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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.

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



Pre-eclampsia, eclampsia, and hypertension  

PubMed Central

Introduction Pre-eclampsia (raised blood pressure and proteinuria) complicates 2% to 8% of pregnancies, and increases morbidity and mortality in the mother and child. Pre-eclampsia is more common in women with multiple pregnancy and in those who have conditions associated with microvascular disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions in women at risk of pre-eclampsia? What are the effects of interventions in women who develop mild to moderate hypertension during pregnancy? What are the effects of interventions in women who develop severe pre-eclampsia or very high blood pressure during pregnancy? What is the best choice of anticonvulsant for women with eclampsia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 69 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticonvulsants, antihypertensive drugs, antioxidants, antiplatelet drugs, atenolol, bed rest, hospital admission, or day care, calcium supplementation, choice of analgesia during labour, early delivery (interventionist care), evening primrose oil, fish oil, glyceryl trinitrate, magnesium supplementation, plasma volume expansion, and salt restriction.



Pubertal development in daughters of women with pre-eclampsia  

Microsoft Academic Search

ObjectiveTo compare clinical signs of puberty onset in daughters of pre-eclampsia and normotensive pregnancies.DesignPopulation based follow-up study.MethodsIn a cohort of 120 daughters of pre-eclampsia pregnancies and 203 daughters of pregnancies without pre-eclampsia, pubic hair growth and breast development were assessed at 11, 12 and 13 years of age by Tanner scores and by self-assessment.ResultsCompared to the normotensive group, pubic hair

Bjorn Ogland; Stein T Nilsen; Michele R Forman; Lars J Vatten



Genetic variants in pre-eclampsia: a meta-analysis.  


BACKGROUND Pre-eclampsia has a clear familial component, suggesting that the condition may be partly attributable to genetic susceptibility. The search for susceptibility genes has led to a drastic increase in the number of published studies associating genetic factors with pre-eclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis assessed the pooled effect of each genetic variant that is reproducibly associated with pre-eclampsia. METHODS Studies that assessed the association between genes and pre-eclampsia were searched in PubMed, Embase and Web of Science. We selected all genetic variants that were significantly associated with pre-eclampsia in an initial study and were subsequently independently reproduced in at least one additional study. All studies that assessed these reproduced variants were then included. The association between genetic variants and pre-eclampsia was calculated at the allele level, and the main measure of effect was a pooled odds ratio in a random-effects model. RESULTS The literature search yielded 2965 articles, of which 542 investigated genetic associations in pre-eclampsia. We identified 22 replicated genetic variants, of which 7 remained significantly associated with pre-eclampsia following meta-analysis. These variants were in or near the following genes: ACE, CTLA4, F2, FV, LPL and SERPINE1. CONCLUSIONS This meta-analysis identified seven genetic variants associated with pre-eclampsia. Importantly, many of these variants are also risk factors for developing cardiovascular disease, revealing that pre-eclampsia and cardiovascular disease have shared genetic risk factors. The contribution of the identified genetic variants in the pathogenesis of pre-eclampsia should be the focus of future studies. PMID:23300202

Buurma, A J; Turner, R J; Driessen, J H M; Mooyaart, A L; Schoones, J W; Bruijn, J A; Bloemenkamp, K W M; Dekkers, O M; Baelde, H J



Pre-eclampsia: is it all in the placenta?  


Hypertensive disorders of pregnancy complicate almost 7 - 10 % of all pregnancies. The dyad of hypertension and proteinuria after 20 weeks of gestation is referred to as pre-eclampsia. It is a major cause of maternal morbidity and mortality and is also associated with increased perinatal problems. Despite intensive research over the years the exact cause of pre-eclampsia remains unknown. Nevertheless, information gleaned from published studies point to the placenta as the probable pathogenetic focus of pre-eclampsia, as the disease usually resolves within 24 - 48 hours after delivery of the placenta. Although the precise involvement of the placenta in pre-eclampsia remains unclear there are indications that the trophoblastic invasion of the uterine spiral arteries is abnormal in women who develop pre-eclampsia. This impaired invasion leads to decreased placental perfusion and ultimately to placental hypoxia. The distressed or ischaemic placenta then secretes a factor(s) into the maternal circulation, which cause/s widespread endothelial cell dysfunction characterized by vasospasm, activation of coagulation system and organ ischaemia. The cause of the defective cytotrophoblastic invasion of the spiral arteries and the link between placental ischaemia and generalized maternal endothelial dysfunction remain unknown. Although the placenta appears to have a major role in the pathogenesis of pre-eclampsia, evidence also suggests that factors like maternal genetic predisposition, dietary, environmental and behaviour, which surface during the stress of pregnancy might also be involved in the development of pre-eclampsia. It is known that not all women with poor cytotrophoblast invasion develop pre-eclampsia and not all women with preeclampsia show poor cytotrophoblast invasion. Over the years, a number of potential risk factors associated with the development of pre-eclampsia are being recognized and it might be appropriate now to develop some preventative strategies based upon the available information. PMID:22589643

Singh, Harbindar Jeet



Prediction and primary prevention of pre-eclampsia.  


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

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



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



Diagnosis and management of pre-eclampsia: an update.  


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



Recent Insights into the pathogenesis of pre-eclampsia.  


Pre-eclampsia is more than pregnancy induced hypertension. The emerging view described in this presentation is that pre-eclampsia is secondary to the interactions of reduced placental perfusion with diverse maternal factors that alter endothelial function. The maternal contribution is from factors that antedate pregnancy and are influenced by the usual metabolic adaptations of pregnancy. The endothelium and other targets for the effects of these interactions are more sensitive to insults during pregnancy because of activation of the inflammatory cascade as a normal part of pregnancy. At least part of the response to reduced placental perfusion may be a fetal adaptive response to attempt to overcome the reduced delivery of nutrients. A reasonable convergence point for the interaction is at the level of oxidative stress. This hypothesis has both encouraging and discouraging corollaries. The diversity of maternal factors argues that there will be no single gene to explain the disorder and no single 'magic bullet' to treat the disorder. However, it is encouraging that the recognition of maternal predisposition to the disorder directs therapy to prevent pre-eclampsia at a specific target in subsets of women. Finally, the suggestion that some of the maternal alterations are due to fetal adaptive responses encourages careful choices of agents and meticulous infant follow up in well planned clinical trials. PMID:12061851

Roberts, J M; Lain, K Y



The role of lipoprotein (a) in pregnancies complicated by pre-eclampsia  

Microsoft Academic Search

Endothelial cell dysfunction is a key feature of the pathogenesis of pre-eclampsia. The cause of the endothelial cell injury is probably multifactorial, but poor placenta perfusion plays a major role. In pre-eclampsia, characteristic pathological lesions in the placenta are fibrin deposits, acute atherosis and thrombosis. The similarity between the lesions of pre-eclampsia and atherosclerosis has led to speculations of a

G. T. R. Manten; Ytje Y. van der Hoek; J. Marko Sikkema; Hieronymus A. M. Voorbij; Ton M. Hameeteman; Gerard H. A. Visser; Arie Franx



Serum Cholesterol and Ceruloplasmin Levels in Second Trimester can Predict Development of Pre-eclampsia  

PubMed Central

Background: Pre-eclampsia is one of the leading causes of high rates of maternal and perinatal mortality and morbidity. Pathophysiology of pre-eclampsia is still obscure. Currently, there are no screening tests for pre-eclampsia that are reliable, valid, and economical. Parameters of oxidative stress could be early markers of endothelial dysfunction that predates clinical pre-eclampsia. Aim: This study was to study ceruloplasmin in nulliparous women as marker of oxidative stress and lipid profile to evaluate their value in prediction of pre-eclampsia. Materials and Methods: Prospective observational study. 306 nulliparous women had their serum lipid profile and ceruloplasmin levels measured at 14-16 weeks period of gestation as sample 1 and at 18-20 weeks as sample 2. All cases were followed up till the end of pregnancy for development of pre-eclampsia. Results: There was no statistically significant difference between the normals and pre-eclampsia cases at 14-16 week for all the oxidative stress parameters (P > 0.05), but at 18-20 week, there was statistically significant difference between the normals and pre-eclampsia cases in cholesterol and ceruloplasmin parameters (P < 0.05). Conclusion: Cholesterol and ceruloplasmin levels in second trimester (18-20 weeks) can predict the development of pre-eclampsia.

Dey, Madhusudan; Arora, Devendra; Narayan, Nagarja; Kumar, Reema



Pre-eclampsia and cardiovascular disease: metabolic syndrome of pregnancy?  


Complications of pregnancy, particularly pre-eclampsia (PET) and intra-uterine growth restriction (IUGR) have been associated with future maternal cardiovascular disease (CVD). Pre-eclampsia, characterised by insulin resistance, widespread endothelial damage and dysfunction, coagulation defects and increased systemic inflammatory response, shares many risk factors with CVD. This review describes the pathology of PET and the maternal metabolic response and discusses the possible underlying mechanisms common to CVD and PET. The contributions of pre-existing risk factors and of the exaggerated atherogenic-like response seen in PET persisting post-partum to future CVD are considered. The potential for interventions based on early assessment of cardiovascular risk is addressed. We conclude that despite the low immediate cardiovascular risk in a population of young women, a pregnancy with multiple complications including PET, premature delivery and IUGR, carries a seven-fold additive risk of future disease. These women may be an appropriate cohort for CVD risk screening and for possible intervention. PMID:15262174

Rodie, Vanessa A; Freeman, Dilys J; Sattar, Naveed; Greer, Ian A



Optimal Glycemic Control, Pre-eclampsia, and Gestational Hypertension in Women With Type 1 Diabetes in the Diabetes and Pre-eclampsia Intervention Trial  

PubMed Central

OBJECTIVE To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes. RESEARCH DESIGN AND METHODS Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA1c (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks’ gestation (n = 592), and at 34 weeks’ gestation (n = 519) and were categorized as optimal (<6.1%: referent), good (6.1–6.9%), moderate (7.0–7.9%), and poor (?8.0%) glycemic control, respectively. RESULTS Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C ?8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17–11.6]) compared with optimal control. At 26 weeks’ gestation, A1C values ?6.1% (good: 2.09 [1.03–4.21]; moderate: 3.20 [1.47–7.00]; and poor: 3.81 [1.30–11.1]) and at 34 weeks’ gestation A1C values ?7.0% (moderate: 3.27 [1.31–8.20] and poor: 8.01 [2.04–31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks’ gestation, and at 34 weeks’ gestation were 0.88 (0.75–1.03), 0.75 (0.64–0.88), 0.57 (0.42–0.78), and 0.47 (0.31–0.70), respectively. Glycemic control was not significantly associated with gestational hypertension. CONCLUSIONS Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.

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



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

Microsoft Academic Search

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

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



Evaluation of Serum Calcium, Magnesium, Copper, and Zinc Levels in Women with Pre-eclampsia  

Microsoft Academic Search

Background: Pre-eclampsia along with its complications seems to be one of the major causes of maternal morbidity and mortality. Despite numerous studies, the etiology of pre- eclampsia has not yet been fully elucidated. According to re- cent studies changes in the level of blood trace elements can be an adverse event in human and animal pregnancy. The pre- sent study

Sariyeh Golmohammad



Cytomegalovirus infection in association with early onset pre-eclampsia  

PubMed Central

This case describes a woman who presented with raised ?-fetoprotein (AFP) on second trimester screening, and developed early onset fetal growth restriction (FGR) and severe pre-eclampsia (PET) before 24 weeks' gestation requiring magnesium sulphate and intravenous antihypertensives. Ultrasonography revealed a structurally normal fetus with estimated weight <3rd centile, abnormal uterine artery Dopplers and deteriorating fetal arterial Dopplers over the following 2 weeks. The pregnancy ended in fetal death before a viable weight was reached. Postmortem examination revealed a growth restricted fetus (birth weight <0.4th centile) and chronic villitis secondary to placental cytomegalovirus (CMV) infection. CMV has previously been associated with PET and FGR. This case highlights its potential role in the pathogenesis of placental failure and has relevance for counselling and management for future pregnancies. Furthermore, raised AFP may represent ongoing placental damage and offers potential for future therapeutic measures—for example, antivirals or immunisations to alter the natural history and prognosis of placental infection.

Higgins, L; Vause, S; Tower, C



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


A retrospective case-control study was conducted to investigate the risk factors for pre-eclampsia - including the protective effect of placenta previa - at Medani Maternity Hospital, Sudan. Medical files of the patients during the period 2003-2010 were reviewed for age, parity, education level, prenatal care, placenta previa, and hemoglobin level. Women with pre-eclampsia were the cases, and women with normal pregnancy were the controls. There were 54,339 singleton deliveries and 1765 women with pre-eclampsia in the hospital, giving the incidence of pre-eclampsia of 3.2%. The risk factors for pre-eclampsia were; women with age >35?years (OR?=?1.4, 95% CI: 1.1-1.8), primiparity (OR?=?3.3, 95% CI: 2.7-4.0), para >5 (OR?=?3.1, 95% CI: 2.4-4.0), and anemia (OR?=?3.3, 95% CI: 2.8-3.9). The risk of pre-eclampsia was inversely increased with education level and prenatal care attendance. The prevalence of placenta previa was 0 (0%) and 55 (3.3%), P?pre-eclampsia (OR?=?0.3, 95% CI: 0.1-0.7). Although, the socio-demographic risk factors for pre-eclampsia observed among women at Medani hospital were similar to those found in other settings; placenta previa was associated with decreased incidence of pre-eclampsia. PMID:23450096

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



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

Microsoft Academic Search

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

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



Severe pre-eclampsia and HELLP syndrome after massive fetomaternal hemorrhage following blunt abdominal trauma  

Microsoft Academic Search

Severe pre-eclampsia and HELLP syndrome developed within 24h after a 31year old nulliparous woman suffered a blunt abdominal trauma with massive fetomaternal hemorrhage and fetal intracranial bleeding. This is the first case reported of fulminating pre-eclampsia and HELLP syndrome following maternal exposure to a large amount of fetal cells and\\/or fetal cell debris as DNA or microparticles.

V. J. Faber; F. J. Klumper; S. Scherjon; W. J. van Wijngaarden



Syncytiotrophoblast Microvesicles Released from Pre-Eclampsia Placentae Exhibit Increased Tissue Factor Activity  

PubMed Central

Background Pre-eclampsia is a complication of pregnancy associated with activation of coagulation. It is caused by the placenta, which sheds increased amounts of syncytiotrophoblast microvesicles (STBM) into the maternal circulation. We hypothesized that STBM could contribute to the haemostatic activation observed in pre-eclampsia. Methodology/Principal Findings STBM were collected by perfusion of the maternal side of placentae from healthy pregnant women and women with pre-eclampsia at caesarean section. Calibrated automated thrombography was used to assess thrombin generation triggered by STBM-borne tissue factor in platelet poor plasma (PPP). No thrombin was detected in PPP alone but the addition of STBM initiated thrombin generation in 14/16 cases. Pre-eclampsia STBM significantly shortened the lag time (LagT, P?=?0.01) and time to peak thrombin generation (TTP, P?=?0.005) when compared to normal STBM. Blockade of tissue factor eliminated thrombin generation, while inhibition of tissue factor pathway inhibitor significantly shortened LagT (p?=?0.01) and TTP (P<0.0001), with a concomitant increase in endogenous thrombin potential. Conclusions/Significance STBM triggered thrombin generation in normal plasma in a tissue factor dependent manner, indicating that TF activity is expressed by STBM. This is more pronounced in STBM shed from pre-eclampsia placentae. As more STBM are shed in pre-eclampsia these observations give insight into the disordered haemostasis observed in this condition.

Gardiner, Chris; Tannetta, Dionne S.; Simms, Carol A.; Harrison, Paul; Redman, Christopher W. G.; Sargent, Ian L.



Cytomegalovirus infection in association with early onset pre-eclampsia.  


This case describes a woman who presented with raised ?-fetoprotein (AFP) on second trimester screening, and developed early onset fetal growth restriction (FGR) and severe pre-eclampsia (PET) before 24 weeks' gestation requiring magnesium sulphate and intravenous antihypertensives. Ultrasonography revealed a structurally normal fetus with estimated weight <3rd centile, abnormal uterine artery Dopplers and deteriorating fetal arterial Dopplers over the following 2 weeks. The pregnancy ended in fetal death before a viable weight was reached. Postmortem examination revealed a growth restricted fetus (birth weight <0.4th centile) and chronic villitis secondary to placental cytomegalovirus (CMV) infection. CMV has previously been associated with PET and FGR. This case highlights its potential role in the pathogenesis of placental failure and has relevance for counselling and management for future pregnancies. Furthermore, raised AFP may represent ongoing placental damage and offers potential for future therapeutic measures--for example, antivirals or immunisations to alter the natural history and prognosis of placental infection. PMID:22789552

Higgins, L; Vause, S; Tower, C



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

PubMed Central

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

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



Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia  

PubMed Central

Pre-eclampsia is a common serious disorder of human pregnancy, which is associated with significant maternal and perinatal morbidity and mortality. The suspected aetiology of pre-eclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Recently, we reported significant linkage to chromosome 2q22 in 34 Australian/New Zealand (Aust/NZ) pre-eclampsia/eclampsia families, and activin A receptor type IIA (ACVR2A) was identified as a strong positional candidate gene at this locus. In an attempt to identify the putative risk variants, we have now comprehensively re-sequenced the entire coding region of the ACVR2A gene and the conserved non-coding sequences in a subset of 16 individuals from these families. We identified 45 single nucleotide polymorphisms (SNPs), with 9 being novel. These SNPs were genotyped in our total family sample of 480 individuals from 74 Aust/NZ pre-eclampsia families (including the original 34 genome-scanned families). Our best associations between ACVR2A polymorphisms and pre-eclampsia were for rs10497025 (P = 0.025), rs13430086 (P = 0.010) and three novel SNPs: LF004, LF013 and LF020 (all with P = 0.018). After correction for multiple hypothesis testing, none of these associations reached significance (P > 0.05). Based on these data, it remains unclear what role, if any, ACVR2A polymorphisms play in pre-eclampsia risk, at least in these Australian families. However, it would be premature to rule out this gene as significant associations between ACVR2A SNPs and pre-eclampsia have recently been reported in a large Norwegian (HUNT) population sample.

Fitzpatrick, E.; Johnson, M.P.; Dyer, T.D.; Forrest, S.; Elliott, K.; Blangero, J.; Brennecke, S.P.; Moses, E.K.



Secular trends in the epidemiology of pre-eclampsia throughout 40 years in Norway: prevalence, risk factors and perinatal survival.  


Pre-eclampsia is a leading complication of pregnancy, associated with maternal and neonatal morbidity. The present study describes the epidemiology of pre-eclampsia in Norway, with data from the Medical Birth Registry of Norway, covering 40 years. We aimed at describing time trends in prevalence, selected risk factors and perinatal mortality. We also analysed time trends in recurrence risk of total pre-eclampsia and pre-eclampsia with preterm delivery. A total of 2,416,501 women giving birth during 1967-2008 were included. Prevalence of pre-eclampsia increased from 1967 to 1999 and decreased thereafter, with an overall prevalence of 3%. Rates increased more over time among younger than older women, resulting in a significantly lower excess risk of pre-eclampsia associated with high maternal age in later years. For example, relative risk (RR) of pre-eclampsia among primiparae aged ?35 relative to <25 years changed from 2.4 [95% confidence interval (CI) 2.1, 2.7] in 1967-1976 to 1.2 [95% CI 1.1, 1.3] in 1999-2008. For recurrence risk, subsequent pregnancies to a mother were linked, with the mother being the unit of analysis. Recurrence risk of pre-eclampsia was high, particularly recurrence of preterm pre-eclampsia, with overall RR close to 50 of a second pregnancy with pre-eclampsia and preterm birth compared with women without pre-eclampsia in first pregnancies. Finally, stillbirth associated with pre-eclampsia decreased more than neonatal mortality over time, and in the last 5 years only a moderate excess risk of stillbirth and neonatal death was observed. PMID:22471678

Klungsøyr, Kari; Morken, Nils Halvdan; Irgens, Lorentz; Vollset, Stein Emil; Skjaerven, Rolv



The human tumor-associated antigen RCAS1 in pregnancies complicated by pre-eclampsia.  


The human tumor-associated antigen RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is considered to play a role in the escape of tumor cells from immune surveillance and, at the same time, participates in the inhibition of the maternal immune response during pregnancy. The aim of our study was to investigate the expression of tumor-associated RCAS1 protein in the placenta and amniotic membranes and to assess and compare its concentration in amniotic fluid, maternal and cord blood sera in pregnancies complicated by pre-eclampsia. Samples were obtained from women with pre-eclampsia (N=9), pre-eclampsia with IUGR (N=4), normotensive IUGR (N=7) and healthy term controls (N=25) after delivery. Placentas were studied by immunohistochemistry, Western blot analysis and real-time (RT)-PCR. For assessment of RCAS1 protein concentrations in biological fluids, ELISA was performed. RCAS1 mRNA expression in the placentas of pre-eclamptic patients was significantly lower than in controls (p<0.01). The maternal blood serum RCAS1 protein concentration in the pre-eclampsia cases was also significantly lower than in controls (p=0.0207). The other study groups did not differ significantly. This study reveals the possible role of the RCAS1 protein in the development of pre-eclampsia through an immunological pathway. PMID:17604121

Tskitishvili, E; Komoto, Y; Kinugasa, Y; Kanagawa, T; Song, M; Mimura, K; Tomimatsu, T; Kimura, T; Shimoya, K



The management of pre-eclampsia: what we think we know.  


The focus of this article is to review and challenge some current concepts surrounding the diagnosis and management of pre-eclampsia as well as considering where our management might head in the future. Pre-eclampsia is a syndrome defined by the new onset of hypertension in the 2nd half of pregnancy that is generally, but not always, accompanied by proteinuria. Whilst in recent times our understanding and management of this condition have improved there are some areas where evidence and opinions differ. In this review we will discuss the diagnosis of pre-eclampsia and the concept of the 'atypical' presentation. We will outline how to identify those women with pre-eclampsia who will have a poorer pregnancy outcome. We will address the question of when to deliver and how to treat if we decide to prolong the pregnancy. Finally we acknowledge that pre-eclampsia is more than a disorder of pregnancy and has lifelong implications for the mother and infant. PMID:22036739

Pettit, Franziska; Brown, Mark A



The expression and concentration of CD40 ligand in normal pregnancy and pre-eclampsia.  


This study investigated the surface expression of the CD154 antigen (CD40L) on peripheral blood CD4+ T lymphocytes and the sera concentrations of soluble CD40L antigens (sCD40L) in non-pregnant women, normal pregnant women, and patients with pre-eclampsia. Twenty-five patients with pre-eclampsia, 18 healthy pregnant women, and 10 healthy non-pregnant women were included in the study. The expression of the CD154 antigen on CD4+ T lymphocytes was determined using flow cytometry. The serum concentration of sCD40L was measured using an ELISA. Statistical analysis was performed using the Mann-Whitney U and ANOVA tests. The expression of the CD154 antigen on CD4+ T lymphocytes and the serum concentration of soluble CD40L were significantly higher in pre-eclampsia than in normal pregnant women. In normal pregnancy the expression of the CD154 antigen on CD4+ T lymphocytes and the concentration of sCD40L were significantly lower than in non-pregnant women. We conclude that during normal pregnancy the levels of these inflammatory mediators are lower than in non-pregnant women. In pre-eclampsia the levels are higher than those in normal pregnancy, but stable compared with the non-pregnant state. These results suggest that in pre-eclampsia, there are disturbances in the mechanisms responsible for the decrease in innate immunity which occurs in normal pregnancy. PMID:19201484

Darmochwal-Kolarz, D; Kolarz, B; Surdacka, A; Rolinski, J; Leszczynska-Gorzelak, B; Oleszczuk, J



Disentangling Fetal and Maternal Susceptibility for Pre-Eclampsia: A British Multicenter Candidate-Gene Study  

PubMed Central

The Genetics of Pre-Eclampsia (GOPEC) collaboration aims to identify genetic factors in U.K. families affected by pre-eclampsia. A number of genetic studies have reported associations with pre-eclampsia, but attempts to replicate these findings have yielded inconsistent results. We describe the results of extensive genotyping of seven candidate genes previously reported as conferring susceptibility to pre-eclampsia. Six hundred fifty-seven women affected by pre-eclampsia and their families were genotyped at 28 single-nucleotide polymorphisms in the genes encoding angiotensinogen, the angiotensin receptors, factor V Leiden variant, methylene tetrahydrofolate reductase, nitric oxide synthase, and TNF?. Genotypes were analyzed by the transmission/disequilibrium test. Genotype risk ratios (GRRs) associated with maternal genotypes had a range of 0.70–1.16; GRRs associated with fetal genotypes had a range of 0.72–1.11. No GRR achieved the prespecified criteria for statistical significance (posterior probability >.05). We conclude that none of the genetic variants tested in this large study of strictly defined pre-eclamptic pregnancies confers a high risk of disease. The results emphasize the importance of conducting rigorously designed studies of adequate size to provide precise genetic risks with narrow confidence intervals, if overreporting of false-positive results is to be avoided.



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.

Williams, Paula J.; Broughton Pipkin, Fiona



GRP78 as a marker of pre-eclampsia: an exploratory study.  


Although the exact mechanisms that lead to shallow invasion or defective trophoblastic differentiation in pre-eclampsia are still unknown, it is widely admitted that the etiology of pre-eclampsia is a defect in trophoblast invasion of the uterine spiral arteries. We have previously observed that the status of a chaperone protein, glucose regulated protein 78 (GRP78) is associated with the invasive properties of cytotrophoblastic cells; we therefore hypothesized that circulating GRP78 could serve as a diagnostic tool in pre-eclampsia. In a prospective case-control study, we quantified GRP78 autoantibodies, complexes of GRP78 with autoantibodies and GRP78 (C-term fragment, N-term fragment and full-length GRP78) by ELISA. Plasma from women diagnosed with pre-eclampsia (n = 16), from women during the first trimester of pregnancy who subsequently developed pre-eclampsia (n = 10) and from healthy pregnant women (controls, n = 58 at term, n = 26 at first trimester) were analysed and compared. We observed no significant difference between pre-eclamptic and healthy pregnant women for autoantibodies-GRP78 complexes or total GRP78 at both first trimester and at delivery. In contrast, the ratio of C-terminal GRP78 over full length GRP78 was significantly different in plasma of pre-eclamptic patients as compared with controls both during first trimester (P < 0.004) and at term (P < 0.0001). Our findings suggest that circulating C-terminal GRP78 reflect the invasive properties of cells, and could be used as a predictive marker for pre-eclampsia early in pregnancy. PMID:19482905

Laverrière, A; Landau, R; Charvet, I; Irion, O; Bischof, P; Morales, M; Cohen, M



Malaria and pre-eclampsia in an area with unstable malaria transmission in Central Sudan  

PubMed Central

Background Placental malaria and pre-eclampsia occur frequently in women in tropics and are leading causes of maternal and perinatal morbidities and mortality. Few data exist concerning the interaction between placental malaria and pre-eclampsia. Methods A case control study was conducted in Medani Hospital, which locates in an area of unstable malaria transmission in Central Sudan. Case (N = 143) were women with pre-eclampsia, which was defined as systolic blood presure?140 mm Hg or diastolic blood pressure ? 90 mm Hg and proteinuria. Controls were parturient women (N = 143) without any blood pressure values > 139/89 mm Hg or proteinuria. Obstetrical and medical characteristics were gathered from both groups through structured questionnaires. Placental histopathology examinations for malaria were performed. Results Twenty-eight (19.6%) vs. 16 (11.2%); P = 0.04 of the cases vs. controls, had placental malaria infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae showed acute, chronic and past infection on histopathology examination in the two groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no infection, P = 0.04. In multivariate analysis, while there were no associations between age, parity, educational level, lack of antenatal care, blood groups and body mass index and pre-eclampsia; family history of hypertension and placental malaria (OR = 2.3, 95% CI = 1.0-5.2; P = 0.04) were significantly associated with pre-eclampsia. Conclusion Placental malaria was associated with pre-eclampsia. Further research is needed.



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



The relationship of serum vitamin D with pre-eclampsia in the Iranian women.  


Vitamin D deficiency may be a risk factor for negative outcome in pregnancy, such as pre-term labour, low birthweight, intrauterine growth retardation and gestational diabetes. This study aimed to evaluate the relationship between vitamin D and pre-eclampsia. This was a case-control study of 59 pre-eclamptic women and 59 healthy pregnant women selected in two hospitals in Ahvaz, Iran. Women with term singleton pregnancy, nulliparous and of reproductive age were selected. Venous blood samples (2?mL) were taken and the level of 25-dihydroxy vitamin D (25-OH-D) was measured. If the levels of 25-OH-D were less than 10?ng?mL(-1) , between 10?ng?mL(-1) and 29?ng?mL(-1) and more than 30?ng?mL(-1) , they were considered as indicating deficient, insufficient and normal 25-OH-D concentrations, respectively. The independent t-test, Mann-Whitney U-test, chi-square and logistic regression were used for analysing the data. Vitamin D deficiency was significantly higher in the pre-eclampsia group [odds ratio (OR)?=?24.04, confidence interval (CI)?=?2.10-274.8, P?=?0.01]. Older women (30-35 years) were more likely to develop pre-eclampsia compared with the control group (OR?=?10.36, CI?=?2.18-49.09, P?=?0.003). The results showed that women with body mass index (BMI) <20 were more likely to develop pre-eclampsia. The ages between 20 years and 30 years and normal BMI were not the risk factors for pre-eclampsia. Vitamin D deficiency has a statistically significant relationship with pre-eclampsia. It seems that the serum vitamin D levels are low in Iranian women because of their particular lifestyle and they may need more than 400?IU day(-1) vitamin D supplement during pregnancy. PMID:23782626

Abedi, Parvin; Mohaghegh, Zainab; Afshary, Poorandokht; Latifi, Mahmood



A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia  

Microsoft Academic Search

Objective: To determine if aspirin (ASA) therapy reduces the incidence of pre-eclampsia in women at high risk of this condition. Study design: Randomised clinical trial. We recruited pregnant women with gestational age at randomisation <14 weeks, who satisfied the following criteria: chronic hypertension, history of severe pre-eclampsia or eclampsia or intrauterine growth retardation (IUGR) or intrauterine foetal death. Nineteen women

Francesca Chiaffarino; Fabio Parazzini; Dario Paladini; Barbara Acaia; Wally Ossola; Luca Marozio; Fabio Facchinetti; Antonio Del Giudice



What Is the Place of Genetics in the Pathogenesis of Pre-Eclampsia?  

Microsoft Academic Search

It is most unlikely that there is a single ‘pre-eclampsia (PE) gene’. We are probably looking for a cluster of polymorphisms which, possibly in conjunction with environmental factors, predispose to the development of the condition. Accurate phenotyping is vital for any genetic studies of PE, and since the disease is only clinically-detectable in the second half of pregnancy, is particularly

F. Broughton Pipkin



How should women with pre-eclampsia be followed up? New insights from mechanistic studies  

Microsoft Academic Search

Understanding of the maternal syndrome of pre-eclampsia has greatly improved over the past 5 years. Specifically, the notion has emerged that the placenta is a source of antiangiogenic factors, such as soluble fms-like tyrosine kinase 1, that can progressively impair the mother's vascular and glomerular function throughout pregnancy. This impairment can be harmless during normal pregnancy, but in cases of

Suzanne Watnick; Helena Strevens; Henri Boulanger; Nadia Berkane; Eric Rondeau; Alexandre Hertig



Cardiovascular risk factor assessment after pre-eclampsia in primary care  

Microsoft Academic Search

BACKGROUND: Pre-eclampsia is associated with an increased risk of development of cardiovascular disease later in life. It is not known how general practitioners in the Netherlands care for these women after delivery with respect to cardiovascular risk factor management. METHODS: Review of medical records of 1196 women in four primary health care centres, who were registered from January 2000 until

Marie-Elise Nijdam; Monique R Timmerman; Arie Franx; Hein W Bruinse; Mattijs E Numans; Diederick E Grobbee; Michiel L Bots



Tests for predicting complications of pre-eclampsia: A protocol for systematic reviews  

PubMed Central

Background Pre-eclampsia is associated with several complications. Early prediction of complications and timely management is needed for clinical care of these patients to avert fetal and maternal mortality and morbidity. There is a need to identify best testing strategies in pre eclampsia to identify the women at increased risk of complications. We aim to determine the accuracy of various tests to predict complications of pre-eclampsia by systematic quantitative reviews. Method We performed extensive search in MEDLINE (1951–2004), EMBASE (1974–2004) and also will also include manual searches of bibliographies of primary and review articles. An initial search has revealed 19500 citations. Two reviewers will independently select studies and extract data on study characteristics, quality and accuracy. Accuracy data will be used to construct 2 × 2 tables. Data synthesis will involve assessment for heterogeneity and appropriately pooling of results to produce summary Receiver Operating Characteristics (ROC) curve and summary likelihood ratios. Discussion This review will generate predictive information and integrate that with therapeutic effectiveness to determine the absolute benefit and harm of available therapy in reducing complications in women with pre-eclampsia.

Thangaratinam, Shakila; Coomarasamy, Arri; Sharp, Steve; O'Mahony, Fidelma; O'Brien, Shaughn; Ismail, Khaled MK; Khan, Khalid S



Maternal ethnicity and pre-eclampsia in New York City, 1995-2003.  


Studies on ethnic differences in the risk of pre-eclampsia are limited. We linked birth records for 902,460 singleton births for the period 1995-2003 in New York City with hospital discharge data to evaluate the association between ethnicity and the risk of pre-eclampsia and compare risks between US-born and foreign-born women. Logistic regression models adjusted for maternal age, maternal education, parity, self-reported pre-pregnancy maternal weight, smoking during pregnancy and year of delivery were used to compare each ethnic group with non-Hispanic White women. The prevalence of pre-eclampsia in this study population was 3.2%. Among the major ethnic groups considered in our study, East Asian women had the lowest risk of pre-eclampsia (1.4%) and Mexican women had the highest risk (5.0%). Compared with non-Hispanic White women, there was a slightly decreased risk for East Asian women (adjusted OR = 0.8, [95% CI 0.7, 0.8]), similar risk for North African women (adjusted OR = 1.1, [95% CI 0.9, 1.3]), and increased risk for all other major ethnic groups (adjusted ORs: 1.3, 2.9), with the highest risk for Mexican women (adjusted OR = 2.9, [95% CI 2.7, 3.1]). No difference in risks was observed for US- vs. foreign-born women with the exception that foreign-born South-East Asian and Pacific Islanders had an increased risk of pre-eclampsia (adjusted OR = 1.8, [95% CI 1.0, 3.1]) relative to those born in the US. We concluded that there was ethnic heterogeneity in the development of pre-eclampsia among women in New York City and that Asian subgroups should be examined separately in future studies on ethnicity. Our results should contribute to screening for pre-eclampsia taking ethnic variation into account, and may help to suggest leads for the study of the aetiology of the condition. PMID:22150707

Gong, Jian; Savitz, David A; Stein, Cheryl R; Engel, Stephanie M



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

PubMed Central

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



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

PubMed Central

Objective To assess the effectiveness and safety of antiplatelet drugs for prevention of pre-eclampsia and its consequences. Design Systematic review. Data sources Register of trials maintained by Cochrane Pregnancy and Childbirth Group, Cochrane Controlled Trials Register, and Embase. Included studies Randomised trials involving women at risk of pre-eclampsia, and its complications, allocated to antiplatelet drug(s) versus placebo or no antiplatelet drug. Main outcomes measures Pre-eclampsia, preterm birth, fetal or neonatal death, and small for gestational age baby. Studies were assessed for quality of concealment of allocation and losses to follow up. Results 39 trials (30?563 women) were included, and 45 trials (>3000 women) excluded. Use of antiplatelet drugs was associated with a 15% reduction in the risk of pre-eclampsia (32 trials, 29?331 women; relative risk 0.85, 95% confidence interval 0.78 to 0.92; number needed to treat 100, 59 to 167). There was also an 8% reduction in the risk of preterm birth (23 trials, 28?268 women; 0.92, 0.88 to 0.97; 72, 44 to 200), and a 14% reduction in the risk of fetal or neonatal death (30 trials, 30?093 women; 0.86, 0.75 to 0.98; 250, 125 to >10?000) for women allocated antiplatelet drugs. Small for gestational age babies were reported in 25 trials (20?349 women), with no overall difference between the groups (relative risk 0.92, 0.84 to 1.01). There were no significant differences in other measures of outcome. Conclusions Antiplatelet drugs, largely low dose aspirin, have small to moderate benefits when used for prevention of pre-eclampsia.

Duley, Lelia; Henderson-Smart, David; Knight, Marian; King, James



Blood pressure rises more in pre-eclampsia than normal pregnancy when acral skin is locally cooled.  


Objective: Investigate blood pressure response to acral skin vasoconstriction in healthy and pre-eclamptic pregnancies. Methods: Healthy women were investigated from gestational week 8 to 52 weeks postpartum and pre-eclampsia subjects at diagnosis. Finger artery ultrasound Doppler, forearm laser Doppler fluximetry and photoplethysmographic blood pressure were recorded. Hand cooling to 19?°C induced vasoconstriction. Results: Acral skin vasoconstriction increases blood pressure from 16 weeks until 12 weeks postpartum (p???0.01), with greatest responses in pre-eclampsia (p?=?0.047). Forearm skin perfusion is higher in pre-eclampsia (p?=?0.04). Conclusion: Acral skin vasoconstriction raises blood pressure in pregnancy, particularly in pre-eclampsia. Pregnancy accentuates important functional differences within skin. PMID:23844619

Hartgill, T W; Pirhonen, J



Biomarkers for the management of pre-eclampsia in pregnant women  

PubMed Central

Pre-eclampsia (PE) is a pregnancy related disorder characterized by hypertension and proteinuria noticeable after 20 wk of gestation. It is a leading cause of maternal and foetal mortality and morbidity worldwide. The aetiology of the disease is unknown, but recent studies have revealed that this disorder appears to originate in placenta and is characterized by widespread maternal endothelial dysfunction. Till date, delivery of placenta is the only cure for the disease. So, there is a need for the identification of highly specific and sensitive biochemical markers that would allow early identification of patients at risk and thus help in providing proper prenatal care. Several promising biomarkers have been proposed, alone or in combination, that may help in predicting women who are likely to develop PE. Maternal serum concentrations of these biomarkers either increase or decrease in PE during gestation. This review focuses on the various biomarkers available and their utility in predicting pre-eclampsia.

Petla, Lakshmi Tanuja; Chikkala, Rosy; Ratnakar, K.S.; Kodati, Vijayalakshmi; Sritharan, V.



Glutathione and Glutathione-related Enzymes in Decidua and Placenta of Controls and Women with Pre-eclampsia  

Microsoft Academic Search

Pre-eclampsia is a major complication of pregnancy with high morbidity and mortality rates. The aetiology is still unclear but impaired detoxification or enhanced levels of reactive (oxygen) metabolites may contribute to the development or maintenance of pre-eclampsia. Glutathione and glutathione-related enzymes, as one of the major detoxificating and free-radical scavenging systems, may play a role in controlling the disease.Seventeen normotensive

M. F. C. M Knapen; W. H. M Peters; T. P. J Mulder; H. M. W. M Merkus; J. B. M. J Jansen; E. A. P Steegers



Contribution of PARP to endothelial dysfunction and hypertension in a rat model of pre-eclampsia  

PubMed Central

BACKGROUND AND PURPOSE Under conditions of increased oxidative stress, such as pre-eclampsia and diabetes, overstimulation of PARP leads to endothelial dysfunction. Inhibition of PARP has been demonstrated to reverse the vascular dysfunction associated with diabetes in vivo. The present study was carried out to investigate the role of PARP in mediating the endothelial dysfunction associated with pre-eclampsia. EXPERIMENTAL APPROACH Uteroplacental perfusion was surgically reduced in pregnant rats to produce the reduced uterine perfusion pressure (RUPP) rat model of pre-eclampsia and the PARP inhibitor, PJ34, was administered either before or after surgery. Mean arterial BP and vascular function were measured in normal pregnant (NP) and both control and PJ34-treated RUPP rats. Mesenteric vessels from NP rats were incubated with either 3% RUPP or NP plasma alone or in combination with PJ34. Finally, immunohistochemical staining was carried out to measure nitrotyrosine (byproduct of peroxynitrite) immunoreactivity. KEY RESULTS RUPP rats were characterized by hypertension, fetal growth restriction and endothelial dysfunction when compared with NP rats. PJ34 administered in vivo before, but not after, surgery prevented the development of both endothelial dysfunction and hypertension. RUPP plasma-induced impaired vasorelaxation was prevented following co-incubation with PJ34 in vitro. Furthermore, the protective effect of PARP inhibition in vivo was accompanied by a reduction in nitrotyrosine immunoreactivity. CONCLUSIONS AND IMPLICATIONS PJ34 prevented the development of both endothelial dysfunction and hypertension and reduced vascular nitrotyrosine immunoreactivity, thus suggesting a role for oxidative–nitrosative stress/PARP activation in the aberration in both vascular and haemodynamic function in this rat model of pre-eclampsia.

