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1

Severe pre-eclampsia and hypertensive crises.  

PubMed

Hypertensive disorders of pregnancy are one of the leading causes of peripartum morbidity and mortality globally. Hypertensive disease in pregnancy is associated with a spectrum of severity, ranging from mild pregnancy-induced hypertension to eclampsia. Although most cases of pre-eclampsia may be managed successfully, severe pre-eclampsia is a life-threatening multisystem disease associated with eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome, acute kidney injury, pulmonary oedema, placental abruption and intrauterine foetal death. Management of severe pre-eclampsia includes identification of high-risk patients, optimisation of antenatal care, early intervention and the identification and early management of complications. In the first instance, oral anti-hypertensive agents, including labetalol, nifedipine and methyldopa, should be tried. If oral anti-hypertensive agents have failed to adequately control blood pressure, intravenous anti-hypertensives should be considered. Commonly used intravenous anti-hypertensives include labetalol, hydralazine and glyceryl trinitrate. In addition to anti-hypertensive agents, close attention should be given to regular clinical examination, assessment of fluid balance, neurologic status and monitoring of other vital signs. Magnesium sulphate should be considered early to prevent seizures. Delivery of the baby is the definitive management of severe pre-eclampsia. PMID:23962474

Arulkumaran, N; Lightstone, L

2013-12-01

2

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

PubMed

Pre-eclampsia continues to be a challenge--to understand the underlying pathogenesis and to prevent or treat in the clinical setting. One area of potential therapies opening up is treatment of maternal lipids and clinical trials are underway using statins in early pre-eclampsia. At present, most potential therapies to treat lipids cannot be recommended for general use in pregnancy and if we were to target maternal lipids to reduce rates of pre-eclampsia, very large numbers of women may need to be treated. Prior to reaching that point, we first need to understand whether maternal lipids are pathogenic in the processes underlying pre-eclampsia. The aim of this review is to examine the role of lipids in the pathogenesis and outcomes of pre-eclampsia, how abnormal lipid genes may be implicated and consider whether treatment of hyperlipidemia has a more general place in the prevention or treatment of pre-eclampsia. PMID:25121342

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

2014-11-01

3

Is human placenta proteoglycan remodeling involved in pre-eclampsia?  

PubMed Central

Impaired placento-fetal communication is a coherent symptom of exaggerated pre-eclampsia. The impact of the cellular expression of different glycosaminoglycans (GAGs) in this event on the placenta in pre-eclampsia is still obscure. This is the first study aimed at discovering the relationship between structural alterations of different sulfated GAGs at the molecular level and the development of pre-eclampsia in inflicted placenta. Sulfated GAGs were isolated and purified from control and pre-eclampsia placentas. The amount and the molecular weight of GAG in each tissue sample were measured. The polydispersity of the recovered GAG samples were determined by polyacrylamide gel electrophoresis. The disaccharide composition of chondroitin sulfate, dermatan sulfate and heparan sulfate were deduced by chondroitinase and heparinase depolymerization followed by liquid chromatography–mass spectrometry. The in vivo sulfo-modulation of GAGs in pre-eclampsia and control placenta were examined using RT-PCR to determine the transcription levels of different sulfotransferases involved in GAG biosynthesis. Marked differences in GAG sulfation patterns and mRNA level of encoding selected GAG O-sulfotransferases were observed in pre-eclampsia. These data suggest a linkage between pre-eclampsia and the observed alterations in placental GAGs and could provide new insights about the modulating role of GAGs in the development and the severity of placental pre-eclampsia. PMID:18161024

Warda, Mohamad; Zhang, Fuming; Radwan, Moustafa; Zhang, Zhenqing; Kim, Nari; Kim, Young Nam

2009-01-01

4

Recent Insights into the Pathogenesis of Pre-eclampsia  

Microsoft Academic Search

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

J. M. Roberts; K. Y. Lain

2002-01-01

5

Monocytes and Macrophages in Pregnancy and Pre-Eclampsia  

PubMed Central

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

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

2014-01-01

6

Diagnosis and management of pre-eclampsia: an update  

PubMed Central

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

Turner, Judi A

2010-01-01

7

[Hemorrheological changes and their clinical relevance in pre-eclampsia].  

PubMed

This review summarizes the hemorheological changes during gestation and their clinical relevance in pre-eclampsia. The gestational disease named pre-eclampsia, characterized by proteinuria (more than 0.3 g/day) and hypertension (blood pressure above 140/90 mmHg), exists from the 20th gestational week until the sixth postpartum week. Its etiology is complex; the pathomechanism mainly involves disturbances in cross talks among the vegetative system, the placenta and the circulatory system. Soluble factors of placenta mediate circulatory changes, which result in adaptive responses in both vegetative and circulatory systems. Derailment of this adaption, however, leads to increased turbulence and local damages in cellular elements of the circulatory system. The initial local lesion progresses to a generalized form. Later, these events will continue to strengthen their own cycle. As a result, an unstable circulatory state will be established, which causes organ damages. PMID:21278025

Fodor, Andrea; Gyorffy, András; Orosz, László; Major, Tamás

2011-02-01

8

Management of pre-eclampsia: issues for anaesthetists.  

PubMed

Pre-eclampsia is a leading cause of maternal morbidity and mortality. Substandard care is often present and many deaths are preventable. The aim of this review is to summarise the key management issues for anaesthetists in the light of the current literature. A systematic literature search of electronic databases was undertaken including MEDLINE, EMBASE and the Cochrane Library using the key words obstetrics, pregnancy, pregnancy complications, maternal, pre-eclampsia, preeclampsia, cardiac function, haemodynamics, haemolysis, elevated liver enzymes, low platelets (HELLP), eclampsia, anaesthesia, anesthesia, neuraxial. Relevant Colleges and Societies websites were examined for pertinent guidelines. The disease is defined within the context of hypertensive diseases, and early recognition of pre-eclampsia and its complications, as well as multidisciplinary expert team management is highlighted. Accurate monitoring and recording of observations including the use of transthoracic echocardiography is discussed. The importance of the treatment of systolic blood pressure>180 mmHg and the use of intravenous antihypertensive medication as well as the use of parenteral magnesium sulphate for the treatment and prevention of eclampsia is emphasised . Restricted intravenous fluid therapy and avoidance of ergometrine is discussed. Neuraxial analgesia and anaesthesia, and general anaesthesia for birth is summarised as well as postpartum management including analgesia, thromboprophylaxis, management of acute pulmonary oedema and the use of pharmacological agents in the setting of breastfeeding. PMID:22731893

Dennis, A T

2012-09-01

9

Expression of antiangiogenic factors in the placental structures in pre-eclampsia.  

PubMed

Comparative morphological study of the placentas was carried out in women with pregnancy aggravated by the development of pre-eclampsia. Immunohistochemical methods showed increased expression of endoglin (CD105) and VEGFR1 in all placental structures. The intensity of endoglin and VEGFR1 expression was maximum in the syncytiotrophoblast and extravillous cytotrophoblast cells in severe pre-eclampsia. PMID:23330145

Shchyogolev, A I; Dubova, E A; Pavlova, K A; Lyapin, V M; Sukhikh, G T

2012-12-01

10

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

E-print Network

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

11

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

PubMed Central

Background Postpartum haemorrhage is a leading cause of maternal morbidity and mortality worldwide. Identifying risk indicators for postpartum haemorrhage is crucial to predict this life threatening condition. Another major contributor to maternal morbidity and mortality is pre-eclampsia. Previous studies show conflicting results in the association between pre-eclampsia and postpartum haemorrhage. The primary objective of this study was to investigate the association between pre-eclampsia and postpartum haemorrhage. Our secondary objective was to identify other risk indicators for postpartum haemorrhage in the Netherlands. Methods A nationwide cohort was used, containing prospectively collected data of women giving birth after 19 completed weeks of gestation from January 2000 until January 2008 (n?=? 1 457 576). Data were extracted from the Netherlands Perinatal Registry, covering 96% of all deliveries in the Netherlands. The main outcome measure, postpartum haemorrhage, was defined as blood loss of ?1000 ml in the 24 hours following delivery. The association between pre-eclampsia and postpartum haemorrhage was investigated with uni- and multivariable logistic regression analyses. Results Overall prevalence of postpartum haemorrhage was 4.3% and of pre-eclampsia 2.2%. From the 31 560 women with pre-eclampsia 2 347 (7.4%) developed postpartum haemorrhage, compared to 60 517 (4.2%) from the 1 426 016 women without pre-eclampsia (odds ratio 1.81; 95% CI 1.74 to 1.89). Risk of postpartum haemorrhage in women with pre-eclampsia remained increased after adjusting for confounders (adjusted odds ratio 1.53; 95% CI 1.46 to 1.60). Conclusion Women with pre-eclampsia have a 1.53 fold increased risk for postpartum haemorrhage. Clinicians should be aware of this and use this knowledge in the management of pre-eclampsia and the third stage of labour in order to reach the fifth Millenium Developmental Goal of reducing maternal mortality ratios with 75% by 2015. PMID:24367496

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

2013-01-01

12

Hypertensive choroidopathy in pre-eclampsia: two consecutive cases.  

PubMed

Hypertensive retinopathy is well known, but choroidopathy is uncommon and associated with acute increases in blood pressure. Nonperfused areas of the choriocapillaris lead to changes of overlying retinal pigment epithelium (RPE), resulting in neurosensory or RPE detachments. The authors describe two patients with serous retinal detachments associated with acute arterial hypertension in pre-eclampsia and HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome. Subretinal fluid was demonstrated on ultra-widefield fundus imaging and optical coherence tomography. Fluorescein angiography and indocyanine green angiography enabled imaging of the choroidal hypoperfusion. All signs and symptoms resolved after 1 and 3 months, respectively, with persistent macular pigmentary changes in both patients. PMID:24972182

Dewilde, Evelien; Huygens, Marc; Cools, Geertrui; Van Calster, Joachim

2014-01-01

13

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

PubMed Central

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

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

2014-01-01

14

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

PubMed Central

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

Williams, Paula Juliet; Morgan, Linda

2012-01-01

15

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

PubMed

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

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

2015-02-01

16

Morphometric characteristics of terminal villi of the placenta in pre-eclampsia.  

PubMed

Comparative morphological study of the placentas from women suffering from pre-eclampsia was carried out. Morphometric studies of histological preparations showed shrinkage and low vascularization of the placental terminal villi determining the development of hypoxia. PMID:23330099

Shchyogolev, A I; Dubova, E A; Pavlov, K A; Lyapin, V M; Kulikova, G V; Shmakov, R G

2012-11-01

17

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

PubMed

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

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

2014-01-01

18

Decidual hemostasis, inflammation, and angiogenesis in pre-eclampsia.  

PubMed

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

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

2011-03-01

19

Cytomegalovirus infection in association with early onset pre-eclampsia.  

PubMed

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

2010-01-01

20

A polymorphism in the gene for microsomal epoxide hydrolase is associated with pre-eclampsia  

PubMed Central

OBJECTIVE—Microsomal epoxide hydrolase is an important enzyme involved in the metabolism of endogenous and exogenous toxicants. Polymorphic variants of the human epoxide hydrolase gene vary in enzyme activity. We determined whether genetic variability in the gene encoding for microsomal epoxide hydrolase contributes to individual differences in susceptibility to the development of pre-eclampsia with or without the syndrome of Haemolysis, Elevated Liver enzymes, and Low Platelets (HELLP).?METHODS—A total of 183 non-pregnant women with a history of pre-eclampsia, 96 of whom had concurrently developed the HELLP syndrome, and 151 healthy female controls were genotyped for the 113Tyr?His polymorphism in exon 3 and the 139His?Arg polymorphism in exon 4 of the epoxide hydrolase gene by a polymerase chain reaction-restriction fragment length polymorphism assay. Chi-square analysis was used for statistical evaluation of differences in polymorphic rates.?RESULTS—In pre-eclampsia a higher frequency (29%) of the high activity genotype Tyr113 Tyr113 in exon 3 was found as compared to controls (16%, OR 2.0, 95% CI 1.2-3.7). There was no difference between groups for the 139His?Arg polymorphism. In women with a history of pre-eclampsia, no difference in epoxide hydrolase genotypes was found between women who either did or did not develop the HELLP syndrome. In addition, a significant association was found between predicted EPHX activity and pre-eclampsia.?CONCLUSIONS—Women with the high activity genotype in exon 3, which could reflect differences in metabolic activation of endogenous or exogenous toxic compounds, may have enhanced susceptibility to pre-eclampsia. However, polymorphisms in the epoxide hydrolase gene do not seem to influence the risk for concurrent development of the HELLP syndrome.???Keywords: pre-eclampsia; HELLP syndrome; epoxide hydrolase; genetic polymorphism PMID:11283205

Zusterzeel, P.; Peters, W.; Visser, W.; Hermsen, K.; Roelofs, H.; Steegers, E.

2001-01-01

21

Mediators of the association between pre-eclampsia and cerebral palsy: population based cohort study  

PubMed Central

Objective To test the hypothesis that pre-eclampsia is a risk factor for cerebral palsy mediated through preterm birth and being born small for gestational age. Design Population based cohort study. Setting Clinical data from the Norwegian Cerebral Palsy Registry were linked with perinatal data prospectively recorded by the Medical Birth Registry of Norway. Participants All singleton babies who survived the neonatal period during 1996-2006 (849 children with cerebral palsy and 616?658 control children). Main outcome measures Cerebral palsy and cerebral palsy subtypes. Results Children exposed to pre-eclampsia had an excess risk of cerebral palsy (unadjusted odds ratio 2.5, 95% confidence interval 2.0 to 3.2) compared with unexposed children. Among children born at term (?37 weeks), exposure to pre-eclampsia was not associated with an excess risk of cerebral palsy in babies not born small for gestational age (1.2, 0.7 to 2.0), whereas children exposed to pre-eclampsia and born small for gestational age had a significantly increased risk of cerebral palsy (3.2, 1.5 to 6.7). Non-small for gestational age babies born very preterm (<32 weeks) and exposed to pre-eclampsia had a reduced risk of cerebral palsy compared with unexposed children born at the same gestational age (0.5, 0.3 to 0.8), although the risk was not statistically significantly reduced among children exposed to pre-eclampsia and born small for gestational age (0.7, 0.4 to 1.3). Exposure to pre-eclampsia was not associated with a specific cerebral palsy subtype. Conclusions Exposure to pre-eclampsia was associated with an increased risk of cerebral palsy, and this association was mediated through the children being born preterm or small for gestational age, or both. Among children born at term, pre-eclampsia was a risk factor for cerebral palsy only when the children were small for gestational age. PMID:23838554

2013-01-01

22

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

PubMed

1. Pre-eclampsia is a serious pregnancy disorder associated with widespread activation of the maternal vascular endothelium. Recent evidence implicates a role for oxidative stress in the aetiology of this condition. 2. Reactive oxygen species, particularly superoxide anions, invokes endothelial cell activation through many pathways. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP) leading to endothelial dysfunction in various pathophysiological conditions (reperfusion, shock, diabetes). 3. We have studied whether the loss of endothelial function in pre-eclampsia is dependent on PARP activity. Endothelium-dependent responses of myometrial arteries were tested following exposure to either plasma from women with pre-eclampsia or normal pregnant women in the presence and absence of a novel potent inhibitor of PARP, PJ34. Additional effects of plasma and PJ34 inhibition were identified in microvascular endothelial cell cultures. 4. In myometrial arteries, PARP inhibition blocked the attenuation of endothelium-dependent responses following exposure to plasma from women with pre-eclampsia. In endothelial cell cultures, plasma from pre-eclamptics induced measurable oxidative stress and a concomitant increase in PARP activity and reduction in cellular ATP. Again, these biochemical changes were reversed by PJ34. 5. These results suggest that PARP activity plays a pathogenic role in the development of endothelial dysfunction in pre-eclampsia and promotes PARP inhibition as a potential therapy in this condition. PMID:15778700

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

2005-03-01

23

Association between an abnormal cerebroplacental ratio and the development of severe pre-eclampsia.  

PubMed

Objective:To study the association between the cerebroplacental ratio (CPR) and the development of pre-eclampsia.Study Design:Three study groups were determined: Group 1-normal umbilical artery (UA; referent), Group 2-abnormal UA and normal CPR and Group 3-abnormal UA and an abnormal CPR. The primary outcome was the development of severe pre-eclampsia.Results:We included 270 women. Women in Group 3 had significantly elevated rates of severe pre-eclampsia versus those in Group 1 and Group 2, 52.5% versus 5.1% and 15.4%, respectively, (P<0.01), adjusted odds ratio 4.14 (95% confidence interval, 2.59 to 6.61). Kaplan-Meier analysis revealed earlier delivery in women with pre-eclampsia in Group 3 versus Group 1, Cox-Mantel hazard ratio 2.39 (1.17 to 4.88), log rank P=0.01.Conclusion:An abnormal CPR is associated with a higher rate severe pre-eclampsia with delivery at earlier gestational ages than with a normal UA or an abnormal UA, but normal CPR.Journal of Perinatology advance online publication, 4 December 2014; doi:10.1038/jp.2014.210. PMID:25474554

Regan, J; Masters, H; Warshak, C R

2014-12-01

24

Late Postpartum HELLP Syndrome 60 Hours after Delivery Associated with Mild Pre-eclampsia  

PubMed Central

The purpose of this report is to present a case of mild Pre-eclampsia which was complicated with postpartum HELLP syndrome. A 25-years-old pregnant woman with mild Pre-eclampsia at 36 weeks of gestation was admitted to our clinic with uterine contractions. A caesarean section was performed, due to her previous caesarean section history. Postpartum period was uneventful until the 2nd day after the caesarean section. Epigastric pain, nausea and vomiting appeared two days after her delivery. In evaluation of the case, laboratory findings which were associated with HELLP syndrome were found to include haemolysis, elevated liver enzymes and low platelet counts. The general condition and laboratory findings of the case returned to normal with supportive and steroid treatment after 3 days. It should be noted that HELLP syndrome can develop in the postpartum period. Therefore, caution should be exercised in patients with pre-eclampsia, for the development of the postpartum HELLP syndrome. PMID:24551706

Cakmak, Bulent; Toprak, Muhammet; Nacar, Mehmet Can; Karatas, Ahmet

2013-01-01

25

Late Postpartum HELLP Syndrome 60 Hours after Delivery Associated with Mild Pre-eclampsia.  

PubMed

The purpose of this report is to present a case of mild Pre-eclampsia which was complicated with postpartum HELLP syndrome. A 25-years-old pregnant woman with mild Pre-eclampsia at 36 weeks of gestation was admitted to our clinic with uterine contractions. A caesarean section was performed, due to her previous caesarean section history. Postpartum period was uneventful until the 2nd day after the caesarean section. Epigastric pain, nausea and vomiting appeared two days after her delivery. In evaluation of the case, laboratory findings which were associated with HELLP syndrome were found to include haemolysis, elevated liver enzymes and low platelet counts. The general condition and laboratory findings of the case returned to normal with supportive and steroid treatment after 3 days. It should be noted that HELLP syndrome can develop in the postpartum period. Therefore, caution should be exercised in patients with pre-eclampsia, for the development of the postpartum HELLP syndrome. PMID:24551706

Cakmak, Bulent; Toprak, Muhammet; Nacar, Mehmet Can; Karatas, Ahmet

2013-12-01

26

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

PubMed

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

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

2002-01-01

27

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

PubMed Central

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

Williams, Paula J.; Broughton Pipkin, Fiona

2011-01-01

28

Association between risk for pre-eclampsia and HLA DR4  

SciTech Connect

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

Not Available

1990-03-17

29

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

PubMed Central

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

Gandhi, Sangeetha; Rao, Vishwas

2014-01-01

30

Pre-eclampsia: the pivotal role of the placenta in its pathophysiology and markers for early detection.  

