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1

Could antioxidant supplementation prevent pre-eclampsia?  

PubMed

Pre-eclampsia is a disorder characterised by pregnancy-induced hypertension and new-onset proteinuria occurring in the second half of pregnancy. Worldwide, approximately 2-3% of all pregnant women develop pre-eclampsia. The condition is a major cause of maternal and fetal morbidity and mortality. Abnormal placentation is an important predisposing factor for pre-eclampsia, while endothelial activation appears to be central to the pathophysiological changes, possibly indicative of a two-stage disorder characterised by reduced placental perfusion and a maternal syndrome. There is increasing evidence that pre-eclampsia is associated with both increased oxidative stress and reduced antioxidant defences, which has led to the hypothesis that oxidative stress may play an important role in the pathogenesis of pre-eclampsia, perhaps acting as the link in a two-stage model of pre-eclampsia. In support of this hypothesis a small, but important, preliminary study has shown a highly significant (P=0.02) reduction in the incidence of pre-eclampsia in women at risk who were taking a supplement of vitamins C and E from mid-pregnancy. Furthermore, these findings support the hypothesis that oxidative stress is at least partly responsible for the endothelial dysfunction of pre-eclampsia. Several larger multicentre trials are currently underway to evaluate the efficacy, safety and cost benefits of antioxidant supplementation during pregnancy for the prevention of pre-eclampsia in both low- and high-risk women, including women with diabetes. The results of these trials are awaited with interest. PMID:16313693

Holmes, Valerie A; McCance, David R

2005-11-01

2

Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia  

Microsoft Academic Search

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

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

1997-01-01

3

Pre-eclampsia: pathophysiology, diagnosis, and management  

PubMed Central

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

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

2011-01-01

4

Hepatocellular lipofuscin in pre-eclampsia.  

PubMed

Thirty liver specimens from 30 pre-eclamptic women with and without liver dysfunction were examined for the amount of lipofuscin pigment deposited. The amount of hepatic lipofuscin correlated positively with plasma urate concentrations. This finding may indicate an involvement of oxygen-free radicals and xanthine oxidase in the pathophysiology of pre-eclampsia. PMID:2597092

Minakami, H; Kimura, K; Tamada, T; Yasuda, Y; Hirota, N

1989-09-01

5

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

6

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

7

Proteinuria as a predictor of complications of pre-eclampsia  

Microsoft Academic Search

Proteinuria is a defining criterion for the diagnosis of pre-eclampsia. The amount of protein lost per day has been thought by some to predict both maternal and fetal outcome. The systematic review of 16 primary papers including over 6700 patients by Thangaratinam and colleagues published this month in BMC Medicine suggests otherwise. This finding may influence our management of pre-eclampsia.

G Justus Hofmeyr; Michael Belfort

2009-01-01

8

Pre-Eclampsia: Is It All In The Placenta?  

PubMed Central

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

Singh, Harbindar Jeet

2009-01-01

9

Severe Hypothyroidism Causing Pre-Eclampsia-Like Syndrome  

PubMed Central

Objective. Analyzing and managing pre-eclampsia-like syndrome due to severe hypothyroidism. Methods. Presentation of a case of severe hypothyroidism due to Hashimoto's syndrome, associated with a severe early-onset preeclampsia-like syndrome, managed in our Gynecology Department. Results. Severe pre-eclampsia led to miscarriage at 24 weeks of gestational age in a 42-year-old woman, although we attempted to correct hypothyroidism with increasing doses of levothyroxine and liothyronine sodium. Conclusion. Recognizing pre-eclampsia-like syndrome caused by overt hypothyroidism from other forms of pregnancy-induced hypertension is essential for choosing the correct treatment. PMID:22937297

Inversetti, Annalisa; Serafini, Audrey; Manzoni, Marco F.; Dolcetta Capuzzo, Anna; Valsecchi, Luca; Candiani, Massimo

2012-01-01

10

Future therapies for pre-eclampsia: beyond treading water.  

PubMed

Pre-eclampsia remains a major burden of disease, accounting for approximately 50,000-70,000 maternal deaths each year worldwide. Frustratingly, the management of pre-eclampsia has remained essentially unchanged for much of the last century and focussed primarily on maternal blood pressure control to allow fetal maturation. Recent advances in the understanding of the pathogenesis of pre-eclampsia and the elucidation of distinct underlying mechanisms offer the genuine prospect of new and effective therapies that may transform outcomes for millions of women and their babies. PMID:24111787

Fenton, Christine; Hobson, Sebastian R; Wallace, Euan M; Lim, Rebecca

2014-02-01

11

Prediction and primary prevention of pre-eclampsia.  

PubMed

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

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

2011-08-01

12

Calreticulin in human pregnancy and pre-eclampsia  

Microsoft Academic Search

Pre-eclampsia is a disorder of human pregnancy that involves pregnancy-induced maternal hypertension and proteinuria. Evidence indicates that pre-eclampsia involves widespread activation of maternal endothelial cells. Calreticulin is a ubiquitously expressed, multi-functional protein that has been shown to have both pro- and anti-inflammatory effects on cultured endothelial cells in vitro and in whole animals. In order to clarify the role of

V. Y. Gu; M. H. Wong; J. L. Stevenson; K. E. Crawford; S. P. Brennecke; N. M. Gude

2008-01-01

13

Antiphospholipid syndrome and pre-eclampsia.  

PubMed

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

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

2011-03-01

14

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

15

Massive ascites in severe pre-eclampsia: a rare complication.  

PubMed

We report a rare case of massive maternal ascites complicating severe pre- eclampsia toxaemia (PET) seen in April 2013. This complication developed in association with the rise of blood pressure of 160/110 mmHg or more, worsening of proteinuria and hyperuricaemia. The onset of massive ascites caused respiratory compromise to the patient, thus necessitating immediate termination of pregnancy. PMID:24579549

Pradhan, P; Sherpa, K; Joshi, A; Pathak, S

2012-12-01

16

Cytomegalovirus infection in association with early onset pre-eclampsia  

Microsoft Academic Search

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

L Higgins; S Vause; C Tower

2010-01-01

17

Multiple Marker Second Trimester Serum Screening for Pre-eclampsia  

Microsoft Academic Search

Objective—To investigate whether an ap- propriate combination of maternal serum inhibin A, free ‚-human chorionic gona- dotropin (free ‚-hCG), unconjugated es- triol (uE3), and alpha-fetoprotein (AFP) may be an e Vective means of screening for pre-eclampsia in the second trimester of pregnancy. Setting—Women who attended an antena- tal clinic in Oxford, from whom serum samples were stored, 19 of whom

N. J. Wald; J. K. Morris

2002-01-01

18

MBL Interferes with Endovascular Trophoblast Invasion in Pre-Eclampsia  

PubMed Central

The spiral arteries undergo physiologic changes during pregnancy, and the failure of this process may lead to a spectrum of pregnancy disorders, including pre-eclampsia. Our recent data indicate that decidual endothelial cells (DECs), covering the inner side of the spiral arteries, acquire the ability to synthesize C1q, which acts as a link between endovascular trophoblast and DECs favouring the process of vascular remodelling. In this study, we have shown that sera obtained from pre-eclamptic patients strongly inhibit the interaction between extravillous trophoblast (EVT) and DECs, preventing endovascular invasion of trophoblast cells. We further demonstrated that mannose-binding lectin (MBL), one of the factor increased in pre-eclamptic patient sera, strongly inhibits the interaction of EVT with C1q interfering with the process of EVT adhesion to and migration through DECs. These data suggest that the increased level of MBL in pre-eclampsia may contribute to the failure of the endovascular invasion of trophoblast cells. PMID:22203857

Agostinis, Chiara; Bossi, Fleur; Masat, Elisa; Radillo, Oriano; Tonon, Maddalena; De Seta, Francesco; Tedesco, Francesco; Bulla, Roberta

2012-01-01

19

MBL interferes with endovascular trophoblast invasion in pre-eclampsia.  

PubMed

The spiral arteries undergo physiologic changes during pregnancy, and the failure of this process may lead to a spectrum of pregnancy disorders, including pre-eclampsia. Our recent data indicate that decidual endothelial cells (DECs), covering the inner side of the spiral arteries, acquire the ability to synthesize C1q, which acts as a link between endovascular trophoblast and DECs favouring the process of vascular remodelling. In this study, we have shown that sera obtained from pre-eclamptic patients strongly inhibit the interaction between extravillous trophoblast (EVT) and DECs, preventing endovascular invasion of trophoblast cells. We further demonstrated that mannose-binding lectin (MBL), one of the factor increased in pre-eclamptic patient sera, strongly inhibits the interaction of EVT with C1q interfering with the process of EVT adhesion to and migration through DECs. These data suggest that the increased level of MBL in pre-eclampsia may contribute to the failure of the endovascular invasion of trophoblast cells. PMID:22203857

Agostinis, Chiara; Bossi, Fleur; Masat, Elisa; Radillo, Oriano; Tonon, Maddalena; De Seta, Francesco; Tedesco, Francesco; Bulla, Roberta

2012-01-01

20

How Does the Maternal Immune System Contribute to the Development of Pre-eclampsia?  

Microsoft Academic Search

An immunological aura has hovered over the study of pre-eclampsia for many years but there has still been little progress in explaining the various ‘immune’ phenomena associated with this elusive disease. When considering the primary defect of placentation that leads to pre-eclampsia the focus should be on the intermingling of the invasive placental trophoblast cells with maternal leukocytes in the

A. Moffett; S. E. Hiby

2007-01-01

21

Plasminogen activator inhibitor-1 gene polymorphisms in pre-eclampsia.  

PubMed

Pre-eclampsia (P-EC) is a multisystem disorder of pregnancy, characterized by new-onset hypertension and proteinuria. Deregulation of the coagulation cascade and hypofibrinolysis appear to play a central role in the development of this disease. After a brief review of the genetic basis of P-EC and the role of genes encoding proteins involved in coagulation, we focus on polymorphisms of the plasminogen activator inhibitor (PAI-1) gene. The most relevant association studies between PAI-1 gene polymorphisms and P-EC are reviewed. Results indicate that the 4G/4G genotype of the -675 4G/5G polymorphism represents a weak risk factor for P-EC. PMID:21370208

D'Elia, Angela V; Fabbro, Dora; Driul, Lorenza; Barillari, Giovanni; Marchesoni, Diego; Damante, Giuseppe

2011-03-01

22

MicroRNAs: are they the missing link between hypoxia and pre-eclampsia?  

PubMed

Pre-eclampsia is a multisystem disorder that occurs in the second half of pregnancy affecting 5% of pregnancies. It remains the leading cause of maternal and perinatal mortality and morbidity worldwide. Impaired placental implantation, hypoxia, endothelial dysfunction and systemic inflammation are thought to have a role in the pathogenesis of pre-eclampsia. MicroRNAs (miRNAs) are short non-coding RNAs. They are important regulators of gene expression and have been found to affect cell development, proliferation, differentiation and function. Specific patterns of miRNAs have been detected in the placenta and there is altered miRNA expression in the placenta of patients with pre-eclampsia to but their role in the pathogenesis remains unclear. Furthermore, deregulated miRNAs have also been reported in human villous trophoblasts during hypoxic stress. One of the more consistently elevated miRNAs by hypoxia and in the placenta of patients with pre-eclampsia is miR-210. Whether such miRNAs are bystander markers of hypoxia, or are directly involved in the pathogenesis of pre-eclampsia, needs to be clarified. There is potential for miRNAs to be used as predictors, markers or therapy in pre-eclampsia. This review provides current knowledge about miRNAs, particularly hypoxia-related miRNAs and the interaction of hypoxia, miRNAs and placenta in pre-eclampsia. PMID:24354525

Li, Jordan Y Z; Yong, Tuck Y; Michael, Michael Z; Gleadle, Jonathan M

2014-02-01

23

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

24

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

25

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

E-print Network

and Vitamin D and the control group (P=0.005). In contrast, no significant difference was found in the incidence of pre-eclampsia between women on Aspirin and women on Calcium and Vitamin D. Key words: Calcium

26

Audit of management of eclampsia and severe pre-eclampsia against RCOG standards  

Microsoft Academic Search

IntroductionConfidential enquiries into maternal deaths show substandard care in a significant percentage of the deaths from eclampsia.1 The RCOG Green Top Guideline No 10(A) (2006)2 makes recommendations to standardise the approach of the management of severe pre-eclampsia\\/eclampsia to improve outcomes.AimTo evaluate the management of women presenting with severe pre-eclampsia and eclampsia to any of our 4 regional maternity units against

J Reiley; H Moss; J Gibson

2011-01-01

27

HSP70-mediated control of endothelial cell apoptosis during pre-eclampsia  

Microsoft Academic Search

ObjectivePre-eclampsia is a hypertensive disorder characterized by maternal vascular endothelial dysfunction. It is likely that this enhanced rate of endothelial cell stress is associated with the pre- and post-partum complications of both mother and fetus. Deciphering the expression pattern of factors involved in altering placental endothelial cell viability in pre-eclampsia aids in identifying components that may protect the fetus from

Ekambaram Padmini; Srinivasan Lavanya

2011-01-01

28

Reversible cerebral, hepatic and renal lesions in severe pre-eclampsia.  

PubMed

Several authors have reported the appearance of reversible hypoattenuated cerebral lesions, representing ischemia, in computed tomography scans of patients with severe pre-eclampsia. Hepatic hemorrhage and sometimes rupture have also been reported in this setting, but these problems have apparently never occurred in a patient with reversible ischemia. The authors describe a 34-year-old patient with severe pre-eclampsia in whom reversible cerebral ischemia developed in combination with hepatic and renal hematomas, which subsequently partially resolved. PMID:1733493

Peterkin, I R; Wee, R; Desmarais, R L

1992-02-01

29

Cytomegalovirus infection in association with early onset pre-eclampsia  

PubMed Central

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

Higgins, L; Vause, S; Tower, C

2010-01-01

30

Cardiovascular risk factor assessment after pre-eclampsia in primary care  

PubMed Central

Background Pre-eclampsia is associated with an increased risk of development of cardiovascular disease later in life. It is not known how general practitioners in the Netherlands care for these women after delivery with respect to cardiovascular risk factor management. Methods Review of medical records of 1196 women in four primary health care centres, who were registered from January 2000 until July 2007 with an International Classification of Primary Care (ICPC) code indicating pregnancy. Records were searched for indicators of pre-eclampsia. Of those who experienced pre-eclampsia and of a random sample of 150 women who did not, the following information on cardiovascular risk factor management after pregnancy was extracted from the records: frequency and timing of blood pressure, cholesterol and glucose measurements - and vascular diagnoses. Additionally the sensitivity and specificity of ICPC coding for pre-eclampsia were determined. Results 35 women experienced pre-eclampsia. Blood pressure was more often checked after pregnancy in these women than in controls (57.1% vs. 12.0%, p < 0.001). In 50% of the cases blood pressure was measured within 3 months after delivery with no further follow-up visit. A check for glucose and cholesterol levels was rare, and equally frequent in PE and control women. 20% of the previously normotensive women in the PE group had hypertension at one or more occasions after three months post partum versus none in the control group. The ICPC coding for pre-eclampsia showed a sensitivity of 51.4% and a specificity of 100.0%. Conclusion Despite the evidence of increased risk of future cardiovascular disease in women with a history of pre-eclampsia, follow-up of these women is insufficient and undeveloped in primary care in the Netherlands. PMID:19995418

2009-01-01

31

Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis  

PubMed Central

Objective To estimate the contributions of biological aging, historical trends, and birth cohort effects on trends in pre-eclampsia in the United States. Design Population based retrospective study. Setting National hospital discharge survey datasets, 1980-2010, United States. Participants 120 million women admitted to hospital for delivery. Main outcome measures Temporal changes in rates of mild and severe pre-eclampsia in relation to maternal age, year of delivery, and birth cohorts. Poisson regression as well as multilevel age-period-cohort models with adjustment for obesity and smoking were incorporated. Results The rate of pre-eclampsia was 3.4%. The age-period-cohort analysis showed a strong age effect, with women at the extremes of maternal age having the greatest risk of pre-eclampsia. In comparison with women delivering in 1980, those delivering in 2003 were at 6.7-fold (95% confidence interval 5.6-fold to 8.0-fold) increased risk of severe pre-eclampsia. Period effects declined after 2003. Trends for severe pre-eclampsia also showed a modest birth cohort effect, with women born in the 1970s at increased risk. Compared with women born in 1955, the risk ratio for women born in 1970 was 1.2 (95% confidence interval 1.1 to 1.3). Similar patterns were also evident for mild pre-eclampsia, although attenuated. Changes in the population prevalence of obesity and smoking were associated with period and cohort trends in pre-eclampsia but did not explain the trends. Conclusions Rates of severe pre-eclampsia have been increasing in the United States and age-period-cohort effects all contribute to these trends. Although smoking and obesity have driven these trends, changes in the diagnostic criteria may have also contributed to the age-period-cohort effects. Health consequences of rising obesity rates in the United States underscore that efforts to reduce obesity may be beneficial to maternal and perinatal health. PMID:24201165

2013-01-01

32

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

PubMed

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

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

2014-05-01

33

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

PubMed Central

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

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

2013-01-01

34

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

35

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

36

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

PubMed

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

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

2014-04-01

37

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

Microsoft Academic Search

The aim of this article is to review the accuracy of tests purported to be predictive of pre-eclampsia, a major cause of maternal and perinatal mortality and morbidity worldwide. A review of systematic reviews was done. A total of 219 studies were evaluated for the accuracy of 27 tests for predicting pre-eclampsia. Study quality assessment and data abstraction were performed

Jeltsje S. Cnossen; Gerben Ter Riet; Ben Willem Mol; Post van der J. A; Mariska M. Leeflang; Catherine A. Meads; Chris Hyde; Khalid S. Khan

2009-01-01

38

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

39

Cardiac troponin levels in pregnant women with severe pre-eclampsia.  

PubMed

Pre-eclampsia is a multisystem disorder that involves vascular endothelial dysfunction and diffuse inflammatory response. The cardiac troponin (cTn-I) levels in pre-eclampsia are controversial. The objective of this study was to compare the cTn-I levels between normal pregnant women and those with severe pre-eclampsia. A total of 78 patients who underwent caesarean section were included in the study. The patients were assigned into two groups as the severe pre-eclamptic pregnant group (study group, n = 36) and normotensive pregnant group (control group, n = 42).The cTn-I levels of all patients were measured preoperatively and postoperatively. A statistically significant difference was not determined between the preoperative and postoperative cTn-I levels (p > 0.05) between the two groups. In the present study, a relation was not determined between pre-eclampsia and increased cTn-I levels. If high cTn-I levels are determined in pre-eclamptic patients, other pathologies that may cause myocardial damage should be investigated. PMID:19757267

Aydin, C; Baloglu, A; Cetinkaya, B; Yavuzcan, A

2009-10-01

40

ST2 and IL-33 in Pregnancy and Pre-Eclampsia  

PubMed Central

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

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

2011-01-01

41

Methodological and technical issues related to the diagnosis, screening, prevention, and treatment of pre-eclampsia and eclampsia.  

PubMed

In contrast with advances made in treating or eliminating many other serious disorders, severe morbidity and mortality associated with pre-eclampsia/eclampsia remain among the leading problems that threaten safe motherhood, particularly in developing countries. This article reviews technical issues related to diagnosis, screening, prevention, and treatment of pre-eclampsia and identifies corresponding needs. The authors stress the lack of standardized definitions of pre-eclampsia and eclampsia and discuss problems in blood-pressure measurements and assessment of urinary protein. They summarize the evidence for prevention strategies and screening tests for early detection. For treatment, magnesium sulfate has been proven effective, but not widely used. The authors outline priorities for narrowing the identified gaps and emphasize the need for coordinated efforts to reduce the morbidity and mortality due to pre-eclampsia/eclampsia. They conclude that the mystery of this disease must be resolved to achieve primary prevention of it. PMID:15147852

Villar, J; Say, L; Shennan, A; Lindheimer, M; Duley, L; Conde-Agudelo, A; Merialdi, M

2004-06-01

42

Development of mHealth Applications for Pre-Eclampsia Triage.  

PubMed

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

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

2014-11-01

43

Maternal and fetal plasma adenosine deaminase, xanthine oxidase and malondialdehyde levels in pre-eclampsia.  

