Note: This page contains sample records for the topic pre-eclampsia from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: August 15, 2014.
1

Pre-eclampsia: An Update.  

PubMed

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

von Dadelszen, Peter; Magee, Laura A

2014-08-01

2

Gastrointestinal complications of pre-eclampsia.  

PubMed

Gastrointestinal complications of pre-eclampsia can occur and have the risk of being life-threatening for the mother and fetus. Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome has been recognized as a complication of pre-eclampsia for decades. Pregnancies complicated by this syndrome require a well-formulated management plan, including assessing and stabilizing the maternal condition as well as evaluating fetal well-being. Patients with HELLP syndrome should receive anti-seizure prophylaxis with magnesium sulfate, treatment for severe hypertension, and correction of coagulopathy, if present. The potential benefits of expectant management of HELLP syndrome in those remote from term and the use of corticosteroids to improve maternal outcome remain experimental. Computed tomography or ultrasound of the abdomen should be performed if a subcapsular hematoma of the liver is suspected. If a ruptured hematoma is confirmed, massive transfusions and laparotomy are indicated. Ischemia associated with pre-eclampsia cannot only damage the liver but also the pancreas and gallbladder. PMID:19464509

Barton, John R; Sibai, Baha M

2009-06-01

3

Pre-eclampsia part 1: current understanding of its pathophysiology.  

PubMed

Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ?20 weeks of gestation. In the absence of proteinuria, hypertension together with evidence of systemic disease (such as thrombocytopenia or elevated levels of liver transaminases) is required for diagnosis. This multisystemic disorder targets several organs, including the kidneys, liver and brain, and is a leading cause of maternal and perinatal morbidity and mortality. Glomeruloendotheliosis is considered to be a characteristic lesion of pre-eclampsia, but can also occur in healthy pregnant women. The placenta has an essential role in development of this disorder. Pathogenetic mechanisms implicated in pre-eclampsia include defective deep placentation, oxidative and endoplasmic reticulum stress, autoantibodies to type-1 angiotensin II receptor, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and the presence of an antiangiogenic state, among which an imbalance of angiogenesis has emerged as one of the most important factors. However, this imbalance is not specific to pre-eclampsia, as it also occurs in intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction (massive perivillous fibrin deposition). The severity and timing of the angiogenic imbalance, together with maternal susceptibility, might determine the clinical presentation of pre-eclampsia. This Review discusses the diagnosis, classification, clinical manifestations and putative pathogenetic mechanisms of pre-eclampsia. PMID:25003615

Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Yeo, Lami; Romero, Roberto

2014-08-01

4

[Pre-eclampsia treatment according to scientific evidence].  

PubMed

Hypertensive disorders in pregnancy deserve special attention in the setting of global public health. Currently, they represent the third cause of maternal mortality in the world and first in Brazil. From a practical standpoint, pre-eclampsia remains a syndrome that leads to serious repercussions on maternal and fetal mortality and its etiology is not well known. Currently, the best treatment for forms of pre-eclampsia is being discussed at different times in pregnancy and puerperium, with the objective to reduce the high rates of maternal and fetal morbidity and mortality. Considering the pathophysiology of the event, anticipation of delivery is the best treatment for pre-eclampsia. The use of magnesium sulfate is recommended in all cases of severe pre-eclampsia and eclampsia for prevention and treatment of seizures. Likewise, treatment of hypertensive crises is recommended. Hydralazine, nifedipine and labetalol have been the most commonly used drugs for this purpose, but their use depends on the familiarity of the treating physician. Antenatal corticoid therapy is indicated whenever there is an imminent risk of preterm delivery between 24 and 34 weeks. In contrast, there is insufficient evidence to recommend bed rest and routine plasma volume expansion, and there is an urgent need for randomized clinical trials to determine whether maintenance antihypertensive treatment in pregnant women has benefits or risks for mothers and fetuses in all clinical forms of disease, particularly in cases of pure pre-eclampsia. PMID:21271152

Noronha Neto, Carlos; de Souza, Alex Sandro Rolland; Amorim, Melania Maria Ramos

2010-09-01

5

Monocytes and Macrophages in Pregnancy and Pre-Eclampsia  

PubMed Central

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

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

2014-01-01

6

Placental Superoxide is Increased in Pre-eclampsia  

Microsoft Academic Search

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

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

2001-01-01

7

Diagnosis and management of pre-eclampsia: an update  

PubMed Central

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

Turner, Judi A

2010-01-01

8

[Nifedipine antihypertensive treatment effects in pre-eclampsia].  

PubMed

Literature analysis has been controversial about pre-eclampsia. It is known that not pregnant patients should be treated due cardiovascular benefits. However, the real benefits of antihypertensive treatment in pre-eclampsia were not demonstrated. Yet, there are many drugs that can be used for antihypertensive treatment in pregnancy. Calcium cannel blockers, particularly nifedipine, are used as a second line treatment. There are just a few evidences about nifedipine treatment in hypertension during pregnancy. Recently, researches were performed to evaluate the effects of nifedipine on maternal-fetal binomial, more safety, efficacy, and effectiveness were found using it. This literature review concludes that hypertension treatment only must be done in severe cases and emergency hypertensive. Therefore nifedipine can be used in antihypertensive treatment during pregnancy without serious complications. PMID:19094810

De Souza, Alex R; Amorim, Melania R; Costa, Aurélio R

2008-01-01

9

Total free radical trapping antioxidant potential in pre-eclampsia  

Microsoft Academic Search

Objective: The aim of the present study was to measure serum urate, tocopherol and ascorbate and to calculate total radical trapping antioxidant potential (TRAP) in pre-eclampsia. Methods: Study samples were taken from 25 pre-eclamptic, 25 normotensive pregnant and 25 non-pregnant healthy females for measuring uric acid, vitamin C and E, total sulfhydryl group. Also lipid peroxidation product malonaldehyde (MDA), the

S. Kharb

2000-01-01

10

Management of pre-eclampsia: issues for anaesthetists.  

PubMed

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

Dennis, A T

2012-09-01

11

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.

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

2012-01-01

12

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

Microsoft Academic Search

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

Y. Wang; S. W. Walsh

1998-01-01

13

An epidemiological study of the immunogenetic aetiology of pre-eclampsia.  

PubMed Central

A population based case-control study of the association between dissimilar race of parents and risk of pre-eclampsia was undertaken. Data on singleton births in Washington State in 1981 were available for analysis from birth certificates. All mothers recorded as having pre-eclampsia and a sample of mothers who did not have pre-eclampsia were eligible for comparison with regard to racial dissimilarity between parents. Women with previously diagnosed cardiovascular disease and diabetes were excluded. After the confounding effects of maternal parity and race had been controlled for, racial dissimilarity of parents was associated with a 1.9-fold increased risk of pre-eclampsia (95% confidence interval = 1.3-2.8; number of cases = 973, of controls = 1480). This finding supports the theory that genetic dissimilarity of father and mother has a role in pre-eclampsia and is consistent with an immunogenetic aetiology.

Alderman, B W; Sperling, R S; Daling, J R

1986-01-01

14

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

PubMed Central

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

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

2013-01-01

15

[Resuscitation in severe forms of pre-eclampsia (short text)].  

PubMed

An expert's conference about Intensive Care in preeclampsia was organized by the French Society of Anesthesiology and Intensive Care (SFAR) associated with the societies of Pediatrics (SFP) and Obstetricians (SFMP and CNGOF). Each expert wrote a chapter according to instructions previously defined by the Referential Committee of Sfar. The coordinator was in charge of a short text which was presented to each society. The main issue was the intensive care management, but chapters about epidemiology, pathology and physiopathology were also included. Principles of care in less severe cases were also added as well as prognosis in mothers and babies. Finally, mandatory anesthetic requirements of were also presented. The aim of this work was to take stock of the state of art in severe preeclampsia. Due to improved knowledge, intensive care strategies for severe pre-eclampsia will have to be updated in the near future. PMID:11319463

Pottecher, T

2001-04-01

16

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

PubMed

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

17

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.

Williams, Paula Juliet; Morgan, Linda

2012-01-01

18

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

PubMed Central

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

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

2012-01-01

19

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.

