and a study into the frequency of nucleated red blood cells in fetomaternal disorders.  

PubMed

We previously reported the separation and recovery of nucleated red blood cells (NRBCs) in maternal blood using the lectin method. In the present study, we verified the lectin method and investigated the appearance of NRBCs during pregnancy. For the concentration of lectin soy bean agglutinin, 7 mL of maternal peripheral blood was collected from 20 subjects, and the relative fluorescence intensity was measured using flowcytometry; 50 mg/mL, used in previous studies, was the optimal concentration. The number of cells recovered at each step of the lectin method was also investigated by FACS using fluorescence-labeled CD11a and CD33, and the results showed the usefulness of the method. Next, 7 mL of maternal peripheral blood was collected from 292 women with a normal single pregnancy (389 specimens), and NRBCs were separated and recovered using the lectin method. NRBCs slightly increased over the course of pregnancy (y = 4.29x + 5.03, r2 = 0.11). When blood was collected multiple times in the same subjects, NRBCs increased in 63 of 77 subjects (83.1%, percent change: 2.4 +/- 19.0). No NRBCs were recovered in 17 subjects (4.7%). Regarding the relationship between fetomaternal disorders and the frequency of NRBCs, 89.4 +/- 92.6 cells appeared per 10 mL of maternal blood in the normal group, but NRBCs increased in patients with 18 trisomy, placenta previa, pre-eclampsia, intrauterine fetal death, and 21 trisomy. NRBC examination may play an assisting role not only in fetal diagnosis but also in fetomaternal diagnosis. PMID:15737128

Ikeya, Miki; Shinya, Masaru; Kitagawa, Michihiro

2005-03-01

228

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

PubMed Central

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

Fischer, Claudia; Voss, Andreas

2014-01-01

229

Ciclosporin use during pregnancy.  

PubMed

Ciclosporin (cyclosporine) is an immunosuppressive drug first approved for use in organ transplantation to prevent rejection. Ciclosporin is also known to be used for the treatment of psoriasis, rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease, among other indications. While it is recommended that all medications that are not absolutely necessary should be avoided during pregnancy, this may not be an option for many women whose quality of life is significantly impacted without treatment, or for those who must continue immunosuppressive therapy to avoid organ rejection. The purpose of this review is to provide a comprehensive report from the literature of ciclosporin exposure during pregnancy. PubMed, MEDLINE and the Cochrane Database of Systematic Reviews were searched for English-language articles published from 1970 to 2012 that included reports of pregnant women treated at any time during pregnancy with ciclosporin. On an initial search, it was evident that much of the available information is limited to pregnancy after transplant, which suggests that ciclosporin use during pregnancy appears to be associated with premature delivery and low birthweight infants. Comorbidities such as hypertension, pre-eclampsia and gestational diabetes mellitus are also reported at higher incidences than the general population. Medical literature concerning women with autoimmune disorders exposed to ciclosporin during pregnancy are currently limited to case reports and registry data, and, as such, it is difficult to determine if any risks associated with ciclosporin therapy during pregnancy are due to exposure to the drug alone or to pre-existing maternal comorbidities. The literature suggests that ciclosporin therapy during pregnancy should be carefully considered by the treating physician, but may be a safe alternative for patients with autoimmune disease refractory to conventional treatment. Continued monitoring of this patient population remains a key component to understanding the risk factors associated with ciclosporin exposure during pregnancy. PMID:23516008

Paziana, Karolina; Del Monaco, Magaly; Cardonick, Elyce; Moritz, Michael; Keller, Matthew; Smith, Bruce; Coscia, Lisa; Armenti, Vincent

2013-05-01

230

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

PubMed Central

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

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

2012-01-01

231

Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy.  

PubMed

AKI in pregnancy remains a cause of significant fetomaternal mortality and morbidity, particularly in developing countries. Hypertensive complications of pregnancy (preeclampsia/eclampsia or hemolysis, elevated liver enzymes, and low platelets count syndrome) are the leading cause of AKI in pregnancy worldwide. Thrombotic microangiopathy is another peculiar and devastating cause of AKI in pregnancy. During the last decade, our understanding, and in some cases, our management, of these causes of AKI in pregnancy has dramatically improved. For instance, convincing data have linked pre-eclampsia/eclampsia to an increase in circulating antiangiogenic factors soluble Flt 1 and endoglin, which induce endothelial cell dysfunction, hypertension, and proteinuria. Several distinct pathogenic mechanisms underlying thrombotic microangiopathy, including thrombotic microangiopathy occurring during pregnancy, have been established. Thrombotic microangiopathy, which can present as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, can be reclassified in four potentially overlapping subtypes: disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency-related thrombotic microangiopathy, complement alternative pathway dysregulation-related thrombotic microangiopathy, secondary thrombotic microangiopathy (verotoxin and antiangiogenic drugs), and thrombotic microangiopathy of undetermined mechanism. In most cases, pregnancy is only a precipitating factor for thrombotic microangiopathy. Treatment of thrombotic microangiopathy occurring during pregnancy should be tailored to the underlying pathogenic mechanism: (1) restoration of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 serum activity in the setting of thrombotic thrombocytopenic purpura through plasma exchanges and in some cases, B cell-depleting therapy and (2) inhibition of complement alternative pathway activation in atypical hemolytic uremic syndrome using antiC5 blocking antibody (eculizumab). PMID:22879435

Fakhouri, Fadi; Vercel, Caroline; Frémeaux-Bacchi, Véronique

2012-12-01

232

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

PubMed Central

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

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

2015-01-01

233

Global alteration in gene expression profiles of deciduas from women with idiopathic recurrent pregnancy loss.  