PubMed

The aim of this study was to evaluate maternal-fetal plasma adenosine deaminase, xanthine oxidase (ADA, XO) activity and malondialdehyde (MDA) levels and the relationship between them in pre-eclampsia. Maternal and umbilical cord whole blood samples were taken from 29 pre-eclamptic and 33 normal pregnants. The plasma ADA, XO activities as well as MDA levels were assayed by spectrophotometric methods. MDA levels and ADA, XO activities were found to be higher in maternal and fetal plasma in pre-eclamptics than in normal pregnancy. The differences were statistically significant between groups (p < 0.05). Increased maternal-fetal plasma XO and ADA activities, as a marker of immunological disorder, may be related to the pathogenesis of pre-eclampsia. In addition, increased MDA levels may be a reflection of increased oxidative stress in pre-eclamptics and their fetuses. PMID:15515122

Karabulut, Aysun Bay; Kafkasli, Ayse; Burak, Feza; Gozukara, Engin M

2005-01-01

44

Second-trimester uterine artery Doppler pulsatility index and maternal serum PP13 as markers of pre-eclampsia  

Microsoft Academic Search

Objective To evaluate whether measurement of maternal serum PP13 at 22 to 24 weeks of gestation, alone or in combination with second-trimester biochemical markers or uterine artery pulsatility measured by Doppler velocimetry, is useful in predicting those women at risk of developing pre-eclampsia. Study Design A nested case-control study of pre-eclampsia cases with controls matched for gestational age and storage

Kevin Spencer; Nicholas J. Cowans; Ilana Chefetz; Joseph Tal; Ido Kuhnreich; Hamutal Meiri

2007-01-01

45

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

PubMed Central

The aim of our study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c+, BDCA-2+) and the CD1c+ : BDCA-2+ ratio in normal pregnant women and in patients with pre-eclampsia. Fifteen women in the first, second and third trimesters of normal pregnancy, and 25 patients with pre-eclampsia were included in the study. The dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies against blood dendritic cell antigens (anti-CD1c, anti-BDCA-2) and estimated using the flow cytometric method. CD1c+ and BDCA-2+ dendritic cells were present in women during all trimesters of physiological pregnancy and in pre-eclamptic patients. It was observed that the numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, CD1c+ : BDCA-2+ ratio was higher than in the other trimesters of physiological pregnancy. All populations of dendritic cells and CD1c+ : BDCA-2+ ratio did not differ in the first and third trimesters of normal pregnancy. The percentage of BDCA-2+ dendritic cells was significantly lower in pre-eclampsia in comparison with healthy women in the third trimester of physiological pregnancy, while CD1c+ : BDCA-2+ ratio was significantly higher in pre-eclamptic patients when compared with control groups. We concluded that dendritic cells may be involved in the immune regulation during physiological pregnancy. CD1c+ and BDCA-2+ cells can influence the Th2 phenomenon which is observed during physiological pregnancy. Furthermore, it seems possible that lower BDCA-2+ cells percentage and higher CD1c+ : BDCA-2+ ratio can be associated with increased Th1-type immunity in patients with pre-eclampsia. PMID:12699426

DARMOCHWAL-KOLARZ, D; ROLINSKI, J; TABARKIEWICZ, J; LESZCZYNSKA-GORZELAK, B; BUCZKOWSKI, J; WOJAS, K; OLESZCZUK, J

2003-01-01

46

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

PubMed

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

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

2014-08-01

47

Plasma xanthine oxidase, superoxide dismutase and glutathione peroxidase activities and uric acid levels in severe and mild pre-eclampsia.  

PubMed

The aim of the present study was to measure plasma uric acid (UA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) activities and to evaluate the relationship between these parameters and the severity of pre-eclampsia. Twenty-five pre-eclamptic, 15 healthy pregnant and 15 non-pregnant women were enrolled in this study. Increased mean plasma XO activity was found to be higher in both pre-eclampsia groups than in the healthy pregnant group. Plasma UA levels were the highest in the severe pre-eclampsia group among the study groups. SOD and GSH-Px activities were significantly lower in both pre-eclampsia groups than in the healthy pregnant group (p < 0.005 and p < 0.001, respectively). Increased XO and decreased SOD and GSH-Px activities may contribute to the pathophysiological mechanisms of pre-eclampsia and increased UA may serve a protective role responding to superoxide radicals arising from increased XO activity or other sources in pre-eclampsia. PMID:15248180

Yildirim, Abdulkadir; Altinkaynak, Konca; Aksoy, Hulya; Sahin, Y Nuri; Akcay, Fatih

2004-01-01

48

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

49

Interleukin 10 gene promoter polymorphisms in women with early-onset pre-eclampsia.  

PubMed

Pre-eclampsia is one of the most serious disorders of human pregnancy and T helper type 1 (Th1)/Th2 imbalance plays a major role in its aetiology. The Th2 cytokine, interleukin (IL)-10, plays a significant role in the maintenance of pregnancy. The present study is aimed at understanding the role of IL-10 promoter polymorphisms (-1082 G/A; -592 A/C and -819 C/T) and their haplotypes in early-onset pre-eclampsia. A total of 120 patients and an equal number of women with normal pregnancy, from Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was carried out for genotyping followed by agarose gel electrophoresis. Appropriate statistical methods were applied to test for the significance of the results. It was found that the IL-10 -819 C allele (P?=?0·003) and -592 A (P?=?0·005) allele frequencies increased significantly in patients compared to controls. No significant difference was found with regard to -1082 promoter polymorphism. Haplotype analysis of the IL-10 single nucleotide polymorphisms (SNPs) revealed a significant association with ACC haplotype with a twofold increased risk in patients compared to controls. The frequencies of two common IL-10 haplotypes (GCC and ATA) did not show any significant difference. Further, the diplotype analysis revealed five genotypes: -1082A with -819C (P?=?0·0016); -1082G with -819C (P?=?0·0018); -819C with -592C (P?=?0·001); -1082A with -592C (P?=?0·032); and -1082G with -592C (P?=?0·005) associated with the disease. These findings support the concept of contribution of IL-10 gene polymorphisms in the pathogenesis of early-onset pre-eclampsia. PMID:24962617

Sowmya, S; Sri Manjari, K; Ramaiah, A; Sunitha, T; Nallari, P; Jyothy, A; Venkateshwari, A

2014-11-01

50

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

51

Circulating levels of the anti-angiogenic thrombospondin 2 are elevated in pre-eclampsia.  

PubMed

An imbalance of maternal circulating pro- and anti-angiogenic factors may play a role in the pathogenesis of pre-eclampsia. Thrombospondin 2 (TSP-2) is a protein expressed mainly by activated endothelial cells, which acts as a potent anti-angiogenic agent. Our aim was to determine whether serum TSP-2 levels are altered in pre-eclampsia. We enrolled 35 pre-eclamptic patients and 35 healthy pregnant women in the study. Thrombospondin 2 levels were determined by enzyme-linked immunosorbent assay, while soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) concentrations were determined by electrochemiluminescence immunoassay. In patients with PE, we demonstrated 1.7-fold higher TSP-2 [13.2 (9.4-18.1) vs. 7.9 (7.2-11.2) ng/ml, p<0.001], 3.8-fold higher sFlt-1 and 4.3-fold lower PlGF levels compared with the control group. There were no associations between TSP-2 and sFlt-1 or PlGF concentrations. We suggest that circulating TSP-2 levels may contribute to the pathogenesis of PE via its anti-angiogenic properties, but in a distinct way from sFlt-1 and PlGF. PMID:21682699

Stenczer, Balázs; Molvarec, Attila; Veresh, Zoltán; Gullai, Nóra; Nagy, Gyula Richárd; Walentin, Szilvia; Szijártó, János; Rigó, János

2011-11-01

52

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

PubMed Central

OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region. RESULTS: Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission. CONCLUSION: Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion. PMID:9719367

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

1998-01-01

53

How Does the maternal immune system contribute to the development of pre-eclampsia?  

PubMed

An immunological aura has hovered over the study of pre-eclampsia for many years but there has still been little progress in explaining the various 'immune' phenomena associated with this elusive disease. When considering the primary defect of placentation that leads to pre-eclampsia the focus should be on the intermingling of the invasive placental trophoblast cells with maternal leukocytes in the uterine wall. The MHC status of trophoblast cells is a crucial factor to be considered, as these molecules can act as ligands for uterine immune cells, including T cells, NK cells and myelomonocytic cells. Extravillous trophoblast cells express an unusual combination of HLA-C, HLA-G and HLA-E molecules and only one of these HLA molecules, HLA-C, shows any appreciable polymorphism. In humans, uNK cells express an array of receptors, some of which are known to bind to the HLA class I molecules expressed by extravillous trophoblast cells. HLA-C is the dominant ligand for killer immunoglobulin-like receptors (KIR) expressed by uterine NK cells that may deliver an inhibitory or activating signal. KIR haplotypes comprise two groups, A and B; these differ principally by having additional activating receptors in the B haplotype. In any pregnancy, the maternal KIR genotype could be AA (no activating KIR) or AB/BB (presence of between one and five activating KIRs). The HLA-C ligands for KIR on trophoblast cells may belong to two groups, C1 and C2 that are defined by a dimorphism at position 80 of the alpha1 domain. This maternal-fetal immunological interaction, occurring at the site of placentation, therefore involves two polymorphic gene systems, maternal KIRs and fetal HLA-C molecules. Uterine NK-cell function is thus likely to vary in each pregnancy. In pre-eclamptic pregnancies we have found that some KIR/HLA-C combinations appear unfavourable to trophoblast-cell invasion due to the overall signals that the NK cell receives. The academic excitement of this work is the realisation that this is a novel form of allorecognition based on NK cells that operates entirely differently from self/non-self discrimination used by T cells. PMID:17292469

Moffett, A; Hiby, S E

2007-04-01

54

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

PubMed

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

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

2006-01-01

55

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

Microsoft Academic Search

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

Y Wang; S. W Walsh

2001-01-01

56

Fetal cells and cell-free fetal DNA in maternal blood: new insights into pre-eclampsia  

Microsoft Academic Search

The examination of fetal cells, specifically erythroblasts, and cell-free fetal DNA from the blood of pregnant women is currently the subject of intense research with the aim of developing new risk-free methods for prenatal diagnosis. An unexpected finding made during these studies was that the traffic of fetal erythroblasts into the maternal peripheral circulation was enhanced in pre-eclampsia. Independent prospective

Sinuhe Hahn; Wolfgang Holzgreve

57

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

Microsoft Academic Search

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

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

2008-01-01

58

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

PubMed

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

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

2009-01-01

59

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

PubMed

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

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

2010-10-01

60

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

PubMed

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

Badria, Layla Francis; Amarin, Zouhair Odeh

2005-11-01

61

Lower macrophage migration inhibitory factor concentrations in maternal serum before pre-eclampsia onset.  

PubMed

Macrophage migration inhibitory factor (MIF) plays a pivotal role in pregnancy-related proinflammatory processes, such as placentation and labor. Differential MIF concentrations have been correlated with pathological events during pregnancy, such as recurrent miscarriages and severe pre-eclampsia (PE). The aim of this study was to prospectively investigate whether maternal MIF serum levels are already altered in early pregnancy before PE onset. Women (n=2,821) before 20 weeks of gestational age were recruited for a prospective study on early markers of PE. Forty-eight consecutive pregnancies that developed PE and 79 normotensive pregnancies that delivered at term were chosen. Maternal MIF serum levels were assessed by ELISA. We found significantly lower MIF serum levels in women who developed PE (4,967 ± 3,119 pg/mL) compared to controls (7,640 ± 5,519 pg/mL) (mean ± standard deviation, P<0.001). Our findings indicate that low maternal MIF serum levels in early pregnancy may contribute to abnormal placental development. PMID:24606610

Cardaropoli, Simona; Ietta, Francesca; Romagnoli, Roberta; Rolfo, Alessandro; Paulesu, Luana; Todros, Tullia

2014-07-01

62

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

PubMed

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

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

2013-05-01

63

Selenium deficiency as a model of experimental pre-eclampsia in rats.  

PubMed

Epidemiological studies and in vitro analysis demonstrate correlations between selenium status and human pre-eclampsia (PET). Selenium is an essential component in the anti-oxidant proteins glutathione peroxidase and thioredoxin reductase, which are produced in lower amounts in pre-eclamptic placenta. This study examined the effect of modulating dietary selenium content in pregnant rats. Rats were fed diets containing no selenium, 239 microg/kg selenium or 1000 microg/kg selenium, four weeks prior to and following conception. Significant pregnancy-specific increases in systolic blood pressure (116.4 +/- 5.2 mmHg vs 108 +/- 6.8 mmHg vs 111.4 +/- 4.7 mmHg) and proteinuria (9.68 +/- 2.12 microg/ml vs 5.93 +/- 1.59 microg/ml vs 4.43 +/- 0.96 microg/ml) were demonstrated in animals fed a selenium free-diet when compared with normal or high selenium diets. Placental weight and pup number were not affected by selenium deprivation, however a significant decrease in the pup weight was evident. Selenium deprivation caused dose-dependent decreases in liver glutathione peroxidase (28.55 +/- 3.82 mmoles/min/mg vs 34.68 +/- 8.64 mmoles/min/mg) and thioredoxin reductase (2.37 +/- 1.25 U/mg vs 6.68 +/- 1.82 U/mg) activity, whereas superoxide dismutase activity remained constant. Placental activity of these enzymes also decreased leading to oxidative stress as measured by increased lipid peroxides (17.92 +/- 1.78 micromoles/mg vs 8.30 +/- 5.52 micromoles/mg) and protein carbonyls in tissue extracts from selenium-free animals. These results suggest that selenium deficiency in pregnant rats leads to symptoms similar to those seen in human PET and may provide an experimental model for studying this complex disease. PMID:15509710

Vanderlelie, J; Venardos, K; Perkins, A V

2004-11-01

64

Circulating ficolin-2 and ficolin-3 in normal pregnancy and pre-eclampsia  

PubMed Central

Ficolins are soluble molecules of the innate immune system that recognize carbohydrate molecules on microbial pathogens, apoptotic and necrotic cells. They act through two distinct routes: initiating the lectin pathway of complement activation and mediating a primitive opsonophagocytosis. In this study, we measured plasma levels of ficolin-2 and ficolin-3 in 60 pre-eclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by enzyme-linked immunosorbent assay (ELISA). Circulating levels of complement activation products (C4d, C3a, SC5b9), angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and markers of endothelial activation (von Willebrand factor antigen), endothelial injury (fibronectin) and trophoblast debris (cell-free fetal DNA) were also determined. Plasma levels of ficolin-2 were significantly lower in healthy pregnant than in healthy non-pregnant women, while ficolin-3 levels did not differ significantly between the two groups. Furthermore, pre-eclamptic patients had significantly lower ficolin-2 and ficolin-3 concentrations than healthy non-pregnant and pregnant women. In the pre-eclamptic group, plasma ficolin-2 levels showed a significant positive correlation with serum placental growth factor (PlGF) concentrations and significant inverse correlations with serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1), blood urea nitrogen and creatinine, serum lactate dehydrogenase activities, as well as with plasma VWF:antigen, fibronectin and cell-free fetal DNA concentrations. In conclusion, circulating levels of ficolin-2 are decreased in the third trimester of normal pregnancy. There is a further decrease in plasma ficolin-2 concentrations in pre-eclampsia, which might contribute to the development of the maternal syndrome of the disease through impaired removal of the trophoblast-derived material released into the maternal circulation by the hypoxic and oxidatively stressed pre-eclamptic placenta. PMID:22670778

Halmos, A; Rigo Jr, J; Szijarto, J; Fust, G; Prohaszka, Z; Molvarec, A

2012-01-01

65

Circulating ficolin-2 and ficolin-3 in normal pregnancy and pre-eclampsia.  

PubMed

Ficolins are soluble molecules of the innate immune system that recognize carbohydrate molecules on microbial pathogens, apoptotic and necrotic cells. They act through two distinct routes: initiating the lectin pathway of complement activation and mediating a primitive opsonophagocytosis. In this study, we measured plasma levels of ficolin-2 and ficolin-3 in 60 pre-eclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by enzyme-linked immunosorbent assay (ELISA). Circulating levels of complement activation products (C4d, C3a, SC5b9), angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and markers of endothelial activation (von Willebrand factor antigen), endothelial injury (fibronectin) and trophoblast debris (cell-free fetal DNA) were also determined. Plasma levels of ficolin-2 were significantly lower in healthy pregnant than in healthy non-pregnant women, while ficolin-3 levels did not differ significantly between the two groups. Furthermore, pre-eclamptic patients had significantly lower ficolin-2 and ficolin-3 concentrations than healthy non-pregnant and pregnant women. In the pre-eclamptic group, plasma ficolin-2 levels showed a significant positive correlation with serum placental growth factor (PlGF) concentrations and significant inverse correlations with serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1), blood urea nitrogen and creatinine, serum lactate dehydrogenase activities, as well as with plasma VWF:antigen, fibronectin and cell-free fetal DNA concentrations. In conclusion, circulating levels of ficolin-2 are decreased in the third trimester of normal pregnancy. There is a further decrease in plasma ficolin-2 concentrations in pre-eclampsia, which might contribute to the development of the maternal syndrome of the disease through impaired removal of the trophoblast-derived material released into the maternal circulation by the hypoxic and oxidatively stressed pre-eclamptic placenta. PMID:22670778

Halmos, A; Rigó, J; Szijártó, J; Füst, G; Prohászka, Z; Molvarec, A

2012-07-01

66

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

PubMed Central

Objectives We assessed the evidence relating pre-term delivery (PTD), low birthweight, small for gestational age (SGA), pre-eclampsia and gestational hypertension to five occupational exposures (working hours, shift work, lifting, standing and physical workload). We conducted a systematic search in MEDLINE and EMBASE (1966–2011), updating a previous search with a further six years of observations. Methods As before, combinations of keywords and MeSH terms were used. Each relevant paper was assessed for completeness of reporting and potential for important bias or confounding, and its effect estimates abstracted. Where similar definitions of exposure and outcome existed we calculated pooled estimates of relative risk in meta-analysis. Results Analysis was based on 86 reports (32 cohort investigations, 57 with usable data on PTD, 54 on birthweight and 11 on pre-eclampsia/gestational hypertension); 33 reports were new to this review. For PTD, findings across a substantial evidence base were generally consistent, effectively ruling out large effects (e.g. RR>1.2). Larger and higher quality studies were less positive, while meta-estimates of risk were smaller than previously and best estimates pointed to modest or null effects (RR 1.04 to 1.18). For SGA, the position was similar but meta-estimates were even closer to the null (eight of nine RRs ? 1.07). For pre-eclampsia/gestational hypertension the evidence base remains insufficient. Conclusions The balance of evidence is against large effects for the associations investigated. As the evidence base has grown, estimates of risk in relation to these outcomes have become smaller. PMID:23343859

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

2013-01-01

67

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

PubMed Central

Background Occupational activities are suspected of having an adverse impact on outcomes of pregnancy. Aim To assess the evidence relating three major adverse outcomes (preterm delivery, low birthweight (LBW) and pre?eclampsia/gestational hypertension) to five common occupational exposures (prolonged working hours, shift work, lifting, standing and heavy physical workload). Methods A systematic search of Medline and Embase (1966–December 2005) using combinations of keywords and medical subject heading terms was conducted. For each relevant paper, standard details were abstracted that were then used to summarise the design features of studies, to rate their methodological quality (completeness of reporting and potential for important bias or confounding) and to provide estimates of effect. For studies with similar definitions of exposure and outcome, pooled estimates of relative risk (RR) in meta?analysis were calculated. Results 53 reports were identified—35 on preterm delivery, 34 on birth weight and 9 on pre?eclampsia or gestational hypertension. These included 21 cohort investigations. For pre?term delivery, extensive evidence relating to each of the exposures of interest was found. Findings were generally consistent and tended to rule out a more than moderate effect size (RR >1.4). The larger and most complete studies were less positive, and pooled estimates of risk pointed to only modest or null effects. For small?for?gestational age, the position was similar, but the evidence base was more limited. For pre?eclampsia and gestational hypertension, it was too small to allow firm conclusions. Conclusions The balance of evidence is not sufficiently compelling to justify mandatory restrictions on any of the activities considered in this review. However, given some uncertainties in the evidence base and the apparent absence of important beneficial effects, it may be prudent to advise against long working hours, prolonged standing and heavy physical work, particularly late in pregnancy. Our review identifies several priorities for future investigation. PMID:17095552

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

2007-01-01

68

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

PubMed Central

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

2013-01-01

69

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

PubMed Central

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

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

2014-01-01

70

Magpie Trial in the UK: methods and additional data for women and children at 2 years following pregnancy complicated by pre-eclampsia  

Microsoft Academic Search

BACKGROUND: The Magpie Trial, a randomised trial comparing magnesium sulphate with placebo for women with pre-eclampsia. This paper describes methods used for follow up in the UK, and presents additional data collected. METHODS: In the UK 774 women and their 827 children were included; excluded were women discharged without a surviving child and families who opted out. General practitioners were

Patsy Spark; Nina Armstrong; Lelia Duley

2009-01-01

71

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

PubMed Central

Background Hypertensive disorders in pregnancy are among the leading causes of maternal and perinatal death in low-income countries, but the aetiology remains unclear. We investigated the relationship between salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in a coastal community. Methods A population-based case-control study was conducted in Dacope, Bangladesh among 202 pregnant women with (pre)eclampsia or gestational hypertension, enrolled from the community served by the Upazilla Health Complex, Dacope and 1,006 matched controls from the same area. Epidemiological and clinical data were obtained from all participants. Urinary sodium and sodium levels in drinking water were measured. Logistic regression was used to calculate odds ratios, and 95% confidence intervals. Findings Drinking water sources had exceptionally high sodium levels (mean 516.6 mg/L, S.D 524.2). Women consuming tube-well (groundwater) were at a higher disease risk than rainwater users (p<0.001). Adjusted risks for (pre)eclampsia and gestational hypertension considered together increased in a dose-response manner for increasing sodium concentrations (300.01–600 mg/L, 600.1–900 mg/L, >900.01 mg/L, compared to <300 mg/L) in drinking water (ORs 3.30 [95% CI 2.00–5.51], 4.40 [2.70–7.25] and 5.48 [3.30–9.11] (p-trend<0.001). Significant associations were seen for both (pre)eclampsia and gestational hypertension separately. Interpretation Salinity in drinking water is associated with increased risk of (pre)eclampsia and gestational hypertension in this population. Given that coastal populations in countries such as Bangladesh are confronted with high salinity exposure, which is predicted to further increase as a result of sea level rise and other environmental influences, it is imperative to develop and evaluate affordable approaches to providing water with low salt content. PMID:25268785

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

2014-01-01

72

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

PubMed Central

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

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

2013-01-01

73

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

74

The Effect of Labour and Placental Separation on the Shedding of Syncytiotrophoblast Microparticles, Cell-free DNA and mRNA in Normal Pregnancy and Pre-eclampsia  

Microsoft Academic Search

The clinical features of the maternal syndrome of pre-eclampsia can be explained by generalised maternal endothelial cell dysfunction, which is a part of a more global maternal systemic inflammatory response. There is growing evidence that these effects are associated with the shedding of cellular debris, including syncytiotrophoblast microparticles (STBM), cell-free DNA and mRNA, from the surface of the placenta (syncytiotrophoblast)

A. Reddy; X. Y. Zhong; C. Rusterholz; S. Hahn; W. Holzgreve; C. W. G. Redman; I. L. Sargent

2008-01-01

75

The C242T-polymorphism of the NADPH\\/NADH oxidase gene p22phox subunit is not associated with pre-eclampsia  

Microsoft Academic Search

Pre-eclampsia is a pregnancy-related multisystem disorder characterised by elevation of blood pressure and proteinuria, in which oxidative stress may play an important role. Blood pressure is partly controlled by O?2 production by NADPH\\/NADH oxidase and recently it was shown that a C242T substitution in the p22phox gene was associated with coronary artery disease, in which elevated blood pressure and oxidative

M T M Raijmakers; E M Roes; E A P Steegers; W H M Peters; WHM Peters

2002-01-01

76

Parallel decrease in arterial distensibility and in endothelium-dependent dilatation in young women with a history of pre-eclampsia.  