PubMed

Pre-eclampsia is the second leading cause of maternal morbidity and mortality in the United States. Infants born to affected mothers face a five-fold increase in death rate [Lain and Roberts 2002; National Heart Lung and Blood Institute 2001]. Although pre-eclampsia has been recognized by physicians for millennia, relatively little is known about its pathogenesis or prevention. Predicting its development is often extremely difficult, perhaps leading the Greeks to use the name 'eklampsis' meaning lightening. Recent studies provide novel insights into the role of the placenta in the development of pre-eclampsia and demonstrate novel markers to assist in predicting the onset of disease and potential therapeutic targets. Following an introduction which highlights the classification of hypertensive disorders of pregnancy and defines incidence and adverse outcomes of pre-eclampsia, this manuscript will discuss the role of the placenta in the pathophysiology of pre-eclampsia and recent markers that may predict its onset. PMID:19124387

Hawfield, Amret; Freedman, Barry I

2009-02-01

31

Trophoblast deportation and the maternal inflammatory response in pre-eclampsia  

Microsoft Academic Search

We have proposed that the maternal syndrome of pre-eclampsia is caused by a systemic inflammatory response involving both leucocytes and endothelium. This inflammatory response is present also in normal pregnancy, but in a milder form. The inflammatory stimulus is most likely to come from the placenta. Syncytiotrophoblast apoptotic debris, which is shed into the maternal circulation in normal pregnancy and

I. L. Sargent; S. J. Germain; G. P. Sacks; S. Kumar; C. W. G. Redman

2003-01-01

32

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

Microsoft Academic Search

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

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

1999-01-01

33

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

PubMed Central

Twenty four women with severe pre-eclampsia diagnosed before 34 weeks' gestation were compared with 48 randomly selected controls matched for age and parity. Subjects were studied in the puerperium using a questionnaire, clinical examination, and review of case records. A history of infertility, headaches (particularly migraine), pre-eclampsia in a previous pregnancy, or a raised serum alpha-fetoprotein concentration at the time of screening for neural tube defect in the index pregnancy were all identified as significant risk factors in the pre-eclamptic women. Maternal age, a history of chronic hypertension or renal disease, or excessive maternal weight were not significantly associated with pre-eclampsia. Almost all the infants of pre-eclamptic women showed retarded growth: 18 were below the 10th centile and only one weighed more than the 25th centile. Four babies died. These observations indicate that pre-eclampsia of early onset may differ from the late onset disease not only in its very high perinatal morbidity and mortality but in its distinctive maternal risk factors. PMID:6411232

Moore, M P; Redman, C W

1983-01-01

34

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

PubMed

Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as chronic hypertension affect early and late sub-types of the syndrome. It also implies that all pregnant women may be destined to get pre-eclampsia but spontaneous or induced delivery averts this outcome in most instances. PMID:24477207

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

2014-02-01

35

Cardiac tamponade in pregnancy during the treatment of severe pre-eclampsia: report of a case.  

PubMed

We present a case of cardiac tamponade that occurred during the course of treatment for severe pre-eclampsia. A 37-year-old woman who underwent cesarean section for severe pre-eclampsia developed cardiac tamponade after delivery. While percutaneous pericardiocentesis temporarily improved her condition, pericardial effusion, dyspnea and tachycardia reappeared 5 days after delivery. A continuous drainage tube placed in the pericardial cavity for 5 days was required to maintain maternal cardiac function. Her clinical course was uneventful after continuous drainage and she was discharged 20 days after delivery. No such causes of symptomatic pericardial effusion were detected in the present case. Physicians should be aware of this complication when dyspnea is accompanied by tachycardia and enlargement of the cardiac silhouette with hypolucent lungs on chest X-ray. Immediate pericardiocentesis is also required to prevent life-threatening cardiac tamponade in such cases. PMID:24738125

Matsuki, Rikako; Nakago, Satoshi; Takaoka, Hideyuki; Oishi, Tetsuya; Kotsuji, Fumikazu

2014-03-01

36

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

Microsoft Academic Search

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

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

1998-01-01

37

Antioxidant status and serum levels of selectins in pre-eclampsia.  

PubMed

Abstract A cross-sectional study was conducted in a university hospital, enrolling 40 patients with pre-eclampsia (case group) and 40 healthy normotensive pregnant women (control group). Plasma activity of antioxidants and some adhesion molecules involved in oxidative stress were measured and compared between the two groups, according to the patients' age. In patients over the age of 30 years, serum levels of L-selectin and E-selectin were lower in pre-eclamptic patients (p < 0.05); antioxidants, catalase and superoxide dismutase did not significantly differ between the two groups, while glutathione peroxidase was significantly higher in the normotensive group (p < 0.05). In patients under the age of 30 years, E-selectin was significantly higher in the pre-eclampsia group (p < 0.05), while P-selectin, catalase and superoxide dismutase were not significantly different between the two groups (p > 0.05). Total antioxidative activity was similar between pre-eclamptic and normotensive patients (p > 0.05). This study revealed no relationship between total antioxidant activity and pre-eclampsia. PMID:25280210

Nasrollahi, S; Hoseini Panah, S M; Tavilani, H; Tavasoli, S; Naderan, M; Shoar, S

2015-01-01

38

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

PubMed

Pregnancy pathologies in general, and pre-eclampsia in particular, are problems usually treated in post-anesthesia recovery and hospitalization units. Pre-eclampsia is the most frequent form of hypertension associated with pregnancy (50%). It affects from 7% to 10% of pregnant women. It is known as pregnancy and puerperium multisystem syndrome. It is due to a reduction of the systemic perfusion generated by the vasospasms and the activation of the coagulation systems. A clinical case is presented of the immediate post-surgery period of a patient, who has been operated on cesarean section after having been diagnosed with pre-eclampsia. A nursing care plan was prepared, based on Marjory Gordon functional patterns and guided by NANDA-NOC-NIC taxonomy, where 6 nursing diagnoses, which are the basis for the fulfillment of this nursing process, are identified: Risk of infection, excess fluid volume, risk of bleeding, insufficient knowledge about its pathological process, severe pain, and anxiety. The application of this care plan leads to an improvement in the patient care and in the work organization. PMID:25482826

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

2014-12-01

39

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

PubMed Central

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

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

2014-01-01

40

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

PubMed

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

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

2014-08-01

41

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

PubMed

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

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

2014-07-14

42

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

PubMed Central

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

Varshney, Shailesh; Gautam, Akansha

2014-01-01

43

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

PubMed Central

Background Epidemiological data link low dietary calcium with pre-eclampsia. Current recommendations are for 1.5–2 g/day calcium supplementation for low-intake pregnant women, based on randomised controlled trials of ?1 g/day calcium supplementation from 20 weeks of gestation. This is problematic logistically in low-resource settings; excessive calcium may be harmful; and 20 weeks may be too late to alter outcomes. Objectives To review the impact of lower dose calcium supplementation on pre-eclampsia risk. Search strategy and selection criteria We searched PubMed and the Cochrane Pregnancy and Childbirth Group trials register. Data collection and analysis Two authors extracted data from eligible randomised and quasi-randomised trials of low-dose calcium (LDC, <1 g/day), with or without other supplements. Main results Pre-eclampsia was reduced consistently with LDC with or without co-supplements (nine trials, 2234 women, relative risk [RR] 0.38; 95% confidence interval [95% CI] 0.28–0.52), as well as for subgroups: LDC alone (four trials, 980 women, RR 0.36; 95% CI 0.23–0.57]); LDC plus linoleic acid (two trials, 134 women, RR 0.23; 95% CI 0.09–0.60); LDC plus vitamin D (two trials, 1060 women, RR 0.49; 0.31–0.78) and a trend for LDC plus antioxidants (one trial, 60 women, RR 0.24; 95% CI 0.06–1.01). Overall results were consistent with the single quality trial of LDC alone (171 women, RR 0.30; 95% CI 0.06–1.38). LDC plus antioxidants commencing at 8–12 weeks tended to reduce miscarriage (one trial, 60 women, RR 0.06; 95% CI 0.00–1.04). Conclusions These limited data are consistent with LDC reducing the risk of pre-eclampsia; confirming this in sufficiently powered randomised controlled trials would have implications for current guidelines and their global implementation. PMID:24621141

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

2014-01-01

44

Vascular endothelial growth factor and its receptors in the placental villi of pregnant patients with pre-eclampsia.  

PubMed

Comparative morphological study of the placentas from women with pre-eclampsia of different severity was carried out. The expression of vascular endothelial growth factor and its receptors (VEGFR-1, VEGFR-2, VEGFR-3) was studied by immunohistochemical methods. Branched angiogenesis processes predominated in the placentas of patients with pre-eclampsia. The syncytiocapillary membranes were thickened, the number of syncytial buds was greater than normally. Immunohistochemical studies showed high expression of VEGF and VEGFR-1 and low expression of VEGFR-2 in the placental villous structures. PMID:23658926

Dubova, E A; Pavlov, K A; Lyapin, V M; Shchyogolev, A I; Sukhikh, G T

2013-04-01

45

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. PMID:22215939

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

2011-01-01

46

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

PubMed

In sub-Saharan Africans, maternal mortality is unacceptably high, with >400 deaths per 100,000 births compared with <10 deaths per 100,000 births in Europeans. One-third of the deaths are caused by pre-eclampsia, a syndrome arising from defective placentation. Controlling placentation are maternal natural killer (NK) cells that use killer-cell immunoglobulin-like receptor (KIR) to recognize the fetal HLA-C molecules on invading trophoblast. We analyzed genetic polymorphisms of maternal KIR and fetal HLA-C in 484 normal and 254 pre-eclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of maternal KIR AA genotypes and fetal HLA-C alleles encoding the C2 epitope associates with pre-eclampsia [P = 0.0318, odds ratio (OR) = 1.49]. The KIR genes associated with protection are located in centromeric KIR B regions that are unique to sub-Saharan African populations and contain the KIR2DS5 and KIR2DL1 genes (P = 0.0095, OR = 0.59). By contrast, telomeric KIR B genes protect Europeans against pre-eclampsia. Thus, different KIR B regions protect sub-Saharan Africans and Europeans from pre-eclampsia, whereas in both populations, the KIR AA genotype is a risk factor for the syndrome. These results emphasize the importance of undertaking genetic studies of pregnancy disorders in African populations with the potential to provide biological insights not available from studies restricted to European populations. PMID:25561558

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

2015-01-20

47

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

Microsoft Academic Search

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

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

2007-01-01

48

Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis  

Microsoft Academic Search

BACKGROUND: Reliable antenatal identification of pre-eclampsia and small for gestational age is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving maternal\\/perinatal outcome. The purpose of this systematic review was to determine the accuracy of five serum analytes used in Down's serum screening for prediction of pre-eclampsia and\\/or small for gestational age.

Rachel K Morris; Jeltsje S Cnossen; Marloes Langejans; Stephen C Robson; Jos Kleijnen; Gerben ter Riet; Ben W Mol; Joris AM van der Post; Khalid S Khan

2008-01-01

49

Maternal endothelial soluble cell adhesion molecules with isolated small for gestational age fetuses: comparison with pre-eclampsia  

Microsoft Academic Search

Objective 1.To evaluate the activation profile of the endothelium in pregnancies complicated by small for gestational age fetuses compared with pre-eclampsia and normal pregnancy, by measuring the plasma levels of soluble adhesion molecules soluble E-selectin, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1. 2. To determine whether soluble adhesion molecules were related to the severity of small for gestational

Florence Bretelle; Florence Sabatier; Andrew Blann; Claude D'Ercole; Brigitte Boutière; Muriel Mutin; Léon Boubli; José Sampol; Françoise Dignat-George

2001-01-01

50

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

PubMed Central

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

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

2014-01-01

51

Objective prioritization of positional candidate genes at a quantitative trait locus for pre-eclampsia on 2q22  

Microsoft Academic Search

Pre-eclampsia\\/eclampsia (PE\\/E) is a common, serious medical disorder of human pregnancy. Familial association of PE\\/E has been recognized for decades, but the genetics are complex and poorly understood. In an attempt to identify PE\\/E susceptibility genes, we embarked on a positional cloning strategy using 34 Australian and New Zealand PE\\/E pedigrees. An initial 10-cM res- olution genome scan revealed a

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

2006-01-01

52

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

2011-01-01

53

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

PubMed

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

Elliot, Michael G; Crespi, Bernard J

2015-03-01

54

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

E-print Network

-eclampsia is supported by several studies and involves both maternal genes and the paternal genes inherited by the fetus (5, 6). The wall of the uterus is the territorial boundary between two genetically different individuals: the mother and the fetus. The uterine... , immune cells that populate the uterus and are essential for successful pregnancy. KIR proteins bind HLA ligands on the implanting placental trophoblast cells. African and European women share similar risk associations for pre-eclampsia, but protection...

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

2015-01-05

55

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

PubMed

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

2012-09-01

56

Evaluation of inflammatory mediators in the deciduas of pregnant women with pre-eclampsia/eclampsia.  

PubMed

Abstract Objective: The objective was to evaluate some inflammatory mediators, i.e. cytokines that induce and inhibit nitric oxide (NO) synthase, in pregnant women with pre-eclampsia/eclampsia (PE/E) compared to clinically normal patients. Methods: Placental fragments were collected from 46 pregnant patients, including 30 clinically normal subjects and 16 women with PE/E, and stored in NP40-containing phosphate buffer in a freezer at -70?°C until the time of solubilization. Cytokines IL-4, IL-10, IL-13, TNF-? and IFN-? were assayed by ELISA and NO was estimated by the Griess reaction after reduction. Results: Patients with PE/E presented significantly lower placental levels of IL-10 and IL-3 than the control group (p?

Peixoto, Alberto Borges; Araujo Júnior, Edward; Ribeiro, João Ulisses; Rodrigues, Denise Bertulucci Rocha; Castro, Eumênia Costa Cunha; Caldas, Taciana Mara Rodrigues Cunha; Rodrigues Júnior, Virmondes

2014-12-01

57

Carboxyhemoglobin levels in umbilical cord blood of women with pre-eclampsia and intrauterine growth restriction.  

PubMed

Abstract Objective: Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are associated with abnormal placentation. Heme oxygenase (HO) and carbon monoxide (CO) are involved in normal placental development and function and vasomotor control in the placenta. The objective of our study was to measure CO levels, as assessed by carboxyhemoglobin (COHb) levels in the umbilical cord arterial blood of women with PE, normotensive IUGR (<10thpercentile for birth weight), and normotensive pregnancies with appropriate-for-gestational age (AGA) infants. Design and methods: We prospectively analyzed COHb levels in the umbilical arterial blood of women with PE, normotensive IUGR, and normotensive AGA pregnancies. Exclusion criteria included cigarette smoke exposure, hemolytic disorders, a positive direct anti-globulin test, chronic hypertension, fever, and any significant medical illness. COHb levels were measured using the ABL 725 blood gas analyzer. Results: There were 41 women in the normotensive AGA group, 42 in the PE group, and 36 in the normotensive IUGR group. Maternal age, mode of delivery, gravidity, parity, and gender of the infants were similar in the three groups. Gestational age and birth weight were significantly higher in the normotensive AGA group compared with the other two groups. COHb levels were significantly lower in the PE group compared with the normotensive AGA group (0.38±0.06% vs. 0.77±0.11%, P<0.05). COHb levels, although lower in the normotensive IUGR group compared with the normotensive AGA group, did not reach statistical significance. Conclusion: Our data suggests the HO-CO system may have a role in the pathogenesis of PE. We also, for the first time, provide information on umbilical arterial COHb levels in normotensive IUGR pregnancies. PMID:23093081

Yusuf, Kamran; Kamaluddeen, Majeeda; Wilson, R Douglas; Akierman, Albert

2012-06-24

58

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

PubMed Central

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

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

2013-01-01

59

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. PMID:21596735

2011-01-01

60

Translating research into policy and practice in developing countries: a case study of magnesium sulphate for pre-eclampsia  

PubMed Central

Background The evidence base for improving reproductive health continues to grow. However, concerns remain that the translation of this evidence into appropriate policies is partial and slow. Little is known about the factors affecting the use of evidence by policy makers and clinicians, particularly in developing countries. The objective of this study was to examine the factors that might affect the translation of randomised controlled trial (RCT) findings into policies and practice in developing countries. Methods The recent publication of an important RCT on the use of magnesium sulphate to treat pre-eclampsia provided an opportunity to explore how research findings might be translated into policy. A range of research methods, including a survey, group interview and observations with RCT collaborators and a survey of WHO drug information officers, regulatory officials and obstetricians in 12 countries, were undertaken to identify barriers and facilitators to knowledge translation. Results It proved difficult to obtain reliable data regarding the availability and use of commonly used drugs in many countries. The perceived barriers to implementing RCT findings regarding the use of magnesium sulphate for pre-eclampsia include drug licensing and availability; inadequate and poorly implemented clinical guidelines; and lack of political support for policy change. However, there were significant regional and national differences in the importance of specific barriers. Conclusion The policy changes needed to ensure widespread availability and use of magnesium sulphate are variable and complex. Difficulties in obtaining information on availability and use are combined with the wide range of barriers across settings, including a lack of support from policy makers. This makes it difficult to envisage any single intervention strategy that might be used to promote the uptake of research findings on magnesium sulphate into policy across the study settings. The publication of important trials may therefore not have the impacts on health care that researchers hope for. PMID:16262902

Aaserud, Morten; Lewin, Simon; Innvaer, Simon; Paulsen, Elizabeth J; Dahlgren, Astrid T; Trommald, Mari; Duley, Lelia; Zwarenstein, Merrick; Oxman, Andrew D

2005-01-01

61

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

Microsoft Academic Search

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

J. G Ray; C. A Laskin

1999-01-01

62

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

Microsoft Academic Search

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

Felipe Vadillo-Ortega; Otilia Perichart-Perera; Salvador Espino; Marco Antonio Avila-Vergara; Isabel Ibarra; Roberto Ahued; Myrna Godines; Samuel Parry; George Macones; Jerome F Strauss

2011-01-01

63

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

PubMed Central

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

2007-01-01

64

Susceptibility allele-specific loss of miR-1324-mediated silencing of the INO80B chromatin-assembly complex gene in pre-eclampsia.  

PubMed

In humans, the elucidation of the genetics underlying multifactorial diseases such as pre-eclampsia remains complex. Given the current day availability of genome-wide linkage- and expression data pools, we applied pathway-guided genome-wide meta-analysis guided by the premise that the functional network underlying these multifactorial syndromes is under selective genetic pressure. This approach drastically reduced the genomic region of interest, i.e. 2p13 linked with pre-eclampsia in Icelandic families, from 8 679 641 bp (region with linkage) to 45 264 bp (coding exons of prioritized genes) (0.83%). Mutation screening of the candidate genes (n = 13) rapidly reduced the minimal critical region and showed the INO80B gene, encoding a novel winged helix domain (pfam14465) and part of the chromatin-remodeling complex, to be linked to pre-eclampsia. The functional defect in placental cells involved a susceptibility allele-dependent loss-of-gene silencing due to increased INO80B RNA stability as a consequence of differential binding of miR-1324 to the susceptibility allele of rs34174194. This risk allele is located at position 1 in an absolutely conserved 7-mer (UUGUCUG) in the 3-UTR of INO80B immediately downstream of a variant Pumillio Recognition Element (UGUANAAG). These data support that pre-eclampsia genes affect a conserved fundamental mechanism that evolved as a consequence of hemochorial placentation. Functionally, this involves founder-dependent, placentally expressed paralogous genes that regulate an essential trophoblast differentiation pathway but act at different entry points. PMID:25143393

Oudejans, Cees B M; Michel, Omar J; Janssen, Rob; Habets, Rob; Poutsma, Ankie; Sistermans, Erik A; Weiss, Marjan M; Incarnato, Danny; Oliviero, Salvatore; Kleiverda, Gunilla; Van Dijk, Marie; Arngrímsson, Reynir

2015-01-01

65

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

PubMed Central

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

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

2013-01-01

66

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

PubMed Central

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

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

2013-01-01

67

Differential expression of microRNAs in decidua-derived mesenchymal stem cells from patients with pre-eclampsia  

PubMed Central

Background Mesenchymal stem cells (MSCs) at maternal-fetal interface are considered to play an important role in the pathogenesis of pre-eclampsia (PE). microRNAs (miRNAs) also have an important influence on differentiation, maturation, and functions of MSCs. Our aim in this study was to determine the differential expression of miRNAs in decidua-derived MSCs (dMSCs) from severe PE and normal pregnancies. Results miRNA expression profiles in dMSCs from five patients with severe PE and five healthy pregnant women were screened using microarray. Then, bioinformatic analysis of the microarray results was performed. Out of 179 differentially expressed miRNAs, 49 miRNAs had significant (p?

2014-01-01

68

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. PMID:22703475

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

2012-01-01

69

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

PubMed Central

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

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

2011-01-01

70

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

PubMed Central

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

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

2014-01-01

71

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

PubMed Central

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

2013-01-01

72

Correlations between serum assays of human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) and pre-eclampsia or intrauterine growth restriction (IUGR) among nulliparas younger than 38 years  

Microsoft Academic Search

Objective: To study the relation between serum human chorionic gonadotrophin (hCG) levels measured at 15–18 weeks and gestational disorders, assess their correlation with the artery uteroplacental Doppler (AUD) at 24 weeks among nulliparas, and assess the predictivity of the hCG\\/hPL (human placental lactogen) ratio for pre-eclampsia. Study Design: Retrospective study of two groups of women younger than 38 years old:

Philippe Merviel; Françoise Müller; Jean Guibourdenche; Nadia Berkane; Rodolphe Gaudet; Gérard Bréart; Serge Uzan

2001-01-01

73

Association between a functional dopamine D4 receptor promoter region polymorphism (-C521T) and pre-eclampsia: a family-based study.  