Walsh, SK; English, FA; Crocker, IP; Johns, EJ; Kenny, LC



Myeloid and lymphoid dendritic cells in normal pregnancy and pre-eclampsia  

PubMed Central

The aim of our study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c+, BDCA-2+) and the CD1c+ : BDCA-2+ ratio in normal pregnant women and in patients with pre-eclampsia. Fifteen women in the first, second and third trimesters of normal pregnancy, and 25 patients with pre-eclampsia were included in the study. The dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies against blood dendritic cell antigens (anti-CD1c, anti-BDCA-2) and estimated using the flow cytometric method. CD1c+ and BDCA-2+ dendritic cells were present in women during all trimesters of physiological pregnancy and in pre-eclamptic patients. It was observed that the numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, CD1c+ : BDCA-2+ ratio was higher than in the other trimesters of physiological pregnancy. All populations of dendritic cells and CD1c+ : BDCA-2+ ratio did not differ in the first and third trimesters of normal pregnancy. The percentage of BDCA-2+ dendritic cells was significantly lower in pre-eclampsia in comparison with healthy women in the third trimester of physiological pregnancy, while CD1c+ : BDCA-2+ ratio was significantly higher in pre-eclamptic patients when compared with control groups. We concluded that dendritic cells may be involved in the immune regulation during physiological pregnancy. CD1c+ and BDCA-2+ cells can influence the Th2 phenomenon which is observed during physiological pregnancy. Furthermore, it seems possible that lower BDCA-2+ cells percentage and higher CD1c+ : BDCA-2+ ratio can be associated with increased Th1-type immunity in patients with pre-eclampsia.




Magnesium taurate for the prevention and treatment of pre-eclampsia\\/eclampsia  

Microsoft Academic Search

The use of parenteral magnesium sulfate for the management of preeclampsia\\/eclampsia is well established. In striking analogy to the effects of hypermagnesemia, taurine has antivasospastic, anti hypertensive, platelet-stabilizing, anticonvulsant and hypoxia-protective properties. Thus parenteral magnesium taurate can reasonably be proposed as a superior alternative to magnesium sulfate in the treatment of pre-eclampsia; administered orally as a component of prenatal supplementation,

M. F. McCarty



Does vitamin D supplementation in infancy reduce the risk of pre-eclampsia?  

Microsoft Academic Search

Vitamin D has been suggested to affect the balance between T helper (Th1) and (Th2) type cytokines by favouring Th2 domination. We investigated the association between infant vitamin D supplementation and later pre-eclampsia, a disorder suggested to be dominated by Th1 response. We used data on 2969 women born in the Northern Finland Birth Cohort 1966 of whom 68 (2.3%)

E Hyppönen; A-L Hartikainen; U Sovio; M-R Järvelin; A Pouta



Differential placental caveolin-1 gene expression in women with pre-eclampsia  

Microsoft Academic Search

BackgroundPre-eclampsia (PE) affects 2–7% of pregnant women and is thought to be associated with structural\\/functional alterations in the placental and maternal vasculature. The main component of caveolae, caveolin-1 (Cav-1) has been shown to be associated with important modulators of cardiovascular homeostasis, such as endothelial nitric oxide synthase. The possible regulation of vascular reactivity and blood pressure by the caveolae are

H D Mistry; A N Czajka; L O Kurlak; F Broughton Pipkin; M J Taggart; R T Tribe



Bilateral permanent concentric visual field defect secondary to severe pre-eclampsia  

PubMed Central

Purpose To present a patient with bilateral permanent concentric visual field defect secondary to severe pre-eclampsia. Case report A forty-year-old woman presented to the ophthalmology department with partial visual field defect affecting her both eyes. She gave a history of emergent uterine curettage for severe uncontrolled pre-eclampsia in the 24th week of her second gestation which was 10 years before. Two days after the procedure, the patient complained of peripheral visual field defect in her both eyes which persisted until her last presentation. Her best-corrected visual acuity, color vision, intraocular pressures, and anterior segment examination findings were normal bilaterally. Fundus examination showed a normal optic nerve head with reduction of arteriole to vein ratio in both eyes. Humphrey Field Analyzer revealed a bilateral concentric visual field defect. Visual Evoked Potentials (VEP) and Electroretinography (ERG) were within normal limits in both eyes. Cranial magnetic resonance imaging (MRI) was normal. Discussion Herein, we presented a case of permanent concentric visual field defect which developed as a complication of severe uncontrolled pre-eclampsia. To the best of our knowledge; such a case has not been reported to date.

Citirik, Mehmet; Simsek, Tulay; Zilelioglu, Orhan



The role of intravenous volume expansion in moderate pre-eclampsia.  


We examined the hemodynamic and hemorheological effects of intravenous volume expansion in women with pre-eclampsia. 20 untreated women with moderate pre-eclampsia were randomized to receive a 500 ml infusion over 4 h of either hydroxyethylstarch (HAES steril 10%, HES) or NaCl 0.9% solution. After completion of the infusion trial all patients received oral antihypertensive drugs, bed rest and free sodium and water intake. The hemodynamic responses were measured by impedance cardiography. Hemorheological parameters and blood pressure were measured before and after (24 h later) infusion. The HES infusion but not NaCl leads to a significant reduction of hematocrit and erythrocyte aggregation. In addition to that there was a nonsignificant increase of the cardiac index in the HES-group but no changes in the heart rate. Intravenous volume expansion in women with pre-eclampsia with a long acting colloid like hydroxyethylstarch is associated with a significant influence on the flow properties (hematocrit and erythrocyte aggregation) of blood. PMID:11847411

Heilmann, L; Gerhold, S; von Tempelhoff, G F; Pollow, K



Decreased expression of apelin in placentas from severe pre-eclampsia patients.  


Objective: It is well documented that anti-angiogenic factors are likely to play essential roles in the etiology of pre-eclampsia. Apelin is a small peptide that may potentially act as an angiogenic factor. The expression of apelin was examined at the RNA and protein levels in this study. Methods: We compared the expression of apelin, examined using quantitative reverse-transcription polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay and immunostaining, between pre-eclamptic patients and normotensive controls. Results: Apelin messenger RNA is significantly decreased in pre-eclamptic placentas compared with normotensive pregnancies (p?pre-eclampsia patients. Immunohistochemical signals for apelin and its receptor APJ were detected mainly in the cytoplasm of syncytiotrophoblasts in chorionic villi and trophoblast-lineage cells in the decidua of term placentas. In early gestation, stronger APJ signals were observed at the cellular membrane. Conclusions: A functional role of the apelin--APJ system is likely in early gestation, and this raises the possibility that a dysfunctional apelin--APJ system contributes to the onset of pre-eclampsia via decreased angiogenic activity in placental implantation. PMID:23844873

Inuzuka, Hiromi; Nishizawa, Haruki; Inagaki, Ayaka; Suzuki, Machiko; Ota, Sayuri; Miyamura, Hironori; Miyazaki, Jun; Sekiya, Takao; Kurahashi, Hiroki; Udagawa, Yasuhiro



Effect of Vitamin E on sP-Selectin Levels in Pre-Eclampsia.  


P-selectin, a cell adhesion molecule is elevated in many inflammatory conditions including preeclampsia which is characterized by generalized endothelial dysfunction and vasoconstriction presumably due to free radicals or mediators released by defective placentation. Vitamin E has been documented to protect cell membranes from oxidative damage and also decrease platelet aggregation. The role of vitamin E in pre-eclampsia is contradictory and hence the study was undertaken. Soluble P-selectin was measured by ELISA and Vitamin-E levels in plasma was estimated spectrofluorometrically. In our study the effect of supplementation of 400 IU/day of Vitamin E (a-tocopheryl acetate) to patients of pre-eclampsia showed significant decreased levels of soluble P-selectin by 2nd week as compared to patients given placebo (P = 0.005). In this short period of study no direct correlations were observed between Vitamin E or P-selectin levels with blood pressure as well as with proteinuria. Future studies may focus on the effect of a-tocopheryl acetate or the phosphate form of Vitamin-E, recently proposed to be the more active form on other inflammatory markers like IL-6, an important stimuli of P-selectin release in pre-eclampsia. PMID:22468044

Wangkheimayum, Sujata; Kumar, Sunil; Suri, Vanita



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.

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



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


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

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



Altered plasma neurokinin B levels in patients with pre-eclampsia  

Microsoft Academic Search

Objective(s)  This study determines the levels of Neurokinin B (NKB) in the plasma of South African coloured pregnant women with and without\\u000a pre-eclampsia (PE) and correlates these results with clinical data. Additionally, the peptide radioimmunoassay (RIA) and peptide\\u000a enzyme immunoassay (EIA) methods were compared in the determination of the Neurokinin B levels, using 58 samples from patients\\u000a with PE.\\u000a \\u000a \\u000a \\u000a Methods  At the

Verena Geissbuehler; Rene Moser; Kathrin Zimmermann; Renate Hillermann; Janusz Czarniecki; Stefan G. Gebhardt; Jakob Eberhard



Helicobacter pylori's virulence and infection persistence define pre-eclampsia complicated by fetal growth retardation  

PubMed Central

AIM: To better understand the pathogenic role of Helicobacter pylori (H. pylori) in pre-eclampsia (PE), and whether it is associated or not with fetal growth retardation (FGR). METHODS: Maternal blood samples were collected from 62 consecutive pregnant women with a diagnosis of PE and/or FGR, and from 49 women with uneventful pregnancies (controls). Serum samples were evaluated by immunoblot assay for presence of specific antibodies against H. pylori antigens [virulence: cytotoxin-associated antigen A (CagA); ureases; heat shock protein B; flagellin A; persistence: vacuolating cytotoxin A (VacA)]. Maternal complete blood count and liver enzymes levels were assessed at delivery by an automated analyzer. RESULTS: A significantly higher percentage of H. pylori seropositive women were found among PE cases (85.7%) compared to controls (42.9%, P < 0.001). There were no differences between pregnancies complicated by FGR without maternal hypertension (46.2%) and controls. Importantly, persistent and virulent infections (VacA/CagA seropositive patients, intermediate leukocyte blood count and aspartate aminotransferase levels) were exclusively associated with pre-eclampsia complicated by FGR, while virulent but acute infections (CagA positive/VacA negative patients, highest leukocyte blood count and aspartate aminotransferase levels) specifically correlated with PE without FGR. CONCLUSION: Our data strongly indicate that persistent and virulent H. pylori infections cause or contribute to PE complicated by FGR, but not to PE without feto-placental compromise.

Cardaropoli, Simona; Rolfo, Alessandro; Piazzese, Annalisa; Ponzetto, Antonio; Todros, Tullia



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


Cerebrovascular accidents are not rare during pregnancy and the postpartum period. Pre-eclampsia is a common condition that is characterized by proteinuria and de novo hypertension that may be complicated by hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Spontaneous cervical artery dissection has been rarely reported in the postpartum period but never in association with HELLP syndrome. We describe a case of pre-eclampsia and HELLP syndrome complicated in the postpartum period by bilateral thalamic infarct as result of left vertebral artery dissection. We speculated about the possible common etiopathologic mechanisms involved in this previously unreported association. PMID:22341668

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



Antihypertensive therapy in patients with pre-eclampsia: A prospective randomised multicentre study comparing dihydralazine with urapidil  

Microsoft Academic Search

BackgroundDrug treatment is imperative for pregnant women with pregnancy-induced hypertension (PIH) and pre-eclampsia. For more than 40 years, dihydralazine has been the drug of choice for this indication. Another particularly effective and better tolerable antihypertensive is urapidil. Yet only a few studies on limited patient collectives have been published on the clinical experience with urapidil in PIH.

Juergen R. Wacker; Barbara K. Wagner; Volker Briese; Burkhard Schauf; Lothar Heilmann; Clemens Bartz; Hartmut Hopp



Apoptosis Signaling Is Altered in CD4+CD25+FoxP3+ T Regulatory Lymphocytes in Pre-Eclampsia  

PubMed Central

The aim of our study was to estimate the surface expressions of CD95 (APO-1/Fas) antigen and the intracellular expressions of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in CD4+CD25+FoxP3+ T regulatory lymphocytes (Tregs) as well as the percentage of CD8+CD28+ T cytotoxic cells in peripheral blood of patients with pre-eclampsia in comparison with healthy pregnant women in the third trimester of physiological pregnancy. Twenty-four women with pre-eclampsia and 20 normal third trimester pregnant women were included in the study. The lymphocytes were isolated from peripheral blood samples and labeled with monoclonal antibodies. The expressions of surface antigens and intracellular proteins were estimated using flow cytometry. The population of CD4+CD25+FoxP3+ Treg cells was significantly lower in peripheral blood of patients with pre-eclampsia when compared to normal third trimester pregnant women. The percentages of CD4+CD25+FoxP3+ Treg cells that express Bcl-2 protein were significantly lower in peripheral blood of patients with pre-eclampsia when compared to healthy pregnant women, whereas the percentages of CD4+CD25+FoxP3+ Treg cells with the expressions of Bax protein did not differ in both groups. Moreover, the mean fluorescence intensity (MFI) of Bcl-2 protein in CD4+CD25+FoxP3+ Treg cells was significantly lower and MFI of Bax protein significantly higher in pre-eclampsia when compared to the control group. The percentage of CD8+CD28+ T cells did not differ in both studied groups but MFI of CD28 antigen on T CD8+ cells was significantly higher in pre-eclampsia when compared to the control group. The obtained results suggest that the deficit of CD4+CD25+FoxP3+ Treg lymphocytes which is observed in pre-eclampsia may be associated with altered apoptosis signaling in Tregs.

Darmochwal-Kolarz, Dorota; Saito, Shigeru; Tabarkiewicz, Jacek; Kolarz, Bogdan; Rolinski, Jacek; Leszczynska-Gorzelak, Bozena; Oleszczuk, Jan



Apoptosis Signaling Is Altered in CD4(+)CD25(+)FoxP3(+) T Regulatory Lymphocytes in Pre-Eclampsia.  


The aim of our study was to estimate the surface expressions of CD95 (APO-1/Fas) antigen and the intracellular expressions of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in CD4(+)CD25(+)FoxP3(+) T regulatory lymphocytes (Tregs) as well as the percentage of CD8(+)CD28(+) T cytotoxic cells in peripheral blood of patients with pre-eclampsia in comparison with healthy pregnant women in the third trimester of physiological pregnancy. Twenty-four women with pre-eclampsia and 20 normal third trimester pregnant women were included in the study. The lymphocytes were isolated from peripheral blood samples and labeled with monoclonal antibodies. The expressions of surface antigens and intracellular proteins were estimated using flow cytometry. The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in peripheral blood of patients with pre-eclampsia when compared to normal third trimester pregnant women. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells that express Bcl-2 protein were significantly lower in peripheral blood of patients with pre-eclampsia when compared to healthy pregnant women, whereas the percentages of CD4(+)CD25(+)FoxP3(+) Treg cells with the expressions of Bax protein did not differ in both groups. Moreover, the mean fluorescence intensity (MFI) of Bcl-2 protein in CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower and MFI of Bax protein significantly higher in pre-eclampsia when compared to the control group. The percentage of CD8(+)CD28(+) T cells did not differ in both studied groups but MFI of CD28 antigen on T CD8(+) cells was significantly higher in pre-eclampsia when compared to the control group. The obtained results suggest that the deficit of CD4(+)CD25(+)FoxP3(+) Treg lymphocytes which is observed in pre-eclampsia may be associated with altered apoptosis signaling in Tregs. PMID:22837649

Darmochwal-Kolarz, Dorota; Saito, Shigeru; Tabarkiewicz, Jacek; Kolarz, Bogdan; Rolinski, Jacek; Leszczynska-Gorzelak, Bozena; Oleszczuk, Jan



Association of pre-eclampsia with the R563Q mutation of the beta-subunit of the epithelial sodium channel.  


The R563Q mutation of the beta-subunit of the epithelial sodium channel (ENaC) is associated with hypertension in black and mixed ancestry (MA) men and women in South Africa. The frequency of the R563Q mutation in black and MA women with pre-eclampsia (n= 230) and in controls (n= 198) was studied. The R563Q mutation was found in 7.8% of the women with pre-eclampsia and in 2.6% of controls (P= 0.014). This remained significant if the black women were analysed separately (P= 0.031). We have demonstrated that a genetic variant of the ENaC is associated with pre-eclampsia. This has implications for understanding the pathogenesis and treatment of pre-eclampsia. PMID:16579800

Dhanjal, M K; Owen, E P; Anthony, J A; Davidson, J S; Rayner, B L



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

SciTech Connect

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

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



Endothelial nitric oxide synthase gene polymorphism (Glu298Asp) and development of pre-eclampsia: a case-control study and a meta-analysis  

Microsoft Academic Search

BACKGROUND: Pre-eclampsia is thought to have an important genetic component. Recently, pre-eclampsia has been associated in some studies with carriage of a common eNOS gene Glu298Asp polymorphism, a variant that leads to the replacement of glutamic acid by aspartic acid at codon 298. METHOD: Healthy women with singleton pregnancies were recruited from 7 district general hospitals in London, UK. Women

Christina KH Yu; Juan P Casas; Makrina D Savvidou; Manpreet K Sahemey; Kypros H Nicolaides; Aroon D Hingorani



The Glu298Asp variant of the endothelial nitric oxide synthase gene is associated with an increased risk for abruptio placentae in pre-eclampsia  

Microsoft Academic Search

Attempts to define a pre-eclampsia susceptibility profile have been hampered by the wide clinical spectrum of the condition and the complex genetics underlying it. Genes that modulate blood pressure, fluid homeostasis and placental vascular development have been considered plausible candidates. Among these are the angiotensinogen (AGT) gene variant Met235Threo, which has been associated with pre-eclampsia and the endothelial nitric oxide

Renate Hillermann; Kashefa Carelse; G. Stefan Gebhardt



Semicarbazide-sensitive amine oxidase in pre-eclampsia: no relation with markers of endothelial cell activation  

Microsoft Academic Search

Background: Semicarbazide sensitive amine-oxidase (SSAO) is an adhesion molecule and thought to play a role in endothelial cell dysfunction (ECD). SSAO has never been associated with markers of ECD. Pre-eclampsia (PE) is, like the early stages of atherosclerosis, characterised by ECD. SSAO could contribute to ECD in PE. Methods: Plasma samples were obtained in 14 pre-eclamptic patients and 14 matched

J. Marko Sikkema; Arie Franx; Rob Fijnheer; Peter G. J Nikkels; Hein W Bruinse; Frans Boomsma



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

Microsoft Academic Search

Objectives To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated.Design Prospective multicentre cohort.Setting Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland.Participants 3572 “healthy” nulliparous women with a singleton pregnancy

Robyn A North; Lesley M E McCowan; Gustaaf A Dekker; Lucilla Poston; Eliza H Y Chan; Alistair W Stewart; Michael A Black; Rennae S Taylor; James J Walker; Philip N Baker; Louise C Kenny



The concentrations of soluble HLA-G protein are elevated during mid-gestation and decreased in pre-eclampsia.  


The aim of our study was to investigate the dynamics of the alterations of soluble human leukocyte antigen-G (sHLA-G) concentrations in sera of healthy non-pregnant women, as well as healthy pregnant women and patients with pre-eclampsia. Thirty five patients with pre-eclampsia, 52 healthy pregnant women, and 24 healthy non-pregnant women were included in the study. Sera concentrations of sHLA-G protein were determined using the immunoenzymatic ELISA method. Statistical analysis was performed using ANOVA and Mann-Whitney U tests. The concentrations of sHLA-G protein in sera of pregnant women in the first, as well as the second and third, trimesters of normal pregnancy were significantly higher in comparison with healthy nonpregnant women. The sera concentrations of sHLA-G in pregnant women in the second trimester of pregnancy were significantly higher compared to the first and third trimesters. The concentrations of sHLA-G in sera of patients with pre-eclampsia were significantly lower than in pregnant women in the third trimester of physiological pregnancy. The results of our study suggest that normal physiological pregnancy is associated with elevated sera concentrations of sHLA-G molecule. The increased concentrations of sHLA-G molecule in mid-gestation could suggest a role for the protein in the second phase of a physiological invasion of extravillous cytotrophoblast to spiral arteries. Furthermore, the results could suggest a role for the decreased sera concentrations of sHLA-G in the pathogenesis of pre-eclampsia. PMID:22763960

Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Rolinski, Jacek; Leszczynska-Gorzelak, Bozena; Oleszczuk, Jan



Placental CLIC3 is increased in fetal growth restriction and pre-eclampsia affected human pregnancies.  


Chloride intracellular channel (CLIC) proteins constitute a subgroup of the glutathione-S-transferase (GSTs) superfamily. In humans, the CLIC family of proteins consists of six members, designated CLIC 1-6, which have a conserved C-terminal 240 residue module and one major transmembrane domain. CLIC proteins regulate fundamental cellular processes including regulation of chloride ion concentration, stabilization of cell membrane potential, trans-epithelial transport, regulation of cell volume and stimulation of apoptotic processes in response to cellular stress. Previously, we described the expression profile of a member of the CLIC family of proteins, CLIC3, in human placentae and fetal membranes. In the current study, we determined CLIC3 expression in placentae from pregnancies complicated with either fetal growth restriction (FGR, n=19), pre-eclampsia (PE, n=16) or both FGR and PE combined (n=12) compared to gestation-matched controls (n=13) using real-time PCR and a CLIC3 specific immunoassay. Significantly increased CLIC3 mRNA and protein were detected in placental extracts from pregnancies with FGR, PE and PE with FGR compared to controls. Our results suggest that increased expression of CLIC3 may play a role in abnormal placental function associated with the human pregnancy disorders FGR and PE. PMID:22795578

Murthi, P; Stevenson, J L; Money, T T; Borg, A J; Brennecke, S P; Gude, N M



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

PubMed Central

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

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



Maternal hepatitis B surface antigen status and incidence of pre-eclampsia.  


The relationship between chronic hepatitis B virus (HBV) infection with atherosclerosis and cardiovascular disorders remains unclear, and the impact of maternal HBV infection on the development of pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) is also controversial. This retrospective cohort study was conducted to examine the relationship between maternal hepatitis B surface antigen (HBsAg) status with PIH and PE in singleton pregnancies that delivered at 24 weeks of gestation and beyond. Among the 86 537 cases in the cohort, 10% were HBsAg positive, and overall 2.0% had PIH, of whom 56.3% developed PE. HBsAg-positive women had higher weight and body mass index (BMI), but lower incidences of advanced age, nulliparity, PIH (1.6% vs 2.0%, P = 0.007) and PE (0.8% vs 1.1%, P = 0.005). On multiple logistic regression analysis adjusting for the effects of nulliparity, advanced age, high BMI, and underlying renal, cardiac and autoimmune diseases, HBsAg carriage was associated with significantly reduced incidence of PIH (aOR 0.79, 95% CI 0.66-0.95) and PE (aOR 0.71, 95% CI 0.56-0.91). Our results indicate that maternal HBsAg carriage is independently associated with reduced PE. As chronic HBV infection alters the immune response of the individual, our observation could be related to enhanced maternal immunotolerance of the foetus and hence a reduction in the incidence of PE. The implications of our findings on the long-term health outcome of the infected women, from cardiovascular morbidity to malignancies, warrant further studies. PMID:23565617

Lao, T T; Sahota, D S; Cheng, Y K Y; Law, L W; Leung, T Y



Promoter hypomethylation of TIMP3 is associated with pre-eclampsia in a Chinese population.  


A study by Yuen RK, Penaherrera MS, von Dadelszen P, McFadden DE, Robinson WP. DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia. Eur J Hum Genet 2010;18:1006-1012 based on a Canadian population found the tissue inhibitor of the metalloproteinase 3 (TIMP3) gene to be hypomethylated in pre-eclampsia (PE) placentas and to be a potential prenatal marker for early onset PE. To further explore the role of TIMP3 in PE and to investigate whether the TIMP3 promoter shows the same methylation pattern in the Han Chinese population, we analyzed a complete methylation assay of TIMP3 including the promoter region studied in the Canadian report and the neighboring CpG island in placentas (cases n = 41, controls n = 22) maternal peripheral blood (cases n = 3; controls n = 6) and umbilical cord blood (cases n = 7; controls n = 8) using MassArray EpiTyper (Sequenom, San Diego, CA, USA). Our results confirmed the finding of aberrant TIMP3 promoter methylation in PE placentas (mean = 0.405) compared with those in controls (mean = 0.534, P = 9.40 × 10(-7)). A tissue-specific methylation pattern between placentas (mean = 0.459) and bloods (mean = 0.961, P = 6.91 × 10(-13)) was also demonstrated in our clinical samples. Furthermore, a nearly 2-fold increase in TIMP3 expression for the hypomethylated promoter was found in PE placentas (P = 0.007), pointing to a negative relationship between TIMP3 methylation and the expression (R = -0.758, P = 0.029). In conclusion, we replicated the findings of Yuen et al. in our Han Chinese-based study, confirming that TIMP3 is likely to be involved in the etiology of PE and that hypomethylated and placenta-specific TIMP3 may be a potential marker for early diagnosis of PE in maternal plasma. PMID:23172037

Xiang, Yuqian; Zhang, Xiaojing; Li, Qiaoli; Xu, Jiawei; Zhou, Xinyao; Wang, Teng; Xing, Qinghe; Liu, Yun; Wang, Lei; He, Lin; Zhao, Xinzhi



eNOS Deficiency Acts through Endothelin to Aggravate sFlt-1-Induced Pre-Eclampsia-Like Phenotype  

PubMed Central

Excess soluble fms-like tyrosine kinase 1 (sFlt-1) of vascular endothelial growth factor receptor 1 secreted from the placenta causes pre-eclampsia–like features by antagonizing vascular endothelial growth factor signaling, which can lead to reduced endothelial nitric oxide synthase (eNOS) activity; the effect of this concomitant decrease in eNOS activity is unknown. We tested whether the decrease in nitric oxide occurring in female mice lacking eNOS aggravates the pre-eclampsia–like phenotype induced by increased sFlt-1. Untreated eNOS-deficient female mice had higher BP than wild-type mice. Adenovirus-mediated overexpression of sFlt-1 increased systolic BP by approximately 27 mmHg and led to severe loss of fenestration of glomerular capillary endothelial cells in both eNOS-deficient and wild-type mice. However, only the eNOS-deficient sFlt-1 mice exhibited severe foot process effacement. Compared with wild-type sFlt-1 mice, eNOS-deficient sFlt-1 mice also showed markedly higher urinary albumin excretion (467±74 versus 174±23 ?g/d), lower creatinine clearance (126±29 versus 452±63 ?l/min), and more severe endotheliosis. Expression of preproendothelin-1 (ET-1) and its ETA receptor in the kidney was higher in eNOS-deficient sFlt-1 mice than in wild-type sFlt-1 mice. Furthermore, the selective ETA receptor antagonist ambrisentan attenuated the increases in BP and urinary albumin excretion and ameliorated endotheliosis in both wild-type and eNOS-deficient sFlt-1 mice. Ambrisentan improved creatinine clearance and podocyte effacement in eNOS-deficient sFlt-1 mice. In conclusion, reduced maternal eNOS/nitric oxide exacerbates the sFlt1-related pre-eclampsia–like phenotype through activation of the endothelin system.

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



Work activities and risk of prematurity, low birthweight and pre-eclampsia: an updated review with meta-analysis  

PubMed Central

Objectives We assessed the evidence relating pre-term delivery (PTD), low birthweight, small for gestational age (SGA), pre-eclampsia and gestational hypertension to five occupational exposures (working hours, shift work, lifting, standing and physical workload). We conducted a systematic search in MEDLINE and EMBASE (1966–2011), updating a previous search with a further six years of observations. Methods As before, combinations of keywords and MeSH terms were used. Each relevant paper was assessed for completeness of reporting and potential for important bias or confounding, and its effect estimates abstracted. Where similar definitions of exposure and outcome existed we calculated pooled estimates of relative risk in meta-analysis. Results Analysis was based on 86 reports (32 cohort investigations, 57 with usable data on PTD, 54 on birthweight and 11 on pre-eclampsia/gestational hypertension); 33 reports were new to this review. For PTD, findings across a substantial evidence base were generally consistent, effectively ruling out large effects (e.g. RR>1.2). Larger and higher quality studies were less positive, while meta-estimates of risk were smaller than previously and best estimates pointed to modest or null effects (RR 1.04 to 1.18). For SGA, the position was similar but meta-estimates were even closer to the null (eight of nine RRs ? 1.07). For pre-eclampsia/gestational hypertension the evidence base remains insufficient. Conclusions The balance of evidence is against large effects for the associations investigated. As the evidence base has grown, estimates of risk in relation to these outcomes have become smaller.

Palmer, Keith T; Bonzini, Matteo; Harris, E Clare; Linaker, Cathy; Bonde, Jens Peter



E-cadherin in the assessment of aberrant placental cytotrophoblast turnover in pregnancies complicated by pre-eclampsia  

Microsoft Academic Search

E-cadherin is a cell–cell adhesion protein expressed in cytotrophoblasts, which is lost as they differentiate and syncytialise.\\u000a We have exploited E-cadherin as a marker of cytotrophoblasts to investigate villous tissue composition in first and third\\u000a trimester placentae, both in normal pregnancy and pregnancies complicated by pre-eclampsia. We have achieved this by measuring\\u000a expression levels of E-cadherin at the mRNA level,

L. M. Brown; H. A. Lacey; P. N. Baker; I. P. Crocker



Proportion of peripheral blood and decidual CD4+ CD25bright regulatory T cells in pre-eclampsia  

PubMed Central

CD4+ CD25bright regulatory T (Treg) cells have been identified as a principle regulator of tolerance during pregnancy. In the setting of pre-eclampsia, however, little is known about the dynamics of these cells. In the current study, we determined CD4+ CD25bright Treg cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3+) cells at the placental bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC) of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non-pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were included. We found the percentage of CD25bright cells within the CD4+ T cell population in PBMC was reduced significantly in both Japanese and Polish pre-eclamptic cases than in normal pregnancy subjects (P < 0·001) and non-pregnant healthy controls (P < 0·001). Also, the percentage of FoxP3+ cells within CD3+ T cells in the placental bed biopsy samples of pre-eclamptic cases were decreased compared to those in normal pregnancy subjects. These findings suggest that a decreased number of Treg cells was present in pre-eclampsia, and these changes might break the maternal tolerance to the fetus.

Sasaki, Y; Darmochwal-Kolarz, D; Suzuki, D; Sakai, M; Ito, M; Shima, T; Shiozaki, A; Rolinski, J; Saito, S



Role of progesterone in TLR4-MyD88-dependent signaling pathway in pre-eclampsia.  


The role of progesterone in the Toll-like receptor 4 (TLR4)-MyD88-dependent signaling pathway in pre-eclampsia was studied. Peripheral blood mononuclear cells (PBMCs) from pre-eclampsia (PE) patients were subjected to primary culture, and stimulated with different concentrations of progesterone (0, 10(-8), 10(-6), and 10(-4) mol/L). The mRNA expression of TLR4, MyD88 and nuclear factor-kappaB (NF-?B) was detected by using real-time PCR. The Ikappa-B protein expression was detected by using Western blotting. The expression of tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in the supernatant was determined by using ELISA. With the concentrations of progesterone increasing, the mRNA expression levels of TLR4, MyD88 and NF-?B in 2(-??CT) value were significantly decreased, and the IkappaB protein expression levels were significantly increased. The TNF-? and IL-6 expression showed a downward trend when the progesterone concentration increased, and there were significant differences among all of the groups (P<0.05). It was suggested that progesterone can inhibit the TLR4-MyD88-dependent signaling pathway in PE significantly and benefit for the pregnancy. PMID:24142728

Zhu, Ying; Wu, Min; Wu, Chao-Ying; Xia, Ge-Qing



A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia.  


Placental trophoblasts (TBs) invade and remodel uterine vessels with an arterial bias. This process, which involves vascular mimicry, re-routes maternal blood to the placenta, but fails in pre-eclampsia. We investigated Notch family members in both contexts, as they play important roles in arterial differentiation/function. Immunoanalyses of tissue sections showed step-wise modulation of Notch receptors/ligands during human TB invasion. Inhibition of Notch signaling reduced invasion of cultured human TBs and expression of the arterial marker EFNB2. In mouse placentas, Notch activity was highest in endovascular TBs. Conditional deletion of Notch2, the only receptor upregulated during mouse TB invasion, reduced arterial invasion, the size of maternal blood canals by 30-40% and placental perfusion by 23%. By E11.5, there was litter-wide lethality in proportion to the number of mutant offspring. In pre-eclampsia, expression of the Notch ligand JAG1 was absent in perivascular and endovascular TBs. We conclude that Notch signaling is crucial for TB vascular invasion. PMID:21693515

Hunkapiller, Nathan M; Gasperowicz, Malgorzata; Kapidzic, Mirhan; Plaks, Vicki; Maltepe, Emin; Kitajewski, Jan; Cross, Jay C; Fisher, Susan J



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


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



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.

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



Antiplatelet agents for prevention of pre-eclampsia and its consequences: a systematic review and individual patient data meta-analysis The Perinatal Antiplatelet Review of International Studies (PARIS) Collaboration Steering Group on behalf of the PARIS Collaboration* and The  

Microsoft Academic Search

Background: There is now good evidence that antiplatelet agents (principally low dose aspirin) prevent pre-eclampsia, a leading cause of morbidity and mortality for pregnant women and their babies. A Cochrane Review identified moderate, but clinically important, reductions in the relative risks of pre-eclampsia (19%), preterm birth (7%) and perinatal mortality (16%) in women allocated antiplatelets, rather than placebo or no


eNOS deficiency acts through endothelin to aggravate sFlt-1-induced pre-eclampsia-like phenotype.  


Excess soluble fms-like tyrosine kinase 1 (sFlt-1) of vascular endothelial growth factor receptor 1 secreted from the placenta causes pre-eclampsia-like features by antagonizing vascular endothelial growth factor signaling, which can lead to reduced endothelial nitric oxide synthase (eNOS) activity; the effect of this concomitant decrease in eNOS activity is unknown. We tested whether the decrease in nitric oxide occurring in female mice lacking eNOS aggravates the pre-eclampsia-like phenotype induced by increased sFlt-1. Untreated eNOS-deficient female mice had higher BP than wild-type mice. Adenovirus-mediated overexpression of sFlt-1 increased systolic BP by approximately 27 mmHg and led to severe loss of fenestration of glomerular capillary endothelial cells in both eNOS-deficient and wild-type mice. However, only the eNOS-deficient sFlt-1 mice exhibited severe foot process effacement. Compared with wild-type sFlt-1 mice, eNOS-deficient sFlt-1 mice also showed markedly higher urinary albumin excretion (467±74 versus 174±23 ?g/d), lower creatinine clearance (126±29 versus 452±63 ?l/min), and more severe endotheliosis. Expression of preproendothelin-1 (ET-1) and its ET(A) receptor in the kidney was higher in eNOS-deficient sFlt-1 mice than in wild-type sFlt-1 mice. Furthermore, the selective ET(A) receptor antagonist ambrisentan attenuated the increases in BP and urinary albumin excretion and ameliorated endotheliosis in both wild-type and eNOS-deficient sFlt-1 mice. Ambrisentan improved creatinine clearance and podocyte effacement in eNOS-deficient sFlt-1 mice. In conclusion, reduced maternal eNOS/nitric oxide exacerbates the sFlt1-related pre-eclampsia-like phenotype through activation of the endothelin system. PMID:22282588

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



Comparison of neonatal outcome in women with severe pre-eclampsia undergoing caesarean section under spinal or general anaesthesia.  


Ideal method of anaesthesia during caesarean section in women with severe pre-eclampsia is difficult to decide. The aim and objective of the study were to compare neonatal outcome in women with severe pre-eclampsia, undergoing caesarean section in intrapartum period, either under general or spinal anaesthesia. Women with severe pre-eclampsia, undergoing caesarean section in intrapartum period, were included in the study. Diastolic blood pressure was kept below 100mm Hg by giving parenteral labetalol pre-operatively. All women received prophylactic magnesium sulphate (5g IV and 10g IM). Maternal blood- gas parameters were measured. Scalp blood pH estimation was done in all cases. Women undergoing caesarean section were randomised into two groups and received either spinal or general anaesthesia. Umbilical arterial catheterisation was done for collecting blood for estimating neonatal blood- gas parameters. Complete data was available in 82 women. Both the groups were comparable in terms of general demographic data, except that percentage of women having an induced labour was significantly more in the general anaesthesia group. Induction of anaesthesia and delivery interval was prolonged for the spinal group. Mean dose of phenylephrine was significantly higher for the spinal anaesthesia group. Preoperative maternal blood-gas parameters and foetal scalp blood pH were comparable in between groups. Difference in neonatal umbilical artery base deficit in between groups was not statistically significant (p = 0.99). Correlation coefficient between maternal base deficit and foetal base deficit was 0.414 (p = 0.01) and 0.06 (p > 0.1) respectively for general and spinal anaesthesia. Subgroup analysis in the population with pre-operative scalp blood pH < 7.2, neonatal umbilical artery base deficit was significantly higher in general anaesthesia group. Five minutes APGAR score was comparable but resuscitation at birth was more common in the general anaesthesia group. Correlation coefficient between maternal base deficit and foetal base deficit in this subgroup was 0.42 (p = 0.05) and -0.57 (p < 0.05) respectively for general and spinal anaesthesia. PMID:22010585

Dasgupta, Subhankar; Chakraborty, Barunoday; Saha, Debdas; Ghosh, Debdutta



Magnesium suflate is not used for pre-eclampsia and eclampsia in Mexico and Thailand as much as it should be  

Microsoft Academic Search

Objective In the past ten years effective treatments for pre-eclampsia and eclampsia have been evaluated and identified following large trials and systematic reviews. We investigated the extent of those effective interventions' implementation. Methods Descriptive analysis of data collected as part of a cluster randomized trial. The trial was assigned the International Standardised Randomized Controlled Trial Number ISRCTN 14055385. Hospitals with

Pisake Lumbiganon; A Metin Gülmezoglu; Gilda Piaggio; Jeremy Grimshawd



Effects of a Combination of Evening Primrose Oil (Gamma Linolenic Acid) and Fish Oil (Eicosapentaenoic + Docahexaenoic Acid) versus Magnesium, and versus Placebo in Preventing Pre-Eclampsia  

Microsoft Academic Search

In a placebo controlled, partially double-blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre-Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension

Arminda DAlmeida; James P. Carter; A. Anatol; Claude Prost



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

PubMed Central

Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. Design Randomised, blinded, placebo controlled clinical trial. Setting Tertiary public hospital in Mexico City. Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy. Main outcome measure Development of pre-eclampsia/eclampsia. Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (?2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (?2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14). Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846.



Inhibin, activin, follistatin, activin receptors and beta-glycan gene expression in the placental tissue of patients with pre-eclampsia.  


The objective of this study was to quantify the relative expression of inhibin alpha, inhibin/activin beta(A), beta(B), beta(C), follistatin, activin receptors and beta-glycan genes in placental tissue of term pre-eclamptic patients and controls to investigate if these genes are up-regulated in the placenta in pre-eclampsia. Seven women with pre-eclampsia symptoms were matched with 10 normal pregnant controls for gestational age, maternal age, and parity. Total RNA was isolated from each sample. Complementary DNA samples produced by reverse transcription were used in the real time PCR to quantify the expression of inhibin alpha subunit, inhibin/activin beta(A), beta(B), beta(C) subunits, follistatin, ACTRIA, ACTRIB, ACTRIIA, ACTRIIB, beta-glycan and GAPDH genes. The ratio between the target and GAPDH expression was calculated to provide relative gene expression. Inhibin alpha:GAPDH and inhibin/activin beta(A): GAPDH ratios were significantly higher in placental tissue from women with pre-eclampsia (P = 0.04 and P = 0.01 respectively) compared with matched control placental gene expression. Placental samples from both groups expressed beta(B), beta(C), follistatin, activin receptors and beta-glycan genes. However, there was no significant difference in the relative expression of these genes between the groups. Increases in the placental expression of inhibin alpha and inhibin/activin beta(A) subunit genes could contribute to the rise in circulating levels of inhibin A and activin A in pre-eclampsia. The mechanism(s) involved in increased gene expression in pre-eclampsia is as yet unclear. PMID:12651901

Casagrandi, D; Bearfield, C; Geary, J; Redman, C W; Muttukrishna, S



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

PubMed Central

Summary Background Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes. Methods We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (?-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045. Findings Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0·81, 95% CI 0·59–1·12). No adverse maternal or neonatal outcomes were reported. Interpretation Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing. Funding The Wellcome Trust.