PubMed

Pre-eclampsia not only complicates 5 to 8% of pregnancies but also increases the risk of maternal cardiovascular disease and mortality later in life. We analyzed three different aspects of arterial function (pulse wave velocity, augmentation index, and flow-mediated dilatation), in 55 nonpregnant, normotensive women (18-33 years old) according to their gestational history: 15 nulliparous, 20 with a previous normotensive, and 20 formerly pre-eclamptic pregnancy. Former pre-eclamptic women showed a significantly higher augmentation index and pulse wave velocity (P < 0.001 and P < 0.05, respectively) and lower flow-mediated dilatation (p = 0.01) compared to control groups. In contrast, sublingual nitroglycerine elicited a comparable vasodilatory response in the three groups. The augmentation index correlated significantly with pulse wave velocity and flow-mediated dilatation (R = 0.28 and R = -0.32, respectively, P < 0.05 for both). No significant correlations were observed between augmentation index or flow-mediated dilatation with age, body mass index (BMI), brachial blood pressure, heart rate, or metabolic parameters (plasma cholesterol, glucose, insulin, or insulin resistance). Birth weight maintained a significantly inverse correlation with the augmentation index (R = -0.51, p < 0.002) but not with flow-mediated dilatation. Our findings revealed a parallel decrease in arterial distensibility and endothelium-dependent dilatation in women with a history of pre-eclampsia compared to nulliparous women and women with a previous normal pregnancy. A high augmentation index was the most consistent alteration associated with a history of pre-eclampsia. The study supports the current view that the generalized arterial dysfunction associated with pre-eclampsia persists subclinically after delivery. PMID:19886852

Pàez, Olga; Alfie, José; Gorosito, Marta; Puleio, Pablo; de Maria, Marcelo; Prieto, Noemì; Majul, Claudio

2009-10-01

77

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; Makikallio, 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; Lahdesmaki, Aija; Mehtala, Susanna; Salmen, Christina

2013-01-01

78

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

PubMed Central

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

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

1993-01-01

79

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

PubMed Central

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

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

2014-01-01

80

Overexpression of calreticulin in pre-eclamptic placentas: effect on apoptosis, cell invasion and severity of pre-eclampsia.  

PubMed

Endoplasmic reticulum (ER) stress has recently been identified as an important process involved in the pathology of pre-eclampsia (PE). Calreticulin (CRT) is an important ER resident protein which participates in the regulation of intracellular Ca(2+) homeostasis, cell adhesion, and cell apoptosis. In order to clarify the role of this protein in normal human pregnancy and in PE, this study has examined the expression of CRT in pre-eclamptic placenta compared with control placenta. The expression of CRT mRNA and protein was elevated in the pre-eclamptic placentas in comparison with control placentas. Furthermore, the expression level was related to the severity of symptoms experienced by PE patients. Therefore, this study aimed to identify the biological characteristics of the CRT gene in trophoblast cells. A CRT-expressing vector was transfected into the JEG-3 human choriocarcinoma cell line. Investigations showed that both proliferation and invasion were inhibited and apoptosis was promoted by CRT expression in JEG-3 cells. These data suggest that augmentation of CRT in the placenta may induce cell apoptosis and impair the invasion of extravillous trophoblast cells, thus leading to shallow placentation in PE. PMID:22415851

Shi, Zhonghua; Hou, Wenwen; Hua, Xiangdong; Zhang, Xiang; Liu, Xiaomei; Wang, Xin; Wang, Xiaoqing

2012-06-01

81

Women Born Preterm or with Inappropriate Weight for Gestational Age Are at Risk of Subsequent Gestational Diabetes and Pre-Eclampsia  

PubMed Central

Introduction Low birthweight, which can be caused by inappropriate intrauterine growth or prematurity, is associated with development of gestational diabetes mellitus (GDM) as well as pre-eclampsia later in life, but the relative effects of prematurity and inappropriate intrauterine growth remain uncertain. Methods Through nation-wide registries we identified all Danish mothers in the years 1989–2007. Two separate cohorts consisting mothers born 1974–1977 (n?=?84219) and 1978–1981 (n?=?32376) were studied, due to different methods of registering birthweight and gestational age in the two periods. Data was linked with information on GDM, pre-eclampsia and education. Results In a multivariate logistic regression model the odds of developing GDM was increased by 5–7% for each week the mother was born before term (p?=?0.018 for 1974–1977, p?=?0.048 for 1978–1981), while the odds were increased by 13–17% for each standard deviation (SD) reduction in birthweight for gestational age for those who were small or normal for gestational age (p<0.0001 and p?=?0.035) and increased by 118–122% for each SD increase above the normal range (p<0.0001 and p?=?0.024). The odds of pre-eclampsia was increased by 3–5% for each week the mother was born before term (p?=?0.064 and p?=?0.04), while the odds were increased 11–12% for each SD reduction in birthweight for gestational age (p<0.0001 and p?=?0.0002). Conclusion In this cohort of young Danish mothers, being born premature or with increasingly low birthweight for gestational age was associated with an increased risk of GDM and pre-eclampsia in adulthood, while increasingly high birthweight for gestational age was associated with an increased risk of GDM and a decreased risk of pre-eclampsia. Inappropriate weight for gestational age was a more important risk factor than prematurity. PMID:22479500

a Rogvi, Rasmus; Forman, Julie Lyng; Damm, Peter; Greisen, Gorm

2012-01-01

82

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

PubMed Central

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

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

2013-01-01

83

Increased endoplasmic reticulum stress in decidual tissue from pregnancies complicated by fetal growth restriction with and without pre-eclampsia  

PubMed Central

Objectives Endoplasmic reticulum (ER) stress has been implicated in both pre-eclampsia (PE) and fetal growth restriction (FGR), and is characterised by activation of three signalling branches: 1) PERK-pEIF2?, 2) ATF6 and 3) splicing of XBP1(U) into XBP1(S). To evaluate the contribution of ER stress in the pathogenesis of PE relative to FGR, we compared levels of ER stress markers in decidual tissue from pregnancies complicated by PE and/or FGR. Study design Whole-genome transcriptional profiling was performed on decidual tissue from women with PE (n = 13), FGR (n = 9), PE+FGR (n = 24) and controls (n = 58), and used for pathway- and targeted transcriptional analyses of ER stress markers. The expression and cellular localisation of ER stress markers was assesses by Western blot and immunofluorescence analyses. Results Increased ER stress was observed in FGR and PE+FGR, including both the PERK-pEIF2? and ATF6 signalling branches, whereas ER stress was less evident in isolated PE. However, these cases demonstrated elevated levels of XBP1(U) protein. ATF6 and XBP1 immunoreactivity was detected in most (> 80%) extravillous trophoblasts, decidual cells and macrophages. No difference in the proportion of immunopositive cells or staining pattern was observed between study groups. Conclusions Increased PERK-pEIF2? and ATF6 signalling have been associated with decreased cellular proliferation and may contribute to the impaired placental growth characterising pregnancies with FGR and PE+FGR. XBP1(U) has been proposed as a negative regulator of ER stress, and increased levels in PE may reflect a protective mechanism against the detrimental effects of ER stress. PMID:21907405

Lian, I.A.; L?set, M.; Mundal, S.B.; Fenstad, M.H.; Johnson, M.P.; Eide, I.P.; Bj?rge, L.; Freed, K.A.; Moses, E.K.; Austgulen, R.

2011-01-01

84

Health System Barriers to Access and Use of Magnesium Sulfate for Women with Severe Pre-Eclampsia and Eclampsia in Pakistan: Evidence for Policy and Practice  

PubMed Central

Severe pre-eclampsia and eclampsia are rare but serious complications of pregnancy that threaten the lives of mothers during childbirth. Evidence supports the use of magnesium sulfate (MgSO4) as the first line treatment option for severe pre-eclampsia and eclampsia. Eclampsia is the third major cause of maternal mortality in Pakistan. As in many other Low- and Middle-Income Countries (LMIC), it is suspected that MgSO4 is critically under-utilized in the country. There is however a lack of information on context-specific health system barriers that prevent optimal use of this life-saving medicine in Pakistan. Combining quantitative and qualitative methods, namely policy document review, key informant interviews, focus group discussions and direct observation at health facility, we explored context-specific health system barriers and enablers that affect access and use of MgSO4 for severe pre-eclampsia and eclampsia in Pakistan. Our study finds that while international recommendations on MgSO4 have been adequately translated in national policies in Pakistan, the gap remains in implementation of national policies into practice. Barriers to access to and effective use of MgSO4 occur at health facility level where the medicine was not available and health staff was reluctant to use it. Low price of the medicine and the small market related to its narrow indications acted as disincentives for effective marketing. Results of our survey were further discussed in a multi-stakeholder round-table meeting and an action plan for increasing access to this life-saving medicine was identified. PMID:23555626

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

2013-01-01

85

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

86

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

PubMed Central

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

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

2009-01-01

87

Circulating angiogenic factors determined by electrochemiluminescence immunoassay in relation to the clinical features and laboratory parameters in women with pre-eclampsia.  

PubMed

The purpose of this study was to determine whether increased serum soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased placental growth factor (PlGF) levels in pre-eclampsia are related to the clinical features and laboratory parameters of the patients, including markers of inflammation, endothelial activation and injury, oxidative stress and trophoblast debris. A total of 54 pre-eclamptic patients, 58 healthy pregnant and 52 healthy non-pregnant women were involved in this case-control study. Serum sFlt-1 and PlGF levels were measured by electrochemiluminescence immunoassay. Serum levels of sFlt-1 and PlGF were significantly higher in pre-eclamptic patients and healthy pregnant women than in healthy non-pregnant women. In addition, pre-eclamptic patients had significantly higher sFlt-1 levels and significantly lower PlGF concentrations compared with healthy pregnant women. According to the subgroup analyses, sFlt-1 levels were significantly higher in severely pre-eclamptic patients than in those with mild pre-eclampsia, whereas pre-eclamptic patients with fetal growth restriction or preterm onset of the disease had significantly lower PlGF concentrations compared with those without intrauterine growth restriction or with a disease onset at term. In the pre-eclamptic group, there were significant positive correlations between serum sFlt-1 levels and systolic and diastolic blood pressure, serum levels of blood urea nitrogen and creatinine, as well as plasma levels of von Willebrand factor antigen, fibronectin and cell-free fetal DNA. Furthermore, serum PlGF concentrations of pre-eclamptic patients showed significant positive correlations with gestational age at disease onset and delivery, as well as with fetal birth weight, and significant inverse correlations with levels of blood urea nitrogen, creatinine and fibronectin. In conclusion, increased serum sFlt-1 and decreased PlGF levels are associated with blood pressure, renal and endothelial dysfunction, trophoblast deportation, as well as with a shorter duration of pregnancy, fetal growth restriction, the severity and preterm onset of the disease in pre-eclampsia. These findings indicate the central role of an angiogenic imbalance in the pathogenesis of this pregnancy-specific disorder. PMID:20535121

Molvarec, Attila; Szarka, András; Walentin, Szilvia; Szucs, Endre; Nagy, Bálint; Rigó, János

2010-09-01

88

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

Microsoft Academic Search

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

2004-01-01

89

The use of angiogenic and antiangiogenic factors in the differential diagnosis of pre-eclampsia, antiphospholipid syndrome nephropathy and lupus nephritis.  

PubMed

Pre-eclampsia (PE) is a major cause of maternal mortality and morbidity, perinatal deaths, preterm birth and intrauterine growth restriction. Differential diagnosis with antiphospholipid syndrome (APS) nephropathy and systemic lupus erythematosus (SLE) nephritis during pregnancy is difficult, if not sometimes impossible, as all three diseases may present hypertension and proteinuria. Improvement in diagnosis of PE has also offered new paths for differential diagnosis with other conditions and the analysis of angiogenic (vascular endothelial growth factor, placental growth factor) and antiangiogenic factors (serum soluble fms-like tyrosine kinase 1, soluble endoglin) is promising for differentiation between PE, APS nephropathy and SLE nephritis. This article reviews published studies about those factors in non-pregnant and pregnant patients with APS and SLE, comparing with patterns described in PE. PMID:25228732

de Jesus, G R; de Jesus, N R; Levy, R A; Klumb, E M

2014-10-01

90

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

91

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

PubMed

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

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

2014-10-01

92

Analysis of Polymorphisms in Interleukin-10, Interleukin-6, and Interleukin-1 Receptor Antagonist in Mexican-Mestizo Women with Pre-eclampsia  

PubMed Central

Due to the fact that studies seeking associations of polymorphisms in regulatory regions of cytokine genes with pre-eclampsia (PE) have not always been consistent in different population analyses, the aim of this study was to investigate the possible association between rs1800896 of interleukin-10 (IL-10), rs1800795 of interleukin-6 (IL-6), and the variable number of tandem repeats (VNTR) in intron 2 of interleukin-1 receptor antagonist (IL-1Ra), as well as gene–gene interactions between these three polymorphisms with the presence of PE in Mexican-Mestizo women and one Amerindian population from México (Maya). A case–control study was performed where 411 pre-eclamptic cases and 613 controls were genotyped. For the rs1800896 of IL-10 and rs1800795 of IL-6, we used real-time polymerase chain reaction (PCR) allelic discrimination and for the VNTR of IL-1Ra, PCR. Allele frequency differences were assessed by Chi-squared test; logistic regression was used to test for associations; a gene–gene interaction was conducted. Genotypic and allelic distribution of the polymorphisms was similar in our population. The estimated of the gene–gene interaction between the polymorphisms did not differ significantly. However, we observed important differences in the distribution of the alleles and genotypes of the three polymorphisms analyzed between Mestiza-Mexicanas and Maya-Mestizo women. In conclusion, we did not find an association between polymorphisms in IL-10, IL-6, and IL-1Ra and PE in Mexican-Mestizo and Maya-Mestizo women. To our knowledge, this is the first time that these three polymorphisms were analyzed together with gene–gene interaction in women with PE. PMID:23013217

Valencia Villalvazo, Elith Yazmin; Canto-Cetina, Thelma; Romero Arauz, Juan Fernando; Coral-Vazquez, Ramon Mauricio; Canizales-Quinteros, Samuel; Coronel, Agustin; Carlos Falcon, Juan; Hernandez Rivera, Jaime; Ibarra, Roberto; Polanco Reyes, Lucila

2012-01-01

93

In-Vitro Study of the Effect of Anti-Hypertensive Drugs on Placental Hormones and Angiogenic Proteins Synthesis in Pre-Eclampsia  

PubMed Central

Introduction Antihypertensive drugs lower the maternal blood pressure in pre-eclampsia (PE) by direct or central vasodilatory mechanisms but little is known about the direct effects of these drugs on placental functions. Objective The aim of our study is to evaluate the effect of labetolol, hydralazine, ?-methyldopa and pravastatin on the synthesis of placental hormonal and angiogenic proteins know to be altered in PE. Design Placental villous explants from late onset PE (n?=?3) and normotensive controls (n?=?6) were cultured for 3 days at 10 and 20% oxygen (O2) with variable doses anti-hypertensive drugs. The levels of activin A, inhibin A, human Chorionic Gonadotrophin (hCG), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in explant culture media on day 1, 2 and 3 using standard immunoassays. Data at day 1 and day 3 were compared. Results Spontaneous secretion of sEndoglin and sFlt-1 were higher (p<0.05) in villous explants from PE pregnancies compared to controls. There was a significant time dependant decrease in the secretion of sFlt-1 and sEndoglin in PE cases, which was seen only for sFlt-1 in controls. In both PE cases and controls the placental protein secretions were not affected by varying doses of anti-hypertensive drugs or the different O2 concentration cultures, except for Activin, A which was significantly (p<0.05) higher in controls at 10% O2. Interpretation Our findings suggest that the changes previously observed in maternal serum hormones and angiogenic proteins level after anti-hypertensive treatment in PE could be due to a systemic effect of the drugs on maternal blood pressure and circulation rather than a direct effect of these drugs on placental biosynthesis and/or secretion. PMID:25251016

Gangooly, Subrata; Jauniaux, Eric

2014-01-01

94

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.

Buke, Bar?s; Topcu, Hasan Onur; Engin-Ustun, Yaprak; Dan?sman, Nuri

2014-01-01

95

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

PubMed Central

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

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

2014-01-01

96

Gene expression profiling of placentae from women with early- and late-onset pre-eclampsia: down-regulation of the angiogenesis-related genes ACVRL1 and EGFL7 in early-onset disease  

PubMed Central

The underlying mechanisms behind the obstetric condition pre-eclampsia (PE) are still unclear. Manifestation of PE is heterogeneous and it has therefore been proposed to be a syndrome with different causes rather than one disease with a specific aetiology. Recently, we showed differences in circulating angiogenic factors between two subgroups—early- and late-onset PE. To further elucidate the differences between the two, we investigated placental gene expression profiles. Whole genome microarray technology and bioinformatic analysis were used to evaluate gene expression profiles in placentae from early- (24–32 gestational weeks, n = 8) and late-onset (36–41 gestational weeks, n = 7) PE. The results were verified by using quantitative real-time (qRT)–PCR. We found significant differences in the expression of 196 genes in early- compared with late-onset PE, 45 of these genes showing a fold change above 2. Bioinformatic analysis revealed alterations in angiogenesis and regulation of cell motility. Two angiogenesis-associated transcripts (Egfl7 and Acvrl1) showed lower expression in early-onset PE versus late-onset PE (P = 0.037 and P = 0.003) and versus gestational age-matched controls (P = 0.007 and P = 0.011). We conclude that angiogenesis-associated genes are regulated in a different manner in the two subgroups, and that the gene expression profiles of early- and late-onset PE diverge, supporting the hypothesis of early- and late-onset PE being at least partly two separate entities. PMID:22013081

Junus, K.; Centlow, M.; Wikstrom, A.-K.; Larsson, I.; Hansson, S.R.; Olovsson, M.

2012-01-01

97

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

PubMed

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

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

2013-03-01

98

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

PubMed

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

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

2014-10-01

99

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

100

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

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

2002-01-01

101

A case of probable labetalol induced hyperkalaemia in pre-eclampsia.  

PubMed

Case description Hyperkalemia can cause altered cardiac electrical conduction resulting in death. We describe a case of a 23-year old pregnant patient who presented with severe epigastric pain and vomiting. She was severely pre- eclamptic and received initial treatment with intravenous labetalol and decision was taken to deliver. She quickly became hyperkalaemic (serum potassium level 6.4 mmol/L) and labetalol was discontinued and intravenous hydralazine commenced. Post-surgery, her potassium levels were normal but due to rapidly rising blood pressure labetalol was recommenced, resulting in elevated potassium levels. Labetolol was discontinued, hydralazine prescribed, and potassium levels normalised. The adverse reaction was classified as 'probably' due to labetolol using the Naranjo Adverse Drug Reaction scale. Conclusion This is the first reported case of labetolol induced hyperkalaemia in pregnancy, with life threatening consequences and hence all health professionals should be alert to this potential effect. PMID:25370900

Thomas, Binny; Abdul Rouf, P V; Kassem, Wessam El; Hail, Moza Al; Stewart, Derek; Tharannum, Asma; Ahmed, Afif; Saadi, Muna Al

2014-12-01

102

Downregulation of Placental Syncytin Expression and Abnormal Protein Localization in Pre-eclampsia  

Microsoft Academic Search

Development of placentation and successful pregnancy depend on co-ordinated interactions between the maternal decidua and myometrium, and the invasive properties of the fetal trophoblast. Syncytin, a protein encoded by the envelope gene of a recently identified human endogenous defective retrovirus, HERV-W, is highly expressed in placental tissue. Previously, we have shown that the major site of syncytin expression is the

X. Lee; J. C. Keith; N. Stumm; I. Moutsatsos; J. M. McCoy; C. P. Crum; D. Genest; D. Chin; C. Ehrenfels; R. Pijnenborg; F. A. van Assche; S. Mi

2001-01-01

103

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

Microsoft Academic Search

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

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

2011-01-01

104

Elevated glucocorticoid metabolism in placental tissue from first trimester pregnancies at increased risk of pre-eclampsia  

Microsoft Academic Search

BackgroundThe local actions of glucocorticoids in the placenta can be modulated by 11?-hydroxysteroid dehydrogenase (11?HSD) enzymes, which catalyse inter-conversion of cortisol with its inert metabolite, cortisone, and are known to be expressed in the term placenta and decidua. However, the expression and activity of these enzymes have not been well characterised in the first trimester placenta. The aim of this

S. Mukherjee; J. L. James; B. Thilaganathan; G. St. J. Whitley; A. E. Michael; J. E. Cartwright

2011-01-01

105

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

Microsoft Academic Search

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

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

2001-01-01

106

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

107

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

Microsoft Academic Search

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

Levente Lázár; Bálint Nagy; Attila Morvarec; János Rigó

108

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

PubMed Central

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

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

2013-01-01

109

Fetal growth retardation and second trimester maternal serum human chorionic gonadotrophin levels  

Microsoft Academic Search

Second trimester maternal serum human chorionic gonadotrophin (hCG) levels in women who remained normotensive but delivered an unexplained growth retarded infant were compared with those from a control group and a group of women who developed pre-eclampsia in a retrospective observational study. Our hypothesis was that the similar placental pathological changes shared by unexplained normotensive IUGR and pre-eclampsia would be

M. J. M. Luckas; R. Sandland; J. Hawe; J. P. Neilson; I. R. McFadyen; J. W. Meekins

1998-01-01

110

Hypertension in pregnancy.  