2009-01-01

20

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. Pre-eclampsia is a complication of pregnancy that threatens the health of both mother and baby. It has recently been discovered that aspirin is an effective treatment of pre-eclampsia, but only if the mother starts taking aspirin before the 12th week of pregnancy. Presently, much research into the development of a method of screening for pre-eclampsia, similar to that currently used to detect Down's syndrome during pregnancy, is underway. Some studies have suggested combining the Down's syndrome and pre-eclampsia screening tests during the first trimester of pregnancy. There are good reasons for this as the time frame for testing is the same and some of the same components can be used in both tests. However, in this paper, we analyse the types of risk and benefits associated with both tests and we find that the type of information required for patients to give consent, and the type of consent required (written, verbal or implicit), are not the same. We find it problematic to combine these tests, and we recommend performing each test independently of the other. PMID:24631382

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

2014-05-01

21

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

PubMed Central

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

2013-01-01

22

Biomarkers in pre-eclampsia: a novel approach to early detection of the disease.  

PubMed

Pre-eclampsia is a unique disorder of human pregnancy with a great impact on maternal and perinatal morbidity and mortality worldwide and especially in developing countries. The aetiology is still unknown and the pathophysiology of the disease is the subject of extensive investigation. Recently, much of the interest of the investigators for the prediction of pre-eclampsia has been aimed at measurable manifestations of abnormal placentation, endothelial dysfunction and feto-maternal unit perfusion. Biomarkers constitute a novel approach to an early detection of the disease. Low maternal serum levels of PAPP-A and PP13 early in pregnancy are predictive for emerging pre-eclampsia. On the other hand, increased levels of homocysteine, ADMA, sEng, leptin and sFlt-1 in the 1st trimester, signal the onset of the disease later in pregnancy. After the onset of pre-eclampsia, increased serum levels of PAPP-A, ADMA, homocysteine and sFlt-1 are associated with the severity of the disease. The identification of biomarkers which can contribute to the early detection of pre-eclampsia is essential. It could then be possible to apply better surveillance and treatment protocols in such patients. PMID:22943702

Masoura, S; Kalogiannidis, I A; Gitas, G; Goutsioulis, A; Koiou, E; Athanasiadis, A; Vavatsi, N

2012-10-01

23

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

PubMed

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

2011-08-01

24

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

PubMed Central

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

Williams, Paula J.; Broughton Pipkin, Fiona

2011-01-01

25

Adverse neonatal outcomes in women with pre-eclampsia in Mulago Hospital, Kampala, Uganda: a cross-sectional study  

PubMed Central

Introduction Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Methods Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Resuls Predictors of adverse neonatal outcomes were: preterm delivery (OR 5.97, 95% CI: 2.97-12.7) and severe pre-eclampsia (OR 5.17, 95% CI: 2.36-11.3). Conclusion Predictors of adverse neonatal outcomes among women with pre-eclampsia were preterm delivery and severe pre-eclampsia. Health workers need to identify women at risk, offer them counseling and, refer them if necessary to a hospital where they can be managed successfully. This may in turn reduce the neonatal morbidity and mortality associated with pre-eclampsia.

Kiondo, Paul; Tumwesigye, Nazarius Mbona; Wandabwa, Julius; Wamuyu-Maina, Gakenia; Bimenya, Gabriel S; Okong, Pius

2014-01-01

26

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

PubMed Central

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

Hawfield, Amret; Freedman, Barry I.

2009-01-01

27

The role of homocysteine, asymmetric dimethylarginine and nitric oxide in pre-eclampsia.  

PubMed

Nitric oxide (NO) contributes to vasodilatation that is observed during normal pregnancy. Hyperhomocysteinaemia (HHcy) is a vascular risk factor associated with placental microvascular diseases and pre-eclampsia. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (NOS) has been linked to endothelial dysfunction. Maternal ADMA has been reported to be higher in women with pre-eclampsia and HHcy leads to accumulation of ADMA. The aim of this presented study is to evaluate the alterations of plasma homocysteine, ADMA and NO levels in mild pre-eclampsia. A total of 40 pre-eclamptic women and 40 healthy controls were included into the study. Mean systolic and diastolic blood pressure, mean serum homocysteine and ADMA levels were significantly higher and NO level was lower in patients. Serum homocysteine, ADMA and NO levels found to be correlated among them and with blood pressure. In conclusion, we found that homocysteine and ADMA levels were increased and NO levels decreased in pre-eclampsia. PMID:22779953

Demir, B; Demir, S; Pasa, S; Guven, S; Atamer, Y; Atamer, A; Kocyigit, Y

2012-08-01

28

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

PubMed Central

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

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

2012-01-01

29

Cardiovascular risk factor assessment after pre-eclampsia in primary care  

Microsoft Academic Search

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

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

2009-01-01

30

Complement Fixing Antibody Against Solubilized Placental Microsomal Fraction in Pre-eclampsia Sera  

PubMed Central

Placental microsomal fraction was prepared from several term human placentae. A major composite protein (molecular weight 30,000-160,000) was separated by gel filtration of solubilized microsomal fraction. Complement fixing antibody against this protein occurred in 40% of normal pregnancy sera, and in 44·6% of pre-eclampsia sera.

Gaugas, J. M.; Curzen, P.

1974-01-01

31

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

Microsoft Academic Search

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

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

2008-01-01

32

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

PubMed Central

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

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

2013-01-01

33

ABO(H) blood groups and pre-eclampsia. A systematic review and meta-analysis.  

PubMed

Pre-eclampsia is associated with both placental thrombosis and thrombophilia. The ABO(H) blood group influences von Willebrand factor, which is a risk factor for arterial and venous thrombosis. Over many years a number of studies have examined the relationship between ABO(H) and pre-eclampsia, but no consensus exists as to whether there is a true association. Correspondingly, a systematic review of studies reporting an association between ABO(H) blood group and pre-eclampsia syndromes was performed. From the 17 eligible studies there was no consistent link between blood group AB and pre-eclampsia, with a pooled odds ratio of group AB versus the remainder of 1.02 (95%CI 0.86 to 1.22). There was no evidence of heterogeneity and individual study estimates were relatively consistent. Comparing a combined group of non-Os (i.e. AA, AB and BB) with group O gave similar results, with a pooled odds ratio of 1.01 (95%CI 0.91 to 1.12), but with some evidence of heterogeneity (p=0.01) and individual study estimate inconsistency (I(2) 49%). However, no specific feature (disease definition, disease severity, date of publication, or ABO(H) distribution in controls) distinguished those few studies giving any form of positive association from the remainder. In summary, no clear association between any ABO(H) blood group and pre-eclampsia can be made from available studies. However, existing data does not allow exclusion of an effect limited to those expressing the least O(H) antigen. PMID:18766264

Clark, Peter; Wu, Olivia

2008-09-01

34

Characterization of changes in mechanical responses to histamine in omental resistance arteries in pre-eclampsia  

PubMed Central

Changes in the effect of histamine on the smooth muscle of resistance arteries in pre-eclampsia were investigated by measuring isometric contractions in endothelium-denuded strips of omental resistance arteries from pre-eclamptic and normotensive pregnant women (pregnancy-term matched). Histamine (0.03–1??M) caused concentration-dependent relaxation of the contraction induced by 9,11-epithio-11,12-methano-thromboxane A2 (STA2) in strips from both groups. Sensitivity (for pre-eclampsia: pD2=6.66±0.04, n=5 and for normotensive pregnant women: pD2=7.07±0.03, n=10, P<0.001) was lower and the maximum response (90.6±0.6% vs 95.5±1.1%, P<0.05) was smaller in strips from pre-eclamptic women. Although 8-bromoadenosine-3?, 5?-cyclic monophosphorothioate (Sp-isomer: Sp-8-Br-cAMPS, 0.1–0.3?mM), a phosphodiesterase (PDE)-resistant activator of adenosine-3?,5?-cyclic monophosphate (cyclic AMP)-dependent protein kinase, concentration-dependently attenuated the contraction induced by STA2 in strips from both groups, the sensitivity (for pre-eclampsia: pD2=3.68±0.04, n=5 and for normotensive pregnant women: 3.94±0.09, n=7, P=0.02) was lower and the maximum response (64.2±2.4% vs 74.9±4.4%, P<0.05) was smaller in pre-eclampsia. In ?-escin-skinned strips, the pD2 value for the contraction-inducing effect of Ca2+ did not differ significantly between the two groups (for pre-eclampsia, n=6; for normotensive pregnant women, n=6). Thus, omental resistance arteries from human subjects with pre-eclampsia showed (i) a weaker H2-receptor-mediated relaxation to histamine and (ii) a weaker cyclic AMP-analogue-induced relaxation, suggesting that the reduced action of histamine may be partly due to a decreased effect of cyclic AMP.