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



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

PubMed Central

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

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



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


In this study we have investigated whether quantitative analysis of placental mRNAs in maternal plasma provides a way to monitor placental status. We measured plasma concentrations of human chorionic gonadotropin beta-subunit (betahCG) and human placental lactogen (hPL) mRNAs as previously reported mRNAs and pregnancy associated plasma protein A (PAPP-A), placenta-specific 1 (PLAC1) and glial cells-missing 1 (GCM1) mRNAs, which have not been measured during the course of normal pregnancy. Firstly, peripheral blood was obtained at various times from healthy pregnant women to clarify the time course of placental mRNAs. Secondly, blood was obtained from women with pre-eclampsia and gestational age-matched controls to examine whether placental mRNAs change in pre-eclampsia. Plasma was separated from these samples for extraction of RNA, followed by reverse transcription polymerse chain reaction analysis. Median concentrations of PLAC1 and GCM1 mRNA in plasma of pre-eclamptic subjects respectively were 1625 and 2141 copies/ml, significantly higher than 195 and 881 copies/ml, the values for controls (Mann-Whitney test, p<0.001). No significant difference was seen in hPL, betahCG, or PAPP-A mRNA concentration between pre-eclamptic and control groups. Plasma PLAC1 and GCM1 mRNAs appear promising as noninvasively measurable molecular markers for pre-eclampsia. PMID:16594548

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



Failure to up-regulate VEGF165b in maternal plasma is a first trimester predictive marker for pre-eclampsia  

PubMed Central

Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria and endothelial dysfunction. VEGF165b, formed by alternative splicing of VEGF (vascular endothelial growth factor) pre-mRNA, inhibits VEGF165-mediated vasodilation and angiogenesis, but has not been quantified in pregnancy. ELISAs were used to measure means±S.E.M. plasma VEGF165b, sEng (soluble endoglin) and sFlt-1 (soluble fms-like tyrosine kinase-1). At 12 weeks of gestation, the plasma VEGF165b concentration was significantly up-regulated in plasma from women who maintained normal blood pressure throughout their pregnancy (normotensive group, 4.90±1.6 ng/ml; P<0.01, as determined using a Mann-Whitney U test) compared with non-pregnant women (0.40±0.22 ng/ml). In contrast, in patients who later developed pre-eclampsia, VEGF165b levels were lower than in the normotensive group (0.467±0.209 ng/ml), but were no greater than non-pregnant women. At term, plasma VEGF165b concentrations were greater than normal in both pre-eclamptic (3.75±2.24 ng/ml) and normotensive (10.58 ng/ml±3.74 ng/ml; P>0.1 compared with pre-eclampsia) pregnancies. Patients with a lower than median plasma VEGF165b at 12 weeks had elevated sFlt-1 and sEng pre-delivery. Concentrations of sFlt-1 (1.20±0.07 and 1.27±0.18 ng/ml) and sEng (4.4±0.18 and 4.1±0.5 ng/ml) were similar at 12 weeks of gestation in the normotensive and pre-eclamptic groups respectively. Plasma VEGF165b levels were elevated in pregnancy, but this increase is delayed in women that subsequently develop pre-eclampsia. In conclusion, low VEGF165b may therefore be a clinically useful first trimester plasma marker for increased risk of pre-eclampsia.

Bills, Victoria L.; Varet, Julia; Millar, Ann; Harper, Steven J.; Soothill, Peter W.; Bates, David O.



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

PubMed Central

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

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



Association of Proteinuria Threshold in Pre-Eclampsia with Maternal and Perinatal Outcomes: A Nested Case Control Cohort of High Risk Women  

PubMed Central

Objectives To evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499mg and ?500mg/24 hours) in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension. Design Secondary analysis of the Vitamins in Pre-Eclampsia Trial. Setting 25 UK hospitals in ten geographical areas. Population 946 women with pre-existing risk factors for pre-eclampsia. Methods Women with pre-eclampsia and proteinuria 300-499mg/24h (PE300, referent group, n=60) or proteinuria ?500 mg/24h (PE500, n=161) were compared with two groups of non-proteinuric women with chronic hypertension (CHT, n=615) or gestational hypertension (GH, n=110). Main Outcome Measures Maternal: progression to severe hypertension. Perinatal: small for gestational age (SGA) <5th centile, gestation at delivery. Results Severe hypertension occurred more frequently in PE500 (35%) and PE300 (27%) than CHT (5.9%; P?0.01) and GH (10%; p?0.001). Gestation at delivery was earlier in PE500 (33.2w) than PE300 (37.3w; P?0.001), and later in CHT (38.3w; P?0.05) and GH (39.1w; P?0.001). SGA infants were more frequent in PE300 (32%) than in CHT (13.3%; P?0.001) and GH (16.5%; P?0.05). Women in PE500 were more likely to have a caesarean section than PE300 (78% vs. 48%; P?0.001), and to receive magnesium sulphate (17% vs. 1.7%, P?0.05). Conclusion Women with PE300 have complication rates above those of women managed as out-patients (GH and CHT), meriting closer surveillance and confirming 300 mg/d as an appropriate threshold for determining in-patient management. Adverse perinatal outcomes are higher still in women with PE500.

Seed, Paul T.; Briley, Annette L.; Poston, Lucilla; Shennan, Andrew H.; Chappell, Lucy C.



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.  


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



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

Microsoft Academic Search

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

P. K. Lala; C. Chakraborty



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



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


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

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



Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre-eclampsia at term? An exploratory analysis of the HYPITAT trial  

PubMed Central

Objective To examine whether cervical favourability (measured by cervical length and the Bishop score) should inform obstetricians’ decision regarding labour induction for women with gestational hypertension or mild pre-eclampsia at term. Design A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT). Setting Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands. Population A total of 756 women diagnosed with gestational hypertension or pre-eclampsia between 36 + 0 and 41 + 0 weeks of gestation randomly allocated to induction of labour or expectant management. Methods Data were analysed using logistic regression modelling. Main outcome measures The occurrence of a high-risk maternal situation defined as either maternal complications or progression to severe disease. Secondary outcomes were caesarean delivery and adverse neonatal outcomes. Results The superiority of labour induction in preventing high-risk situations in women with gestational hypertension or mild pre-eclampsia at term varied significantly according to cervical favourability. In women who were managed expectantly, the longer the cervix the higher the risk of developing maternal high-risk situations, whereas in women in whom labour was induced, cervical length was not associated with a higher probability of maternal high-risk situations (test of interaction P = 0.03). Similarly, the beneficial effect of labour induction on reducing the caesarean section rate was stronger in women with an unfavourable cervix. Conclusion Against widely held opinion, our exploratory analysis showed that women with gestational hypertension or mild pre-eclampsia at term who have an unfavourable cervix benefited more from labour induction than other women. Trial registration The trial has been registered in the clinical trial register as ISRCTN08132825.

Tajik, P; van der Tuuk, K; Koopmans, CM; Groen, H; van Pampus, MG; van der Berg, PP; van der Post, JA; van Loon, AJ; de Groot, CJM; Kwee, A; Huisjes, AJM; van Beek, E; Papatsonis, DNM; Bloemenkamp, KW; van Unnik, GA; Porath, M; Rijnders, RJ; Stigter, RH; de Boer, K; Scheepers, HC; Zwinderman, AH; Bossuyt, PM; Mol, BW



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.

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



LEPR c.668A>G polymorphism in a cohort of Sri Lankan women with pre-eclampsia / pregnancy induced hypertension: a case control study  

PubMed Central

Background Leptin is known to be elevated in pre-eclampsia/ pregnancy induced hypertension (PE/PIH). However the reports on the association of leptin receptor (LEPR) c.668A>G polymorphism with PE/PIH are inconsistent. Findings LEPR c.668A>G polymorphism was studied in a cohort of women with PE/PIH (N?=?61) and normotensive pregnancies (N?=?40) by polymerase chain reaction / restriction fragment length polymorphism. Genotype and allele frequencies were in Hardy-Weinberg equilibrium within both groups (Chi square test). Allele and genotype frequencies were not significantly different between PE/PIH and normotensive pregnancies (Chi square test). Leptin levels (Kruskal Wallis analysis of variance) and leptin/body mass index (one way analysis of variance) were not significantly different between genotypes within each group. However, leptin (Mann Whitney U test) and leptin normalised to body mass index (unpaired t test) were significantly higher in PE/PIH women homozygous and heterozygous for the G668 allele than in respective normotensives. Conclusions Whether the leptin receptor c.668A>G polymorphism increases the risk of developing PE/PIH in Sri Lankan women remains inconclusive in view of the smaller sample studied. However leptin levels in PE/PIH appeared to be modulated by this polymorphism.



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.

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



Pre-eclampsia and pregnancy-induced hypertension are associated with severe diabetic retinopathy in type 1 diabetes later in life.  


To investigate whether pre-eclampsia (PE) or pregnancy-induced hypertension (PIH) predicts the development of severe diabetic retinopathy (SDR) in type 1 diabetes. Altogether, 203 women with type 1 diabetes who were followed during pregnancy were re-examined within the Finnish Diabetic Nephropathy Study. After excluding patients with pre-pregnancy hypertension and those who had had laser treatment or whose retinopathy was graded as proliferative at the index pregnancy, 158 were prospectively studied. As a surrogate marker for SDR, retinal laser photocoagulation was used. The time from pregnancy to SDR (N = 21) or follow-up was 16 years (interquartile range, 11-19). HbA1c was repeatedly measured both during pregnancy and follow-up. Women with prior PE (26 % vs. 6 %, P = 0.003) or PIH (24 % vs. 6 %, P = 0.008) had more often incident SDR during follow-up compared to those with normotensive pregnancy. The hazard ratios (HR) remained associated with the progression to SDR after adjustment for duration of diabetes and diabetic nephropathy in a Cox regression analysis [PE: 3.5 (95 % CI 1.1-10.9); P = 0.03 and for PIH: 3.2 (1.1-9.8); P = 0.04]. The association between PIH and incident SDR did not change after inclusion of mean HbA1c, measured during pregnancy (all 3 trimesters) and serial HbA1c measurements during follow-up, 3.5 (1.1-11.8; P = 0.03). However, in a similar model, the HR for PE was no more significant 2.0 (0.6-6.8; P = NS). The results suggest that women with type 1 diabetes and a hypertensive pregnancy have an increased risk of severe diabetic retinopathy later in life. PMID:22955518

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



Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial  

PubMed Central

Background Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term. Methods/Design Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised. Discussion This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity. Trial Registration NTR1792 Clinical trial registration:



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

Microsoft Academic Search

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

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



Hemoconcentration and pre-eclampsia  

Microsoft Academic Search

Zusammenfassung Bei einem Patientengut von 155 unkomplizierten Schwangeren bestimmten wir die Erythrozytenaggregation unter normierten Bedingungen. Dabei wurde die physiologisch vorhandene Hämodilution in der Schwangerschaft berücksichtigt.

L. Heilmann; U. Siekmann; H. Schmid-Schönbein; H. Ludwig



The expression of B7-H1 and B7-H4 co-stimulatory molecules on myeloid and plasmacytoid dendritic cells in pre-eclampsia and normal pregnancy.  


The aim of our study was to estimate the expression of B7-H1 and B7-H4 molecules on myeloid and plasmacytoid dendritic cells (DCs) in the peripheral blood of patients with pre-eclampsia, normal pregnant women and healthy non-pregnant women. Thirty-three patients with pre-eclampsia, 26 normal pregnant women, and 12 healthy non-pregnant women were included in the study. Dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies against blood dendritic cell antigens and B7-H1 and B7-H4 molecules and estimated using flow cytometry. The expression of B7-H1 and B7-H4 molecules was significantly higher on CD1c(+) myeloid and CD303(+) plasmacytoid DCs in the first trimester of pregnancy than in the luteal phase of the ovarian cycle (CD1c(+)B7-H1(+): 19.19±10.55% vs. 11.99±6.79%; p<0.05; CD1c(+)B7-H4(+): 12.01±9.15% vs. 3.98±1.97%, p<0.001; CD303(+)B7-H1(+): 4.15±2.38% vs. 1.70±0.87%, p<0.05; CD303(+)B7-H4(+): 5.44±2.93% vs. 2.33±1.54%, p<0.01). Moreover, the expression of the B7-H1 molecule on CD1c(+) DCs in the second trimester of normal pregnancy was significantly higher than in the first trimester, but in the third trimester they decreased compared with the second trimester (II vs. I trimester: 32.23±11.30% vs. 19.19±10.55%, p<0.01; III vs. II trimester: 32.23±11.30% vs. 22.39±8.19%, p<0.01). The expression of B7-H1 molecule on CD1c(+) myeloid and CD303(+) plasmacytoid DCs was significantly lower in pre-eclampsia than in healthy third-trimester pregnant women (CD1c(+)B7-H1(+): 13.78±6.26% vs. 22.39±8.19%, p<0.05; CD303(+)B7-H1(+): 3.66±2.46% vs. 8.65±3.15%, p<0.01). Higher expressions of B7-H1 and B7-H4 molecules on CD1c(+) myeloid and CD303(+) plasmacytoid DCs in the first trimester of pregnancy suggest the role they play in the immunomodulation during early pregnancy. PMID:23773232

Darmochwal-Kolarz, Dorota; Kludka-Sternik, Magdalena; Kolarz, Bogdan; Chmielewski, Tomasz; Tabarkiewicz, Jacek; Rolinski, Jacek; Leszczynska-Gorzelak, B; Oleszczuk, Jan



Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis  

PubMed Central

Objective To determine the diagnostic accuracy of two “spot urine” tests for significant proteinuria or adverse pregnancy outcome in pregnant women with suspected pre-eclampsia. Design Systematic review and meta-analysis. Data sources Searches of electronic databases 1980 to January 2011, reference list checking, hand searching of journals, and contact with experts. Inclusion criteria Diagnostic studies, in pregnant women with hypertension, that compared the urinary spot protein to creatinine ratio or albumin to creatinine ratio with urinary protein excretion over 24 hours or adverse pregnancy outcome. Study characteristics, design, and methodological and reporting quality were objectively assessed. Data extraction Study results relating to diagnostic accuracy were extracted and synthesised using multivariate random effects meta-analysis methods. Results Twenty studies, testing 2978 women (pregnancies), were included. Thirteen studies examining protein to creatinine ratio for the detection of significant proteinuria were included in the multivariate analysis. Threshold values for protein to creatinine ratio ranged between 0.13 and 0.5, with estimates of sensitivity ranging from 0.65 to 0.89 and estimates of specificity from 0.63 to 0.87; the area under the summary receiver operating characteristics curve was 0.69. On average, across all studies, the optimum threshold (that optimises sensitivity and specificity combined) seems to be between 0.30 and 0.35 inclusive. However, no threshold gave a summary estimate above 80% for both sensitivity and specificity, and considerable heterogeneity existed in diagnostic accuracy across studies at most thresholds. No studies looked at protein to creatinine ratio and adverse pregnancy outcome. For albumin to creatinine ratio, meta-analysis was not possible. Results from a single study suggested that the most predictive result, for significant proteinuria, was with the DCA 2000 quantitative analyser (>2 mg/mmol) with a summary sensitivity of 0.94 (95% confidence interval 0.86 to 0.98) and a specificity of 0.94 (0.87 to 0.98). In a single study of adverse pregnancy outcome, results for perinatal death were a sensitivity of 0.82 (0.48 to 0.98) and a specificity of 0.59 (0.51 to 0.67). Conclusion The maternal “spot urine” estimate of protein to creatinine ratio shows promising diagnostic value for significant proteinuria in suspected pre-eclampsia. The existing evidence is not, however, sufficient to determine how protein to creatinine ratio should be used in clinical practice, owing to the heterogeneity in test accuracy and prevalence across studies. Insufficient evidence is available on the use of albumin to creatinine ratio in this area. Insufficient evidence exists for either test to predict adverse pregnancy outcome.



Changes observed in Doppler studies of the fetal circulation in pregnancies complicated by pre-eclampsia or the delivery of a small-for-gestational-age baby. I. Cross-sectional analysis.  


The aim of this study was to compare changes in Doppler ultrasound studies of the fetal circulation in normal pregnancies with a group of pregnancies complicated by proteinuric pregnancy-induced hypertension (PPIH), delivery of a small-for-gestational-age (SGA) baby, or both. A total of 167 uncomplicated pregnancies with a term delivery of an appropriately grown baby (AGA) were used to define the normal range. Altogether, 123 high-risk pregnancies with a known outcome constituted the study group. A color duplex ultrasound machine was used to perform biometry and fetal Doppler studies. Measurements obtained from the fetal circulation included the umbilical artery (UA) pulsatility index (PI), the middle cerebral artery (MCA) PI and time-averaged velocity (TAV), the thoracic aorta (AO) PI and TAV. In addition, the ratio between the MCA PI and UA PI, the MCA PI and the AO PI, and the product of the MCA PI and AO TAV were used in the analysis. A total of 105 pregnancies had a complicated outcome. They were divided into three categories: PPIH only (pregnancies complicated by PPIH with the delivery of an AGA fetus, n = 17), SGA only (delivery of an SGA baby, with no evidence of PPIH, n = 55), and PPIH + SGA (pregnancies complicated by pre-eclampsia and delivery of an SGA baby, n = 37). The PPIH + SGA group represented true clinical intrauterine growth retardation. Cross-sectional reference ranges were created using the observations from the normal group. z-scores (standard deviation from the mean of the normal range) of the last observations made before delivery were calculated for each of the vessel velocimetry measurements and ratios. The statistical significance of z-score values was calculated using analysis of variance. The MCA and UA PI values showed the greatest deviation for any single-vessel parameter. The ratios of fetal Doppler indices (MCA/UA PI ratio, MCA/AO PI ratio and the MCA PI/AO TAV index) demonstrated greater deviation from normal than any individual vessel. The UA PI z-score for PPIH+SGA delivering < 34 weeks gestation (2.92) was significantly greater than the z-score for PPIH+SGA delivering > or = 34 weeks (1.20, p < 0.05). Fetal Doppler indices, in particular ratios that include measurements obtained from the cerebral circulation, help in the recognition of the small fetus that is growth-retarded. At term, evidence of fetal hemodynamic redistribution may exist in the presence of a normal umbilical artery PI. Fetal Doppler indices provide information that is not readily obtained from more conventional tests of fetal well-being.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8528796

Harrington, K; Carpenter, R G; Nguyen, M; Campbell, S



Letter: Prostaglandins and pre-eclampsia.  


Professor Brosens and colleagues (April 27, p.808) questions the safety of prostaglandins (PGs) for the induction of labor when pregnancy is complicated by hypertensive states, especially preeclampsia. Objections are based on the possibility that the uteroplacental bloodflow, which may already be compromised in these situations, could be further reduced by vasoconstrictive effects of the PGs on uterine, placental, and umbilical vessels. We have been using PGs extensively in this department and for the past year have been carrying out a double-blind trial of PGE2 and oxytocin by intravenous infusion after amniotomy for induction of labor in primigravidae. In 23 of the patients included thus far, labor was induced between 36 and 38 weeks because of moderate or severe preeclampsia. Of these, 12 have received oxytocin and 11 PGE2. In all cases, elective epidural analgesia has been employed and continuous fetal heartrate and intrauterine pressure recordings performed throughout. 1 patient in the group required an emergency cesarean section because of fetal distress; 2 others (1 from each group) were delivered by cesarean section because of failure to progress in labor. The remainder delivered vaginally with no evidence of increased incidence of fetal distress in the PG group. No perinatal deaths occurred. In an additional 18 primigravidae labor was induced at 36-38 weeks because of hypertensive complications of pregnancy by local PGE2 administration as previously described. These patients were assessed as clinically unfavorable for induction. 2 patients developed fetal distress and required cesarean sections; the others delivered vaginally. Experience with PGF2alpha is much less extensive but there is no reason to believe that this compound would behave differently, except with regard to maternal side effects. Thus it seems beneficial to use PGs for inducing labor in pregnancies complicated by hypertension and preeclampsia; no evidence of the suggested theoretical hazards has been seen. The suggested dangers may be questioned on 2 bases. It seems premature, based on existing knowledge, to infer that spiral arteries in hypertensive pregnancies are adversely affected by vasoconstrictor substances. Also, it is probable that high concentrations of PGs occur naturally in reproductive tissues and a rapid increase of PG in amniotic fluid occurs in spontaneous labors as well as those induced with oxytocin or PGs. Due caution must be exercised in using PGs where placental function may be impaired. The results-to-date which have been obtained with careful monitoring of the fetal heartrate and intrauterine pressure, show no evidence of adverse effects on the fetus as a result of PG use in preeclampsia and suggest they represent a valuable therapeutic agent in the management of this condition. PMID:4134436

Calder, A A; Bonnar, J; Sheppard, B; Embrey, M P; Turnbull, A C



The global impact of pre-eclampsia and eclampsia.  


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

Duley, Lelia



[Anesthetic management of parturients with pre-eclampsia and eclampsia].  


Preeclampsia is a pregnancy-associated illness affecting multiple organ systems. Symptoms typically occur after the 20th week of gestation and consist of hypertension (>140/90 mmHg) and proteinuria (>300 mg/day). It is one of the leading causes of premature birth worldwide and early diagnosis and treatment are essential for both fetal and maternal health. Therapy is aimed at lowering blood pressure sufficiently to prevent the most severe complications such as intracranial hemorrhages. At the same time attention must be paid to the possible untoward effects of blood pressure medications on uteroplacental perfusion and fetal well being. Magnesium is the cornerstone for both prevention and control of eclamptic cerebrovascular events. In cases of severe preeclampsia and eclampsia prompt delivery is indicated, often carried out by Cesarean section (>34 weeks of gestation). Compared to general anesthesia, regional anesthesia techniques offer certain advantages to both mother and fetus and in the absence of contraindications are the methods of choice. PMID:18209976

Fetsch, N I; Bremerich, D H



Pre-eclampsia is associated with sleep-disordered breathing and endothelial dysfunction.  


Pre-eclamptic toxaemia (PET) may be associated with both endothelial dysfunction (ED) and sleep-disordered breathing (SDB). It was hypothesised that females with PET would demonstrate both SDB and ED, and that a correlation between these two would suggest a potential causative association. A total of 17 females with PET and 25 matched females with uncomplicated pregnancy were studied. They underwent a nocturnal ambulatory sleep study (using Watch_PAT100) and noninvasive evaluation of endothelial function utilising the reactive hyperaemia test (using Endo_PAT 2000). A higher ratio of post- to pre-occlusion pulse-wave amplitude (endothelial function index (EFI)) indicated better endothelial function. Females with PET had a significantly higher respiratory disturbance index (RDI) and lower EFI than controls (18.4+/-8.4 versus 8.3+/-1.3.h(-1), and 1.5+/-0.1 versus 1.8+/-0.1, respectively). Blood pressure significantly correlated with RDI and with EFI. EFI tended to correlate with RDI. In conclusion, these results suggest that both sleep-disordered breathing and endothelial dysfunction are more likely to occur in females with pre-eclamptic toxaemia than in females with uncomplicated pregnancies. The current authors speculate that respiratory disturbances contribute to the functional abnormality of the blood vessels seen in females with pre-eclamptic toxaemia, although causality cannot be determined based on this study. PMID:16452588

Yinon, D; Lowenstein, L; Suraya, S; Beloosesky, R; Zmora, O; Malhotra, A; Pillar, G



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



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



Cytokine secretion by decidual lymphocytes in transient hypertension of pregnancy and pre-eclampsia.  

PubMed Central

BACKGROUND: Transient hypertension (TH) and preeclampsia (PE) are believed to have different pathophysiology. However, 15-25% of pregnant women initially diagnosed as having TH develop PE. To clarify the immuno-pathogenetical connections between the two syndromes, we studied the pattern of T helper cell (Th)1/Th2 cytokine balance disturbances existing inside maternal decidua in normal pregnancy (NP) and pregnancies complicated with TH and PE. METHODS: Third-trimester decidual tissue was obtained by curettage of uterine cavity during elective caesarean sections in NP (n = 11), TH (n = 17) and PE (n = 21) patients. Cell suspensions were prepared by an electromechanical dispersal method and centrifugated using a standard gradient sedimentation technique. Isolated lymphocytes were placed in medium (RPMI 1640, 10% fetal calf serum, L-glutamine, penicillin, streptomycin) and cultured for 72 h with or without mitogen phytohaemaglutinine (PHA). The enzyme-linked immunosorbent assay method was used for estimation of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and interferon-gamma (IFN-gamma) in culture supernatant. STATISTICAL ANALYSIS: The Kruskal-Wallis and the Mann-Whitney U tests were used (p < 0.05). RESULTS: Both spontaneous and PHA-stimulated secretion of Th2-type cytokines IL-6 and IL-10 was decreased in PE patients compared with TH and NP patients. The concentration of Th1-type cytokine IFN-gamma was increased in patients suffering both from TH and PE. CONCLUSION: On the base of decidual cytokine secretion, both PE and TH are syndromes of local Th1/Th2 cytokine balance disturbances as compared with NP, and TH seems to be an intermediate step to PE.

Wilczynski, Jacek R; Tchorzewski, Henryk; Glowacka, Ewa; Banasik, Malgorzata; Lewkowicz, Przemyslaw; Szpakowski, Marian; Zeman, Krzysztof; Wilczynski, Jan



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

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



Patient with antiphospholipid syndrome accompanied by pre-eclampsia who developed hellp syndrome and eclampsia after abortion.  


Antiphospholipid syndrome (APS) refers to a group of clinical symptoms and signs caused by antiphospholipid antibody (aPLA). We reported a rare case of poor outcome of a pregnant woman with APS. The pregnant woman had APS, hemolytic anemia, elevated liver function and low platelet count (HELLP) syndrome, and eclampsia and had a poor outcome from a second pregnancy. She was treated with antispasmodics, sedatives, and anti-hypertensive agents, along with anticoagulant therapy and infusion of immunoglobulin. APS during pregnancy often makes pregnancy even more complex and risky. Obstetricians should carry out anticoagulation treatment throughout the perinatal period. PMID:23158159

Wang, Yong-qing; Niu, Ji-hong; Wang, Jia-lue; Ye, Rong-hua; Zhao, Yang-yu



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.

Ustuner, Is?k; Akdogan, Remzi Adnan; Guven, Emine Seda Guvendag; Sahin, Figen K?r; Senturk, Senol; Akdogan, Elif; Tasc?, Filiz



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


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

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



Population-based estimate of sibling risk for preterm birth, preterm premature rupture of membranes, placental abruption and pre-eclampsia  

Microsoft Academic Search

BACKGROUND: Adverse pregnancy outcomes, such as preterm birth, preeclampsia and placental abruption, are common, with acute and long-term complications for both the mother and infant. Etiologies underlying such adverse outcomes are not well understood. As maternal and fetal genetic factors may influence these outcomes, we estimated the magnitude of familial aggregation as one index of possible heritable contributions. Using the

Jevon Plunkett; Ingrid Borecki; Thomas Morgan; David Stamilio; Louis J Muglia



Screening for pre-eclampsia and fetal growth restriction in twin pregnancies at 23 weeks of gestation by transvaginal uterine artery Doppler  

Microsoft Academic Search

Objective To assess the value of transvaginal uterine artery Doppler at 23 weeks of gestation in predicting the develop- ment of adverse perinatal outcomes in twin pregnancies. Patients and methods Women with twin pregnancies attending for routine ultrasound examination at 23 weeks in any one of seven hospitals underwent Doppler assessment of the uterine arteries. The right and left uterine

C. K. H. Yu; A. T. Papageorghiou; A. Boli; A. M. Cacho; K. H. Nicolaides



Leisure time physical activity during pregnancy and impact on gestational diabetes mellitus, pre-eclampsia, preterm delivery and birth weight: a review  

Microsoft Academic Search

Background. It has been questioned whether leisure time physical activity (LTPA) during pregnancy is beneficial or deleterious to pregnancy outcome, and whether a sedentary lifestyle during pregnancy has a negative impact on pregnancy. Answers to these questions are of general interest, since some young women are very physically active during leisure time, while others have a sedentary lifestyle. Method. In

Hanne K. Hegaard; Bente K. Pedersen; Birgitte Bruun Nielsen; Peter Damm



The Correlation of Circulating Cell-Free DNA, Cell-Free Fetal DNA and MicroRNA 325 Levels to Clinical Characteristics and Laboratory Parameters in Pre-eclampsia  

Microsoft Academic Search

\\u000a Objective: Elevated amounts of circulating DNA in maternal plasma have been detected in pregnancies complicated by preeclampsia.\\u000a In order to confirm this, we simultaneously examined whether increased circulating cell-free DNA and microRNA levels are related\\u000a to the clinical and laboratory parameters of preeclamptic patients. The quantity of total plasma-free DNA did not correlate\\u000a with most of the laboratory parameters except

Levente Lázár; Bálint Nagy; Attila Morvarec; János Rigó


Doppler assessment of the uterine and uteroplacental circulation in the second trimester in pregnancies at high risk for pre-eclampsia and/or intrauterine growth retardation: comparison and correlation between different Doppler parameters.  


During a 20-month period we studied 175 pregnant women at high risk for hypertensive disorders of pregnancy or intrauterine growth retardation, and 172 patients at low risk, in a prospectively designed cross-sectional trial. Using duplex pulsed wave Doppler ultrasound, we recorded blood velocity waveforms from both main uterine arteries, the uteroplacental arteries in the region of placental implantation and the umbilical artery at 21-24 weeks of gestation. Persistent notches in the main stem uterine arteries and elevated resistance indices of > 0.68 in the uterine arteries and > 0.38 in the uteroplacental arteries were defined as abnormal waveforms. The incidence of proteinuric pregnancy-induced hypertension (PPIH) and intrauterine growth retardation (IUGR) were recorded as main outcome measures. Doppler proved to be more efficient at predicting a complicated pregnancy in those patients who were at high risk: a positive medical history alone was associated with a three-fold greater risk of developing PPIH and/or IUGR. In the high-risk group a single pathological Doppler sign accounted for an additional three- to four-fold increased risk, and the combination of all three pathological signs, a seven-fold additional risk for later disease. In this group PPIH and/or IUGR was found in 58.3%, compared to 8.3% if Doppler results were normal. The criterion for the definition of pathological Doppler results, whether persistent notching, the resistance index (RI) of the main stem uterine artery, or the RI in the arteries of the uteroplacental bed, was of minor importance, as all Doppler parameters were strongly correlated. However, the combination of all parameters was superior to a single parameter, and a bilateral notch was superior to a unilateral notch in terms of minimizing false-positive results. However, Doppler was less powerful in the population at low risk. Here PPIH and/or IUGR was seen in 6.1-6.4% in the group with abnormal Doppler findings compared to 5.2% in pregnancies with normal findings. None of the patients showed bilateral notching. In conclusion, pathological Doppler velocimetry of the uterine and uteroplacental circulation was a powerful predictor of PPIH and/or IUGR in high-risk pregnancies, identifying a group in which 58.3% would suffer from disease later in pregnancy. A combination of several Doppler parameters was superior to a single parameter, although the parameters were strongly correlated with each other. PMID:9201877

Zimmermann, P; Eiriö, V; Koskinen, J; Kujansuu, E; Ranta, T



Methylenetetrahydrofolate C677T polymorphism and pre-eclamptic Egyptian women  

Microsoft Academic Search

Thrombosis of the maternal spiral arteries can be one of the causative events in pre-eclampsia disease, it has been suggested that the C677T polymorphism may also play a role in the pathogenesis of pre-eclampsia.

Zakia Mahdy Ibrahim; Mohamed Abd Elhamid Metawie; Ahmed Mohamed El-Baz; Mohamed Ahmed El-Bahie


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

Microsoft Academic Search

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

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



Norepinephrine Transporter (NET), Serotonin Transporter (SERT), Vesicular Monoamine Transporter (VMAT2) and Organic Cation Transporters (OCT1, 2 and EMT) in Human Placenta from Pre-eclamptic and Normotensive Pregnancies  

Microsoft Academic Search

Pre-eclampsia is one of the most common causes of perinatal and maternal morbidity and mortality. High blood pressure and proteinuria are important clinical signs of pre-eclampsia. Sympathetic overactivity and elevated level of circulating vaso active substances, such as monoamines has been shown. Extracellular concentrations of monoamines are normally kept low by specific transporter proteins of which many are expressed in

B. Bottalico; I. Larsson; J. Brodszki; E. Hernandez-Andrade; B. Casslen; K. Marsal; S. R. Hansson



32 CFR 732.16 - Emergency care requirements.  

Code of Federal Regulations, 2010 CFR

...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....



32 CFR 732.16 - Emergency care requirements.  

Code of Federal Regulations, 2010 CFR

...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....



32 CFR 732.16 - Emergency care requirements.  

Code of Federal Regulations, 2013 CFR

... (1) Medical or surgical conditions which would constitute an emergency in the nonpregnant state. (2) Spontaneous abortion, with first trimester hemorrhage. (3) Premature or term labor with delivery. (4) Severe pre-eclampsia....



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

PubMed Central

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

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



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


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

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



Genomewide Oligonucleotide Microarray Analysis on Placentae of Pre-Eclamptic Pregnancies  

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

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



Inferior vena cava thrombosis presenting as non-immune hydrops in the fetus of a woman with diabetes.  


We present a rare case of non-immune hydrops fetalis (NIHF) caused by a thrombus in the inferior vena cava in a neonate with low levels of anti-thrombin III. The diagnosis of (NIHF) was made in utero in a 43-year-old woman with poorly controlled gestational diabetes who subsequently developed pre-eclampsia. Cesarean section was performed due to fetal compromise and worsening pre-eclampsia. The thrombus resolved after neonatal treatment with heparin. PMID:14770403

Weissmann-Brenner, A; Ferber, A; O'Reilly-Green, C; Avila, C; Grassi, A; Divon, M Y



Imbalance of angiogenic factors and avascular edematous cystic villi in a trisomy 13 pregnancy: a case report.  


The incidence of pre-eclampsia is significantly higher in trisomy 13 pregnancies than in normal pregnancies. Soluble fms-like tyrosine kinase-1 (sFlt-1), located on chromosome 13, is an anti-angiogenic molecule derived from the placenta and contributes to the pathogenesis of pre-eclampsia. Elevated sFlt-1 and reduced placental growth factor (PlGF) are associated with trisomy 13 pregnancies and may play a pathogenic role in the subsequent development of pre-eclampsia. Here we present a case of a trisomy 13 pregnancy without any signs of pre-eclampsia that showed alterations in circulating angiogenic factors and abnormal placental appearance. The placenta developed edematous changes and contained multiple small cysts. Histology of the placenta confirmed avascular edematous cystic villi and did not show the typical appearance of a partial mole or mesenchymal dysplasia. The sFlt-1/PlGF ratio in maternal serum (134) was much higher than that in gestational age-matched women who were normotensive (2.9-7.2; mean, 5.0). Immunostaining for Flt-1 and endoglin was more intense in our case compared with gestational age-matched controls, and at a similar level to a case of pre-eclampsia. Placental findings that showed avascular edematous cystic villi in our case may be associated with angiogenic imbalance involved in the pathogenesis of pre-eclampsia in trisomy 13 pregnancies. PMID:23611482

Kakigano, A; Mimura, K; Kanagawa, T; Nakayama, M; Kanayama, T; Fujita, S; Kinugasa-Taniguchi, Y; Endo, M; Tomimatsu, T; Kimura, T



Serum Calcium Level among Normal Pregnant and Pre-Eclamptic Women in a Sub Urban Area of Bangladesh.  


Pre-eclampsia along with its complications seems to be one of the major causes of maternal morbidity and mortality. Despite numerous studies, the etiology of pre-eclampsia has not yet been fully elucidated. The present study prospectively determines and evaluate whether maternal serum levels of calcium has any association with pre-eclampsia. It was a cross sectional study carried out in the department of Biochemistry, Mymensingh Medical College from July 2009 to June 2010. A total of 76 subjects were selected with the duration of pregnancy from 28th wks to term. Among them 42 were normal pregnant women and 32 were pre-eclamptic, admitted in the department of obstetrics and gynaecology Mymensingh Medical College Hospital. The mean±SD serum calcium of normal pregnant women and that of the pre-eclamptic were 7.62±0.24 and 7.32±0.28mg/dl respectively. There was significant (p<0.001) decrease in serum calcium in subject with pre-eclampsia in comparison to that of the normal pregnancy. So, level of calcium may be significantly decreased in pre-eclampsia. PMID:23982526

Jafrin, W; Paul, S K; Sultana, S; Rabeya, S; Hoque, M R; Muttalib, M A



Air pollution exposure in early pregnancy and adverse pregnancy outcomes: a register-based cohort study  

PubMed Central

Objectives Our aim was to study the possible associations between exposure to elevated levels of air pollution, ozone (O3) and vehicle exhaust (NOx), during early gestation, and adverse pregnancy outcomes such as pre-eclampsia, preterm birth and small for gestational age. Design Prospective register-based cohort study. Setting The Swedish Medical Birth Register includes data on all deliveries during 1998 to 2006 in Greater Stockholm, Sweden. The national Patient Register and the Prescribed Drug Register were used to collect information on maternal asthma. Participants All singleton pregnancies, conceived at the earliest in August 1997 and at the latest in February 2006, were included, n=120?755. Outcome measures We studied preterm birth, small for gestational age and pre-eclampsia. Results 4.4% of pregnancies resulted in a preterm birth. The prevalence of pre-eclampsia was 2.7%. We observed an association between first trimester O3 and preterm birth (OR 1.04, 95% CI 1.01 to 1.08) as well as an association with pre-eclampsia (OR 1.04, 95% CI 1.01 to 1.08), per 10?µg/m3 increase in O3. We observed no association between first trimester NOx and adverse pregnancy outcomes. No associations were observed between any of the air pollutants and small for gestational age. Conclusions Increased levels of O3 during the first trimester increased the risk of pre-eclampsia and preterm birth. Air pollutants did not exhibit any effects on fetal growth restriction. We estimated 1 in every 20 cases of pre-eclampsia to be associated with O3 exposure.

Olsson, David; Mogren, Ingrid; Forsberg, Bertil



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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

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




Microsoft Academic Search

Magnesium is essential for human life and is involved in the activation of hundreds of enzyme systems. However, only relatively recently has it been recognised as a drug with important clinical uses; the World Health Organisation (WHO) recommends the use of magnesium in the management of pre-eclampsia and eclampsia, it is used in the management of tetanus and increasingly for

Emily Shardlow


Leukocyte Pyruvate Kinase Expression is Reduced in Normal Human Pregnancy but not in Preeclampsia  

PubMed Central

Problem Emerging evidence suggests that metabolism influences immune cell signaling and immunoregulation. To examine the immunoregulatory role of glycolysis in pregnancy, we evaluated the properties of pyruvate kinase in leukocytes from non-pregnant women and those with normal pregnancy and pre-eclampsia. Method of study We evaluated pyruvate kinase expression in lymphocytes and neutrophils from non-pregnant, pregnant, and pre-eclampsia patients using fluorescence microscopy and flow cytometry. Leukocyte pyruvate kinase activity and pyruvate concentrations were also evaluated. To study pyruvate’s effect on signaling, we labeled Jurkat T cells with Ca2+ dyes and measured cell responses in the presence of agents influencing intracellular pyruvate. Results The expression of pyruvate kinase is reduced in lymphocytes and neutrophils from normal pregnant women in comparison to those of non-pregnant women and pre-eclampsia patients. Similarly, the activity of pyruvate kinase and the intracellular pyruvate concentration are reduced in leukocytes of normal pregnant women in comparison to non-pregnant women and women with pre-eclampsia. Using Jurkat cells as a model of leukocyte signaling, we have shown that perturbations of intracellular pyruvate influence Ca2+ signals. Conclusion Normal pregnancy is characterized by reduced pyruvate kinase expression within lymphocytes and neutrophils. We speculate that reduced pyruvate kinase expression modifies immune cell responses due to reduced pyruvate concentrations.

Xu, Yi; Madsen-Bouterse, Sally A.; Romero, Roberto; Hassan, Sonia; Mittal, Pooja; Elfline, Megan; Zhu, Aiping; Petty, Howard R.



Capgras' syndrome with organic disorders  

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

Thomas Vauvert F. Hviid; Ole B. Christiansen



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



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

Microsoft Academic Search

BACKGROUND: Observational studies have demonstrated various correlations between hypertensive disorders of pregnancy and different weather parameters. We aim to study if a correlation exists between the incidence of eclampsia and pre-eclampsia and various weather parameters in the tropical coastal city of Mumbai which has the distinction of having relatively uniform meteorological variables all throughout the year, except for the monsoon

Vidya Subramaniam



Clinicopathological study of neurological complications due to hypertensive disorders of pregnancy  

Microsoft Academic Search

Forty-three women with neurological complications secondary to eclampsia or severe pre-eclampsia were studied by CT scanning and in six intracranial pressure (ICP) monitoring was carried out. In seven women who died, neuropathological findings were correlated with clinical features. Cerebral oedema was present in 27 of the patients studied and the severity of oedema correlated to the duration of intermittent seizures.