PubMed

Formal assessment of the risk of pre-eclampsia should be made early in pregnancy and antenatal care planned accordingly. Recommendations will emerge by the end of this year in a consensus statement (PRECOG guidelines) prepared by clinicians and the lay organisation Action on Pre-eclampsia (APEC) www.apec.org.uk. Some hospitals complement clinical risk assessment with Doppler screening of uterine artery waveforms in mid-pregnancy. Severe pre-eclampsia often takes an explosive course, evolving over a period of hours. Recognition may, therefore, not be amenable to intermittent blood pressure recording and urine testing, but requires women reporting relevant symptoms and GPs being sensitive to the possible significance of complaints such as vomiting and epigastric pain. Severe hypertension demands urgent antihypertensive treatment in hospital. Magnesium sulphate now has an accepted role in the prevention of eclampsia. Possible prevention of pre-eclampsia by antioxidant therapy is the subject of a clinical trial. Low-dose aspirin has a modest but beneficial effect in high-risk women. Delivery remains the definitive treatment for pre-eclampsia, but there may be initial deterioration after birth, especially in the HELLP syndrome. PMID:15491015

Meher, Shireen; Neilson, Jim

2004-10-01

111

Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy  

PubMed Central

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

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

2012-01-01

112

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

113

Trophoblast oxidative stress, antioxidants and pregnancy outcome--a review.  

PubMed

Placental oxidative stress has been implicated in pre-eclampsia and miscarriage. The review briefly summarizes the definition of oxidative stress, methods of estimation and likely sources in the placenta. Experimental evidence favouring a role for trophoblast oxidative stress in pre-eclampsia includes reports of lipid peroxidation and deficiencies in antioxidant defences. The potential sources of free radical generation include enhanced enzymatic synthesis of superoxide by xanthine oxidase and NAD(P)H oxidase. Studies employing immunohistochemical markers of oxidative stress also implicate free radical induced damage in placentae from women with early pregnancy loss. The overwhelming evidence for oxidative stress in the placenta and the maternal circulation in pre-eclampsia has led to the suggestion that antioxidant prophylaxis may prevent oxidant stress and so ameliorate or prevent the disease. Several clinical trials currently underway will not only determine whether antioxidants are of use in pre-eclampsia prevention but also provide an ideal opportunity to investigate the aetiology and consequences of trophoblast oxidative stress. PMID:15033311

Poston, L; Raijmakers, M T M

2004-04-01

114

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

Microsoft Academic Search

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

M Akhtar; R Tildesley; H Cliffe; J Topping

2010-01-01

115

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

Microsoft Academic Search

Extravillous trophoblasts are major participants in placental development and remodelling of spiral arteries. Trophoblast invasion is regulated by maternal immune cells, and abnormal leucocyte subpopulation composition has been reported in implantation failure. In pre-eclampsia (PE), with or without foetal growth restriction (FGR), superficial trophoblast invasion and insufficient remodelling of spiral arteries are common findings. In the present study, we have

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

2006-01-01

116

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

? ( ) ( ) Were pregnancy, labor & delivery complication-free (examples: pre- eclampsia, high blood pressure? ( ) ( ) Was your baby discharged home without problems, such as jaundice? Was the pregnancy free of alcohol, smoking, and other drugs? ( ) ( ) Review of Nutrition Yes No Is your baby being breastfed exclusively

Borenstein, Elhanan

117

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

PubMed

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

Talaulikar, Vikram Sinai; Manyonda, Isaac T

2011-07-01

118

Extracellular control of TGF? signalling in vascular development and disease  

Microsoft Academic Search

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

Peter ten Dijke; Helen M. Arthur

2007-01-01

119

Observations on the alkaline phosphatase isoenzyme distribution in maternal and amniotic fluid compartments in Nigerian parturients.  

PubMed

Estimation of the alkaline phosphates isoenzymes in paired maternal serum and amniotic fluids in term uncomplicated pregnancies and in patients with pre-eclampsia, showed poor correlation coefficients between the levels of both heat stable and heat labile isoenzymes. There was a statistically significant fall in AF (P less than .05) HSAP in pre-eclampsia and a highly significant rise of HLAP in meconial liquor. It is concluded that the poor correlation between the levels of HSAP in maternal serum and amniotic fluid (despite their common source of origin), the normal levels of HLAP in maternal serum in the presence of significantly high levels of HSAP in maternal serum in the presence of significantly diminished levels in amniotic fluid point to a state of relatively diminished permeability of the chorioamniotic membranes to the alkaline phosphatase isoenzymes in Nigerians. PMID:3359645

Okpere, E; Okorodudu, A; Gbinigie, O

1988-01-01

120

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

121

Cerebrovascular complications of pregnancy and the postpartum period.  

PubMed

Cerebrovascular complications of pregnancy, though uncommon, threaten women with severe morbidity or death, and they are the main causes of major long-term disability associated with pregnancy. In this review, we discuss the epidemiology, pathophysiology, presentation and diagnosis, and management and outcomes of ischemic and hemorrhagic stroke and cerebral venous thrombosis. We also discuss the posterior reversible encephalopathy syndrome, the reversible cerebral vasoconstriction syndrome including postpartum cerebral angiopathy, and their relationship as overlapping manifestations of pre-eclampsia-eclampsia. PMID:25239155

Razmara, Ali; Bakhadirov, Khamid; Batra, Ayush; Feske, Steven K

2014-10-01

122

Reproductive and Obstetrical Consequences of the Polycystic Ovary Syndrome  

Microsoft Academic Search

Polycystic ovary syndrome (PCOS) is a disorder associated with infertility and subfecundity. There is evidence that both the\\u000a oocyte and the endometrium have abnormalities that contribute to these disorders. These reproductive abnormalities include\\u000a anovulation, increased early pregnancy wastage, and probable increased risk for a number of pregnancy complications including\\u000a gestational diabetes and hypertensive disorders of pregnancy, such as pre-eclampsia. Ovulation

Mary C. Johnson; Richard S. Legro

123

Acute pulmonary edema after intramyometrial prostodin.  

PubMed

A 25 year old, 68 kg, primigravida, was taken up for emergency caesarean section for meconium stained liquor and fetal distress. She was a known case of pre eclampsia and her blood pressure was controlled on tab methyl dopa. she was administered general anaesthesia. after delivery of baby she went into postpartum hemorrhage which was controlled with intramyometrial prostodin. but immediately after its administration she went into acute pulmonary edema. PMID:21772700

Baduni, Neha; Sanwal, Manoj K; Jain, Aruna

2011-04-01

124

Acute pulmonary edema after intramyometrial prostodin  

PubMed Central

A 25 year old, 68 kg, primigravida, was taken up for emergency caesarean section for meconium stained liquor and fetal distress. She was a known case of pre eclampsia and her blood pressure was controlled on tab methyl dopa. she was administered general anaesthesia. after delivery of baby she went into postpartum hemorrhage which was controlled with intramyometrial prostodin. but immediately after its administration she went into acute pulmonary edema. PMID:21772700

Baduni, Neha; Sanwal, Manoj K; Jain, Aruna

2011-01-01

125

Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials  

Microsoft Academic Search

Maternal–child health benefits of optimizing vitamin D status during pregnancy may include a reduced risk of pre-eclampsia, improved fetal growth and beneficial effects on infant immune function. These hypotheses require evaluation by randomized controlled antenatal vitamin D supplementation trials using doses that are high enough to elevate serum 25-hydroxyvitamin D concentrations into the range believed to be associated with improved

D E Roth

2011-01-01

126

Leptin receptor gene polymorphisms in severely pre-eclamptic women.  

PubMed

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

Rigó, János; Szendei, György; Rosta, Klára; Fekete, Andrea; Bögi, Krisztina; Molvarec, Attila; Rónai, Zsolt; Vér, Agota

2006-09-01

127

Capgras' syndrome with organic disorders.  

PubMed Central

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

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

1990-01-01

128

Cushing's syndrome in pregnancy with a severe maternal complication: a case report.  

PubMed

Cushing's syndrome (CS) in pregnancy may be confused with a complication of pregnancy, such as pre-eclampsia or gestational diabetes. We managed a case of CS in pregnancy that was considered to be severe pre-eclampsia due to uncontrolled hypertension. The fetus was delivered via emergency cesarean section at 31 weeks' gestation because of severe pre-eclampsia and pulmonary edema. The parturient was admitted to the intensive care unit for severe maternal complications, including pulmonary hemorrhage, acute renal failure, disseminated intravascular coagulopathy, and congestive heart failure. A spine magnetic resonance image and 99m-technetium whole-body scan obtained postpartum showed multiple thoracolumbar spine compression fractures (Deleted; t-2,5,8,10,11, and -12; and L-1,2,3,4, and -5), multiple rib fractures, and a left iliac bone fracture due to osteoporosis. As a result of diagnosing CS after delivery, an adrenal cortical adenoma of the right adrenal gland was demonstrated and a laparoscopic adrenalectomy was successfully performed. PMID:21159041

Choi, Won Jun; Jung, Tae Sik; Paik, Won Young

2011-02-01

129

Influence of mineral and vitamin supplements on pregnancy outcome.  

PubMed

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

Hovdenak, Nils; Haram, Kjell

2012-10-01

130

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

PubMed Central

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

2013-01-01

131

Advanced glycation end products as an upstream molecule triggers ROS-induced sFlt-1 production in extravillous trophoblasts: a novel bridge between oxidative stress and preeclampsia.  

PubMed

Although abnormal soluble fms-like tyrosine kinase-1 (sFlt-1) production is thought to be an important factor in the pathogenesis of pre-eclampsia, the mechanisms that regulate the production of sFlt-1 during pre-eclampsia are unclear. Accumulation of advanced glycation end products (AGEs) is prevalent in obesity, advanced maternal age, diabetes mellitus, and polycystic ovary syndrome. Alterations in the regulation and signaling of angiogenic pathways have been considered as a link between these conditions and pre-eclampsia. The purpose of this study was to explore the possible effects of AGEs on sFlt-1 secretion in extravillous trophoblasts (EVT). A EVT cell line (HRT-8/SVneo) was treated with various concentrations of AGEs-BSA. The mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in EVT were detected with real-time polymerase chain reaction. The secretion of sFlt-1, VEGF, and PlGF protein from EVT was measured with ELISA. The levels of intracellular reactive oxygen species (ROS) production were determined by DCFH-DA. Exposure of EVT to AGEs-BSA induced increased intracellular ROS generation and overexpression of sFlt-1 at mRNA and protein levels in a dose dependent manner. Anti-RAGE immunoglobulin G or apocynin (an inhibitors of NADPH oxidase) could decrease the intracellular ROS generation and subsequently suppressed the production of sFlt-1 at mRNA and protein levels. Our data suggested that AGEs may be a new class of important mediator in the regulation of angiogenic pathways of EVT. Accumulation of AGEs might contribute to the pathogenesis of preeclampsia by promoting sFlt-1 production through activation of RAGE/NADPH oxidase dependent pathway in EVT. PMID:24144948

Huang, Q T; Zhang, M; Zhong, M; Yu, Y H; Liang, W Z; Hang, L L; Gao, Y F; Huang, L P; Wang, Z J

2013-12-01

132

Clinico-pathological profile of 12 cases of chorangiosis.  

PubMed

Chorangiosis is one of the vascular lesions that involves terminal chorionic villi. It is commonly associated with various feto-maternal conditions like pre-eclampsia, diabetes etc. However, the clinical significance of this pathological finding has not been studied extensively. The aim of this study was to identify the various conditions associated with chorangiosis and to determine its clinical significance. A retrospective study to identify the cases of placentas diagnosed with chorangiosis was carried out and the clinical and morphological details of these cases were reviewed. Immunostaining for CD34 and muscle-specific actin was also performed to confirm chorangiosis and to exclude chorangiomatosis. A total of 12 cases of chorangiosis were retrieved, most of them were of term gestation. Five of these 12 cases were associated with various maternal conditions including syphilis (2 cases) and single cases of pre-eclampsia, diabetes and jaundice. One case in each had abruptio placenta and non-immune hydrops. Of these 12 cases, seven were stillborn. Microscopically, all 12 cases showed extensive chorangiosis involving terminal villi. In addition, two cases showed focal infarction and one had extensive calcification. Immunostaining for CD34 confirmed increased number of capillaries while muscle-specific actin was negative, excluding chorangiomatosis. The clinico-pathological profile presented in this study suggests that chorangiosis has characteristic pathological features for its recognition and needs to be differentiated from similar conditions like chorangioma and chorangiomatosis. Also, chorangiosis has potential clinical significance and should be mentioned in the pathology report and the patient should be investigated for associated conditions like syphilis, pre-eclampsia, diabetes etc. PMID:16208478

Gupta, Ruchika; Nigam, Sonu; Arora, Prerna; Khurana, Nita; Batra, Swaraj; Mandal, Ashish Kumar

2006-04-01

133

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

PubMed Central

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

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

1996-01-01

134

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

135

Plasma sFlt-1-to-PlGF ratio is correlated with inflammatory but not with oxidative stress in Chinese preeclamptic women  

Microsoft Academic Search

Purpose  Considerable interest has been focused on angiogenic factors and angiogenic imbalance in the field of pre-eclampsia (PE),\\u000a owing to its gaining role in the development of PE. This study was addressed to investigate the associations of sFlt-1-to-PlGF\\u000a plasma ratios with oxidative stress assessed by the level of 8-isoprostane, and inflammation measured by the level of high-sensitive\\u000a C-reactive protein (hs-CRP), and

Yan-Qiong Ouyang; Si-Jian Li; Qing Zhang; Wen-Pei Xiang; Hong-Ling Shen; Han-Ping Chen; Hong Chen; Hui-Zhen Chen

2009-01-01

136

?-Methyldopa-induced hepatitis during the postpartum period.  

PubMed

A 34-year-old woman, with a history of pre-eclampsia, was diagnosed with ?-methyldopa-induced hepatotoxicity, after she presented with severe jaundice and hepatitis 8 weeks following delivery. Laboratory investigations and liver biopsy ruled out other causes of hepatitis. She continued to improve clinically after cessation of ?-methyldopa, and was discharged 10 days after admission. This case report emphasises that it may not be possible to predict which patients may develop ?-methyldopa-induced hepatitis, hence regular monitoring of liver function tests during treatment should be implemented. PMID:24577181

Kashkooli, Soleiman; Baraty, Brandon; Kalantar, Jamshid

2014-01-01

137

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

138

Perinatal and infant mortality in term and preterm births among women with type 1 diabetes  

Microsoft Academic Search

Aims\\/hypothesis  The aim of this study was to estimate the risks of adverse birth outcomes such as stillbirth, infant death, preterm birth\\u000a and pre-eclampsia in women with type 1 diabetes, compared with the background population. We further aimed to explore the\\u000a risks of adverse birth outcomes in preterm and term deliveries separately.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  By linkage of two nationwide registries, the Medical Birth

I. Eidem; S. Vangen; K. F. Hanssen; S. E. Vollset; T. Henriksen; G. Joner; L. C. Stene

139

Hypercalcaemia due to parathyroid carcinoma presenting in the third trimester of pregnancy.  

PubMed

Primary hyperparathyroidism (pHPT) in pregnancy may be associated with significant maternal and fetal morbidity and mortality. Medical management of pHPT in pregnancy is limited, and surgery is the only definitive therapeutic option. The ideal timing for surgery is mid-second trimester, but surgery may also be safely performed in the third trimester. Delayed parathyroid surgery may result in a hypercalcaemic crisis postpartum owing to loss of active placental calcium transfer. We present a case of parathyroid carcinoma in pregnancy presenting with pre-eclampsia at 32 weeks' gestation. PMID:22188427

Paul, Ryan G; Elston, Marianne S; Gill, Anthony J; Marsh, Deborah; Beer, Ian; Wolmarans, Louise; Conaglen, John V; Meyer-Rochow, Goswin Y

2012-04-01

140

[Emergency obstetrics].  

PubMed

Sudden bleeding in the advanced stage of pregnancy is usually caused by abruptio placentae. Pre-eclampsia may develop rapidly into eclampsia and should lead to immediate hospitalization of the patient. A pregnant woman suffering from high blood pressure, headaches and epigastric pains, might be developing the life threatening HELLP syndrome. Sudden labour at term, either at home or in the ambulance, does not usually involve major complications. Hypothermia of the newborn baby should be avoided by drying it and placing it at the mother's breast. The umbilical chord is cut at the obstetrical department. PMID:8322352

Sande, H A

1993-06-20

141

Perinatal case report of unexpected thalassemia Hb Bart.  

PubMed

Homozygous alpha-thalassaemia Hb Bart is a very rare illness in North America and Western Europe, but is a common cause of NIHF especially in South East Asia. It causes severe hydrops fetalis with lethal outcome and maternal complications as preterm labour, pre-eclampsia and retained placenta. A case report of an immigrant from Laos with preterm labour and fetal ascites, but without signs of pre-eclampsia is demonstrated. Fetal heart rate (FHR) trace and biophysical profile were pathological, while umbilical Doppler flow was normal due to hypoxaemia, but with hypervolumina and a high cardiac output. An amniocentesis and puncture of the ascites were performed, but FBS was not successful. Before receiving the results a caesarean section had to be done for deterioration of the FHR trace. A 1,370-g female infant was born who died of cardiovascular failure due to an alpha-thalassaemia Hb Bart and respiratory distress 5 days post partum. The parents had both an alpha-zero-thalassaemia. alpha-Thalassaemia is still a very unknown illness in Germany, but with the increasing numbers of immigrants from South East Asia it should be considered at the differential diagnosis of hydrops fetalis. A prenatal diagnosis should be offered to parents with alpha-zero-thalassaemia. PMID:8286033

Hofstaetter, C; Gonser, M; Goelz, R

1993-01-01

142

Risk factors of hypertensive pregnancies in women with diabetes and the influence on their future life.  

PubMed

Abstract Diabetic women carry a 2-4 times increased risk of a hypertensive pregnancy compared to non-diabetic people. This risk is related to presence of diabetic nephropathy, but also poor glycaemic control. Efforts to improve glycaemic control have decreased perinatal morbidity and mortality related to diabetic nephropathy. Despite good glycaemic control, overt nephropathy is associated with a variety of pregnancy complications, such as fetal growth restriction and pre-eclampsia. General population studies show that women with a history of pre-eclampsia are more prone to develop cardiovascular disease later in life than women with a history of normotensive pregnancy. Furthermore, recent data regarding the long-term effects of hypertensive pregnancies on late diabetic complications indicate that these women should be followed and treatment should be started early. In this review we summarize data on risk factors and long-term effects of hypertensive pregnancies on late diabetic complications that may be of clinical relevance in the prevention of these complications. PMID:25045927

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

2014-11-01

143

Managing lupus patients during pregnancy  

PubMed Central

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

Lateef, Aisha; Petri, Michelle

2013-01-01

144

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

PubMed Central

Heparin-binding EGF-like growth factor (HBEGF), which is expressed in the placenta during normal pregnancy, is downregulated in pre-eclampsia, a human pregnancy disorder associated with poor trophoblast differentiation and survival. This growth factor protects against apoptosis during stress, suggesting a role in trophoblast survival in the relatively low O2 (?2%) environment of the first trimester conceptus. Using a well-characterized human first trimester cytotrophoblast cell line, we found that a 4-hour exposure to 2% O2 upregulates HBEGF synthesis and secretion independently of an increase in its mRNA. Five other expressed members of the EGF family are largely unaffected. At 2% O2, signaling via HER1 or HER4, known HBEGF receptors, is required for both HBEGF upregulation and protection against apoptosis. This positive-feedback loop is dependent on metalloproteinase-mediated cleavage and shedding of the HBEGF ectodomain. The restoration of trophoblast survival by the addition of soluble HBEGF in cultures exposed to low O2 and metalloproteinase inhibitor suggests that the effects of HBEGF are mediated by autocrine/paracrine, rather than juxtacrine, signaling. Our results provide evidence that a post-transcriptional mechanism induced in trophoblasts by low O2 rapidly amplifies HBEGF signaling to inhibit apoptosis. These findings have a high clinical significance, as the downregulation of HBEGF in pre-eclampsia is likely to be a contributing factor leading to the demise of trophoblasts. PMID:16407398

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

2006-01-01

145

The imbalance of circulating angiogenic/antiangiogenic factors is mild or absent in obese women destined to develop preeclampsia.  