Suzuki, Yoshikatsu; Saitoh, Michihiro; Suzumori, Kaoru; Kajikuri, Junko; Itoh, Takeo

2000-01-01

35

ST2 and IL33 in Pregnancy and Pre-Eclampsia  

Microsoft Academic Search

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.

Ingrid Granne; Jennifer H. Southcombe; James V. Snider; Dionne S. Tannetta; Tim Child; Christopher W. G. Redman; Ian L. Sargent; Jacques Zimmer

2011-01-01

36

[Correction of endothelial dysfunction by L-arginine under experimental pre-eclampsia conditions].  

PubMed

The ADMA-like pre-eclampsia in pregnant rats was modeled by daily introduction of L-NAME in a dose of 25 mg/kg for 7 days. L-arginine (200 mg/kg) prevented the development of arterial hypertension and a decrease in placentary microcirculation and microalbuminuria. The possibility of using L-arginine for the prevention of competitive eNOS inhibition by ADMA is discussed. PMID:22550853

Pokrovski?, M V; Pokrovskaia, T G; Gureev, V V; Barsuk, A A; Proskuriakova, E V; Korokin, M V; Gudyrev, O S; Belous, A S; Kochkarov, V I; Danilenko, L M; Levashova, O V; Mal'tseva, N V; Polianskaia, O S

2012-01-01

37

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

PubMed Central

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

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

2012-01-01

38

Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia.  

PubMed

Proteins secreted from adipocytes - so-called adipokines - influence metabolic and vascular function. Recent data suggest that various adipokines are dysregulated in gestational diabetes mellitus (GDM) and pre-eclampsia (PE) and might be of pathophysiological and prognostic significance in these complications of pregnancy. This review gives an overview on the regulation and pathophysiology of leptin and adiponectin in GDM and PE. Furthermore, data on novel adipokines including resistin, visfatin, retinol-binding protein 4 and vaspin are summarized. PMID:21951069

Miehle, Konstanze; Stepan, Holger; Fasshauer, Mathias

2012-01-01

39

PPO.67?Atypical Pre-eclampsia with Post-Partum Cardiac Dysfunction.  

PubMed

: Atypical pre-eclampsia presents a diagnostic challenge without classic symptoms of hypertension and proteinuria; patients with atypical features may progress to unexpectedly severe disease as described below. Case 1: A 36 year old multipara with essential hypertension underwent elective caesarean section at 38 weeks gestation. Blood pressure was well controlled antenatally, without proteinuria. She was readmitted day four post-partum, developing progressive dyspnoea and orthopnoea. Investigations showed hypoxia and pulmonary oedema, responding to IV diuretics. Echocardiogram (previously normal) revealed mild left ventricular dilation with normal systolic function and ejection fraction (EF) 55%. Repeat echocardiogram nine days later following increased hypertension demonstrated moderate global impairment in systolic function with EF 45%. Subsequent normal coronary angiogram six months later and complete resolution of echocardiogram changes one year later led to a retrospective diagnosis of atypical pre-eclampsia. Case 2: A 36 year old multipara with a previous history of pre-eclampsia remained normotensive until elective delivery at 36 weeks gestation. She presented day six post-operatively with progressive dyspnoea, chest tightness and headaches. Blood pressure 154/91mmHg with trace proteinuria, PaO2 8.5 kPa and normal ECG. CTPA revealed moderate pleural effusions, symptoms improved with IV diuretics. Subsequent echocardiogram demonstrated moderate mitral regurgitation, borderline LV systolic function with EF 50-55%, with BNP of 2100- working diagnosis peripartum cardiomyopathy. This progressed in three days to severe mitral regurgitation on repeat echocardiogram, BNP reduced to 289. Four weeks post-discharge echocardiogram showed mild mitral regurgitation with normal left ventricular systolic function, EF 55%. Multidisciplinary discussion reached a diagnosis of atypical pre-eclampsia. PMID:25021159

Malone, C; Adams, B

2014-06-01

40

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

Microsoft Academic Search

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

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

2008-01-01

41

Reduced function of endothelial prostacyclin in human omental resistance arteries in pre-eclampsia  

PubMed Central

It remains unclear in pre-eclampsia whether or not a functional change occurs in the role played by prostacyclin in endothelium-dependent relaxation in resistance arteries. We examined this using human omental resistance arteries (obtained from pre-eclamptic or normotensive pregnant women) in the presence of NG-nitro-l-arginine (l-NNA, an inhibitor of nitric oxide synthase). In endothelium-intact strips from both groups, 9,11-epithio-11,12-methano-thromboxane A2 (STA2, a thromboxane A2 mimetic) produced a contraction. Diclofenac (an inhibitor of cyclooxygenase) enhanced the STA2 contraction only in the normotensive pregnant group (1.4 times control, P < 0.01). In the presence of STA2, bradykinin (0.1 ?m) produced an endothelium-dependent relaxation in both groups, the relaxation being significantly smaller for the pre-eclamptic group (P < 0.002). Diclofenac significantly attenuated the bradykinin-induced relaxation only for the normotensive pregnant group (31 % inhibition, P < 0.001). The bradykinin-induced membrane hyperpolarization consisted of diclofenac-sensitive and -insensitive components. The former, but not the latter, was significantly smaller in pre-eclampsia (-4.3 vs. ?2.6 mV, P < 0.05). The concentrations of 6-keto-PGF1? (a stable metabolite of prostacyclin) in these arteries were significantly lower in pre-eclampsia in both the absence and presence of bradykinin (about 0.2-0.4 times the normotensive pregnant value in each case, P < 0.01). By contrast, both the relaxation and the membrane hyperpolarization in response to beraprost (10 nm, a stable analogue of prostacyclin) were similar between the two groups. We conclude that, in pre-eclampsia, a reduced part is played by prostaglandins in the endothelium-dependent relaxation seen in resistance arteries and that this may be due to a reduced production of prostacyclin by the endothelium.

Suzuki, Yoshikatsu; Hattori, Tomonori; Kajikuri, Junko; Yamamoto, Tamao; Suzumori, Kaoru; Itoh, Takeo

2002-01-01

42

PAPPA2 is increased in severe early onset pre-eclampsia and upregulated with hypoxia.  

PubMed

Severe early onset pre-eclampsia is a serious pregnancy complication, believed to arise as a result of persistent placental hypoxia due to impaired placentation. Pregnancy-associated plasma protein A2 (PAPPA2) is very highly expressed in the placenta relative to all other tissues. There is some evidence that PAPPA2 mRNA and protein are increased in association with pre-eclampsia. The aim of the present study was to characterise the mRNA and protein expression, as well as localisation, of PAPPA2 in an independent cohort of severe early onset pre-eclamptic placentas. We also examined whether exposing placental explants to hypoxia (1% oxygen) changed the expression of PAPPA2. Expression of PAPPA2 mRNA and protein was upregulated in severe early onset pre-eclamptic placentas compared with preterm controls and localised to the syncytiotrophoblast. Interestingly, protein localisation was markedly reduced in term placenta. Syncytialisation of BeWo cells did not change PAPPA2 expression. However, hypoxia upregulated PAPPA2 mRNA and protein expression in primary placental explants. Together, our data suggest that PAPPA2 may be upregulated in severe pre-eclampsia and, functionally, this may be mediated via increased placental hypoxia known to occur with this pregnancy disorder. PMID:23484525

Macintire, Kate; Tuohey, Laura; Ye, Louie; Palmer, Kirsten; Gantier, Michael; Tong, Stephen; Kaitu'u-Lino, Tu'uhevaha J

2014-01-01

43

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

PubMed Central

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

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

1997-01-01

44

Review: Does size matter? Placental debris and the pathophysiology of pre-eclampsia.  