PubMed

Although many candidate genes have been studied in pre-eclampsia (PE), the important class of catecholamine receptors that contribute to sympathetic tone and blood pressure regulation has yet to be investigated. We therefore examined the dopamine D4 receptor (DRD4) gene. We performed a prospective family-based study in 50 families (patient and both her parents) who were genotyped for three DRD4 promoter regions. These single-nucleotide polymorphisms (SNPs) were tested for association using family-based association test (FBAT) that also included two quantitative measures, aspartate aminotransferase [serum glutamic oxalacetic transaminase (SGOT)] and systolic blood pressure. SNPs were assayed using a commercially available SNAPSHOT kit and PCR products were analysed in an ABI 310 DNA analyser. A significant association (preferential transmission of the T allele from a heterozygous parent to affected mother) was observed between the -C521T SNP and PE (P = 0.019). Significant association was also observed between the -521T allele and two-dimensional measures of PE : GOT (P = 0.039) and systolic blood pressure (P = 0.036). The DRD4 promoter region -C521T SNP that reduces transcriptional efficiency of this gene is suggested to contribute to developing PE. Additionally, DRD4 -521 TT homozygosity may be a marker for severe PE. PMID:16455620

Korobochka, Roman; Gritsenko, Inga; Gonen, Ron; Ebstein, Richard P; Ohel, Gonen

2006-02-01

74

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

PubMed

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

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

2015-02-01

75

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

PubMed

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

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

2014-12-01

76

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

PubMed Central

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

2007-01-01

77

Serum calcium and magnesium levels in women presenting with pre-eclampsia and pregnancy-induced hypertension: a case¿control study in the Cape Coast metropolis, Ghana.  

PubMed

BackgroundHypertensive disorders of pregnancy are important causes of morbidity and mortality. The levels of calcium (Ca2+) and magnesium (Mg2+) in pregnancy may implicate their possible role in pregnancy-induced hypertension. This study assessed serum Ca2+ and Mg2+ levels in women with PIH (pregnancy-induced hypertension) and PE (pre-eclampsia), compared to that in normal pregnancy.MethodsThis case¿control study was conducted on 380 pregnant women (¿20 weeks gestation) receiving antenatal care at three hospitals in the Cape Coast metropolis, Ghana. This comprised 120 women with PIH, 100 women with PE and 160 healthy, age-matched pregnant women (controls). Demographic, anthropometric, clinical and obstetric data were gathered using an interview-based questionnaire. Venous blood samples were drawn for the estimation of calcium and magnesium.ResultsSystolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly raised in women with PIH (p¿=¿0.001) and PE (p¿=¿0.001). Women with hypertensive disorders (PE and PIH) had significantly lower serum calcium and magnesium levels than those in the control group (p¿<¿0.0001 each). Of those with PIH, SBP correlated positively with BMI (r¿=¿0.575, p¿<¿0.01) and Ca2+ correlated positively with Mg2+ (r¿=¿0.494, p¿<¿0.01). This was similar amongst the PE group for SBP and BMI as well as for Ca2+and Mg2+ but was not significant. Multivariate analysis showed that women aged ¿40 years were at a significant risk of developing PIH (OR¿=¿2.14, p¿=¿0.000).ConclusionIn this study population, serum calcium and magnesium levels are lower in PIH and PE than in normal pregnancy. Mineral supplementation during the antenatal period may influence significantly, the occurrence of hypertensive disorders in pregnancy. PMID:25410280

Ephraim, Richard; Osakunor, Derick; Denkyira, Seth; Eshun, Henrietta; Amoah, Samuel; Anto, Enoch

2014-11-20

78

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

PubMed Central

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

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

2013-01-01

79

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

PubMed Central

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

Büke, Bar??; Topçu, Hasan Onur; Engin-Üstün, Yaprak; Dan??man, Nuri

2014-01-01

80

The favorable effects of garlic intake on metabolic profiles, hs-CRP, biomarkers of oxidative stress and pregnancy outcomes in pregnant women at risk for pre-eclampsia: randomized, double-blind, placebo-controlled trial.  

PubMed

Abstract Objective: This study was performed to determine the favorable effects of garlic on metabolic status and pregnancy outcomes among pregnant women at risk for pre-eclampsia. Methods: This randomized, double-blind, placebo-controlled trial was conducted among 44 pregnant women, primigravida, aged 18-40 years old at 27 weeks' gestation with positive roll-over test. Participants were randomly assigned to receive either one garlic tablet (equal to 400?mg garlic and 1?mg allicin) (n?=?22) or placebo (n?=?22) once daily for 9 weeks. Fasting blood samples were taken at baseline and after 9 weeks' intervention to measure metabolic profiles and biomarkers of oxidative stress. Results: Administration of garlic compared with the placebo resulted in decreased levels of serum high sensitivity C-reactive protein (hs-CRP) (-1425.90 versus 1360.50?ng/mL, p?=?0.01) and increased plasma glutathione (GSH) (+98.10 versus. -49.87?µmol/l, p?=?0.03). A trend toward a significant effect of garlic intake on reducing fasting plasma glucose (FPG) (p?=?0.07), insulin (p?=?0.09) and increasing quantitative insulin sensitivity check (QUICKI) (p?=?0.05) was also observed. Conclusion: Consumption of garlic for 9 weeks among pregnant women at risk for pre-eclampsia led to decreased hs-CRP and increased GSH, but did not affect lipid profiles, total antioxidant capacity (TAC) and pregnancy outcomes. PMID:25316559

Aalami-Harandi, Rezvan; Karamali, Maryam; Asemi, Zatollah

2014-11-01

81

Pre-eclampsia: clinical manifestations and molecular mechanisms.  

PubMed

Preeclampsia affects 3-5% of pregnancies and can have a significant impact on health for both mother and fetus. Risk factors include maternal co-morbidities such as obesity and chronic hypertension, paternal factors, and genetic factors. New hypertension and proteinuria during the second half of pregnancy are key diagnostic criteria, but the clinical features and associated prognostic implications are somewhat heterogeneous and may reflect different mechanisms of disease. Renal dysfunction and proteinuria correspond to the pathologic finding of glomerular endotheliosis, and generally resolve after cure of preeclampsia through fetal and placenta delivery. The molecular mechanisms behind this disease are being discovered and refined. The initial etiologic agents are currently unknown. Pathologic studies show abnormal development of an ischemic placenta with a high-resistance vasculature, which cannot deliver an adequate blood supply to the fetoplacental unit. Endothelial dysfunction plays a central role in the pathogenesis of the maternal syndrome. Dysfunctional endothelial cells produce altered quantities of vasoactive mediators, which lead to a tip in the balance towards vasoconstriction. An imbalance in circulating angiogenic factors is emerging as a prominent mechanism that mediates the endothelial dysfunction and the clinical signs and symptoms of preeclampsia. Soluble fms-like tyrosine kinase 1 (sFlt1), an endogenous anti-angiogenic factor that is a potent vascular endothelial growth factor (VEGF) antagonist, is highly elevated in preeclampsia. VEGF is not only important in angiogenesis, but also in maintaining endothelial health including the formation of endothelial fenestrae (a hallmark of the glomerular vascular endothelium). sFlt1 overexpression in animals induces glomerular endotheliosis with the loss of endothelial fenestrae that resembles the renal histological lesions of preeclampsia. More severe forms of preeclampsia, including the HELLP syndrome, may be explained by a concomitant elevation in both sFlt1 and soluble endoglin, another anti-angiogenic factor. Unraveling of the molecular mechanisms behind preeclampsia may help to expand our armamentarium to treat patients in a more directed fashion, as current management consists of supportive care and expedited delivery. Finally, long-term outcomes of women with preeclampsia include a significantly increased risk for hypertension and cardiovascular disease, including mortality, which may warrant more aggressive screening and treatment in this population. PMID:17570933

Baumwell, Suzanne; Karumanchi, S Ananth

2007-01-01

82

Pre-Eclampsia, Birth Weight, and Autism Spectrum Disorders  

ERIC Educational Resources Information Center

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

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

2010-01-01

83

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

ERIC Educational Resources Information Center

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

Mann, Joshua R.; McDermott, Suzanne

2011-01-01

84

Influence of maternal pre-eclampsia on VEGF/PlGF heterodimer levels in preterm infants.  

PubMed

Abstract Objective: To measure VEGF/PlGF heterodimer levels in preterm infants born to mothers with preeclampsia. Methods: Neonates with birth weight <2000?g and gestational age ?34 weeks were divided into two groups: born to mothers with Preeclampsia (PE) and controls. Neonates transferred from outside after the 72nd hour of life, death before blood collection, major congenital malformations or inborn errors of metabolism, and mothers with multiple pregnancies, STORCH complex infections, HIV or autoimmune conditions were excluded. Blood was collected within 72?h of birth and again at 28 days. VEGF/PlGF heterodimer levels were measured by ELISA. Results: We included 73 neonates (24 born to mothers with PE and 49 without PE). Mean gestational age was 30.32?±?2.88 weeks and mean birth weight was 1288.62?±?462.22?g. Median VEGF/PlGF levels were significantly higher in infants born to mothers with PE. VEGF/PlGF levels were inversely proportional to birth weight. There were no between-group differences in blood samples collected at age 28 days. Conclusion: Higher VEGF/PlGF levels were higher in neonates exposed to PE, and there was a significant negative correlation between birth weight and VEGF/PlGF levels. Further studies to elucidate the role of this substance in the fetal and neonatal period are needed. PMID:25354293

Hentges, Cláudia R; Silveira, Rita C; Ferrelli, Régis S; Procianoy, Renato S

2014-11-14

85

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. PMID:12061422

Wilczy?ski, Jacek R; Tchórzewski, Henryk; G?owacka, Ewa; Banasik, Ma?gorzata; Lewkowicz, Przemyslaw; Szpakowski, Marian; Zeman, Krzysztof; Wilczy?ski, Jan

2002-01-01

86

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

ClinicalTrials.gov

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

2013-12-11

87

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

PubMed Central

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

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

2014-01-01

88

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

PubMed

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

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

2015-01-01

89

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

PubMed

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of 'omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution. PMID:24315655

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

2014-02-01

90

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

2004-01-01

91

[Immunological aspects of preeclampsia].  

PubMed

Pre-eclampsia is a common obstetric syndrome affecting about 7-10% of pregnant women. Symptoms of this syndrome: hypertension and impaired renal function appear during the second or third trimester of pregnancy. Despite intensive efforts to find mechanisms and markers induced pre-eclampsia, no specific etiological factor has been identified until now. It is known that pre-eclampsia is a placental disorder developing in two stages. The first lies in the poor placentation with acute atheroma. It seems that abnormal cell adhesion molecule (integrin) expression can contribute to inappropriate invasion of trophoblasts. Furthermore, T helper 1 type cytokines which are present in decidua of patients with pre-eclampsia can alter the trophoblast invasion. Lower expression level of HLA-G molecule in pre-eclamptic placenta can influence on the profile of cytokines which are produced in pre-eclampsia. The second stage of the disease development comprises the consequences of placental ischemia. It has been suggested that TNF-alpha is produced by ischemic placenta and causes endothelial activation. It seems that some types of pre-eclampsia can be autoimmune origin, with the autoantibodies directed against phospholipids, laminin and endothelium. The events leading to pre-eclampsia are not known, but it seems that abnormal activation of the immune system may play a role in the etiology of this disorder. PMID:11002546

Leszczy?ska-Gorzelak, B; Darmochwa?-Kolarz, D

2000-06-01

92

Guidelines for the management of hypertensive disorders of pregnancy 2008.  

PubMed

This is the Executive Summary of updated guidelines developed by the Society of Obstetric Medicine of Australia and New Zealand for the management of hypertensive diseases of pregnancy. They address a number of challenging areas including the definition of severe hypertension, the use of automated blood pressure monitors, the definition of non-proteinuric pre-eclampsia and measuring proteinuria. Controversial management issues are addressed such as the treatment of severe hypertension and other significant manifestations of pre-eclampsia, the role of expectant management in pre-eclampsia remote from term, thromboprophylaxis, appropriate fluid therapy, the role of prophylactic magnesium sulfate and anaesthetic issues for women with pre-eclampsia. The guidelines stress the need for experienced team management for women with pre-eclampsia and mandatory hospital protocols for treatment of hypertension and eclampsia. New areas addressed in the guidelines include recommended protocols for maternal and fetal investigation of women with hypertension, preconception management for women at risk of pre-eclampsia, auditing outcomes in women with hypertensive diseases of pregnancy and long-term screening for women with previous pre-eclampsia. PMID:19566552

Lowe, Sandra A; Brown, Mark A; Dekker, Gustaaf A; Gatt, Stephen; McLintock, Claire K; McMahon, Lawrence P; Mangos, George; Moore, M Peter; Muller, Peter; Paech, Michael; Walters, Barry

2009-06-01

93

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

2008-01-01

94

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

PubMed

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

2013-07-01

95

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

PubMed

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

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

2014-11-01

96

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

PubMed Central

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

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

2014-01-01

97

The risk of pregnancy-induced hypertension: black and white differences in a military population.  

PubMed Central

The relationship between race and risk of pregnancy-induced hypertension was investigated in a cohort of active-duty military women who gave birth during the period 1987 through 1989. Cases were identified through hospital discharge diagnoses and included transient gestational hypertension, pre-eclampsia, eclampsia, and unspecified hypertension complicating pregnancy. Multivariate analysis showed nulliparous Black women to be at a slightly increased risk for all pregnancy-induced hypertension (risk ratio [RR] = 1.2) and for pre-eclampsia (RR = 1.3) compared with nulliparous White women. Black parous women were found to have a slightly reduced risk of all pregnancy-induced hypertension (RR = 0.77) and pre-eclampsia (RR = 0.38) compared with White parous women. PMID:8092384

Irwin, D E; Savitz, D A; Hertz-Picciotto, I; St André, K A

1994-01-01

98

Analysis of purine metabolites in maternal serum for evaluating the risk of gestosis.  

PubMed

Metabolome analysis of the serum from pregnant patients aimed at detection of low-molecular-weight biomarkers of gestation process disorders indicated a relationship between the metabolic profile of maternal serum and risk of gestosis. In women with pre-eclampsia or preterm delivery, analysis of serum purine metabolites revealed changes in the metabolite concentrations, associated with pregnancy complications. PMID:24288739

Senyavina, N V; Khaustova, S A; Grebennik, T K; Pavlovich, S V

2013-09-01

99

Carbon Monoxide Inhibits Hypoxia/Reoxygenation-Induced Apoptosis and Secondary Necrosis in Syncytiotrophoblast  

PubMed Central

Pre-eclampsia, a hypertensive disorder of pregnancy, affects 5 to 7% of pregnancies. Oxidative stress-induced placental injury and subsequent release of placental debris into the maternal circulation are key pathogenic events in the progression of pre-eclampsia. Women who smoke cigarettes throughout pregnancy are 33% less likely to develop this disorder than nonsmoking women. We postulated that elevated carbon monoxide concentrations in serum of smoking women inhibits apoptosis and debris shedding of trophoblast cells exposed to ischemia-reperfusion injury because carbon monoxide has cytoprotective effects on endothelial and smooth muscle cells in culture. This may be responsible for the reduced risk of pre-eclampsia in smoking women. To assess the cytoprotective properties of carbon monoxide within placental tissue, carbon monoxide treatments were administered to in vitro hypoxia/reoxygenation-insulted villous explants cultured from term human placenta. Induction of apoptosis was assessed using molecular and morphological approaches. Placental villous explants treated with carbon monoxide demonstrated 60% less hypoxia/reoxygenation-induced apoptosis in the differentiated syncytiotrophoblast layer compared with untreated explants undergoing a similar insult. In addition, retention of intact syncytial membranes was observed in carbon monoxide-treated explants. These observations indicate that carbon monoxide has potent antiapoptotic properties within human placenta and may hold therapeutic potential in the treatment of pre-eclampsia. PMID:16936254

Bainbridge, Shannon A.; Belkacemi, Louiza; Dickinson, Michelle; Graham, Charles H.; Smith, Graeme N.

2006-01-01

100

LETTER doi:10.1038/nature10897 Role of corin in trophoblast invasion and uterine  

E-print Network

-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice-eclampsia. Pregnancy poses a serious challenge for maintaining normal blood pressure. Pregnancy-induced hypertension is a cardiac hormone that regulates blood pressure and sodium homeostasis15 . In mice, lack of CORIN prevents

101

Maternal Nutrition Navigating for Success Training Day Record  

E-print Network

. Hypertension (high blood pressure) Increased blood flow throughout the body. Pre-eclampsia is a condition to eclampsia with a sudden rise in blood pressure late in pregnancy accompanied by spilling protein due to increasing weight and increased blood volume, but can also be a symptom of iron deficiency. Eat

102

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

Microsoft Academic Search

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

Vicki L. Clifton

2005-01-01

103

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

Microsoft Academic Search

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

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

1976-01-01

104

Management of the critically ill obstetric patient  

Microsoft Academic Search

In the United Kingdom only one-third of cases ending in maternal deaths are admitted to intensive care facilities. This situation can be improved by better interdisciplinary communication, faster referral and more staffed beds. Standardized mortality ratios are lower than expected based on illness severity scores. The most common conditions requiring intensive care support are haemorrhage, pre-eclampsia and eclampsia, sepsis and

David A Male; Martin Stockwell; Stas Jankowski

2002-01-01

105

Baby's Name Baby's Birth Date Please fill out the following questionnaire. It will allow the provider to focus on your main concerns during the visit, and allow  

E-print Network

Baby's Name Baby's Birth Date Please fill out the following questionnaire. It will allow on day of birth? ( ) ( ) Birth weight? Was it a vaginal delivery? ( ) ( ) Passed hearing screen? ( ) ( ) Were pregnancy, labor & delivery complication-free (examples: pre- eclampsia, high blood pressure

Borenstein, Elhanan

106

Chorangiosis: The potential role of smoking and air pollution  

Microsoft Academic Search

Chorangiosis is considered to be strongly associated with various fetal, maternal, and placental disorders, including pre-eclampsia, diabetes, hypertension, and major congenital anomalies, and has been found to correlate with increased fetal morbidity and mortality. In this study, we investigated the pathologic effects of maternal smoking and air pollution on the pathogenesis of chorangiosis.We investigated 92 placentas macroscopically and microscopically over

Metin Akbulut; Hulya Cetin Sorkun; Ferda Bir; Ayhan Eralp; Ender Duzcan

2009-01-01

107

Inadequate vitamin D status in pregnancy: evidence for supplementation.  

PubMed

The role of vitamin D in maintaining a healthy pregnancy has seen emerging interest among clinicians and researchers in recent years. The functions of this hormone are widespread and complex, and during pregnancy and breastfeeding it facilitates crucial transfer of calcium from mother to child for skeletal development. Aside from the role of vitamin D in bone development and health, a myriad of other physiological actions are now known, and it is hypothesized that maternal deficiency may increase susceptibility to adverse pregnancy events during pregnancy such as pre-eclampsia. The role of vitamin D in pregnancy and breastfeeding is summarized and applied to the knowledge from studies associating vitamin D deficiency with a range of adverse pregnancy outcomes, including pre-eclampsia and childhood asthma. Current clinical guidelines for vitamin D supplementation in pregnancy are discussed in the context of the available evidence. The need for robust randomized controlled trials to address areas of existing uncertainty is highlighted. PMID:22007763

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

2012-02-01

108

Management of hypertensive disorders in pregnancy.  

PubMed

Hypertensive disorders are the most common medical complication of pregnancy, with an incidence of 5-10%, and a common cause of maternal mortality in the USA. Incidence of pre-eclampsia has increased by 25% in the past two decades. In addition to being among the lethal triad, there are likely up to 100 other women who experience 'near miss' significant maternal morbidity that stops short of death for every pre-eclampsia-related mortality. The purpose of this review is to present the new task force statement and novel definitions, as well as management approaches to each of the hypertensive disorders in pregnancy. The increased understanding of the pathophysiology of hypertension in pregnancy, as well as advances in medical therapy to minimize risks of fetal toxicity and teratogenicity, will improve our ability to prevent and treat hypertension in pregnancy. Fetal programming and fetal origins of adult disease theories extrapolate the benefit of such therapy to future generations. PMID:25259900

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

2014-07-01

109

Pregnancy and catastrophic antiphospholipid syndrome.  