PubMed

Recurrent pregnancy loss (RPL) occurs in ?5% of women. However, the etiology is still poorly understood. Defects in decidualization of the endometrium during early pregnancy contribute to several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction (IUGR), and are believed to be important in the pathogenesis of idiopathic RPL. We performed microarray analysis to identify gene expression alterations in the deciduas of idiopathic RPL patients. Control patients had one antecedent term delivery, but were undergoing dilation and curettage for current aneuploid miscarriage. Gene expression differences were evaluated using both pathway and gene ontology (GO) analysis. Selected genes were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A total of 155 genes were found to be significantly dysregulated in the deciduas of RPL patients (>2-fold change, P < 0.05), with 22 genes up-regulated and 133 genes down-regulated. GO analysis linked a large percentage of genes to discrete biological functions, including immune response (23%), cell signaling (18%) and cell invasion (17.1%), and pathway analysis revealed consistent changes in both the interleukin 1 (IL-1) and IL-8 pathways. All genes in the IL-8 pathway were up-regulated while genes in the IL-1 pathway were down-regulated. Although both pathways can promote inflammation, IL-1 pathway activity is important for normal implantation. Additionally, genes known to be critical for degradation of the extracellular matrix, including matrix metalloproteinase 26 and serine peptidase inhibitor Kazal-type 1, were also highly up-regulated. In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage. PMID:22505054

Krieg, S A; Fan, X; Hong, Y; Sang, Q-X; Giaccia, A; Westphal, L M; Lathi, R B; Krieg, A J; Nayak, N R

2012-09-01

234

Transcriptional regulation of human thromboxane synthase gene expression  

SciTech Connect

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.

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

1994-09-01

235

Effectiveness of continuous glucose monitoring during diabetic pregnancy (GlucoMOMS trial); a randomised controlled trial  

PubMed Central

Background Hyperglycemia in pregnancy is associated with poor perinatal outcome. Even if pregnant women with diabetes are monitored according to current guidelines, they do much worse than their normoglycaemic counterparts, marked by increased risks of pre-eclampsia, macrosomia, and caesarean section amongst others. Continuous Glucose Monitoring (CGM) is a new method providing detailed information on daily fluctuations, used to optimize glucose control. Whether this tool improves pregnancy outcome remains unclear. In the present protocol, we aim to assess the effect of CGM use in diabetic pregnancies on pregnancy outcome. Methods/design The GlucoMOMS trial is a multicenter open label randomized clinical trial with a decision and cost-effectiveness study alongside. Pregnant women aged 18 and over with either diabetes mellitus type 1 or 2 on insulin therapy or with gestational diabetes requiring insulin therapy before 30 weeks of gestation will be asked to participate. Consenting women will be randomly allocated to either usual care or complementary CGM. All women will determine their glycaemic control by self-monitoring of blood glucose levels and HbA1c. In addition, women allocated to CGM will use it for 5–7 days every six weeks. Based on their CGM profiles they receive dietary advice and insulin therapy adjustments if necessary. The primary outcome measure is rate of macrosomia, defined as a birth weight above the 90th centile. Secondary outcome measures will be birth weight, composite neonatal morbidity, maternal outcome and costs. The analyses will be according to the intention to treat principle. Discussion With this trial we aim at clarifying whether the CGM improves pregnancy outcome when used during diabetic pregnancies. Trial registration Nederlands Trial Register: NTR2996 PMID:23270328

2012-01-01

236

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

PubMed Central

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

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

2008-01-01

237

Lack of exercise is a major cause of chronic diseases.  

PubMed

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

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

2012-04-01

238

The ubiquitin ligase ASB4 promotes trophoblast differentiation through the degradation of ID2.  

PubMed

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

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

2014-01-01

239

Preterm Prelabor Rupture of Membranes and Outcome of Very-Low-Birth-Weight Infants in the German Neonatal Network  

PubMed Central

Objective It was the aim of our study to evaluate the independent effect of preterm prelabor rupture of membranes (PPROM) as a cause of preterm delivery on mortality during primary hospital stay and significant morbidities in very-low-birth-weight (VLBW) infants < 32 weeks of gestation. Design Observational, epidemiological study design. Setting Population-based cohort, German Neonatal Network (GNN). Population 6102 VLBW infants were enrolled in GNN from 2009-2012, n=4120 fulfilled criteria for primary analysis (< 32 gestational weeks, no pre-eclampsia, HELLP (highly elevated liver enzymes and low platelets syndrome) or placental abruption as cause of preterm birth). Methods Multivariable logistic regression analyses included PPROM as potential risk factors for adverse outcomes and well established items such as gestational age in weeks, birth weight, antenatal steroids, center, inborn delivery, multiple birth, gender and being small-for-gestational-age. Results PPROM as cause of preterm delivery had no independent effect on the risk of early-onset sepsis, clinical sepsis and blood-culture proven sepsis, while gestational age proved to be the most important contributor to sepsis risk. The diagnosis of PPROM was associated with an increased risk for bronchopulmonary dysplasia (BPD; OR: 1.25, 95% CI: 1.02-1.55, p=0.03) but not with other major outcomes. Conclusions The diagnosis of PPROM per se is not associated with adverse outcome in VLBW infants < 32 weeks apart from a moderately increased risk for BPD. Randomized controlled trials with primary neonatal outcomes are needed to determine which subgroup of VLBW infants benefit from expectant or intentional management of PPROM. PMID:25856083

Hanke, Kathrin; Hartz, Annika; Manz, Maike; Bendiks, Meike; Heitmann, Friedhelm; Orlikowsky, Thorsten; Müller, Andreas; Olbertz, Dirk; Kühn, Thomas; Siegel, Jens; von der Wense, Axel; Wieg, Christian; Kribs, Angela; Stein, Anja; Pagel, Julia; Herting, Egbert; Göpel, Wolfgang; Härtel, Christoph

2015-01-01

240

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

PubMed

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

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

2014-03-01

241

Technology introduction: the safe birth example.  

PubMed

This issue describes how well planned technology introduction programs (the process by which a technology is field tested, refined, retested, and introduced into widespread use), are essential if people are to benefit from new birth-care technologies to confront the tragedy of maternal mortality and morbidity. PATH's safe birth programs have been conducted in project sites in Bangladesh, Malawi, the Yemen Arab Republic, and Zambia. Staff in each project collected qualitative and quantitative data, reviewing existing data from research studies or service statistics, interviewing local experts, conducting focus group discussions, and carrying out small surveys. 3 effective, inexpensive, and easy-to-use technologies were introduced (Birthweight, PATHstrips, Pictorial record-keeping and referral cards). They were also culturally and politically acceptable, environmentally harmless, and could be manufactured locally. Related policies were designed in each situation: what to do when low birth-weight is detected, where to send women of complicated delivery. Safe birth program has been emphasizing solid logistical support: hands-on training of the traditional birth attendants, consistent and effective supervision, maintenance and resupply issues were addressed before national introduction begins. Antenatal technologies described include maternal records keeping, diagnostic and treatment of anemia, maternal stature determination, maternal weight gain and pre-eclampsia detecting. Delivery care technologies are also covered: delivery kits, disinfection methods, and how to deal with obstructed labor. Post partum technologies covered are how to react in case of hemorrhage, detect low birthweight, prevent sexually transmitted diseases, maintain newborn warmth, and prevent dangerous subsequent births. The issue concludes with management technologies: referral systems, transportation, and organizing of supervision visits. PMID:12281653

1988-01-01

242

Sleep disordered breathing in women of childbearing age & during pregnancy.  