PubMed

We thank Dr Rana et al. ( 1 ) for their interesting study clarifying the clinical profile of preeclamptic patients with normal angiogenic profile. In their study, the patients with non-angiogenic preeclampsia were more obese, although with large overlapping of body mass index (BMI) between the groups [BMI: 35.2 (31.6, 38.7) versus 31.1 (28.0, 39.0), p?=?0.04]. We performed a case-control study assessing the predictive value of sFlt-1 and PlGF for preeclampsia in a population with high-obesity prevalence ( 2 ). Both BMI and circulating mean concentrations of sFlt-1 were significantly higher in the preeclampsia group. However, a two-variable model associating sFlt-1 and PlGF dosages was not better than the model including only age and BMI in the prediction of preeclampsia. In line with these findings, Suwaki et al. ( 3 ) reported that overweight patients with pre-eclampsia had lower levels of sFlt1 and higher levels of PlGF than women with pre-eclampsia who were of normal weight. All these data support the fact that in obese pregnant women who will develop preeclampsia, the imbalance of circulating angiogenic/antiangiogenic factors is mild or absent, suggesting that in these patients the extra benefit of the dosages of angiogenic factors appears to be of limited value. PMID:24842148

Carbillon, Lionel

2014-11-01

146

Effect of Antihypertensive Therapy with Alpha Methyldopa on Levels of Angiogenic Factors in Pregnancies with Hypertensive Disorders  

PubMed Central

Background Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy. Methodology/Principal Findings In a study conducted at University College Hospital and the Homerton University Hospital in London, we recruited 51 women with PE, 29 with gestational hypertension (GH), and 80 matched normotensive controls. Eight (16%) of the women with PE had severe disease. Placental samples were obtained from a further 48 women (14 PE, 10 GH and 24 matched controls). Serum levels of angiogenic factors were measured before and 24–48 hours after commencing antihypertensive therapy with alpha methyldopa for clinical indications. The same parameters were measured in placental extracts. In both PE (P<0.0001) and GH (P<0.05), serum sFlt-1 was increased and PlGF reduced at all gestations (P<0.001) compared to controls. Serum sEng levels were also increased in PE. Placental concentration of sFlt-1 and sEng was significantly higher in women with PE compared to controls and women with GH (P<0.0001). The concentration of PlGF was significantly lower in the placental tissue of women with PE compared to GH (P?=?0.008). Antihypertensive treatment was associated with a significant fall in serum and placental content of sFlt1 and sEng in PE only. Conclusions Our data suggest that alpha methyldopa may have a specific effect on placental and/or endothelial cell function in pre-eclampsia patients, altering angiogenic proteins. PMID:18648513

Khalil, Asma; Muttukrishna, Shanthi; Harrington, Kevin; Jauniaux, Eric

2008-01-01

147

Helicobacter pylori and pregnancy-related disorders  

PubMed Central

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

Cardaropoli, Simona; Rolfo, Alessandro; Todros, Tullia

2014-01-01

148

Endogenous digitalis  

PubMed Central

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

Bagrov, Alexei Y; Shapiro, Joseph I

2008-01-01

149

Management of paroxysmal hypertension due to incidental pheochromocytoma in pregnancy  

PubMed Central

A 25-year-old, full-term pregnant woman diagnosed with pre-eclampsia was referred to our tertiary care hospital with severe resistant hypertension. Her blood pressure remained labile despite the usual medications, which led to the suspicion of an underlying endocrinological problem. Further biochemical and radiological investigations confirmed the diagnosis of pheochromocytoma. The patient was invasively monitored and treated with alpha blockade, beta blocker, and vasodilators. The primary goals for the management of pheochromocytoma in pregnancy are early diagnosis, avoidance of a hypertensive crisis during delivery, and definitive surgical treatment. This case illustrates that one needs to be cautious when such a presentation of paroxysmal hypertension is present. With a multidisciplinary team approach, proper planning, and adequate preoperative medical management, pheochromocytoma in pregnancy can be managed successfully. PMID:21887038

Lata, Indu; Sahu, Sandeep

2011-01-01

150

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

PubMed

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

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

2013-01-01

151

Oxidative stress  

PubMed Central

Considerable evidence implicates oxidative stress in the pathophysiology of many complications of human pregnancy, and this topic has now become a major focus of both clinical and basic science research. Oxidative stress arises when the production of reactive oxygen species overwhelms the intrinsic anti-oxidant defences. Reactive oxygen species play important roles as second messengers in many intracellular signalling cascades aimed at maintaining the cell in homeostasis with its immediate environment. At higher levels, they can cause indiscriminate damage to biological molecules, leading to loss of function and even cell death. In this chapter, we will review how reactive oxygen species are generated and detoxified in the human placenta, and what roles they may play at homeostatic concentrations. We will then consider their involvement in normal placental development, and in complications ranging from miscarriage to pre-eclampsia and premature rupture of the membranes. PMID:21130690

Burton, Graham J.; Jauniaux, Eric

2011-01-01

152

Neurology of pregnancy.  

PubMed

Pregnancy creates alterations in maternal physiology which predispose to unique neurologic disorders. Pre-eclampsia, eclampsia, certain types of ischemic and hemorrhagic stroke, reversible cerebral vasoconstriction syndrome, posterior reversible encephalopathy syndrome, and thunderclap headache all appear to share a common origin from vascular endothelial dysfunction, with overlapping clinical presentations. Multiple sclerosis often improves during pregnancy. Compression mononeuropathies may occur in the extremities. Myasthenia gravis may affect second stage labor. Various inflammatory peripheral neuropathies, dystrophies, myopathies may occur during pregnancy. The safety of specific immune suppressants is reviewed. Epilepsy does not have a significant effect upon the course of pregnancy, albeit there is a modest increase in the need for cesarean section. Certain antiepileptic drugs may produce fetal malformations, most notably valproic acid. Brain tumors are rare during pregnancy, but may increase in size due to activation of hormonal receptors on tumor cells surfaces, water retention, and engorged blood vessels. PMID:24365437

Block, H Steven; Biller, José

2014-01-01

153

Hypertension in women  

PubMed Central

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

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

2013-01-01

154

Extracellular vesicles and reproduction-promotion of successful pregnancy  

PubMed Central

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

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

2014-01-01

155

Coagulation and Placenta-Mediated Complications  

PubMed Central

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

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

2014-01-01

156

Birthweight below the tenth percentile: the relative and attributable risks of maternal tobacco consumption and other factors.  

PubMed

Analysis of 7776 singleton births defined a cohort of babies with birthweight below the 10th percentile after adjusting for gestational age and sex. The relative risk of a baby being small for gestational age in respect to a number of factors, such as parental anthropometry, demographic factors, behavior patterns (tobacco, cannabis, alcohol, and caffeine consumption), maternal pathology, and fetal abnormality, was calculated. The highest relative risks are associated with severe antepartum hemorrhage, severe pre-eclampsia, and severe fetal abnormality. As these are relatively rare events, a more accurate calculation of overall risk to the population as opposed to the individual can be obtained by studying the percent attributable risk of each of the factors. This demonstrates that maternal tobacco consumption is the major environmental risk factor in our population. PMID:8143631

Morrison, J; Williams, G M; Najman, J M; Andersen, M J; Keeping, J D

1993-10-01

157

Stillbirth in diabetic pregnancies.  

PubMed

Pregnancy in women with pregestational diabetes is associated with high perinatal morbidity and mortality. Stillbirth accounts for the majority of cases with perinatal death. Intrauterine growth restriction, pre-eclampsia, foetal hypoxia and congenital malformations may be contributing factors, but more than 50% of stillbirths are unexplained. Majority of stillbirths are characterised by suboptimal glycaemic control during pregnancy. Foetal hypoxia and cardiac dysfunction secondary to poor glycaemic control are probably the most important pathogenic factors in stillbirths among pregnant diabetic women. There is thus a need for new strategies for improving glycaemic control to near-normal levels throughout pregnancy and for preventing and treating hypertensive disorders in pregnancy. Antenatal surveillance tests including ultrasound examinations of the foetal growth rate, kick counting and non-stress testing of foetal cardiac function are widely used. However, future research should establish better antenatal surveillance tests to identify the infants susceptible to stillbirth before it happens. PMID:21256813

Mathiesen, Elisabeth R; Ringholm, Lene; Damm, Peter

2011-02-01

158

Pregnancy in essential thrombocythaemia: experience with 40 pregnancies.  

PubMed

In this study, the course of 40 pregnancies in 16 women with essential thrombocythaemia (ET) was analysed retrospectively. Of the pregnancies, 45% were complicated, 55% uncomplicated, and 62% resulted in live birth. The most common complication was spontaneous abortion during the first trimester seen in 33% of all pregnancies and comprising 72% of all complications. Two intrauterine foetal deaths occurred at weeks 22 and 28. Three pregnancies were complicated by eclampsia or pre-eclampsia. Nine of 16 women with 29 pregnancies had at least one complicated pregnancy. In seven of 16 women, all 11 pregnancies were uneventful. The non-pregnancy-related symptoms of ET or the platelet count before conception or during pregnancy did not correlate with the risk of pregnancy complications. Treatment with low-dose acetylsalicylic acid (ASA) alone during pregnancy or platelet-lowering drugs before or during pregnancy reduced the risk of complications. PMID:15522066

Niittyvuopio, Riitta; Juvonen, Eeva; Kaaja, Risto; Oksanen, Kalevi; Hallman, Heikki; Timonen, Timo; Ruutu, Tapani

2004-12-01

159

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

PubMed

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

Blickstein, Dorith; Hod, Moshe; Bar, Jacob

2003-12-01

160

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

PubMed

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

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

2014-02-01

161

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

PubMed Central

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. Detailed cytogenetic studies, using banding and fluorescence techniques, were performed on fetus and parents. Meiotic studies were made on the fetal ovaries. Muscle cell differentiation and electrophysiological relationships of cultured skin fibriblasts were examined in an attempt to study the way in which the extra haploid set of chromosomes exerts its effect on the phenotype. The antenatal diagnosis of late triploidy is discussed. The finding that 25 per cent of late triploids have spina bifida is further evidence that meningomyelocele has a genetic component and strongly suggests that this results from chromosomal imbalance or a regulatory gene disturbance. Images PMID:1034015

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

1976-01-01

162

Thrombophilia in pregnancy  

PubMed Central

Thrombophilia can be defined as a predisposition to thrombosis. Abnormalities in haemostasis that are associated with clinical thrombophilia include heritable defects, such as mutations in the genes encoding the natural anticoagulants antithrombin, protein C, and protein S, or clotting factors prothrombin and factor V, and acquired defects, such as antiphospholipids. Women with thrombophilic defects have been shown to be at increased risk, not only of pregnancy associated thromboembolism, but also of other vascular complications of pregnancy, including pre-eclampsia and fetal loss. Routine thrombophilia screening of all women attending antenatal clinics is not recommended. Because some thrombophilic defects—for example, type 1 antithrombin deficiency and antiphospholipids—are associated with a high risk of recurrent thrombosis or other pregnancy complications, it is suggested that selected women (those with a personal or confirmed family history of venous thromboembolism or with a history of recurrent fetal loss) are screened for these defects to allow pregnancy management planning. Key Words: thrombophilia • pregnancy PMID:11002758

Walker, I.

2000-01-01

163

Pregnancy and cardiovascular risk for women with Turner syndrome.  

PubMed

Most women with Turner syndrome (TS) are infertile due to primary ovarian failure. However, approximately 5% experience spontaneous pregnancy, and recently, more women with TS have used assisted reproductive technology with donated oocytes (ART-OD) to become pregnant. The first generation of Turner patients undergoing ART-OD demonstrated a high rate of fatal aortic dissection in late pregnancy or postpartum. More recent observations, particularly from Nordic countries, suggest a lesser risk of dissection, but confirm a high rate of pre-eclampsia in ART-OD pregnancies. This article reviews publications since 2000 concerning maternal outcomes for pregnancies in women with TS to determine if specific risk factors such as type of pregnancy, age, or presence of underlying congenital cardiovascular disease may identify women at special risk. PMID:25259906

Bondy, Carolyn

2014-07-01

164

Infertility today: the management of female medical causes.  

PubMed

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

Tinneberg, Hans-Rudolf; Gasbarrini, Antonio

2013-12-01

165

[Normotensive HELLP syndrome: report of one case].  

PubMed

HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) represents a severe form of preeclampsia associated with serious maternal and fetal morbidities and even death. Usually HELLP syndrome appears during the evolution of a severe preeclampsia; however HELLP syndrome can have atypical clinical manifestations. We report a 22-year-old female who consulted at 20 weeks of pregnancy for lumbar pain, dysuria and fever. A urinalysis revealed the presence of white blood cells. The patient was admitted to hospital and treated with antimicrobials. Forty eight hours after admission a proteinuria of 440 mg/24 h was detected. A severe pre eclampsia-HELLP syndrome was diagnosed. However the patient remained with normal blood pressure. An elevation of liver enzymes and creatinine were observed. Five days later fetal death was confirmed and an abortion was induced. The patient required a platelet transfusion. Four days after the abortion, the patient was discharged in good conditions. PMID:24718475

Garrido, María Fernanda; Carvajal, Jorge Andrés

2013-11-01

166

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.

167

Coagulation and placenta-mediated complications.  

PubMed

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

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

2014-10-01

168

Melatonin and pregnancy in the human.  

PubMed

The purpose of this systematic review is to access the current state of knowledge concerning the role for melatonin in human pregnancy. Melatonin is a neuroendocrine hormone secreted nightly by pineal gland and regulates biological rhythms. The nighttime serum concentration of melatonin shows an incremental change toward the end of pregnancy. This small lipophilic indoleamine crosses the placenta freely without being altered. Maternal melatonin enters the fetal circulation with ease providing photoperiodic information to the fetus. Melatonin works in a variety of ways as a circadian rhythm modulator, endocrine modulator, immunomodulator, direct free radical scavenger and indirect antioxidant and cytoprotective agent in human pregnancy, and it appears to be essential for successful pregnancy. It also seems to be involved in correcting the pathophysiology of complications during pregnancy including those due to abortion, pre-eclampsia and fetal brain damage. The scientific evidence supporting a role for melatonin in human pregnancy is summarized. PMID:18485664

Tamura, Hiroshi; Nakamura, Yasuhiko; Terron, M Pilar; Flores, Luis J; Manchester, Lucien C; Tan, Dun-Xian; Sugino, Norihiro; Reiter, Russel J

2008-04-01

169

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

PubMed

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

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

2010-03-01

170

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

PubMed Central

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

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

2014-01-01

171

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

SciTech Connect

Using PIXE (proton-induced X-ray emission), we simultaneously determined the concentrations of Se, Ca, Fe, Cu, Zn, Br, and Pb in blood serum from 56 pregnant women, 25 healthy controls, and 31 others with twin pregnancy or some complicating condition (diabetes, hypertension, epilepsy, hepatosis gravidarum, pre-eclampsia, small baby), and in cord-blood serum from 21 newborns. Pellets, pressed from the serum samples after addition of yttrium as an internal standard, mixing, and evaporating at 30 degrees C with or without reduced pressure (less than 1 kPa), were bombarded by 2.2 MeV protons from a Van de Graaff accelerator in the air and the induced X-rays collected by a Ge(Li) detector. Relative to mean Se values for early six- to 12-week pregnancy (0.045 ppm), those for 35-42 week pregnancy (0.028 ppm) were low (p less than 0.001). Umbilical cord blood serum showed even lower values (0.016 ppm, p less than 0.001)--findings in harmony with the incidence pattern of Keshan cardiomyopathy. Pb crossed the placenta; values for cord serum were not significantly different from those in pregnancy serum. Cu, Zn, Fe, and Ca showed the significant expected patterns in the different groups. Compared with the late-pregnancy controls, Fe was high in mothers of small-birth-weight babies (1.70 ppm, p less than 0.02). Br was high in pre-eclampsia (3.59 ppm, p less than 0.05) and mothers with twins (3.61 ppm, p less than 0.05).

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

1984-04-01

172

Glomerular endothelium: a porous sieve and formidable barrier.  

PubMed

The glomerular capillary endothelium is highly specialized to support the selective filtration of massive volumes of plasma. Filtration is driven by Starling forces acting across the glomerular capillary wall, and depends on its large surface area and extremely high water permeability. Glomerular endothelial cells are extremely flat and perforated by dense arrays of trans-cellular pores, the fenestrae. This phenotype is critical for the high glomerular water permeability and depends on podocyte-derived VEGF, as well as TGF-beta. Endothelial cell-derived PDGFB, in turn, is necessary for the establishment of mesangial cells, which sculpt the glomerular loop structure that underlies the large filtration surface area. In pre-eclampsia, inhibition of the VEGF- and TGF-beta signaling pathways leads to endothelial swelling and loss of fenestrae, reducing the glomerular filtration rate. Similarly, in the thrombotic microangiopathies, glomerular endothelial cell injury coupled with inappropriate VWF activation leads to intracapillary platelet aggregation and loss of the flat, fenestrated phenotype, thus reducing the glomerular filtration rate. Normally, a remarkably small fraction of albumin and other large plasma proteins passes across the glomerular capillary wall despite the massive filtration of water and small solutes. An elaborate glycocalyx, which covers glomerular endothelial cells and their fenestrae forms an impressive barrier that, together with other components of the glomerular capillary wall, prevents loss of plasma proteins into the urine. Indeed, microalbuminuria is a marker for endothelial glycocalyx disruption, and most forms of glomerular endothelial cell injury including pre-eclampsia and thrombotic microangiopaties can cause proteinuria. PMID:22465480

Obeidat, Marya; Obeidat, Motaz; Ballermann, Barbara J

2012-05-15

173

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

PubMed Central

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

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

2009-01-01

174

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

175

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

PubMed Central

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

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

2012-01-01

176

Suramin-restricted blood volume in the placenta of normal and diabetic rats is normalized by vitamin E treatment.  

PubMed

Previously maternal and fetal alterations resembling human pre-eclampsia were induced in pregnant rats by injections of the angiogenesis inhibitor Suramin. These alterations were aggravated by maternal diabetes and partly rectified by vitamin E supplementation. In the present study we evaluated the morphology of placentae and kidneys in this model. Non-diabetic and streptozotocin-induced diabetic pregnant rats of two rat strains (U and H) were treated with Suramin or saline, and given standard or vitamin E-enriched food. On gestational day 20 one placenta and the left kidney of the mother were collected for morphological and stereological analysis. In the placental trophospongium Suramin treatment caused cysts, which were further enhanced by maternal diabetes. Vitamin E treatment had no effect on the vacuolization. In the placental labyrinth of the non-diabetic rats Suramin treatment restricted maternal placental blood volume and increased the interface between maternal and fetal circulation. These changes were reversed by vitamin E treatment. Diabetes increased slightly the interface between the circulations in both rat strains. Suramin treatment decreased the interface, and vitamin E further decreased the interface in the diabetic U rats, whereas neither treatment affected the maternal-fetal interface in the diabetic H rats. The kidneys of Suramin-treated and diabetic rats were heavier compared to controls. Suramin treatment and maternal diabetes damaged renal glomeruli to a similar extent. Vitamin E treatment diminished the Suramin- and diabetes-induced glomerular damage in U rats, but not in H rats. The average cell count per glomerulus was decreased by Suramin in the U rats. Vitamin E treatment did not affect cell number per glomerulus in any group. We conclude that Suramin-injected pregnant rats constitute a valid animal model for placental dysfunction and pre-eclampsia, also from the histological perspective. The present work supports the notion that one important effect of untreated maternal diabetes may be impaired placentation, leading to oxidative stress, morphological damage, and compromised placental function. PMID:16920189

Nash, P; Eriksson, U J

2007-01-01

177

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

178

Diagnosis and management of subclinical hypothyroidism in pregnancy.  

PubMed

In prospective studies, the prevalence of undiagnosed subclinical hypothyroidism in pregnant women ranges from 3% to 15%. Subclinical hypothyroidism is associated with multiple adverse outcomes in the mother and fetus, including spontaneous abortion, pre-eclampsia, gestational hypertension, gestational diabetes, preterm delivery, and decreased IQ in the offspring. Only two prospective studies have evaluated the impact of levothyroxine therapy in pregnant women with subclinical hypothyroidism, and the results were mixed. Subclinical hypothyroidism is defined as raised thyrotropin combined with a normal serum free thyroxine level. The normal range of thyrotropin varies according to geographic region and ethnic background. In the absence of local normative data, the recommended upper limit of thyrotropin in the first trimester of pregnancy is 2.5 mIU/L, and 3.0 mIU/L in the second and third trimester. The thyroid gland needs to produce 50% more thyroid hormone during pregnancy to maintain a euthyroid state. Consequently, most women on levothyroxine therapy before pregnancy require an increase in dose when pregnant to maintain euthyroidism. Ongoing prospective trials that are evaluating the impact of levothyroxine therapy on adverse outcomes in the mother and fetus in women with subclinical hypothyroidism will provide crucial data on the role of thyroid hormone replacement in pregnancy. PMID:25288580

Negro, Roberto; Stagnaro-Green, Alex

2014-01-01

179

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

180

Safety of protease inhibitors in HIV-infected pregnant women  

PubMed Central

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

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

2013-01-01

181

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

PubMed Central

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

Poolsup, Nalinee; Suksomboon, Naeti; Amin, Muhammad

2014-01-01

182

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

183

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

PubMed Central

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

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

2011-01-01

184

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

185

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

186

Acute and chronic modulation of placental chorionic plate artery reactivity by reactive oxygen species.  