PubMed

Antiphospholipid syndrome (APS) is clearly related to maternal morbidity. The most characteristic feature is pregnancy loss; however, several other serious complications had been reported including fetal growth restriction, uteroplacental insufficiency, fetal distress, pre-eclampsia, and HELLP syndrome. Herein, we review the different aspects of obstetric APS features, with special emphasis on its life-threatening variant known as catastrophic APS (Asherson's syndrome) and its relationship with a thrombotic microangiopathy such as HELLP syndrome. PMID:19052924

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

2009-06-01

110

Angiotensin II Activates the Calcineurin\\/NFAT Signaling Pathway and Induces Cyclooxygenase2 Expression in Rat Endometrial Stromal Cells  

Microsoft Academic Search

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

Florencia Abraham; Flavia Sacerdoti; Romina De León; Teresa Gentile; Andrea Canellada

2012-01-01

111

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

2006-01-01

112

Pregnancy complications in polycystic ovary syndrome patients.  

PubMed

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

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

2015-02-01

113

Change in paternity and select perinatal outcomes: causal or confounded?  

PubMed

Select social, behavioural and maternal characteristics were evaluated to determine if they were confounding factors in the association between paternity change and pre-eclampsia, small for gestational age (SGA) and pre-term delivery, in a sample of 1,409 women. Multivariate logistic regression analysis was used to determine if any of these risk factors modified the association between changing paternity and the selected perinatal outcomes. Results of the analysis showed that women who changed partners were more likely to possess potentially confounding risk factors compared with those who had not. Paternity change was 2.75 times more likely to be associated with the development of pre-eclampsia (95% CI 1.33; 5.68) and 2.25 times more likely to be associated with an SGA infant on weight (95% CI 1.13; 4.47), after adjusting for selected risk factors. Paternity change remains a significant risk factor for pre-eclampsia and SGA in the presence of select risk factors. PMID:22943712

Bandoli, G; Lindsay, S; Johnson, D L; Kao, K; Luo, Y; Chambers, C D

2012-10-01

114

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

PubMed

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

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

1996-10-01

115

Race/Ethnicity, Educational Attainment, and Pregnancy Complications in New York City Women with Pre-existing Diabetes  

PubMed Central

Background More women are entering pregnancy with pre-existing diabetes. Disease severity, glycaemic control, and predictors of pregnancy complications may differ by race/ethnicity or educational attainment, leading to differences in adverse pregnancy outcomes. Methods We used linked New York City hospital record and birth certificate data for 6291 singleton births among women with pre-existing diabetes between 1995 and 2003. We defined maternal race/ethnicity as non-Hispanic white, non-Hispanic black, Hispanic, South Asian, and East Asian, and education level as <12, 12, and >12 years. Our outcomes were pre-eclampsia, preterm birth (PTB) (<37 weeks gestation and categorised as spontaneous or medically indicated), as well as small-for-gestational age (SGA) and large-for-gestational age (LGA). Using multivariable binomial regression, we estimated the risk ratios for pre-eclampsia, SGA, and LGA. We used multivariable multinomial regression to estimate odds ratios (OR) for PTB. Results Compared with non-Hispanic white women with pre-existing diabetes, non-Hispanic black and Hispanic women with pre-existing diabetes had a 1.50-fold increased risk of pre-eclampsia compared with non-Hispanic whites with pre-existing diabetes, after full adjustment. Non-Hispanic black and Hispanic women with pre-existing diabetes had adjusted ORs of 1.72 [adj. 95% confidence interval (CI) 1.38, 2.15] and 1.65 [adj.95% CI 1.32, 2.05], respectively, for medically indicated PTB. South Asian women with pre-existing diabetes had the highest risk for having an SGA infant [adj. OR: 2.29; adj. 95% CI 1.73, 3.03]. East Asian ethnicity was not associated with these pregnancy complications. Conclusions Non-Hispanic black, Hispanic, and South Asian women with pre-existing diabetes may benefit from targeted interventions to improve pregnancy outcomes. PMID:24354778

James-Todd, Tamarra; Janevic, Teresa; Brown, Florence M; Savitz, David A

2014-01-01

116

Pregnancy Close to the Edge: An Immunosuppressive Infiltrate in the Chorionic Plate of Placentas from Uncomplicated Egg Cell Donation  

PubMed Central

In pregnancies achieved after egg donation (ED) tolerance towards a completely allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of which numerous aspects are still unknown. A distinct lesion not described previously in the literature, was repeatedly found in the chorionic plate in a substantial portion of placentas from ED pregnancies, but never in placentas from normal term pregnancies. The aim of this study was to assess its origin and its cellular composition. The relation between the lesion, the clinical and histological parameters were assessed. In addition we investigated the relation with the number of HLA-mismatches and KIR genotype of mother and child. In ten out of twenty-six (38.5%) placentas from ED pregnancies an inflammatory lesion was present in the chorionic plate. A significantly lower incidence of pre-eclampsia was found in the group with the lesion; 0% versus 45.5%. A significant relation was found between this lesion and the presence of intervillositis, chronic deciduitis, presence of plasma cells and fibrin deposition in the decidua. Fluorescent in situ hybridisation with X/Y-chromosome probes showed that the majority of cells present in the lesion are of maternal origin. The expression of the macrophage marker CD14+ and of the type 2 macrophage (M2) marker CD163+ was significantly higher in the lesion. The incidence of a fetal HLA-C2 genotype was significantly higher in cases with a lesion compared to the group without the lesion. In conclusion, a striking relationship was observed between the presence of a not previously described inflammatory lesion in the chorionic plate and the absence of pre-eclampsia in ED pregnancies. The lesion consists of mainly maternal cells with a higher expression of the macrophage marker CD14+ and the M2 marker CD163+. These findings suggest a protective immune mechanism which might contribute to the prevention of severe clinical complications like pre-eclampsia. PMID:22479322

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

2012-01-01

117

Adverse pregnancy outcomes and subsequent risk of cardiovascular disease in women with systemic lupus erythematosus  

PubMed Central

Background/objective Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcomes and cardiovascular disease (CVD). The objective of this exploratory study was to investigate the association between a history of adverse pregnancy outcomes and subsequent risk of subclinical CVD assessed by imaging studies and verified clinical CVD events in 129 women with SLE. Methods The occurrence of adverse pregnancy outcomes, specifically pre-eclampsia, preterm birth and low birth weight was ascertained by questionnaire. Subclinical CVD was assessed by coronary artery calcium (CAC) as measured by electron beam CT and carotid plaque measured by B mode ultrasound. Clinical CVD events were verified by medical record review. Logistic regression was used to estimate the association of pregnancy complications with occurrence of subclinical CVD and clinical CVD with a priori adjustment for age, which is associated with CVD and SLE disease duration as a measure of SLE disease burden. Results Fifty-six women reported at least one pregnancy complication while 73 had none. Twenty-six women had at least one pregnancy complicated by pre-eclampsia and were more likely to have a CAC score greater than or equal to 10 (adjusted OR=3.7; 95% CI 1.2 to 11.9), but the presence of plaque was not associated with this pregnancy complication, OR=1.1, (95% CI 0.4 to 2.8). Low birth weight and preterm birth were not associated with CAC or plaque. Conclusions Patients with SLE with a history of pre-eclampsia had a higher rate of subclinical CVD as measured by CAC score. Future studies are needed to confirm the relationship between adverse pregnancy outcomes and subsequent subclinical CVD and clinical CVD events. PMID:25379191

Lin, Pin; Rhew, Elisa; Ness, Roberta B; Peaceman, Alan; Dyer, Alan; McPherson, David; Kondos, George T; Edmundowicz, Daniel; Sutton-Tyrrell, Kim; Thompson, Trina; Ramsey-Goldman, Rosalind

2014-01-01

118

Complete hydatidiform mole coexisting with a live fetus.  

PubMed

Hydatidiform mole co-existing with a normal fetus is very rare. We report a case of a 36 year old woman Para 4+0 who presented with amenorrhoea of twenty four weeks duration, vaginal bleeding, abdominal pain and pre-eclampsia. Ultrasound examination revealed a hydatidiform mole coexisting with a normal living fetus. The patient underwent a caesarean section at twenty eight weeks for maternal distress due to unbearable abdominal pain. The baby died after seven days. Post operatively she had an eclamptic fit and developed oliguria and persistent trophoblastic disease which were all successfully treated. PMID:24946461

Ezem, Bamidele Uche; Okeudo, Chijioke; Ukah, Cornelius Ozobia; Anozie, Uchechukwu Martin

2014-01-01

119

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

PubMed

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

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

2014-12-01

120

Daily plasma-exchange for life-threatening class I HELLP syndrome with prevalent pulmonary involvement.  

PubMed

HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) is a thrombotic microangiopathy affecting a minority of women with pre-eclampsia and usually resolves after delivery. The role of plasma exchange in HELLP syndrome has to be defined. Herein is reported a case of a primipara with a class I HELLP syndrome with prevalent pulmonary involvement successfully treated with 8 consecutive plasma exchange plus corticosteroids. In class I HELLP syndrome with cardiopulmonary complications early plasma exchange could be considered a therapeutic option. PMID:16376616

Del Fante, Claudia; Perotti, Cesare; Viarengo, Gianluca; Gallini, Giuseppe Sala; Tinelli, Carmine; Salvaneschi, Laura

2006-02-01

121

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

PubMed Central

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

2014-01-01

122

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

PubMed Central

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

Shahien, Radi; Bowirrat, Abdalla

2011-01-01

123

Lateral geniculate lesions causing reversible blindness in a pre-eclamptic patient with a variant of posterior reversible encephalopathy syndrome.  

PubMed

Bilateral lateral geniculate nucleus (LGN) injury is a rare cause of vision loss. We describe a patient with pre-eclampsia who developed profound but reversible bilateral vision loss, bilateral serous retinal detachments, and magnetic resonance imaging signs of a variant of posterior reversible encephalopathy syndrome (PRES) that affected both LGNs and spared the retrogeniculate pathways. We provide evidence that the visual loss was not from the chorioretinal lesions but from the LGN lesions. The concurrence of PRES and lesions attributed to choroidal hypoperfusion provides support for the notion that vasoconstriction also underlies the pathogenesis of PRES. PMID:24739995

Stem, Maxwell S; Fahim, Abigail; Trobe, Jonathan D; Parmar, Hemant A; Ibrahim, Mohannad

2014-12-01

124

Partial HELLP syndrome with unilateral exudative retinal detachment treated conservatively.  

PubMed

Peripartum vision loss, an uncommon, often reversible complication of pregnancy usually occurs in the setting of pre-eclampsia or eclampsia. The HELLP syndrome is characterized by hypertension, elevated liver enzymes and low platelets. This is a rare case of unilateral exudative retinal detachment associated with the Partial HELLP syndrome that occurred after delivery in a 23-year-old Indian woman. The retinal detachment subsequently reattached with good visual improvement under conservative treatment. This case highlights the importance of early intervention by the ophthalmologist when pregnant women complain about visual symptoms. PMID:25473354

Pradeep, A V; Rao, Sonali; Ramesh Kumar, R

2014-10-01

125

Managing pregnancy in inflammatory rheumatological diseases  

PubMed Central

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

2011-01-01

126

Combining mid-trimester maternal plasma homocysteine with uterine artery doppler velocimetry: is it useful?  

Microsoft Academic Search

Objective  To investigate the possible association between mid-trimester maternal plasma homocysteine concentration, uterine artery Doppler\\u000a measurements in a two-stage screening strategy, and outcome of pregnancy.\\u000a \\u000a \\u000a \\u000a Materials and methods  This prospective observational study was conducted on healthy women undergoing screening for pre-eclampsia by uterine artery\\u000a Doppler velocimetry at 20–22 and 24–26 weeks of gestation. Abnormal uterine artery blood flow was defined as an average

Melih A. Guven; Ibrahim Egemen Ertas; Metin Kilinc; Ayhan Coskun; Hasan Ekerbicer

2007-01-01

127

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

PubMed Central

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

Spencer, RN; Carr, DJ; David, AL

2014-01-01

128

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

PubMed

Angiotensin converting enzyme (ACE) inhibitors are the mainstay of treatment for diabetic nephropathy to slow progression of disease. Diabetic women of childbearing age with nephropathy should be treated with ACE inhibitors as per guidelines in the pre-pregnancy period. ACE inhibitor use and exposure in the first trimester is controversial and requires counselling pre-pregnancy regarding the risks and benefits of use up to the first trimester, as well as the need to stop ACE inhibitors prior to the second trimester. Current evidence does not suggest that ACE inhibitors in the first trimester are associated with a greater risk of fetal malformations when compared to other antihypertensives. This topic is reviewed in depth, along with blood pressure targets in pregnant women with diabetic proteinuric disease, evidence for prevention of pre-eclampsia, self-monitoring of blood pressures at home in the latter half of pregnancy and the signs and symptoms of pre-eclampsia, proteinuria evolution in pregnancy, renal function prognosis, and restarting ACE inhibitors when breast feeding in the post-partum period. PMID:25546023

Podymow, Tiina; Joseph, Geena

2015-02-01

129

Maternal and placental melatonin: actions and implication for successful pregnancies.  

PubMed

Melatonin is one of the main sources of mitochondrial protection and its protective effects are equal or even better if compared with several consecrated antioxidants. Furthermore, the activation of specific melatonin receptors triggers several cellular pathways that improve the oxidoreduction and inflammatory cellular state. The discovery of the melatoninergic machinery in placental cells was the first step to understand the effects of this indoleamine during pregnancy. In critical points of pregnancy, melatonin has been pointed as a protagonist and its beneficial effects have been shown as essential for the control of trophoblastic function and development. On the contrary of the plasmatic melatonin (produced in pineal gland), placental melatonin does not vary according to the circadian cycle and acts as an autocrine, paracrine, intracrine, and endocrine hormone. The important effects of melatonin in placenta have been demonstrated in the physiopathology of pre-eclampsia with alterations in the levels of melatonin and in the expression of its receptors and synthetizing enzymes. Some authors suggested melatonin as a biomarker of pre-eclampsia and as a possible treatment for this disease and other obstetric pathologies associated with placental defect and increases in oxidative stress. This review will approach the beneficial effects of melatonin on placenta homeostasis and consequently on pregnancy and fetal health. PMID:24971781

Sagrillo-Fagundes, L; Soliman, A; Vaillancourt, C

2014-06-01

130

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

PubMed

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

2013-08-15

131

Magnesium sulphate: a life saving drug.  

PubMed

A retrospective study of 68 eclamptic women who received Magnesium sulphate at Koshi Zonal Hospital were analyzed during a one year period (2006-2007 AD). Maternal conditions at admission, associated complications in mothers and babies, delivery outcomes and cause of death were also studied in each case. There were 5240 deliveries during the period of analysis. Of which 4976 were live births, pregnancy induced hypertension was 0.89% (47), 0.74% (39) presented with pre-eclampsia, 0.30 (16) cases with severe pre-eclampsia and 0.43 (23) cases with mild pre-eclampsia. During this period 1.3% (68) of eclampsia presented to the hospital. Of which 67.7% presented with ante-partum eclampsia, 22.1% with intrapartum eclampsia and 10.3% with post partum eclampsia. Majority of women (63.2%) were between 20-25 years of age, while teenage pregnancy contributed 30.88% of eclamptic cases. The diastolic blood pressure was >110 mm of Hg in 45.6% of cases, 90-110 mmHg in 50% of cases and in 4.4% the it was <90 mmHg. 94.1% presented to the hospital in an unconscious state, 79.4% of eclamptic women received the full dose of magnesium sulphate (initial loading plus maintenance dose), while rest failed to receive the full dose. Nine women with severe pre-eclampsia received magnesium sulphate as a prophylactic measure. 17.7% women had home delivery, one patient left against medical advice and one was referred to a tertiary care center. Caesarian Section (Lower Segment) was performed in 35.2% of cases, 30.8% had normal vaginal deliveries and 5.8% had pre term delivery. About 69.6% babies were born alive, 8.7% were still births, 11.6% were neonatal deaths and 4.4% of babies had to be admitted to the neonatal intensive care. Eclamptic women stayed less than one week in the hospital in majority of cases (64.7%), between 1-2 weeks in 32.4% and more than two weeks in 2.9%. Maternal complications included decreased urinary output, pulmonary edema in three cases; chest and wound infection two cases each; post partum psychosis, vulval haematoma, severe headache one case each. There were seven maternal deaths during this period and eclampsia contributed to one of the deaths. Eclampsia is a major cause of maternal and perinatal morbidity and mortality in our setup. Magnesium sulphate is an excellent drug of choice in management of eclampsia and pre-eclampsia. Wider coverage of pre-natal care, timely referral and optimal management of cases of eclampsia with magnesium sulphate in hospitals are key issues to prevent mortality/morbidity associated with it. PMID:19079372

Thapa, K; Jha, R

2008-01-01

132

HELLP syndrome: the experience at Ile-Ife, Nigeria.  

PubMed

Between 1 January and 31 December, 2006, 34 consecutive cases of severe pre-eclampsia (12), imminent eclampsia (10) and eclampsia (12) who were admitted at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife in the south-western part of Nigeria, were investigated for the development of HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome in a prospective study. The ages of the women ranged from 18 to 38 years, parity 0-5 and the estimated gestational age from 18-41 weeks at presentation. A total of 26 (76.5%) of the patients were unbooked, six (17.6%) of the 34 cases developed HELLP syndrome. Four (33%) of the 12 eclamptics developed HELLP syndrome, while only one (10%) of the cases of imminent eclampsia and 1 (8.3%) of severe pre-eclamptic cases developed the syndrome. Using the Mississippi Triple class system, none of the HELLP syndrome cases belonged to Class I; 4 were categorised in Class II while 2 were in Class III. All of the four eclamptic cases with HELLP syndrome died giving a 100% fatality rate while none of the imminent eclamptic and severe pre-eclamptic patients with the syndrome died. Furthermore, there were six (15.8%) perinatal deaths among the 38 infants delivered by the 34 mothers with severe pre-eclampsia/eclampsia. Our data suggest that the development of HELLP syndrome is more likely in eclamptic patients and when it occurs in them, it is highly fatal. Most of the cases in this study were unbooked. Substandard care may have contributed to the progression of the disease state and consequently, to maternal mortality. It is imperative to draw up an action plan for the identification of the risk factors for the development of pre-eclampsia/eclampsia at peripheral hospitals and maternity centres and for prompt referral of such cases afterwards. Efforts should also be geared towards the minimising of treatment delay in all phases, so as to minimise both perinatal and maternal morbidity and mortality. PMID:19358023

Makinde, O N; Adegoke, O A; Adediran, I A; Ndububa, D A; Adeyemi, A B; Owolabi, A T; Kuti, O; Orji, E O; Salawu, L

2009-04-01

133

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. PMID:21162717

2010-01-01

134

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

PubMed Central

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

Chaturvedi, Sarika; Randive, Bharat

2013-01-01

135

Availability of treatment for eclampsia in public health institutions in Maharashtra, India.  

PubMed

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

Chaturvedi, Sarika; Randive, Bharat; Mistry, Nerges

2013-03-01

136

Helicobacter pylori and pregnancy-related disorders.  

PubMed

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

Cardaropoli, Simona; Rolfo, Alessandro; Todros, Tullia

2014-01-21

137

Secondary headaches attributed to arterial hypertension  

PubMed Central

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

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

2013-01-01

138

Reproductive & Cardiovascular Disease Research Group  

NSDL National Science Digital Library

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

Dash, Phil.

139

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

PubMed

Oral infections have been implicated in adverse pregnancy outcomes such as pre-eclampsia, premature delivery and growth retardation. A 28-year-old and 9 months pregnant otherwise healthy woman with a complaint of facial swelling and dental pain was referred to the Department of Oral and Maxillofacial Surgery. Oral examination revealed perimandibular and masticator space infection related to the left mandibular third molar tooth. Eight hours after surgical intervention, fetal distress developed. The patient was immediately taken into surgery and a male baby delivered by Caesarean section. The baby was then admitted to the intensive care unit. On the twelfth day of his admission, the baby was discharged in good health. Severe maxillofacial infection in pregnancy is a medically complicated situation which should be treated by an oral and maxillofacial surgeon in consultation with an obstetric and gynaecology service. PMID:23441802

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

2013-03-01

140

A Short History of Sonography in Obstetrics and Gynaecology  

PubMed Central

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

Campbell, S.

2013-01-01

141

Endoplasmic reticulum stress is induced in the human placenta during labour  

PubMed Central

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

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

2015-01-01

142

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. PMID:24024167

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

2013-01-01

143

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. PMID:24082665

Samra, Khawla Abu

2013-01-01

144

Pregnancy in peritoneal dialysis and an infant with a ventricular septal defect.  