PubMed

Obstructive sleep apnoea (OSA) affects 11 per cent of pre-menopausal women though it often remains undetected. Women may present differently than men, and the classic findings of snoring, witnessed apnoeas and sleepiness may not be observed. Factors which predispose to OSA include polycystic ovarian syndrome, obesity, retromicrognathia, and hypothyroidism. OSA may contribute to neurocognitive dysfunction, depression, hypertension and metabolic syndrome. Emerging evidence indicates that snoring and OSA increase during pregnancy. For normal women with normotensive, low-risk pregnancies the prevalence of OSA is very low. Among normotensive pregnant women with high risk pregnancies, the prevalence of OSA is high and is even higher among those with gestational hypertension/preeclampsia during pregnancy. Incident snoring, which is a marker for OSA, is associated with an increased risk of developing gestational hypertension. Recent studies indicate that OSA per se is an independent risk factor for gestational hypertension/pre-eclampsia and may contribute to other poor obstetrical outcomes. The diagnostic test of choice for OSA is a polysomnography with electroencephalogram. Milder degree of disease than what is usually considered clinically significant among men or non-pregnant women appears to be relevant for foetomaternal outcomes. There seems to be benefit for blood pressure control to treating even milder degrees of OSA with CPAP, both acutely and over the 9 months of pregnancy. Chronic hypertensive women should be strongly considered for diagnosis and treatment of OSA prior to or beginning as early as possible in pregnancy to help maintain blood pressure control. Increasing awareness of OSA among maternal health care providers is important given the potential benefits for pregnancy and other health-related outcomes associated with identification and treatment of OSA. PMID:20308754

Champagne, Katéri Agnès; Kimoff, R John; Barriga, Peter Charles; Schwartzman, Kevin

2010-02-01

243

Maternal History and Uterine Artery Doppler in the Assessment of Risk for Development of Early- and Late-Onset Preeclampsia and Intrauterine Growth Restriction  

PubMed Central

Objective. To examine the value of one-step uterine artery Doppler at 20 weeks of gestation in the prediction pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). Methods. A prospective multicentre study that included all women with singleton pregnancies at 19–22 weeks of gestation (w). The mean pulsatility index (mPI) of both uterine arteries was calculated. Receiver-operating characteristics curves (ROC) were drawn to compare uterine artery Doppler and maternal risk factors for the prediction of early-onset PE and/or IUGR (before 32 w) and late-onset PE and/or IUGR. Results. 6,586 women were included in the study. Complete outcome data was recorded for 6,035 of these women (91.6%). PE developed in 75 (1.2%) and IUGR in 69 (1.1%) cases. Uterine Doppler mPI was 0.99 and the 90th centile was 1.40. For 10% false-positive rate, uterine Doppler mPI identified 70.6% of pregnancies that subsequently developed early-onset PE and 73.3% of pregnancies that developed early-onset IUGR. The test had a lower detection rate for the late-onset forms of the disease (23.5% for PE and 30% for IUGR). Maternal history has a low sensitivity in the detection of early-onset cases, although it is better at detecting late-onset PE. Conclusion. Uterine artery Doppler and maternal risk factors seem to select two different populations - early and late-onset PE which might suggest a different pathogenesis. PMID:19936122

Llurba, Elisa; Carreras, Elena; Gratacós, Eduard; Juan, Miquel; Astor, Judith; Vives, Angels; Hermosilla, Eduard; Calero, Ines; Millán, Pilar; García-Valdecasas, Bárbara; Cabero, Lluís

2009-01-01

244

Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?  

PubMed Central

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

Miles, Brodie; Abdel-Ghaffar, Khaled A.; Gamal, Ahmed Y.; Baban, Babak; Cutler, Christopher W.

2014-01-01

245

Activation of endocrine-related gene expression in placental choriocarcinoma cell lines following DNA methylation knock-down.  

PubMed

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

Hogg, K; Robinson, W P; Beristain, A G

2014-07-01

246

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

PubMed

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

Fischer, Claudia; Voss, Andreas

2014-01-01

247

Comparison of obstetric outcome in pregnant women with and without microalbuminuria  

PubMed Central

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

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

2015-01-01

248

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

PubMed Central

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

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

2015-01-01

249

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

PubMed Central

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

2013-01-01

250

Intercellular adhesion molecule-1/LFA-1 cross talk is a proximate mediator capable of disrupting immune integration and tolerance mechanism at the feto-maternal interface in murine pregnancies.  

PubMed

Our understanding why a woman's immune system does not reject her histoincompatible fetus is still very limited. Distinct insights into the mechanisms involved in pregnancy maintenance may help us to prevent pregnancy complications, e.g., miscarriages or pre-eclampsia. Immune integration and tolerance at the feto-maternal interface appear to be indispensable for successful pregnancy maintenance. Little is known about the cross talk between ICAM-1, expressed on epithelium, endothelium, and APC, and its ligand, LFA-1, at the feto-maternal interface. However, based on the role of ICAM-1/LFA-1 in allograft acceptance or rejection upon transplantation, adhesion molecules are likely to interfere with successful pregnancy outcome. In this study, we tested the hypothesis that ICAM-1/LFA-1 pathways may be involved in pregnancy rejection in murine models. By blocking ICAM-1/LFA-1-mediated intercellular adhesion events, we show that fetal immune acceptance is restored in challenged pregnancies (e.g., upon exposure to sound stress), and adoptive transfer of LFA-1 cells into pregnant mice induces rejection only in abortion-prone mouse models. ICAM-1/LFA-1 cross talk leads to increased recruitment of proinflammatory cells to the implantation site, promotes dendritic cell maturation in the decidua, and subsequently induces additional local Th1 polarization via mature dendritic cells. Furthermore, our observations clearly point out that mechanisms of fetal tolerance, e.g., indoleamine 2,3-dioxygenase expression, presence of CD4+CD25bright regulatory T cells, and synthesis of asymmetric Abs, are ICAM-1/LFA-1 dependent. Hence, our data shed light on a hierarchical network of immune integration at the feto-maternal interface, in which ICAM-1/LFA-1 cross talk is clearly a proximate mediator capable of disrupting successful pregnancy maintenance. PMID:15699108

Blois, Sandra; Tometten, Mareike; Kandil, Judith; Hagen, Evelin; Klapp, Burghard F; Margni, Ricardo A; Arck, Petra C

2005-02-15

251

NADPH- and iron-dependent lipid peroxidation inhibit aromatase activity in human placental microsomes.  