A Richards; D Graham; R Bullock



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


Epidemiological data suggest that diets rich in antioxidants protect against diseases associated with free radical damage, including cancer, cardiovascular disease and diabetes. Early observations also suggested that vitamin supplements with antioxidant properties, like vitamins C and E, could also prevent or ameliorate pre-eclampsia, but most large randomized clinical trials have failed to show any benefit. Vitamin C given orally, even at high doses, does not achieve sustained serum levels that might be required for effective antioxidant activity. This may explain the failure of the numerous clinical trials involving its use in pre-eclampsia, cancers, cardiovascular diseases, etc. Vitamin C supplementation to stave off pre-eclampsia, cancer and other diseases is a 'nutraceutical' industry-driven myth which should be abandoned. We do not dispute a role for oxidative stress in the pathophysiology of pre-eclampsia, nor the possibility of amelioration of the disease by an anti-oxidant given at the right time and in the correct dosage. We simply wish to make a case that the massive and expensive clinical trials of vitamins C and E should cease until further rigorous scientific research is undertaken. PMID:21507551

Talaulikar, Vikram Sinai; Manyonda, Isaac T



Audit of vitamin D deficiency in ethnic pregnant population at Liverpool Womens Hospital  

Microsoft Academic Search

IntroductionIt is suggested that vitamin D deficiency during pregnancy is associated with increased risk of pre-eclampsia, insulin resistance and gestational diabetes. Experimental data demonstrate that vitamin D is important for fetal development and immunological function. Vitamin D deficiency in pregnancy may impair maternal skeletal preservation and fetal skeletal formation. Moreover, deficiency may affect fetal ‘imprinting’ increasing susceptibility to chronic disease

M Akhtar; R Tildesley; H Cliffe; J Topping



Innate Immune Response by Ficolin Binding in Apoptotic Placenta Is Associated with the Clinical Syndrome of Preeclampsia  

Microsoft Academic Search

Background: Unidentified circulating factors derived from placenta are thought to be responsible for the exaggerated systemic inflammation leading to pre- eclampsia. Our aim was to identify the circulating factors present in preeclampsia and to investigate their relationship to the underlying systemic immune re- sponse responsible for the associated clinical manifes- tations. Methods: We obtained blood samples from pregnant women with

Chi Chiu Wang; Ka Wing Yim; Terence C. W. Poon; Kwong Wai Choy; Ching Yan Chu; Wai Ting Lui; Tze Kin Lau; Michael S. Rogers; Tse Ngong Leung


Prospective prevention of neonatal hyperammonaemia in argininosuccinic acidura by arginine therapy  

Microsoft Academic Search

Argininosuccinic aciduria, due to deficiency of argininosuccinic acid lyase, is generally associated with severe neonatal hyperammonaemia and its neurological sequelae. The cases of two siblings with this autosomal recessive disorder are presented. Both infants were preterm and delivered by Caesarean section for maternal pre-eclampsia. The first infant was not diagnosed until after the development of severe hyperammonaemia and, despite adequate

S. M. Donn; J. G. Thoene



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



Circulating biomarkers of oxidative stress in complicated pregnancies  

Microsoft Academic Search

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

Hilmi Orhan; Lütfü Önderoglu; Aykan Yücel; Gönül Sahin



Biomarkers for placental abnormality  

Microsoft Academic Search

Obstetrical complications including recurrent miscarriage, pre-eclampsia and intrauterine growth restriction (IUGR) affect 1%-5% of pregnant women (Younis and Samueloff 2003). Dysfunctional trophoblasts, impaired development of spiral arteries, imbalance in systems controlling the dilation and contraction of spiral arteries, placental fibrin clots and intervillous thrombosis are all possible factors that can result in an insufficient placental circulation. The combination of the

Cathal McCarthy



Obstetric outcome in women with polycystic ovarian syndrome  

Microsoft Academic Search

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

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



Thyroid hormone alteration in pre-eclamptic women.  


This study sought a possible relationship between pre-eclampsia and thyroid profile. In a case-control setting, total thyroxine (T4), total tri-iodothyronine (T3), free T4, free T3, thyroxine binding globulin (TBG) and thyrotropin (TSH) levels in 39 pre-eclamptic patients were measured and compared with the levels in 42 healthy controls. We examined possible variations with regard to the severity of pre-eclampsia by dividing cases into mild (n = 17) and severe (n = 22) subgroups. Patients with mild pre-eclampsia showed significantly increased free T4 and TSH levels compared to healthy controls. In severe cases, TSH level was higher, but free T3 and free T4 levels were significantly lower than in controls. Other tests returned non-significant differences between the groups. Our findings suggest that primary hypofunctioning of the thyroid can accompany mild pre-eclampsia and possibly contribute to the pathogenesis. Elevated levels of free thyroid hormones in severe cases, however, may have reflected a preceding thyroid disorder. PMID:15195501

Larijani, B; Marsoosi, V; Aghakhani, S; Moradi, A; Hashemipour, S



(Epi)genetics of pregnancy-associated diseases  

PubMed Central

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

van Dijk, Marie; Oudejans, Cees



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



Oxygen and placental villous development: Origins of fetal hypoxia  

Microsoft Academic Search

The increasing practice of preterm delivery in the fetal interest for conditions such as pre-eclampsia or intrauterine growth restriction (IUGR) has provided an opportunity to study placental structure in pregnancies with prenatal evidence of fetal compromise. These data suggest that the origin of fetal hypoxia in IUGR with absent end-diastolic flow in the umbilical arteries is due to a failure

J. C. P. Kingdom; P. Kaufmann



[Clinical analysis of eleven patients with chronic myeloproliferative disorders complicating pregnancy.  


OBJECTIVE: To investigate the clinical characteristics, the antenatal management, the outcome and prognosis of chronic myeloproliferative disorders(CMPD) complicating pregnancy. METHODS: Retrospectively analyze the clinical data of eleven patients with CMPD complicating pregnancy hospitalized in Peking University People's Hospital from 2000 to 2009, including five patients with essential thrombocythemia, one with primary myelofibrosis and five with chronic myeloid leukemia. RESULTS: (1) Five pregnancies had periodic antenatal care and laboratory monitorings like full blood count. Reasonable anti-coagulation therapy was given to prevent the complications. One patient with PMF diagnosed before conception had her first pregnancy ended with mild pre-eclampsia and intrauterine death at the gestational age of 32 weeks. During the first trimester of her second pregnancy two years later, the test for anti-?2 glycoprotein antibody was positive. She received low-dose aspirin and low-molecular-weight heparin as anti-coagulants. An uneventful course was obtained and she delivered a healthy term infant. (2) Five pregnancies had occasional antenatal examination, including two patients with ET and three patients with CML. One patient with ET developed severe pre-eclampsia at the gestational age of 25 weeks. Umbilical artery Doppler showed reversed end-diastolic velocity. The management with anti-convulsants, anti-hypertensives and anti-coagulants showed no effect. An emergency cesarean section had to be performed because of the aggressive hypertension and placental abruption, with still birth as a result. Two pregnancies never had an antenatal care. Both of them were admitted on labor and the diagnoses of CML were made. (3) Four pregnancies developed oligohydramnios and three developed preelampsia (two severe pre-eclampsia and one mild pre-eclampsia). There was no other hemorrhage and thrombosis event. (4) Eight pregnancies reached full-term with four cesarean sections and four vaginal births. Two preterm cesarean sections were performed because of a progressive oligohydramnios. The ten live neonates weighed 1820 - 3600 g. All were appropriate for gestational age, except one fetal growth retardation (FGR) developed in one patient with severe pre-eclampsia. (5) As for the CMPD, the eleven patients were all in stable conditions. Three patients with CML received hydroxyurea in the third trimester, four with ET and one with CML had platelet-pheresis before delivery with favorable effect. All patients were uneventful postpartum, except one with CML who died in 5 months after childbirth. CONCLUSIONS: The pregnancy outcomes for patients with CMPD are mostly good. However, antenatal care should pay more attention to the complications such as thromboembolic accidents, pre-eclampsia, still birth and fetal growth retardation. Management including reasonable anti-coagulation therapy should be considered, which may help improve the prognosis. PMID:21211419

Bai, Yue-Ting; Zhang, Chao; Wang, Jian-Liu; Liang, Mei-Ying; Zhang, Xiao-Hong



Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study  

PubMed Central

Objective To examine the association between hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) and the development of circulatory diseases in later life. Design Cohort study of women who had pre-eclampsia during their first singleton pregnancy. Two comparison groups were matched for age and year of delivery, one with gestational hypertension and one with no history of raised blood pressure. Setting Maternity services in the Grampian region of Scotland. Participants Women selected from the Aberdeen maternity and neonatal databank who were resident in Aberdeen and who delivered a first, live singleton from 1951 to 1970. Main outcome measures Current vital and cardiovascular health status ascertained through postal questionnaire survey, clinical examination, linkage to hospital discharge, and mortality data. Results There were significant positive associations between pre-eclampsia/eclampsia or gestational hypertension and later hypertension in all measures. The adjusted relative risks varied from 1.13-3.72 for gestational hypertension and 1.40-3.98 for pre-eclampsia or eclampsia. The adjusted incident rate ratio for death from stroke for the pre-eclampsia/eclampsia group was 3.59 (95% confidence interval 1.04 to 12.4). Conclusions Hypertensive diseases of pregnancy seem to be associated in later life with diseases related to hypertension. If greater awareness of this association leads to earlier diagnosis and improved management, there may be scope for reducing a proportion of the morbidity and mortality from such diseases. What is already known on this topicMuch is known about the effect of cardiovascular risks factors that are shared by men and women, but less on those specific to womenRetrospective studies, based on patient recall, suggest that hypertension in pregnancy may be associated with increased risk of cardiovascular diseases in later lifeWhat this study addsProspective recording of blood pressure and proteinuria shows that women who experienced raised blood pressure in pregnancy have a long term risk of hypertensionWomen who experience raise blood pressure in pregnancy have an increased risk of stroke and, to a lesser extent, an increased risk of ischaemic heart diseaseLong term cardiovascular risks are greater for women who had pre-eclampsia than those who experienced gestational hypertension (hypertension without proteinuria)

Wilson, Brenda J; Watson, M Stuart; Prescott, Gordon J; Sunderland, Sarah; Campbell, Doris M; Hannaford, Philip; Smith, W Cairns S



Liver abnormalities in pregnancy.  


Abnormalities of liver function (notably rise in alkaline phosphatase and fall in serum albumin) are common in normal pregnancy, whereas rise in serum bilirubin and aminotransferase suggest either exacerbation of underlying pre-existing liver disease, liver disease related to pregnancy or liver disease unrelated to pregnancy. Pregnant women appear to have a worse outcome when infected with Hepatitis E virus. Liver diseases associated with pregnancy include abnormalities associated hyperemesis gravidarum, acute fatty liver disease, pre-eclampsia, cholestasis of pregnancy and HELLP syndrome. Prompt investigation and diagnosis is important in ensuring a successful maternal and foetal outcome. In general, prompt delivery is the treatment of choice for acute fatty liver, pre-eclampsia and HELLP syndrome and ursodeoxycholic acid is used for cholestasis of pregnancy although it is not licenced for this indication. PMID:24090943

Than, Nwe Ni; Neuberger, James



Ovarian stimulation and liver dysfunction: Is a clinical relationship possible? A case of hepatic failure after repeated cycles of ovarian stimulation.  


Liver damage induced by ovarian stimulation has been demonstrated in some cases reported in the literature. However, there has never been a fruitful debate on this topic. The present manuscript tried to fill this gap. We reported a case of a 35-year-old nulliparous woman admitted to our obstetric emergency room for severe pre-eclampsia. She had been subjected to four cycles of controlled ovarian stimulation for intrauterine insemination. At 32 weeks of gestation, she developed severe pre-eclampsia, which led to HELLP syndrome complicated by fatal liver failure. The etiological link between ovarian stimulation and HELLP syndrome is intriguing. Further investigations are needed to understand whether repeated ovarian stimulation may represent a risk factor in pre-eclamptic patients. PMID:23614115

Giugliano, Emilio; Cagnazzo, Elisa; Pansini, Giancarlo; Vesce, Fortunato; Marci, Roberto



Pheochromocytoma and Pregnancy: A Difficult and Dangerous Ordeal  

PubMed Central

Pheochromocytoma during pregnancy is potentially disastrous to the mother and fetus. Its ambiguous presentation is often mistaken for pre-eclampsia, although it may imitate other problems during pregnancy. Early diagnosis and timely, appropriate management reduces possible maternal and fetal complications. We identified a case of pheochromocytoma during pregnancy; the condition was initially diagnosed as pre-eclampsia complicated with gestational diabetes. Surgical intervention via left adrenalectomy was successfully performed in the second trimester. After surgery, all of the patient’s medical problems nearly subsided and she did not require further treatment. However, her fetus displayed restricted intrauterine growth, and the patient eventually had premature delivery via a caesarean section. A multidisciplinary team to identify and treat pheochromocytoma is mandatory to ensure optimal conditions for tumour removal and to anticipate any possible catastrophic events.

Mohamed Ismail, Nor Azlin; Abd Rahman, Rahana; Abd Wahab, Norasyikin; Muhammad, Rohaizak; Nor Azmi, Kamaruddin



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.

Huang, Xiao; Jain, Arjun; Baumann, Marc; Korner, Meike; Surbek, Daniel; Butikofer, Peter; Albrecht, Christiane



[Selected polymorphisms of Renin-Angiotensin System in the pathology of hypertensive disorders of pregnancy].  


Pregnancy induced hypertension and pre-eclampsia, defined as hypertension and proteinuria after 20 weeks of pregnancy with no history of such symptoms, are a great challenge in the field of perinatology They are a serious threat to the mother and the child. Regardless of numerous studies on the subject, the pathogenesis of pregnancy-induced hypertension and pre-eclampsia is still unknown, although a crucial role of genetic factors combined with environmental factors has been confirmed. New theory based on genetic analysis of Renin-Angiotensin System and its impact on blood pressure in pregnant women, has been subject to much debate recently Numerous genes have been studied but angiotensinogen remains to be the best known. Little is known about angiotensin receptor type 1 and 2. This paper presents the knowledge about selected genes of RAS and their impact on pregnancy PMID:23700850

Ku?mierska-Urban, Katarzyna; Rytlewski, Krzysztof; Rero?, Alfred



Ovarian stimulation and liver dysfunction: Is a clinical relationship possible? A case of hepatic failure after repeated cycles of ovarian stimulation  

PubMed Central

Liver damage induced by ovarian stimulation has been demonstrated in some cases reported in the literature. However, there has never been a fruitful debate on this topic. The present manuscript tried to fill this gap. We reported a case of a 35-year-old nulliparous woman admitted to our obstetric emergency room for severe pre-eclampsia. She had been subjected to four cycles of controlled ovarian stimulation for intrauterine insemination. At 32 weeks of gestation, she developed severe pre-eclampsia, which led to HELLP syndrome complicated by fatal liver failure. The etiological link between ovarian stimulation and HELLP syndrome is intriguing. Further investigations are needed to understand whether repeated ovarian stimulation may represent a risk factor in pre-eclamptic patients.

Cagnazzo, Elisa; Pansini, Giancarlo; Vesce, Fortunato; Marci, Roberto



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



Amniotic fluid 25-hydroxyvitamin D concentrations in normal and complicated pregnancy.  


The concentration of 25-hydroxyvitamin D (25(OH)D) was measured in 85 samples of amniotic fluid (AF) obtained near term from mothers with normal pregnancy, diabetes, pre-eclampsia or intrahepatic cholestasis of pregnancy. Significantly lower AF 25(OH)D levels were found in diabetic mothers than in the three other groups. Our results suggest that the vitamin D status of the fetoplacental unit may be somewhat impaired in diabetic pregnancy. PMID:3956825

Koskinen, T; Kuoppala, T; Tuimala, R



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

Microsoft Academic Search

Miscarriage and pre-eclampsia are the most common disorders of human pregnancy. Both are placental-related and exceptional in other mammalian species. Ultrasound imaging has enabled events during early pregnancy to be visual- ized in vivo for the first time. As a result, a new understanding of the early materno-fetal relationship has emerged and, with it, new insight into the pathogenesis of

Eric Jauniaux; Lucilla Poston; Graham J. Burton



Reversible posterior leukoencephalopathy induced by carboplatin and etoposide  

Microsoft Academic Search

Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare neurologic condition characterised by specific clinical\\u000a and radiologic findings. It usually manifests subacutely as insidious onset of headache, visual disturbance, altered consciousness\\u000a and seizures in association with MRI findings of posterior white matter vasogenic oedema. RPLS has been reported in a wide\\u000a variety of clinical settings. Hypertension, eclampsia, pre-eclampsia, renal impairment, autoimmune

S. A. Ryan; P. MacEneaney; S. P. O’Reilly; E. J. Moylan; D. G. Power


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

Microsoft Academic Search

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

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



Unexpected neurological deficits following recovery from anaesthesia  

Microsoft Academic Search

Two cases of neurological dysfunction are presented. Neurological deficits after recovery from anaesthesia are unusual in\\u000a young women perioperatively. In the first case, a 39-yr-old woman presented at 36-wk gestation with antepartum haemorrhage\\u000a and in labour. Pregnancy had been complicated by pre-eclampsia and she underwent emergency Caesarean section under general\\u000a anaesthesia without complication. The trachea was extubated when she was

J. Porter; L. Lynch; S. Hart; C. Keohane



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



Effect of low-dose aspirin treatment on vascular resistance in the uterine, uteroplacental, renal and umbilical arteries — A prospective longitudinal study on a high risk population with persistent notch in the uterine arteries  

Microsoft Academic Search

Objective: The study focuses on the changes of Doppler flow velocity waveforms in the uterine, uteroplacental, maternal intrarenal and umbilical artery in a selected population at high risk for pre-eclampsia or IUGR with original abnormal Doppler of the uterine arteries, defined as persistent bilateral notches at 22–24 weeks of gestation, who were randomised treated with low-dose aspirin compared to no

Peter Zimmermann; Vuokko Eiriö; Juhani Koskinen; Kyrö Niemi; Ralf Nyman; Erkki Kujansuu; Tapio Ranta



Clinical significance of low serum magnesium in pregnant women attending the University of Benin Teaching Hospital.  


Objective: Magnesium level is known to decline during pregnancy. A suggested role for magnesium deficiency in conditions like pre-eclampsia and pre-term birth has prompted studies with conflicting evidence. The primary objective of this study was to determine the prevalence of hypomagnesemia in pregnancy, while the secondary objectives attempted to define maternal and fetal outcome due to hypomagnesemia. Subjects and Methods: A pilot study was performed to determine the mean serum magnesium level for the population of female patients attending the University of Benin Teaching Hospital. The result of the pregnant population in the pilot study was used as a reference for hypomagnesemia in this study. Thereafter, a prospective cohort study of antenatal women recruited in the second trimester and followed-up till delivery and 1 week post-partum was done. Serum magnesium estimates were done with samples collected at recruitment and delivery. The magnesium levels determined at recruitment were used to divide the subjects into two groups of hypomagnesemic and normomagnesemic patients. Their sociodemographic and clinical characteristics were used to generate a database for analysis. Results: The prevalence of magnesium deficiency was 16.25%. Hypomagnesemia was significantly correlated with the occurrence of pre-eclampsia ( P = 0.011), leg cramps ( P = 0.000) and pre-term birth ( P = 0.030). A logistic regression analysis showed that hypomagnesemia had an Odds ratio of 22 for pre-eclampsia. There was no maternal mortality or early neonatal death. Conclusion: Pre-eclampsia and pre-term birth are associated with hypomagnesemia in pregnancy; hence, magnesium supplementation or magnesium-rich diet consisting of green leafy vegetables, soy milk and legumes may improve outcome. PMID:23974737

Enaruna, N O; Ande, Aba; Okpere, E E


Cerebrovascular disease in pregnancy  

Microsoft Academic Search

Opinion statement  Stroke during pregnancy is a special category of stroke in young women. Although the absolute risk is small, there are diverse\\u000a causes, including those inherent to the pregnant state, that may have a significant impact on maternal and fetal outcome.\\u000a Severe pre-eclampsia and eclampsia are commonly associated with ischemic and hemorrhagic stroke, but must not be presumed\\u000a the sole

Michael A. Sloan; Barney J. Stern



The laser diffractoscope – a new and fast system to analyse red blood cell flexibility with high accuracy  

Microsoft Academic Search

Red blood cell (RBC) flexibility is one of the determining parameters of the microcirculation. As capillaries are smaller\\u000a in diameter than RBC, RBC can only pass through by deformation. Reduced flexibility is associated with a reduced microcirculation.\\u000a In obstetrics, pre-eclampsia and intrauterine growth retardation are regarded as diseases exhibiting a reduced microcirculation.\\u000a With this new system it might be possible

B. Schauf; B. Aydeniz; R. Bayer; D. Wallwiener



Pregnancy and Catastrophic Antiphospholipid Syndrome  

Microsoft Academic Search

Antiphospholipid syndrome (APS) is clearly related to maternal morbidity. The most characteristic feature is pregnancy loss;\\u000a however, several other serious complications had been reported including fetal growth restriction, uteroplacental insufficiency,\\u000a fetal distress, pre-eclampsia, and HELLP syndrome. Herein, we review the different aspects of obstetric APS features, with\\u000a special emphasis on its life-threatening variant known as catastrophic APS (Asherson’s syndrome) and

Jose A. Gómez-Puerta; Jose Sanin-Blair; Claudio Galarza-Maldonado



How obstetricians manage hypertension in pregnancy  

Microsoft Academic Search

One thousand and ninety-three obstetricians answered a questionnaire on the management of pregnant women with pre-existing hypertension and pre-eclampsia. They reported that they frequently used antihypertensive drugs (most often methyldopa and diuretics) in severe essential hypertension but tended to give sedatives in mild cases. Renal impairment was considered more important that raised blood pressure as an indication for terminating pregnancy;

G V P CHAMBERLAIN; P J Lewis; M De Swiet; C J Bulpitt



Postnatal trends in creatinemia and its covariates in extremely low birth weight (ELBW) neonates  

Microsoft Academic Search

To document trends and covariates of creatinemia (Scr) in extremely low birth weight (ELBW, < 1,000 g) neonates, maternal\\u000a characteristics [betamethasone, premature preterm rupture of membranes (PPROM), pre-eclampsia, maternal Scr], characteristics\\u000a at delivery [gestational age (GA), birth weight (BW), small for GA (SGA), Apgar, intubation] and during neonatal stay [ventilation,\\u000a oxygen, parenteral nutrition, ibuprofen, steroids, intraventricular hemorrhage, retinopathy of prematurity

Isabel George; Djalila Mekahli; Maissa Rayyan; Elena Levtchenko; Karel Allegaert


Familial Occurrence of Peripartum Cardiomyopathy Presages a Genetic Rather Than an Environmental Cause  

Microsoft Academic Search

Peripartum cardiomyopathy (PPCM) is an uncommon form of left ventricular dysfunction associated with pregnancy and triggered\\u000a by a number of obstetric factors including pre-eclampsia, plural gestations and multiparity. PPCM is the most frequent cause\\u000a of pregnancy-related maternal death. Although the clinical outcome of PPCM has been determined, its patho-etiology has not\\u000a been elucidated. Two recent studies have demonstrated for the

Martin St. John Sutton; John Sutton



Hydatoxi lualba: The worm that wasn't!  


Pre-eclampsia is a disorder that occurs only during pregnancy and the postpartum period and affects both the mother and the unborn child. Affecting at least 5-8% of all pregnancies, it can be a rapidly progressive condition characterised by hypertension and proteinuria. Oedema, sudden weight gain, headaches and changes in vision are important symptoms. However, some women with rapidly advancing disease report few symptoms. PMID:24127949

Phadnis, S V; Irvine, L M



Selective induction of labour.  

PubMed Central

In a prospective study of 1000 consecutive primigravidae labour was induced on 95 occasions. None of 16 perinatal deaths and none of 4 cases of suspected brain damage occurred after prolonged pregnancy or pre-eclampsia. It is concluded that a low incidence of induction is compatible with good results and that enthusiasm for the statistical concept of high risk in obstetric practice should be reviewed in the interest of mothers and children as individuals. Images p729-a

O'Driscol, K; Carroll, C J; Coughlan, M



Obstetric morbidity in south India: Results from a community survey  

Microsoft Academic Search

A sample of 3600 mothers with at least one pre-school age child were interviewed in detail about obstetric problems associated with their last confinement. About 10% reported one or more of the classic symptoms of pre-eclampsia; and 8% reported symptoms of potentially life-threatening conditions during delivery, most notably prolonged labour of over 18 hr. Disorders during the post-partum period were

Jagdish C. Bhatia; John Cleland



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

Microsoft Academic Search

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

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



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



Quantitative Abnormalities of Fetal DNA in Maternal Serum in Preeclampsia  

Microsoft Academic Search

Background: There is much recent interest in the bio- logic and diagnostic implication of cell-free non-host DNA in the plasma and serum of human subjects. To determine if quantitative abnormalities of circulating non-host DNA may be associated with certain patho- logic processes, we used circulating fetal DNA in pre- eclampsia as a model system. Methods: We studied 20 preeclamptic women

Y. M. Dennis Lo; Tse N. Leung; Mark S. C. Tein; Ian L. Sargent; Jun Zhang; Tze K. Lau; Christopher J. Haines; Christopher W. G. Redman


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.

Jenum, Anne Karen; Sommer, Christine; Sletner, Line; M?rkrid, Kjersti; Baerug, Anne; Mosd?l, Annhild



Effect of Heme Oxygenase1 Deficiency on Placental Development  

Microsoft Academic Search

Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway and highly expressed in the placenta. Deficiencies in HO-1, the inducible isoform, have been associated with pregnancy disorders, such as recurrent miscarriages, intrauterine growth retardation, and pre-eclampsia. The aim of this study was to identify if a deficiency in HO-1 affects placental development using a mouse model. When

H. Zhao; R. J. Wong; F. S. Kalish; N. R. Nayak; D. K. Stevenson



Epidermal growth factor rescues trophoblast apoptosis induced by reactive oxygen species  

Microsoft Academic Search

Pre-eclampsia and intrauterine growth restriction are associated with increased apoptosis of placental villous trophoblast.\\u000a This may result from placental hypoperfusion, leading to the generation of reactive oxygen species (ROS). Apoptosis can be\\u000a induced in villous trophoblast following exposure to oxidative stress. Epidermal growth factor (EGF) reduces trophoblast apoptosis\\u000a resulting from exposure to hypoxia. We hypothesised that exposure to hydrogen peroxide,

Sarah J. Moll; Carolyn J. P. Jones; Ian P. Crocker; Philip N. Baker; Alexander E. P. Heazell



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.

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



Increased cystatin C expression in the pre-eclamptic placenta  

Microsoft Academic Search

Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C inhibits cysteine proteinases. The serum concen- tration of cystatin C is increased in late pregnancy and pre-eclampsia. We aimed to investigate whether the expression of cystatin C is increased in the pre-eclamptic placenta and to investigate the expression pattern of cystatin C mRNA and protein in placental tissue. Tissue

Karl Kristensen; I. Larsson; S. R. Hansson



Altered Sphingolipid Composition in Wharton’s Jelly of Pre-Eclamptic Newborns  

Microsoft Academic Search

Objectives: Wharton’s jelly is a myxomatous substance surrounding the umbilical cord (UC) vessels to protect them against extension, bending, twisting and compression. Pre-eclampsia (hypertension, oedema, proteinuria) is the most common pregnancy-associated pathological syndrome. It is accompanied by significant alterations in UC composition. Here we describe the sphingolipids of Wharton’s jelly from 10 newborns delivered by healthy mothers and from 10

Lech Romanowicz



Whole-genome microarray and targeted analysis of angiogenesis-regulating gene expression (ENG, FLT1, VEGF, PlGF) in placentas from pre-eclamptic and small-for-gestational-age pregnancies  

Microsoft Academic Search

Objective. To compare the placental pathology associated with pre-eclampsia (PE) and\\/or fetal growth restriction, the transcriptomes of placental tissues from PE and small-for-gestational-age (SGA) pregnancies were explored. In addition, a targeted analysis of angiogenesis-regulating gene expression was performed. Methods. Whole-genome microarray analysis was performed on placental tissue from gestational age-matched PE (n ¼ 10), SGA (n ¼ 8) and PE

Johanne Holm Toft; Ingrid Alsos Lian; Adi Laurentiu Tarca; Offer Erez; Jimmy Espinoza; Irina Poliakova Eide; Line Bjørge; Sorin Draghici; Roberto Romero; Rigmor Austgulen



Role of the VEGF-A Signaling Pathway in the Glomerulus: Evidence for Crosstalk between Components of the Glomerular Filtration Barrier  

Microsoft Academic Search

Background\\/Aims: Vascular endothelial growth factor is a major regulator of angiogenesis and vascular permeability [Carmeliet et al.: Nature 1996;380:435–439]. The podocyte, the outermost layer of the glomerular filtration barrier, produces large amounts of VEGF-A. The observation that levels of VEGF-A are altered in glomerular diseases, the identification of a link between pre-eclampsia and elevated levels of a circulating soluble VEGF

Vera Eremina; Hans J. Baelde; Susan E. Quaggin



Gap junctions and hydrogen peroxide are involved in endothelium-derived hyperpolarising responses to bradykinin in omental arteries and veins isolated from pregnant women  

Microsoft Academic Search

Altered endothelial function may underlie human cardiovascular diseases, including hypertension, diabetes and pre-eclampsia. While much is known about endothelial function in small arteries, very little is known about endothelial responses in small veins isolated from humans. Therefore, we assessed endothelium-dependent responses in omental arteries and veins isolated from healthy pregnant women, focussing on endothelium-dependent hyperpolarising (EDH) mechanisms. Human omental arteries

Stephanie Hammond; Alastair M. Mathewson; Philip N. Baker; Terry M. Mayhew; William R. Dunn



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

Microsoft Academic Search

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

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



Increased leptin concentration in preterm infants of pre-eclamptic mothers  

PubMed Central

AIM—To study the effect of maternal pre-eclampsia on cord plasma leptin concentrations in preterm infants.?METHODS—Leptin concentration was analysed in cord plasma of 74 preterm infants, gestational age 24 to 32 weeks. Of these, 14 were born to pre-eclamptic mothers, in 10 intrauterine growth retardation (IUGR) was present, and 59 had been exposed antenatally to corticosteroids.?RESULTS—The mean (SD) concentration of cord plasma leptin was 1.31 (0.88) µg/l. A significant correlation was found between leptin concentration and gestational age (r = 0.336; p = 0.0037). Leptin levels were higher in infants of pre-eclamptic mothers (p = 0.0007), in those with IUGR (p = 0.0005), and in infants exposed antenatally to corticosteroids (p = 0.02). In multiple regression analysis, leptin was associated with gestational age and maternal pre-eclampsia (both p < 0.05), but not with antenatal corticosteroids.?CONCLUSIONS—Increased fetal leptin in maternal pre-eclampsia may reflect a physiological adaptation to fetal stress such as hypoxia.??

Hytinantti, T.; Koistinen, H.; Koivisto, V.; Karonen, S.; Rutanen, E.; Andersson, S.; BEREZIN, A.; MELO, M.



Vascular endothelial growth factor and placental growth factor release in cultured trophoblast cells under different oxygen tensions.  


The oxygen status of the placenta during pregnancy is unclear although it has been hypothesised that in pre-eclampsia large regions of the placenta are hypoxic. Circulating levels of vascular endothelial growth factor (VEGF) are increased in women with pre-eclampsia, while circulating placental growth factor (PlGF) levels are decreased. We hypothesise that secreted levels of VEGF are increased in cultures of trophoblast cells under lowered oxygen conditions while secreted levels of PlGFare alternatively regulated. Primary isolates of first trimester and term cytotrophoblasts cells were cultured in 20 and 5% oxygen for 24h. There was a significant increase in the levels of VEGF secreted fromfirst trimester and term cytotrophoblast cells cultured under lowered oxygen conditions compared to the controls while there was a significant decrease in the secreted levels of PIGF in the same cell populations (as measured by ELISA). In first trimester and term trophoblast cells the presence of VEGF (121, 165 and 189) and PlGF (132 and 152) mRNA were demonstrated in both groups by reverse transcription-polymerase chain reaction (RT-PCR). These altered levels of secreted VEGF andPIGF may be released as compensatory molecules in the pathogenesis of diseases such as pre-eclampsia and intrauterine growth restriction. PMID:12708795

Lash, G E; Taylor, C M; Trew, A J; Cooper, S; Anthony, F W; Wheeler, T; Baker, P N



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


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



Hyperemesis gravidarum and risks of placental dysfunction disorders: a population-based cohort study  

PubMed Central

Objective To study whether pregnancies complicated by hyperemesis gravidarum in the first (<12 weeks) or second (12–21 weeks) trimester are associated with placental dysfunction disorders. Design Population-based cohort study. Setting Sweden. Population All pregnancies in the Swedish Medical Birth Register estimated to have started on 1 January 1997 or later and ended in a single birth on 31 December 2009 or earlier (n = 1 156 050). Methods Odds ratios with 95% confidence intervals were estimated for placental dysfunction disorders in women with an inpatient diagnosis of hyperemesis gravidarum, using women without inpatient diagnosis of hyperemesis gravidarum as reference. Risks were adjusted for maternal age, parity, body mass index, height, smoking, cohabitation with the infant's father, infant's sex, mother's country of birth, education, presence of hyperthyreosis, pregestational diabetes mellitus, chronic hypertension and year of infant birth. Main outcome measures Placental dysfunction disorders, i.e. pre-eclampsia, placental abruption, stillbirth and small for gestational age (SGA). Results Women with hyperemesis gravidarum in the first trimester had only a slightly increased risk of pre-eclampsia. Women with hyperemesis gravidarum with first admission in the second trimester had a more than doubled risk of preterm (<37 weeks) pre-eclampsia, a threefold increased risk of placental abruption and a 39% increased risk of an SGA birth (adjusted odds ratios [95% confidence intervals] were: 2.09 [1.38–3.16], 3.07 [1.88–5.00] and 1.39 [1.06–1.83], respectively). Conclusions There is an association between hyperemesis gravidarum and placental dysfunction disorders, which is especially strong for women with hyperemesis gravidarum in the second trimester.

Bolin, M; Akerud, H; Cnattingius, S; Stephansson, O; Wikstrom, AK



High temperature requirement A1 in placental tissues and serum from pre-eclamptic pregnancies with or without fetal growth restriction  

PubMed Central

Introduction Pre-eclampsia (PE) is the most serious syndrome of human pregnancy and it is potentially life-threatening for both mother and fetus. The aim of the study was to identify the role of high temperature requirement A1 (HtrA1) in pre-eclampsia. Material and methods One hundred consecutive pregnancies complicated by PE and 100 normal controls were included in our study. The changes in serum HtrA1 and fetal growth restriction were recorded. The placentae after delivery was also obtained for laboratory analyses. Results High temperature requirement A1 expressed positively in all placenta tissues, but showed higher expression from control, PE with AGA (pre-eclamptic pregnancies with appropriate-for-gestational-age newborns) to PE with fetal growth restriction (FGR) groups. Early-onset PE happened more frequently while in PE with AGA, late-onset PE was more common. Additionally, we found that only during ?28-32 gestational weeks, sera HtrA1 level of PE with AGA and PE with FGR was increased significantly compared with the control group (p < 0.05). In contrast, there was no significant difference between groups in other gestational ages in the third trimester (p > 0.05). Conclusions HtrA1 could potentially affect trophoblast migration and invasion during placentation, resulting in the shallow invasion noted in pre-eclampsia. HtrA1 may play an important role in the etiology and severity of PE and FGR. But the actual mechanism still needs deep research.

Wang, Lijuan; Huang, Pu; Shao, Wenyu; Song, Yu



Pregnancy outcomes associated with viral hepatitis.  


The aim of this study was to examine the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to pregnancy-related complications including gestational diabetes mellitus (GDM), preterm birth (PTB), intrauterine growth restriction (IUGR), pre-eclampsia, antepartum haemorrhage and cholestasis. The Nationwide Inpatient Sample was queried for all pregnancy-related discharges, pregnancy complications and viral hepatitis from 1995 to 2005. Logistic regression was used to examine the association between HBV, HCV, HBV?+?HCV and pregnancy-related complications including GDM, PTB, IUGR, pre-eclampsia, antepartum haemorrhage, cholestasis and caesarean delivery. Model covariates included maternal age, race, insurance status, substance use and medical complications including liver complication, hypertension, HIV, anaemia, thrombocytopenia and sexually transmitted infections. Of 297?664 pregnant women data available for analysis, 1446 had a coded diagnosis of HBV, HCV or both. High-risk behaviours, such as smoking, alcohol and substance use were higher in women with either HBV or HCV. Women with HBV had an increased risk for PTB (aOR 1.65, CI [1.3, 2.0]) but a decreased risk for caesarean delivery (aOR 0.686, CI [0.53, 0.88]). Individuals with HCV had an increased risk for GDM (aOR 1.6, CI [1.0, 2.6]). Individuals with both HBV and HCV co-infection had an increased risk for antepartum haemorrhage (aOR 2.82, CI [1.1, 7.2]). There was no association of viral hepatitis with IUGR or pre-eclampsia. Women with hepatitis have an increased risk for complications during pregnancy. Research to determine the efficacy and cost-effectiveness of counselling patients about potential risks for adverse outcomes is warranted. PMID:21692952

Reddick, K L B; Jhaveri, R; Gandhi, M; James, A H; Swamy, G K



[Detecting high risk pregnancy].  


Antenatal care is aiming to reduce maternal land foetal mortality and morbidity. Maternal and foetal mortality can be due to different causes. Their knowledge allows identifying pregnancy (high risk pregnancy) with factors associated with an increased risk for maternal and/or foetal mortality and serious morbidity. Identification of high risk pregnancies and initiation of appropriate treatment and/or surveillance should improve maternal and/or foetal outcome. New risk factors are continuously described thanks to improvement in antenatal care and development in biology and cytopathology, increasing complexity in identifying high risk pregnancies. Level of risk can change all over the pregnancy. Ideally, it should be evaluated prior to the pregnancy and at each antenatal visit. Clinical examination is able to screen for intra-uterin growth restriction, pre-eclampsia, threatened for preterm labour; ultrasounds help in the diagnosis of foetal morphological anomalies, foetal chromosomal anomalies, placenta praevia and abnormal foetal growth; biological exams are used to screen for pre-eclampsia, gestational diabetes, trisomy 21 (for which screening method just changed), rhesus immunisation, seroconversion for toxoplasmosis or rubeola, unknown infectious disease (syphilis, hepatitis B, VIH). During pregnancy, most of the preventive strategies have to be initiated during the first trimester or even before conception. Prevention for neural-tube defects, neonatal hypocalcemia and listeriosis should be performed for all women. On the opposite, some measures are concerning only women with risk factors such as prevention for toxoplasmosis, rhesus immunization (which recently changed), tobacco complications and pre-eclampsia and intra-uterine growth factor restriction. PMID:20058762

Doret, Muriel; Gaucherand, Pascal



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

PubMed Central

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

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



Recurrent posterior reversible encephalopathy syndrome (PRES).  


Posterior reversible encephalopathy syndrome is a proposed cliniconeuroradiological entity characterized by headache, altered mental status, cortical blindness, seizures, and other focal neurological signs, and a diagnostic magnetic resonance imaging picture. A variety of different etiologies have been reported like hypertension, pre-eclampsia/eclampsia, cyclosporin A or tacrolimus neurotoxicity, uraemia and porphyria. With early diagnosis and prompt treatment, the syndrome is usually fully reversible. We report a case of recurrent PRES of unknown aetiology following intensive care unit treatment and only moderately elevated blood pressure. Clinicians as well as radiologists must be familiar with this clinically frightening, underdiagnosed condition to assure timely diagnosis and treatment to prevent persistent deficits. PMID:15037879

Hagemann, G; Ugur, T; Witte, O W; Fitzek, C



Multifocal atrial tachycardia responsive to parenteral magnesium.  


Two groups of patients with multifocal atrial tachycardia (MAT) were treated with the intramuscular and continuous intravenous magnesium sulphate regimens used in pre-eclampsia. Both routes of administration were successful in causing reversion to sinus rhythm but the intramuscular regimen, by attaining a higher and more sustained serum magnesium concentration, converted the arrhythmia to normal sinus rhythm in a shorter period of time (1-2 hours) than the intravenous regimen (4-8 hours). Magnesium-sparing diuretics should be used in the treatment of patients with chronic obstructive pulmonary disease and congestive heart failure, which are both conditions associated with magnesium deficiency and MAT. PMID:3275209

Cohen, L; Kitzes, R; Shnaider, H



Postpartum HELLP syndrome--the case of lost battle  

PubMed Central

Unexpected rapid maternal death after delivery due to HELLP syndrome is rarely encountered and may become the subject of forensic expertise. Unexpectedness, suddenness, and fulminant course of this syndrome as well as absence of classical signs of pre-eclampsia can confuse physicians and lead to diagnostic delay. A definitive post-mortem diagnosis of HELLP syndrome in questionable cases of maternal death should be based on accepted laboratory criteria and characteristic histopathological alterations. We present a case of acute postpartum HELLP syndrome complicated by disseminated intravascular coagulation and acute renal failure which caused rapid maternal death only 20 hours after a caesarean section following an uncomplicated pregnancy.

Antic, Vladimir; Kopitovic, Vesna; Popovic, Jasmina; Trenkic, Milan; Vacic, Nikola



Anaesthesia for lower-segment caesarean section: Changing perspectives  

PubMed Central

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

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



Ocular complications of pregnancy.  


Pregnancy is often associated with ocular changes, most often transient in nature, though occasionally permanent. It can be associated with development of new conditions, or can exacerbate pre-existing conditions. The ocular effects of pregnancy may be divided into physiologic changes, pathologic conditions or modifications of pre-existing conditions. Pathologic conditions include entities such as pre-eclampsia and eclampsia, along with conditions that are seen with increased frequency during pregnancy such as central serous retinopathy. The most significant modified pre-existing condition is diabetes mellitus. The various effects of pregnancy on the eye will be reviewed in this article. PMID:11734686

Sheth, B P; Mieler, W F



Successful pregnancy after in-vitro fertilization and transmyometrial embryo transfer in a patient with congenital atresia of cervix: case report.  