PubMed

Fertility is markedly reduced in dialysis patients. Estimates of the frequency of conception in dialysis patients range from 1.4% per year in Saudi Arabia to 0.5% in the United States. The reasons for the rarity of pregnancy in dialysis patients are not well understood. In addition, there is a marked increase in the risk of pre-eclampsia, hydramnios, hypertension crisis, early uterine contractions and pre-term delivery. Herein, we report a 38-year-old Saudi woman with chronic renal failure who completed the full term of pregnancy uneventfully on peritoneal dialysis. Using a biocompatible dialysate solution, adequate metabolic and blood pressure control were achieved during pregnancy. The delivered infant was small for gestational age and was born with a ventricular-septal defect. To the best of our knowledge, this is the first case report in the literature of ventricular-septal defect in an infant born to a mother on peritoneal dialysis. PMID:25579727

Alhwiesh, Abdullah

2015-01-01

145

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

PubMed

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

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

2015-01-01

146

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

PubMed

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

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

2014-10-22

147

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

PubMed

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

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

2014-01-01

148

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

PubMed

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

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

2014-12-01

149

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

PubMed Central

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

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

2012-01-01

150

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

PubMed

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

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

2014-11-01

151

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

PubMed

The tachykinin neurokinin B (NKB) has been implicated in the hypertension that characterises pre-eclampsia, a condition where tissue oedema is also observed. The ability of NKB, administered intradermally or intravenously, to induce oedema formation (assessed as plasma extravasation) was examined by extravascular accumulation of intravenously injected (125)I-albumin in wild-type and tachykinin NK(1) receptor knockout mice. Intradermal NKB (30-300 pmol) caused dose-dependent plasma extravasation in wild-type (P < 0.05) but not NK(1) knockout mice, indicating an essential role for the NK(1) receptor in mediating NKB-induced skin oedema. Intravenous administration of NKB to wild-type mice produced plasma extravasation in skin, uterus, liver (P < 0.05) and particularly in the lung (P < 0.01). Surprisingly, the same doses of NKB led to plasma extravasation in the lung and liver of NK(1) knockout mice. By comparison, the tachykinin substance P induced only minimal plasma extravasation in the lungs of wild-type mice. The plasma extravasation produced by NKB in the lungs of NK(1) receptor knockout mice was unaffected by treatment with the NK(2) receptor antagonist SR48968 (3 mg kg(-1)), by the NK(3) receptor antagonists SR142801 (3 mg kg(-1)) and SB-222200 (5 mg kg(-1)) or by the cyclo-oxygenase (COX) inhibitor indomethacin (20 mg kg(-1)). L-Nitro-arginine methyl ester (15 mg kg(-1)), an inhibitor of endothelial nitric oxide synthase (eNOS), produced only a partial inhibition. We conclude that NKB is a potent stimulator of plasma extravasation through two distinct pathways: via activation of NK(1) receptors, and via a novel neurokinin receptor-independent pathway specific to NKB that operates in the mouse lung. These findings are in keeping with a role for NKB in mediating plasma extravasation in diseases such as pre-eclampsia. PMID:12231654

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

2002-09-15

152

Hypertensive disorders of pregnancy and the recent increase in obstetric acute renal failure in Canada: population based retrospective cohort study  

PubMed Central

Objective To examine whether changes in postpartum haemorrhage, hypertensive disorders of pregnancy, or other risk factors explain the increase in obstetric acute renal failure in Canada. Design Retrospective cohort study. Setting Canada (excluding the province of Quebec). Participants All hospital deliveries from 2003 to 2010 (n=2?193?425). Main outcome measures Obstetric acute renal failure identified by ICD-10 diagnostic codes. Methods Information on all hospital deliveries in Canada (excluding Quebec) between 2003 and 2010 (n=2?193?425) was obtained from the Canadian Institute for Health Information. Temporal trends in obstetric acute renal failure were assessed among women with and without postpartum haemorrhage, hypertensive disorders of pregnancy, or other risk factors. Logistic regression was used to determine if changes in risk factors explained the temporal increase in obstetric acute renal failure. Results Rates of obstetric acute renal failure rose from 1.66 to 2.68 per 10?000 deliveries between 2003-04 and 2009-10 (61% increase, 95% confidence interval 24% to 110%). Adjustment for postpartum haemorrhage, hypertensive disorders, and other factors did not attenuate the increase. The temporal increase in acute renal failure was restricted to deliveries with hypertensive disorders (adjusted increase 95%, 95% confidence interval 38% to 176%), and was especially pronounced among women with gestational hypertension with significant proteinuria (adjusted increase 171%, 71% to 329%). No significant increase occurred among women without hypertensive disorders (adjusted increase 12%, ?28 to 72%). Conclusions The increase in obstetric acute renal failure in Canada between 2003 and 2010 was restricted to women with hypertensive disorders and was especially pronounced among women with pre-eclampsia. Further study is required to determine the cause of the increase among women with pre-eclampsia. PMID:25077825

Liu, Shiliang; Bartholomew, Sharon; Hutcheon, Jennifer A; Magee, Laura A; Kramer, Michael S; Liston, Robert M; Joseph, K S

2014-01-01

153

Mechanisms of renal NaCl retention in proteinuric disease.  

PubMed

In diseases with proteinuria, for example nephrotic syndrome and pre-eclampsia, there often are suppression of plasma renin-angiotensin-aldosterone system components, expansion of extracellular volume and avid renal sodium retention. Mechanisms of sodium retention in proteinuria are reviewed. In animal models of nephrotic syndrome, the amiloride-sensitive epithelial sodium channel ENaC is activated while more proximal renal Na(+) transporters are down-regulated. With suppressed plasma aldosterone concentration and little change in ENaC abundance in nephrotic syndrome, the alternative modality of proteolytic activation of ENaC has been explored. Proteolysis leads to putative release of an inhibitory peptide from the extracellular domain of the ? ENaC subunit. This leads to full activation of the channel. Plasminogen has been demonstrated in urine from patients with nephrotic syndrome and pre-eclampsia. Urine plasminogen correlates with urine albumin and is activated to plasmin within the urinary space by urokinase-type plasminogen activator. This agrees with aberrant filtration across an injured glomerular barrier independent of the primary disease. Pure plasmin and urine samples containing plasmin activate inward current in single murine collecting duct cells. In this study, it is shown that human lymphocytes may be used to uncover the effect of urine plasmin on amiloride- and aprotinin-sensitive inward currents. Data from hypertensive rat models show that protease inhibitors may attenuate blood pressure. Aberrant filtration of plasminogen and conversion within the urinary space to plasmin may activate ? ENaC proteolytically and contribute to inappropriate NaCl retention and oedema in acute proteinuric conditions and to hypertension in diseases with chronic microalbuminuria/proteinuria. PMID:23216619

Svenningsen, P; Friis, U G; Versland, J B; Buhl, K B; Møller Frederiksen, B; Andersen, H; Zachar, R M; Bistrup, C; Skøtt, O; Jørgensen, J S; Andersen, R F; Jensen, B L

2013-03-01

154

The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women  

PubMed Central

Objective: To study the characteristics of the haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome in the antiphospholipid syndrome (APS) and its influence on the subsequent pregnancies. Methods: This was a retrospective analysis of 16 episodes of HELLP complicating APS in 15 women. Results: HELLP was complete in 10 cases and partial in six. It occurred during the second trimester in seven cases (the earliest at 18 weeks' gestation), the third trimester in seven cases, and the day following delivery in two cases. Pre-eclampsia was present in six cases and eclampsia in five. Outcome of pregnancies was: live birth (n = 8), stillbirth (n = 2) and fetal death (n = 6). APS was primary in nine women and secondary to systemic lupus erythematosus (SLE) in six. HELLP revealed primary APS in six cases. Seven women were not treated. Low dose aspirin was empirically prescribed in one woman whose APS had been undiagnosed despite a history of two fetal deaths. In the other women, therapy consisted of aspirin (n = 8), low molecular weight heparin with a dose varying between 3000 and 12 000 U daily (n = 5), and high dose immunoglobulin every 4 weeks (n = 2), hydroxychloroquine (n = 4), and prednisone (n = 6). Six women had seven subsequent pregnancies, 3–6 years after the complicated pregnancy. HELLP recurred at 33 weeks' gestation in one woman with SLE treated with prednisone, hydroxychloroquine, aspirin, and enoxaparin, and pregnancy ended in live birth. One woman became pregnant after in vitro fertilisation and embryo transfer, but pregnancy ended in fetal death despite prednisone, hydroxychloroquine, and enoxaparin. Four women had five uneventful pregnancies with 100 mg daily aspirin and heparin. Conclusions: APS may be revealed by HELLP. In APS, HELLP is associated with pre-eclampsia/eclampsia in most cases and seems to occur earlier than in the general population. Heparin plus aspirin may prevent obstetric complications in the subsequent pregnancies. PMID:15647435

Le Thi, Thuong D; Tieulie, N; Costedoat, N; Andreu, M; Wechsler, B; Vauthier-Brouzes, D; Aumaitre, O; Piette, J

2005-01-01

155

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

PubMed

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

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

2014-07-01

156

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

PubMed

The aim of this study was to investigate whether or not increased uterine natural killer (uNK) cell numbers in the peri-implantation endometrium are associated with an increased risk of hypertensive disorders in a subsequent pregnancy. This is a retrospective study including 80 women with a history of unexplained recurrent miscarriage or recurrent implantation failure. Precisely timed endometrial biopsies were obtained from women 7-9 days after the luteinising hormone surge. uNK cells were immunostained for CD56+ and expressed as a percentage of total stromal cells. Patients were defined as having a high uNK cell count if the percentage of total stromal cells was more than 13.9%. Five out of 29 (17.2%) women in the high uNK cell count group and 5 out of 51 (9.8%) women in the normal uNK cell count group developed gestational hypertension. Pre-eclampsia was diagnosed in 2 (6.9%) patients in the high uNK cell count group and 1 (2.0%) patient from the normal uNK cell count group. There was no significant difference in the incidence of either gestational hypertension (P=0.483) and pre-eclampsia (P=0.296) between groups. The overall incidence of hypertensive disease in women with high uNK cell count (24.1%) was two times higher than women with normal uNK cell count (11.8%), but it was not statistically significant (P=0.208). An increased uNK cells count in the peri-implantation period in a cycle prior to conception did not appear to significantly increase the likelihood of hypertensive disease of pregnancy. PMID:25023194

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

2014-12-01

157

Diagnosis and management of non-criteria obstetric antiphospholipid syndrome.  

PubMed

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

Arachchillage, D R J; Machin, S J; Mackie, I J; Cohen, H

2015-01-01

158

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. PMID:21501459

2011-01-01

159

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

PubMed Central

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

2014-01-01

160

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

PubMed Central

Background Proteinuria and dilatation of the urinary tract are both relatively common in pregnancy, the latter with a spectrum of symptoms, from none to severe pain and infection. Proteinuria is a rare occurrence in acute obstructive nephropathy; it has been reported in pregnancy, where it may pose a challenging differential diagnosis with pre-eclampsia. The aim of the present study is to report on the incidence of proteinuria (?0.3; ?0.5 g/day) in association with symptomatic-severe urinary tract dilatation in pregnancy. Methods Case series. Setting: Nephrological-Obstetric Unit dedicated to pregnancy and kidney diseases (January 2000-April 2011). Source: database prospectively updated since the start of the Unit. Retrospective review of clinical charts identified as relevant on the database, by a nephrologist and an obstetrician. Results From January 2000 to April 2011, 262 pregnancies were referred. Urinary tract dilatation with or without infection was the main cause of referral in 26 cases (predominantly monolateral in 19 cases): 23 singletons, 1 lost to follow-up, 1 twin and 1 triplet. Patients were referred for urinary tract infection (15 cases) and/or renal pain (10 cases); 6 patients were treated by urologic interventions (“JJ” stenting). Among them, 11 singletons and 1 triple pregnancy developed proteinuria ?0.3 g/day (46.1%). Proteinuria was ?0.5 g/day in 6 singletons (23.1%). Proteinuria resolved after delivery in all cases. No patient developed hypertension; in none was an alternative cause of proteinuria evident. No significant demographic difference was observed in patients with renal dilatation who developed proteinuria versus those who did not. An association with the presence of “JJ” stenting was present (5/6 cases with proteinuria ?0.5 g/day), which may reflect both severer obstruction and a role for vescico-ureteral reflux, induced by the stent. Conclusions Symptomatic urinary tract dilatation may be associated with proteinuria in pregnancy. This association should be kept in mind in the differential diagnosis with other causes of proteinuria in pregnancy, including pre-eclampsia. PMID:23446427

2013-01-01

161

Antiphospholipid Syndrome during pregnancy: the state of the art  

PubMed Central

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

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

2011-01-01

162

The antiphospholipid syndrome.  

PubMed

The antiphospholipid syndrome encompasses a wide spectrum of presentations cutting across all subspecialties of medicine. It is characterized by recurrent thrombotic events involving both the arterial and venous systems. Large arteries and veins as well as the microcirculation are involved. Recurrent strokes, myocardial infarction, pulmonary embolism, gangrene of the digits, etc. cause much morbidity and mortality in affected patients. It is recognized as an important cause of recurrent pregnancy loss. The risk in pregnancy extends to a propensity towards pre-eclampsia, abruptio placentae and intrauterine growth retardation. It often manifests as asymptomatic thrombocytopenia and sometimes as a life-threatening form called catastrophic anti-phospholipid syndrome. The management of thrombotic events rests on high grade anticoagulation (INR 3-4) as lower values of INR than this often fail to prevent recurrence. Aspirin is generally added in case of arterial thrombosis. A combination of heparin and aspirin at least in the first trimester and sometimes throughout pregnancy is used to prevent foetal loss. PMID:14765622

Grover, Rahul; Kumar, Ashok

2003-01-01

163

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. PMID:22624100

Bajwa, Sukhwinder Kaur; Bajwa, Sukhminder Jit Singh

2012-01-01

164

Management of High-Risk Pregnancy: Report of a Combined Obstetrical and Neonatal Intensive Care Unit  

PubMed Central

The methodology, equipment and personnel required to carry out an intensive-care program in the management of high-risk pregnancies have been outlined. The perinatal mortality rate has been determined and its etiology has been analyzed. There appear to be three conditions in which the degree of high risk is such as to warrant provision of the complete facilities of the service we described, viz., (a) severe pre-eclampsia; (b) marked intrauterine growth retardation with placental insufficiency as determined from serial measurements of uterine growth and estriol determinations; and (c) irreversible labour in premature pregnancies where a birth weight of 2200 g. or less is anticipated. Numerous other conditions that we have monitored have perhaps had their good outcome because of monitoring facilities. A less sophisticated and more easily applied method of monitoring should be available within the context of routine labour and delivery rooms. There is a pressing need to re-evaluate and change some of our methods of educating our undergraduate, postgraduate and practising physicians and to provide continuing education in the realm of prenatal care and recognition of high-risk pregnancy. Regionalization and centralization of this type of intensive care for high-risk pregnancies are required. Indispensable to the success of this type of project is the incorporation, without physical, emotional or intellectual barriers, of both a pediatric and an obstetrical component within the intensive-care unit. ImagesFIG. 3 PMID:5344991

Effer, S. B.

1969-01-01

165

Seasonal variation and hypertensive disorders of pregnancy in eastern Sudan.  

PubMed

Abstract The aim of this study was to investigate the seasonal variation and hypertensive disorders of pregnancy in eastern Sudan, in the period between January 2008 and December 2010. The medical files of women attending at Kassala hospital, eastern Sudan with hypertension, with or without proteinuria were retrospectively retrieved. The data of patients with hypertensive disorders of pregnancy were compared with a similar number of controls that were normotensive and non-proteinuric. During the study period, there were 9,578 deliveries; 153 patients had hypertensive disorders of pregnancy, yielding an incidence rate of 1.6%. Of all cases and controls (306), there were 183 (59.8%) deliveries in winter, 84 (27.5%) in summer and 39 (12.7%) in autumn. The highest rate of pre-eclampsia was in winter (1.1%) (CI = 1.1-2.7, OR = 1.7, p = 0.004) and the lowest rate was in autumn (0.2%) (CI = 0.4-1.8, OR = 0.8, p = 0.758.). Our study revealed significant association between the incidence of hypertensive disorders of pregnancy and the winter season (103 (67.3%) vs 80 (52.3%), p = 0.001). Thus, more attention in the winter season might reduce the morbidity and mortality of hypertensive disorders of pregnancy. PMID:25141293

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

2015-02-01

166

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. PMID:23772281

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

2013-01-01

167

Prenatal diagnosis of lethal fetal malformation in Irish obstetric practice.  

PubMed

The diagnosis of lethal fetal malformation prenatally has profound implications for the pregnancy, the expectant couple and the medical care provided. The aim of this study was to investigate these implications and the medical factors pertaining to prenatal diagnosis of lethal fetal abnormality in current obstetric practice in Ireland. Data was collected prospectively from all cases of lethal fetal malformation diagnosed at the Fetal Medicine Unit, University College Hospital Galway from December 1997 to June 1998 inclusive. Diagnosis was made on the basis of ultrasound findings and invasive procedures (amniocentesis and chorionic villus sampling). Thirteen cases of lethal fetal abnormality were diagnosed: Edward's syndrome, Patau's syndrome, bilateral multicystic renal dysplasia, Potters sequence, hypoplastic left heart, anencephaly with craniorrhachischisis, lethal osteogenesis imperfecta and non-immune hydrops. Intrauterine death occurred in four cases. Four women had preterm complications e.g. preterm premature rupture of membranes, preterm labour, placental abruption, coagulopathy and severe pre-eclampsia. Three pregnancies progressed to term, two of which had a vaginal delivery and one had an elective caesarean section for malpresentation, all of which were early neonatal deaths. Three women chose to travel abroad in order to obtain a termination of pregnancy. Obstetric and neonatal dilemmas in management of lethal fetal malformation are discussed. PMID:10360111

Byrne, B M; Morrison, J J

1999-03-01

168

Difficulties in obstetric practice in a hill subdivision.  

PubMed

The present study includes 2249 cases of delivery over a period of 4 years. Difficulties faced, complications and their management were highlighted. Teen-age pregnancy was 14.98% while 52.33% cases were in the age group of 20-25 years. A total of 26.30% cases were booked. There were 53.66% primigravida cases, 43.88% cases from gravida II to gravida IV and 2.44% were grande multipara. Noted complications were pre-eclampsia 7.4%, eclampsia 0.4% and pulmonary tuberculosis 3.7%. All the patients were anaemic. Severe anaemia was noted in 3% cases, moderate in 21% cases and mild in 76% cases. Abortion cases both spontaneous and induced or criminal were 17.02%. While considering the total number of pregnancy cases, caesarean section was performed in 4.22%. Male babies were 51.30% whereas 48.68% were females. Majority (41.48%) of the babies weighed between 2.1 and 2.5 kg range. Fresh and macerated stillbirths were 7.4%. PMID:8854624

Ray, A

1996-04-01

169

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

PubMed

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

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

2014-09-01

170

Effects of Parity on Blood Pressure among African-American Women  

PubMed Central

It has been well established that age, ethnicity, weight, and lifestyle behaviors can affect blood pressure (BP). Co-morbid conditions such as HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), pre-eclampsia, and previous hypertension diagnosis might also be risks for chronic hypertension among women who have had children. Although parity has been linked to changes in blood pressure in White women, these findings have not been replicated among African-American women. The purpose of this study was to determine if the number of pregnancies urban African-American women have effects BMI and blood pressure readings later in life. Results indicated that women with a previous diagnosis of hypertension had higher SBP and DBP, and a slightly higher BMI than women who had never been diagnosed. Additionally, women with a prior history of hypertension had more children than those without a diagnosis of hypertension. As parity increased, SBP increased. However, DBP decreased after 3 to 4 children, even with increases in BMI. This study shows that parity may increase African-American women’s risk for hypertension in terms of increased SBP and BMI with increased parity. However, increased parity and BMI may also serve as protective factors in lowering DBP. Further studies, with larger samples followed throughout their pregnancies, is needed before more definitive statements may be drawn about the effects of parity on BMI and blood pressure readings among African-American women can be made. PMID:19397049

Taylor, Jacquelyn Y.; Chambers, Angelina N.; Funnell, Beth; Wu, Chun Yi

2010-01-01

171

Magnesium Metabolism and its Disorders  

PubMed Central

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

Swaminathan, R

2003-01-01

172

 

PubMed Central

OBJECTIVE: To determine, through a review of published articles, whether a higher prevalence of pregnancy complications is associated with residency in medicine. DATA SOURCES: Articles published between January 1980 and December 1992 found through a MEDLINE search using the MeSH terms "pregnancy complications" and "internship and residency" and through a review of the bibliographies of articles found. STUDY SELECTION: Of the 17 articles found, 6 contained data on the prevalence of pregnancy complications in residents. DATA EXTRACTION: The methodologic quality of the studies was evaluated systematically with the use of a grid. Data on the prevalence of the six most common pregnancy complications were retained. DATA SYNTHESIS: Four of the six articles had methodologic weaknesses (missing or inappropriate control groups, poorly controlled historical bias). The best study showed a higher prevalence of premature labour, pre-eclampsia and voluntary abortion in the residents than in the control subjects. CONCLUSIONS: It is difficult to draw definitive conclusions from a single study that met the criteria for methodologic quality. More and better-controlled studies involving larger numbers of subjects are needed. PMID:8199955

Ménard, L; Gagnon, R

1994-01-01

173

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

PubMed

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

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

2014-11-01

174

Renal function in normal and disordered pregnancy  

PubMed Central

Purpose of review Renal dysfunction during pregnancy is a common and serious complication. Understanding normal physiology during pregnancy provides a context to further describe changes in pregnancy that lead to renal dysfunction and may provide clues to better management. Recent findings Hormonal changes during pregnancy allow for increased blood flow to the kidneys and altered autoregulation such that glomerular filtration rate (GFR) increases significantly through reductions in net glomerular oncotic pressure and increased renal size. The mechanisms for maintenance of increased GFR change through the trimesters of pregnancy, continuing into the postpartum period. Important causes of pregnancy-specific renal dysfunction have been further studied, but much needs to be learned. Pre-eclampsia is due to abnormal placentation, with shifts in angiogenic proteins and the renin–angiotensin–aldosterone system leading to endothelial injury and clinical manifestations of hypertension and organ dysfunction. Other thrombotic microangiopathies occurring during pregnancy have been better defined as well, with new work focusing on the contribution of the complement system to these disorders. Summary Advances have been made in understanding the physiology of the kidney in normal pregnancy. Diseases that affect the kidney during pregnancy alter this physiology in various ways that inform clinicians on pathogenesis and may lead to improved therapeutic approaches and better outcomes of pregnancy. PMID:24247824

Hussein, Wael; Lafayette, Richard A.