PubMed

During pregnancy placenta is the most significant source of lipid hydroperoxides and other reactive oxygen species (ROS). The increased production of lipid peroxides and other ROS is often linked to pre-eclampsia. It is already proved that placental endoplasmic reticulum may be an important place of lipid peroxides and superoxide radical production. In the present study we revealed that NADPH- and iron-dependent lipid peroxidation in human placental microsomes (HPM) inhibit placental aromatase--a key enzyme of estrogen biosynthesis in human placenta. We showed that significant inhibition of this enzyme is caused by small lipid peroxidation (TBARS (thiobarbituric acid-reactive substances)<4nmol/mg microsomal protein (m.p.)). More intensive lipid peroxidation (TBARS>9nmol/mg microsomal protein) diminishes aromatase activity to value being less than 5% of initial value. NADPH- and iron-dependent lipid peroxidation also causes disappearance of cytochrome P450 parallel to observed aromatase activity inhibition. EDTA, alpha-tocopherol, MgCl(2) and superoxide dismutase (SOD) prevent aromatase activity inhibition and cytochrome P450(AROM) degradation. Mannitol and catalase have not effect on TBARS synthesis, aromatase activity and cytochrome P450 degradation. In view of the above we postulate that the inhibition of aromatase activity observed is mainly a consequence of cytochrome P450(AROM) degradation induced by lipid radicals. The role of hydroxyl radical in cytochrome P450 degradation is negligible in our experimental conditions. The results presented here also suggest that the inhibition of aromatase activity can also take place in placenta at in vivo conditions. PMID:18499441

Milczarek, Ryszard; Soko?owska, Ewa; Hallmann, Anna; Kaletha, Krystian; Klimek, Jerzy

2008-06-01

252

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

PubMed

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

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

2015-03-01

253

Chronic infection during placental malaria is associated with up-regulation of cycloxygenase-2  

PubMed Central

Background Placental malaria (PM) is associated with poor foetal development, but the pathophysiological processes involved are poorly understood. Cyclooxygenase (COX) and lipoxygenase (LOX) which convert fatty acids to prostaglandins and leukotrienes, play important roles in pregnancy and foetal development. COX-2, currently targeted by specific drugs, plays a dual role as it associates with both pre-eclampsia pathology and recovery during infection. The role of COX during PM was questioned by quantifying at delivery COX-1, COX-2, 15-LOX, and IL-10 expression in two groups of malaria infected and uninfected placenta. Methods Placental biopsies were collected at delivery for mRNA isolation and quantification, using real time PCR. Results COX-2 and IL-10 mRNAs increased mainly during chronic infections (nine- and five-times, respectively), whereas COX-1 transcripts remained constant. COX-2 over-expression was associated with a higher birth weight of the baby, but with a lower rate of haemoglobin of the mother. It was associated with a macrophage infiltration of the placenta and with a low haemozoin infiltration. In the opposite way, placental infection was associated with lower expression of 15-LOX mRNA. A high degree of haemozoin deposition correlates with low birth weight and decreased expression of COX-2. Conclusion These data provide evidence that COX-2 and IL-10 are highly induced during chronic infection of the placenta, but were not associated with preterm delivery or low birth weight. The data support the involvement of COX-2 in the recovery phase of the placental infection. PMID:20144201

2010-01-01

254

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

PubMed Central

Objective To investigate obstetric and perinatal outcomes among female survivors of adolescent and young adult (AYA) cancers and their offspring. Methods Using multivariate analysis of statewide linked data, outcomes of all first completed pregnancies (n?=?1894) in female survivors of AYA cancer diagnosed in Western Australia during the period 1982–2007 were compared with those among females with no cancer history. Comparison pregnancies were matched by maternal age-group, parity and year of delivery. Results Compared with the non-cancer group, female survivors of AYA cancer had an increased risk of threatened abortion (adjusted relative risk 2.09, 95% confidence interval 1.51–2.74), gestational diabetes (2.65, 2.08–3.57), pre-eclampsia (1.32, 1.04–1.87), post-partum hemorrhage (2.83, 1.92–4.67), cesarean delivery (2.62, 2.22–3.04), and maternal postpartum hospitalization>5 days (3.01, 1.72–5.58), but no excess risk of threatened preterm delivery, antepartum hemorrhage, premature rupture of membranes, failure of labor to progress or retained placenta. Their offspring had an increased risk of premature birth (<37 weeks: 1.68, 1.21–2.08), low birth weight (<2500 g: 1.51, 1.23–2.12), fetal growth restriction (3.27, 2.45–4.56), and neonatal distress indicated by low Apgar score (<7) at 1 minute (2.83, 2.28–3.56), need for resuscitation (1.66, 1.27–2.19) or special care nursery admission (1.44, 1.13–1.78). Congenital abnormalities and perinatal deaths (intrauterine or ?7 days of birth) were not increased among offspring of survivors. Conclusion Female survivors of AYA cancer have moderate excess risks of adverse obstetric and perinatal outcomes arising from subsequent pregnancies that may require additional surveillance or intervention. PMID:25485774

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

2014-01-01

255

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

PubMed Central

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

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

2014-01-01

256

A Grhl2-dependent gene network controls trophoblast branching morphogenesis.  