PubMed

Control of vascular resistance and blood flow in the fetoplacental circulation is incompletely understood. Reactive oxygen species (ROS), physiological and pathophysiological regulators of vascular tone, are elevated in preeclampsia (PE), a disease of pregnancy characterized by increased fetoplacental vascular resistance. We tested the hypothesis that ROS modulate vascular reactivity in placental chorionic plate arteries. Wire myography was used to examine (1) the effects of acute exposure to ROS on arterial function in normal pregnancy and (2) the effects of maternal antioxidant supplementation on arterial reactivity in women at high risk for PE participating in the Vitamins in Pre-eclampsia (VIP) trial. ROS generated by xanthine plus xanthine oxidase enhanced basal tension, vasoconstriction in response to the thromboxane mimetic U46619, and relaxation in response to sodium nitroprusside. Hydrogen peroxide and peroxynitrite increased basal tone and relaxed preconstricted arteries (U44619), respectively. In women at risk for PE, chorionic plate artery constriction in response to U46619 was greater in the women receiving placebo compared to the women supplemented with the antioxidant vitamins C and E. ROS may regulate fetoplacental vascular resistance and blood flow in the short term, and chronic exposure to raised ROS could contribute to elevated fetoplacental vascular resistance in PE and fetal growth restriction (FGR). PMID:19389471

Mills, Tracey A; Wareing, Mark; Shennan, Andrew H; Poston, Lucilla; Baker, Philip N; Greenwood, Susan L

2009-07-15

187

A redox switch in angiotensinogen modulates angiotensin release  

PubMed Central

Blood pressure is critically controlled by angiotensins1, vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen, a non-inhibitory member of the serpin family of protease inhibitors2,3. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1Å resolution show that the angiotensin cleavage-site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in a 4.4Å structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. We show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidised sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia - the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child. PMID:20927107

Zhou, Aiwu; Carrell, Robin W; Murphy, Michael P; Wei, Zhenquan; Yan, Yahui; Stanley, Peter L.D.; Stein, Penelope E; Pipkin, Fiona Broughton; Read, Randy J

2010-01-01

188

Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia  

PubMed Central

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

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

2009-01-01

189

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

190

B-1a B Cells Regulate T Cell Differentiation Associated with Pregnancy Disturbances  

PubMed Central

During pregnancy, the maternal immune system faces a double dilemma: tolerate the growing semi-allogeneic fetus and at the same time protect the mother and the progeny against pathogens. This requires a fine and extremely regulated equilibrium between immune activation and tolerance. As professional antigen presenting cells, B cells and in particular B-1a B cells, can activate or tolerize T cells and thus participate in the generation or regulation of the immune response. B-1a B cells were involved in the humoral immune response leading to pre-eclampsia, one of the main medical complications during pregnancy. Here we demonstrated that B-1a B cells are additionally involved in cellular immune mechanisms associated with pregnancy complications. Using a mouse model of pregnancy disturbances, we showed that B-1a B cells from animals suffering pregnancy disturbances but not from those developing normal pregnancies induce the differentiation of naïve T cells into Th17 and Th1 cells. This differential role of B-1a B cells during pregnancy seems to be associated with the co-stimulatory molecule CD86 as normal pregnant mice showed lower percentages of CD86 expressing B-1a B cells as compared to pregnant mice developing pregnancy disturbances or to non-pregnant animals. Our data bring to light a new and not explored role of B-1a B cells in the context of pregnancy. PMID:24478775

Muzzio, Damian Oscar; Soldati, Rocio; Rolle, Luise; Zygmunt, Marek; Zenclussen, Ana Claudia; Jensen, Federico

2014-01-01

191

Body mass index and labour outcome in Egyptian women.  

PubMed

We conducted a cross-sectional descriptive study to evaluate the impact of body mass index (BMI) on maternal medical disorders, progress of labour, mode of delivery and neonatal outcome in Cairo University hospital between September 2012 and March 2013. A total of 574 parturients were divided into two groups: group A with a BMI < 30 and group B with a BMI ? 30. A statistically significant difference was found in favour of group B, regarding medical disorders, especially gestational hypertension and pre- eclampsia (p < 0.001), caesarean deliveries (p < 0.001) and neonatal birth weight (p = 0.001). There was no difference regarding gestational age at delivery, progress of labour (cervical dilatation, cervical effacement, duration of first and second stage of labour) and neonatal outcome (Apgar score at 1 and 5 min and neonatal deaths). Our conclusion is that increased maternal BMI is associated with an increased incidence of medical disorders during pregnancy, caesarean section rate and fatal macrosomia. PMID:24294988

Shaban, M M; Bassiouny, Y A; Elzahaby, I M; Hassan, A A

2014-04-01

192

Pathological assessment of intrauterine growth restriction.  

PubMed

Intrauterine growth restriction (IUGR) is a major cause of foetal and neonatal morbidity and mortality. During post mortem, the pathologist is well placed to diagnose the presence and cause of IUGR in a stillborn baby. This article describes the approach of the pathologist in diagnosing IUGR and some of the pitfalls. We distinguish between reduced growth potential (formerly symmetrical IUGR) and nutritional IUGR (formerly asymmetrical IUGR). Aetiologically, restricted growth can be of foetal, maternal and placental origin. We discuss the importance of identifying the cause of IUGR in a clinicopathological context and the pathological findings in some of the more frequent causes of IUGR presenting at post mortem. Based on an accurate gestational age, ideally determined by the obstetrician in early pregnancy, the pathologist can derive a birth weight centile. However, the pathologist is also able to identify other indicators of IUGR, such as an elevated brain/liver weight ratio, atrophic thymus and changes in other internal organs. Placental examination plays a major role in the investigation as the majority of IUGR cases have significant placental pathology. This includes pre-eclampsia-related changes, abnormalities of the villous parenchyma and pathology of the umbilical cord. The potential benefit of a meticulous workup of IUGR foetuses is to provide an explanation of the pathological condition and to identify avoidable causes. PMID:19854107

Cox, Phillip; Marton, Tamas

2009-12-01

193

[Obstetric problems followed by stroke].  

PubMed

Obstetrical problems sometimes portend manifestations of atherosclerosis, as illustrated by two case reports. The first patient had the combination of hyperhomocysteinaemia due to chronic vitamin deficiencies in the diet, and smoking. The second was also a smoker and had a genetically determined mild hyperhomocysteinaemia, aggravated by chronic vitamin deficiencies resulting from poor dietary habits; she also had an increased folic acid requirement because of use of anti-epileptic drugs in combination with a familial predisposition for premature atherosclerotic manifestations. The first patient had four pregnancies, two of which ended in intrauterine foetal death due to placental infarction, and one in the birth of a dysmature boy. The second patient's four pregnancies ended twice in abortion and twice in the birth of a dysmature child; in one of the latter cases placental infarction was observed. Both women subsequently suffered cerebrovascular accidents while in addition, older cerebral infarctions were found to be present. Women with recurrent abortion, pre-eclampsia, placental infarction, placental detachment and foetal growth retardation should be examined, even if other risk factors are also present, for (mild) hyperhomocysteinaemia, and treated for it with vitamin suppletion (folic acid, vitamins B6 and B12), even although admittedly more research is necessary to make certain that such treatment has a preventive effect on the manifestations of this disorder. PMID:10347622

Lubbers, M F; Aarnoudse, J G; van Doormaal, J J

1999-04-01

194

Diabetes mellitus and pregnancy  

PubMed Central

Diabetes mellitus is the most common medical complication of pregnancy and it carries a significant risk to the foetus and the mother. Congenital malformations and perinatal morbidity remain common compared with the offspring of non diabetic pregnancies. Diabetic mothers are at risk of progression of microvascular diabetic complications as well as early pregnancy loss, pre-eclampsia, polyhydramnios and premature labour. Glycaemic control before and during pregnancy is critical and the benefit may result in a viable, healthy off spring. Gestational diabetes mellitus (GDM) which manifests for the first time during pregnancy is common and on the increase, its proper management will reduce the risk of neonatal macrosomia and hypoglycaemia. Post-partum evaluation of glucose tolerance and appropriate counselling in women with GDM may help decrease the high risk of subsequent type 2 diabetes in the longterm. This article will briefly review the changes in the carbohydrate metabolism that characterise normal pregnancy and will focus on a practical approach to the care of patients with pre-existing diabetes as well as GDM. PMID:21526019

Abourawi, Fathi I

2006-01-01

195

Maternal use of oral contraceptives and risk of hypospadias - a population-based case-control study.  

PubMed

The aim of this population-based case-control study was to examine the risk of isolated hypospadias in boys born to mothers who have used oral contraceptives in early pregnancy. The study was based on data from the Hungarian Case-Control Surveillance of Congenital Abnormalities from 1980 to 1996, and included 3,038 boys with hypospadias (cases), 24,799 boys without congenital abnormalities (CA-free controls), and 11,881 boys with abnormalities other than hypospadias. We used unconditional logistic regression to adjust for birth order, maternal age, maternal employment status, maternal diabetes, and pre-eclampsia. When comparing cases with CA-free controls the OR for maternal use of OC was 1.21 (95% CI: 0.67-2.17). When comparing cases with boys with other abnormalities, the OR for maternal use of OC was 0.83 (95% CI: 0.46-1.50). Our data showed that self-reported maternal use of oral contraceptives during pregnancy was not associated with an increased risk of hypospadias in the offspring. PMID:17077991

Wogelius, Pia; Horváth-Puhó, Erzsébet; Pedersen, Lars; Nørgaard, Mette; Czeizel, Andrew E; Sørensen, Henrik Toft

2006-01-01

196

New Horizons in Platelets Flow Cytometry  

PubMed Central

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

Saboor, Muhammad; Moinuddin, Moinuddin; Ilyas, Samina

2013-01-01

197

Pregnancy and liver disease.  

PubMed

Liver disease in pregnancy should be considered in 3 categories: pre-existing disease, disease peculiar to pregnancy and coincident acute liver or gall-stone disease. In addition the time of onset of diagnosis in terms of the trimester of gestation must be verified, as the diseases peculiar to pregancy have a characteristic time of onset. In the last trimester closes obstetric management is required for the constellation of abnormal liver function tests, nausea and/or vomiting and abdominal pain. This may be due to severe pre-eclampsia, HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome or acute fatty liver of pregnancy with or without sub-capsular hepatic haematomas, amongst which there is an overlap. Early delivery is curative. A molecular basis consisting of long chain 3-hydroxyl CoA dehydroxegenase deficiency in heterozygote mothers underlies this clinical syndrome. Ursodeoxycholic acid is now established treatment for intra-hepatic cholestasis of pregnancy and appears to improve foetal outcome. Hepatitis B vaccination and immunoglobulin at birth prevents chronic hepatitis B in children of HBsAg (hepatitis B surface antigen) positive carrier mothers. PMID:9514993

Burroughs, A K

1998-01-01

198

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

PubMed

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

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

2012-01-01

199

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

200

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

PubMed

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

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

2014-10-01

201

LAGB in pregnancy: slippage after hyperemesis gravidarum. Report of a case.  

PubMed

Bariatric surgery procedures are more and more performed in women of reproductive age, whose fertility often increases after weight loss, so they frequently become pregnant. In this condition they require appropriate management, according to the type of procedure, malabsorptive or restrictive. If health risks related to obesity (gestational diabetes, pregnancy induced hypertension, pre-eclampsia) decrease after weight loss, other risks related to bariatric procedures could appear. LAGB is a safe and well-tolerated procedure, but some complications could appear more frequently during pregnancy; some symptoms could be suggestive for important complications, that if not treated in the best way could threaten mother and child's health. Emesis of the first trimester could favor slippage, thus influencing feeding and fetal growth. The slippage of the band is a common complication of LAGB, that usually does not lead to serious conditions, but in our case the pregnant risked a lot because of malnutrition. The purpose of this article is to present an obstetric case study of a woman who experienced this complication postbariatric surgery and the implications for mother and child. A correct diagnosis and management of the clinical case led to a positive conclusion, thus underlining bariatric surgery and its complications should be known and taken into account by every physician. PMID:23064305

Pilone, Vincenzo; Di Micco, Rosa; Monda, Angela; Villamaina, Elisabetta; Gentile, Maurizio; Forestieri, Pietro

2012-01-01

202

Maternal mortality in a Nigerian teaching hospital - a continuing tragedy.  

PubMed

The aim of this review is to determine the maternal mortality ratio (MMR) in a Nigerian tertiary health institution (University of Ilorin Teaching Hospital, Ilorin, Nigeria). The review was done through a retrospective analysis of maternal mortality records. The MMR for the 6-year period (1997-2002) was 825 per 100,000 live births. The common causes of maternal mortality included severe pre-eclampsia/eclampsia, 30 (27.8%); haemorrhage, 22 (20.4%) and complications of unsafe abortion 16 (14.8%). Grandmultiparous and patients aged 40 years and above were at the highest risk. This hospital-based MMR is very high and when compared with previous reports showed a 150% increase. Most of the maternal deaths are, however, preventable. Increased efforts at educating women, improvement of the socioeconomic conditions of the populace and strong political commitment in making emergency obstetric care available in rural and district hospitals are some of the measures that need to be adopted to reduce this avoidable tragedy. PMID:17540085

Aboyeji, A P; Ijaiya, M A; Fawole, A A

2007-04-01

203

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

PubMed

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

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

2014-10-01

204

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

PubMed

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

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

2004-06-01

205

[Hyperhomocysteinemia: associated obstetric diabetes and fetal malformations].  

PubMed

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

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

2005-12-01

206

Retrospective study of maternal mortality in a tertiary hospital in Egypt  

PubMed Central

Background: Making efforts to decrease maternal mortality rate is a moral, economic and human rights related issue. This issue could not be handled without investigation of maternal mortality related factors. The role of anesthesia in maternal mortality in developing countries is obscure. The aim of the study is to estimate the prevalence, causes and risk factors of maternal mortality related to anesthesia. Patients and Methods: An observational retrospective study was carried out in our university hospital from January 2004 till December 2008. Results: The study revealed that maternal mean age of death was 34.9 years, 59% of women came from rural areas and 41% from urban ones, 65% delivered inside the hospital while 35% delivered outside, 71% were multiparous, 65% had no antenatal care and 29.7% irregular one, 12% were complaining of concomitant diseases, 77.5% labored with cesarean section, 17% died before labor, 36% during and 47% after labor. Causes of death are given in the order of the most leading cause of death to the least as follows: postpartum hemorrhage, eclampsia, pre-eclampsia, postpartum eclampsia, ruptured uterus, amniotic fluid embolism, accidental hemorrhage, anesthesia and at last unexplained causes. Conclusions: Maternal mortality was 953 per 100,000 cases and the greatest number of deaths took place among women considered to be at low risk. Anesthesia was responsible for about 8% of the causes of death. Difficult airway management during general anesthesia was the major anesthetic reason for maternal mortality.

El Daba, Ahmed A.; Amr, Yasser M.; Marouf, Hesham M.; Mostafa, Manal

2010-01-01

207

Advanced Poincaré plot analysis differentiates between hypertensive pregnancy disorders.  

PubMed

Hypertensive pregnancy disorders affect 6% to 8% of all pregnancies and can result in severe complications for the mother and the foetus of which pre-eclampsia (PE) has the worst perinatal outcome. Several studies suggested that the autonomic nervous system plays an important role in the process of developing hypertensive pregnancy disorders, especially PE. The aim of this retrospective study was to investigate whether women with PE could be differentiated from women with various other hypertensive pregnancy disorders, by employing an enhanced Poincaré plot analysis (PPA), the segmented Poincaré plot analysis (SPPA), to their beat-to-beat interval and blood pressure signals. Sixty-nine pregnant women with hypertensive disorders (29 PE, 40 with chronic or gestational hypertension) were included. The SPPA as well as the traditional PPA found significant differences between PE and other hypertensive disorders of diastolic blood pressure (p < 0.001 versus p < 0.001) but only the SPPA method revealed significant differences (p < 0.001) also of the systolic blood pressure. Further on, linear discrimination analysis demonstrated that indices derived from SPPA are more suitable for differentiation between chronic and gestational hypertension and PE than those from traditional PPA (area under the ROC curve 0.85 versus 0.69). Therefore this procedure could contribute to the differential diagnosis of hypertensive pregnancy disorders. PMID:21896969

Seeck, A; Baumert, M; Fischer, C; Khandoker, A; Faber, R; Voss, A

2011-10-01

208

Getting too sweet: galectin-1 dysregulation in gestational diabetes mellitus.  

PubMed

Galectin-1 (gal-1) is a prototype carbohydrate-binding protein, whose dysregulation is associated with adverse pregnancy outcomes such as spontaneous abortion and pre-eclampsia. Furthermore, it is known that faulty gal-1 protein production or gene regulation can be caused by single-nucleotide polymorphisms in the LGALS1 gene. Gestational diabetes mellitus (GDM) is also an adverse pregnancy outcome and the most common metabolic disorder during gestation. However, gal-1 expression patterns during GDM remain largely unknown. Our aims were to define local and peripheral gal-1 expression patterns during pregnancy, and to investigate LGALS1 gene polymorphisms in GDM patients. Circulating gal-1 levels were determined by ELISA in GDM patients and normal pregnant controls, and LGALS1 gene polymorphisms were assessed for association with GDM. Placental tissues were collected from control and GDM term pregnancies to evaluate local gal-1 expression by immunofluorescence. Our results show that GDM is associated with a failure to increase circulating gal-1 levels during the second and third trimester, as well as overexpression of gal-1 in placental tissue. Additionally, the LGALS1 polymorphism rs4820294 was associated with the development of GDM. In pregnancies complicated by GDM, we observed gal-1 dysregulation both locally in the placenta and peripherally in the circulation. Furthermore, the association between the LGALS1 polymorphism and GDM may indicate a genetic contribution to this adverse pregnancy outcome. PMID:24637109

Blois, Sandra M; Gueuvoghlanian-Silva, Barbara Y; Tirado-González, Irene; Torloni, Maria R; Freitag, Nancy; Mattar, Rosiane; Conrad, Melanie L; Unverdorben, Laura; Barrientos, Gabriela; Knabl, Julia; Toldi, Gergely; Molvarec, Attila; Rose, Matthias; Markert, Udo R; Jeschke, Udo; Daher, Silvia

2014-07-01

209

Interventions for preventing and treating hyperthyroidism in pregnancy  

PubMed Central

Background Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption. Objectives To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 July 2010). Selection criteria We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism. Data collection and analysis Two review authors would have assessed trial eligibility and risk of bias, and extracted data. Main results No trials were located. Authors’ conclusions As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid drugs for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil. PMID:20824882

Earl, Rachel; Crowther, Caroline A; Middleton, Philippa

2014-01-01

210

Pregnancy outcome of overweight and obese Chinese women with gestational diabetes.  

PubMed

Abstract We investigated the pregnancy outcome of overweight and obese Chinese women with gestational diabetes mellitus (GDM). Patients diagnosed as GDM from January 2010 to December 2011 were categorised into three groups, as normal weight, overweight and obese, according to the maternal pre-pregnancy body mass index (BMI) (kg/m(2)), 18.5-24.9, 25-29.9 and ? 30, respectively. Of the 604 GDM cases, 241 (39.9%), 211 (34.9%) and 152 (25.2%) subjects were normal weight, overweight and obese, respectively. Compared with subjects of normal weight, the incidence of assisted reproductive technology (ART) pregnancy, advanced maternal age, fetal macrosomia and emergency caesarean delivery were significantly higher in overweight and obese groups (p < 0.05). Obese women were at increased risk of premature rupture of membranes, pre-eclampsia and caesarean section compared with the other two groups (p < 0.05). Overweight and obese women with GDM have an increased risk of adverse pregnancy outcomes, even with good glycaemic control. PMID:24911378

Zhang, Y; Wang, Z-L; Liu, B; Cai, J

2014-11-01

211

Stress Questionnaires and Stress Biomarkers during Pregnancy  

PubMed Central

Abstract Objective Both self-reported indicators of stress and hormones such as cortisol and corticotrophin-releasing hormone (CRH) have been examined in relation to preterm birth. Although these hormones have been interpreted as biomarkers of stress, it is unclear whether psychosocial measures are empirically associated with biomarkers of stress in pregnant women. Methods We analyzed data from 1,587 North Carolina pregnant women enrolled in the Pregnancy, Infection, and Nutrition study during 2000–2004 who provided at least one saliva sample for cortisol measurement or blood samples for CRH at 14–19 and 24–29 weeks' gestation. Cortisol measures were limited to those taken between 8 and 10 a.m. Perceived stress, state-trait anxiety, coping style, life events, social support, and pregnancy-specific anxiety were measured by questionnaires and interviews. Spearman correlations and multiple regressions were used to describe the relationship among the measures of stress. Results No correlations larger than r?=?0.15 were seen between reported psychosocial measures and cortisol or CRH. Women with demographic characteristics associated with poor pregnancy outcomes (unmarried, African-American, young, low pre-pregnancy body mass index) reported higher levels of stress but did not consistently have higher levels of stress hormones. Pre-eclampsia was associated with higher CRH, but not with higher cortisol. Conclusions The relationship between measurements of reported stress and biomarkers is not straightforward in large epidemiological studies of pregnancy. For online Supplementary Material, see www.liebertonline.com. PMID:19757520

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

2009-01-01

212

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; Pena-Rosas, Juan Pablo

2013-01-01

213

The impact of close surveillance on pregnancy outcome among women with a prior history of antepartum complications attributed to thrombosis: a cohort study  

PubMed Central

Background There is limited evidence, so far, as to the optimal management of women with a prior obstetric history of antepartum complications attributed to thrombosis. We aimed to investigate the contribution of close antepartum surveillance on pregnancy outcome among women with prior antepartum complications attributed to thrombosis. Methods The study was conducted on all women who were delivered, conceived and delivered again between January 2000 and January 2006 at a university teaching hospital. Women included were managed in previous pregnancy at a low risk setting and had unpredicted antepartum complications occurring at a gestational age of 23 weeks or more. Antepartum complications considered were intrauterine fetal death, neonates who were small for gestational age, severe pre-eclampsia and placental abruption. All women were tested for the presence of thrombophilia after delivery. In the following pregnancy, only women found to have any thrombophilia (thrombophilic group) were treated with enoxaparin. Both the thrombophilic group and the non-thrombophilic group (tested negatively for thrombophilia) were managed and observed closely at our high-risk pregnancy clinic. Results Ninety-seven women, who conceived at least once after the diagnosis of the relevant antepartum complications, were included in this study. Forty-nine had any thrombophilia and 48 tested negatively. Composite antepartum complications (all antepartum complications considered) were reduced significantly after close antepartum surveillance in both groups. Mean birth weight and mean gestational age improved significantly and were comparable between the groups. Conclusion Close antepartum surveillance may contribute to improvement in the perinatal outcomes of women with prior antepartum complications attributed to thrombosis. PMID:19025596