PubMed

A variety of 'debris' is shed from the syncytial surface of the human placenta ranging from large deported multinuclear fragments to sub-cellular components. It is increasingly clear that at least some of this material has signalling functions. Many categories of circulating debris are increased in pre-eclampsia, and exhibit proteins that are pro-inflammatory and could contribute to the systemic inflammatory response in normal pregnancy, which is exaggerated in pre-eclampsia. It is now evident that there is a large 'hidden' population of microvesicles and nanovesicles (including exosomes) which are hard to investigate because of their size. We have used a new technology, nanoparticle tracking analysis, to measure the size and concentration of syncytiotrophoblast vesicles prepared by placental perfusion. The vesicles range in size from 50 nm to 1 ?m with the majority being <500 nm (which includes both exosomes and microvesicles). We speculate whether changes not only in the numbers, but also in the size (beneficial syncytiotrophoblast exosomes and harmful microvesicles) might be important in the maternal syndrome of pre-eclampsia. PMID:22217911

Redman, C W G; Tannetta, D S; Dragovic, R A; Gardiner, C; Southcombe, J H; Collett, G P; Sargent, I L

2012-02-01

45

Acute Maternal Infection and Risk of Pre-Eclampsia: A Population-Based Case-Control Study  

PubMed Central

Background Infection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection) are associated with an increased risk of pre-eclampsia. Methods and Findings We used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls). Cases (n?=?1533) were individually matched with up to ten controls (n?=?14236) on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14–1.44) and in women with urinary tract infection (adjusted odds ratio 1.22;1.03–1.45). We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72–1.16). Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings. Conclusions Women who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying mechanism of this association and to determine whether, among women who acquire infections in pregnancy, prompt treatment or prophylaxis against infection might reduce the risk of pre-eclampsia.

Minassian, Caroline; Thomas, Sara L.; Williams, David J.; Campbell, Oona; Smeeth, Liam

2013-01-01

46

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

47

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

PubMed

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

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

2014-07-01

48

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

PubMed

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

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

2014-08-01

49

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

Microsoft Academic Search

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

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

2011-01-01

50

Association of maternal sleep practices with pre-eclampsia, low birth weight, and stillbirth among Ghanaian women  

PubMed Central

Objective To assess sleep practices, and investigate their relationship with maternal and fetal outcomes, among pregnant Ghanaian women. Methods In a cross-sectional study conducted at Korle Bu Teaching Hospital, Accra, Ghana, between June and July 2011, postpartum women were interviewed within 48 hours of delivery about sleep quality and practices during pregnancy. Interviews were coupled with a systematic review of participants’ medical charts for key outcomes including maternal hypertension, pre-eclampsia, premature delivery, low birth weight, and stillbirth. Results Most women reported poor sleep quality during pregnancy. Snoring during pregnancy was independently associated with pre-eclampsia (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.4–8.5; P=0.007). The newborns of women who reported supine sleep during pregnancy were at increased risk of low birth weight (OR, 5.0; 95% CI, 1.2–20.2; P=0.025) and stillbirth (OR, 8.0; 95% CI, 1.5–43.2; P=0.016). Low birth weight was found to mediate the relationship between supine sleep and stillbirth. Conclusion The present findings in an African population demonstrate that maternal sleep, a modifiable risk factor, has a significant role in pre-eclampsia, low birth weight, and subsequently stillbirth.

Owusu, Jocelynn T.; Anderson, Frank J.; Coleman, Jerry; Oppong, Samuel; Seffah, Joseph D.; Aikins, Alfred; O'Brien, Louise M.

2013-01-01

51

Predictive biomarkers of pre-eclampsia and effectiveness of preventative interventions for the disease.  

PubMed

Introduction: Pre-eclampsia (PE) is one of the most common pregnancy complication characterized by placental and maternal vascular dysfunction. It affects about 3 - 8% of women during the second half of pregnancy and represents one of the major causes of neonatal morbidity and mortality. The etiology of PE largely remains unknown. Areas covered: PE is considered a syndrome with multisystem involvement, so the ideal predictive test for it should utilize a combination of many predictors. Measurement in early pregnancy of a variety of biophysical and biochemical markers implicated in the pathophysiology of PE associated with clinical risk factors has been proposed to predict the development of the syndrome, thereby mitigating an adverse outcome. Expert opinion: The identification of reliable indicators is a clinically relevant issue that could result in early therapeutic intervention and leading to the prevention of maternal and fetal injuries before the manifestation of clinical signs. Many factors complicate the prevention of PE cases. Most are attributed to unknown etiology, the low predictive value of current screening tests and the several presentations of the disease. Although preventative treatments have been studied extensively, an effective intervention to avoid the development of PE has not yet been discovered. PMID:24766211

Inversetti, Annalisa; Smid, Maddalena; Candiani, Massimo; Ferrari, Maurizio; Galbiati, Silvia

2014-08-01

52

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

53

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.

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

2012-01-01

54

Risk for Recurrence of Pre-eclampsia in the Subsequent Pregnancy  

PubMed Central

Background: Pre-eclampsia (PE) is the commonest type of pregnancy induced hypertension and it affects nearly 5% of pregnant women. Besides short term morbidity and mortality that are associated with pregnancy, PE is associated with long term morbidity in women. There is a lack of information on the risk of recurrence of PE in pregnant Asian Indian women. Aim: To determine the rates and risk factors which were associated with recurrence of PE in the subsequent pregnancies of women with PE in index pregnancies. Settings and Design: A retrospective, observational study done at a single tertiary care centre in southern India. Material and Methods: The study included pregnant women with PE, who delivered at the study institute in 2008 and received care for their subsequent pregnancies at the study institute. Hypertension in pregnancy was categorized, based on the criteria of the International Society for the Study of Hypertension in Pregnancy. Point estimates and the 95% confidence intervals around point estimates of rates of recurrence of PE and associations of potential clinical and laboratory parameters with recurrence were determined by using bivariate analysis, logistic regression models and area under Receiver Operator Characteristic (ROC) curves. Results: The study included 82 pregnant women with PE in their index pregnancies. Twenty two (26.83%, 95% CI: 17.03, 36.62) of these 82 women developed recurrence of PE in their subsequent pregnancies. Recurrence of PE was significantly higher (OR 3.94, 95% CI: 1.05, 14.80, p=0.04) among women who were nulliparous in their index pregnancies. Recurrence of PE was not significantly associated with clinical factors or laboratory parameters in the index pregnancies. Conclusion: Nearly one in four of pregnant women with PE developed recurrences in their subsequent pregnancies, although a large proportion of pregnant women with PE (63.38% to 82.97%) in their index pregnancies were normotensive in their subsequent pregnancies.

Surapaneni, Tarakeswari; Bada, Vidyavati Patil; Nirmalan, C. Praveen Kumar

2013-01-01

55

Polymorphisms of the adiponectin gene in gestational hypertension and pre-eclampsia.  