PubMed

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

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

2015-03-15

257

Effect of the integrated approach of yoga therapy on platelet count and uric acid in pregnancy: A multicenter stratified randomized single-blind study  

PubMed Central

Background: Yoga improves maternal and fetal outcomes in pregnancy. Platelet Count and Uric acid (Ua) are valuable screening measures in high-risk pregnancy. Aim: To examine the effect of yoga on platelet counts and serum Ua in high-risk pregnancy. Materials and Methods: This stratified randomized controlled trial, conducted by S-VYASA University at St. John's Medical College Hospital and Gunasheela Maternity Hospital, recruited 68 women with high-risk pregnancy (30 yoga and 38 controls) in the twelfth week of pregnancy. The inclusion criteria were: Bad obstetrics history, twin pregnancies, maternal age < 20 or > 35 years, obesity (BMI > 30), and genetic history of pregnancy complications. Those with normal pregnancy, anemia (< 10 grams%dl), h/o clotting disorders; renal, hepatic or heart disease; seizure disorder; or structural abnormalities in the pelvis, were excluded. The yoga group practiced simple meditative yoga (three days / week for three months). Results: At baseline, all women had normal platelet counts (> 150×109/L) with a decrease as pregnancy advanced. Ua (normal at baseline) increased in both groups. No one developed abnormal thrombocytopenia or hyperuricemia. Healthy reduction in platelet count (twelfth to twentieth week) occurred in a higher (P < 0.001, Chi2 test) number of women in the yoga group than the control group. A similar trend was found in uric acid. Significantly lesser number of women in the yoga group (n = 3) developed pregnancy-induced hypertension (PIH) / pre-eclampsia (PE) than those in the control group (n = 12), with absolute risk reduction (ARR) by 21%. Conclusion: Antenatal integrated yoga from the twelfth week is safe and effective in promoting a healthy progression of platelets and uric acid in women with high-risk pregnancy, pointing to healthy hemodilution and better physiological adaptation. PMID:23440456

Jayashree, R; Malini, A; Rakhshani, A; Nagendra, HR; Gunasheela, S; Nagarathna, R

2013-01-01

258

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

PubMed Central

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

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

2014-01-01

259

Essential pre-pregnancy and pregnancy interventions for improved maternal, newborn and child health  

PubMed Central

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

2014-01-01

260

Prevalence of antiphospholipid antibodies and risk of subsequent adverse obstetric outcomes in women with prior pregnancy loss.  

PubMed

The reported prevalence of antiphospholipid antibodies in women with a chief complaint of pregnancy loss varies, as does the risk of adverse outcomes in subsequent pregnancies. Our objectives were to assess the prevalence of antiphospholipid antibodies meeting revised Sapporo thresholds among women presenting with a chief complaint of pregnancy loss and risks in subsequent pregnancies for these women. We examined a retrospective cohort of patients presenting with a chief complaint of pregnancy loss between 2003 and 2012. Antiphospholipid antibodies were assessed at the providers' discretion, and patients were considered positive if they met the revised Sapporo criteria. Patient data were obtained by review of the medical records. 338/390 women (86.7%) presented with a chief complaint of pregnancy loss and had testing for antiphospholipid antibodies. 19/338 women (5.6%) persistently tested positive for at least one antiphospholipid antibody. Seven women who tested positive had isolated recurrent early pregnancy loss ?10 weeks, and 12 women who tested positive had venous thromboembolism (VTE), systemic lupus erythematosus (SLE), delivery <34 weeks for pre-eclampsia, and/or placental insufficiency, or fetal demise >10 weeks. Subsequent pregnancy outcomes were available for 13 patients. Compared with women with recurrent early pregnancy loss alone, subsequent obstetric morbidity was significantly more likely in those patients with a history of SLE and/or VTE (p=0.048). We conclude that the prevalence of positive antiphospholipid antibodies in women with a chief complaint of pregnancy loss and without autoimmune disease or prior thrombosis is low and that among these women, subsequent pregnancy outcomes are largely favorable. PMID:25453202

Bowman, Zachary S; Wünsche, Vera; Porter, T Flint; Silver, Robert M; Branch, D Ware

2015-02-01

261

The WHO antenatal care randomised controlled trial: rationale and study design.  

PubMed

The World Health Organisation and collaborating institutions in developing countries are conducting a multicentre randomised controlled trial to evaluate a new antenatal care (ANC) programme, consisting of tests, clinical procedures and follow-up actions scientifically demonstrated to be effective in improving maternal and newborn outcomes. These activities are distributed, for practical reasons, over four visits during the course of pregnancy and are aimed at achieving predetermined goals. The study is taking place in four countries, Argentina, Cuba, Saudi Arabia and Thailand. Recruitment of study subjects started on 1 May 1996. All 53 ANC clinical units had been enrolled by December 1996. Clinics in each country were randomly allocated (cluster randomisation) to provide either the new programme or the traditional programme currently in use. Approximately 24,000 women presenting for ANC at these clinics over an average period of 18 months will have been recruited. As women attending the control clinics receive the 'best standard treatment' as currently offered in these clinics, individual informed consent is requested only from women attending the intervention clinics. Authorities of the corresponding health districts and all participating clinics have provided written institutional informed consent before randomisation. The primary outcome of the trial in relation to maternal conditions is the rate of a morbidity indicator index, defined as the presence of at least one of the following conditions for which ANC is relevant: (a) pre-eclampsia or eclampsia during pregnancy or within 24 h of delivery; (b) postpartum anaemia (haemoglobin < 90 g/L); or (c) severe urinary tract infection/pyelonephritis, defined as an episode requiring antibiotic treatment and/or hospitalisation. The primary fetal outcome is the rate of low birthweight (< 2500 g). Adverse maternal and fetal outcomes are expected for approximately 10% of the control group. Several maternal and perinatal secondary outcomes are also considered. A comprehensive cost-effectiveness analysis and women's and providers' satisfaction evaluation are performed concurrently with the trial. Health-care programmes should be rigorously evaluated by randomised controlled trials, which are feasible in developing countries and should be conducted before introducing new treatments or health interventions. PMID:9805722

Villar, J; Bakketeig, L; Donner, A; al-Mazrou, Y; Ba'aqeel, H; Belizán, J M; Carroli, G; Farnot, U; Lumbiganon, P; Piaggio, G; Berendes, H

1998-10-01

262

Nitric oxide synthase in human placenta and umbilical cord from normal, intrauterine growth-retarded and pre-eclamptic pregnancies.  