Salim, Raed; Czarnowicki, Tali; Nachum, Zohar; Shalev, Eliezer

2008-01-01

214

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

PubMed Central

Human leucocyte antigen (HLA) -G is expressed on trophoblast cells during pregnancy, suggesting a role in protection of the semiallogeneic fetus. Published data suggest that HLA-G protects a cell against natural killer cell lysis. It has been hypothesized that HLA-G may also protect the fetus by preventing allo-cytotoxic T lymphocyte (CTL) responses. To test this hypothesis, we assayed the effects of various concentrations of purified HLA-G on CTL response in a mixed lymphocyte culture (MLC) system. We found that concentrations ? 0·1 µg/ml of HLA-G suppressed the allo-CTL response by 30–100% over the control, but, paradoxically, concentrations of 0·01–0·05 µg/ml of HLA-G augmented the allo-CTL response by 25–50% over the control. Concentrations ? 0·001 µg/ml HLA-G had no effect. Addition of HLA-G to preprimed allo-CTL effector cells did not affect their killing ability. Allo-CTL suppressive doses of HLA-G induced a T helper type 2 (Th2) cytokine response, whereas allo-CTL-enhancing doses of HLA-G induced a Th1-type cytokine response. HLA-G purified from first-trimester placenta does not affect allo-proliferative responses nor does it alter the percentage of CD4+ or CD8+ T cells in MLCs. These findings support a potential role for HLA-G-mediated suppression of allo-CTL formation in normal pregnancies. In addition, the effects observed at lower concentrations of HLA-G may have interesting implications for the condition of pre-eclampsia in which concentrations of this HLA class I molecule are reduced. PMID:11012772

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

2000-01-01

215

Mood disorders and parity – A clue to the aetiology of the postpartum trigger  

PubMed Central

Background Episodes of postpartum psychosis have been associated with first pregnancies in women with bipolar I disorder. It is unclear, however, if the effect extends to episodes at other times in relation to childbirth and to women with other mood disorders such as major depression and bipolar II disorder. This primiparity effect, which is also seen in other pregnancy related conditions such as pre-eclampsia, is a potentially important clue to the aetiology of childbirth related mood episodes. Methods Participants were interviewed and case notes reviewed. Best-estimate diagnoses were made according to DSM-IV criteria. Data on the occurrence of episodes in pregnancy and the postpartum were available on 3345 full term deliveries from 1667 participants, 934 with bipolar I disorder (BD-I), 278 with bipolar II disorder (BD-II) and 455 with recurrent major depression (RMD). Results Onsets of psychosis/mania within 6 weeks of childbirth were overrepresented in primiparae (p=0.007) with BD-I. Although primiparity was not associated with perinatal bipolar depression, there was an association with the onset of depression within 6 weeks in women with RMD (p=0.035). Whilst women experiencing a postpartum episode were less likely to go on to have further children, this did not account for the association with primiparity. Limitations Data were collected retrospectively. Information on pharmacological treatment was not available. Conclusions Primiparity is associated not only with postpartum psychosis/mania in BD-I, but also with postpartum depression in RMD. Psychosocial factors and biological differences between first and subsequent pregnancies may play a role and are candidates for examination in further studies. PMID:24446553

Di Florio, Arianna; Jones, Lisa; Forty, Liz; Gordon-Smith, Katherine; Robertson Blackmore, Emma; Heron, Jess; Craddock, Nick; Jones, Ian

2014-01-01

216

Effect of hypoxia, oxidative stress and lipopolysaccharides on the release of prostaglandins and cytokines from human term placental explants.  

PubMed

Placental hypoxia, ischaemia, reperfusion and resultant oxidative stress, with the release of various factors into the maternal vasculature acting as mediators of endothelial cell dysfunction, play an important role in the development of pre-eclampsia. Human term placental tissue explants were exposed to different stressors, e.g. hypoxia, oxidative stress and lipopolysaccarides, and the effect on the release of prostanoids and cytokines was determined. The hypoxic environment consisted of 2 per cent O2, 5 per cent CO2and 93 per cent N2. Oxidative stress was induced by addition of xanthine together with xanthine oxidase to the incubation medium. As a third experimental variable, lipopolysaccharide was added to the medium. Prostaglandins (8-iso-PGF(2alpha), or 6-keto-PGF(1alpha)and TXB(2)as stable metabolites of prostacyclin and thromboxane, respectively) and cytokines (TNF-alpha, IL-1alpha, IL-1beta, IL-6) were measured using commercial ELISA assays. Under control conditions, the production of prostaglandins in ng/24 h (mean +/- s.d.) was 6 +/- 3 for 8-iso-PGF(2alpha), 19 +/- 9 for 6-keto-PGF(1alpha)and 5 +/- 2 for TXB2. The production of cytokines was 13 +/- 6 pg for TNF-alpha, 7 +/- 2 pg for IL-1alpha, 5 +/- 3 pg for IL-1beta and 18 +/- 9 ng for IL-6. Under hypoxia the production of prostaglandins remained unchanged and of the cytokines only IL-1beta showed a 15-fold increase. Oxidative stress resulted in an increase in the release of prostaglandins and of cytokines of 4- to 15- and 3- to 130-fold, respectively. Lipopolysaccharides and oxidative stress had a similar effect on the production of prostaglandins, whereas the stimulatory effect of lipopolysaccharides on cytokines was significantly higher than that of oxidative stress. PMID:11312628

Malek, A; Sager, R; Schneider, H

2001-04-01

217

Prospective study of liver dysfunction in pregnancy in Southwest Wales  

PubMed Central

Background: Liver dysfunction in pregnancy has serious consequences. Its frequency and characteristics have not been systematically documented in Britain. We have prospectively determined incidence, causes, and outcome of liver dysfunction in pregnancy in an obstetric unit in Southwest Wales, UK. Methods: A central laboratory identified all abnormal liver tests (bilirubin >25 ?mol/l, aspartate transaminase >40 U/l, or ? glutamyl transpeptidase >35 U/l) from patients in antenatal clinics and wards of an obstetric unit serving a population of 250 000. Patients with abnormal liver tests were assessed and followed through after pregnancy. Medical advice was provided to obstetric teams. Findings: There were 4377 deliveries during the 15 month study. A total of 142 patients had abnormal liver tests. There were 206 contributing diagnoses, the great majority being pregnancy specific. Among the most important were pre-eclampsia (68), HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome (30), obstetric cholestasis (23), hyperemesis gravidarum (11), acute fatty liver of pregnancy (five), and hepatic infarct (one). Sepsis, postoperative factors, and placental pathology (51) were not uncommonly responsible but incidental or pre-existing hepatobiliary disease was infrequent (17). Sixty five patients were delivered early by induction or caesarean section because of liver dysfunction. Despite substantial liver related morbidity, there were no maternal deaths and only two intrauterine deaths. Conclusions: Liver dysfunction was seen in 3% of deliveries during a 15 month prospective study and was usually directly related to pregnancy with spontaneous recovery in the puerperium. Incidence of the most serious conditions, acute fatty liver of pregnancy and HELLP syndrome, was much greater than previously reported. Profound effects on maternal and infant health were observed but close medical and obstetric collaboration ensured low mortality. PMID:12427793

Ch'ng, C L; Morgan, M; Hainsworth, I; Kingham, J G C

2002-01-01

218

Clinical review: Special populations - critical illness and pregnancy  

PubMed Central

Critical illness is an uncommon but potentially devastating complication of pregnancy. The majority of pregnancy-related critical care admissions occur postpartum. Antenatally, the pregnant patient is more likely to be admitted with diseases non-specific to pregnancy, such as pneumonia. Pregnancy-specific diseases resulting in ICU admission include obstetric hemorrhage, pre-eclampsia/eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, amniotic fluid embolus syndrome, acute fatty liver of pregnancy, and peripartum cardiomyopathy. Alternatively, critical illness may result from pregnancy-induced worsening of pre-existing diseases (for example, valvular heart disease, myasthenia gravis, and kidney disease). Pregnancy can also predispose women to diseases seen in the non-pregnant population, such as acute respiratory distress syndrome (for example, pneumonia and aspiration), sepsis (for example, chorioamnionitis and pyelonephritis) or pulmonary embolism. The pregnant patient may also develop conditions co-incidental to pregnancy such as trauma or appendicitis. Hemorrhage, particularly postpartum, and hypertensive disorders of pregnancy remain the most frequent indications for ICU admission. This review focuses on pregnancy-specific causes of critical illness. Management of the critically ill mother poses special challenges. The physiologic changes in pregnancy and the presence of a second, dependent, patient may necessitate adjustments to therapeutic and supportive strategies. The fetus is generally robust despite maternal illness, and therapeutically what is good for the mother is generally good for the fetus. For pregnancy-induced critical illnesses, delivery of the fetus helps resolve the disease process. Prognosis following pregnancy-related critical illness is generally better than for age-matched non-pregnant critically ill patients. PMID:21888683

2011-01-01

219

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

220

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

221

Chronic sleep loss during pregnancy as a determinant of stress: impact on pregnancy outcome.  

PubMed

Short sleep duration, poor sleep quality, and insomnia frequently characterize sleep in pregnancy during all three trimesters. We aimed: (i) to review the clinical evidence of the association between conditions of sleep loss during pregnancy and adverse pregnancy outcomes; and (ii) to discuss the potential pathophysiological mechanisms that may be involved. A systematic search of cross-sectional, longitudinal studies using Medline, Embase, and PsychINFO, and MeSH headings and key words for conditions of sleep loss such as 'insomnia', 'poor sleep quality', 'short sleep duration', and 'pregnancy outcome' was made for papers published between January 1, 1960 and July 2013. Twenty studies met inclusion criteria for sleep loss and pregnancy outcome: seven studies on prenatal depression, three on gestational diabetes, three on hypertension, pre-eclampsia/eclampsia, six on length of labor/type of delivery, eight on preterm birth, and three on birth grow/birth weight. Two main results emerged: (i) conditions of chronic sleep loss are related to adverse pregnancy outcomes; and (ii) chronic sleep loss yields a stress-related hypothalamic-pituitary-adrenal axis and abnormal immune/inflammatory, reaction, which, in turn, influences pregnancy outcome negatively. Chronic sleep loss frequently characterizes sleep throughout the course of pregnancy and may contribute to adverse pregnancy outcomes. Common pathophysiological mechanisms emerged as being related to stress system activation. We propose that in accordance to the allostatic load hypothesis, chronic sleep loss during pregnancy may also be regarded as both a result of stress and a physiological stressor per se, leading to stress 'overload'. It may account for adverse pregnancy outcomes and somatic and mental disorders in pregnancy. PMID:24994566

Palagini, Laura; Gemignani, Angelo; Banti, Susanna; Manconi, Mauro; Mauri, Mauro; Riemann, Dieter

2014-08-01

222

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

PubMed Central

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

2012-01-01

223

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

PubMed Central

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

2011-01-01

224

Thrombophilia risk factors are associated with intrauterine foetal death and pregnancy-related venous thromboembolism.  

PubMed

Pregnancy in healthy women is accompanied by hypercoagulable changes that may interact with thrombophilia risk factors and threaten pregnancy. However, the literature on this issue is conflicting. In investigating the relationship between pregnancy-associated complications and the presence of thrombophilia risk factors, we studied the records of 414 women who had been examined for inherited and acquired thrombophilia in the period 1996 to 2006 because of pregnancy-associated complications. Of a total of 885 pregnancies among the women, 397 were recorded as foetal loss/intrauterine foetal death during the first (62 %), second (25 %) or third trimester (13 %). One-hundred-and-two (25 %) women had had a thromboembolic event during one of their pregnancies, and 98 (24 %) had had pre-eclampsia on at least one occasion. Intrauterine growth restriction was found in 105 (25 %) of the women, and 29 (7 %) suffered placental abruption. We found that 120 (29 %) women had at least one thrombophilia risk factor. Factor V Leiden heterozygosity was the most common thrombophilia factor (n = 52), mostly linked with the risk of venous thromboembolism during pregnancy or postpartum and to foetal death during the second or third trimester. Fifty-three (13 %) women had antiphospholipid antibodies (lupus anticoagulant and/or anti-beta2-glycoprotein 1 antibodies) mainly associated with the risk of spontaneous abortion during the first trimester. In conclusion, thrombophilia was found to be considerably more common in women with pregnancy-associated complications in comparison with the general population, and most frequently in conjunction with venous thromboembolism during pregnancy and the postpartum period. PMID:19031171

Hvas, Anne-Mette; Ingerslev, Jorgen; Salvig, Jannie Dalby

2009-01-01

225

Fetal growth restriction is associated with reduced FasL expression by decidual cells.  

PubMed

The Fas-Fas ligand (FasL) system contributes to immune tolerance at the feto-maternal site and has been ascribed a role in implantation and placental development by regulating trophoblast invasion and spiral artery remodelling. In the present study, we have examined FasL expression in decidual tissue from pregnancies with impaired placental development. Women with pre-eclampsia (PE) and/or fetal growth restriction (FGR) were enrolled as cases (n=33), and women with normal pregnancies were used as controls (n=27). Decidua basalis tissue was obtained by vacuum suction of the placental bed after delivery. FasL expression by extravillous trophoblasts (EVTs) and decidual cells (DeCs), together with EVT apoptosis, were assessed by immunohistochemistry. Levels of soluble FasL in maternal serum and apoptosis-related gene expression in decidual tissue were determined. The proportion of FasL-expressing DeCs was high in controls (72.0+/-10.2%), with a significant reduction among cases (58.1+/-19.7%; p=0.002), especially in those with FGR (54.3+/-19.9%; p<0.001). EVTs had a lower proportion of FasL expression than DeCs, with a less pronounced reduction in cases compared to controls (10.9+/-3.9 and 8.3+/-4.0%, respectively; p=0.02). Decidual FasL expression correlated with placental growth. The EVT apoptosis rate did not differ between cases and controls (1.1+/-1.9 and 1.1+/-1.3%, respectively). These findings indicate a reduction of immune privilege in decidua of PE/FGR pregnancies by reduced FasL expression and that DeCs may have a central role in the Fas-FasL-based feto-maternal immune balance. PMID:17196256

Eide, Irina P; Isaksen, Christina V; Salvesen, Kjell A; Langaas, Mette; Günther, Clara-Cecilie; Iversen, Ann-Charlotte; Austgulen, Rigmor

2007-06-01

226

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

227

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

228

EFFECT OF PREGNANCY ON AUTOREGULATION OF CEREBRAL BLOOD FLOW IN ANTERIOR VERSUS POSTERIOR CEREBRUM  

PubMed Central

Severe pre/eclampsia are associated with brain edema that forms preferentially in the posterior cerebral cortex possibly due to decreased sympathetic innervation of posterior cerebral arteries and less effective autoregulation during acute hypertension. In the present study, we examined the effect of pregnancy on the effectiveness of cerebral blood flow autoregulation using laser Doppler flowmetry and edema formation by wet:dry weight in acute hypertension induced by phenylephrine infusion in the anterior and posterior cerebrum from nonpregnant (n=8) and late-pregnant (n=6) Sprague Dawley rats. In addition, we compared the effect of pregnancy on sympathetic innervation by tyrosine hydroxylase staining of posterior and middle cerebral arteries (n=5–6/group) and endothelial and neuronal nitric oxide synthase expression using quantitative polymerase chain reaction (n=3/group). In nonpregnant animals, there was no difference in autoregulation between anterior and posterior cerebrum. However, in late-pregnant animals, the threshold of cerebral blood flow autoregulation was shifted to lower pressures in the posterior cerebrum, which was associated with increased neuronal nitric oxide synthase expression in the posterior cerebral cortex vs. anterior. Compared to the nonpregnant state, pregnancy increased the threshold of autoregulation in both brain regions that was related to decreased expression of endothelial nitric oxide synthase. Lastly, acute hypertension during pregnancy caused greater edema formation in both brain cortices that was not due to changes in sympathetic innervation. These findings suggest that although pregnancy shifted the cerebral blood flow autoregulatory curve to higher pressures in both the anterior and posterior cortices, it did not protect from edema during acute hypertension. PMID:22824983

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

2012-01-01

229

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

PubMed

The statistics related to pregnancy and its outcomes are staggering: annually, an estimated 250000-280000 women die during childbirth. Unfortunately, a large number of women receive little or no care during or before pregnancy. At a period of critical vulnerability, interventions can be effectively delivered to improve the health of women and their newborns and also to make their pregnancy safe. This paper reviews the interventions that are most effective during preconception and pregnancy period and synergistically improve maternal and neonatal outcomes. Among pre-pregnancy interventions, family planning and advocating pregnancies at appropriate intervals; prevention and management of sexually transmitted infections including HIV; and peri-conceptual folic-acid supplementation have shown significant impact on reducing maternal and neonatal morbidity and mortality. During pregnancy, interventions including antenatal care visit model; iron and folic acid supplementation; tetanus Immunisation; prevention and management of malaria; prevention and management of HIV and PMTCT; calcium for hypertension; anti-Platelet agents (low dose aspirin) for prevention of Pre-eclampsia; anti-hypertensives for treating severe hypertension; management of pregnancy-induced hypertension/eclampsia; external cephalic version for breech presentation at term (>36 weeks); management of preterm, premature rupture of membranes; management of unintended pregnancy; and home visits for women and children across the continuum of care have shown maximum impact on reducing the burden of maternal and newborn morbidity and mortality. All of the interventions summarized in this paper have the potential to improve maternal mortality rates and also contribute to better health care practices during preconception and periconception period. PMID:25178042

Lassi, Zohra S; Mansoor, Tarab; Salam, Rehana A; Das, Jai K; Bhutta, Zulfiqar A

2014-08-21

230

Quantitative research of capillaries in terminal villi of mature placentae.  

PubMed

Advanced maternal age is known to be a risk factor for placental dysfunctions. The most common obstetric complications among older women would be considered as follows: gestational diabetes; pre-eclampsia; placenta praevia; preterm premature rupture of membranes and the risk of preterm delivery. The aims of research were to determine the impact of maternal age on the structure of terminal villi. The study was conducted on 60 human placentae of term pregnancy divided into two groups: the control group (30 placentae in pregnant women of age between 20 and 34) and the experimental group (30 placentae in pregnant women of 35 years of age and older). Stereological methods were applied to determine the volume density, surface density, total volume and total capillary surface area in terminal villi of placenta. The mean value of volume density of capillaries in terminal villi of placentae in older pregnant women is: Vvkks = (0,376 +/- 0,033) mm(0), and the mean value of total volume is: Vkks = (157,047 +/- 25,022) cm(3). The mean value of surface density is: Svkks = (64,783 +/- 2,543) mm(-1), and the mean value of total surface area is: Skks = (29,959 +/- 7,873) m(2). Volume density of capillaries in terminal villi of placentae is significantly lower in older pregnant women (p<0.001) in comparison to the younger pregnant women. The total volume, surface density and total capillary surface area in terminal villi of placentae are also significantly lower in older pregnant women (p<0.005) in comparison to the younger pregnant women. Statistically significant lower values of volume density, total volume, surface density and total capillary surface area indicate that there is a decreased metabolic transfer between mother and foetus. PMID:20507296

Zigi?, Zlata; Markovi?, Sergije; Grbesa, Durdica; Rami?, Suada; Halilovi?, Almir

2010-05-01

231

Priority Medicines for Maternal and Child Health: A Global Survey of National Essential Medicines Lists  

PubMed Central

Background In April 2011, the World Health Organization (WHO) published a list of “priority medicines” for maternal and child health based on 1) the global burden of disease and 2) evidence of efficacy and safety. The objective of this study was to examine the occurrence of these priority medicines on national essential medicines lists. Methods and Findings All essential medicines lists published since 1999 were selected from the WHO website collection. The most-up-to date list for each country was then selected, resulting in 89 unique country lists. Each list was evaluated for inclusion of medicines (chemical entity, concentration, and dosage form) on the Priority Medicines List. There was global variation in the listing of the Priority Medicines. The most frequently listed medicine was paracetamol, on 94% (84/89) of lists. Sodium chloride, gentamicin and oral rehydration solution were on 93% (83/89) of lists. The least frequently listed medicine was the children's antimalarial rectal artesunate, on 8% of lists (7/89); artesunate injection was on 16% (14/89) of lists. Pediatric artemisinin combination therapy, as dispersible tablets or flexible oral solid dosage form, appeared on 36% (32/89) of lists. Procaine benzylpenicillin, for treatment of pediatric pneumonia and neonatal sepsis, was on 50% (45/89) of the lists. Zinc, for treatment of diarrhoea in children, was included on only 15% (13/89) of lists. For prevention and treatment of postpartum hemorrhage in women, oxytocin was more prevalent on the lists than misoprostol; they were included on 55 (62%) and 31 (35%) of lists, respectively. Cefixime, for treatment of uncomplicated anogenital gonococcal infection in woman was on 26% (23/89) of lists. Magnesium sulfate injection for treatment of severe pre-eclampsia and eclampsia was on 50% (45/89) of the lists. Conclusions The findings suggest that countries need to urgently amend their lists to provide all priority medicines as part of the efforts to improve maternal and child health. PMID:22675435