2014-01-01

175

A review of the literature on the effects of acetaminophen on pregnancy outcome.  

PubMed

Acetaminophen is commonly used during pregnancy. Experimental animal studies do not suggest increased malformations after therapeutic use of single-ingredient acetaminophen during pregnancy. Cohort studies in humans in which exposure is prospectively ascertained show no detectable increase in congenital malformation risk associated with single-ingredient acetaminophen use during pregnancy. A case-control study identified an association between acetaminophen use during pregnancy and risk of gastroschisis in the offspring, but the study was limited by recall bias, unblinded interviewers, possible misclassification of gastroschisis, confounding by indication, difficulty in separating out the effects of combination products, and possible selection bias. Two case-control studies failed to identify a statistically significant association between acetaminophen use during pregnancy and gastroschisis. No other malformation has been shown to be causally associated with single-ingredient acetaminophen. A reported association between pre-eclampsia, preterm birth, and acetaminophen may be explained by reverse causation. Concerns expressed about childhood asthma and prenatal acetaminophen use has been addressed in a separate review. The use of single-ingredient acetaminophen during pregnancy can be justified based on outcome data. Data on the effects of acetaminophen cannot necessarily be extended to acetaminophen combination products. PMID:20659550

Scialli, Anthony R; Ang, Robert; Breitmeyer, James; Royal, Mike A

2010-12-01

176

The science of implantation emerges blinking into the light.  

PubMed

Although embryo implantation is essential for human survival, it remains an enigmatic biological phenomenon. Following fertilization, the resulting blastocyst must signal its presence to the mother, attach to the luminal epithelium of the endometrium and embed into the decidualising stroma. Failure to do so results in infertility, which affects around 9% of women. Subsequent placental development requires remodelling of maternal blood vessels by trophoblast cells from the placenta, that invade deep into the decidua. Failure in these very early stages can compromise fetal development, resulting in diseases of pregnancy such as intrauterine growth restriction or pre-eclampsia which can also impact on health in adulthood. Abnormal implantation therefore constitutes a significant disease burden in humans. Although we have known for many years that successful implantation requires an embryo that is competent to implant and an endometrium that is receptive, the molecular basis of these processes remains poorly understood. Our inability to identify implantation-competent embryos or to diagnose/treat the non-receptive endometrium therefore limits our ability to intervene through assisted reproduction techniques. This Implantation Symposium aims to review recent exciting developments in our understanding of the biology of early implantation and to highlight the rapid progress being made to translate these into improved diagnosis and treatment. PMID:24055396

Sharkey, Andrew M; Macklon, Nick S

2013-11-01

177

Kiss1 mutant placentas show normal structure and function in the mouse  

PubMed Central

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

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

2015-01-01

178

The proprotein convertase furin is required for trophoblast syncytialization  

PubMed Central

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

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

2013-01-01

179

How does variability of immune system genes affect placentation?  

PubMed Central

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

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

2011-01-01

180

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

PubMed

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

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

2008-01-01

181

Overweight and Obesity before, during and after Pregnancy  

PubMed Central

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

Stupin, J. H.; Arabin, B.

2014-01-01

182

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

PubMed

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

Weinert, Letícia Schwerz; Silveiro, Sandra Pinho

2015-01-01

183

The use of magnesium sulfate for women with severe preeclampsia or eclampsia diagnosed during the postpartum period.  

PubMed

Abstract This was a systematic review of randomized controlled trials comparing anticonvulsants with placebo or no anticonvulsant for prevention (a) of eclampsia in women with severe preeclampsia diagnosed during the postpartum period or diagnosed before delivery but without previous treatment and (b) prevention of seizures recurrence in women with eclampsia postpartum. We did not find study with full inclusion criteria. However, a total of two randomised controlled trials meet inclusion criteria as subgroup analysis; one for severe preeclampsia diagnosed during the postpartum period and one for eclampsia postpartum. For severe preeclampsia diagnosed during postpartum, there was no clear difference between the groups reporting eclampsia (relative risk: 0.54, 95% confidence interval: 0.16-1.80). For seizure recurrence, magnesium sulfate was superior to diazepam, but there was no significant difference compared with phenytoin. No conclusion can be drawn on the role of magnesium sulfate post partum as established in antepartum pre-eclampsia/eclampsia management because of lack of powered randomised controlled trials. PMID:25373431

Vigil-De Gracia, Paulino; Ludmir, Jack

2014-11-27

184

Pregnancy outcome in women with pre-existing lupus nephritis.  

PubMed

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

2004-09-01

185

Complement activation and pregnancy failure.  

PubMed

Pregnancy represents a physiologic condition where maternal immune system tolerates the semi-allogenic fetus. The fetal tissues are directly exposed to the maternal blood with potential attacks from maternal immune system, including the activation of complement cascade. Small amounts, of both early and late components, of complement are physiologically found in the placenta, maybe in relation to the vascular remodeling process. A significant increase of complement activation was associated with different pathologic pregnancy outcomes, namely pre-eclampsia, recurrent spontaneous abortions, intra-uterine growth retardation, and anti-phospholipid syndrome (APS). In some, but not in all, mice models of APS, complement activation plays a major role in pregnancy loss, with a massive accumulation of C3 in the placenta, while C3 deficient mice didn't show fetal resorption. Basing on these findings, anti-phospholipid antibodies and complement activation (via C3a, C5a, and MAC) may cooperate in triggering a local inflammatory process, eventually leading to placental thrombosis, hypoxia, and neutrophil infiltration. However, histological analysis of human placenta tissues from APS women shows small rather than widespread inflammation. In a similar manner, complement activation can be detected in human APS placentas but without any relationship with pregnancy outcome and therapy. Further studies are necessary to investigate whether complement activation and inflammatory processes found in animal models are really taking place in APS. PMID:19936969

Tincani, Angela; Cavazzana, Ilaria; Ziglioli, Tamara; Lojacono, Andrea; De Angelis, Valentina; Meroni, Pierluigi

2010-12-01

186

The anti-angiogenic isoforms of VEGF in health and disease.  

PubMed

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 VEGF(165)b 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 VEGF(xxx)b isoforms to the pro-angiogenic VEGF(xxx) 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 VEGF(xxx)b 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. PMID:19909248

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

2009-12-01

187

Placental drug transporters and their role in fetal protection.  

PubMed

The human placenta has a number of protective mechanisms that help to prevent potentially harmful compounds from entering the fetal compartment. Two important transporter proteins are phospho-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) which are mainly expressed in the syncytiotrophoblast where they actively extrude a wide range of xenobiotics. The expression profile of these transporters varies with advancing gestation. P-gp has been shown to decline near term, leaving the fetus susceptible to potentially teratogenic drugs commonly administered to pregnant women (i.e., synthetic glucocorticoids, selective serotonin reuptake inhibitors, glyburide, antiretrovirals, etc.). Drug transporter expression is regulated by a number of transcription factors, and steroid hormones present during pregnancy, such as progesterone, estrogen and corticosteroids. Drug transporter levels have also been found to be altered in pathological pregnancies (preterm, pre-eclampsia, growth restriction and infection). Genetic variation in the genes that encode these drug transporters can significantly alter transporter function and may play a significant role in determining the susceptibility of a fetus to maternally-administered therapeutic drugs. Understanding the regulation of placental drug transporters in normal and pathological pregnancies is critical to further our knowledge of fetal development, and may lead to the development of more selectively-targeted maternal and fetal drug treatments. PMID:22265855

Iqbal, M; Audette, M C; Petropoulos, S; Gibb, W; Matthews, S G

2012-03-01

188

Urinary tract stones in pregnancy.  

PubMed

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

1995-02-01

189

Future directions of clinical laboratory evaluation of pregnancy  

PubMed Central

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

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

2014-01-01

190

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

PubMed

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

2013-03-01

191

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. PMID:22937489

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

2012-01-01

192

Concise guidance: Pregnancy - occupational aspects of management  

PubMed Central

Summary Most pregnant women are exposed to some physical activity at work. This 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 birthweight, 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 may be explicable in terms of chance, bias, or confounding, while larger and better studies yield lower estimated risks than smaller and weaker studies. In general, patients may 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

2013-01-01

193

Serum concentrations of homocysteine are elevated during early pregnancy in rodent models of fetal programming.  

PubMed

Maternal malnutrition can lead to fetal abnormalities and increase susceptibility to disease in later life. Rat models have been developed to study the physiology and metabolism underlying this phenomenon. One particular model of 50 % protein restriction during pregnancy, the low-protein diet (LPD) supplemented with methionine, has been developed to investigate the underlying mechanisms. Recent studies have shown that rats fed a LPD during only the first 4 d of pregnancy produce offspring that develop hypertension. These results suggest that the very earliest stages of embryo development are susceptible to diet-induced heritable changes. We demonstrate a marked elevation of maternal serum homocysteine (hcy) concentrations during the initial phases of pregnancy in both rats and mice fed an LPD. Fetal growth and many of the circulating amino acids are similarly perturbed in both rats and mice fed the LPD during pregnancy, indicating that the response to the LPD diet is similar in rats and mice. These findings allow us to exploit the advantages of the mouse experimental system in future analyses aimed at understanding the molecular basis of fetal programming. Our present findings are discussed with particular reference to mechanisms which may initiate fetal programming, and to the feasibility of dietary interventions aimed at reducing early pregnancy loss and pre-eclampsia in man. PMID:12425727

Petrie, Linda; Duthie, Susan J; Rees, William D; McConnell, Josie M L

2002-11-01

194

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. PMID:20028508

2009-01-01

195

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

SciTech Connect

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

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

1997-02-01

196

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. PMID:22336854

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

2013-01-01

197

[Pregnancy and antiphospholipid syndrome].  

PubMed

Antiphospholipid syndrome (APS) is associated with a risk of obstetrical complications, affecting both the mother and the fetus. Obstetrical APS is defined by a history of three consecutive spontaneous miscarriages before 10 weeks of gestation (WG), an intra-uterine fetal death after 10 WG, or a premature birth before 34 WG because of severe pre-eclampsia, eclampsia or placental adverse outcomes (intrauterine growth retardation, oligohydramnios). Pregnancy in women with a diagnosis of obstetric APS is at increased risk for placental abruption, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome and thrombosis that may be part of a catastrophic antiphospholipid syndrome (CAPS). A previous thrombosis and the presence of a lupus anticoagulant are risk factors for pregnancy failure. A multidisciplinary approach, associating the internist, the anesthesiologist and the obstetrician, is recommended for these high-risk pregnancies. Preconception counseling is proposed to identify pregnancy contraindications, and to define and adapt the treatment prior and during the upcoming pregnancy. Heparin and low-dose aspirin are the main treatments. The choice between therapeutic or prophylactic doses of heparin will depend on the patient's medical history. The anticoagulant therapeutic window for delivery should be as narrow as possible and adapted to maternal thrombotic risk. There is a persistent maternal risk in the postpartum period (thrombosis, HELLP syndrome, CAPS) justifying an antithrombotic coverage during this period. We suggest a monthly clinical and biological monitoring which can be more frequent towards the end of pregnancy. The persistence of notches at the Doppler-ultrasound evaluation seems to be the best predictor for a higher risk of placental vascular complications. Treatment optimization and multidisciplinary antenatal care improve the prognosis of pregnancies in women with obstetric APS, leading to a favorable outcome most of the time. PMID:22341691

Costedoat-Chalumeau, N; Guettrot-Imbert, G; Leguern, V; Leroux, G; Le Thi Huong, D; Wechsler, B; Morel, N; Vauthier-Brouzes, D; Dommergues, M; Cornet, A; Aumaître, O; Pourrat, O; Piette, J-C; Nizard, J

2012-04-01

198

Risk Factors for Birth Asphyxia in an Urban Health Facility in Cameroon  

PubMed Central

Objective The World Health Organization (WHO) estimates that 4 million children are born with asphyxia every year, of which 1 million die and an equal number survive with severe neurologic sequelae. The purpose of this study was to identify the risk factors of birth asphyxia and the hospital outcome of affected neonates. Materials & Methods This study was a prospective case-control study on term neonates in a tertiary hospital in Yaounde, with an Apgar score of < 7 at the 5th minute as the case group, that were matched with neonates with an Apgar score of ? 7 at the 5th minute as control group. Statistical analysis of relevant variables of the mother and neonates was carried out to determine the significant risk factors. Results The prevalence of neonatal asphyxia was 80.5 per 1000 live births. Statistically significant risk factors were the single matrimonial status, place of antenatal visits, malaria, pre-eclampsia/eclampsia, prolonged labor, arrest of labour, prolonged rupture of membranes, and non-cephalic presentation. Hospital mortality was 6.7%, that 12.2% of them had neurologic deficits and/or abnormal transfontanellar ultrasound/electroencephalogram on discharge, and 81.1% had a satisfactory outcome. Conclusion The incidence of birth asphyxia in this study was 80.5% per1000 live birth with a mortality of 6.7%. Antepartum risk factors were: place of antenatal visit, malaria during pregnancy, and preeclampsia/eclampsia. Whereas prolonged labor, stationary labor, and term prolonged rupture of membranes were intrapartum risk faktors. Preventive measures during prenatal visits through informing and communicating with pregnant women should be reinforced. PMID:24665306

CHIABI, Andreas; NGUEFACK, Seraphin; MAH, Evelyne; NODEM, Sostenne; MBUAGBAW, Lawrence; MBONDA, Elie; TCHOKOTEU, Pierre-Fernand; DOH FRCOG, Anderson

2013-01-01

199

Sickle cell disease and pregnancy: analysis of 34 patients followed at the Regional Blood Center of Ribeirão Preto, Brazil  

PubMed Central

Objective The objective of this study was to verify the evolution of pregnancies in sickle cell patients followed at one institution over a period of 12 years (January 2000 to June 2012). Methods The study evaluated 34 pregnant women with sickle cell disease with a mean age of 23.9 ± 5.3 years. The incidence of obstetric complications, non-obstetric complications linked to sickle cell disease and complications in the newborn were analyzed. Results A total of 26% of the cases reported previous miscarriages, 20% had preterm labor, 10% had pre-eclampsia, and 5% had gestational diabetes. Forty-one percent of the deliveries were cesarean sections and 29% of patients required blood transfusions. In respect to sickle cell disease, 62% of patients had vaso-occlusive crises, 29% had acute chest syndrome, 23% had urinary tract infection, 15% had impaired cardiac function and 6% developed pulmonary hypertension. Only one patient died in the postnatal period due to acute chest syndrome. The mean gestational age was 37.8 ± 2.63 weeks, and mean newborn weight was 2.809 ± 643.8 g. There were seven fetal losses, including three stillbirths and four miscarriages. The impact of transfusion therapy on the incidence of maternal–fetal complications during pregnancy was evaluated. Conclusions Pregnancy in sickle cell patients is still associated with complications. Although no statistical difference was observed between transfused and non-transfused women, there were no deaths (fetal or maternal) in transfused patients whereas one maternal death and three stillbirths occurred in non-transfused women. A larger study of sickle cell pregnant women will be necessary to elucidate the actual role of transfusion during pregnancy in sickle cell disease. PMID:25305164

Silva-Pinto, Ana Cristina; de Oliveira Domingues Ladeira, Simery; Brunetta, Denise Menezes; De Santis, Gil Cunha; de Lucena Angulo, Ivan; Covas, Dimas Tadeu

2014-01-01

200

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

PubMed Central

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

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

2014-01-01

201

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

PubMed Central

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

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

2014-01-01

202

Placental adaptive responses and fetal programming  

PubMed Central

Fetal programming occurs when the normal pattern of fetal development is disrupted by an abnormal stimulus or ‘insult’ applied at a critical point in in utero development. This then leads to an effect, for example diabetes or hypertension, which manifests itself in adult life. As the placenta is the regulator of nutrient composition and supply from mother to fetus and the source of hormonal signals that affect maternal and fetal metabolism, appropriate development of the placenta is crucial to normal fetal development. Placental function evolves in a carefully orchestrated developmental cascade throughout gestation. Disruption of this cascade can lead to abnormal development of the placental vasculature or of the trophoblast. Timing of a developmental ‘insult’ will be critical in consequent placental function and hence programming of the fetus. The ‘insults’ that alter placental development include hypoxia and abnormal maternal nutrient status, to which the placenta may adapt by alterations in transporter expression and activity to maintain fetal growth or by epigenetic regulation of placental gene expression. Hypoxia is physiological for organogenesis and placental tissue normally exists in a relatively hypoxic environment, but intrauterine growth restriction (IUGR) and pre-eclampsia are associated with a greater degree of trophoblast hypoxia. The metabolic activity of placental mitochondria leads to oxidative stress even in normal pregnancy which is exacerbated further in IUGR, diabetic and pre-eclamptic pregnancies and may also give nitrative stress known to lead to covalent modification and hence altered activity of proteins. Hypoxia, oxidative and nitrative stress all alter placenta development and may be a general underlying mechanism that links altered placental function to fetal programming. PMID:16469781

Myatt, Leslie

2006-01-01

203

Increased risk of gestational vascular complications in women with low free tissue factor pathway inhibitor plasma levels out of pregnancy.  