A case report of a patient with congenital cervical atresia diagnosed at the age of 24 years is given. The attempts to create a neocervix were unsuccessful. Since no signs of retrograde menstruation or haematometra were observed, in agreement with the patient hysterectomy was not performed. At the age of 32 years, a successful pregnancy was achieved after an in-vitro fertilization and transmyometrial embryo transfer. Due to rapidly progressing pre-eclampsia, an elective Caesarean section was performed at 32 weeks gestation. A 1610 g healthy male infant in breech presentation was born. The post-partum period was uneventful. PMID:10357993

Anttila, L; Penttilä, T A; Suikkari, A M



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

Microsoft Academic Search

Plasminogen activator inhibitor-1 (PAI-1) is a major inhibitor of fibrinolysis, and a single nucleotide insertion\\/deletion\\u000a (4G\\/5G) polymorphism in the promoter region of the PAI-1 gene has been identified. Subjects homozygous for the 4G allele have\\u000a the highest PAI-levels due to increased PAI-1 gene transcription. Pre-eclampsia, and one of its most severe forms, the HELLP\\u000a (hemolysis, elevated liver enzymes, low platelets)

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



Factors associated with size and proportionality at birth in term Jamaican infants.  


The objective of this study was to identify the factors associated with size and proportionality at birth in a cohort of term infants established to investigate their growth and development. One hundred and forty term low-birth-weight (birth-weight < 2,500 g) infants and 94 normal birth-weight infants (2,500- < 4,000 g) were recruited within 48 hours of birth at the main maternity hospital, Kingston, Jamaica. Birth anthropometry and gestational age were measured, and maternal information was obtained by interview and from hospital records. Controlling for gestational age, variables independently associated with birth-weight were rate of weight gain in the second half of pregnancy, maternal height, haemoglobin level < 9.5 microg/dL, time of first attendance in antenatal clinic, birth order, pre-eclampsia, and consumption of alcohol, with 33% of the variance in birth-weight explained. Birth length was associated only with maternal height and age, while measures of proportionality (ponderal index and head/length ratio) were associated with characteristics of the environment in late pregnancy, including rate of weight gain, weight in late pregnancy, and pre-eclampsia. The variation in maternal characteristics associated with size or proportionality at birth may reflect the times during gestation when different aspects of growth are most affected. PMID:13677439

Walker, S P; Ewan-Whyte, C; Chang, S M; Powell, C A; Fletcher, H; McDonald, D; Grantham-McGregor, S M



Dimethyl acetals, an indirect marker of the endogenous antioxidant plasmalogen level, are reduced in blood lipids of Sudanese pre-eclamptic subjects whose background diet is high in carbohydrate.  


In Sudanese women with (n = 60) and without (n = 65) pre-eclampsia, circulating lipids, plasma and red cell saturated and monounsaturated fatty (MUFA) acids and dimethyl acetals (DMAs) were investigated. DMAs are an indirect marker of levels of plasmalogens, endogenous antioxidants, which play a critical role in oxidative protection, and cholesterol homeostasis. The pre-eclamptics had higher C18:1n-9 (p < 0.001) and ?MUFA (p < 0.01) in plasma free fatty acids, C16:1n-7, C18:1n-9, ?MUFA; 16:0/16:1n-7 (p < 0.01) in erythrocyte choline phosphoglycerides (ePC) and 16:1n-7, 18:1n-7 and 16:0/16:1n-7 (p < 0.01) in erythrocyte ethanolamine phosphoglycerides (ePE). In contrast, the DMAs 18:0, 18:1 and ?DMAs in ePE, and 16:0, 18:0 and ?DMAs in ePC were reduced (p < 0.001) in the pre-eclamptic women. This study of pregnant women with high carbohydrate and low fat background diet suggests pre-eclampsia is associated with oxidative stress and enhanced activity of the microsomal enzyme stearyl-CoA desaturase (delta 9 desaturase), as assessed by palmitic/palmitoleic (C16:0/C16:n-1) and stearic/oleic (C18/C18:1n-9) ratios. PMID:22369396

Bueno, A A; Ghebremeskel, K; Bakheit, K H; Elbashir, M I; Adam, I



Population-based trends of pregnancy outcome in obese mothers: what has changed over 15 years.  


Maternal obesity is a growing concern worldwide. We aimed to determine trends of obesity in women of reproductive age over a 15-year period, the relationship between prepregnancy weight status and pregnancy-related outcomes, and possible changes over a 15-year period. Data was derived from two identical, cross-sectional National Perinatal Surveys (NPSs). Analysis was restricted to the mothers of healthy, full-term, singleton infants. Overall, the study population consisted of 18,752 mother-infant pairs (7,208 from the 1st NPS and 11,544 from the 2nd NPS). The prevalence of overweight and obese women prior to pregnancy increased significantly between the two surveys, from 12 to 15.3% and 2.1 to 4.7%, respectively. In both study periods, prepregnancy weight status was positively associated with pre-eclampsia (P < 0.001) and method of delivery (P < 0.001). After adjusting for potential confounders, overweight and obese women had higher odds for caesarian section (adjusted (odd ratio) OR = 1.87) and pre-eclampsia (adjusted OR = 2.59) than normal-weight women. These associations did not change between the study periods. In conclusion, prepregnancy maternal obesity is steadily increasing over time. The magnitude of the problem underlies the need for public health programs to focus on obesity prevention, particularly among women of reproductive age, and re-evaluate the guidelines for various perinatal practices. PMID:21253002

Alexandra, Palili; Vassilios, Bakoulas; Alexandra, Veltsista; George, Kavadias; Vassiliki, Lekea; Chryssa, Bakoula



Regulation of myometrial circulation and uterine vascular tone by constitutive nitric oxide.  


Pregnancy is a physiological state that involves an increase in uterine blood flow, which is mediated in part by nitric oxide (NO) liberated from the endothelium and nitrergic neurons. The main focus of this review article is to provide information about how endogenous NO regulates uterine and placental blood flow and vascular tone in experimental animals and humans in vivo or in vitro in non-pregnant and pregnant states as well as pregnancy with pre-eclampsia. Uterine arteries from non-pregnant women respond to NO liberated from the endothelium and nitrergic nerves with relaxations, and the release of endothelial NO is influenced by the phase of the estrous cycle, with its enhanced release at the follicular phase when the estrogen level is high. NO bioavailability in the uteroplacental circulatory system is gradually increased during pregnancy. Pre-eclamptic pregnancies with or without intrauterine growth restriction show impaired uteroplacental blood flow accompanied by reduced NO synthesis due to down-regulation of eNOS as well as asymmetric dimethylarginine accumulation and by augmented NO degradation by oxidative stress. Further studies are expected to provide new mechanistic insights into the fascinating process of maternal uterine adaptation in humans and novel prophylactic and therapeutic measures against pre-eclampsia. PMID:23872378

Toda, Noboru; Toda, Hiroshi; Okamura, Tomio



Maternal and neonatal outcome after laparoscopic adjustable gastric banding: a systematic review.  


The number of women of reproductive age undergoing bariatric surgery, including laparoscopic adjustable gastric banding (LAGB), has increased in recent years. The objective of this study was to list both maternal and neonatal outcomes in pregnancies in obese women (BMI???30 kg/m(2)) after LAGB and compare them with pregnancies in obese or normal weight women without LAGB. Studies showed a lower incidence of gestational diabetes, pregnancy-induced hypertension (PIH), pre-eclampsia, caesarean section (CS), macrosomia, and low birth weight babies in post-LAGB pregnancies compared to pregnancies in obese women without LAGB. Gestational weight gain was also lower in post-LAGB pregnancies. However, the incidence of PIH, pre-eclampsia, CS, preterm birth, large for gestational age, spontaneous abortion, and NICU admission was higher in post-LAGB pregnancies than in normal weight pregnancies. In conclusion, LAGB seems to improve pregnancy outcomes in obese women, even when obesity is still present at the onset of pregnancy. However, further research is needed and pregnant women with a gastric band should always be closely monitored by a multidisciplinary team. PMID:22903514

Vrebosch, L; Bel, S; Vansant, G; Guelinckx, I; Devlieger, R



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


A prospective study of cord blood for coagulability, evidence for disseminated intravascular coagulation (DIC), and hematocrit was done in 106 infants who were offspring of mothers with high-risk pregnancies (pre-eclampsia, diabets mellitus, third-trimester bleeders, severe erythroblastosis fetalis, maternal hypertension, fetal distress, and spontaneous premature labor). Significant changes of hypercoagulability (low AT-III and abnormal TEG) were seen in the third-trimester bleeder and premature labor groups which also had the highest incidence of IRDS and necrotizing. Infants undergoing "stress" (pre-eclampsia, fetal distress) had elevated levels of factors V and VIII but were not hypercoagulable or AT-III deficient. Except for mild thrombocytopenia, infants of the diabetic mothers, a group with increased thrombotic complications, did not show any cord blood abnormalities. Offspring of third-trimester bleeders were anemic. The EBF infants were also anemic, severely hypercoagulable, and showed coagulation changes compatible with severe liver disease and/or DIC. Mild changes compatible with intravascular coagulation were seen in six infants and were not related to the the development of IRDS. PMID:1115115

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



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


Time-resolved spectroscopy (TRS-20) measures tissue oxygen saturation (%) by evaluating the absolute concentrations of oxygenated, deoxygenated and total haemoglobin based on measurement of the transit time of individual photons through a tissue of interest. We measured tissue oxygen saturation in the prefrontal lobes of the brain by TRS-20 in eighteen pregnant women during caesarean section. In a case of placenta previa, massive bleeding immediately decreased cerebral oxygen saturation from 67·2% to 54·2%, but did not alter peripheral tissue oxygenation as measured by pulse oximetry. Four cases of pre-eclampsia revealed chronic changes in elevated base levels of cerebral oxygen saturation, though peripheral oxygen saturation was similar to that in normotensive pregnant women. Average cerebral oxygen saturation in the cases of pre-eclampsia before the introduction of anaesthesia was 73·6 ± 4·4 (SD)% (n = 4), significantly higher than in normotensive pregnant women, 67·2 ± 4·3% (n = 13, P<0·05). Z-scores of cerebral oxygen saturation prior to anaesthesia positively correlated with those of systolic or diastolic blood pressure. TRS-20 could detect acute as well as chronic changes in brain oxygen saturation in response to pregnancy-associated complications. PMID:23383688

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



[Ultrasound Doppler sonography in obstetrics. A comparison between simple Doppler methods (continuous or pulsed Doppler) and the duplex system (combination of B-image and pulse Doppler)].  


120 pregnant women between the 26th and 42nd week of gestation have been examined using simple Doppler-units with pulsed- or continuous-wave technique and duplex Doppler-units (combined B-mode and pulsed-wave Doppler). The umbilical and uterine arteries were measured with both units in a semi-recumbent position at the same time by the same examiner. Only ideal flow profiles were taken to calculate the S/D-ratio. Our results were correlated to the fetal outcome, to all cases of pre-eclampsia and to all cases of intra-uterine growth retardation. Except in one of these cases we got the majority of pathological results using simple Doppler-units. Only in pre-eclampsia the duplex Doppler-units had the majority of pathological results. Even in normal fetal outcome the majority of simple Doppler-unit results are pathological. This finding is due to the impossibility to localize the vessel exactly using simple Doppler-units. Sensitivity is higher in simple Doppler-techniques (74.3% to 52.9%), specificity is higher in duplex Doppler-technique (77.9% to 52.6%). PMID:1926969

Jörn, H; Fendel, H; Christ, B


Gestational weight gain, prepregnancy body mass index related to pregnancy outcomes in KAZERUN, FARS, IRAN  

PubMed Central

Objective: The aim of this study was to evaluate associations between pregnancy outcomes and prepregnancy body mass index and gestational weight gain among pregnant women who regularly attended health centers of Kazerun, Fars, Iran. Methods: In this descriptive study records from 5172 pregnant women were considered in this study, based on the methodology criteria. Women were distributed across 4 prepregnancy categories according to the Institute of Medicine (IOM) (1990) classification of body mass index, and to 4 end-of-pregnancy categories according to median weekly gestational weight gain. Results: The risks for gestational diabetes, gestational hypertension, pre-eclampsia, and preterm premature rupture of membranes were higher for those who were overweight or obese before becoming pregnant (P < 0.05). Moreover, a gestational weight gain of 0.50 kg per week or greater was associated with a higher risk for gestational hypertension, preterm premature rupture of membranes, and fetal macrosomia (P < 0.05). Women in the highest quartile for weight gain (? 0.59 kg per week) were at higher risk for pre-eclampsia (P < 0.05). Discussion: The results seems to indicate that excessive gestational weight gain and high prepregnancy body mass index were associated with increased risks for adverse pregnancy outcomes.

Tabatabaei, Mozhgan



Human trophoblast survival at low oxygen concentrations requires metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor.  


Heparin-binding EGF-like growth factor (HBEGF), which is expressed in the placenta during normal pregnancy, is down regulated in pre-eclampsia, a human pregnancy disorder associated with poor trophoblast differentiation and survival. This growth factor protects against apoptosis during stress, suggesting a role in trophoblast survival in the relatively low O(2) ( approximately 2%) environment of the first trimester conceptus. Using a well-characterized human first trimester cytotrophoblast cell line, we found that a 4-hour exposure to 2% O(2) upregulates HBEGF synthesis and secretion independently of an increase in its mRNA. Five other expressed members of the EGF family are largely unaffected. At 2% O(2), signaling via HER1 or HER4, known HBEGF receptors, is required for both HBEGF upregulation and protection against apoptosis. This positive-feedback loop is dependent on metalloproteinase-mediated cleavage and shedding of the HBEGF ectodomain. The restoration of trophoblast survival by the addition of soluble HBEGF in cultures exposed to low O(2) and metalloproteinase inhibitor suggests that the effects of HBEGF are mediated by autocrine/paracrine, rather than juxtacrine, signaling. Our results provide evidence that a post-transcriptional mechanism induced in trophoblasts by low O(2) rapidly amplifies HBEGF signaling to inhibit apoptosis. These findings have a high clinical significance, as the downregulation of HBEGF in pre-eclampsia is likely to be a contributing factor leading to the demise of trophoblasts. PMID:16407398

Armant, D Randall; Kilburn, Brian A; Petkova, Anelia; Edwin, Samuel S; Duniec-Dmuchowski, Zophia M; Edwards, Holly J; Romero, Roberto; Leach, Richard E



Late sporadic miscarriage is associated with abnormalities in spiral artery transformation and trophoblast invasion.  


Trophoblast invasion of uterine decidua and myometrium, and spiral artery transformation, are essential for the development of normal pregnancy; this process is impaired in pre-eclampsia, fetal growth restriction, and pre-term labour. The hypothesis that late miscarriage is associated with reduced trophoblast invasion and spiral artery transformation was tested in a large series of placental bed biopsies containing decidua and myometrium from late, karyotyped, embryonic miscarriage (>or=13 weeks' gestation; n = 26; n = 96 spiral arteries) and gestationally matched ultrasound-dated normal pregnancies (n = 74; n = 236 spiral arteries). Cryostat sections were immunostained using an avidin-biotin peroxidase technique for cytokeratin, desmin, and von Willebrand factor to detect trophoblast, myometrium, and vascular smooth muscle and endothelium, respectively. Trophoblast invasion and individual features of spiral artery transformation were assessed and analysed using a logistic regression model. Compared with normal pregnancy, myometrial spiral arteries in late miscarriage showed reduced endovascular (4% vs. 31%, p = 0.001) and intramural trophoblast (76% vs. 88%, p = 0.05), and less extensive fibrinoid change (4% vs. 18%, p = 0.01). In contrast, endovascular trophoblast in decidual spiral arteries was increased (40% vs. 66%, p = 0.04). These findings suggest that, in common with pre-eclampsia, late sporadic miscarriage may be associated with reduced trophoblast invasion and inadequate transformation of myometrial spiral arteries. PMID:16402350

Ball, E; Bulmer, J N; Ayis, S; Lyall, F; Robson, S C



Neurodevelopmental fetal assessment using KANET scoring system in low and high risk pregnancies.  


Objective: To assess and compare fetal behavior and neurodevelopment (KANET) between low and high risk pregnancies. Methods: Prospective, comparative, cohort study. One hundred and fifty-two consecutive pregnant women presenting for routine 2nd trimester and 3rd trimester scan had four dimensional ultrasound examinations (4D US) in order to assess fetal behavior and neurodevelopment. This was achieved by the study of: (1) isolated head movements, (2) isolated hand movements, (3) isolated leg movements, (4) cranial sutures, (5) hand to face/head movements, (6) finger movements, (7) yawning - mouthing, (8) facial expressions, (9) isolated eye blinking, (10) "Gestalt" perception. According to the maternal background risk, the population of the study was classified in low risk pregnancies (n = 78) and high risk pregnancies (n = 74) with IUGR fetuses (n = 12), diabetes mellitus (n = 24), and pre-eclampsia (n = 38). Results: The neurodevelopmental score was statistically significant higher in the low risk group compared to the high risk group (p < 0.0004). The diabetes subgroup score was statistically significantly higher compared to the IUGR and the pre-eclampsia subgroup (p = 0.0001). Conclusions: The neurodevelopment fetal assessment by 4D ultrasound appears to be a feasible technique in the evaluation of high risk pregnancies. Further studies where any association between KANET score and neurological outcome of the childhood are warranted. PMID:23211123

Athanasiadis, Apostolos P; Mikos, Themistoklis; Tambakoudis, George P; Theodoridis, Theodoros D; Papastergiou, Maria; Assimakopoulos, Efstratios; Tarlatzis, Basil C



Identifying barriers to the availability and use of Magnesium Sulphate Injection in resource poor countries: A case study in Zambia  

PubMed Central

Background Pre-eclampsia and eclampsia are serious complications of pregnancy and major causes of maternal mortality and morbidity worldwide. According to systematic reviews and WHO guidelines magnesium sulphate injection (MgSO4) should be the first -line treatment for severe pre-eclampsia and eclampsia. Studies have shown that this safe and effective medicine is unavailable and underutilized in many resource poor countries. The objective of this study was to identify barriers to the availability and use of MgSO4 in the Zambian Public Health System. Methods A 'fishbone' (Ishikawa) diagram listing probable facilitators to the availability and use of MgSO4 identified from the literature was used to develop an assessment tool. Barriers to availability and use of MgSO4 were assessed at the regulatory/government, supply, procurement, distribution, health facility and health professional levels. The assessment was completed during August 2008 using archival data, and observations at a pragmatic sample of health facilities providing obstetric services in Lusaka District, Zambia. Results The major barrier to the availability of MgSO4 within the public health system in Zambia was lack of procurement by the Ministry of Health. Other barriers identified included a lack of demand by health professionals at the health centre level and a lack of in-service training in the use of MgSO4. Where there was demand by obstetricians, magnesium sulphate injection was being procured from the private sector by the hospital pharmacy despite not being registered and licensed for use for the treatment of severe pre-eclampsia and eclampsia by the national Pharmaceutical Regulatory Authority. Conclusions The case study in Zambia highlights the complexities that underlie making essential medicines available and used appropriately. The fishbone diagram is a useful theoretical framework for illustrating the complexity of translating research findings into clinical practice. A better understanding of the supply system and of the pattern of demand for MgSO4 in Zambia should enable policy makers and stakeholders to develop and implement appropriate interventions to improve the availability and use of MgSO4.



Diagnosis of acute neurological emergencies in pregnant and post-partum women.  


Acute neurological symptoms in pregnant and post-partum women could be caused by exacerbation of a pre-existing neurological condition, the initial presentation of a non-pregnancy-related problem, or a new acute-onset neurological problem that is either unique to or occurs with increased frequency during or just after pregnancy. Pregnant and postpartum patients with headache and neurological symptoms are often diagnosed with pre-eclampsia; however, a range of other causes must also be considered, such as cerebral venous sinus thrombosis and reversible cerebral vasoconstriction syndrome. Precise diagnosis is essential to guide subsequent management. Our ability to differentiate between the specific causes of acute neurological symptoms in pregnant and post-partum patients is likely to improve as we learn more about the pathogenesis of these disorders. PMID:23332362

Edlow, Jonathan A; Caplan, Louis R; O'Brien, Karen; Tibbles, Carrie D



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

PubMed Central

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

Samra, Khawla Abu



Management of paroxysmal hypertension due to incidental pheochromocytoma in pregnancy  

PubMed Central

A 25-year-old, full-term pregnant woman diagnosed with pre-eclampsia was referred to our tertiary care hospital with severe resistant hypertension. Her blood pressure remained labile despite the usual medications, which led to the suspicion of an underlying endocrinological problem. Further biochemical and radiological investigations confirmed the diagnosis of pheochromocytoma. The patient was invasively monitored and treated with alpha blockade, beta blocker, and vasodilators. The primary goals for the management of pheochromocytoma in pregnancy are early diagnosis, avoidance of a hypertensive crisis during delivery, and definitive surgical treatment. This case illustrates that one needs to be cautious when such a presentation of paroxysmal hypertension is present. With a multidisciplinary team approach, proper planning, and adequate preoperative medical management, pheochromocytoma in pregnancy can be managed successfully.

Lata, Indu; Sahu, Sandeep



Full-term abdominal extrauterine pregnancy complicated by post-operative ascites with successful outcome: a case report  

PubMed Central

Introduction Advanced abdominal (extrauterine) pregnancy is a rare condition with high maternal and fetal morbidity and mortality. Because the placentation in advanced abdominal pregnancy is presumed to be inadequate, advanced abdominal pregnancy can be complicated by pre-eclampsia, which is another condition with high maternal and perinatal morbidity and mortality. Diagnosis and management of advanced abdominal pregnancy is difficult. Case presentation We present the case of a 33-year-old African woman in her first pregnancy who had a full-term advanced abdominal pregnancy and developed gross ascites post-operatively. The patient was successfully managed; both the patient and her baby are apparently doing well. Conclusion Because most diagnoses of advanced abdominal pregnancy are missed pre-operatively, even with the use of sonography, the cornerstones of successful management seem to be quick intra-operative recognition, surgical skill, ready access to blood products, meticulous post-operative care and thorough assessment of the newborn.



Serum and urine electrolytes in primigravid Africans during pregnancy and postnatal period.  


Serum and urine electrolyte changes were studied in 55 primigravid African women during pregnancy and the postnatal period. The findings suggest that there is a fall in the serum sodium in the first trimester, which is followed by a gradual and steady rise throughout pregnancy. The serum potassium did not show any consistent pattern, while the serum chloride generally followed that of the serum sodium. These findings are similar to those reported for the Caucasian, although the African subject displays a lower serum sodium level and a much higher chloride level throughout pregnancy and the postnatal period. It is suggested that the reduction in sodium excretion noted in the third trimester is a reflection of the increasing sodium concentration in the blood with advancing pregnancy. The few patients who developed oedema and pre-eclampsia excreted relatively larger amounts of sodium in the puerperium. PMID:719896

Isichei, U P; Egwuatu, V E; Umez-Eronini, E M



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


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

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



An antithrombotic role for nutritional antioxidants: implications for tumor metastasis and other pathologies.  


Nutritional antioxidants support prostacyclin synthesis by preventing lipid hydroperoxide-mediated inhibition of prostacyclin synthetase. Recent preliminary clinical studies indicate that supplementary antioxidants exert antithrombotic effects in vivo that are most likely attributable to enhanced prostacyclin production. Optimal antioxidant nutrition may thus have preventive and therapeutic value for disorders in which inappropriate platelet aggregation plays an etiologic role, including MI, stroke, atherogenesis, pre-eclampsia, and the vascular complications of diabetes. In light of evidence that platelet aggregation encourages the implantation of hematogenous tumor metastases, supplemental antioxidants should also impede tumor dissemination--an effect which will be complemented by the immunostimulant actions of these nutrients. By exerting anticarcinogenic, immunostimulant and anti-metastatic effects, nutritional antioxidants should act to inhibit neoplasia at each stage of its development. PMID:3520253

McCarty, M F



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


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



Adverse outcomes in Type I diabetic pregnant women with proliferative diabetic retinopathy  

PubMed Central

AIM To report maternal and fetal adverse outcomes, in spite of appropriate treatment and regular follow up, in diabetic pregnant women with proliferative diabetic retinopathy. METHODS Case series of four young pregnant diabetics aged between 20 and 25 years with type I diabetes mellitus and proliferative diabetic retrinopathy. RESULTS The maternal adverse outcomes were abortion in one patient, pre-eclampsia and preterm delivery in one patient, and renal failure requiring dialysis in one patient. The fetal adverse outcomes were neonatal death in one case and premature baby in another case. CONCLUSION These cases highlight the fact that diabetic pregnant women should be closely followed up by the obstetricians and physicians when they have proliferative retinopathy. The proliferative diabetic retinopathy should be considered as a part of the assessment when counseling a diabetic woman in antenatal check up and also in the follow up visits during pregnancy.

Helen, C C T; Tajunisah, I; Reddy, S C



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.

Nadeau, M.; Best, L.



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.

Lalitha, Rejani; Opio, Christopher Kenneth



[Antiphospholipid syndrome and pregnancy].  


Antiphospholipid syndrome is characterized by arterial and venous thromboembolic events and persistent laboratory evidence of antiphospholipid antibodies. Obstetric complications such as recurrent miscarriage, early delivery, oligohydramnios, prematurity, intrauterine growth restriction, fetal distress, fetal or neonatal thrombosis, pre-eclampsia/eclampsia, and HELLP syndrome are also hallmarks of antiphospholipid syndrome. This syndrome is one of the diseases associated with the most severe thrombotic risk. Changes in the hemostatic system during normal pregnancy also result in a hypercoagulable state resulting in elevated thrombotic risk. Thromboembolic events are responsible of the vast majority of maternal and fetal deaths. Administration of appropriate thromboprophylaxis helps prevent thromboembolic complications during pregnancy in women with antiphospholipid syndrome and also give birth to healthy children. It is important to centralize the medication and management of these patients. It helps in the thoughtful care of these pregnant women encountering serious problems. PMID:22846489

Gadó, Klára; Domján, Gyula



Maternal-fetal lead poisoning from a 15-year-old bullet.  


Blood lead was mildly elevated (31 microg/dl, where 25 microg/dl is the upper limit of the normal range) in a woman with lumbar bullet fragments who was evaluated for anemia in the 23rd week of pregnancy. She required Cesarean section at term for pre-eclampsia and fetal distress. The infant had multiple congenital abnormalities. Postpartum maternal blood lead level was 75-85 microg/dl. The infant's blood lead level was also elevated. Chelation lowered the infant's blood lead level, but not the mother's. Surgical debulking of the lumbar lead deposits was followed by a fall in blood lead level from 65 to 52 microg/dl. This case demonstrates a remarkable gestational rise in maternal blood lead level. The infant's congenital abnormalities could be causally related to lead. PMID:12380612

Raymond, L W; Ford, M D; Porter, W G; Saxe, J S; Ullrich, C G



Endogenous digitalis  

PubMed Central

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

Bagrov, Alexei Y; Shapiro, Joseph I



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


Haemodynamic changes that occur during pregnancy are maximal between 28 and 34 weeks. In the pregnant woman with several associated diseases, such as hypertensive myocardiopathy and pre-gestational diabetes, these changes can lead to a difficult control of pulmonary hypertension and acute pulmonary oedema. We report the case of a pregnant woman with long term type 1 diabetes mellitus who suffered pre-eclampsia in a previous pregnancy, and since then developed hypertensive cardiomyopathy. She was admitted at 30 week gestation for metabolic and blood pressure control, and developed congestive cardiac failure after the administration of betamethasone for foetal lung maturity. A transthoracic echocardiogram showed a non-dilated hypertrophic left ventricle with good systolic function, restrictive diastolic dysfunction and moderate pulmonary arterial hypertension. When her general condition improved, we performed a caesarean section under regional anaesthesia to prevent the complications of pulmonary and systemic hypertension. We present the anaesthetic management and resolution of complications after oxytocin administration. PMID:22565223

Holgado, C M; Coves, S



Adenosine deaminase activity in normal pregnancy and pregnancy associated disorders.  


Adenosine deaminase (ADA) is an enzyme of purine salvage pathway and has two important isoenzymes ADA1 and ADA2. The activity of ADA has been changed in diseases characterized by altered cell-mediated immunity. It was observed that total serum ADA activity was decreased during normal pregnancy compared with non-pregnant women. However, total serum ADA activity and serum ADA2 activity was increased in hyperemesis gravidarum and pre-eclampsia in pregnant women. Less information is available regarding role of ADA in abortions (recurrent and missed) and anembryonic pregnancies. Here, we review the activity of ADA and its isoenzymes. Despite these findings, it will be interesting to know whether activity of ADA will be same if ADA is estimated throughout the pregnancy and in pregnancy related complications from early first trimester to third trimester, as all studies until now were carried out at a particular stage of pregnancy. PMID:23527577

Jadhav, Ashish Anantrao; Jain, Anuradha



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

PubMed Central

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

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



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


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



Oxidative stress-induced S100B protein from placenta and amnion affects soluble Endoglin release from endothelial cells.  


Oxidative stress with elevated intracellular Ca(2+) concentration as well as endothelial dysfunction is a component of pre-eclampsia. Our aim was to investigate the oxidative stress-dependent expression of Endoglin and Ca(2+)-binding S100B protein from villous and amniotic tissue cultures, and to assess sEng expression from S100B protein-stimulated endothelial cells. We initially examined Endoglin and Hydroxy-nonenal-(HNE)-modified proteins in the placentas and amnion obtained from women with pre-eclampsia (n = 8), and healthy controls (n = 8) by immunohistochemistry. To examine oxidative stress and the S100B protein effect on sEng expression from endothelial cells, normal villous and amniotic tissue cultures were stimulated by 4-HNE, sodium fluoride and xanthine/xanthine oxidase, whereas human umbilical vein endothelial cell cultures were treated with S100B protein in a dose- and time-dependent manner at 37 degrees C in an environment of 95% air and 5% of CO(2). Culture supernatants were assessed using ELISA. Cell viability was determined using MTS assay. The concentrations of sEng and S100B protein were significantly increased in the villous and amniotic tissue culture supernatants under oxidative stress. S100B protein-stimulated endothelial cells released sEng into conditioned media with a significantly higher expression levels at a concentration of 200 pM-20 nM S100B by 2 h, whereas treated with 200 nM of S100B endothelial cells significantly expressed sEng by 12 h and stimulated the cell proliferation by the same period of time. Our findings show that oxidative stress affects sEng and S100B protein expression from villous and amniotic tissues, and picomolar and low nanomolar concentrations of S100B protein significantly up-regulate sEng release from endothelial cells leading to endothelial dysfunction. PMID:19939849

Tskitishvili, E; Sharentuya, N; Temma-Asano, K; Mimura, K; Kinugasa-Taniguchi, Y; Kanagawa, T; Fukuda, H; Kimura, T; Tomimatsu, T; Shimoya, K



Impact of Janani Suraksha Yojana on Institutional Delivery Rate and Maternal Morbidity and Mortality: An Observational Study in India  

PubMed Central

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

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



How to manage hypertension in pregnancy effectively  

PubMed Central

The hypertensive disorders of pregnancy (HDP) are a leading cause of maternal mortality and morbidity in both well and under-resourced settings. Maternal, fetal, and neonatal complications of the HDP are concentrated among, but not limited to, women with pre-eclampsia. Pre-eclampsia is a systemic disorder of endothelial cell dysfunction and as such, blood pressure (BP) treatment is but one aspect of its management. The most appropriate BP threshold and goal of antihypertensive treatment are controversial. Variation between international guidelines has more to do with differences in opinion rather than differences in published data. For women with severe hypertension [defined as a sustained systolic BP (sBP) of ?160 mmHg and/or a diastolic BP (dBP) of ?110 mmHg], there is consensus that antihypertensive therapy should be given to lower the maternal risk of central nervous system complications. The bulk of the evidence relates to parenteral hydralazine and labetalol, or to oral calcium channel blockers such as nifedipine capsules. There is, however, no consensus regarding management of non-severe hypertension (defined as a sBP of 140–159 mmHg or a dBP of 90–109 mmHg), because the relevant randomized trials have been underpowered to define the maternal and perinatal benefits and risks. Although antihypertensive therapy may decrease the occurrence of BP values of 160–170/100–110 mmHg, therapy may also impair fetal growth. The potential benefits and risks do not seem to be associated with any particular drug or drug class. Oral labetalol and methyldopa are used most commonly, but many different ?-adrenoceptor blockers and calcium channel blockers have been studied in clinical trials.

Magee, Laura A; Abalos, Edgardo; von Dadelszen, Peter; Sibai, Baha; Easterling, Tom; Walkinshaw, Steve



Hypertensive crisis during pregnancy and postpartum period.  


Hypertension affects 10% of pregnancies, many with underlying chronic hypertension, and approximately 1-2% will undergo a hypertensive crisis at some point during their lives. Hypertensive crisis includes hypertensive urgency and emergency; the American College of Obstetricians and Gynecologists describes a hypertensive emergency in pregnancy as persistent (lasting 15 min or more), acute-onset, severe hypertension, defined as systolic BP greater than 160 mmHg or diastolic BP >110 mmHg in the setting of pre-eclampsia or eclampsia. Pregnancy may be complicated by hypertensive crisis, with lower blood pressure threshold for end-organ damage than non-pregnant patients. Maternal assessment should include a thorough history. Fetal assessment should include heart rate tracing, ultrasound for growth and amniotic assessment, and Doppler evaluation if growth restriction is suspected. Initial management of hypertensive emergency (systolic BP >160 mmHg or diastolic BP >110 mmHg in the setting of pre-eclampsia or eclampsia) generally includes the rapid reduction of blood pressure through the use of intravenous antihypertensive medications, with goal systolic blood pressure between 140 mmHg and 150 mmHg and diastolic pressure between 90 mmHg and 100 mmHg. First-line intravenous drugs include labetalol and hydralazine, but other agents may be used, including esmolol, nicardipine, nifedipine, and, as a last resort, sodium nitroprusside. Among patients with hypertensive urgency, slower blood pressure reduction can be provided with oral agents. The objective of this article is to review the current understanding, diagnosis, and management of hypertensive crisis during pregnancy and the postpartum period. PMID:23916027

Too, Gloria T; Hill, James B



Pregnancy in past or present lupus nephritis: a study of 32 pregnancies from a single centre  

PubMed Central

OBJECTIVE—To study maternal and fetal outcome in women with past or present histologically proven systemic lupus erythematosus (SLE) nephritis.?METHOD—Retrospective study of 32 pregnancies in 22 women with past or present histologically proven SLE nephritis in a single French centre.?RESULTS—Pregnancy (25 planned and 7 not planned) occurred in a mean (SD) of 8 (5) years after SLE diagnosis and 6 (4) years after renal disease onset. Seven occurred in women with antiphospholipid syndrome. At pregnancy onset, all but one woman had creatininaemia below 100 µmol/l, five had proteinuria >0.5 g/day, none had hypertension. Twelve pregnancies occurred in women previously treated with immunosuppressant drugs. Treatment comprised prednisone (n=31), hydroxychloroquine (n=11), aspirin (n=22), heparin (n=12), and azathioprine in one patient with steroid resistant nephrotic syndrome disclosing SLE. No therapeutic abortion was done. During pregnancy or the postpartum period, or both, proteinuria >0.5 g/day occurred in 10 women (five related to pre-eclampsia, four to renal flare, one to stable nephrotic syndrome). One flare consisted of mild arthralgias. Pregnancy outcome comprised one feto-maternal death in SLE disclosed by pregnancy, five embryonic losses, two fetal deaths, and 18 premature (one neonatal death) and six full term births. No criterion appeared to influence fetal survival significantly. At long term, one patient died during an SLE flare, three women had renal relapses. At the last visit, all had creatininaemia below 100 µmol/l except one woman with creatinine level 115 µmol/l, nine had proteinuria >0.5 g/day, and one was treated for hypertension.?CONCLUSION—Pregnancy need not be discouraged in women with a history of SLE nephritis with normal or mildly impaired renal function. Deterioration of renal function rarely occurs. However, these pregnancies are at high risk of pre-eclampsia and prematurity.??

Huong, D; Wechsler, B; Vauthier-Brouzes, D; Beaufils, H; Lefebvre, G; Piette, J



Shift work and pregnancy outcomes: a systematic review with meta-analysis of currently available epidemiological studies  

PubMed Central

Background Varying work schedules are suspected of increasing risks to pregnant women and to fetal wellbeing. In particular, maternal hormonal disturbance arising from sleep deprivation or circadian rhythm disruption might impair fetal growth or lead to complications of pregnancy. Two independent meta-analyses (from 2000 and 2007) reported a small adverse effect of shift work on the risk of preterm delivery (PTD). However, these reviews were based on few high quality studies. Objectives To provide an updated review of the associations of shift work with PTD, low birthweight (LBW), small for gestational age (SGA), and pre-eclampsia. Search strategy and Selection Criteria We conducted a systematic search of MEDLINE using combinations of keywords and MeSH terms. Data Collection and Analysis for each relevant paper we abstracted standard details, used to summarize design features and rate methodological quality. We calculated pooled estimates of relative risk (RR) in random-effect meta-analyses. Main Results We retrieved 23 relevant studies. The pooled estimate of RR for PTD was 1.16 (95%CI 1.00-1.33, 16 studies), but when five reports of poorer methodological quality were excluded, the estimated RR reduced to 1.03 (95%CI 0.93-1.14). We also observed increased RRs for LBW (1.27, 95%CI 0.93-1.74) and for SGA (1.12, 95%CI 1.03-1.22), which varied little by study quality. Little evidence was found on pre-eclampsia. Conclusions These findings suggest that overall, any risk of PTD, LBW, or SGA arising from shift-work in pregnancy is small.

Matteo, Bonzini; Palmer, Keith T; David, Coggon; Michele, Carugno; Antonella, Cromi; Ferrario, Marco M



Quantifying the fall in mortality associated with interventions related to hypertensive diseases of pregnancy  

PubMed Central

Background In this paper we review the evidence of the effect of health interventions on mortality reduction from hypertensive diseases in pregnancy (HDP). We chose HDP because they represent a major cause of death in low income countries and evidence of effect on maternal mortality from randomised studies is available for some interventions. Methods We used four approaches to review the evidence of the effect of interventions to prevent or treat HDP on mortality reduction from HDP. We first reviewed the Cochrane Library to identify systematic reviews and individual trials of the efficacy of single interventions for the prevention or treatment of HDP. We then searched the literature for articles quantifying the impact of maternal health interventions on the reduction of maternal mortality at the population level and describe the approaches used by various authors for interventions related to HDP. Third, we examined levels of HDP-specific mortality over time or between regions in an attempt to quantify the actual or potential reduction in mortality from HDP in these regions or over time. Lastly, we compared case fatality rates in women with HDP-related severe acute maternal morbidity with those reported historically in high income countries before any effective treatment was available. Results The Cochrane review identified 5 effective interventions: routine calcium supplementation in pregnancy, antiplatelet agents during pregnancy in women at risk of pre-eclampsia, Magnesium sulphate (MgS04) for the treatment of eclampsia, MgS04 for the treatment of pre-eclampsia, and hypertensive drugs for the treatment of mild to moderate hypertension in pregnancy. We found 10 studies quantifying the effect of maternal health interventions on reducing maternal mortality from HDP, but the heterogeneity in the methods make it difficult to draw uniform conclusions for effectiveness of interventions at various levels of the health system. Most authors include a health systems dimension aimed at separating interventions that can be delivered at the primary or health centre level from those that require hospital treatment, but definitions are rarely provided and there is no consistency in the types of interventions that are deemed effective at the various levels. The low levels of HDP related mortality in rural China and Sri Lanka suggest that reductions of 85% or more are within reach, provided that most women give birth with a health professional who can refer them to higher levels of care when necessary. Results from studies of severe acute maternal morbidity in Indonesia and Bolivia also suggest that mortality in women with severe pre-eclampsia or eclampsia in hospital can be reduced by more than 84%, even when the women arrive late. Conclusions The increasing emphasis on the rating of the quality of evidence has led to greater reliance on evidence from randomised controlled trials to estimate the effect of interventions. Yet evidence from randomised studies is often not available, the effects observed on morbidity may not translate in to mortality, and the distinction between efficacy and effectiveness may be difficult to make. We suggest that more use should be made of observational evidence, particularly since such data represent the actual effectiveness of packages of interventions in various settings.



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

PubMed Central

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

Ebbing, Cathrine; Kiserud, Torvid; Johnsen, Synn?ve Lian; Albrechtsen, Susanne; Rasmussen, Svein



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


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

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



?-Tocopheryl phosphate--an activated form of vitamin E important for angiogenesis and vasculogenesis?  