PubMed

Adiponectin is a hormone involved in energy homeostasis by regulating glucose and lipid metabolism. In addition, the adiponectin gene (ADIPOQ) has polymorphisms that can modulate the circulating concentration of adiponectin. Abnormal adiponectin levels have been associated with pre-eclampsia (PE); however, the influence of genetic polymorphisms on the development of hypertensive disorders of pregnancy is unclear. The aim of this study was to examine whether ADIPOQ polymorphisms are associated with gestational hypertension (GH) and/or PE. We studied 401 pregnant women: 161 healthy pregnant (HP), 113 pregnant with GH and 127 pregnant with PE. ADIPOQ polymorphisms -11391G>A (rs17300539), -11377C>G (rs266729), 45T>G (rs2241766) and 276G>T (rs1501299) were genotyped by allelic discrimination assays using real-time PCR. Haplotypes were inferred using the PHASE 2.1 program. We observed that the genotypic frequencies of the -11377C>G polymorphism were different in PE compared with HP (P<0.0125), with the CT genotype being more commonly found in PE patients than in HP women (P<0.0125). However, allelic frequencies of this single-nucleotide polymorphism were similar between PE and HP (P>0.0125). No difference was observed when GH and HP groups were compared (both P>0.0125). In addition, we found no difference in genotype or allele distributions for the -11391G>A, 45T>G and 276G>T polymorphisms when we compared GH or PE with HP (all P>0.0125). In conclusion, we found a modest association between the CG genotype of the -11377C>G polymorphism and PE. PMID:23803590

Machado, J S R; Palei, A C T; Amaral, L M; Bueno, A C; Antonini, S R; Duarte, G; Tanus-Santos, J E; Sandrim, V C; Cavalli, R C

2014-02-01

56

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

NASA Astrophysics Data System (ADS)

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

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

2007-03-01

57

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

PubMed Central

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

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

2013-01-01

58

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

PubMed Central

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

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

2012-01-01

59

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

60

Clinical features of isolated gestational proteinuria progressing to pre-eclampsia: retrospective observational study  

PubMed Central

Objectives Some women with isolated gestational proteinuria (IGP) later develop hypertension and are diagnosed with pre-eclampsia (PE). This study was performed to determine whether clinical features of such proteinuria preceding PE (P-PE) differ from those of other PE (O-PE). Design Retrospective observational study after approval of the institutional review board of ethics. Setting A single university hospital. Proteinuria was defined as a protein-to-creatinine ratio (mg/mg; P/Cr) of ?0.27 in the spot urine specimen. IGP was defined as proteinuria in the absence of hypertension. P-PE was defined as PE in which proteinuria preceded hypertension by more than 2?days. Participants All of 10 and 18 consecutive women with P-PE and O-PE, respectively, who gave birth between January 2008 and August 2013. Results Proteinuria appeared earlier (at 30.2±3.0 vs 35.3±4.3?weeks, p=0.001), the P/Cr level was greater at birth (7.28±2.14 vs 3.19±2.49, p<0.001), net maternal weight gain during the last antenatal 1?week was greater (3.1±1.8 vs 1.3±1.7?kg, p=0.023) and length of pregnancy was shorter (32.5±1.9 vs 36.1±3.6?weeks, p=0.001) in women with P-PE than in O-PE. The duration of IGP was 10.0±5.9?days (range 3–20), and the time interval until delivery after diagnosis of PE was 6.1±8.2?days (range 0–23) in 10 women with P-PE. The P/Cr levels at birth were significantly inversely correlated with the antenatal lowest antithrombin activity and fibrinogen levels among the 28 women with PE. Conclusions Women with P-PE were likely to exhibit greater proteinuria in the urine, greater water retention in the interstitial space and more enhanced coagulation–fibrinolysis, thus suggesting that they may constitute a more severe form of PE than women with O-PE do.

Akaishi, Rina; Yamada, Takahiro; Morikawa, Mamoru; Nishida, Ryutaro; Minakami, Hisanori

2014-01-01

61

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.

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

2014-01-01

62

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

PubMed

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

2014-05-01

63

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

PubMed Central

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

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

2013-01-01

64

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

PubMed Central

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

2011-01-01

65

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

PubMed Central

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

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

2005-01-01

66

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.

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

2013-01-01

67

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

PubMed Central

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

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

2010-01-01

68

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

PubMed Central

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

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

2013-01-01

69

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

PubMed Central

Background Reliable antenatal identification of pre-eclampsia and small for gestational age is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving maternal/perinatal outcome. The purpose of this systematic review was to determine the accuracy of five serum analytes used in Down's serum screening for prediction of pre-eclampsia and/or small for gestational age. Methods The data sources included Medline, Embase, Cochrane library, Medion (inception to February 2007), hand searching of relevant journals, reference list checking of included articles, contact with experts. Two reviewers independently selected the articles in which the accuracy of an analyte used in Downs's serum screening before the 25th gestational week was associated with the occurrence of pre-eclampsia and/or small for gestational age without language restrictions. Two authors independently extracted data on study characteristics, quality and results. Results Five serum screening markers were evaluated. 44 studies, testing 169,637 pregnant women (4376 pre-eclampsia cases) and 86 studies, testing 382,005 women (20,339 fetal growth restriction cases) met the selection criteria. The results showed low predictive accuracy overall. For pre-eclampsia the best predictor was inhibin A>2.79MoM positive likelihood ratio 19.52 (8.33,45.79) and negative likelihood ratio 0.30 (0.13,0.68) (single study). For small for gestational age it was AFP>2.0MoM to predict birth weight < 10th centile with birth < 37 weeks positive likelihood ratio 27.96 (8.02,97.48) and negative likelihood ratio 0.78 (0.55,1.11) (single study). A potential clinical application using aspirin as a treatment is given as an example. There were methodological and reporting limitations in the included studies thus studies were heterogeneous giving pooled results with wide confidence intervals. Conclusion Down's serum screening analytes have low predictive accuracy for pre-eclampsia and small for gestational age. They may be a useful means of risk assessment or of use in prediction when combined with other tests.

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

2008-01-01

70

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.

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

71

Decreased expression of the angiogenic regulators CYR61 (CCN1) and NOV (CCN3) in human placenta is associatedwith pre-eclampsia  

Microsoft Academic Search

The pregnancy disorder pre-eclampsia (PE) is thought to be caused in part by shallow invasion of the extravillous trophoblast (EVT) leading to uteroplacental insufficiency and hypoxia. Here, we focused on the expressions of cysteine-rich 61 (CYR61, CCN1) and nephroblastoma overexpressed (NOV, CCN3), members of the CCN family of angiogenic regulators, in human pla- centa during normal pregnancy compared with pre-eclamptic

Alexandra Gellhaus; Markus Schmidt; Caroline Dunk; Stephen J. Lye; Rainer Kimmig; Elke Winterhager

2006-01-01

72

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

73

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

PubMed Central

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

Hsu, Peter; Nanan, Ralph Kay Heinrich

2014-01-01

74

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

PubMed Central

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

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

2014-01-01

75

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

PubMed Central

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

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

2013-01-01

76

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

Microsoft Academic Search

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

Karen Daniels; Simon Lewin

2008-01-01

77

Cardiac arrest and resuscitation with an automatic mechanical chest compression device (LUCAS) due to anaphylaxis of a woman receiving caesarean section because of pre-eclampsia.  

PubMed

We report a case of anaphylaxis with pulseless electrical activity (PEA)(verified by ECG and a radial intra-arterial line) in a 30-year-old woman who received 3G Promiten (dextran-1) and a prophylactic intra-venous infusion of Macrodex (dextran) for postoperative thromboembolism during caesarean section for pre-eclampsia in the 24th week of gestation. Manual chest compressions, followed by mechanical chest compressions (LUCAS, Jolife, Lund, Sweden), were performed for 50min before restoration of spontaneous circulation (ROSC). She awoke the next day with no sequelae. She had some suction cup marks on the sternum but otherwise no complications of the chest compressions. At follow up by phone 1 month later, she and her baby were doing well. PMID:16221521

Vatsgar, Tor Thomas; Ingebrigtsen, Ola; Fjose, Lars Olav; Wikstrøm, Bente; Nilsen, Jan Erik; Wik, Lars

2006-01-01

78

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

PubMed

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

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

2013-09-01

79

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

PubMed Central

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

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

2012-01-01

80

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

PubMed Central

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

2013-01-01

81

A systematic review and meta-analysis of the diagnostic accuracy of the spot urinary protein creatinine ratio (PCR) and the spot urinary albumin creatinine ratio (ACR) in the management of suspected pre-eclampsia  

Microsoft Academic Search

ObjectiveTo determine the diagnostic accuracy of the albumin creatinine ratio (ACR) and protein creatinine ratio (PCR) compared to the 24 h total urine (24 h TU) and how well they predict adverse outcomes for mother and baby in women with suspected pre-eclampsia (PE).MethodsSystematic searches in electronic databases, reference lists and contact with experts. All studies reporting on ACR and\\/or PCR