Hill, Suzanne; Yang, Annie; Bero, Lisa

2012-01-01

232

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

PubMed Central

Protocadherins are a group of transmembrane proteins with homophilic binding activity, members of the cadherin superfamily. Apart from their role in adhesion, the cellular functions of protocadherins are essentially unknown. Protocadherin (PCDH)12 was previously identified in invasive trophoblasts and endothelial and mesangial cells in the mouse. Invalidation studies revealed that the protein was required for optimal placental development. In this article, we show that its human homolog is abundantly expressed in various trophoblast subtypes of the human placenta and at lower levels in endothelial cells. We demonstrate that PCDH12 is shed at high rates in vitro. The shedding mechanism depends on ADAM10 and results in reduced cellular adhesion in a cell migration assay. PCDH12 is subsequently cleaved by the ?-secretase complex, and its cytoplasmic domain is rapidly degraded by the proteasome. PCDH12 shedding is regulated by interlinked intracellular pathways, including those involving protein kinase C, PI3K, and cAMP, that either increase or inhibit cleavage. In endothelial cells, VEGF, prostaglandin E2, or histamine regulates PCDH12 shedding. The extracellular domain of PCDH12 was also detected in human serum and urine, thus providing evidence of PCDH12 shedding in vivo. Importantly, we observed an increase in circulating PCDH12 in pregnant women who later developed a pre-eclampsia, a frequent pregnancy syndrome and a major cause of maternal and fetal morbidity and mortality. In conclusion, we speculate that, like in mice, PCDH12 may play an important role in human placental development and that proteolytic cleavage in response to external factors, such as cytokines and pathological settings, regulates its activity. PMID:21402705

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

2011-01-01

233

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

PubMed

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

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

2014-11-01

234

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

PubMed Central

Background Maternal mortality is high the world over, especially in sub-Saharan Africa, including Nigeria. Nigeria has consistently demonstrated one of the most abysmally poor reproductive health indices in the world, maternal mortality inclusive. This is a sad reminder that, unless things are better organized, Southeast Nigeria, which Nnamdi Azikiwe University Teaching Hospital (NAUTH) represents, may not join other parts of the world in attaining Millennium Development Goal 5 to improve maternal health in 2015. Objectives This study was conducted to assess NAUTH’S progress in achieving a 75% reduction in the maternal mortality ratio (MMR) and to identify the major causes of maternal mortality. Materials and methods This was a 10-year retrospective study, conducted between January 1, 2003 and December 31, 2012 at Nnamdi Azikiwe University Teaching Hospital, Nnewi, Southeast Nigeria. Results During the study period, there were 8,022 live births and 103 maternal deaths, giving an MMR of 1,284/100,000 live births. The MMR was 1,709 in 2003, reducing to 1,115 in 2012. This is to say that there was a 24.86% reduction over 10 years, hence, in 15 years, the reduction should be 37%. This extrapolated reduction over 15 years is about 38% less than the target of 75% reduction. The major direct causes of maternal mortality in this study were: pre-eclampsia/eclampsia (27%), hemorrhage (22%), and sepsis (12%). The indirect causes were: anemia, anesthesia, and HIV encephalopathy. Most of the maternal deaths occurred in unbooked patients (98%) and within the first 48 hours of admission (76%). Conclusion MMRs in NAUTH are still very high and the rate of reduction is very slow. At this rate, it will take this health facility 30 years, instead of 15 years, to achieve a 75% reduction in maternal mortality. PMID:23901299

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

2013-01-01

235

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

PubMed Central

Background Despite clear emphasis through the Millennium Development Goals, the problem of high maternal mortality persists especially within low and middle income countries. Various studies report remarkably high maternal mortality rates in northern Nigeria, where maternal mortality rates exceed 1,000 deaths per 100,000 live births and eclampsia contributes approximately 40% of maternal deaths. Across Nigeria, diazepam is routinely used for the management of eclampsia. Prior to February 2008, diazepam was widely used for the management of eclampsia in Kano State (within northern Nigeria) with case fatality rate being over 20%. While magnesium sulphate (MgSO4) is recognized as the most effective drug for the management of eclampsia; this study aims to compare MgSO4 therapy with diazepam therapy in terms of case fatality rates and costs. Findings This retrospective study, including 1045 patients with eclampsia and pre-eclampsia during the years 2008 and 2009, reports a drop in case fatality rates from 20.9% (95% CI: 18.7, 23.2) to 2.3% (95% CI: 1.4, 3.2) among eclampsia patients following the MgSO4 intervention. The study observed no significant difference in the cost of using MgSO4 therapy compared to diazepam therapy. Conclusions The study found a remarkable reduction in case fatality rate due to eclampsia in those who received MgSO4 therapy with minimal increase in costs when compared to diazepam therapy. Concerted efforts should be focused on properly introducing MgSO4 into emergency obstetric protocols especially within developing countries to reduce maternal mortality and also impact on health system performance. PMID:22873658

2012-01-01

236

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

PubMed Central

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

Llurba, Elisa; Carreras, Elena; Gratacos, Eduard; Juan, Miquel; Astor, Judith; Vives, Angels; Hermosilla, Eduard; Calero, Ines; Millan, Pilar; Garcia-Valdecasas, Barbara; Cabero, Lluis

2009-01-01

237

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

238

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

PubMed Central

BACKGROUND: Health professionals face the adverse health effects of climate change and air pollution in their practices. This review underscores the effects of these environmental factors on maternal and children's health, as the most vulnerable groups to climate change and air pollution. METHODS: We reviewed electronic databases for a search of the literature to find relevant studies published in English from 1990 to 2011. RESULTS: Environmental factors, notably climate change and air pollution influence children's health before conception and continue during pregnancy, childhood, and adolescence. Experts have suggested that such health hazards may represent the greatest public health challenge that humanity has faced. The accumulation of greenhouse gases such as carbon dioxide, primarily from burning fossil fuels, results in warming which has an impact on air pollution particularly on levels of ozone and particulates. Heat-related health effects include increased rates of pregnancy complications, pre-eclampsia, eclampsia, low birth weight, renal effects, vector-borne diseases as malaria and dengue, increased diarrheal and respiratory disease, food insecurity, decreased quality of foods (notably grains), malnutrition, water scarcity, exposures to toxic chemicals, worsened poverty, natural disasters and population displacement. Air pollution has many adverse health effects for mothers and children. In addition to short-term effects like premature labour, intrauterine growth retardation, neonatal and infant mortality rate, malignancies (notably leukaemia and Hodgkin lymphoma), respiratory diseases, allergic disorders and anaemia, exposure to criteria air pollutants from early life might be associated with increase in stress oxidative, inflammation and endothelial dysfunction which in turn might have long-term effects on chronic non-communicable diseases. CONCLUSIONS: Health professionals have an exclusive capability to help prevent and reduce the harmful effects of environmental factors for high-risk groups, and should consider this capacity in their usual practice. PMID:22224116

Poursafa, Parinaz; Kelishadi, Roya

2011-01-01

239

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

240

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

PubMed Central

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

2014-01-01

241

Expression of AT1R, AT2R and AT4R and their roles in extravillous trophoblast invasion in the human.  

PubMed

The placental renin-angiotensin system (RAS) is active from early pregnancy and may have a role in placentation. Angiotensin II (AngII) acts via binding to receptor types AT1R and AT2R. Recently smaller peptide members of the angiotensin family have been recognised as having biological relevance. Angiotensin (3-8) (AngIV) has a specific receptor (AT4R) and evokes hypertrophy, vasodilatation and vascular inflammatory response. The aim of this study was to characterise placental expression of AT1R, AT2R and AT4R, and to determine whether AngII and AngIV regulate extravillous trophoblast (EVT) invasion, apoptosis and proliferation. Placental samples were obtained from women undergoing elective surgical termination of pregnancy (TOP) at 8-10 weeks gestation (early TOP), 12-14 weeks gestation (mid TOP) or at delivery following normal pregnancy or with pre-eclampsia (PE). Immunohistochemistry and qRT-PCR were performed to determine placental mRNA and protein expression of AT1R, AT2R and AT4R at all gestational ages. EVT invasion following culture with AngII or AngIV was assessed in early placental tissue using Matrigel invasion assays. Invasion was assessed on day 6 of culture and placental explants were harvested for immunohistochemical analysis of apoptosis and proliferation. The results from qRT-PCR and immunohistochemistry showed placental AT1R expression which did not vary with gestation. The highest levels of expression of AT2R were found in early and mid TOP placentae compared to term pregnancy. Expression of AT4R was increased in term placentae, with a significant reduction in PE placentae. Moreover, culture with AngIV or AngII increased EVT invasion from placental explants, which showed increased trophoblast proliferation and reduced apoptosis. This study has characterised expression of AT4R and AT1R and AT2R in human placenta throughout normal pregnancy and in PE. Both AngIV and AngII may play an important role in normal pregnancy. PMID:20304486

Williams, P J; Mistry, H D; Innes, B A; Bulmer, J N; Broughton Pipkin, F

2010-05-01

242

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

243

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

244

Interventions for the control of diarrhoeal diseases among young children: prevention of low birth weight*  

PubMed Central

The effect of low birth weight (LBW) on diarrhoea morbidity and mortality is analysed and interventions to increase birth weights are reviewed. Birth weight is a major determinant of infant mortality and, in developed countries at least, its effect on neonatal mortality is independent of socioeconomic status. We have located no satisfactory data on LBW as a determinant of diarrhoea mortality or morbidity. The strong association between LBW and mortality, however, makes it likely that there is an association between LBW and diarrhoea mortality in developing countries where diarrhoea is a major cause of infant death. Poor maternal nutrition, certain infections, pre-eclampsia, arduous work after mid-pregnancy, short birth intervals, and teenage pregnancy are likely to be causally associated with LBW in developing countries. Tobacco and alcohol consumption are additional risk factors. Of the interventions examined, maternal food supplementation has been the most studied. If targeted to mothers at nutritional risk, and if the food is consumed in addition to the usual diet, the prevalence of LBW can be expected to be reduced. However, food supplementation can be expensive and the results from carefully supervised feeding trials may be better than those that can be achieved in national programmes. The effect of supplementation with iron, zinc or folate requires further study. If it were possible to intervene in maternal nutrition, health and life-style in a developing country in a way that reduced the prevalence of LBW from around 30% to around 15%, a fall in the infant mortality rate of around 26% would be expected. The fall in infant diarrhoea mortality rate might be similar. The scarce data on relative risk of morbidity by birth weight do not allow any comparable computations for morbidity reductions to be made. This review confirms that whatever its association with diarrhoea, LBW is an important determinant of infant mortality. For the more general goal of reducing infant mortality it is necessary to know more about the nature, etiology, and prevention of LBW in developing countries. PMID:3886185

Ashworth, Ann; Feachem, R. G.

1985-01-01

245

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

246

Risk factos for pregnancy-related mortality: A prospective study in rural Nepal  

PubMed Central

Summary Objectives This study examined the risk factors of mortality related to pregnancy for the first year post partum in a cohort of 25,580 pregnancies. Study design Longitudinal cohort follow-up. Methods Details of socio-economic status, mid-upper arm circumference (MUAC), diet, illness, work, substance use and previous pregnancy history were collected during early to mid-gestation, and these women were followed for 1 year post partum. All-cause mortality rates per 100,000 pregnancies were calculated for deaths during pregnancy or up to 42 days post partum (early period) and 43?364 days post partum (late period). Odds ratios (OR) of mortality were estimated using five groups of risk factors: biological; morbidity; dietary; lifestyle; and socio-economic. Significant factors within each group were included in a single risk model for each time period. Results Early and late pregnancy-related mortality rates were 469 [95% confidence interval (CI) 385?553] and 254 (95% CI 192?316), respectively. Maternal age ?35 years was associated with a three- to four-fold increase in mortality, whereas increasing parity conferred increasing protection. In the final model, a larger MUAC and consumption of dark green leaves were associated with decreased risk of death in the early period (OR 0.76, 95% CI 0.67?0.87 and 0.64, 95% CI 0.41?0.99, respectively). A larger MUAC was also associated with a lower risk of death in the late period. Diarrhoea/dysentery and pre-eclampsia were associated with increased risk of death in the early period (OR 2.78, 95% CI 1.40?5.51 and 2.95, 95% CI 1.48?5.90, respectively). Factors weakly associated (P<0.1) with mortality in both periods included night blindness, strenuous work activity and cigarette smoking. No socio-economic factors were significant in the models. Conclusions Maternal age, parity, MUAC, diet and illness in early to mid-gestation were associated with risk of death during pregnancy and the first year post partum in rural Nepal. PMID:17826810

Christian, Parul; Katz, Joanne; Wu, Lee; Kimbrough-Pradhan, Elizabeth; Khatry, Subarna K.; LeClerq, Steven C.; West, Keith P.

2008-01-01

247

Reducing stillbirths: interventions during labour  

PubMed Central

Background Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined. Methods We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies. Results We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed. Conclusion Although the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs. PMID:19426469

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

2009-01-01

248

Retrospective cohort study of the effects of obesity in early pregnancy on maternal weight gain and obstetric outcomes in an obstetric population in Africa  

PubMed Central

Objective The purpose of this study was to compare maternal weight gain in pregnancy and obstetric outcomes between women with obesity in early pregnancy and those with a normal body mass index (BMI) in early pregnancy. Methods This was a retrospective cohort study of women with obesity in early pregnancy and those with a normal BMI who were seen at three teaching hospitals in South-East Nigeria. Statistical analysis was performed using Statistical Package for the Social Sciences version 17.0 software, with descriptive and inferential statistics at the 95% level of confidence. Results The study sample consisted of 648 women (324 obese and 324 healthy-weight). The mean age of the obese women was 26.7 ± 5.1 years and that of the healthy-weight women was 26.6 ± 4.9 years. Although both excessive weight gain (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.23–0.54) and inadequate weight gain (OR 0.08, 95% CI 0.04–0.15) were less common in women with early pregnancy obesity than in healthy-weight women, a significantly higher proportion of obese women with excessive weight gain had adverse fetomaternal outcomes. Also, a significantly higher proportion of obese women had specific complications, such as premature rupture of membranes (OR 2.36, 95% CI 1.12–5.04), gestational hypertension/pre-eclampsia (OR 2.31, 95% CI 1.12–5.04), antepartum hemorrhage (OR 2.78, 95% CI 1.02–7.93), gestational diabetes (OR 4.24, 95% CI 1.62–11.74), cesarean delivery (OR 2.3, 95% CI 1.2–5.44), macrosomia (OR 4.08, 95% CI 1.06–8.41), severe birth asphyxia (OR 2.8, 95% CI 1.2–6.63), abnormal Apgar scores (OR 2.67, 95% CI 1.46–4.93), and newborn special care admissions (OR 1.18, 95% CI 1.0–3.29). Conclusion Early pregnancy obesity was associated with a wide range of adverse fetomaternal outcomes, and could be a genuine risk factor for increased pregnancy-related morbidity and/or mortality in this population. Interventions to reduce prepregnancy obesity could therefore be useful in this low-resource African setting. PMID:23983492

Iyoke, Chukwuemeka A; Ugwu, George O; Ezugwu, Frank O; Lawani, Osaheni L; Onyebuchi, Azubuike K

2013-01-01

249

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

PubMed Central

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

2010-01-01

250

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

PubMed Central

The effects of DNA repair and transcription gene abnormalities in human pre-natal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10?6) recessive disorder caused by mutations in genes involved in nucleotide excision repair (NER) pathway and in transcription. Based on our novel clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD-affected offspring (n = 24) with respect to abnormalities during their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (n = 18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD-affected pregnancies. Small for gestational age (SGA) <10th percentile [Relative risk (RR) = 9.3, 95% CI = 1.4–60.5, p = 0.02], SGA <3rd percentile (RR = 7.2, 95% CI = 1.1–48.1, p = 0.04), and neonatal intensive care unit (NICU) hospitalization (RR = 6.4, 95% CI = 1.4–29.5, p = 0.02) occurred more frequently among TTD-affected neonates compared with their unaffected siblings. Compared with reference values from general obstetrical population, pregnancies that resulted in TTD-affected infants were significantly more likely to be complicated by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (RR = 35.7, 95% CI = 7.6–92.5, p = 0.0002), elevated mid-trimester maternal serum human chorionic gonadotropin (hCG) levels (RR = 14.3, 95% CI = 7.0–16.6, p < 0.0001), SGA <3rd percentile (RR = 13.9, 95% CI = 7.4–21.1, p < 0.0001), pre-term delivery (<32 weeks) (RR = 12.0, 95% CI = 4.9–21.6, p < 0.0001), pre-eclampsia (RR = 4.0, 95% CI = 1.6–7.4, p = 0.006), and decreased fetal movement (RR = 3.3, 95% CI = 1.6–5.2, p = 0.0018). Abnormal placental development is an underlying mechanism that may explain the constellation of observed complications in our study. Thus, we hypothesize that TTD DNA repair and transcription genes play an important role in normal human placental development. PMID:20002457

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

2012-01-01

251

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

PubMed Central

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

2010-01-01

252

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

PubMed Central

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

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

2013-01-01

253

Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes in 220 Saudi Women  

PubMed Central

Objectives To assess the maternal and fetal complications of pregnancy in mothers with gestational diabetes mellitus (GDM) compared with non-diabetic patients who delivered in the hospital during the study period. Methods The outcome of pregnancy in 220 Saudi patients with GDM identified from the delivery register/hospital database and matched for age, parity and body mass index with 220 non-diabetic controls were studied retrospectively from their case files. Patients with multiple pregnancies and abnormal presentation of the fetus were excluded from the study. Results The GDM patients were treated with either diet alone or with additional insulin in some patients who required better control of their blood sugar levels. Patients with GDM had a significantly higher incidence of pre-eclampsia (p<0.0001); preterm delivery (p=0.0226); induction of labor (p<0.0001); cesarean section (p=0.0019); higher mean birth weight (p<0.0001) of babies; large for gestational age infants (p=0.0011); macrosomia (p=0.0186); and admission to the neonatal intensive care unit (p=0.0003), compared with the control group. However, the rates of Apgar score <7 at 5 minutes, respiratory distress syndrome, neonatal hypoglycemia, hyperbilirubinemia and the need for phototherapy were similar in both groups of patients. Congenital anomalies and perinatal mortality rates were not significantly different in the two groups. Conclusion GDM is recognized to be associated with increased rates of adverse maternal and neonatal outcomes, which are supported by the findings of this study. Even the mild form of GDM seems to have significant consequences for women and their offspring and is recommended to be aggressively treated. Evidence suggests that early diagnosis and strict control of blood sugar levels throughout the pregnancy can significantly reduce maternal and fetal complications. A multicenter, randomized controlled trial, based on universally accepted criteria for GDM screening test, standardized diagnostic OGTT and management of all patients with GDM versus the standard obstetric management of the control is warranted. PMID:22496940

Gasim, Turki

2012-01-01

254

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

PubMed

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

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

2014-11-01

255

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

256

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

257

Component therapy.  

PubMed

The dramatic advances that have taken place in recent years in the care of sick and premature infants also have been matched by a similar increase in the use of blood transfusion therapy. Haematological features indicate that a newborn has a blood volume of 85-125 ml/kg the foetal haemoglobin is 60-85% and average Hb in full term infant is 18 gm/dl. By 2-3 months it falls to 11-12 g/dl the main cause of anemia are iron poor diet, weaning diets recurrent or chronic infections and hemolytic episodes in malarious areas. The red cells transfusions are usually top up transfusions, exchange transfusions, partial exchange transfusions. Top up- are for investigational losses and correction of mild degrees of anemias, upto to 5-15 ml/kg. They comprise 90% of all neonatal transfusions and are used in low birth babies in special care units for a maximum of 9-10 episodes. The walk in donor programs once popular are not much in vogue. The threshold for transfusion is 8-10 g/dl Hb for upto 5 weeks. Exchange transfusions are done for correction of anemia, removal of bilirubin, removal of antibodies and replacement of red cells. Ideally plasma reduced red cells that are not older than 5 days are used. It is prepared by removal of 120 ml of standard whole blood donation. The advantage of fresh cells is that hyperkalemia is avoided and good post transfusion survival acceptable red cell oxygen affinity. However it has to be screened for sickle cell disease and G6PD deficiency. Indications for exchange transfusion are kernicterus, neonatal hemolysis, G6PD deficiency, ARDS, neonatal sepsis, DIC and neonatal isoimmune thrombocytopaenia. Complications include over transfusion, perforation of major vessels, hypocalcaemia, citrate toxicity, hypothermia, hypoglycaemia, thrombocytopenia, necrotizing enterocolitis, GVHD, bacterial, viral infections. Partial exchange transfusions are done for symptomatic anemia, where Hb<10 g/dl, it is indicated in polycythemia and hyperviscosity syndromes. Exchange volume = Blood volume x (observed Hct-Desired HCt) divided observed Hct. Points to consider-there is weak expression of ABO antigens so particular care while grouping. Transfusing volumes should be 2-5 ml/kg/hour in paediatric bags of 50-100 ml with infusion devices. Platelet transfusion are indicated in neonatal throbocytopaenia, thrombocytopaenia due to sepsis, DIC, bacterial pathogens, CMV, TORCHS, Obstetric conditions such as pre eclampsia, intrauterine death abruption placenta birth injury hypoxia schock neonatal iso immune thrombocytopaenia and maternal ITP. Administration 1 RDE/pack per 2.5 kg single dose of fresh platelets less than 24hrs which contains 55 x 10(9) cells. This also contributes fresh plasma so is useful for coagulation defects also, though there is a risk of CMV and GVHD due to leucocyte contamination. Granulocyte concentrate; Gravity leucopheresis-1:8 ratio of 60 ml of 6% HES made to stand for 1hr. PMID:14510088

Radhakrishnan, K M; Chakravarthi, Srikumar; Pushkala, S; Jayaraju, J

2003-08-01

258

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