Vitamin E was originally discovered as a dietary factor essential for reproduction in rats. Since then, vitamin E has revealed many important molecular properties such as the scavenging of reactive oxygen and nitrogen species or the modulation of signal transduction and gene expression in antioxidant and nonantioxidant manners. A congenital disease, ataxia with vitamin E deficiency, which is characterized by impaired enrichment of ?-tocopherol (?T) in plasma due to mutations in the ?-tocopherol transfer protein gene, has been discovered. An effect of vitamin E on angiogenesis and vasculogenesis has been observed in several studies, and recently, it has been demonstrated in the placenta of pregnant ewes, possibly involving the stimulation of vascular endothelial growth factor (VEGF) expression. We recently observed that the phosphorylated form of ?T, ?-tocopheryl phosphate (?TP), increases the expression of VEGF. We propose that the stimulatory effect of ?T on angiogenesis and vasculogenesis is potentiated by phosphorylation to ?TP, which may act as a cofactor or active lipid mediator increasing VEGF expression. Increased VEGF expression and consequent enhanced angiogenesis and vasculogenesis induced by ?TP may explain not only the essential roles of vitamin E on reproduction, but also its beneficial effects against pre-eclampsia, ischemia/reperfusion injury, and during wound healing. It may also serve as a survival factor for brain and muscle cells. The finding that ?TP may regulate vasculogenesis may indicate potential, important pathophysiological implications. PMID:22281871

Zingg, Jean-Marc; Meydani, Mohsen; Azzi, Angelo



The epidemiology of preterm labour--why have advances not equated to reduced incidence?  


The major burden of preterm birth is in the developing world, where most of the increasing death and morbidity is secondary to infectious diseases such as malaria, HIV, tuberculosis, bacterial vaginosis and intestinal parasites. In some developing countries, the growth of medical care has outstripped the growth of preventive public health, with an associated increase in iatrogenic preterm births. In developed countries, more than one-third of preterm births are medically indicated because of conditions such as fulminating pre-eclampsia or severe intrauterine growth restriction. Neither of these conditions is currently preventable. One in five preterm births is associated with multiple pregnancy, and these have been greatly increased by assisted reproduction techniques. The use of tocolytics has proved disappointing perhaps because inflammation rather than spontaneous uterine activity is increasingly recognised as the final common pathway. Inappropriate antibiotics used late in pregnancy are ineffective and may have adverse effects. Currently, the most promising interventions are public health related and include reducing the transmission of communicable diseases, improvements in the management of diabetes and reduction in harmful behaviours such as smoking and drug abuse. PMID:17206958

Steer, P J



Haplotype M2 in the annexin A5 (ANXA5) gene and the occurrence of obstetric complications.  


Inherited or acquired thrombophilias have been largely explored as a cause of pregnancy complications. However, pathogenesis of obstetric complications, as fetal loss and pregnancy-related hypertensive disorders is still partly unexplained. Recently, a common haplotype (M2) within the annexin A5 (ANXA5) gene has been described as a risk factor in recurrent fetal losses (RFL). It has been demonstrated to reduce the promoter activity of the ANXA5 promoter in luciferase reporter assays. Aim of this study was to investigate the prevalence of M2 haplotype in three different settings of women with previous obstetric complications: RFL, intra-uterine fetal death (IUFD) and pregnancy-related hypertension (gestational hypertension [GH] and pre-eclampsia [PE]). One hundred three patients with previous RFL, 54 with IUFD, 158 with hypertensive disease (67 GH, 91 PE) were investigated. As controls, 195 women from the same ethnic background with uneventful pregnancies were enrolled. Logistic regression, correcting for age, gravidity and parity showed that the ANXA5 haplotype is significantly and independently associated with the occurrence of RFL (3.1; 95%CI: 1.1-9.5; p = 0.047) and pregnancy-related hypertensive disorders (2.1; 95%CI: 1.2-3.5; p = 0.008). The M2 haplotype might be a new and relevant risk factor for obstetric complications. PMID:19652881

Tiscia, Giovanni; Colaizzo, Donatella; Chinni, Elena; Pisanelli, Daniela; Sciannamè, Natale; Favuzzi, Giovanni; Margaglione, Maurizio; Grandone, Elvira



Disseminated intravascular coagulation in obstetric disorders and its acute haematological management.  


As activation of the coagulation pathway is a physiological response to injury, the development of disseminated intravascular coagulation (DIC) is a warning signal to the clinician that the primary pathological disease state is decompensating. In pregnancy, DIC can occur in several settings, which include emergencies such as placental abruption and amniotic fluid embolism as well as complications such as pre-eclampsia. Whilst the acuteness of the event and the proportionality in the coagulant and fibrinolytic responses may vary between these different conditions, a common theme for pregnancy-associated DIC is the pivotal role played by the placenta. Removal of the placenta is the linchpin to treatment in most cases but appropriate blood product support is also key to management. This is necessary because DIC itself can have pathological consequences that translate clinically into a worse prognosis for affected patients. This article will describe how pregnancy-associated DIC can be diagnosed promptly and how treatment should be managed strategically. It also discusses the latest developments in our understanding of haemostatic mechanisms within the placenta and how these may have relevance to new diagnostic approaches as well as novel therapeutic modalities. PMID:19442424

Thachil, Jecko; Toh, Cheng-Hock



Interferon gamma contributes to pre-implantation embryonic development and to implantation site structure in NOD mice  

PubMed Central

Background Pre-eclampsia, a syndrome usually accompanied by incomplete spiral arterial modification, occurs at increased frequency in diabetic women. Hyperglycemia in type 1 diabetic non-obese diabetic (NOD) mice impairs gestational spiral arterial remodelling despite high local levels of interferon gamma (Ifng), the triggering cytokine in mice. Pregnancies in NOD.Ifng?/? mice were assessed to investigate this enigma. Methods Fecundity was assessed using breeding history, flushing of pre-implantation embryos and histological and morphometric studies of implantation sites in normoglycemic (n-) and hyperglycemic (d-) females of NOD.Ifng?/? and NOD genotypes. Results NOD.Ifng?/? but not NOD mice are infertile. In NOD.Ifng?/?, copulation often does not result in postimplantation pregnancy. Defective fertilization and delayed pre-implantation development limit n-NOD.Ifng?/? fertility; both mechanisms are exacerbated by hyperglycemia. At midgestation, implantation sites in n-NOD.Ifng?/? and n-NOD mice are histologically similar. In d-NOD.Ifng?/?, there is minimal development of spiral arteries, hypertrophy of the myometrial region containing uterine Natural Killer (uNK) cells and a deficit in cytoplasmic granule formation in the uNK cells. Conclusions Ifng contributes to the success of fertilization and to the rate of pre-implantation mouse embryo development in normogylcemic and hyperglycemic pregnancies. A physiological role for this cytokine in human pre-implantation development merits investigation.

Seaward, A. V. C.; Burke, S. D.; Croy, B. A.



Obstetric complications in women with schizophrenia.  


It is not known whether schizophrenic women have increased incidence of complications during pregnancy and delivery. Data from the Danish Medical Birth Register were used to compare 2212 births to 1537 schizophrenic women in Denmark with a random sample of all deliveries in Denmark during 1973-1993 (122931 births to 72742 women). The schizophrenic women had fewer antenatal care visits. They were at lower risk of pre-eclampsia, but tended to have lower Apgar scores. There were no other differences in the incidence of specific complications such as placenta previa, placental abruption, and abnormal fetal presentation. Schizophrenic women were at increased risk of interventions such as Cesarean section, vaginal assisted delivery, amniotomy, and pharmacological stimulation of labor. There were no important differences between the deliveries to schizophrenic women who gave birth before and after their first admission to a psychiatric department. These results show no evidence that schizophrenic women have a greater frequency of specific obstetric complications than non-schizophrenic women. Nevertheless, they are at increased risk for interventions during delivery. PMID:11278134

Bennedsen, B E; Mortensen, P B; Olesen, A V; Henriksen, T B; Frydenberg, M



Delivering obstetrical critical care in developing nations  

PubMed Central

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

Bajwa, Sukhwinder Kaur; Bajwa, Sukhminder Jit Singh



Possible role of RKIP in cytotrophoblast migration: immunohistochemical and in vitro studies.  


Raf kinase inhibitor protein (RKIP) regulates growth and differentiation signaling of mitogen-activated protein kinases (MAPK), GRK2 and NF-kappaB pathways each of which regulates cytotrophoblast differentiation and normal placental development. We show here that RKIP is expressed in human normal and preeclampic placentas as detected by immunostaining. RKIP was detected in villous cytotrophoblast in normal placenta and switched to syncytiotrophoblast in pre-eclampsia (PE)-complicated pregnancies. RKIP was also localized in extravillous cytotrophoblast of cell islands and cell columns both in normal and in PE placentas, although staining was less uniform in the latter specimens. In order to test RKIP involvement in cytotrophoblast function, we performed in vitro studies on HTR-8/SVneo cells, a first trimester cytotrophoblast cell line. We show that the RKIP inhibitor locostatin reduces ERK phosphorylation and impairs HTR-8/SV neo cells motility in wound closure experiments. We also document the presence of GRK2 mRNA, the reduction of phosphorylated RKIP expression by locostatin and the induction of PAI mRNA expression in HTR-8/SV neo cells, suggesting the involvement of GRK2 and NF-kappaB pathways in these cells. In conclusion, our work provides evidence that RKIP is a novel factor expressed in cytotrophoblast cells where it likely regulates cell migration. PMID:21732351

Ciarmela, Pasquapina; Marzioni, Daniela; Islam, Md Soriful; Gray, Peter Clarke; Terracciano, Luigi; Lorenzi, Teresa; Todros, Tullia; Petraglia, Felice; Castellucci, Mario



Pregnancy outcome in women with pre-existing lupus nephritis.  


The aim of the present study was to assess the fetal and maternal outcome in a cohort of patients with lupus nephritis. Twenty-four pregnancies in 22 women with lupus nephritis occurring between 1991 and 2000 were analysed retrospectively. Lupus nephritis was biopsy proven before pregnancy in all cases. Women were followed from the beginning of pregnancy up to 6 months postpartum. Close fetal-maternal monitoring and frequent laboratory investigations were applied routinely to all patients. All women were prescribed steroid therapy from the beginning of the pregnancy. There were 18 live births, four spontaneous abortions and two stillbirths. Of the 18 live births, 14 were premature and four were term deliveries, representing a 25% fetal loss rate and 58% prematurity rate. There were two fetuses with congenital heart block. We recorded hypertension in 42%, proteinuria in 50% and pre-eclampsia in 25% of our patients. Proteinuria was irreversible in four cases. No maternal deaths or postpartum exacerbation of the disease were recorded in the study period. All renal flares were reversed postpartum. Patients positive for antiphospholipid antibodies had a worse perinatal outcome. Hypertension, proteinuria and antiphospholipid antibodies appear to be associated with adverse perinatal outcome and pregnancy complications. Pregnancy is not contraindicated in women with lupus nephritis, but is associated with significant fetal and maternal risks. PMID:16147600

Soubassi, L; Haidopoulos, D; Sindos, M; Pilalis, A; Chaniotis, D; Diakomanolis, E; Antsaklis, A; Zerefos, N



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.

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



New frontiers in heart hypertrophy during pregnancy  

PubMed Central

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

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



Residential traffic exposure and pregnancy-related outcomes: a prospective birth cohort study  

PubMed Central

Background The effects of ambient air pollution on pregnancy outcomes are under debate. Previous studies have used different air pollution exposure assessment methods. The considerable traffic-related intra-urban spatial variation needs to be considered in exposure assessment. Residential proximity to traffic is a proxy for traffic-related exposures that takes into account within-city contrasts. Methods We investigated the association between residential proximity to traffic and various birth and pregnancy outcomes in 7,339 pregnant women and their children participating in a population-based cohort study. Residential proximity to traffic was defined as 1) distance-weighted traffic density in a 150 meter radius, and 2) proximity to a major road. We estimated associations of these exposures with birth weight, and with the risks of preterm birth and small size for gestational age at birth. Additionally, we examined associations with pregnancy-induced hypertension, (pre)eclampsia, and gestational diabetes. Results There was considerable variation in distance-weighted traffic density. Almost fifteen percent of the participants lived within 50 m of a major road. Residential proximity to traffic was not associated with birth and pregnancy outcomes in the main analysis and in various sensitivity analyses. Conclusions Mothers exposed to residential traffic had no higher risk of adverse birth outcomes or pregnancy complications in this study. Future studies may be refined by taking both temporal and spatial variation in air pollution exposure into account.



New horizons in platelets flow cytometry.  


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

Saboor, Muhammad; Moinuddin, Moinuddin; Ilyas, Samina



Probing the mechanical properties of TNF-? stimulated endothelial cell with atomic force microscopy  

PubMed Central

TNF-? (tumor necrosis factor-?) is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-? is elevated (> 1 pg/mL) in several pathologies, including rheumatoid arthritis, atherosclerosis, cancer, pre-eclampsia; in obese individuals; and in trauma patients. To test whether circulating TNF-? could induce similar alterations in different districts along the vascular system, three endothelial cell lines, namely HUVEC, HPMEC, and HCAEC, were characterized in terms of 1) mechanical properties, employing atomic force microscopy; 2) cytoskeletal organization, through fluorescence microscopy; and 3) membrane overexpression of adhesion molecules, employing ELISA and immunostaining. Upon stimulation with TNF-? (10 ng/mL for 20 h), for all three endothelial cells, the mechanical stiffness increased by about 50% with a mean apparent elastic modulus of E ~5 ± 0.5 kPa (~3.3 ± 0.35 kPa for the control cells); the density of F-actin filaments increased in the apical and median planes; and the ICAM-1 receptors were overexpressed compared with controls. Collectively, these results demonstrate that sufficiently high levels of circulating TNF-? have similar effects on different endothelial districts, and provide additional information for unraveling the possible correlations between circulating pro-inflammatory cytokines and systemic vascular dysfunction.

Lee, Sei-Young; Zaske, Ana-Maria; Novellino, Tommaso; Danila, Delia; Ferrari, Mauro; Conyers, Jodie; Decuzzi, Paolo



Low-molecular weight heparin in patients with recurrent early miscarriages of unknown aetiology.  


The aim of this randomised prospective study was to assess the efficacy of early thromboprophylaxis with low-molecular weight heparin (LMWH) in women with a history of recurrent first trimester spontaneous abortion or miscarriages without identifiable causes vs no treatment. The study comprised of 340 women with unexplained spontaneous recurrent miscarriages. Patients in group A were prescribed LMWH (Enoxaparin sodium 0.2 ml, 20 mg, once daily subcutaneously) from the time of confirmation of fetal viability by ultrasonography until 34 weeks' gestation, and folic acid tablets 0.5 mg daily until 13 weeks' gestation. Patients in group B were given folic acid tablets 0.5 mg daily until 13 weeks' gestation. Termination of pregnancy was the primary outcome. There was a significant difference in the incidence of both early (4.1% vs 8.8%) and late miscarriages (1.1% vs 2.3%) in group A than in group B, respectively. There were no differences between both groups as regards the occurrence of pre-eclampsia, placental abruption, caesarean delivery, intra-partum bleeding or ecchymosis at operative wounds. There were no differences in most of the neonatal values between both groups. However, the mean birth weight was significantly higher in group A. LMWH seems to be a safe drug and effective in significantly reducing the incidence of recurrent miscarriages of unknown aetiology when given in the first trimester and continued throughout pregnancy. PMID:18569468

Badawy, A M; Khiary, M; Sherif, L S; Hassan, M; Ragab, A; Abdelall, I



Urinary calcium excretion in severe preeclampsia and eclampsia.  


Urinary calcium levels in women with mild preeclampsia, severe preeclampsia and eclampsia were evaluated in this study. We collected 24-h urine samples from 35 mild preeclamptic (Group 1), 30 severe preeclamptic (Group 2), and 17 eclamptic patients (Group 3). The control group (Group 4) consisted of 35 healthy pregnant women. Serum levels of total calcium and creatinine, and urinary calcium were measured. These values were compared in the four groups. The mean maternal age and parity were similar in all groups. There were no statistically significant differences in the serum levels of total calcium and creatinine (p > 0.05). Urinary calcium excretion in patients with preeclampsia and eclampsia was significantly lower than in controls (p < 0.0001). Urinary calcium levels between mild preeclampsia and severe pre-eclampsia, and severe preeclampsia and eclampsia were similar (p > 0.05), but were lower in eclampsia than in mild preeclampsia (p < 0.05). In conclusion, urinary calcium excretion is reduced in patients with severe preeclampsia or eclampsia. However, the decrease in urinary calcium excretion cannot be used to identify the severity of preeclampsia, or to predict impending eclampsia. PMID:16375585

Ingec, Metin; Nazik, Hakan; Kadanali, Sedat



Ischemic Stroke during Pregnancy and Puerperium  

PubMed Central

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

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



Endothelial caveolar subcellular domain regulation of endothelial nitric oxide synthase.  


Complex regulatory processes alter the activity of endothelial nitric oxide synthase (eNOS) leading to nitric oxide (NO) production by endothelial cells under various physiological states. These complex processes require specific subcellular eNOS partitioning between plasma membrane caveolar domains and non-caveolar compartments. Translocation of eNOS from the plasma membrane to intracellular compartments is important for eNOS activation and subsequent NO biosynthesis. We present data reviewing and interpreting information regarding: (i) the coupling of endothelial plasma membrane receptor systems in the caveolar structure relative to eNOS trafficking; (ii) how eNOS trafficking relates to specific protein-protein interactions for inactivation and activation of eNOS; and (iii) how these complex mechanisms confer specific subcellular location relative to eNOS multisite phosphorylation and signalling. Dysfunction in the regulation of eNOS activation may contribute to several disease states, in particular gestational endothelial abnormalities (pre-eclampsia, gestational diabetes etc.), that have life-long deleterious health consequences that predispose the offspring to develop hypertensive disease, Type 2 diabetes and adiposity. PMID:23745825

Ramadoss, Jayanth; Pastore, Mayra B; Magness, Ronald R



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.

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



Unexpected neurological deficits following recovery from anaesthesia.  


Two cases of neurological dysfunction are presented. Neurological deficits after recovery from anaesthesia are unusual in young women perioperatively. In the first case, a 39-yr-old woman presented at 36-wk gestation with antepartum haemorrhage and in labour. Pregnancy had been complicated by pre-eclampsia and she underwent emergency Caesarean section under general anaesthesia without complication. The trachea was extubated when she was awake but almost immediately she became hypertensive, obtunded and reintubation was required. Her pupils became fixed and dilated but the Computerised Axial Tomogram (CT) was normal. A coagulopathy was evident. She made a full neurological recovery within 24 hr. On the same day, a previously healthy 41-yr-old woman who had undergone uneventful surgery for uterine prolapse 24 hr previously developed headache, nausea and over the next four hours signs of progressive brainstem ischaemia. The CT scan showed oedema of the mid- and hindbrain. Brainstem death was confirmed 12 hr later and the post-mortem revealed acute dissection of the vertebral artery secondary to cystic medial necrosis. Such dramatic neurological sequelae are rare but the importance of identifying "at risk" groups is underlined as is early recognition of neurological injury postoperatively. PMID:8004739

Porter, J; Lynch, L; Hart, S; Keohane, C



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


The XPD(ERCC2) gene encodes a DNA helicase involved in DNA repair and transcription. Patients with mutations in XPD may have different autosomal recessive phenotypes including trichothiodystrophy (TTD) or xeroderma pigmentosum (XP). TTD patients have sulfur-deficient, brittle hair, short stature and developmental delay. In contrast, XP patients have freckle-like pigmentation and a greatly increased risk of sun-induced skin cancers. Mothers of TTD patients have been reported to have a high frequency of pregnancy and neonatal complications. We performed a molecular epidemiological study of 15 mothers of 17 TTD patients and 13 mothers of 17 XP patients, all with XPD mutations. We found that 94% (16/17) of the TTD pregnancies had pre-term delivery, pre-eclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, prematurity or low birth weight. None of the 17 XP pregnancies had these complications (P<0.001). As mutations in XPD may have differential effects on DNA repair and transcription, these observations should provide insights into the role of XPD in human pregnancy and fetal development. PMID:22617342

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



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.

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



Leptin and interferon-gamma as possible predictors of cesarean section among women with hypertensive disorders of pregnancy  

PubMed Central

Summary Background This study was designed to evaluate maternal levels of leptin and interferon-gamma (IFN-gamma) in pregnancy complicated with hypertension and to assess the role of cytokines in predicting the risk of cesarean section. Material/Methods This was a cohort study with a prospective follow-up. After proportional sampling procedure, the study included the follow-up of 40 women with hypertensive disorders of pregnancy (pregnancy-induced hypertension [PIH] or preeclampsia [PE]) and 40 uncomplicated pregnancies. Women were followed from the time of admission to the delivery. Levels of leptin and interferon-gamma were measured in serum samples from all women. A p-value <0.05 was considered as significant. Results Significant increase in IFN-gamma and leptin concentration in women with pre-eclampsia was observed. We found a significant 1.4-fold increase in the risk of birth by cesarean section associated with the increase of the IFN-gamma concentration by 0.1 pg/ml and almost 3-fold increase in the risk associated with the increase of the leptin concentration. Conclusions IFN-? and leptin might be risk markers of cesarean section in hypertension disorders of pregnancy, but further studies supporting this evidence are needed.

Rytlewski, Krzysztof; Huras, Hubert; Kusmierska-Urban, Katarzyna; Galas, Aleksander; Reron, Alfred



[Effects of folic acid supplementation on pregnancy outcomes: a review of randomized clinical trials].  


Despite the causal association between defects of the metabolism of the folate (hyperhomocysteinemia) and risk of neural tube defects are both well documented, the association between folate deficiency and other pregnancy pathologies is still not entirely clear. The present article aims to gather the data published about the relationship between serum folate and pregnancy pathologies, distinguishing between the evidences emerged from the observational studies and the results of the clinical trials. We carried out a brief examination of the relationships between folate metabolism and homocysteine. Observational studies have suggested that a good level of folate in pregnancy is associated with higher birthweight, increased placental weight and fewer preterm birth. These results were not entirely consistent with findings from clinical trials. We have identified 12 randomized clinical studies with folate supplementation versus placebo. In the clinical studies where folic acid (FA) could improve pregnancy outcomes, its effect was not statistically significant, except for three studies where FA showed a significant decrease of low birthweight. With regard to preterm birth, pre-eclampsia and abruptio placentae, although in some observational studies AF was found to be associated with a reduction of these adverse outcomes, in currently available controlled clinical trials, FA supplementation had no statistically significant effects. PMID:20827247

Chiaffarino, F; Ascone, G B; Bortolus, R; Mastroia-Covo, P; Ricci, E; Cipriani, S; Parazzini, F



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

PubMed Central

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



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


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

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



Laboratory findings in hypertensive disorders of pregnancy.  

PubMed Central

This study sought to determine whether a normal platelet count is a reliable predictor of the absence of other coagulation abnormalities in patients with a hypertensive disorder of pregnancy. A retrospective review of laboratory data obtained from 80 patients with hypertensive disorders of pregnancy was carried out. Results of complete blood cell count, prothrombin time (PT), partial thromboplastin time (PTT), D-dimer, fibrin split products, and fibrinogen, bilirubin, and liver enzyme levels were reviewed. Minor abnormalities of PT, PTT, and fibrinogen level were frequent, even in the presence of a normal platelet count. These were found mostly in patients with severe pre-eclampsia. A baseline complete blood cell count including platelet count is probably sufficient in patients with a hypertensive disorder of pregnancy. Fibrinogen level and PT and PTT determinations are recommended in patients who have severe preeclampsia and for whom operative delivery or regional anesthesia is planned. This will detect minor abnormalities in a few patients despite a normal platelet count. This information may help prevent bleeding complications.

FitzGerald, M. P.; Floro, C.; Siegel, J.; Hernandez, E.



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

PubMed Central

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

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



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


Globally, about 20 million infants are born with low birth weight (LBW; <2500 g). Of all LBW infants, approximately 95% are born in developing countries. The greatest incidence of LBW occurs in South-Central Asia; the second greatest is in Africa. The two main reasons for LBW are preterm birth (<37 weeks) and intrauterine growth restriction (IUGR), which are risk factors for increased morbidity and mortality in newborn infants. Maternal nutrition status is one of the most important risk factors for LBW/IUGR. Providing balanced protein energy and multiple micronutrient supplements to pregnant women will reduce incidence of IUGR. Calcium supplementation during pregnancy will reduce the incidence of pre-eclampsia and preterm birth in developing countries. Exclusive breastfeeding is protective for a mother and her infant and has been shown to reduce morbidity and mortality in infancy. Kangaroo mother care for preterm infants will reduce severe morbidity and mortality as well. Community-based intervention packages are among the most effective methods of reducing morbidity and mortality in mothers and children. Future research should focus on improving triage of preterm and IUGR infants. Exclusive breastfeeding should be promoted, and appropriate alternative food supplements should be provided when breastfeeding is not possible. PMID:23445841

Imdad, Aamer; Bhutta, Zulfiqar A



Lung ultrasound-guided management of acute breathlessness during pregnancy.  


Lung ultrasonography is a standard tool in the intensive care unit and in emergency medicine, but has not been described in the particular setting of the labour ward. During pregnancy, acute respiratory failure and pulmonary oedema are not uncommon life-threatening events. We present two case reports outlining the potential of lung ultrasonography in parturients. In case 1, lung ultrasonography allowed early diagnosis and treatment of acute dyspnoea in a parturient admitted for suspected asthma exacerbation. Lung ultrasonography revealed a 'B-pattern' of vertical lines radiating into the lung tissue, indicating severe pulmonary oedema complicating previously undiagnosed pre-eclampsia. In case 2, a pre-eclamptic patient was managed with combined transthoracic echocardiography and lung ultrasonography. The accuracy of lung ultrasonography in detecting interstitial oedema at a pre-clinical stage allowed adequate fluid resuscitation in this patient who had a high risk of alveolar pulmonary oedema. We believe that these cases strongly support the prospective validation of lung ultrasound for management of lung disorders in pregnant women. PMID:23088788

Zieleskiewicz, L; Lagier, D; Contargyris, C; Bourgoin, A; Gavage, L; Martin, C; Leone, M



Type 2 diabetes and pregnancy.  


Type 2 diabetes is a growing concern, with the number of new cases increasing and occurring at a younger age due to obesity. Consequently the number of cases arising in women of child-bearing age is increasing, and the condition will be encountered more frequently in the antenatal clinic. Type 2 diabetes is often perceived as a benign form of diabetes, but this is not the case when one examines pregnancy outcomes. Rates of perinatal mortality (25/1000) and congenital malformation (99/1000) are significantly greater than those in background populations and at least as poor as those in type 1 diabetes. The rates of hypertension, pre-eclampsia and postpartum haemorrhage are greater than the general maternity population, as is the rate of operative delivery. To improve outcomes we need to dispel the myth that type 2 diabetes is a benign condition. Educational programmes, population screening, and strategies to help vulnerable groups access the services available will increase our ability to identify and counsel women with type 2 diabetes early enough to make a difference. PMID:15921969

Dunne, Fidelma



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)



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


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



The management of thrombosis in pregnancy: role of low-molecular-weight heparin.  


Fatal pulmonary embolism remains the most common cause of mortality among pregnant women in many Western countries. The physiological changes of pregnancy produce a hypercoagulable state that increases the risk of venous thromboembolism (VTE). Women with inherited or acquired thrombophilias are at particularly high risk of VTE during pregnancy, and thromboprophylaxis may be advisable in some cases. Thrombophilia is also associated with complications of pregnancy, including fetal loss, pre-eclampsia, intra-uterine growth restriction, and placental abruption. The antithrombotic agents available for the prevention and treatment of VTE during pregnancy, and pregnancy complications, include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) and aspirin. Vitamin K antagonists are contra-indicated in pregnancy. Low-dose aspirin may have a role in the prevention of some pregnancy complications, although its safety in early and late pregnancy is uncertain. The efficacy and safety of LMWHs have been demonstrated for the prevention and treatment of VTE in pregnancy. These agents are increasingly being used in place of UFH, which is associated with a higher incidence of side effects compared with LMWH, in addition to the need for regular laboratory monitoring. Evidence is also emerging to support the use of LMWH in the prevention of recurrent fetal loss, although further trials are needed to explore the role of LMWHs in this indication and in the prevention of other complications of pregnancy. PMID:17393011

Kher, André; Bauersachs, Rupert; Nielsen, Jorn Dalsgaard



Time-qualified reference values for 24 h ambulatory blood pressure monitoring.  


BACKGROUND: The development of automatic instrumentation for ambulatory blood pressure monitoring makes it possible to follow the time-course of blood pressure variation over 24h or more in large groups of individuals. Whenever samples from a reference group of individuals are available, one may construct a prediction interval that is expected to include any single future observation from the reference population, with a specified confidence. Alternatively, the reference interval may consist of a tolerance interval that will include at least a specified proportion of the population with a stated confidence. OBJECTIVE: To examine prospectively whether a new, combined tolerance-hyperbaric test approach of establishing tolerance intervals for the circadian variability of blood pressure as a function of gestational age and then computing the hyperbaric index as a measure of blood pressure excess provides high sensitivity and specificity in the early identification of pregnant women who subsequently will develop gestational hypertension or pre-eclampsia. METHODS: We used data sampled for 48 h from 148 normotensive men and women to compute and compare time-specified tolerance and prediction intervals for blood pressure. Once the threshold, given by the upper limit of the tolerance interval, was available, the hyperbaric index, as a measure of blood pressure excess, could be calculated by numerical integration as the total area of any given patient PMID:10490866

Hermida, R C


[Blood pressure circadian rhythms during development of hypertension in healthy pregnant women].  


Investigation of systolic (SBP) and diastolic blood pressures (DBP) circadian chronological structure changes by means of blood pressure monitoring in healthy pregnant women during development of gestational hypertension (GH) and pre-eclampsia (PE) was carried out. 72 hours blood pressure monitoring (TM-2421 device, Tokyo, Japan) was carried out in 34 healthy pregnant women. Parametric and non-parametric indices of circadian rhythms were determined, which allowed us to include in group A 17 women who had normal BP until delivery. Group B consisted of 17 women with hypertension in II and III trimesters. Increase of hyperbaric index (HBI) of SBP was revealed in the I trimester in women in whom hypertension was developed later in pregnancy. HBI was used as a prognostic criterion of developing MESOR-hypertension long before its clinical manifestation. In the II and III trimesters HBI, per cent time of elevation (PTE%) and MESORs of SBP and DBP circadian rhythms progressively augmented. Pregnant women with hypertension belonged to type non-dipper according to D/N% changes (less then 10%). This may be the result of insufficient decrease of night values of SBP in group B pregnant women, which is characteristic of GH and PE. PMID:17057308

Shaginian, M G



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


Fortified beverages and supplementary foods, when given during pregnancy, have been shown to have positive effects on preventing maternal anaemia and iron deficiency. Studies show that use of micronutrient fortified supplementary foods, especially those containing milk and/or essential fatty acids during pregnancy, increase mean birthweight by around 60-73 g. A few studies have also shown that fortified supplementary foods have impacts on increasing birth length and reducing preterm delivery. Fortification levels have ranged generally from 50% to 100% of the recommended nutrient intake (RNI). Iron, zinc, copper, iodine, selenium, vitamins A, D, E, C, B1, B2, B6, and B12, folic acid, niacin and pantothenic acid are important nutrients that have been included in fortified beverages and supplemental foods for pregnant and lactating women. While calcium has been shown to reduce the risk of pre-eclampsia and maternal mortality, calcium, phosphorus, potassium, magnesium and manganese can have negative impacts on organoleptic properties, so many products tested have not included these nutrients or have done so in a limited way. Fortified food supplements containing milk and essential fatty acids offer benefits to improving maternal status and pregnancy outcome. Fortified beverages containing only multiple micronutrients have been shown to reduce micronutrient deficiencies such as anaemia and iron deficiency. PMID:21929634

Yang, Zhenyu; Huffman, Sandra L



A patient with bilateral pheochromocytoma as part of a Von Hippel-Lindau (VHL) syndrome type 2C  

PubMed Central

Background Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disease. It is relatively recent that type 2C was identified as a separate group solely presenting with pheochromocytomas. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. It proved to be the first manifestation of bilateral pheochromocytomas. The family history may indicate the diagnosis, but only identification of a germ line mutation in the DNA of a patient will confirm carriership. Case presentation A 27 year pregnant patient with intra uterine growth retardation presented with hypertension and pre-eclampsia. Magnetic resonance imaging revealed bilateral adrenal pheochromocytoma. She underwent laparoscopic adrenelectomy and a missense mutation (Gly93Ser) in exon 1 of the VHL gene on chromosome 3 (p25 – p26) was shown in the patient, her father and her daughter confirming the diagnosis of VHL. Conclusion In almost all VHL families molecular genetic analysis of DNA will demonstrate an inherited mutation. Because of the involvement in several organs, periodic clinical evaluation should take place in a well coordinated, multidisciplinary setting. VHL disease can be classified into several subtypes. VHL type 2C patients present with pheochromocytomas without evidence of haemangioblastomas in the central nervous system and/or retina and a low risk of renal cell carcinoma. Therefore, in such families, periodic clinical screening can be focussed on pheochromocytomas.

Schreinemakers, Jennifer MJ; Zonnenberg, Bernard A; Hoppener, Jo WM; Hes, Frederik J; Rinkes, Inne HM Borel; Lips, Cornelis JM



Do Molecular Signals from the Conceptus Influence Endometrium Decidualization in Rodents?  

PubMed Central

A critical period in establishing pregnancy occurs after the onset of implantation but before placental development. Evidence strongly suggests that abnormalities occurring during this period can result in pregnancy termination or in pre-eclampsia; the latter may lead to small-for-gestational-weight offspring that are likely to be unhealthy. Clearly, events occurring in the endometrium during the implantation process are crucial for proper fetal development and for optimal offspring health. In several mammalian species bi-directional communication between the conceptus and endometrium during implantation is required for successful pregnancy. Although different implantation and placentation modes occur in different mammalian species, common aspects of this bi-directional signaling may exist. The molecular signals from the trophoblast cells of the conceptus, which direct endometrial changes during implantation progression, are well known in some non-rodent species. Currently, we know little about such signaling in rodents during implantation progression, when the endometrium undergoes decidualization. This review focuses on data that support the hypothesis that paracrine signals from the rodent conceptus influence decidualization. Where possible, these findings are compared and contrasted to information currently known in other species that exhibit different implantation modes.

Herington, Jennifer L.; Bany, Brent M.



A young woman with dyspnea.  


A 35-year-old Sri Lankan woman (gravida 3, para 3, abortus 0) presented to the Jewish General Hospital (Montreal, Quebec) with shortness of breath and diffuse swelling. She was five months postpartum of her most recent delivery, which was complicated by pre-eclampsia and gestational diabetes. She described a three-week history of progressive exertional dyspnea, orthopnea and paroxysmal nocturnal dyspnea. There was no history of recent viral illness, and the patient had no traditional risk factors for coronary artery disease. A physical examination, laboratory results and echocardiography were typical for heart failure. A presumptive diagnosis of peripartum cardiomyopathy was made. To initiate a transplant referral, coronary angiography was performed. Six discrete atherosclerotic lesions were found, notably left main equivalent disease. A diagnosis of ischemic cardiomyopathy was made, and the patient was referred for high-risk coronary artery bypass surgery and transplant. The present case illustrates the excess burden of coronary artery disease borne in south Asian patient populations. PMID:18612506

Povitz, Marcus; Tangri, Navdeep



A young woman with dyspnea  

PubMed Central

A 35-year-old Sri Lankan woman (gravida 3, para 3, abortus 0) presented to the Jewish General Hospital (Montreal, Quebec) with shortness of breath and diffuse swelling. She was five months postpartum of her most recent delivery, which was complicated by pre-eclampsia and gestational diabetes. She described a three-week history of progressive exertional dyspnea, orthopnea and paroxysmal nocturnal dyspnea. There was no history of recent viral illness, and the patient had no traditional risk factors for coronary artery disease. A physical examination, laboratory results and echocardiography were typical for heart failure. A presumptive diagnosis of peripartum cardiomyopathy was made. To initiate a transplant referral, coronary angiography was performed. Six discrete atherosclerotic lesions were found, notably left main equivalent disease. A diagnosis of ischemic cardiomyopathy was made, and the patient was referred for high-risk coronary artery bypass surgery and transplant. The present case illustrates the excess burden of coronary artery disease borne in south Asian patient populations.

Povitz, Marcus; Tangri, Navdeep



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


This 2006 study investigated ethnicity-related factors contributing to sub-standard maternity care and the effects on severe maternal morbidity among immigrant women in the Netherlands. In-depth interviews were carried out with 40 immigrant and 10 native Dutch women. The immigrant women reported that health care providers often paid insufficient attention to their pregnancy-related complaints, especially in cases of pre-eclampsia. They also reported delays in receiving information about diagnosis and treatment. Obstetricians who reviewed 20 of these cases judged sub-standard care to have played a role in the development of complications in 16 of them. The women themselves had problems identifying medically significant complications, presenting their complaints to health care providers effectively, and taking an active role as patients. Even highly educated migrant women showed low health literacy skills in their interaction with doctors. Patients' perspectives are valuable as one of the tools to evaluate the quality of maternity care. Communication by maternal health professionals can be improved through more sensitivity to social factors that affect immigrant women's health problems. Women with limited health literacy should be empowered through education about danger signs in pregnancy and information about preferences and policies in obstetrics in the Netherlands. They should also be invited to participate in medical decision-making. PMID:21555095

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



Urinary tract stones in pregnancy.  


The presence of stones during an otherwise uneventful pregnancy is a dramatic and potentially serious issue for the mother, the fetus, and the treating physicians alike. The incidence and predisposing factors are generally the same as in nonpregnant, sexually active, childbearing women. Unique metabolic effects in pregnancy such as hyperuricuria and hypercalciuria, changes in inhibitors of lithiasis formation, stasis, relative dehydration, and the presence of infection all have an impact on stone formation. The anatomic changes and physiologic hydronephrosis of pregnancy make the diagnosis and treatment more challenging. Presenting signs and symptoms include colic, flank pain, hematuria, urinary tract infection, irritative voiding, fever, premature onset or cessation of labor, and pre-eclampsia. The initial evaluation and treatment are again similar to those used for the nonpregnant population. The most appropriate first-line test is renal ultrasonography, which may, by itself, allow the diagnosis to be made and provide enough information for treatment. Radiographic studies, including an appropriately performed excretory urogram, give specific information as to size and location of the stones, location of the kidneys, and differential renal function and can be used safely, but the ionizing radiation risks should be considered. All forms of treatment with the exception of extracorporeal shock wave lithotripsy and some medical procedures are appropriate in the pregnant patient. Close coordination by the urologist, the obstetrician, the pediatrician, the anesthesiologist, and the radiologist is required for the appropriate care of these patients. PMID:7855714

Swanson, S K; Heilman, R L; Eversman, W G



[Smokeless tobacco].  


Use of smokeless tobacco (ST) (chewing tobacco and snuff) can lead to a number of consequences detrimental to health. ST rapidly delivers high doses of nicotine, which can lead to dependence and is also a source of carcinogenic nitrosamines. Changes usually develop in the mouth area where the ST is most often placed. Non-malignant oral lesions include leuko-oedema, hyperkeratotic lesions of the oral mucosa and localised periodontal disease. Oral premalignant lesions are leukoplakia, erythroplakia, submucosal fibrosis and lichen planus. Betel chewing, with or without tobacco, may increase the incidence of oral cancer. There is conflicting evidence with regard to snuff users about the risk of oral and gastro-oesophageal cancer. ST use is a risk factor for pancreatic cancer and may increase the risk of fatal myocardial infarction and ischemic stroke. During pregnancy, ST is associated with an increase in pre-eclampsia, preterm delivery and stillbirth. Nicotine replacement therapy and bupropion reduce withdrawal symptoms and tobacco craving during ST cessation. However, they have not been shown to help long-term abstinence. Information concerning the potential hazards of ST products should be incorporated into educational programmes to discourage its use and to help users to quit. Smokeless tobacco is not recommended to help smoking cessation. PMID:22099403

Underner, M; Perriot, J



Obesity in pregnancy: problems and potential solutions.  


Recent years have witnessed an increase in the prevalence of maternal obesity during pregnancy in the United States and worldwide. Obese women have increased risks for gestational problems, such as diabetes, hypertension, and pre-eclampsia. Further, gestational obesity can adversely impact fetal growth and result in macrosomia, congenital abnormalities, and even fetal death. Measures must be taken to reduce maternal adiposity, as even a modest weight loss during pregnancy is beneficial for the health of mothers and fetus. Calorie restriction and moderate exercise are proven safe methods of stopping weight gain and/or inducing white-fat loss in these subjects. Additionally, therapeutic drugs that activate the AMP-activated protein kinase signaling pathway may be effective in ameliorating pathological conditions in obese patients. Finally, dietary supplementation with L-arginine or its effective precursor (L-citrulline) may be beneficial for managing overweight or obese gestating women by reducing white-fat accretion. Because of ethical concerns over human studies, animal models (e.g., sheep, pigs, baboons, rats, and mice) are warranted to test novel hypotheses with enormous biological significance and clinical applications. PMID:21196324

McKnight, Jason R; Satterfield, M Carey; Li, Xilong; Gao, Haijun; Wang, Junjun; Li, Defa; Wu, Guoyao



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


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

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



Pregnancy: occupational aspects of management: concise guidance.  


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



Management of maternal obesity prior to and during pregnancy.  