R K Morris; M Doug; M D Kilby

2011-01-01

82

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

Microsoft Academic Search

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

Sanna Heino; Milja Kaare; Sture Andersson; Hannele Laivuori

2008-01-01

83

Serum levels of tumor necrosis factor-?, interleukin-15 and interleukin-10 in patients with pre-eclampsia in comparison with normotensive pregnant women  

PubMed Central

Background: Pre-eclampsia (PE) is a pregnancy associated disorder characterized by hyper-tension and proteinuria. The first 2 stages of PE cause dysfunction in uteroplacental perfusion and oxidative stress while the third stage of PE is due to the release of inflammatory and angiogenic factors, which could lead to maternal endothelial damage and systemic inflammatory response. In this study, we compared the serum levels of tumor necrosis factor-? (TNF-?), interleukin-15 (IL-15), and interleukin-10 (IL-10) in PE and normotensive women. Materials and Methods: Serum samples of 84 pregnant women (44 PE and 40 normotensive) were evaluated for TNF-?, IL-15 and IL-10 by sandwich ELISA assay. Results: The women with PE showed significantly higher serum levels of TNF-? and IL-15 (P = 0.001 and 0.01 respectively) in comparison with normotensive pregnant women. Conversely, the serum levels of IL-10 in normotensive women were significantly higher compared to PE patients (P = 0.01). Conclusion: The results of this study demonstrated that inflammatory T helper 1-type responses are increased in PE women compared to normotensive pregnant women.

Kalantar, Fathollah; Rajaei, Samira; Heidari, Amir Behzad; Mansouri, Reza; Rashidi, Nesa; Izad, Maryam Hosseinali; Mirahmadian, Mahroo

2013-01-01

84

A label-free selected reaction monitoring workflow identifies a subset of pregnancy specific glycoproteins as potential predictive markers of early-onset pre-eclampsia.  

PubMed

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

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

2013-11-01

85

Analysis of polymorphisms in interleukin-10, interleukin-6, and interleukin-1 receptor antagonist in Mexican-Mestizo women with pre-eclampsia.  

PubMed

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-Vázquez, Ramón Mauricio; Canizales-Quinteros, Samuel; Coronel, Agustín; Carlos Falcón, Juan; Hernández Rivera, Jaime; Ibarra, Roberto; Polanco Reyes, Lucila; Canto, Patricia

2012-11-01

86

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.

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

87

microRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells.  

PubMed

PE (pre-eclampsia), a pregnancy-specific disorder, is characterized by increased trophoblast cell death and deficient trophoblast invasion and reduced trophoblast-mediated remodelling of spiral arteries. The present study was performed to determine the function of miR-29b (microRNA-29b) in trophoblast cells and its underlying role in the pathogenesis of PE. The prediction of miR-29b target genes was performed using computer-based programs, including Targetscan, Pictar and miRBase. The function of these target genes was analysed further by gene ontology (GO). The effects of miR-29b on apoptosis, and invasion and angiogenesis of trophoblast cell lines (HTR-8/SVneo, BeWo and JAR) were examined by flow cytometry and Matrigel assay respectively. We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin ?1) genes by directly binding to their 3'-UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. Taken together, these findings support a novel role for miR-29b in invasion, apoptosis and angiogenesis of trophoblast cells, and miR-29b may become a new potential therapeutic target for PE. PMID:22716646

Li, Pengfei; Guo, Wei; Du, Leilei; Zhao, Junli; Wang, Yaping; Liu, Liu; Hu, Yali; Hou, Yayi

2013-01-01

88

Volumes and numbers of intervillous pores and villous domains in placentas associated with intrauterine growth restriction and/or pre-eclampsia.  

PubMed

The intrauterine environment has an important influence on placental development. In pre-eclampsia (PE) and intrauterine growth restriction (IUGR), early remodelling of spiral arteries has repercussions for uteroplacental blood flow. The IUGR placenta exhibits compromised growth of villous trees, a smaller intervillous space and a lower diffusive conductance. Here, we test whether or not term placentas associated with PE or IUGR also exhibit changes in structural quantities (notably, sizes and numbers of intervillous pores and villous domains) pertinent to uteroplacental haemodynamics. Paraffin wax sections were sampled at random locations and orientations and structural quantities obtained by combining design-based stereological estimates of total and star volumes with model-based estimates of pore hydraulic diameters. Total volumes of intervillous pores and villi were estimated by point counting, total villous surface by intersection counting and star volumes by measuring point-sampled intercept lengths. Other quantities were derived secondarily and group estimates compared by two-way analysis of variance. We found significant main effects of IUGR but no main or interaction effects involving PE. In IUGR, there were fewer intervillous pores and these had larger hydraulic diameters. IUGR also produced fewer villous domains but these were constant in star volume and villi had a constant mean diameter and volume fraction. We concluded that IUGR compromises placental development by producing intervillous pores and villous trees different in size and shape from those in control and PE pregnancies. Calculations suggest that Darcian conductances in the intervillous space improve in IUGR but, in reality, placental performance is compromised by other physiological and structural constraints including the known decline in diffusive conductances. PMID:20444500

Rainey, A; Mayhew, T M

2010-07-01

89

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

PubMed Central

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

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

2014-01-01

90

Two Variants of the C-Reactive Protein Gene Are Associated with Risk of Pre-Eclampsia in an American Indian Population  

PubMed Central

Background The etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease. Methods This study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped. Results A nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother's age, nulliparity and BMI attenuated the effect (OR 1.58, P?=?0.066, 95% CI 0.97–2.58) for rs876538 and (OR 2.59, P?=?0.050, 95% CI 1.00–6.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P?=?0.013, 95% CI 1.16–3.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR?=?1.55, P?=?0.01, 95% CI 2.16–1.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants. Conclusion The CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE.

Best, Lyle G.; Saxena, Richa; Anderson, Cindy M.; Barnes, Michael R.; Hakonarson, Hakon; Falcon, Gilbert; Martin, Candelaria; Castillo, Berta Almoguera; Karumanchi, Ananth; Keplin, Kylie; Pearson, Nichole; Lamb, Felicia; Bercier, Shellee; Keating, Brendan J.

2013-01-01

91

"Takahashi Winn Birome Silio Martinelli Marcos York Coury R. G. Lopes S. A. Garcia and Amiret Gaza Lippe. Assessment of serum lipids in pregnant women aged over 35 years and their relation with pre-eclampsia. einstein 6 (2008): 63-7."  

EPA Pesticide Factsheets

Did you mean: "Takahashi Winn Birome Silio Martinelli Marcos York Coury R. G. Lopes S. A. Garcia and Amiret Gaza Lippe. Assessment of serum lipids in pregnant women aged over 35 years and their relation with pre-eclampsia. einstein 6 (2008): 63-7." ?

92

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

PubMed Central

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

2012-01-01

93

Pre-Eclampsia: Clinical Manifestations and Molecular Mechanisms  

Microsoft Academic Search

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

Suzanne Baumwell; S. Ananth Karumanchi

2007-01-01

94

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

95

Serial plasma oncotic pressure levels and echoencephalography during and after delivery in severe pre-eclampsia.  

PubMed

Plasma colloid osmotic pressure (PCOP) and echoencephalograms were monitored serially during and after labour in nine nulliparous severe pre-eclamptics receiving parenteral fluids, including infusions of magnesium sulphate and hydralazine. Nine normotensive, age-matched, nulliparous women in labour served as controls. PCOP, lower in the pre-eclamptics (16.1 +/- SD 0.6 mm Hg vs 19.9 +/- 0.7 mm Hg in controls, p less than 0.001) before the start of parenteral infusions, decreased in both groups and at delivery it was 14.1 +/- 0.5 mm Hg in the hypertensive women and 17.2 +/- 0.6 mm Hg in the controls p less than 0.001). After reaching a nadir between 16 and 18 h post partum (pre-eclamptics: 13.8 +/- 0.5 mm Hg; controls 16.2 +/- 0.8 mm Hg; p less than 0.001) the levels rose and at 6 weeks post partum they were greater in the pre-eclamptics (26.2 +/- 1.1 mm Hg vs 22.7 +/- 0.8 mm Hg; p less than 0.01) although the blood pressure in this group had returned to normal. Middle cerebral ventricle width was similar in the pre-eclamptic and normotensive women and remained unchanged during labour and 1 day and 6 weeks post partum. No echographic evidence of brain swelling or symptoms suggestive of pulmonary congestion were observed in either group. The potentially dangerous low PCOPs during and after labour in pre-eclamptic women emphasise the need for minimising crystalloid therapy in pre-eclamptics during labour. PMID:2860445

Zinaman, M; Rubin, J; Lindheimer, M D

1985-06-01

96

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

ClinicalTrials.gov

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

2013-12-11

97

[Hemolysis, elevated liver enzymes and thrombocytopenia: the HELLP syndrome--a manifestation of severe pre-eclampsia].  