PubMed Central

1. It has been suggested that a deficiency of nitric oxide (NO) may explain many of the pathophysiological features of pre-eclampsia (PE) and intra-uterine (foetal) growth retardation (IUGR). To elucidate further the role of NO in the pathophysiology of pregnancy we have determined the relative amount and activity of NO synthase (NOS) in first trimester and normal-term placental tissues, as well as in the placenta and umbilical cord in pregnancies complicated by PE and IUGR, using NG-nitro-L-[2,3,4,5(-3)H]-arginine ([3H]-L-NOARG) binding, quantitative in vitro autoradiography, [3H]-arginine to [3H]-citrulline conversion and Western blotting. 2. Specific, high affinity (KD = 38 nM) [3H]-L-NOARG binding was demonstrated in the villous trophoblast of normal-term placentae. Binding was calcium-independent, stereoselective and exhibited a rank order of inhibition by NOS inhibitors and substrate (L-NOARG > or = L-NMMA > or = 7-NI > L-NAME > L-Arg > or = L-NIO > ADMA). 3. [3H]-L-NOARG binding density and NOS activity were both significantly greater in placental tissues from first trimester and PE or IUGR complicated pregnancies compared to normal-term placentae. 4. Western blotting, using an endothelial NOS peptide antiserum, demonstrated a approximately 140 KDa protein band in placental extracts and indicated that the amount of immunoreactive material was significantly greater in first trimester compared to normal-term placentae. 5. Specific [3H]-L-NOARG binding was also localized to the endothelial lining of umbilical arteries and veins, binding density being greater in the artery than the vein. [3H]-L-NOARG binding to the umbilical artery endothelium was significantly lower in PE and IUGR complicated pregnancies compared to normal-term controls. 6. The role of trophoblast-derived NO in human placental pathophysiology remains to be established, but differences in the amount of placental [3H]-L-NOARG binding, NOS activity and immunoreactive material indicate that expression of NOS in the villous trophoblast falls during pregnancy. Conversely, the apparent reduction in NOS in the umbilical artery endothelium in PE and IUGR complicated pregnancies may be indicative of endothelial dysfunction. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 11 PMID:8719783

Rutherford, R. A.; McCarthy, A.; Sullivan, M. H.; Elder, M. G.; Polak, J. M.; Wharton, J.

1995-01-01

263

A systematic review of the relationship between severe maternal morbidity and post-traumatic stress disorder  

PubMed Central

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

2012-01-01

264

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

PubMed Central

Chorionic plate arteries (CPA) are located at the maternofetal interface where they are able to respond to local metabolic changes. Unlike many other types of vasculature, the placenta lacks nervous control and requires autoregulation for controlling blood flow. The placental circulation, which is of low-resistance, may become hypoxic easily leading to fetal acidosis and fetal distress however the role of the ion channels in these circumstances is not well-understood. Active potassium channel conductances that are subject to local physicochemical modulation may serve as pathways through which such signals are transduced. The aim of this study was to investigate the modulation of CPA by pH and the channels implicated in these responses using wire myography. CPA were isolated from healthy placentae and pre-contracted with U46619 before testing the effects of extracellular pH using 1 M lactic acid over the pH range 7.4 - 6.4 in the presence of a variety of ion channel modulators. A change from pH 7.4 to 7.2 produced a 29±3% (n?=?9) relaxation of CPA which increased to 61±4% at the lowest pH of 6.4. In vessels isolated from placentae of women with pre-eclampsia (n?=?6), pH responses were attenuated. L-methionine increased the relaxation to 67±7% (n?=?6; p<0.001) at pH 6.4. Similarly the TASK 1/3 blocker zinc chloride (1 mM) gave a maximum relaxation of 72±5% (n?=?8; p<0.01) which compared with the relaxation produced by the TREK-1 opener riluzole (75±5%; n?=?6). Several other modulators induced no significant changes in vascular responses. Our study confirmed expression of several ion channel subtypes in CPA with our results indicating that extracellular pH within the physiological range has an important role in controlling vasodilatation in the human term placenta. PMID:25490401

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

2014-01-01

265

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

SciTech Connect

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

Latham, Antony M.; Odell, Adam F. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom)] [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Mughal, Nadeem A. [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom)] [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Issitt, Theo; Ulyatt, Clare; Walker, John H. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom)] [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Homer-Vanniasinkam, Shervanthi [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom)] [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Ponnambalam, Sreenivasan, E-mail: s.ponnambalam@leeds.ac.uk [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom)] [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom)

2012-11-01

266

Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM)  

PubMed Central

Background Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications. Methods/Design We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy. Discussion The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are specifically prevented by low-molecular-weight heparin. Systematic review registration PROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249 PMID:24969227

2014-01-01

267

Vitamin D during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and meta-analysis  

PubMed Central

Summary Vitamin D has well-defined classical functions related to calcium metabolism and bone health but also has non-classical effects that may influence other aspects of health. There has been considerable recent interest in the role of vitamin D on outcomes related to pregnancy and young child health but few efforts have been made to systematically consolidate this evidence to inform the research and policy agenda for low income countries. A systematic review was undertaken to identify intervention and observational studies of vitamin D supplementation, intake, or status (25-hydroxy-vitamin D) during pregnancy on perinatal and infant health outcomes. Data from trials and observational studies isolating the effect of vitamin D supplementation and intake were extracted and study quality was evaluated. Meta-analysis was used to pool effect estimates. We identified 5 randomized trials with outcomes of relevance to our review. All had small sample size and dosage amount, duration, and frequency varied as did the ability to correct deficiency. Pooled analysis of trials using fixed effects models suggested protective effects of supplementation on low birthweight (3 trials, Risk ratio (RR)=0.40 [95% confidence interval (CI), 0.23, 0.71]) and non-significant but suggestive effects of daily supplementation on small-for-gestational age (SGA) (2 trials, RR=0.67, [0.40, 1.11]. No effect on preterm delivery (<37 weeks) was evident (2 trials, RR=0.77 [0.35, 1.66]). Little evidence from trials exists to evaluate the effect of vitamin D supplementation during pregnancy on maternal, perinatal or infant health outcomes. Based on both trials and observational studies, we recommend that future research explore SGA, preterm delivery, pre-eclampsia, and maternal and childhood infections, as outcomes of interest. Trials should focus on populations with a high prevalence of vitamin D deficiency, explore the relevance of timing of supplementation, and the dosage used in such trials should be sufficient to correct deficiency. PMID:22742603

Thorne-Lyman, Andrew; Fawzi, Wafaie W.