The prevalence of obesity is high and rising worldwide. The greatest prevalence of obesity is found in the western world and in urban developing countries. There is an increased maternal mortality associated with maternal obesity. There are increased risks of most maternal complications in pregnancy including pre-eclampsia, gestational and pre-existing type 2 diabetes mellitus and thromboembolic disorders. There is an increased perinatal mortality associated with maternal obesity; there are increased risks of congenital malformation, fetal macrosomia and indeed risks for the fetus as a child and adult in the years to come. There are increased risks of complications of pregnancy including caesarean section, traumatic delivery and a reduced chance of breastfeeding. Maternal obesity in pregnancy predicts long-term risks for that mother. The management includes increased surveillance for these risks and lifestyle modulation during pregnancy. This includes dietary measures and encouraging modest increase in exercise. Ideally, the mother should achieve closer to an ideal body mass index prior to pregnancy using lifestyle intervention but possibly with pharmacological therapy or bariatric surgery. The ideal weight gain for an obese mother is less than the ideal weight gain for a lean mother. PMID:19945927

Shaikh, H; Robinson, S; Teoh, T G



Socio-demographic characteristics of women sustaining injuries during pregnancy: a study from the Danish National Birth Cohort  

PubMed Central

Objectives To describe adverse birth outcomes associated with hospital-treated injuries that took place among women in the Danish National Birth Cohort. Design Longitudinal cohort study. Setting Denmark. Participants 90?452 women and their offspring selected from the Danish National Birth Cohort. Primary and secondary outcome measures To determine if injured women were more likely to deliver an infant preterm, with low birth weight, stillborn or have a spontaneous abortion, the authors estimated HRs. ORs were generated to assess APGAR scores and infants born small for gestational age (SGA). Models were adjusted for maternal smoking and drinking during pregnancy, household socioeconomic status, eclampsia/pre-eclampsia or gestational diabetes status during pregnancy and maternal age at birth; estimates for preterm birth were also adjusted for prior history of preterm birth. Results In the cohort of 90?452 pregnant women, 3561 (3.9%) received medical treatment for an injury during pregnancy. Injured pregnant women were more likely to deliver infants that were stillborn or have pregnancies terminated by spontaneous abortion. The authors did not detect an adverse effect between injuries sustained during pregnancy and delivery of preterm, low birth weight or SGA infants, or infants with an APGAR score of <7. Conclusions The study shows that injuries occurring among women from an unselected population may not have an adverse effect on birth weight, gestational age, APGAR score or SGA status but may adversely affect the risk of stillbirth and spontaneous abortions in some situations.

Hsu, Paul; Olsen, J?rn



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


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



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

PubMed Central

Objective Nuclear factor kappa B (NF-?B) pathway and oxidative stress participate in endothelial dysfunction, which is one of the causes of pre-eclampsia. Among the human antioxidant mechanisms, there are the enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). Our aim was to measure NF-?B, its inhibitor (IKK) and oxidative stress in placenta and umbilical cord of pregnant women submitted to a supervised nutritional program. Methods Two groups were conformed: A) 14 pregnant women with individualized nutritional counseling, and B) 12 pregnant women without nutritional guidance. NF-?B and IKK were assessed by real time PCR (RT-PCR). Enzymatic activity of CAT, GPx, lipoperoxidation (LPO) and SOD were also evaluated. Results Pregnant women that followed a supervised nutritional program had lower levels of systolic (p=0.03) and diastolic pressure (p=0.043) although they were heavier than the control group (p=0.048). Among all the women, the Spearman correlation was positive between weight gain and placental NF-?B expression (1, p?0.01). In the placenta, women with nutritional advice had lower enzymatic activity of GPx (p?0.038) and showed a tendency of IKK to be higher than in women without a nutritional supervised program. Conclusion A supervised nutritional program in pregnancy offers a proven option to control weight gain, hypertension, NF-?B/IKK complex expression and oxidative stress reactions in the placenta.

Zeron, Hugo Mendieta; Flores, Alejandro Parada; Chavez, Araceli Amaya; Alanis, Adriana Garduno; Ferreyra, Maria del Carmen Colin; Benitez, Jonnathan Guadalupe Santillan; Castaneda, Violeta Sarai Morales; Garcia, Ma. Victoria Dominguez



Autoantibodies as predictors of pregnancy complications.  


Certain autoantibodies which are found in autoimmune diseases including CTDs can impair fertility. Reproductive failure may present as pregnancy loss, either as miscarriage, intrauterine fetal death or stillbirth. There are also late obstetric complications such as intrauterine growth restriction, pre-eclampsia and pre-term birth. This review summarizes the possible influences of autoantibodies in reproductive failure, and particularly their predictive value (if available). The aPLs detectable by lupus anticoagulant, anti-cardiolipin or anti-beta2 glycoprotein I assays are associated with pregnancy loss and have a positive predictive value (PPV) of 75%. In spite of the general consensus on the management of pregnant aPL-positive women, few well-designed clinical trials have been reported and there is also insufficient data about the PPV of treatment. Anti-thyroid antibodies have been associated with pregnancy loss, and indeed have a PPV of 40%. However, no antibody is pathognomic for pregnancy loss. It may be more appropriate to assess a combination of antibodies rather than one antibody. However, a large meta-analysis of published trials is required in order to determine the prevalence of each particular autoantibody and different combinations of antibodies in different forms of reproductive failure. PMID:18504286

Carp, H J A; Meroni, P L; Shoenfeld, Y



The anti-angiogenic isoforms of VEGF in health and disease  

PubMed Central

Anti-angiogenic VEGF (vascular endothelial growth factor) isoforms, generated from differential splicing of exon 8, are widely expressed in normal human tissues but down-regulated in cancers and other pathologies associated with abnormal angiogenesis (cancer, diabetic retinopathy, retinal vein occlusion, the Denys-Drash syndrome and pre-eclampsia). Administration of recombinant VEGF165b inhibits ocular angiogenesis in mouse models of retinopathy and age-related macular degeneration, and colorectal carcinoma and metastatic melanoma. Splicing factors and their regulatory molecules alter splice site selection, such that cells can switch from the anti-angiogenic VEGFxxxb isoforms to the pro-angiogenic VEGFxxx isoforms, including SRp55 (serine/arginine protein 55), ASF/SF2 (alternative splicing factor/splicing factor 2) and SRPK (serine arginine domain protein kinase), and inhibitors of these molecules can inhibit angiogenesis in the eye, and splice site selection in cancer cells, opening up the possibility of using splicing factor inhibitors as novel anti-angiogenic therapeutics. Endogenous anti-angiogenic VEGFxxxb isoforms are cytoprotective for endothelial, epithelial and neuronal cells in vitro and in vivo, suggesting both an improved safety profile and an explanation for unpredicted anti-VEGF side effects. In summary, C-terminal distal splicing is a key component of VEGF biology, overlooked by the vast majority of publications in the field, and these findings require a radical revision of our understanding of VEGF biology in normal human physiology.

Qiu, Yan; Hoareau-Aveilla, Coralie; Oltean, Sebastian; Harper, Steven J.; Bates, David O.



Serious foetal growth restriction is associated with reduced proportions of natural killer cells in decidua basalis.  


Extravillous trophoblasts are major participants in placental development and remodelling of spiral arteries. Trophoblast invasion is regulated by maternal immune cells, and abnormal leucocyte subpopulation composition has been reported in implantation failure. In pre-eclampsia (PE), with or without foetal growth restriction (FGR), superficial trophoblast invasion and insufficient remodelling of spiral arteries are common findings. In the present study, we have compared spiral artery remodelling and leucocyte composition in decidual tissue from 30 cases (PE=8, FGR=5, PE + FGR=17) and 31 controls. Six histological remodelling criteria were established, and each pregnancy obtained a remodelling score. Numbers of natural killer (NK) cells (CD56+), T cells (CD3+) and activated (CD25+ or CD69+) leucocytes were determined and related to total leucocyte (CD45+) numbers in serial sections. Cases demonstrated significantly impaired spiral artery remodelling, inappropriate placental growth and reduced NK cell proportions, as compared to controls (P=0.02, P<0.001 and P=0.01, respectively). Reduced NK cell proportion was primarily found in pregnancies complicated by FGR, with or without PE, and a significant positive correlation was observed between NK cell proportion, trophoblast infiltration and placental growth. Our in vivo observations support the hypothesized association between NK cells, impaired placental development and pathogenesis of PE/FGR. PMID:16328353

Eide, Irina P; Rolfseng, Toril; Isaksen, Christina V; Mecsei, Reidun; Roald, Borghild; Lydersen, Stian; Salvesen, Kjell A; Harsem, Nina K; Austgulen, Rigmor



Seminal fluid and the generation of regulatory T cells for embryo implantation.  


T regulatory (Treg) cells are essential mediators of the maternal immune adaptation necessary for embryo implantation. In mice, insufficient Treg cell activity results in implantation failure, or constrains placental function and fetal growth. In women, Treg cell deficiency is linked with unexplained infertility, miscarriage, and pre-eclampsia. To devise strategies to improve Treg cell function, it is essential to define the origin of the Treg cells in gestational tissues, and the regulators that control their functional competence and recruitment. Male seminal fluid is a potent source of the Treg cell-inducing agents TGF? and prostaglandin E, and coitus is one key factor involved in expanding the pool of inducible Treg cells that react with paternal alloantigens shared by conceptus tissues. In mice, coitus initiates a sequence of events whereby female dendritic cells cross-present seminal fluid antigens and activate T cells, which in turn circulate via the blood to be sequestered into the endometrium. Similar events may occur in the human genital tract, where seminal fluid induces immune cell changes that appear competent to prime Treg cells. Improved understanding of how seminal fluid influences Treg cells in women should ultimately assist in the development of new therapies for immune-mediated pathologies of pregnancy. PMID:23480148

Robertson, Sarah A; Prins, Jelmer R; Sharkey, David J; Moldenhauer, Lachlan M



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

PubMed Central

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.

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



[Hyperhomocysteinemia: associated obstetric diabetes and fetal malformations].  


In its biological complexity, pregnancy represents a challenge both for the maternal organism and the fetal development and growth. During this period, some peculiar pathologies of pregnancy can occur which can involve or the fetus only i.e.: spontaneous pregnancy loss, intrauterine growth retardation, defects of neural tube, until the intrauterine fetal death; or pathologies occurring in the placenta and thus involving maternal organism and fetus too, such as pre-eclampsia. All these pathologies recognize many risk factors, among them the hyperhomocysteinemia. Hyperhomocysteinoemia can be caused by enzymatic defects or lack of some vitamins cofactors (vitamin B6, vitamin B12 and folic acid). The genetic defects which, as homozygous genotype, cause high plasma levels of homocysteine are already well known; they lead to an activity reduction of the enzymes responsible for their metabolism, for example: the deficiency of cystathionine beta-synthase; the deficiency of the methylcobalamine production; the deficit of the 5-10 methylenetethrahydrofolate reductase (MTHFR). However, even the heterozygous genotypes, which have a variable incidence from 1/70 to 1/200 and directly of 5-15% for the C677T mutation of the 5-10 MTHFR, can determine a mild hyperhomocysteinemia with a consequent cardiovascular risk. The close implications, widely demonstrated in the international literature, between hyperhomocysteinemia and the maternal-fetal diseases are described. PMID:16306866

Rugolo, S; Mirabella, D; Cantone, S M; Giuffrida, A



Maternal and neonatal outcomes of hospital vaginal deliveries in Tibet  

PubMed Central

Introduction To determine the outcomes of vaginal deliveries in three study hospitals in Lhasa, Tibet Autonomous Region (TAR), People's Republic of China (PRC), at high altitude (3,650 m). Methods Prospective observational study of 1,121 vaginal deliveries. Results Pre-eclampsia/gestational hypertension (PE/GH) was the most common maternal complication 18.9% (n=212), followed by postpartum hemorrhage (blood loss ? 500 ml) 13.4%. There were no maternal deaths. Neonatal complications included: low birth weight (10.2%), small for gestational age (13.7%), preterm delivery (4.1%) and low Apgar (3.7%). There were 11 stillbirths (9.8/1,000 live births) and 19 early neonatal deaths (17/1,000 live births). Conclusion This is the largest study of maternal and newborn outcomes in Tibet. It provides information on the outcomes of institutional vaginal births among women delivering infants at high altitude. There was a higher incidence of PE/GH and low birth weight; rates of PPH were not increased compared to those at lower altitudes.

Miller, S; Tudor, C; Nyima; Thorsten, VR; Sonam; Droyoung; Craig, S; Le, P; Wright, LL; Varner, MW



Postpartum spontaneous colonic perforation due to antiphospholipid syndrome.  


The antiphospholipid syndrome (APS) is a multi-systemic disease being characterized by the presence of antiphospholipid antibodies that involves both arterial and venous systems resulting in arterial or venous thrombosis, fetal loss, thrombocytopenia, leg ulcers, livedo reticularis, chorea, and migraine. We document a previously unreported case of a 37-year-old female in whom APS was first manifested by infarction and cecal perforation following cesarean section. At laparotomy the underlying cause of colonic perforation was not clear and after resection of the affected bowel an ileo-colostomy was performed. The diagnosis of APS was established during post-operative hospital stay and the patient was commenced on warfarin. Eventually, she made a full recovery and had her stoma reversed after 4 mo. Pregnancy poses an increased risk of complications in women with APS and requires a more aggressive approach to the obstetric care. This should include full anticoagulation in the puerperium and frequent doppler ultrasound monitoring of uterine and umbilical arteries to detect complications such as pre-eclampsia and placental insufficiency. PMID:19152458

Ahmed, Kamran; Darakhshan, Amir; Au, Eleanor; Khamashta, Munther A; Katsoulis, Iraklis E



Postpartum spontaneous colonic perforation due to antiphospholipid syndrome  

PubMed Central

The antiphospholipid syndrome (APS) is a multi-systemic disease being characterized by the presence of antiphospholipid antibodies that involves both arterial and venous systems resulting in arterial or venous thrombosis, fetal loss, thrombocytopenia, leg ulcers, livedo reticularis, chorea, and migraine. We document a previously unreported case of a 37-year-old female in whom APS was first manifested by infarction and cecal perforation following cesarean section. At laparotomy the underlying cause of colonic perforation was not clear and after resection of the affected bowel an ileo-colostomy was performed. The diagnosis of APS was established during post-operative hospital stay and the patient was commenced on warfarin. Eventually, she made a full recovery and had her stoma reversed after 4 mo. Pregnancy poses an increased risk of complications in women with APS and requires a more aggressive approach to the obstetric care. This should include full anticoagulation in the puerperium and frequent doppler ultrasound monitoring of uterine and umbilical arteries to detect complications such as pre-eclampsia and placental insufficiency.

Ahmed, Kamran; Darakhshan, Amir; Au, Eleanor; Khamashta, Munther A; Katsoulis, Iraklis E



Vitamin D supplementation for women during pregnancy  

PubMed Central

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

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



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



Protocadherin-12 Cleavage Is a Regulated Process Mediated by ADAM10 Protein  

PubMed Central

Protocadherins are a group of transmembrane proteins with homophilic binding activity, members of the cadherin superfamily. Apart from their role in adhesion, the cellular functions of protocadherins are essentially unknown. Protocadherin (PCDH)12 was previously identified in invasive trophoblasts and endothelial and mesangial cells in the mouse. Invalidation studies revealed that the protein was required for optimal placental development. In this article, we show that its human homolog is abundantly expressed in various trophoblast subtypes of the human placenta and at lower levels in endothelial cells. We demonstrate that PCDH12 is shed at high rates in vitro. The shedding mechanism depends on ADAM10 and results in reduced cellular adhesion in a cell migration assay. PCDH12 is subsequently cleaved by the ?-secretase complex, and its cytoplasmic domain is rapidly degraded by the proteasome. PCDH12 shedding is regulated by interlinked intracellular pathways, including those involving protein kinase C, PI3K, and cAMP, that either increase or inhibit cleavage. In endothelial cells, VEGF, prostaglandin E2, or histamine regulates PCDH12 shedding. The extracellular domain of PCDH12 was also detected in human serum and urine, thus providing evidence of PCDH12 shedding in vivo. Importantly, we observed an increase in circulating PCDH12 in pregnant women who later developed a pre-eclampsia, a frequent pregnancy syndrome and a major cause of maternal and fetal morbidity and mortality. In conclusion, we speculate that, like in mice, PCDH12 may play an important role in human placental development and that proteolytic cleavage in response to external factors, such as cytokines and pathological settings, regulates its activity.

Bouillot, Stephanie; Tillet, Emmanuelle; Carmona, Guillaume; Prandini, Marie-Helene; Gauchez, Anne-Sophie; Hoffmann, Pascale; Alfaidy, Nadia; Cand, Francine; Huber, Philippe



Adenoviral Delivery of VEGF121 Early in Pregnancy Prevents Spontaneous Development of Preeclampsia in BPH/5 Mice  

PubMed Central

An imbalance in circulating pro-angiogenic and anti-angiogenic factors is postulated to play a causal role in pre-eclampsia (PE). We have described an inbred mouse strain, BPH/5, which spontaneously develops a PE-like syndrome including late-gestational hypertension, proteinuria, and poor feto-placental outcomes. Here we tested the hypothesis that an angiogenic imbalance during pregnancy in BPH/5 mice leads to the development of PE-like phenotypes in this model. Similar to clinical findings, plasma from pregnant BPH/5 showed reduced levels of free vascular endothelial growth factor (VEGF) and placental growth factor (PGF) compared to C57BL/6 controls. This was paralleled by a marked decrease in VEGF protein and Pgf mRNA in BPH/5 placentae. Surprisingly, antagonism by the soluble form of the FLT1 receptor (sFLT1) did not appear to be the cause of this reduction, as sFLT1 levels were unchanged or even reduced in BPH/5 compared to controls. Adenoviral-mediated delivery of VEGF121 (Ad-VEGF) via tail vein at e7.5 normalized both the plasma free VEGF levels in BPH/5 and restored the in vitro angiogenic capacity of serum from these mice. Ad-VEGF also reduced the incidence of fetal resorptions and prevented the late-gestational spike in blood pressure and proteinuria observed in BPH/5. These data underscore the importance of dysregulation of angiogenic factors in the pathogenesis of PE, and suggest the potential utility of early pro-angiogenic therapies in treating this disease.

Woods, Ashley K.; Hoffmann, Darren S.; Weydert, Christine J.; Butler, Scott D.; Zhou, Yi; Sharma, Ram V.; Davisson, Robin L.



Birthweight of Offspring and Mortality of Parents: The Jerusalem Perinatal Study Cohort  

PubMed Central

Purpose To examine the association between birthweight in offspring and mortality in their parents. Distinguishing between risks of outcomes in mothers from fathers potentially provides clues as to the relative roles of genetic versus non-genetic mechanisms underlying these associations.. Methods We studied total and cause-specific mortality in a population-based cohort of 37,718 mothers and 38,002 fathers whose offspring were delivered in West Jerusalem during 1964–76, after an average follow-up of 34.12 years Results Hazard models controlling for socio-demographic and lifestyle characteristics indicated a U-shaped relationship between offspring’s birthweight and overall mortality, deaths from CHD, circulatory and other non-neoplastic causes in their mothers. Higher CHD mortality rates were observed among mothers who gave birth to babies with low (HR=2.13; 95%CI 1.40–3.25) and high birthweight (HR=1.98; 95%CI 1.36–2.88), as compared to mothers whose offspring weighed 2500–3999 gr at birth. Adjustment for maternal pre-eclampsia, slightly attenuated these results. Multivariate models indicated a negative linear relationship (HR=0.95, 95%CI 0.91–0.99) between offspring’s birthweight and overall mortality in their fathers. Unlike the association in mothers, the relation was noted primarily with deaths from “other causes”. Conclusions Birthweight of offspring is associated with parental mortality although the relation differs for fathers and mothers. These findings broaden previous observations that intra-uterine events have long-term consequences for adult health and support the need to explore genetic and/or environmental mechanisms underlying these associations.

Friedlander, Yechiel; Paltiel, Ora; Manor, Orly; Deutsch, Lisa; Yanetz, Rivka; Calderon, Ronit; Siscovick, David S.; Harlap, Susan



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


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



Relationships among maternal nutrient intake and placental biomarkers during the 1st trimester in low-income women  

PubMed Central

Purpose Pre-eclampsia is a multi-system disorder caused by inadequate placentation in early pregnancy; however, little is known about the influence of nutrient intake on placental development during the crucial 1st trimester. The objective of this study was to examine the relationships between nutrient intake and the raw values and ratios of angiogenic [placental growth factor (PlGF)] and antiangiogenic [soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng)] placental biomarkers in the 1st trimester. Methods A cross-sectional study of low-income, pregnant women (n = 118). Average nutrient intake was calculated from three 24-h dietary recalls. Biomarker values were adjusted for gestational age and nutrients were adjusted for energy. Results The angiogenic to antiangiogenic ratio [PlGF/(sFlt-1 × sEng)] was positively related to intake of vitamin D (r = 0.24), vitamin B2 (r = 0.25), B12 (r = 0.20), dietary folate equivalents (r = 0.19), iron (r = 0.19), and zinc (r = 0.19) and negatively related to transfats (r = ?0.24). Principal component analysis revealed that a vitamin/mineral factor [t (112) = 2.58, p = 0.011] and transfats factor [t (112) = ?2.03, p = 0.045] were significant predictors of the PlGF/(sFlt-1 × sEng) ratio. The vitamin and mineral factor was a significant predictor of sFlt-1 [t (122) = 2.29, p = 0.024]. Conclusions Expression of placental biomarkers in the early weeks of pregnancy may be influenced by intake of nutrients. Understanding the influence of maternal nutrient intake and placental development in the 1st trimester may provide the opportunity to avert the development or blunt the severity of preeclampsia.

Walker, Lorraine O.; Marti, C. Nathan; Ruiz, Roberta Jeanne; Wommack, Joel; Bryant, Miranda; Kim, SungHun; Timmerman, Gayle M.




PubMed Central

Severe pre/eclampsia are associated with brain edema that forms preferentially in the posterior cerebral cortex possibly due to decreased sympathetic innervation of posterior cerebral arteries and less effective autoregulation during acute hypertension. In the present study, we examined the effect of pregnancy on the effectiveness of cerebral blood flow autoregulation using laser Doppler flowmetry and edema formation by wet:dry weight in acute hypertension induced by phenylephrine infusion in the anterior and posterior cerebrum from nonpregnant (n=8) and late-pregnant (n=6) Sprague Dawley rats. In addition, we compared the effect of pregnancy on sympathetic innervation by tyrosine hydroxylase staining of posterior and middle cerebral arteries (n=5–6/group) and endothelial and neuronal nitric oxide synthase expression using quantitative polymerase chain reaction (n=3/group). In nonpregnant animals, there was no difference in autoregulation between anterior and posterior cerebrum. However, in late-pregnant animals, the threshold of cerebral blood flow autoregulation was shifted to lower pressures in the posterior cerebrum, which was associated with increased neuronal nitric oxide synthase expression in the posterior cerebral cortex vs. anterior. Compared to the nonpregnant state, pregnancy increased the threshold of autoregulation in both brain regions that was related to decreased expression of endothelial nitric oxide synthase. Lastly, acute hypertension during pregnancy caused greater edema formation in both brain cortices that was not due to changes in sympathetic innervation. These findings suggest that although pregnancy shifted the cerebral blood flow autoregulatory curve to higher pressures in both the anterior and posterior cortices, it did not protect from edema during acute hypertension.

Cipolla, Marilyn J.; Bishop, Nicole; Chan, Siu-Lung



Maternal mortality at Nnamdi Azikiwe University Teaching Hospital, Southeast Nigeria: a 10-year review (2003-2012)  

PubMed Central

Background Maternal mortality is high the world over, especially in sub-Saharan Africa, including Nigeria. Nigeria has consistently demonstrated one of the most abysmally poor reproductive health indices in the world, maternal mortality inclusive. This is a sad reminder that, unless things are better organized, Southeast Nigeria, which Nnamdi Azikiwe University Teaching Hospital (NAUTH) represents, may not join other parts of the world in attaining Millennium Development Goal 5 to improve maternal health in 2015. Objectives This study was conducted to assess NAUTH’S progress in achieving a 75% reduction in the maternal mortality ratio (MMR) and to identify the major causes of maternal mortality. Materials and methods This was a 10-year retrospective study, conducted between January 1, 2003 and December 31, 2012 at Nnamdi Azikiwe University Teaching Hospital, Nnewi, Southeast Nigeria. Results During the study period, there were 8,022 live births and 103 maternal deaths, giving an MMR of 1,284/100,000 live births. The MMR was 1,709 in 2003, reducing to 1,115 in 2012. This is to say that there was a 24.86% reduction over 10 years, hence, in 15 years, the reduction should be 37%. This extrapolated reduction over 15 years is about 38% less than the target of 75% reduction. The major direct causes of maternal mortality in this study were: pre-eclampsia/eclampsia (27%), hemorrhage (22%), and sepsis (12%). The indirect causes were: anemia, anesthesia, and HIV encephalopathy. Most of the maternal deaths occurred in unbooked patients (98%) and within the first 48 hours of admission (76%). Conclusion MMRs in NAUTH are still very high and the rate of reduction is very slow. At this rate, it will take this health facility 30 years, instead of 15 years, to achieve a 75% reduction in maternal mortality.

Obiechina, NJ; Okolie, VE; Okechukwu, ZC; Oguejiofor, CF; Udegbunam, OI; Nwajiaku, LSA; Ogbuokiri, C; Egeonu, R



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.

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



Placental water content and distribution.  


The percentage of total placental water (%H2O(T)), maternal (%MBV) and fetal (%FBV) blood volumes, non-vascular extracellular (%EW) and intracellular (%IW) water, and villous histology were studied in placentas from 12 normal term pregnancies after a normal vaginal delivery, 19 caesarean sections at term after a normal pregnancy and history of a previous caesarean section and 47 caesarean sections at term or preterm due to pregnancy complications. Values were derived from change in placental dry weight, maternal and fetal haemoglobin content and 51CrEDTA space after incubation of placental fragments. Normal ranges (mean +/- SD) after term vaginal delivery were: H2O(T) 83.9 +/- 0.2%, MBV 10.9 +/- 0.2%, FBV 7.4 +/- 0.9%, EW 57.3 +/- 1.3% and IW 11.2 +/- 0.6%. %H2O(T) was higher after caesarean section; other measurements were not affected. There were no differences between placentas after 33-37 and after 38-42 weeks gestation. Three of eight placentas after rhesus incompatibility had %H2O(T) above the mean +2SD of term placentas and five of 17 IUGR placentas were below the mean -2SD. The remaining placentas following maternal pre-eclampsia, hypertension, or diabetes had no apparent alteration in %H2O(T). A blind histological diagnosis of 'true' oedema was associated with both a significantly high %IW and %H2O(T). Perhaps this is due to alteration in placental cell volume regulation in certain situations. PMID:8208669

Barker, G; Boyd, R D; D'Souza, S W; Donnai, P; Fox, H; Sibley, C P



Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy.  


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



Pregnancy-associated retinal diseases and their management.  


Pregnancy-associated retinal diseases are conditions that may occur uniquely in pregnancy or, more commonly, general conditions that may worsen or alter during pregnancy as a result of hematologic, hormonal, metabolic, cardiovascular, and immunologic changes. Diabetic retinopathy (DR) is by far the most common retinal condition that is altered by pregnancy. However, there are currently no widely accepted, precise clinical guidelines regarding its management during pregnancy. At present it is not possible to predict who will regress and who will progress without treatment. Some of the variation in progression of DR in pregnancy may be a result of well-known risk factors such as hypertension or inadequate glycemic control prior to pregnancy. Other pregnancy-associated retinal diseases are relatively uncommon, and their treatments are poorly characterized. Pre-existing conditions include the white dot syndromes, such as punctuate inner choroidopathy and ocular histoplasmosis syndrome, as well as chorioretinal neovascularization from many other etiologies. Retinal and chorioretinal disorders that can arise during pregnancy include central serous chorioretinopathy and occlusive vasculopathy such as retinal artery occlusion (Purtschers-like retinopathy) and retinal vein occlusion. There remains a small group that appear to be unique to pregnancy, with pre-eclampsia- and eclampsia-associated retinopathy, disseminated intravascular coagulopathy, or amniotic fluid embolism being the best described. In angiogenic retinal diseases outside of pregnancy, the use of anti-vascular endothelial growth factor (anti-VEGF agents) has proven helpful. There are no safety data about the use of anti-VEGF agents during pregnancy, and conventionally the proposed interventions have been laser photocoagulation and systemic or intravitreal injections of steroids. Most of the literature on the treatment of pregnancy associated-chorioretinal neovascularization is anecdotal. PMID:23410822

Errera, Marie-Hélène; Kohly, Radha P; da Cruz, Lyndon


ATLANTIC DIP: pregnancy outcomes for women with type 1 and type 2 diabetes.  


ATLANTIC DIP prospectively evaluated the perinatal and maternal outcomes of pregnancies complicated by Type 1 and Type 2 diabetes during 2006/2007 in 5 antenatal centres. All women with established diabetes for at least 6 months prior to the index pregnancy and booking for antenatal care between 1/1/2006 and 31/12/2007 were included in the study. Results were collected electronically via the DIAMOND Diabetes Information System. Pregnancy outcome was compared with that of the background population receiving antenatal care in the region during the same time. There were 104 singleton pregnancies during the period of study. The stillbirth rate (SBR) of 25/1000 was 5 times greater than that reported in the background population at 5/1000 and the perinatal mortality rate (PMR) of 25/1000 was 3.5 times greater than background 7/1000. The congenital malformation rate (CMR) of 24/1000 was twice that observed in the background population. Women were not well prepared for pregnancy with 28% receiving pre pregnancy care (PPC), 43% receiving pre pregnancy folic acid and 51% achieving a HbA1C < = 7% at first antenatal visit. Pregnancy induced hypertension (PIH) and/or pre eclampsia toxaemia (PET) were three times more common than in women in the background population. In conclusion women are not well prepared for pregnancy. Maternal and infant morbidity and infant mortality are greater in women with diabetes. A regional pre pregnancy care (PPC) programme and centralised glucose management are urgently needed. PMID:22838098

Dunne, F P; Avalos, G; Durkan, M; Mitchell, Y; Gallacher, T; Keenan, M; Hogan, M; Carmody, L A; Gaffney, G



HLA-G has a concentration-dependent effect on the generation of an allo-CTL response  

PubMed Central

Human leucocyte antigen (HLA) -G is expressed on trophoblast cells during pregnancy, suggesting a role in protection of the semiallogeneic fetus. Published data suggest that HLA-G protects a cell against natural killer cell lysis. It has been hypothesized that HLA-G may also protect the fetus by preventing allo-cytotoxic T lymphocyte (CTL) responses. To test this hypothesis, we assayed the effects of various concentrations of purified HLA-G on CTL response in a mixed lymphocyte culture (MLC) system. We found that concentrations ? 0·1 µg/ml of HLA-G suppressed the allo-CTL response by 30–100% over the control, but, paradoxically, concentrations of 0·01–0·05 µg/ml of HLA-G augmented the allo-CTL response by 25–50% over the control. Concentrations ? 0·001 µg/ml HLA-G had no effect. Addition of HLA-G to preprimed allo-CTL effector cells did not affect their killing ability. Allo-CTL suppressive doses of HLA-G induced a T helper type 2 (Th2) cytokine response, whereas allo-CTL-enhancing doses of HLA-G induced a Th1-type cytokine response. HLA-G purified from first-trimester placenta does not affect allo-proliferative responses nor does it alter the percentage of CD4+ or CD8+ T cells in MLCs. These findings support a potential role for HLA-G-mediated suppression of allo-CTL formation in normal pregnancies. In addition, the effects observed at lower concentrations of HLA-G may have interesting implications for the condition of pre-eclampsia in which concentrations of this HLA class I molecule are reduced.

Kapasi, K; Albert, S E; Yie, S-M; Zavazava, N; Librach, C L



ELF5-enforced transcriptional networks define an epigenetically regulated trophoblast stem cell compartment in the human placenta.  


The first definitive cell fate decision in development occurs at the blastocyst stage with establishment of the trophoblast and embryonic cell lineages. In the mouse, lineage commitment is achieved by epigenetic regulation of a critical gatekeeper gene, the transcription factor Elf5, that reinforces placental cell fate and is necessary for trophoblast stem (TS) cell self-renewal. In humans, however, the epigenetic lineage boundary seems to be less stringent since human embryonic stem (ES) cells, unlike their murine counterparts, harbour some potential to differentiate into trophoblast derivatives. Here, we show that ELF5 is expressed in the human placenta in villous cytotrophoblast cells but not in post-mitotic syncytiotrophoblast and invasive extravillous cytotrophoblast cells. ELF5 establishes a circuit of mutually interacting transcription factors with CDX2 and EOMES, and the highly proliferative ELF5(+)/CDX2(+) double-positive subset of cytotrophoblast cells demarcates a putative TS cell compartment in the early human placenta. In contrast to placental trophoblast, however, ELF5 is hypermethylated and largely repressed in human ES cells and derived trophoblast cell lines, as well as in induced pluripotent stem cells and murine epiblast stem cells. Thus, these cells exhibit an embryonic lineage-specific epigenetic signature and do not undergo an epigenetic reprogramming to reflect the trophoblast lineage at key loci such as ELF5. Our identification of the trophoblast-specific transcriptional circuit established by ELF5 will be instrumental to derive human TS cell lines that truly reflect early placental trophoblast and that will be most beneficial to gain insights into the aetiology of common pregnancy complications, including intra-uterine growth restriction and pre-eclampsia. PMID:20354077

Hemberger, Myriam; Udayashankar, Ramya; Tesar, Paul; Moore, Harry; Burton, Graham J



A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer--experiences of the mother  

PubMed Central

Background We undertook a systematic review and meta-analysis of perinatal variables in relation to testicular cancer risk, with a specific focus upon characteristics of the mother. Methods EMBASE, PubMed, Scopus and Web of Science databases were searched using sensitive search strategies. Meta-analysis was undertaken using STATA 10. Results A total of 5865 references were retrieved, of which 67 met the inclusion criteria and contributed data to at least one perinatal analysis. Random effects meta-analysis found maternal bleeding during pregnancy [odds ratio (OR) 1.33, 95% confidence interval (CI) 1.02–1.73], birth order (primiparous vs not, 1.08, 95% CI 1.01–1.16; second vs first, OR 0.94, 95% CI 0.88–0.99; third vs first, OR 0.91, 95% CI 0.83–1.01; fourth vs first, OR 0.80, 95% CI 0.69–0.94) and sibship size (2 vs 1, OR 0.93, 95% CI 0.75–1.15; 3 vs 1, OR 0.89, 95% CI 0.74–1.07; 4 vs 1, OR 0.75, 95% CI 0.62–0.90) to be associated with testicular cancer risk. Meta-analyses that produced summary estimates which indicated no association included maternal age, maternal nausea, maternal hypertension, pre-eclampsia, breech delivery and caesarean section. Meta-regression provided evidence that continent of study is important in the relationship between caesarean section and testicular cancer (P = 0.035), and a meta-analysis restricted to the three studies from the USA was suggestive of association (OR 1.67, 95% CI 1.07–2.56). Conclusions This systematic review and meta-analysis has found evidence for associations of maternal bleeding, birth order, sibship size and possibly caesarean section with risk of testicular cancer.

Cook, Michael B; Akre, Olof; Forman, David; Madigan, M Patricia; Richiardi, Lorenzo; McGlynn, Katherine A



Study on primary cesarean section.  


Cesarean delivery has become a commonly used measure for delivery of the fetus. In the recent years incidence of Cesarean section (CS) has increased dramatically with massive pubic interest. It is called Primary Cesarean section when it is performed for the first time on a pregnant woman. This is a cross sectional study conducted on primary cesarean section from January to December 2004 in Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital, Dhaka. A total of 100 cases were selected for the study. The major findings of the study were as follows: Overall cesarean section rate was 57.87 percent and among them 74.34 percent were primary cesarean section. The median age group of patients being operated was 20 to 25 years. Most of the operations were carried out on primigravid patient due to various indications. The main indications were fetal distress (35%), pre-eclampsia (14%) and cervical dystocia (12%). The rate of emergency Cesarean section rate was 70% while elective Cesarean section was 30%. Most of the Cesarean section was performed under spinal anesthesia (96%). Maternal morbidity was 20%. Among those, post-operative infections (45%) and UTI (25%) were the most common. The less common complications were Post Partum Haemorrhage (PPH), puerperal-pyrexia, urinary bladder injury and spinal headache. 88% of the babies were born with good APGAR score (Appearance, Pulse, Grimace, Activity, and Respiration). Perinatal mortality was found to be 4%. The death cases were severe perinatal asphyxia, very LBW (Low Birth Weight) and stillborn. Most of the patients (69%) were discharged from hospital within 8 days of operation. PMID:21522103

Saha, L; Chowdhury, S B



Hypospadias in males with intrauterine growth restriction due to placental insufficiency: the placental role in the embryogenesis of male external genitalia.  


Our aim was to define the association between early onset intra-uterine growth restriction (IUGR) due to placental insufficiency and hypospadias in males. We prospectively studied a cohort of small-for-gestational age (SGA) male infants with hypospadias managed by a multidisciplinary team over a 5-year period. Thirty SGA male infants were diagnosed with hypospadias/abnormal genitalia after birth, and four of them were diagnosed antenatally. Five cases occurred in the smaller pair of discordant IUGR twins, where the larger co-twin had normal male genitalia. Serial ultrasounds demonstrated features of early-onset IUGR in all cases at a median gestational age of 21 weeks (range 14-31weeks). Twenty-one (70%) pregnancies were subsequently complicated by absent/reversed end-diastolic flow in the umbilical arteries indicating severe IUGR, and 17 (57%) women developed severe pre-eclampsia. There were 27 (90%) live births at a median gestational age of 31 weeks (range 27-37); 23 (77%) of the neonates had birth weights <3rd centile. All newborns had normal male karyotypes. In 62% (18/29) the hypospadias was severe. A correlation was found between the severity of the IUGR and the severity of hypospadias as significantly more infants with severe hypospadias were less than the 3rd centile compared to the mild-moderate hypospadias group: 94% (17/18) versus 55% (6/11), respectively (P = 0.02). In conclusion, SGA male newborns with hypospadias exhibit a high rate of early-onset severe IUGR due to placental insufficiency. Early placental development likely influences male external genitalia formation. Careful sonographic evaluation of the genitalia is advised when early-onset placentally mediated IUGR is found. PMID:20014131

Yinon, Yoav; Kingdom, John C P; Proctor, Leslie K; Kelly, Edmond N; Salle, Joao L Pippi; Wherrett, Diane; Keating, Sarah; Nevo, Ori; Chitayat, David



Why We Do Caesars: A Comparison of the Trends in Caesarean Section Delivery over a Decade.  


Introduction: In the United Kingdom, caesarean section (CS) rates have increased from 9% of deliveries in 1980 to 21% in 2001. A similar increase in CS rates has been seen in many developed countries. This is beyond the World Health Organisation's (WHO's) recommended level of 15%. This is a worrying trend as the risks of placenta previa, placenta accreta, hysterectomies, bladder and bowel injuries are increased with subsequent CS. We aim to ascertain the commonest indications for CS in a tertiary hospital and make recommendations to decrease future CS rates. Materials and Methods: This retrospective analysis compares the 5 most common indications for CS in 1999 and 2009. CS rates in the 2 study periods are tabulated and analysed as well. Results: In the first study period between January and December 1999, there were 2048 deliveries of which 365 were via CS. In the second study period of a decade later from January to December 2009, there were 1572 deliveries of which 531 were via CS. This gives an increase in CS rate from 17.8% in 1999 to 34% in 2009. The main indications for CS in 1999 were: cephalopelvic disproportion (18.6%), breech (14.2%), non-reassuring fetal status (11.8%), 1 previous CS (11.2%) and pregnancy-induced hypertension/pre-eclampsia/eclampsia (6.6%). The main indications for CS in 2009 were: 1 previous CS (18.1%), non-reassuring fetal status (12.2%), cephalopelvic disproportion (10.5%), 2 or more previous CS (7.9%) and breech (7.7%). Conclusion: There is a signifi cant increase in CS rates over the last decade with an increased percentage of CS done because of a previous CS. This is associated with increased risk of complications as well. Recommendations are suggested with the view to decrease future CS rates. PMID:24045377

Wang, Candice Py; Tan, Wei Ching; Kanagalingam, Devendra; Tan, Hak Koon



The consequences of obesity and excess weight gain in pregnancy.  