PubMed

On the basis of a review of the literature and five case histories, the pathophysiological and clinical features in pregnant women with haemolysis, elevated liver enzymes and thrombocytopenia which together constitute the HELLP syndrome (haemolysis, elevated liver enzymes and low platelet count) are illustrated. This syndrome describes a complicated obstetric course with greatly increased neonatal and maternal morbidities. Hypertension/proteinuria are common but are not obligatory. The condition should be suspected in pregnant women with pain under the right rib margin and unexplained jaundice. The diagnosis is verified by the blood picture, liver enzyme count and a blood smear. Women with verified HELLP syndrome and gestational age greater than 34 weeks should be delivered immediately. Women with the same syndrome and gestational age less than 32 weeks should be delivered if the condition cannot be rapidly controlled. In exceptional cases cesarean section may be necessary. On the basis of the coagulation status, the defective plasma components may be supplied (e.g. fresh frozen plasma and antithrombin-III). Plasmapheresis and specific pharmacological intervention must be considered as experimental at present, although these present promising therapeutic possibilities. PMID:2042240

Møller, L M; Jørgensen, H S; Jessen, A L; Hartmann-Andersen, J F

1991-05-01

98

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

PubMed Central

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

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

2013-01-01

99

Comparison of gestational diabetes mellitus and pre-eclampsia in women with high hemoglobin in the first trimester of pregnancy: A longitudinal study.  

PubMed

Objective: To determine the association between high hemoglobin with gestational diabetes mellitus (GDM) and preeclampsia in pregnant women in the first trimester. Methods: This cohort study was conducted among 973 pregnant women who started their antenatal booking in the first trimester (first 14 weeks of gestation). Women with first-visit high Hb levels (> 12.5 g/L) on first visit of the pregnancy period were selected as the study group and were compared with those who had normal Hb value (< 12.5 g/L) as controls. Adverse pregnancy outcomes including preeclampsia and GDM were compared between the two groups. Results: Complete obstetric records of 448 women with high Hb levels and 486 women with normal Hb levels were studied. The follow up showed that the women with high Hb levels had significantly higher rates of preeclampsia and GDM than those with normal Hb levels; the risks were 5.4 (95% cl; 2.8 to 10.5) and 3.7 (95%cl; 2.2 to 6.4), respectively. Conclusion: This study found that high Hb in the first trimester is associated with higher risk of subsequent preeclampsia and gestational diabetes mellitus (GDM). PMID:24353673

Mehrabian, Ferdous; Hosseini, Seyyed Mohammad

2013-07-01

100

Comparison of gestational diabetes mellitus and pre-eclampsia in women with high hemoglobin in the first trimester of pregnancy: A longitudinal study  

PubMed Central

Objective: To determine the association between high hemoglobin with gestational diabetes mellitus (GDM) and preeclampsia in pregnant women in the first trimester. Methods: This cohort study was conducted among 973 pregnant women who started their antenatal booking in the first trimester (first 14 weeks of gestation). Women with first-visit high Hb levels (> 12.5 g/L) on first visit of the pregnancy period were selected as the study group and were compared with those who had normal Hb value (< 12.5 g/L) as controls. Adverse pregnancy outcomes including preeclampsia and GDM were compared between the two groups. Results: Complete obstetric records of 448 women with high Hb levels and 486 women with normal Hb levels were studied. The follow up showed that the women with high Hb levels had significantly higher rates of preeclampsia and GDM than those with normal Hb levels; the risks were 5.4 (95% cl; 2.8 to 10.5) and 3.7 (95%cl; 2.2 to 6.4), respectively. Conclusion: This study found that high Hb in the first trimester is associated with higher risk of subsequent preeclampsia and gestational diabetes mellitus (GDM).

Mehrabian, Ferdous; Hosseini, Seyyed Mohammad

2013-01-01

101

Preeclampsia - a risk factor for osteoporosis? Analysis of maternal Sclerostin levels and markers of bone turnover in patients with pre-eclampsia.  

PubMed

Introduction: The role of preeclampsia (PE) in affecting bone metabolism could not be clarified in the past years. Recently Sclerostin, a new marker of bone metabolism which is known to have an inhibitory effect on bone formation causing osteoporosis, was discovered. Objective: To investigate serum levels of Sclerostin and markers of bone turnover in women with normotensive pregnancies and pregnancies complicated by PE. Methods: In this prospective study we enrolled 22 women with PE and 22 healthy pregnant women to observe serum levels of carboxyterminal propeptide of type I collagen (PICP), cross-linked carboxyl terminal telopeptide of the type I collagen (ICTP), calcium, phosphate, 25-hydroxyvitamin D and parathyroid hormone. In 16 preeclamptic and 16 healthy pregnant women, serum Sclerostin levels were analyzed. Results: Serum levels of Sclerostin (mean?±?standard deviation: healthy 10.5?±?8.1?pmol/l versus PE 11.5?±?9.4?pmol/l, p?=?0.768), ICTP (healthy 0.3?±?0.2?ng/ml versus PE 0.4?±?0.1?ng/ml, p?=?0.462), PICP (healthy 59.9?±?49.9?ng/ml versus PE 89.0?±?62.0?ng/ml, p?=?0.094), phosphate (healthy 1.1?±?0.2?mmol/l versus PE 1.2?±?0.4?mmol/l, p?=?0.162) and parathyroid hormone (healthy 26.9?±?14?pg/ml versus PE 35.3?±?17.6?pg/ml, p?=?0.08) showed no significant differences between the groups. Significantly lower serum calcium (healthy 2.3?±?0.1?mmol/l versus PE 2.2?±?0.2?mmol/l, p?

Wild, Julia; Pateisky, Petra; Küssel, Lorenz; Huf, Wolfgang; Ott, Johannes; Haslinger, Peter; Knöfler, Martin; Zeisler, Harald

2014-08-01

102

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

103

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

Microsoft Academic Search

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

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

2004-01-01

104

Use of inhaled corticosteroids during pregnancy and risk of pregnancy induced hypertension: nested case-control study  

PubMed Central

Objective To determine whether the use of inhaled corticosteroids during pregnancy increases the risk of pregnancy induced hypertension and pre-eclampsia among asthmatic women. Design Nested case-control study. Setting Three administrative health databases from Quebec: RAMQ, MED-ECHO, and Fichier des événements démographiques. Participants 3505 women with asthma, totalling 4593 pregnancies, between 1990 and 2000. Main outcome measures Pregnancy induced hypertension and pre-eclampsia. Results 302 cases of pregnancy induced hypertension and 165 cases of pre-eclampsia were identified. Use of inhaled corticosteroids from conception until date of outcome was not associated with an increased risk of pregnancy induced hypertension (adjusted odds ratio 1.02, 95% confidence interval 0.77 to 1.34) or pre-eclampsia (1.06, 0.74 to 1.53). No significant dose-response relation was observed between inhaled corticosteroids and pregnancy induced hypertension or pre-eclampsia. Oral corticosteroids were significantly associated with the risk of pregnancy induced hypertension (adjusted odds ratio 1.57, 1.02 to 2.41), and a trend was seen for pre-eclampsia (1.72, 0.98 to 3.02). Conclusion No significant increase of the risk of pregnancy induced hypertension or pre-eclampsia was detected among users of inhaled corticosteroids during pregnancy, while markers of uncontrolled and severe asthma were found to significantly increase the risks of pregnancy induced hypertension and pre-eclampsia.