PubMed

Tissue factor pathway inhibitor (TFPI) plays a crucial role in haemostasis by regulating TF-induced initiation of coagulation. Since it is expressed by endothelial and trophoblastic cells, TFPI is of particular importance at the placental level and might be involved in the occurrence of gestational vascular complications (GVC). In the present study, we investigated plasma free TFPI antigen in four groups of women: healthy non-pregnant women without history of pregnancy complications; women at the beginning (<12 weeks) and women during the third trimester of a normal pregnancy; women with late pregnancy complications (pre-eclampsia / HELLP syndrome, intra-uterine fetal death, fetal growth retardation) at the time of obstetrical event and/or at distance from pregnancy. In normal pregnancy, TFPI increased between first trimester and delivery (median 5.0 ng/ml vs. 7.1 ng/ml; p<0.0001) but remained lower than in non-pregnant controls (median 8.2 ng/ml; p<0.0001). In patients, when measured concomitantly to the obstetrical event, TFPI showed no difference with normal late pregnancy levels. In contrast, at distance from pregnancy, in the absence of any hormonal influence, TFPI was significantly lower than in non-pregnant controls (median 5.9 vs. 8.2ng/ml, p < 0.0001). After categorisation into quartiles, an inverse dose-effect relationship was demonstrated between TFPI categories recorded apart from pregnancy and GVC risk, with a crude odds ratio of 43.5 (95% confidence interval 8.2-230) for patients with TFPI values in the lowest quartile (< 5.7 ng/ml). In conclusion, low free TFPI at distance from pregnancy appears to be a strong indicator of GVC risk. PMID:20978710

Ittel, Antoine; Bretelle, Florence; Gris, Jean-Christophe; Chau, Cécile; Sébahoun, Gérard; Boubli, Léon; Arnoux, Dominique

2011-01-01

204

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

PubMed Central

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

Fischer, Claudia; Voss, Andreas

2014-01-01

205

CYP3A Variation and the Evolution of Salt-Sensitivity Variants  

PubMed Central

Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous substrates, environmental carcinogens, and clinically important exogenous compounds, such as prescription drugs and therapeutic agents. In particular, the CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics, since they metabolize >50% of the drugs on the market. However, known genetic variants at these two loci are not sufficient to account for the observed phenotypic variability in drug response. We used a comparative genomics approach to identify conserved coding and noncoding regions at these genes and resequenced them in three ethnically diverse human populations. We show that remarkable interpopulation differences exist with regard to frequency spectrum and haplotype structure. The non-African samples are characterized by a marked excess of rare variants and the presence of a homogeneous group of long-range haplotypes at high frequency. The CYP3A5*1/*3 polymorphism, which is likely to influence salt and water retention and risk for salt-sensitive hypertension, was genotyped in >1,000 individuals from 52 worldwide population samples. The results reveal an unusual geographic pattern whereby the CYP3A5*3 frequency shows extreme variation across human populations and is significantly correlated with distance from the equator. Furthermore, we show that an unlinked variant, AGT M235T, previously implicated in hypertension and pre-eclampsia, exhibits a similar geographic distribution and is significantly correlated in frequency with CYP3A5*1/*3. Taken together, these results suggest that variants that influence salt homeostasis were the targets of a shared selective pressure that resulted from an environmental variable correlated with latitude. PMID:15492926

Thompson, E. E.; Kuttab-Boulos, H.; Witonsky, D.; Yang, L.; Roe, B. A.; Di Rienzo, A.

2004-01-01

206

Transcriptional regulation of human thromboxane synthase gene expression  

SciTech Connect

The human thromboxane synthase (TS) gene encodes a microsomal enzyme catalyzing the conversion of prostaglandin endoperoxide into thromboxane A{sub 2}(TxA{sub 2}), a potent inducer of vasoconstriction and platelet aggregation. A deficiency in platelet TS activity results in bleeding disorders, but the underlying molecular mechanism remains to be elucidated. Increased TxA{sub 2} has been associated with many pathophysiological conditions such as cardiovascular disease, pulmonary hypertension, pre-eclampsia, and thrombosis in sickle cell patients. Since the formation of TxA{sub 2} is dependent upon TS, the regulation of TS gene expression may presumably play a crucial role in vivo. Abrogation of the regulatory mechanism in TS gene expression might contribute, in part, to the above clinical manifestations. To gain insight into TS gene regulation, a 1.7 kb promoter of the human TS gene was cloned and sequenced. RNase protection assay and 5{prime} RACE protocols were used to map the transcription initiation site to nucleotide A, 30 bp downstream from a canonical TATA box. Several transcription factor binding sites, including AP-1, PU.1, and PEA3, were identified within this sequence. Transient expression studies in HL-60 cells transfected with constructs containing various lengths (0.2 to 5.5 kb) of the TS promoter/luciferase fusion gene indicated the presence of multiple repressor elements within the 5.5 kb TS promoter. However, a lineage-specific up-regulation of TS gene expression was observed in HL-60 cells induced by TPA to differentiate along the macrophage lineage. The increase in TS transcription was not detectable until 36 hr after addition of the inducer. These results suggest that expression of the human TS gene may be regulated by a mechanism involving repression and derepression of the TS promoter.

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

1994-09-01

207

Cellular and Molecular Regulation of Spiral Artery Remodelling: Lessons from the Cardiovascular Field  

PubMed Central

A number of important changes take place in the maternal uterine vasculature during the first few weeks of pregnancy resulting in increased blood flow to the intervillous space. Vascular endothelial and smooth muscle cells are lost from the spiral arteries and are replaced by fetal trophoblast cells. Failure of the vessels to remodel sufficiently is a common feature of pregnancy pathologies such as early pregnancy loss, intrauterine growth restriction and pre-eclampsia. There is evidence to suggest that some vascular changes occur prior to trophoblast invasion, however, in the absence of trophoblasts remodelling of the spiral arteries is reduced. Until recently our knowledge of these events has been obtained from immunohistochemical studies which, although extremely useful, can give little insight into the mechanisms involved. With the development of more complex in vitro models a picture of events at a cellular and molecular level is beginning to emerge, although some caution is required in extrapolating to the in vivo situation. Trophoblasts synthesise and release a plethora of cytokines and growth factors including members of the tumour necrosis factor family. Studies suggest that these factors may be important in regulating the remodelling process by inducing both endothelial and vascular smooth muscle cell apoptosis. In addition, it is evident from studies in other vascular beds that the structure of the vessel is influenced by factors such as flow, changes in the composition of the extracellular matrix, the phenotype of the vascular cells and the local immune cell environment. It is the aim of this review to present our current knowledge of the mechanisms involved in spiral artery remodelling and explore other possible pathways and cellular interactions that may be involved, informed by studies in the cardiovascular field. PMID:20359743

Whitley, G.St.J.; Cartwright, J.E.

2010-01-01

208

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. PMID:23799096

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

2013-01-01

209

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

PubMed Central

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

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

2012-01-01

210

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

PubMed

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

Ikeya, Miki; Shinya, Masaru; Kitagawa, Michihiro

2005-03-01

211

Clinical practice guidelines within the Southern African development community: a descriptive study of the quality of guideline development and concordance with best evidence for five priority diseases  

PubMed Central

Background Reducing the burden of disease relies on availability of evidence-based clinical practice guidelines (CPGs). There is limited data on availability, quality and content of guidelines within the Southern African Development Community (SADC). This evaluation aims to address this gap in knowledge and provide recommendations for regional guideline development. Methods We prioritised five diseases: HIV in adults, malaria in children and adults, pre-eclampsia, diarrhoea in children and hypertension in primary care. A comprehensive electronic search to locate guidelines was conducted between June and October 2010 and augmented with email contact with SADC Ministries of Health. Independent reviewers used the AGREE II tool to score six quality domains reporting the guideline development process. Alignment of the evidence-base of the guidelines was evaluated by comparing their content with key recommendations from accepted reference guidelines, identified with a content expert, and percentage scores were calculated. Findings We identified 30 guidelines from 13 countries, publication dates ranging from 2003-2010. Overall the 'scope and purpose' and 'clarity and presentation' domains of the AGREE II instrument scored highest, median 58%(range 19-92) and 83%(range 17-100) respectively. 'Stakeholder involvement' followed with median 39%(range 6-75). 'Applicability', 'rigour of development' and 'editorial independence' scored poorly, all below 25%. Alignment with evidence was variable across member states, the lowest scores occurring in older guidelines or where the guideline being evaluated was part of broader primary healthcare CPG rather than a disease-specific guideline. Conclusion This review identified quality gaps and variable alignment with best evidence in available guidelines within SADC for five priority diseases. Future guideline development processes within SADC should better adhere to global reporting norms requiring broader consultation of stakeholders and transparency of process. A regional guideline support committee could harness local capacity to support context appropriate guideline development. PMID:22221856

2012-01-01

212

Frequency and clinical significance of placental histological lesions in an unselected population at or near term.  

PubMed

Associations between specific placental histological abnormalities and obstetric outcomes are reported. However, most data are based either on high-risk cases or relate to case-control studies selected from those with abnormal placental histology findings, with the unavoidable biases that these approaches entail. This study reports the frequency of the several common, objective and predefined histological abnormalities of the placenta as identified by pathologists blinded to all clinical information. A total 1,153 women were recruited from an unselected population delivering at 34-43 weeks. Histological findings in common obstetric outcome groups were compared to those of the unselected population, and odds ratios and predictive values were calculated. Normal histological findings were present in 72.1% of pregnancies with normal outcomes and in 79.1%, 66.6%, 80%, and 74.8% of pregnancies affected by pre-eclampsia (PET), pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small for gestational age (SGA), respectively. Chronic placental underperfusion was seen more frequently in PIH (odds ratio (OR) 2) and SGA (OR 1.4), while villitis of unknown aetiology was observed more commonly in cases with PIH (OR 3.2). Fetal thrombotic vasculopathy was twice as common in cases with GDM whilst massive perivillous fibrin deposition was much more frequent in those with PET (OR 20.2) and SGA (OR 8.9). Chorangiomata were 13 times more common in pregnancies with PET. However, in all cases, positive predictive values were low, with the majority of cases with histological abnormalities being associated with normal outcome. At term, specific placental histological lesions are significantly more common in complicated pregnancies, but the clinical significance of such lesions in a specific case remains uncertain, since the majority will be identified from clinically uncomplicated normal pregnancies. PMID:22038509

Pathak, Sangeeta; Lees, Christoph C; Hackett, Gerald; Jessop, Flora; Sebire, Neil J

2011-12-01

213

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

PubMed Central

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

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

2014-01-01

214

Animal models of human placentation--a review.  

PubMed

This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however, substantive differences, including a different mode of implantation, a prominent yolk sac placenta, and fewer placental hormones in the mouse. Crucially, trophoblast invasion is very limited in the mouse and transformation of uterine arteries depends on maternal factors. The mouse also has a short gestation and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial, there is no trophoblast invasion of uterine vessels, and the immunology of pregnancy may be quite different. We conclude that continued research on non-human primates is needed to clarify embryonic-endometrial interactions. The interstitial implantation of human is unusual, but the initial interaction between trophoblast and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque, baboon and human. Non-human primates are therefore important models for understanding the dysfunction that has been linked to pre-eclampsia and fetal growth restriction. Models that are likely to be established in the wake of comparative genomics include the marmoset, tree shrew, hedgehog tenrec and nine-banded armadillo. PMID:17196252

Carter, A M

2007-04-01

215

Bevacizumab-induced hypertension: pathogenesis and management.  

PubMed

Bevacizumab, a recombinant humanized monoclonal antibody targeting the vascular endothelial growth factor (VEGF), has been approved in the US as first- and second-line treatment of colorectal cancer and in the first-line treatment of advanced non-small cell lung cancer. The US FDA has also granted approval for the use of bevacizumab for the treatment of patients with metastatic renal cell carcinoma and glioblastoma, and in Europe, it is also approved in metastatic breast cancer in combination with paclitaxel. Bevacizumab is under investigation in the first-line and adjuvant setting of almost all types of solid tumors. However, anti-VEGF therapy is associated with significant toxicity. The incidence of grade 3-4 hypertension differs among the various malignancies in which bevacizumab is administered, possibly because of drug interactions with co-administered chemotherapy drugs. Hypertension appears to be dose dependent, and it is under investigation as a biomarker for VEGF inhibition efficacy. There are three main theories concerning the underlying pathophysiology: (i) the nitric oxide theory; (ii) the renal impairment theory; and (iii) the pre-eclampsia-like theory. The correct evaluation of the levels of hypertension is of critical importance and home blood pressure monitoring seems to be the most effective technique. A baseline assessment and follow-up monitoring of blood pressure is considered necessary for all patients receiving bevacizumab. There are no evidence-based recommendations regarding which antihypertensives are more appropriate for the management of bevacizumab-related hypertension. It has been suggested that the benefits from antihypertensive treatment are largely independent of the drugs used, as long as they adequately lower blood pressure. Randomized prospective studies are necessary to provide data that will be useful for the development of specific guidelines for the management of bevacizumab-related hypertension. In the meantime, treatment of anti-VEGF-induced hypertension should follow current guidelines for diagnosis and management of hypertension in general. PMID:21627340

Syrigos, Kostas N; Karapanagiotou, Eleni; Boura, Paraskevi; Manegold, Christian; Harrington, Kevin

2011-06-01

216

Pregnancy-associated retinal diseases and their management.  

PubMed

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

2013-01-01

217

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

PubMed Central

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

King, Bridget; Bryan, Phil

2014-01-01

218

Pregnancies in women with and without renal scarring after urinary infections in childhood.  

PubMed Central

OBJECTIVE--To compare the outcome of pregnancy in women with and without renal scarring after childhood urinary infections with that in unmatched controls. DESIGN--Retrospective study of pregnancies in women prospectively followed up from their first recognised urinary infection. SETTING--Tertiary referral centre in Gothenburg. SUBJECTS--111 Women attending an outpatient clinic for women with urinary infection during 1975-83, of whom 41 (65 pregnancies) were studied (19 women with renal scarring (32), 22 without scarring (33)), and 65 controls (65) randomly selected and matched for parity, age, smoking habits, and date of delivery. MAIN OUTCOME MEASURES--Urinary infections and complications in pregnancy. RESULTS--The incidence of bacteriuria during first pregnancies was significantly greater in women with (9, 47%) and without (6, 27%) renal scarring after childhood urinary infection than in controls (1, 2%) (p less than 0.001, 0.01 respectively). Symptomatic infections were seen only among women with a history of urinary infection: four women with renal scarring (three of whom had vesicoureteric reflux) developed pyelonephritis and three cystitis, and one woman without scarring developed pyelonephritis. Mean blood pressure was higher among women with severe renal scarring than controls (4/11 v 3/44; p less than 0.05) before and during pregnancy. There was no significant difference in the incidence of pre-eclampsia, operative delivery, prematurity, or birth weight. CONCLUSIONS--Women with a history of previous urinary infections had a high incidence of bacteriuria during pregnancy, and those with renal scarring and persistent reflux were prone to develop acute pyelonephritis. The risk of serious complications in pregnancy, however, was not increased in women with severe renal scarring, possibly owing to their continuous clinical supervision. PMID:2337697

Martinell, J; Jodal, U; Lidin-Janson, G

1990-01-01

219

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

PubMed Central

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

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

2014-01-01

220

C-B5-02: H1N1 Vaccine Safety Monitoring in the Vaccine Safety Datalink Project: New Challenges and Useful Lessons  

PubMed Central

Background and Aims: The worldwide introduction of influenza A (H1N1) vaccines in fall 2009 has raised widespread public questions about the safety of these new vaccines. The Vaccine Safety Datalink Project, a collaboration among CDC and eight health care systems in the HMORN, began accelerated monitoring of this vaccine’s safety in early fall 2009. Methods: The VSD Project conducts near real-time monitoring of potential adverse events following vaccination for all new vaccines. Each week, each site updates dynamic data files, and the coordinating center analyzes all data cumulatively. Repeated analysis of the same data requires adjustment for multiple testing. To address this issue, VSD uses sequential statistical methods. Evaluation of H1N1 vaccine safety poses special challenges, including confounding by indication, seasonality, and new priority groups including pregnant women. We are using several analytic methods, including: Self-controlled case-series, which compares exposed vs. unexposed time windows within the same individual; Poisson, which compares the outcomes during the current season with expected rates based on historical data for seasonal influenza vaccine; and Difference-in-difference, which compares the relative risk in exposed vs. unexposed time windows for H1N1 vaccine during the current season with the relative risk for seasonal influenza vaccine during cumulative prior seasons. Results: Pre-specified outcomes of interest include: Guillain-Barre syndrome, neuropathies, seizures, encephalitis, Bell’s palsy, ataxia, anaphylaxis, spontaneous abortion, pre-eclampsia, stroke, myocarditis and wheezing. Historical rates of these outcomes were calculated for time windows after seasonal influenza vaccination in prior seasons (2000/01–2008/09). The sequential analysis methods above will be used, and relative and absolute risks will be estimated for each outcome. For outcomes found associated with vaccination in preliminary analyses, additional evaluation will be conducted using temporal scan analyses, logistic regression, and when appropriate, medical record review.

Lieu, Tracy; Greene, Sharon; Yin, Ruihua; Li, Rong; Kulldorff, Martin; Weintraub, Eric; Fireman, Bruce; Baxter, Roger; Nordin, James; Jacobsen, Steven; Lewis, Edwin; Baggs, James; Rett, Melisa; Platt, Richard; Lee, Grace

2010-01-01

221

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

PubMed Central

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

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

2014-01-01

222

Alterations in Polyadenylation and Its Implications for Endocrine Disease  

PubMed Central

Introduction: Polyadenylation is the process in which the pre-mRNA is cleaved at the poly(A) site and a poly(A) tail is added – a process necessary for normal mRNA formation. Genes with multiple poly(A) sites can undergo alternative polyadenylation (APA), producing distinct mRNA isoforms with different 3? untranslated regions (3? UTRs) and in some cases different coding regions. Two thirds of all human genes undergo APA. The efficiency of the polyadenylation process regulates gene expression and APA plays an important part in post-transcriptional regulation, as the 3? UTR contains various cis-elements associated with post-transcriptional regulation, such as target sites for micro-RNAs and RNA-binding proteins. Implications of alterations in polyadenylation for endocrine disease: Alterations in polyadenylation have been found to be causative of neonatal diabetes and IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked) and to be associated with type I and II diabetes, pre-eclampsia, fragile X-associated premature ovarian insufficiency, ectopic Cushing syndrome, and many cancer diseases, including several types of endocrine tumor diseases. Perspectives: Recent developments in high-throughput sequencing have made it possible to characterize polyadenylation genome-wide. Antisense elements inhibiting or enhancing specific poly(A) site usage can induce desired alterations in polyadenylation, and thus hold the promise of new therapeutic approaches. Summary: This review gives a detailed description of alterations in polyadenylation in endocrine disease, an overview of the current literature on polyadenylation and summarizes the clinical implications of the current state of research in this field. PMID:23658553

Rehfeld, Anders; Plass, Mireya; Krogh, Anders; Friis-Hansen, Lennart

2013-01-01

223

Management of pregnancy in women with type 1 diabetes.  

PubMed

Type 1 diabetes is increasingly common, thus affecting more women of childbearing potential. Inadequate glycemic control complicates pregnancy and can result in significant morbidity and mortality. Fetal consequences include congenital malformations, recurrent miscarriages, growth anomalies and stillbirth. Maternal consequences include worsening of diabetes vascular complications, pre-eclampsia, eclampsia and increased likelihood of caesarian section. Hence, pregnancies should be carefully planned in advance and managed by a multi-disciplinary team of experienced diabetologists, diabetes educators, and maternal-fetal medicine specialists. Educating the patient is the cornerstone of care. Preventing unplanned pregnancies, particularly in the context of uncontrolled diabetes, excellent glycemic control in the months leading to discontinuation of birth control, recognition and stabilization of associated co-morbidities and diabetic complications are some of the measures shown to improve pregnancy outcome in diabetes. During pregnancy, glycemic targets are typically set lower than the non-pregnant state (i.e., fasting blood glucose <90 mg/dL [5.0 mmol/L] and peak, 1 h post-prandial <120 mg/dL [6.7 mmol/L]) with a target glycated hemoglobin close to or possibly lower than 6%. Several insulin analogues are now approved for use in pregnancy, facilitating insulin administration, while many patients elect insulin pump therapy (with or without the addition of continuous glucose monitor sensing). Stringent glucose control is maintained through labor, and insulin requirements decrease to pre-pregnancy levels after delivery. Women who choose to pursue breastfeeding should be encouraged to do so, and supported by minimizing mother/baby separation and providing access to a lactation specialist. PMID:24285102

Azar, M; Lyons, T J

2013-12-01

224

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. PMID:24040389

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

2013-01-01

225

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

PubMed Central

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

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

2013-01-01

226

Clinical and therapeutic aspects associated to phospholipid binding antibodies (lupus anticoagulant and anticardiolipin antibodies).  