2013-01-01

268

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

PubMed Central

We aimed to determine whether the ACE A11860G genotype is associated with small for gestational age babies (SGA) and to determine whether the association is affected by environmental factors and fetal sex. Overall, 3234 healthy nulliparous women with singleton pregnancies, their partners and babies were prospectively recruited in Adelaide, Australia and Auckland, New Zealand. Data analyses were confined to 2121 Caucasian parent–infant trios, among which 216 were pregnancies with SGA infants and 1185 were uncomplicated pregnancies. Women with the ACE A11860G GG genotype in the combined and Adelaide cohorts had increased risk for SGA [odds ratios (OR) 1.5, 95% confidence interval (CI) 1.1–2.1 and OR 2.0, 95% CI 1.3–3.3, respectively) and delivered lighter babies (P = 0.02; P = 0.007, respectively) compared with those with AA/AG genotypes. The maternal ACE A11860G GG genotype was associated with higher maternal plasma ACE concentration at 15 weeks' gestation than AA/AG genotypes (P < 0.001). When the Adelaide cohort was stratified by maternal socio-economic index (SEI) and pre-pregnancy green leafy vegetable intake, the ACE A11860G GG genotype was only associated with an increased risk for SGA (OR 4.9, 95% CI 1.8–13.4 and OR 3.3, 95% CI 1.6–7.0, respectively) and a reduction in customized birthweight centile (P = 0.006 and P = 0.03) if superimposed on maternal SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day. Furthermore, the associations of maternal ACE A11860G with customized birthweight centile observed among Adelaide women with SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day were female specific. The current study identified a novel association of maternal ACE A11860G with SGA. More interestingly, this association was modified by environmental factors and fetal sex, suggesting ACE A11860G–environment–fetal sex interactions. Trial Registry Name: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, SGA babies and spontaneous preterm birth. URL: http://www.anzctr.org.au. Registration number: ACTRN12607000551493. PMID:23615722

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

2013-01-01

269

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

PubMed Central

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

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

2015-01-01

270

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

PubMed Central

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

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

2014-01-01

271

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

PubMed Central

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

2014-01-01

272

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

PubMed

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

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

273

Human immunodeficiency virus and AIDS and other important predictors of maternal mortality in Mulago Hospital Complex Kampala Uganda  

PubMed Central

Background Women with severe maternal morbidity are at high risk of dying. Quality and prompt management and sometimes luck have been suggested to reduce on the risk of dying. The objective of the study was to identify the direct and indirect causes of severe maternal morbidity, predictors of progression from severe maternal morbidity to maternal mortality in Mulago hospital, Kampala, Uganda. Methods This was a longitudinal follow up study at the Mulago hospital's Department of Obstetrics and Gynaecology. Participants were 499 with severe maternal morbidity admitted in Mulago hospital between 15th November 2001 and 30th November 2002 were identified, recruited and followed up until discharge or death. Potential prognostic factors were HIV status and CD4 cell counts, socio demographic characteristics, medical and gynaecological history, past and present obstetric history and intra- partum and postnatal care. Results Severe pre eclampsia/eclampsia, obstructed labour and ruptured uterus, severe post partum haemorrhage, severe abruptio and placenta praevia, puerperal sepsis, post abortal sepsis and severe anaemia were the causes for the hospitalization of 499 mothers. The mortality incidence rate was 8% (n = 39), maternal mortality ratio of 7815/100,000 live births and the ratio of severe maternal morbidity to mortality was 12.8:1. The independent predictors of maternal mortality were HIV/AIDS (OR 5.1 95% CI 2-12.8), non attendance of antenatal care (OR 4.0, 95% CI 1.3-9.2), non use of oxytocics (OR 4.0, 95% CI 1.7-9.7), lack of essential drugs (OR 3.6, 95% CI 1.1-11.3) and non availability of blood for transfusion (OR 53.7, 95% CI (15.7-183.9) and delivery of amale baby (OR 4.0, 95% CI 1.6-10.1). Conclusion The predictors of progression from severe maternal morbidity to mortalitywere: residing far from hospital, low socio economic status, non attendance of antenatal care, poor intrapartum care, and HIV/AIDS. There is need to improve on the referral system, economic empowerment of women and to offer comprehensive emergency obstetric care so as to reduce the maternal morbidity and mortality in our community. PMID:21756355

2011-01-01

274

Reducing stillbirths: interventions during labour  

PubMed Central

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

Darmstadt, Gary L; Yakoob, Mohammad Yawar; Haws, Rachel A; Menezes, Esme V; Soomro, Tanya; Bhutta, Zulfiqar A

2009-01-01

275

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

PubMed Central

Background In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis. The first aim of this review is to assess whether sildenafil benefits or harms these babies. The second aim is to analyse if these effects are modified in a clinically meaningful way by factors related to the women or the trial protocol. Methods/Design The STRIDER (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction) Individual Participant Data (IPD) Study Group will conduct a prospective IPD and aggregate data systematic review with meta-analysis and trial sequential analysis. The STRIDER IPD Study Group started trial planning and funding applications in 2012. Three trials will be launched in 2014, recruiting for three years. Further trials are planned to commence in 2015. The primary outcome for babies is being alive at term gestation without evidence of serious adverse neonatal outcome. The latter is defined as severe central nervous system injury (severe intraventricular haemorrhage (grade 3 and 4) or cystic periventricular leukomalacia, demonstrated by ultrasound and/or magnetic resonance imaging) or other severe morbidity (bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, or necrotising enterocolitis requiring surgery). The secondary outcomes are improved fetal growth velocity assessed by ultrasound abdominal circumference measurements, gestational age and birth weight (centile) at delivery, and age-adequate performance on the two-year Bayley scales of infant and toddler development-III (composite cognitive score and composite motor score). Subgroup and sensitivity analyses in the IPD meta-analysis include assessment of the influence of several patient characteristics: an abnormal or normal serum level of placental growth factor, absent/reversed umbilical arterial end diastolic flow at commencement of treatment, and other patient characteristics available at baseline such as gestational age and estimated fetal weight. The secondary outcomes for mothers include co-incidence and severity of the maternal syndrome of pre-eclampsia, mortality, and other serious adverse events. Discussion Trials are expected to start in 2013–2014 and end in 2016–2017. Data analyses of individual trials are expected to finish in 2019. Given the pre-planned and agreed IPD protocol, these results should be available in 2020. PMID:24618418

2014-01-01

276

Utero-placental Doppler ultrasound for improving pregnancy outcome  

PubMed Central

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

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

2014-01-01

277

Acute renal failure in pregnancy: our experience.  