The prevalence of obesity in pregnancy is rising exponentially; about 15-20% of pregnant women now enter pregnancy with a BMI which would define them as obese. This paper provides a review of the strong links between obesity and adverse pregnancy outcome which operate across a range of pregnancy complications. For example, obesity is associated with an increased risk of maternal mortality, gestational diabetes mellitus, thromboembolism, pre-eclampsia and postpartum haemorrhage. Obesity also complicates operative delivery; it makes operative delivery more difficult, increases complications and paradoxically increases the need for operative delivery. The risk of the majority of these complications is amplified by excess weight gain in pregnancy and increases in proportion to the degree of obesity, for example, women with extreme obesity have OR of 7·89 for gestational diabetes and 3·84 for postpartum haemorrhage compared to their lean counterparts. The consequences of maternal obesity do not stop once the baby is born. Maternal obesity programmes a variety of long-term adverse outcomes, including obesity in the offspring at adulthood. Such an effect is mediated at least in part via high birthweight; a recent study has suggested that the odds of adult obesity are two-fold greater in babies weighing more than 4 kg at birth. The mechanism by which obesity causes adverse pregnancy outcome is uncertain. This paper reviews the emerging evidence that hyperglycaemia and insulin resistance may both play a role: the links between hyperglycaemia in pregnancy and both increased birthweight and insulin resistance have been demonstrated in two large studies. Lastly, we discuss the nature and rationale for possible intervention strategies in obese pregnant women. PMID:21880162

Norman, Jane E; Reynolds, Rebecca M; Reynolds, Rebecca



Cost effectiveness analysis of strategies for maternal and neonatal health in developing countries  

PubMed Central

Objective To determine the costs and benefits of interventions for maternal and newborn health to assess the appropriateness of current strategies and guide future plans to attain the millennium development goals. Design Cost effectiveness analysis. Setting Two regions classified by the World Health Organization according to their epidemiological grouping: Afr-E, those countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, comprising countries in South East Asia with high adult and high child mortality. Data sources Effectiveness data from several sources, including trials, observational studies, and expert opinion. For resource inputs, quantities came from WHO guidelines, literature, and expert opinion, and prices from the WHO choosing interventions that are cost effective database. Main outcome measures Cost per disability adjusted life year (DALY) averted in year 2000 international dollars. Results The most cost effective mix of interventions was similar in Afr-E and Sear-D. These were the community based newborn care package, followed by antenatal care (tetanus toxoid, screening for pre-eclampsia, screening and treatment of asymptomatic bacteriuria and syphilis); skilled attendance at birth, offering first level maternal and neonatal care around childbirth; and emergency obstetric and neonatal care around and after birth. Screening and treatment of maternal syphilis, community based management of neonatal pneumonia, and steroids given during the antenatal period were relatively less cost effective in Sear-D. Scaling up all of the included interventions to 95% coverage would halve neonatal and maternal deaths. Conclusion Preventive interventions at the community level for newborn babies and at the primary care level for mothers and newborn babies are extremely cost effective, but the millennium development goals for maternal and child health will not be achieved without universal access to clinical services as well.

Adam, Taghreed; Lim, Stephen S; Mehta, Sumi; Bhutta, Zulfiqar A; Fogstad, Helga; Mathai, Matthews; Zupan, Jelka; Darmstadt, Gary L



Clinical review: Special populations - critical illness and pregnancy  

PubMed Central

Critical illness is an uncommon but potentially devastating complication of pregnancy. The majority of pregnancy-related critical care admissions occur postpartum. Antenatally, the pregnant patient is more likely to be admitted with diseases non-specific to pregnancy, such as pneumonia. Pregnancy-specific diseases resulting in ICU admission include obstetric hemorrhage, pre-eclampsia/eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, amniotic fluid embolus syndrome, acute fatty liver of pregnancy, and peripartum cardiomyopathy. Alternatively, critical illness may result from pregnancy-induced worsening of pre-existing diseases (for example, valvular heart disease, myasthenia gravis, and kidney disease). Pregnancy can also predispose women to diseases seen in the non-pregnant population, such as acute respiratory distress syndrome (for example, pneumonia and aspiration), sepsis (for example, chorioamnionitis and pyelonephritis) or pulmonary embolism. The pregnant patient may also develop conditions co-incidental to pregnancy such as trauma or appendicitis. Hemorrhage, particularly postpartum, and hypertensive disorders of pregnancy remain the most frequent indications for ICU admission. This review focuses on pregnancy-specific causes of critical illness. Management of the critically ill mother poses special challenges. The physiologic changes in pregnancy and the presence of a second, dependent, patient may necessitate adjustments to therapeutic and supportive strategies. The fetus is generally robust despite maternal illness, and therapeutically what is good for the mother is generally good for the fetus. For pregnancy-induced critical illnesses, delivery of the fetus helps resolve the disease process. Prognosis following pregnancy-related critical illness is generally better than for age-matched non-pregnant critically ill patients.



PPAR? Regulates Trophoblast Proliferation and Promotes Labyrinthine Trilineage Differentiation  

PubMed Central

Background Abnormal trophoblast differentiation and function is the basis of many placenta-based pregnancy disorders, including pre-eclampsia and fetal growth restriction. PPAR?, a ligand-activated nuclear receptor, plays essential roles in placental development; null murine embryos die at midgestation due to abnormalities in all placental layers, in particular, small labyrinth and expanded giant cell layer. Previous studies have focused mostly on the role of PPAR? in trophoblast invasion. Based on the previously reported role of PPAR? in preadipocyte differentiation, we hypothesized that PPAR? also plays a pivotal role in trophoblast differentiation. To test this hypothesis, we report derivation of wild-type and PPAR?-null trophoblast stem (TS) cells. Methodology/Principal Findings PPAR?-null TS cells showed defects in both proliferation and differentiation, specifically into labyrinthine trophoblast. Detailed marker analysis and functional studies revealed reduced differentiation of all three labyrinthine lineages, and enhanced giant cell differentiation, particularly the invasive subtypes. In addition, rosiglitazone, a specific PPAR? agonist, reduced giant cell differentiation, while inducing Gcm1, a key regulator in labyrinth. Finally, reintroducing PPAR? into null TS cells, using an adenovirus, normalized invasion and partially reversed defective labyrinthine differentiation, as assessed both by morphology and marker analysis. Conclusions/Significance In addition to regulating trophoblast invasion, PPAR? plays a predominant role in differentiation of labyrinthine trophoblast lineages, which, along with fetal endothelium, form the vascular exchange interface with maternal blood. Elucidating cellular and molecular mechanisms mediating PPAR? action will help determine if modulating PPAR? activity, for which clinical pharmacologic agonists already exist, might modify the course of pregnancy disorders associated with placental dysfunction.

Parast, Mana M.; Yu, Heather; Ciric, Aleksandar; Salata, Mark W.; Davis, Vannessa; Milstone, David S.



Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis  

PubMed Central

Objective To summarise the benefits and harms of treatments for women with gestational diabetes mellitus. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Embase, Medline, AMED, BIOSIS, CCMed, CDMS, CDSR, CENTRAL, CINAHL, DARE, HTA, NHS EED, Heclinet, SciSearch, several publishers’ databases, and reference lists of relevant secondary literature up to October 2009. Review methods Included studies were randomised controlled trials of specific treatment for gestational diabetes compared with usual care or “intensified” compared with “less intensified” specific treatment. Results Five randomised controlled trials matched the inclusion criteria for specific versus usual treatment. All studies used a two step approach with a 50 g glucose challenge test or screening for risk factors, or both, and a subsequent 75 g or 100 g oral glucose tolerance test. Meta-analyses did not show significant differences for most single end points judged to be of direct clinical importance. In women specifically treated for gestational diabetes, shoulder dystocia was significantly less common (odds ratio 0.40, 95% confidence interval 0.21 to 0.75), and one randomised controlled trial reported a significant reduction of pre-eclampsia (2.5 v 5.5%, P=0.02). For the surrogate end point of large for gestational age infants, the odds ratio was 0.48 (0.38 to 0.62). In the 13 randomised controlled trials of different intensities of specific treatments, meta-analysis showed a significant reduction of shoulder dystocia in women with more intensive treatment (0.31, 0.14 to 0.70). Conclusions Treatment for gestational diabetes, consisting of treatment to lower blood glucose concentration alone or with special obstetric care, seems to lower the risk for some perinatal complications. Decisions regarding treatment should take into account that the evidence of benefit is derived from trials for which women were selected with a two step strategy (glucose challenge test/screening for risk factors and oral glucose tolerance test).



Heme oxygenase-1 in placental development and pathology.  


Pregnancy is accompanied by several adaptations in the mother, such as increased blood volume, higher cardiac output and reduced peripheral vascular resistance. Inability to accomplish these changes places both her and her pregnancy at risk of major placental complications such severe pre-eclampsia (sPE) or severe intra-uterine growth restriction (sIUGR). sPE is characterized by wide-spread maternal vascular dysfunction expressed as increased systemic vascular resistance; this state is accompanied by elevated levels of anti-angiogenic factors and lower production of vasodilatory gases. One of the key molecules implicated in sPE pathogenesis is heme oxygenase-1 (HO-1), a rate-limiting enzyme that breaks down heme into carbon monoxide (CO), biliverdin and free iron. CO and bilirubin (a downstream product of biliverdin processing) account for the angiogenic, vasodilatory and anti-oxidant properties of HO-1. These collective actions of the heme breakdown metabolites generated by HO-1 offer protection against cytotoxicity, inflammation, hypoxia and other forms of cellular stress that are central to the pathogenesis of sPE. Placental HO-1 expression and exhaled CO levels are both lower in women with sPE, consistent with a pathogenic role of HO-1. In vitro experiments demonstrate that induction of HO-1 downregulates secretion of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) and increases CO production. Advancing our understanding of regulatory pathways promoting placental HO-1 expression may offer new pharmacological tools to reduce maternal and perinatal morbidity in severe placental insufficiency syndromes, especially in women at greatest risk of developing sPE. PMID:23403148

Levytska, K; Kingdom, J; Baczyk, D; Drewlo, S



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


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. PMID:22796052

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



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.

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



[Automatic application of clinical guidelines - from theory to practice].  


ClinicaL guidelines (GLs) have been shown to be a powerful tool for enhancing the uniformity and quality of care, reducing its costs. However, since they are typically represented in free text, this leads to low rates of compliance. Therefore, physicians might benefit from GL automated decision support. It should be noted that not many studies evaluate the effect of providing support for the application of GLs over significant stretches of time on the quality of medical decisions. In this paper, we will describe the general architecture of medical decision support systems, review several known GL application frameworks, and focus on the research performed in the medicaL informatics research center at Ben-Gurion University [BGU] of the Negev which developed the Digital ELectronic Guideline Library, called DeGeL. In particular, we will describe a new GL application framework called PICARD that is intended for GL application over time, while ensuring that the GLs recommendations were followed. We will briefly introduce a technical evaluation of PICARD in the cardiology domain to manage patients according to a Coumadin [Warfarin] protocoL, and a functional evaluation in a complex pre-eclampsia/ eclampsia GL in the OB/GYN domain, which we performed with 36 physicians. The results showed that the PICARD creates independence in the quality of the decisions from any particular physician, level of expertise, clinicaL scenario, or decision type within the scenarios. CurrentLy, PICARD is a core component in the EU Mobiguide project, which focuses on remote monitoring and care of chronic patients, using mobile devices to send alerts and recommendations. PMID:23885450

Shalom, Erez; Shahar, Yuval; Lunenfeld, Eitan



A stereological perspective on placental morphology in normal and complicated pregnancies  

PubMed Central

Stereology applied to randomly-generated thin sections allows minimally-biased and economical quantitation of the 3D structure of the placenta from molecular to whole-organ levels. With these sampling and estimation tools, it is possible to derive global quantities (tissue volumes, interface surface areas, tubule lengths and particle numbers), average values (e.g. mean cell size or membrane thickness), spatial relationships (e.g. between compartments and immunoprobes) and functional potential (e.g. diffusive conductance). This review indicates ways in which stereology has been used to interpret the morphology of human and murine placentas including the processes of villous growth, trophoblast differentiation, vascular morphogenesis and diffusive transport. In human placenta, global quantities have shown that villous maturation involves differential growth of fetal capillaries and increases in endothelial cell number. Villous trophoblast is a continuously renewing epithelium and, through much of gestation, exhibits a steady state between increasing numbers of nuclei in cytotrophoblast (CT) and syncytiotrophoblast (ST). The epithelium gradually becomes thinner because its surface expands at a faster rate than its volume. These changes help to ensure that placental diffusing capacity matches the growth in fetal mass. Comparable events occur in the murine placenta. Some of these processes are perturbed in complicated pregnancies: 1) fetoplacental vascular growth is compromised in pregnancies accompanied by maternal asthma, 2) changes in trophoblast turnover occur in pre-eclampsia and intrauterine growth restriction, and 3) uteroplacental vascular development is impoverished, but diffusive transport increases, in pregnant mice exposed to particulate urban air pollution. Finally, quantitative immunoelectron microscopy now permits more rigorous analysis of the spatial distributions of interesting molecules between subcellular compartments or shifts in distributions following experimental manipulation.

Mayhew, Terry M



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

PubMed Central

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

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



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.

Poursafa, Parinaz; Kelishadi, Roya



The frequency and clinical significance of intra-amniotic infection and/or inflammation in women with placenta previa and vaginal bleeding: an unexpected observation  

PubMed Central

Objective Idiopathic vaginal bleeding, a common complication of pregnancy, increases the risk of SGA neonate, pre-eclampsia and preterm delivery and can be the only clinical manifestation of intra-amniotic infection and/or inflammation (IAI). Placenta previa is thought to be protective against ascending intrauterine infection, yet an excess of histologic chorioamnionitis has been reported in this condition. The aim of this study was to determine the frequency and clinical significance of IAI in women with placenta previa and vaginal bleeding in the absence of preterm labor. Study design A retrospective cohort study including 35 women with placenta previa and vaginal bleeding <37 weeks of gestation who underwent amniocentesis was undertaken. Patients with multiple gestations were excluded. Intra-amniotic infection was defined as a positive culture for microorganisms, and intra-amniotic inflammation as an elevated amniotic fluid interleukin (IL)-6 concentration. IL-6 concentrations were determined by ELISA in 28 amniotic fluid samples available. Non-parametric statistics were used for analysis. Results 1) The prevalence of intra-amniotic infection was 5.7% (2/35), and that of IAI was 17.9% (5/28); 2) the gestational age at delivery was lower in patients with IAI than in those without IAI (29.4 weeks, IQR: 23.1–34.7 vs. 35.4 weeks, IQR: 33.9–36.9; p=0.028); and 3) patients with placenta previa and IAI had a higher rate of delivery within 48 hours (80% (4/5) vs. 19% (4/21); p=0.008) than those without IAI. Conclusions Patients with placenta previa presenting with vaginal bleeding have intra-amniotic infection in 5.7% of the cases, and intra-amniotic infection and/or inflammation in 17.9%. Intra-amniotic infection and/or inflammation in patients with placenta previa and vaginal bleeding is a risk factor for preterm delivery within 48 hours.

Madan, Ichchha; Romero, Roberto; Kusanovic, Juan Pedro; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Dong, Zhong; Mazaki-Tovi, Shali; Vaisbuch, Edi; Savasan, Zeynep Alpay; Yeo, Lami; Kim, Chong Jai; Hassan, Sonia S.



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.

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



Benefits of using magnesium sulphate (MgSO4) for eclampsia management and maternal mortality reduction: lessons from Kano State in Northern Nigeria  

PubMed Central

Background Despite clear emphasis through the Millennium Development Goals, the problem of high maternal mortality persists especially within low and middle income countries. Various studies report remarkably high maternal mortality rates in northern Nigeria, where maternal mortality rates exceed 1,000 deaths per 100,000 live births and eclampsia contributes approximately 40% of maternal deaths. Across Nigeria, diazepam is routinely used for the management of eclampsia. Prior to February 2008, diazepam was widely used for the management of eclampsia in Kano State (within northern Nigeria) with case fatality rate being over 20%. While magnesium sulphate (MgSO4) is recognized as the most effective drug for the management of eclampsia; this study aims to compare MgSO4 therapy with diazepam therapy in terms of case fatality rates and costs. Findings This retrospective study, including 1045 patients with eclampsia and pre-eclampsia during the years 2008 and 2009, reports a drop in case fatality rates from 20.9% (95% CI: 18.7, 23.2) to 2.3% (95% CI: 1.4, 3.2) among eclampsia patients following the MgSO4 intervention. The study observed no significant difference in the cost of using MgSO4 therapy compared to diazepam therapy. Conclusions The study found a remarkable reduction in case fatality rate due to eclampsia in those who received MgSO4 therapy with minimal increase in costs when compared to diazepam therapy. Concerted efforts should be focused on properly introducing MgSO4 into emergency obstetric protocols especially within developing countries to reduce maternal mortality and also impact on health system performance.



Confirmed association between neonatal phototherapy or neonatal icterus and risk of childhood asthma.  


We have previously demonstrated an association between neonatal phototherapy and/or neonatal icterus and risk of hospitalization for childhood asthma. This study included children who were prescribed anti-asthmatic medication on a population basis to study exposures during the foetal and neonatal period and risk of childhood asthma. The Swedish Medical Birth Register was linked to the Swedish Prescribed Drug Register. Perinatal data for singleton children who were prescribed anti-asthmatic medication (n = 61,256) were compared with corresponding data for all singleton children born in Sweden from 1 January 1990 to 30 June 2003 and surviving to 1 July 2005 (n = 1,338,319). Mantel-Haenszel's odds ratios were calculated after adjustment for various known confounders. Being the first-born child, maternal age above 44 yr, involuntary childlessness for more than 1 yr, maternal smoking during pregnancy, maternal diabetes mellitus of any kind, pre-eclampsia, caesarean section, and instrumental vaginal delivery were all associated with an increased prescription of anti-asthmatic medication during childhood. Preterm birth, low birth weight, being small for gestational age, respiratory problems, mechanical ventilation, and sepsis and/or pneumonia were also associated with increased drug prescriptions. Neonatal phototherapy and/or icterus were risk determinants for children who developed asthma before the age of 12. After controlling for confounders, the odds ratio for phototherapy and/or icterus remained at 1.30 (95% confidence interval 1.16-1.47). In conclusion, this large population-based study confirms an association between some maternal and perinatal factors and childhood asthma, including neonatal phototherapy and/or icterus. PMID:20444150

Aspberg, Sara; Dahlquist, Gisela; Kahan, Thomas; Källén, Bengt



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



IBC CARe Microarray Allelic Population Prevalences in an American Indian Population  

PubMed Central

Background The prevalence of variant alleles among single nucleotide polymorphisms (SNPs) is not well known for many minority populations. These population allele frequencies (PAFs) are necessary to guide genetic epidemiology studies and to understand the population specific contribution of these variants to disease risk. Large differences in PAF among certain functional groups of genes could also indicate possible selection pressure or founder effects of interest. The 50K SNP, custom genotyping microarray (CARe) was developed, focusing on about 2,000 candidate genes and pathways with demonstrated pathophysiologic influence on cardiovascular disease (CVD). Methods The CARe microarray was used to genotype 216 unaffected controls in a study of pre-eclampsia among a Northern Plains, American Indian tribe. The allelic prevalences of 34,240 SNPs suitable for analysis, were determined and compared with corresponding HapMap prevalences for the Caucasian population. Further analysis was conducted to compare the frequency of statistically different prevalences among functionally related SNPs, as determined by the DAVID Bioinformatics Resource. Results Of the SNPs with PAFs in both datasets, 9.8%,37.2% and 47.1% showed allele frequencies among the American Indian population greater than, less than and either greater or less than (respectively) the HapMap Caucasian population. The 2,547 genes were divided into 53 functional groups using the highest stringency criteria. While none of these groups reached the Bonferroni corrected p value of 0.00094, there were 7 of these 53 groups with significantly more or less differing PAFs, each with a probability of less than 0.05 and an overall probability of 0.0046. Conclusion In comparison to the HapMap Caucasian population, there are substantial differences in the prevalence among an American Indian community of SNPs related to CVD. Certain functional groups of genes and related SNPs show possible evidence of selection pressure or founder effects.

Best, Lyle G.; Anderson, Cindy M.; Saxena, Richa; Almoguera, Berta; Chandrupatla, Hareesh; Martin, Candelaria; Falcon, Gilbert; Keplin, Kylie; Pearson, Nichole; Keating, Brendan J.



A simple-potentiometric method for determination of acid and alkaline phosphatase enzymes in biological fluids and dairy products using a nitrophenylphosphate plastic membrane sensor.  


A novel poly(vinyl chloride) matrix membrane sensor responsive to 4-nitrophenylphosphate (4-NPP) substrate is described, characterized and used for the potentiometric assay of acid (ACP) and alkaline (ALP) phosphatase enzymes. The sensor is based on the use of the ion-association complex of 4-NPP anion with nickel(II)-bathophenanthroline cation as an electroactive material and nitrophenyloctyl ether (NPOE) as a solvent mediator. The sensor displays good selectivity and stability and demonstrates a near-Nernstian response for 4-NPP over the concentration range 9.6x10(-6) to 1.0x10(-2) M with an anionic slope of 28.6+/-0.3 mV decade(-1) and a detection limit of 6.3x10(-6) M over the pH range 4.5-10. The sensor is used to measure the decrease of a fixed concentration of 4-NPP substrate as a function of acid and alkaline phosphatase enzyme activities at optimized conditions of pH and temperature. A linear relationship between the initial rate of 4-NPP substrate hydrolysis and enzyme activity holds over 0.05-3.0 and 0.03-3.4 IU L(-1) of ACP and ALP enzymes, respectively. Validation of the method by measuring the lower detection limit, range, accuracy, precision, within-day repeatability and between-day-variability reveals good performance characteristics of the proposed sensor. The sensor is used for the determination of acid and alkaline phosphatase enzyme activities in biological fluids of some patients suffering from alcoholic cirrhosis, acute myelocytic leukemia, pre-eclampsia and prostatic cancer. The sensor is also utilized for assessment of alkaline phosphatase enzyme in milk and dairy products. The results obtained agree fairly well with data obtained by the standard spectrophotometric methods. PMID:19362623

Hassan, Saad S M; Sayour, Hossam E M; Kamel, Ayman H



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

PubMed Central

Background Criteria-based audits (CBA) have been used to improve clinical management in developed countries, but have only recently been introduced in the developing world. This study discusses the use of a CBA to improve quality of care among eclampsia patients admitted at a University teaching hospital in Dar es Salaam Tanzania. Objective The prevalence of eclampsia in MNH is high (?6%) with the majority of cases arriving after start of convulsions. In 2004–2005 the case-fatality rate in eclampsia was 5.1% of all pregnant women admitted for delivery (MNH obstetric data base). A criteria-based audit (CBA) was used to evaluate the quality of care for eclamptic mothers admitted at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania after implementation of recommendations of a previous audit. Methods A CBA of eclampsia cases was conducted at MNH. Management practices were evaluated using evidence-based criteria for appropriate care. The Ministry of Health (MOH) guidelines, local management guidelines, the WHO manual supplemented by the WHO Reproductive Health Library, standard textbooks, the Cochrane database and reviews in peer reviewed journals were adopted. At the initial audit in 2006, 389 case notes were assessed and compared with the standards, gaps were identified, recommendations made followed by implementation. A re-audit of 88 cases was conducted in 2009 and compared with the initial audit. Results There was significant improvement in quality of patient management and outcome between the initial and re-audit: Review of management plan by senior staff (76% vs. 99%; P=0.001), urine for albumin test (61% vs. 99%; P=0.001), proper use of partogram to monitor labour (75% vs. 95%; P=0.003), treatment with steroids for lung maturity (2.0% vs. 24%; P=0.001), Caesarean section within 2 hours of decision (33% vs. 61%; P=0.005), full blood count (28% vs. 93%; P=0.001), serum urea and creatinine (44% vs. 86%; P=0.001), liver enzymes (4.0% vs. 86%; P=0.001), and specialist review within 2 hours of admission (25% vs. 39%; P=0.018). However, there was no significant change in terms of delivery within 24 hours of admission (69% vs. 63%; P=0.33). There was significant reduction of maternal deaths (7.7% vs. 0%; P=0.001). Conclusion CBA is applicable in low resource setting and can help to improve quality of care in obstetrics including management of pre-eclampsia and eclampsia.



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.



Fatal atypical reversible posterior leukoencephalopathy syndrome: a case report  

PubMed Central

Introduction Reversible posterior leukoencephalopathy syndrome – a reversible subacute global encephalopathy clinically presenting with headache, altered mental status, visual symptoms such as hemianopsia or cortical blindness, motor symptoms, and focal or generalized seizures – is characterized by a subcortical vasogenic edema symmetrically affecting posterior brain regions. Complete reversibility of both clinical signs and magnetic resonance imaging lesions is regarded as a defining feature of reversible posterior leukoencephalopathy syndrome. Reversible posterior leukoencephalopathy syndrome is almost exclusively seen in the setting of a predisposing clinical condition, such as pre-eclampsia, systemic infections, sepsis and shock, certain autoimmune diseases, various malignancies and cytotoxic chemotherapy, transplantation and concomitant immunosuppression (especially with calcineurin inhibitors) as well as episodes of abrupt hypertension. We describe for the first time clinical, radiological and histological findings in a case of reversible posterior leukoencephalopathy syndrome with an irreversible and fatal outcome occurring in the absence of any of the known predisposing clinical conditions except for a hypertensive episode. Case presentation A 58-year-old Caucasian woman presented with a two-week history of subacute and progressive occipital headache, blurred vision and imbalance of gait and with no evidence for raised arterial blood pressure during the two weeks previous to admission. Her past medical history was unremarkable except for controlled arterial hypertension. Cerebral magnetic resonance imaging demonstrated cortical and subcortical lesions with combined vasogenic and cytotoxic edema atypical for both venous congestion and arterial infarction. Routine laboratory and cerebrospinal fluid parameters were normal. The diagnosis of reversible posterior leukoencephalopathy syndrome was established. Within hours after admission the patient showed a rapidly decreasing level of consciousness, extension and flexion synergisms, bilaterally extensor plantar responses and rapid cardiopulmonary decompensation requiring ventilatory and cardiocirculatory support. Follow-up cerebral imaging demonstrated widespread and confluent cytotoxic edematous lesions in different arterial territories, global cerebral swelling, and subsequent upper and lower brainstem herniation. Four days after admission, the patient was declared dead because of brain death. Conclusion This case demonstrates that fulminant and fatal reversible posterior leukoencephalopathy syndrome may occur spontaneously, that is, in the absence of any of the known predisposing systemic conditions.



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

PubMed Central

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

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



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: Registration number: ACTRN12607000551493.

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



Perinatal complications and three-year follow up of infants of diabetic mothers with diabetic nephropathy stage IV.  


The objective of the study was to evaluate differences in the perinatal complications and in the 3-year follow up of infants of diabetic mothers with and without diabetic nephropathy stage IV. We compared the fetal and maternal complications and the early postpartal development until 3 years after delivery in 10 children of nephropathic diabetic mothers and 30 children of diabetic mothers without nephropathy. The mean (+/-SD) birthweight of the infants of nephropathic women was 2,250 +/- 496 g versus 3,544 +/- 435 g in the women without nephoropathy (p < 0.01). Births were premature in six pregnancies (60%) of the nephrotic women but in none of the women without nephropathy (p < 0.01). Three infants (30%) of the women with nephropathy showed respiratory distress syndrome in contrast to two babies (6%) of the women without nephropathy. Pre-eclampsia or eclampsia occurred in 6 (60%) pregnant women with and in two women (6%) without diabetic nephropathy (p < 0.01). Nephrotic syndrome was observed in 7 nephrotic women (70%) in contrast to none women without nephropathy. Three years postpartum, six of the children (60%) of nephropathic women had a body weight < the 50th percentile but none of the children of the women without nephropathy did so (p < 0.01). In addition, the children of nephropathic mothers started to speak significantly later (15 +/- 3 versus 12 +/- 13 months postpartum, p < 0.05) and had infectious diseases more commonly (60% versus 6%, p < 0.01) than the children of women without nephropathy. It can be concluded that in pregnancies of diabetic women the birth weights of the infants are significantly smaller and the fetal as well as maternal complication-rates significantly higher than in those of women without nephropathy. Also 3 years after delivery, the body weight of the children of nephropathic diabetic women is significantly lower than that of children of diabetic women without nephropathy. Additionally, children of nephropathic women are retarded in terms of linguistic development and their resistance to infections is reduced. PMID:11041289

Biesenbach, G; Grafinger, P; Zazgornik, J; Helmut; Stöger



Strengthening the emergency healthcare system for mothers and children in The Gambia  

PubMed Central

A system to improve the management of emergencies during pregnancy, childbirth, infancy and childhood in a region of The Gambia (Brikama) with a population of approximately 250,000 has been developed. This was accomplished through formal partnership between the Gambian Ministry of Health, the World Health Organisation, Maternal Childhealth Advocacy International and the Advanced Life Support Group. Since October 2006, the hospital in Brikama has been renovated and equipped and more efficiently provided with emergency medicines. An emergency ambulance service now links the community with the hospital through a mobile telephone system. Health professionals from community to hospital have been trained in obstetric, neonatal and paediatric emergency management using skills' based education. The programme was evaluated in log books detailing individual resuscitations and by external assessment. The hospital now has constant water and electricity, a functioning operating theatre and emergency room; the maternity unit and children's wards have better emergency equipment and there is a more reliable supply of oxygen and emergency drugs, including misoprostol (for treating post partum haemorrhage) and magnesium sulphate (for severe pre-eclampsia). There is also a blood transfusion service. Countrywide, 217 doctors, nurses, and midwives have undergone accredited training in the provision of emergency maternal, newborn and child care, including for major trauma. 33 have received additional education through Generic Instructor Courses and 15 have reached full instructor status. 83 Traditional Birth Attendants and 48 Village Health Workers have been trained in the recognition and initial management of emergencies, including resuscitation of the newborn. Eleven and ten nurses underwent training in peri-operative nursing and anaesthetics respectively, to address the acute shortage required for emergency Caesarean section. Between May 2007 and March 2010, 109 patients, mostly pregnant mothers, were stabilised and transported to hospital by the new emergency ambulance service. 293 resuscitation attempts were documented in personal logbooks. A sustainable system for better managing emergencies has been established and is helping to negate the main obstacle impeding progress: the country's lack of available trained medical and nursing staff. However, insufficient attention was paid to improving staff morale and accommodation representing significant failings of the programme.



Statistical Analysis of Individual Participant Data Meta-Analyses: A Comparison of Methods and Recommendations for Practice  

PubMed Central

Background Individual participant data (IPD) meta-analyses that obtain “raw” data from studies rather than summary data typically adopt a “two-stage” approach to analysis whereby IPD within trials generate summary measures, which are combined using standard meta-analytical methods. Recently, a range of “one-stage” approaches which combine all individual participant data in a single meta-analysis have been suggested as providing a more powerful and flexible approach. However, they are more complex to implement and require statistical support. This study uses a dataset to compare “two-stage” and “one-stage” models of varying complexity, to ascertain whether results obtained from the approaches differ in a clinically meaningful way. Methods and Findings We included data from 24 randomised controlled trials, evaluating antiplatelet agents, for the prevention of pre-eclampsia in pregnancy. We performed two-stage and one-stage IPD meta-analyses to estimate overall treatment effect and to explore potential treatment interactions whereby particular types of women and their babies might benefit differentially from receiving antiplatelets. Two-stage and one-stage approaches gave similar results, showing a benefit of using anti-platelets (Relative risk 0.90, 95% CI 0.84 to 0.97). Neither approach suggested that any particular type of women benefited more or less from antiplatelets. There were no material differences in results between different types of one-stage model. Conclusions For these data, two-stage and one-stage approaches to analysis produce similar results. Although one-stage models offer a flexible environment for exploring model structure and are useful where across study patterns relating to types of participant, intervention and outcome mask similar relationships within trials, the additional insights provided by their usage may not outweigh the costs of statistical support for routine application in syntheses of randomised controlled trials. Researchers considering undertaking an IPD meta-analysis should not necessarily be deterred by a perceived need for sophisticated statistical methods when combining information from large randomised trials.

Stewart, Gavin B.; Altman, Douglas G.; Askie, Lisa M.; Duley, Lelia; Simmonds, Mark C.; Stewart, Lesley A.



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

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



Angiotensin II Activates the Calcineurin/NFAT Signaling Pathway and Induces Cyclooxygenase-2 Expression in Rat Endometrial Stromal Cells  

PubMed Central

Cyclooxygenase (COX)-2, the inducible isoform of cyclooxygenase, plays a role in the process of uterine decidualization and blastocyst attachment. On the other hand, overexpression of COX-2 is involved in the proliferation of the endometrial tissue during endometriosis. Deregulation of the renin-angiotensin-system plays a role in the pathophysiology of endometriosis and pre-eclampsia. Angiotensin II increases intracellular Ca2+ concentration by targeting phospholypase C-gamma in endometrial stromal cells (ESC). A key element of the cellular response to Ca2+ signals is the activity of the Ca2+- and calmodulin-dependent phosphatase calcineurin. Our first aim was to study whether angiotensin II stimulated Cox-2 gene expression in rat ESC and to analyze whether calcineurin activity was involved. In cells isolated from non-pregnant uteri, COX-2 expression -both mRNA and protein- was induced by co-stimulation with phorbol ester and calcium ionophore (PIo), as well as by angiotensin II. Pretreatment with the calcineurin inhibitor cyclosporin A inhibited this induction. We further analyzed the role of the calcineurin/NFAT signaling pathway in the induction of Cox-2 gene expression in non-pregnant rat ESC. Cyclosporin A abolished NFATc1 dephosphorylation and translocation to the nucleus. Cyclosporin A also inhibited the transcriptional activity driven by the Cox-2 promoter. Exogenous expression of the peptide VIVIT -specific inhibitor of calcineurin/NFAT binding- blocked the activation of Cox-2 promoter and the up-regulation of COX-2 protein in these cells. Finally we analyzed Cox-2 gene expression in ESC of early-pregnant rats. COX-2 expression -both mRNA and protein- was induced by stimulation with PIo as well as by angiotensin II. This induction appears to be calcineurin independent, since it was not abrogated by cyclosporin A. In conclusion, angiotensin II induced Cox-2 gene expression by activating the calcineurin/NFAT signaling pathway in endometrial stromal cells of non-pregnant but not of early-pregnant rats. These results might be related to differential roles that COX-2 plays in the endometrium.

Abraham, Florencia; Sacerdoti, Flavia; De Leon, Romina; Gentile, Teresa; Canellada, Andrea



Porphyromonas gingivalis, Treponema denticola and toll-like receptor 2 are associated with hypertensive disorders in placental tissue: a case-control study.  


AIM(S): To explore the associations between the presence of periodontal pathogens and the expression of toll-like receptors (TLR-2 and TLR-4) in the placental tissue of patients with hypertensive disorders compared to the placentas of healthy normotensive patients. MATERIAL AND METHODS: A case-control study was performed. From a cohort composed of 126 pregnant women, 33 normotensive healthy pregnant women were randomly selected, and 25 cases of patients with hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, were selected. Placental biopsy was obtained after aseptic placental collection at the time of delivery. All of the samples were processed and analysed for the detection of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Treponema denticola and Tannerella forsythia using the polymerase chain reaction (PCR) technique. Determination of the expressions of TLR-2 and TLR-4 was performed in samples of total purified protein isolated from placental tissues and analysed by ELISA. The data were assessed using descriptive statistics. The associations among variables were estimated through multiple logistic regression models and the Mann-Whitney test to evaluate the differences between the two groups. RESULTS: A significant increase was observed in the expression of TLR-2 in the placentas of patients with hypertensive disorders (p = 0.04). Additionally, the multiple logistic regression models demonstrated an association between the presence of T. denticola and P. gingivalis in placental tissues and hypertensive disorders (OR: 9.39, p = 0.001, CI 95% 2.39-36.88 and OR: 7.59, p = 0.019, CI 95% 1.39-41.51, respectively). CONCLUSIONS: In the present study, pregnant women with periodontal disease presented an association in the placental tissue between the presence of T. denticola and P. gingivalis and hypertensive disorders. Additionally, increased expression of TLR-2 was observed. However, further studies are required to determine the specific roles of periodontal pathogens and TLRs in the placental tissue of patients with pregnancy-related hypertensive disorders. PMID:23711357

Chaparro, A; Blanlot, C; Ramírez, V; Sanz, A; Quintero, A; Inostroza, C; Bittner, M; Navarro, M; Illanes, S E



Multiple gestation pregnancy. The ESHRE Capri Workshop Group.  


Multiple gestation pregnancy rates are high in assisted reproductive treatment cycles because of the perceived need to stimulate excess follicles and transfer excess embryos in order to achieve reasonable pregnancy rates. Perinatal mortality rates are, however, 4-fold higher for twins and 6-fold higher for triplets than for singletons. Since the goal of infertility therapy is a healthy child, and multiple gestation puts that goal at risk, multiple pregnancy must be regarded as a serious complication of assisted reproductive treatment cycles. The 1999 ESHRE Capri Workshop addressed the psychological, medical, social and financial implications of multiple pregnancy and discussed how it might be prevented. Multiple gestations are high risk pregnancies which may be complicated by prematurity, low birthweight, pre-eclampsia, anaemia, postpartum haemorrhage, intrauterine growth restriction, neonatal morbidity and high neonatal and infant mortality. Multiple gestation children may suffer long-term consequences of perinatal complications, including cerebral palsy and learning disabilities. Even when the babies are healthy they must share their parents' attention and may experience slow language development and behavioural problems. Current data indicate that the average hospital cost per multiple gestation delivery is greater than the average cost of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles. Prevention is the most important means of decreasing multiple gestation rates. Multiple gestation rates in ovulation induction and superovulation cycles can be reduced by using lower dosage gonadotrophin regimens. If there are more than three mature follicles, the cycle should be converted to an IVF cycle, or it should be cancelled and intercourse should be avoided. In IVF cycles two embryos can be transferred without reducing birth rates in most circumstances. Embryo reduction involves extremely difficult decisions for infertile couples and should be used only as a last resort. Assisted reproductive treatment centres and registries should express cycle results as the proportion of singleton live births; twin and triplet rates should be reported separately as complications of the procedures. Reducing the multiple gestation pregnancy rate should be a high priority for assisted reproductive treatment programmes, despite the pressure from some patients to transfer more embryos in order to improve success. If nothing is done, public concern may lead to legislation in many countries, a step that would be unnecessary if assisted reproductive treatment programmes and registries took suitable steps to reduce multiple pregnancy rates. PMID:10920117



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.



[Posterior reversible encephalopathy syndrome].  


INTRODUCTION: Reversible Posterior Leukoencephalopathy Syndrome was introduced into clinical practice in 1996 in order to describe unique syndrome, clinically expressed during hypertensive and uremic encephalopathy, eclampsia and during immunosuppressive therapy [1]. First clinical investigations showed that leucoencephalopathy is major characteristic of the syndrome, but further investigations showed no significant destruction in white cerebral tissue [2, 3, 4]. In majority of cases changes are localise in posterior irrigation area of the brain and in the most severe cases anterior region is also involved. Taking into consideration all above mentioned facts, the suggested term was Posterior Reversible Encephalopathy Syndrome (PRES) for the syndrome clinically expressed by neurological manifestations derived from cortical and subcortical changes localised in posterior regions of cerebral hemispheres, cerebral trunk and cerebellum [5]. CASE REPORT: Patient, aged 53 years, was re-hospitalized in Cardiovascular Institute "Dediwe" two months after successful aorto-coronary bypass performed in June 2001 due to the chest bone infection. During the treatment of the infection (according to the antibiogram) in September 2001, patient in evening hours developed headache and blurred vision. The recorded blood pressure was 210/120 mmHg so antihypertensive treatment was applied (Nifedipin and Furosemid). After this therapy there was no improvement and intensive headache with fatigue and loss of vision developed. Neurological examination revealed cortical blindness and left hemiparesis. Manitol (20%, 60 ccm every 3 hours) and i.v. Nytroglicerin (high blood pressure). Brain CT revealed oedema of parieto-occipital regions of both hemispheres, more emphasized on the right. (Figure 1a, b, c). There was no sign of focal ischemia even in deeper sections (Figure 1d, e, f). Following three days enormous high blood pressure values were registered. On the fourth day the significant clinical improvement occurred with lowering of blood pressure, better mental state and better vision. There was no sign of left hemiparesis on the 7th day. On the 9th day there were no symptoms or sign of disease. Control brain CT (15th day) was normal. ETHIOPATHOGENESIS: Most common causes of PRES are hypertensive encephalopathy [6-8], pre-eclampsia/eclampsia [9-12] cyclosporin A administration [13-22] and uremic encephalopathy [23]. There are several theories about the mechanism for PRES in hypertensive encephalopathy (reversible vasospasm and hyperperfusion) and administration of cyclosporin A (neurotoxic effect). CLINICAL PICTURE: Most common symptoms are headache, nausea, vomiting, confusion, behavioural changes, changes of conciousness (from somnolencia to stupor), vision disturbances (blurred vision, haemianopsia, cortical blindness) and epileptic manifestations (mostly focal attacks with secondary generalisation). Mental functions are characterised with decreased activity and reactivity, confusion, loss of concentration and mild type of amnesia. Lethargy is often initial sign, sometimes accompanied with phases of agitation. Stupor and coma rarely occurred. DIAGNOSIS: In patients with hypertensive encephalopathy and eclampsia high blod pressure is registered. Neurological examination revealed vision changes and damages of mental function as well as increased reflex activity. Today, brain MRI and CT are considered the most important diagnostic method for the diagnosis and follow-up of patients with PRES [6]. Brain MRI better detects smaller focal parenhim abnormalities than brain CT. The most often neuroradiological finding is relatively symmetrical oedema of white cerebral tissue in parieto-occipital regions of both cerebral hemispheres. Gray cerebral tissue is sometimes involved, usually in mild form of disease. Diagnosis of this "cortical" form of PRES is possible by MR FLAIR (Fluid-Attenuated Inversion Recovery) technique [5]. TREATMENT: Therapeutic strategy depends on the cause of PRES and clinical picture. Most important are blood pres

Petrovi?, Branko; Kosti?, Vladimir; Sterni?, Nadezda; Kolar, Jovo; Tasi?, Nebojsa


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