PubMed

Antiphospholipid antibodies (APA) comprise a family of immunoglobulins characterized by their pattern of reactivity in a number of laboratory tests. Included in this family are lupus anticoagulant (LA) anticardiolipin antibodies (ACA) and antibodies causing biologic false positive serologic tests for syphilis (BFP-STS). LA and ACA occur in a variety of conditions, including other autoimmunes disorders, infectious diseases, neoplasic disorders, in association with certain drugs and in otherwise healthy individuals. Clinical interest in LA and ACA is increasing. Antiphospholipid antibody syndrome is characterized by a triad of clinical features which include fetal loss, thromboembolic disease and thrombocytopenia. Other clinical manifestations related with APA are livedo reticularis, cutaneous necrosis, hemolytic anemia, heart valve disease, chorea, migraine and obstetric problems as fetal growth retardation, pre-eclampsia, post-partum serositis or neonatal thrombosis or catastrophic antiphospholipid syndrome. Therapy is mainly directed against the widespread and diverse manifestations associated with the obstruction of small and large vessels. Long-term treatment with oral anticoagulation therapy is advised, even if the venous or arterial occlusion occurred many years previously. In patients with primary antiphospholipid syndrome there is no evidence that the prophylactic administration of steroids or immunosuppression will prevent thromboembolic events. Although the administration of more energetic immunosuppression with cyclophosphamide in pulse form is effective in reducing elevated antibody levels, there is usually a rapid rebound to pretreatment levels shortly after discontinuation of the therapy. A history of recurrent fetal loss requires mandatory treatment during pregnancy. Although the actual prospective risk of pregnancy loss in women with antiphospholipid syndrome and prior pregnancy loss is unknown, it may exceed 60%. Because of this many investigators have treated women with antiphospholipid syndrome with either antiplatelet agents, immunosuppressive agents, or anticoagulants in an attempt to improve pregnancy outcome. Unfortunately, there is no unequivocal proof that any of these therapies are fully efficacious. Despite varying treatment protocols, the live birth rate with treatment was 70%, similar to that reported in the recent randomized clinical trial. Thrombocytopenia and autoimmune hemolytic anemia in patients with APA are treated similarly as patients without APA. Treatment of asymptomatic patients isn't indicated, because only approximately 10-15% of patients with APA developed complications. PMID:7988946

Ordi-Ros, J; Pérez-Pemán, P; Monasterio, J

1994-01-01

227

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

PubMed Central

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

2014-01-01

228

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

PubMed Central

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

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

2014-01-01

229

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

PubMed

A system to improve the management of emergencies during pregnancy, childbirth, infancy and childhood in a region of The Gambia (Brikama) with a population of approximately 250,000 has been developed.This was accomplished through formal partnership between the Gambian Ministry of Health, the World Health Organisation, Maternal Childhealth Advocacy International and the Advanced Life Support Group.Since October 2006, the hospital in Brikama has been renovated and equipped and more efficiently provided with emergency medicines. An emergency ambulance service now links the community with the hospital through a mobile telephone system. Health professionals from community to hospital have been trained in obstetric, neonatal and paediatric emergency management using skills' based education. The programme was evaluated in log books detailing individual resuscitations and by external assessment.The hospital now has constant water and electricity, a functioning operating theatre and emergency room; the maternity unit and children's wards have better emergency equipment and there is a more reliable supply of oxygen and emergency drugs, including misoprostol (for treating post partum haemorrhage) and magnesium sulphate (for severe pre-eclampsia). There is also a blood transfusion service.Countrywide, 217 doctors, nurses, and midwives have undergone accredited training in the provision of emergency maternal, newborn and child care, including for major trauma. 33 have received additional education through Generic Instructor Courses and 15 have reached full instructor status. 83 Traditional Birth Attendants and 48 Village Health Workers have been trained in the recognition and initial management of emergencies, including resuscitation of the newborn. Eleven and ten nurses underwent training in peri-operative nursing and anaesthetics respectively, to address the acute shortage required for emergency Caesarean section.Between May 2007 and March 2010, 109 patients, mostly pregnant mothers, were stabilised and transported to hospital by the new emergency ambulance service.293 resuscitation attempts were documented in personal logbooks.A sustainable system for better managing emergencies has been established and is helping to negate the main obstacle impeding progress: the country's lack of available trained medical and nursing staff. However, insufficient attention was paid to improving staff morale and accommodation representing significant failings of the programme. PMID:20718979

Cole-Ceesay, Ramou; Cherian, Meena; Sonko, Alieu; Shivute, Nestor; Cham, Mamady; Davis, Michael; Fatty, Famara; Wieteska, Susan; Baro, Momodou; Watson, Diane; Phillips, Barbara; Macdonald, Rhona; Hayden, Brigid; Southall, David

2010-01-01

230

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

PubMed Central

Background The incidence of severe maternal morbidity is increasing in high-income countries as a consequence, in part, of increased obstetric intervention and increasingly complex medical needs of women who become pregnant. Access to emergency obstetric care means that for the majority of women in these countries, an experience of severe maternal morbidity is unlikely to result in loss of life. However, little is known about the subsequent impact on postnatal psychological health resulting in an evidence gap to support provision of appropriate care for these women. There has recently been increasing recognition that childbirth can be a cause of post-traumatic stress disorder (PTSD). The combination of experiencing a life-threatening complication and its management may culminate in psychological trauma. This systematic review examined the association between women’s experience of severe maternal morbidity during labour, at the time of giving birth or within the first week following birth, and PTSD and its symptoms. Methods Relevant literature was identified through multiple databases, including MEDLINE, PsycINFO, EMBASE, CINAHL, British Nursing Index, Web of Science, Cochrane library and the British Library, using predetermined search strategies. The search terms included "post-traumatic stress disorder", "PTSD", "stress disorders, post-traumatic", "maternal morbidity", “pregnancy complications” “puerperal disorders”, "obstetric labo(u)r complication", "postpartum h(a)emorrhage", "eclampsia”. Studies identified were categorised according to pre-defined inclusion and exclusion criteria. The quality of included studies was assessed using the relevant CASP appraisal tools. Results Eleven primary studies met review criteria. Evidence of a relationship between severe maternal morbidity and PTSD/PTSD symptoms was inconsistent and findings varied between studies. Nevertheless, there is some evidence that severe pre-eclampsia is a risk factor for PTSD and its symptoms, an association possibly mediated by other factors such as fetal/neonatal condition. Conclusions Despite the absence of robust evidence regarding the relationship between severe maternal morbidity and PTSD/PTSD symptoms, it is crucially important that clinicians and policy makers are aware of a potential higher risk of PTSD among women who experience severe morbidity. Further studies are now needed to confirm this risk as well as to understand underlying mechanisms in order to minimise the longer term psychiatric impact of severe maternal morbidity. PMID:23140343

2012-01-01

231

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

PubMed Central

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

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

2014-01-01

232

Development of GC-MS/MS method with programmable temperature vaporization large volume injection for monitoring of 17?-estradiol and 2-methoxyestradiol in plasma.  

PubMed

Monitoring of estradiol and its metabolites in biological samples is essential for the accurate diagnosis of a number of endocrine diseases. In this study, a sensitive, precise and specific GC-MS/MS method for the quantification of 17?-estradiol (17-BE) and its main metabolite, 2-methoxyestradiol (2-MEOE), in plasma was developed and validated. Plasma concentrations of these steroids are currently investigated as diagnostic markers for pre-eclampsia, a systematic disorder of pregnancy and a leading cause of maternal and fetal morbidity and mortality worldwide. The method comprised treatment of the plasma sample by protein precipitation and subsequent isolation of steroids by solid phase extraction, derivatization of steroids by trifluoroacetic anhydride and GC-MS/MS analysis of the derivatized steroids. The large volume (10 ?L) injection with the assistance of a Programmed Temperature Vaporization (PTV) injector in solvent split mode allowed a substantial increase in the sensitivity of the method. The ion trap MS was operated in optimized Product Ion Scan. By increasing the damping gas flow in the ion trap from the conventional 0.3 mL min(-1) to 2 mL min(-1), ion fragmentation was reduced and the instrument response was enhanced substantially. As a result, mass spectra with predominant molecular ions were acquired and molecular ions of the steroids of interest were used as precursor ions thus increasing specificity of the method. Under optimized GC-MS/MS conditions in product ion mode, the Limit of Detection (LOD) of the analyzed steroids ranged from 18.4 pg mL(-1) for 17-BE to 5.5 pg mL(-1) for 2-MEOE (S/N=3). The instrument response was linear in the investigated concentration range from 0.1 to 10 ng mL(-1) with R(2)>0.99 for 17-BE and 2-MEOE. The intra-batch accuracy obtained for quality control samples at the concentration levels of 0.1, 1, 3, 7 ng mL(-1) ranged from 94.9% to 109.9% for 17-BE and from 99.9% to 104.5% for 2-MEOE. PMID:22122934

Tsakalof, A K; Gkagtzis, D C; Koukoulis, G N; Hadjichristodoulou, C S

2012-01-01

233

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

PubMed Central

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

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

2014-01-01

234

The Effect of Changing Patterns of Obstetric Care in Scotland (1980–2004) on Rates of Preterm Birth and Its Neonatal Consequences: Perinatal Database Study  

PubMed Central

Background Rates of preterm birth are rising worldwide. Studies from the United States and Latin America suggest that much of this rise relates to increased rates of medically indicated preterm birth. In contrast, European and Australian data suggest that increases in spontaneous preterm labour also play a role. We aimed, in a population-based database of 5 million people, to determine the temporal trends and obstetric antecedents of singleton preterm birth and its associated neonatal mortality and morbidity for the period 1980–2004. Methods and Findings There were 1.49 million births in Scotland over the study period, of which 5.8% were preterm. We found a percentage increase in crude rates of both spontaneous preterm birth per 1,000 singleton births (10.7%, p<0.01) and medically indicated preterm births (41.2%, p<0.01), which persisted when adjusted for maternal age at delivery. The greater proportion of spontaneous preterm births meant that the absolute increase in rates of preterm birth in each category were similar. Of specific maternal complications, essential and pregnancy-induced hypertension, pre-eclampsia, and placenta praevia played a decreasing role in preterm birth over the study period, with gestational and pre-existing diabetes playing an increasing role. There was a decline in stillbirth, neonatal, and extended perinatal mortality associated with preterm birth at all gestation over the study period but an increase in the rate of prolonged hospital stay for the neonate. Neonatal mortality improved in all subgroups, regardless of obstetric antecedent of preterm birth or gestational age. In the 28 wk and greater gestational groups we found a reduction in stillbirths and extended perinatal mortality for medically induced but not spontaneous preterm births (in the absence of maternal complications) although at the expense of a longer stay in neonatal intensive care. This improvement in stillbirth and neonatal mortality supports the decision making behind the 34% increase in elective/induced preterm birth in these women. Although improvements in neonatal outcomes overall are welcome, preterm birth still accounts for over 66% of singleton stillbirths, 65% of singleton neonatal deaths, and 67% of infants whose stay in the neonatal unit is “prolonged,” suggesting this condition remains a significant contributor to perinatal mortality and morbidity. Conclusions In our population, increases in spontaneous and medically induced preterm births have made equal contributions to the rising rate of preterm birth. Despite improvements in related perinatal mortality, preterm birth remains a major obstetric and neonatal problem, and its frequency is increasing. Please see later in the article for the Editors' Summary PMID:19771156

Norman, Jane E.; Morris, Carole; Chalmers, James

2009-01-01

235

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

PubMed Central

Discussion continues as to whether de novo hypertension in pregnancy with significant proteinuria (pre-eclampsia; PE) and non-proteinuric new hypertension (gestational hypertension; GH) are parts of the same disease spectrum or represent different conditions. Non-pregnant hypertension, pregnancy and PE are all associated with oxidative stress. We have established a 6 weeks postpartum clinic for women who experienced a hypertensive pregnancy. We hypothesized that PE and GH could be distinguished by markers of oxidative stress; thiobarbituric acid reactive substances (TBARS) and antioxidants (ferric ion reducing ability of plasma; FRAP). Since the severity of PE and GH is greater pre-term, we also compared pre-term and term disease. Fifty-eight women had term PE, 23 pre-term PE, 60 had term GH and 6 pre-term GH, 11 pre-existing (essential) hypertension (EH) without PE. Limited data were available from normotensive pregnancies (n = 7) and non-pregnant controls (n = 14). There were no differences in postpartum TBARS or FRAP between hypertensive states; TBARS (P = 0.001) and FRAP (P = 0.009) were lower in plasma of non-pregnant controls compared to recently-pregnant women. Interestingly FRAP was higher in preterm than term GH (P = 0.013). In PE and GH, TBARS correlated with low density lipoprotein (LDL)-cholesterol (P = 0.036); this association strengthened with inclusion of EH (P = 0.011). The 10 year Framingham index for cardiovascular risk was positively associated with TBARS (P = 0.003). Oxidative stress profiles do not differ between hypertensive states but appear to distinguish between recently-pregnant and non-pregnant states. This suggests that pregnancy may alter vascular integrity with changes remaining 6 weeks postpartum. LDL-cholesterol is a known determinant of oxidative stress in cardiovascular disease and we have shown this association to be present in hypertensive pregnancy further emphasizing that such a pregnancy may be revealing a pre-existing cardiovascular risk. PMID:25202276

Kurlak, Lesia O.; Green, Amanda; Loughna, Pamela; Broughton Pipkin, Fiona

2014-01-01

236

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

SciTech Connect

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

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

2012-11-01

237

Association between vitamin D insufficiency and adverse pregnancy outcome: global comparisons  

PubMed Central

Background Vitamin D insufficiency has been associated with a number of adverse pregnancy outcomes, and has been recognized as a public health concern. Aim The objective of this study was to determine the impact of vitamin D deficiency on maternal complications like gestational diabetes mellitus (GDM), anemia, iron deficiency, and preeclampsia among pregnant women. Subjects and methods This was a cohort study undertaken at antenatal clinics at the Women’s Hospital of Hamad Medical Corporation in Doha. A total of 2,487 Arab pregnant women above 24 weeks’ gestation with any maternal complication were approached, and 1,873 women (75.3%) consented to participate in the study. Data on sociodemographic and clinical characteristics by interview and biochemistry parameters were retrieved from medical records. Multivariate logistic regression analysis was performed to determine the associated risk factors. Results Of the studied pregnant women, nearly half of them had vitamin D deficiency (48.4%). Younger women below 30 years old (43.2%, P = 0.032), housewives (65.3%, P = 0.008), and those on low monthly household incomes (QR5,000–9,999) (49.2%, P = 0.03) were significantly more likely to have lower vitamin D compared with those who had sufficient vitamin D levels. Exposure to sunlight (63.4%, P = 0.05), daily physical activity (64.4%, P = 0.05), and vitamin D supplement intake (89.7%, P < 0.001) were significantly lower in deficient pregnant women. In the study sample of pregnant women, 13.9% had GDM, 11.5% had anemia, 8.6% had iron deficiency, and 6.9% had preeclampsia. Severe vitamin D deficiency was significantly higher in pregnant women with GDM (16.5% vs 11%), anemia (17.1% vs 11%), iron deficiency (18.5% vs 11.2%), and preeclampsia (19.8% vs 11.4%) when compared to the uncomplicated group. Socioeconomic status was low in pregnant women with complications like GDM, anemia, iron deficiency, and pre-eclampsia. Pregnancy complications like GDM (52.7%), anemia (53.2%), iron deficiency (55.6%), and preeclampsia (51.9%) were higher in Qataris. Also, GDM (66.2%), anemia (66.2%), iron deficiency (68.5%), and preeclampsia (58.1%) were observed more commonly among housewives compared to working women. Obesity was significantly more common in pregnant women with GDM (41.5%) and preeclampsia (41.1%). Conclusion The study findings revealed that maternal vitamin D deficiency in pregnancy is significantly associated with elevated risk for GDM, anemia, and preeclampsia. The risk of vitamin D deficiency was higher in Qataris, housewives and those with low monthly household income. PMID:24043954

Bener, Abdulbari; Al-Hamaq, Abdulla OAA; Saleh, Najah M

2013-01-01

238

Elevated Soluble VEGF Receptor sFlt-1 Correlates with Endothelial Injury in IgA Nephropathy  

PubMed Central

Background Endothelial injury, which may present clinically as hypertension, proteinuria and increased von Willebrand Factor (vWF) level, is a common manifestation in IgA nephropathy (IgAN). However, causal factors for endothelial injury in IgAN are not completely understood. An imbalance of vascular endothelial growth factor/Soluble fms-like tyrosine kinase-1 (VEGF/sFlt-1) has been observed in many diseases with endothelial dysfunction, including pre-eclampsia and diabetic retinopathy, but whether it contributes to endothelial injury in IgAN requires further exploration. Methods Initially, 96 IgAN patients and 22 healthy volunteers were enrolled as a discovery cohort. VEGF/sFlt-1, sFlt-1 and VEGF levels were compared between patients with IgAN and healthy volunteers to explore the underlying factors that contribute to endothelial injury in IgAN. The identified contributor (sFlt-1) was further confirmed in a replication cohort, which included 109 IgAN patients and 30 healthy volunteers. Correlations of sFlt-1 with hypertension, proteinuria, Oxford-E score and plasma vWF were further evaluated in the combined 205 patients with IgAN. Results VEGF/sFlt-1 levels were significantly lower in IgAN patients than healthy volunteers (0.33±0.27 vs. 0.43±0.22, p?=?0.02) in the discovery cohort. Within the ratio, plasma sFlt-1 levels were significantly elevated (101.18±25.19 vs. 79.73±18.85 pg/ml, p<0.001), but plasma VEGF levels showed no significant differences. Elevated sFlt-1 levels in the replication cohort were confirmed in IgAN patients (93.40±39.78 vs. 71.92±15.78 pg/ml, p<0.001). Plasma sFlt-1 levels in IgAN patients correlated with proteinuria (severe (>3.5 g/d) vs. moderate (1–3.5 g/d) vs. mild (<1 g/d) proteinuria: 115.95±39.09 vs. 99.89±28.55 vs. 83.24±33.92 pg/ml; severe vs. mild: p<0.001, moderate vs. mild p?=?0.001, severe vs. moderate: p?=?0.014), hypertension (with vs. without hypertension: 107.87±31.94 vs. 87.32±32.76 pg/ml, p?=?0.015) and vWF levels (r?=?0.161, p?=?0.021). Conclusions The present study found elevated sFlt-1 in IgAN patients and further identified its correlation with proteinuria, hypertension and vWF levels. These results suggested that elevated sFlt-1 contributes to endothelial injury in IgAN. PMID:25007257

Zhai, Ya-Ling; Zhu, Li; Shi, Su-Fang; Liu, Li-Jun; Lv, Ji-Cheng; Zhang, Hong

2014-01-01

239

In Vitro Fertilization and Multiple Pregnancies  

PubMed Central

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

2006-01-01

240

Exercise, vascular wall and cardiovascular diseases: an update (Part 1).  

PubMed

Cardiovascular disease (CVD) remains the leading cause of morbidity and premature mortality in both women and men in most industrialized countries, and has for some time also established a prominent role in developing nations. In fact, obesity, diabetes mellitus and hypertension are now commonplace even in children and youths. Regular exercise is rapidly gaining widespread advocacy as a preventative measure in schools, medical circles and in the popular media. There is overwhelming evidence garnered from a number of sources, including epidemiological, prospective cohort and intervention studies, suggesting that CVD is largely a disease associated with physical inactivity. A rapidly advancing body of human and animal data confirms an important beneficial role for exercise in the prevention and treatment of CVD. In Part 1 of this review we discuss the impact of exercise on CVD, and we highlight the effects of exercise on (i) endothelial function by regulation of endothelial genes mediating oxidative metabolism, inflammation, apoptosis, cellular growth and proliferation, increased superoxide dismutase (SOD)-1, down-regulation of p67phox, changes in intracellular calcium level, increased vascular endothelial nitric oxide synthase (eNOS), expression and eNOS Ser-1177 phosphorylation; (ii) vascular smooth muscle function by either an increased affinity of the Ca2+ extrusion mechanism or an augmented Ca2+ buffering system by the superficial sarcoplasmic reticulum to increase Ca2+ sequestration, increase in K+ channel activity and/or expression, and increase in L-type Ca2+ current density; (iii) antioxidant systems by elevation of Mn-SOD, Cu/Zn-SOD and catalase, increases in glutathione peroxidase activity and activation of vascular nicotinamide adenine dinucleotide phosphate [(NAD(P)H] oxidase and p22phox expression; (iv) heat shock protein (HSP) expression by stimulating HSP70 expression in myocardium, skeletal muscle and even in human leucocytes, probably through heat shock transcription factor 1 activity; (v) inflammation by reducing serum inflammatory cytokines such as high-sensitivity C-reactive protein (hCRP), interleukin (IL)-6, IL-18 and tumour necrosis factor-alpha and by regulating Toll-like receptor 4 pathway. Exercise also alters vascular remodelling, which involves two forms of vessel growth including angiogenesis and arteriogenesis. Angiogenesis refers to the formation of new capillary networks. Arteriogenesis refers to the growth of pre-existent collateral arterioles leading to formation of large conductance arteries that are well capable to compensate for the loss of function of occluded arteries. Another aim of this review is to focus on exercise-related cardiovascular protection against CVD and associated risk factors such as aging, coronary heart disease, hypertension, heart failure, diabetes mellitus and peripheral arterial diseases mediated by vascular remodelling. Lastly, this review examines the benefits of exercise in mitigating pre-eclampsia during pregnancy by mechanisms that include improved blood flow, reduced blood pressure, enhanced placental growth and vascularity, increased activity of antioxidant enzymes, reduced oxidative stress and restored vascular endothelial dysfunction. PMID:19026018

Leung, Fung Ping; Yung, Lai Ming; Laher, Ismail; Yao, Xiaoqiang; Chen, Zhen Yu; Huang, Yu

2008-01-01