PubMed

Acute renal failure (ARF) is a serious medical complication during pregnancy, and, in the post-partum period, is associated with significant maternal morbidity and mortality as well as fetal loss. The objective of our study is to find the etiology and maternal outcome of ARF during pregnancy. The study was conducted at the Obstetrics and Gynecology Department of the Institute of Kidney Disease and Research Center, Ahmedabad, India from January 2009 to January 2011. Fifty previously healthy patients who developed ARF, diagnosed on oliguria and serum creatinine >2 mg%, were included in the study. Patients with a known history of renal disease, diabetes and hypertension were excluded from the study. All patients were followed-up for a period of six months. Patient re-cords, demographic data, urine output on admission and preceding history of antepartum hemorrhage (APH), post-partum hemorrhage (PPH), septicemia, operative interventions and retained product of conception were noted and need for dialysis was considered. Patients were thoroughly examined and baseline biochemical investigations and renal and obstetrical ultrasound were performed on each patient and bacterial culture sensitivity on blood, urine or vaginal swabs were performed in selected patients. The age range was 19-38 years (mean 26 ± 3.8). The first trimester, second trimester and puerperal groups comprised of four (8%), 25 (50%) and 21 patients (42%), respectively. Hemorrhage was the etiology for ARF in 15 (30%), APH in ten (20%) and PPH in five (10%) patients. Eleven (22%) patients had lower segment cesarian section (LSCS) while 36 (78%) patients had normal vaginal delivery. In 20 (40%) patients, puerperal sepsis was the etiological factor, while pre-eclampsia, eclampsia and HELLP syndrome accounted for 18 (36%) patients. Two (4%) patients had disseminated intravascular coagulation on presentation while one (2%) patient was diagnosed with hemolytic uremic syndrome. Maternal mortality was 12% (n = 6). Of the 38 (88%) surviving patients, 21 (42%) had complete recovery of renal function, eight (16%) patients had partial and 15 (30%) patients required dialysis on a long-term basis. ARF in pregnancy is associated with poor maternal and renal outcome if not detected and treated in time. PMID:24626025

Aggarwal, Rohina S; Mishra, Vineet V; Jasani, Anil F; Gumber, Manoj

2014-03-01

278

In Vitro Fertilization and Multiple Pregnancies  

PubMed Central

Executive Summary Objective The objective of this health technology policy assessment was to determine the clinical effectiveness and cost-effectiveness of IVF for infertility treatment, as well as the role of IVF in reducing the rate of multiple pregnancies. Clinical Need: Target Population and Condition Typically defined as a failure to conceive after a year of regular unprotected intercourse, infertility affects 8% to 16% of reproductive age couples. The condition can be caused by disruptions at various steps of the reproductive process. Major causes of infertility include abnormalities of sperm, tubal obstruction, endometriosis, ovulatory disorder, and idiopathic infertility. Depending on the cause and patient characteristics, management options range from pharmacologic treatment to more advanced techniques referred to as assisted reproductive technologies (ART). ART include IVF and IVF-related procedures such as intra-cytoplasmic sperm injection (ICSI) and, according to some definitions, intra-uterine insemination (IUI), also known as artificial insemination. Almost invariably, an initial step in ART is controlled ovarian stimulation (COS), which leads to a significantly higher rate of multiple pregnancies after ART compared with that following natural conception. Multiple pregnancies are associated with a broad range of negative consequences for both mother and fetuses. Maternal complications include increased risk of pregnancy-induced hypertension, pre-eclampsia, polyhydramnios, gestational diabetes, fetal malpresentation requiring Caesarean section, postpartum haemorrhage, and postpartum depression. Babies from multiple pregnancies are at a significantly higher risk of early death, prematurity, and low birth weight, as well as mental and physical disabilities related to prematurity. Increased maternal and fetal morbidity leads to higher perinatal and neonatal costs of multiple pregnancies, as well as subsequent lifelong costs due to disabilities and an increased need for medical and social support. The Technology Being Reviewed IVF was first developed as a method to overcome bilateral Fallopian tube obstruction. The procedure includes several steps: (1) the woman’s egg is retrieved from the ovaries; (2) exposed to sperm outside the body and fertilized; (3) the embryo(s) is cultured for 3 to 5 days; and (4) is transferred back to the uterus. IFV is considered to be one of the most effective treatments for infertility today. According to data from the Canadian Assisted Reproductive Technology Registry, the average live birth rate after IVF in Canada is around 30%, but there is considerable variation in the age of the mother and primary cause of infertility. An important advantage of IVF is that it allows for the control of the number of embryos transferred. An elective single embryo transfer in IVF cycles adopted in many European countries was shown to significantly reduce the risk of multiple pregnancies while maintaining acceptable birth rates. However, when number of embryos transferred is not limited, the rate of IVF-associated multiple pregnancies is similar to that of other treatments involving ovarian stimulation. The practice of multiple embryo transfer in IVF is often the result of pressures to increase success rates due to the high costs of the procedure. The average rate of multiple pregnancies resulting from IVF in Canada is currently around 30%. An alternative to IVF is IUI. In spite of reported lower success rates of IUI (pregnancy rates per cycle range from 8.7% to 17.1%) it is generally attempted before IVF due to its lower invasiveness and cost. Two major drawbacks of IUI are that it cannot be used in cases of bilateral tubal obstruction and it does not allow much control over the risk of multiple pregnancies compared with IVF. The rate of multiple pregnancies after IUI with COS is estimated to be about 21% to 29%. Ontario Health Insurance Plan Coverage Currently, the Ontario Health Insurance Plan covers the cost of IVF for women with bilaterally blocked Fallopian tubes only, in which case i

2006-01-01

279

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

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

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