Martel, Marie-Josee; Rey, Evelyne; Beauchesne, Marie-France; Perreault, Sylvie; Lefebvre, Genevieve; Forget, Amelie; Blais, Lucie

2005-01-01

105

Plasmatic regulation of vascular prostacyclin in pregnancy.  

PubMed Central

Activity of prostacyclin-stimulating factor was measured in six normal, non-pregnant women, six women in early normal pregnancy, six in late normal pregnancy, and six in late pregnancy complicated by severe pre-eclampsia. The activity was lower in the women in late pregnancy than in those in early pregnancy and the controls but was about normal in those with severe pre-eclampsia. These results may be relevant to the physiology of pregnancy and the pathogenesis of pre-eclampsia.

Remuzzi, G; Zoja, C; Marchesi, D; Schieppati, A; Mecca, G; Misiani, R; Donati, M B; de Gaetano, G

1981-01-01

106

32 CFR 732.16 - Emergency care requirements.  

Code of Federal Regulations, 2010 CFR

...nonpregnant state. (2) Spontaneous abortion, with first trimester hemorrhage. (3) Premature or term labor with delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy with...

2009-07-01

107

32 CFR 732.16 - Emergency care requirements.  

Code of Federal Regulations, 2010 CFR

...nonpregnant state. (2) Spontaneous abortion, with first trimester hemorrhage. (3) Premature or term labor with delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy with...

2010-07-01

108

Higher hypertension risk in pregnancy using donated eggs.  

PubMed

Women who become pregnant using donated eggs are three times more likely to develop pregnancy-induced hypertension than routine IVF patients, and four times as likely to develop pre-eclampsia, suggests a study in France. PMID:25052650

2014-07-23

109

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

PubMed

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

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

2013-07-01

110

Serum calcium level among normal pregnant and pre-eclamptic women in a sub urban area of Bangladesh.  

PubMed

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

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

2013-07-01

111

(Epi)genetics of pregnancy-associated diseases  

PubMed Central

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

van Dijk, Marie; Oudejans, Cees

2013-01-01

112

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

Microsoft Academic Search

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

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

1976-01-01

113

Reversible posterior leukoencephalopathy syndrome in children with nephrotic syndrome: a case report.  

PubMed

REVERSIBLE posterior leukoencephalopathy syndrome (RPLS) is a rare neurological syndrome characterized by headache, altered mental status, seizures, and visual disturbance, associated with reversible white matter changes.1 It has been commonly reported in patients with severe hypertension and pre-eclampsia. Here we report a case with nephrotic syndrome complicated by RPLS. PMID:24698681

Liu, Sheng-da; Shen, Qing-min; Lv, Chun-feng

2014-03-01

114

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

Microsoft Academic Search

BACKGROUND: Placental malaria (PM) is associated with poor foetal development, but the pathophysiological processes involved are poorly understood. Cyclooxygenase (COX) and lipoxygenase (LOX) which convert fatty acids to prostaglandins and leukotrienes, play important roles in pregnancy and foetal development. COX-2, currently targeted by specific drugs, plays a dual role as it associates with both pre-eclampsia pathology and recovery during infection.

Demba Sarr; Delphine Aldebert; Laurence Marrama; Emilie Frealle; Alioune Gaye; Hamoud O Brahim; Makhtar Niang; Jean Marie Dangou; Odile Mercereau-Puijalon; Jean Yves Lehesran; Ronan Jambou

2010-01-01

115

Circulating biomarkers of oxidative stress in complicated pregnancies  

Microsoft Academic Search

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

Hilmi Orhan; Lütfü Önderoglu; Aykan Yücel; Gönül Sahin

2003-01-01

116

Mid thoracic syndrome in pregnancy: a rare cause of secondary hypertension  

Microsoft Academic Search

Severe secondary hypertension in pregnancy can be complicated by maternal intracerebral haemorrhage, cardiac or renal failure, superimposed pre-eclampsia, maternal death and fetal spontaneous abortion or perinatal death. The authors present the case of a 17 year old girl with no previous medical or surgical history, who booked for antenatal care at 15 weeks with a BP of 215\\/110 mm Hg

SN Johnson; T Kelleher; SO Neill; P Crean; J Cosgrave; J Meaney; K Astbury; C Regan; B Byrne

2010-01-01

117

Comparison between umbilical artery and vein endogenous digoxin-like immuno-active factor levels in normal and pre-eclamptic patients.  

PubMed

Recent studies have pointed to the existence of an endogenous digoxin-like immuno-active factor (DLIF), which may be associated with hypertension and pre-eclampsia. The DLIF levels in the umbilical venous and umbilical arterial blood of neonates, as well as the maternal serum of primigravidas and multigravidas with and without pre-eclampsia, were determined by means of a commercially available radioimmunoassay kit, which is cross-reactive with DLIF, in 44 mothers and their babies in search for a possible placental, fetal or maternal origin of the DLIF. The mean placental and neonatal masses were significantly lower in the pre-eclampsia group than in the control group (P less than 0.01). However, the DLIF levels in the maternal serum, umbilical cord venous and umbilical cord arterial serum were statistically significantly higher in the pre-eclampsia group than in the control pregnant group (P less than 0.05). A very strong correlation was found between umbilical cord venous and arterial DLIF levels (r = 0.90; P = 0.001, Spearman rank-correlation coefficient). Although the mean DLIF level in cord arterial serum was lower than that of cord venous serum, statistical significance was not reached if the Bonferroni adjustment was applied to the P value. PMID:1996437

Schabort, I; Odendaal, H J; Lombard, C J; Bredell, L

1991-02-16

118

Increased cystatin C expression in the pre-eclamptic placenta.  

PubMed

Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C inhibits cysteine proteinases. The serum concentration of cystatin C is increased in late pregnancy and pre-eclampsia. We aimed to investigate whether the expression of cystatin C is increased in the pre-eclamptic placenta and to investigate the expression pattern of cystatin C mRNA and protein in placental tissue. Tissue samples from the central part of the placenta from 13 normal and 22 pre-eclamptic pregnancies were included. We used real-time polymerase chain reaction (RT-PCR) and in situ hybridization for mRNA expression analysis and immunohistochemistry and Western blotting for protein expression analysis. RT-PCR showed a significantly higher expression of cystatin C mRNA in pre-eclampsia than in normal pregnancy, with the highest expression in cases with severe pre-eclampsia. In situ hybridization revealed a distinct pattern of high expression in the extravillous trophoblast cells of the basal plate and low expression in the syncytiotrophoblast covering villi. The cystatin C protein distribution matched the mRNA expression pattern. Western blot analysis revealed an increased protein expression in cases with severe pre-eclampsia and confirmed the presence of cystatin C in amniotic fluid samples. The high expression of cystatin C mRNA in the extravillous trophoblast cells of the basal plate suggests a role for cystatin C in the regulation of proteases in placentation. Placental expression and secretion of cystatin C could contribute to the elevated maternal plasma levels seen in pre-eclampsia. PMID:17227816

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

2007-03-01

119

The Association of Factor V Leiden and Prothrombin Gene Mutation and Placenta-Mediated Pregnancy Complications: A Systematic Review and Meta-analysis of Prospective Cohort Studies  

PubMed Central

Background Factor V Leiden (FVL) and prothrombin gene mutation (PGM) are common inherited thrombophilias. Retrospective studies variably suggest a link between maternal FVL/PGM and placenta-mediated pregnancy complications including pregnancy loss, small for gestational age, pre-eclampsia and placental abruption. Prospective cohort studies provide a superior methodologic design but require larger sample sizes to detect important effects. We undertook a systematic review and a meta-analysis of prospective cohort studies to estimate the association of maternal FVL or PGM carrier status and placenta-mediated pregnancy complications. Methods and Findings A comprehensive search strategy was run in Medline and Embase. Inclusion criteria were: (1) prospective cohort design; (2) clearly defined outcomes including one of the following: pregnancy loss, small for gestational age, pre-eclampsia or placental abruption; (3) maternal FVL or PGM carrier status; (4) sufficient data for calculation of odds ratios (ORs). We identified 322 titles, reviewed 30 articles for inclusion and exclusion criteria, and included ten studies in the meta-analysis. The odds of pregnancy loss in women with FVL (absolute risk 4.2%) was 52% higher (OR?=?1.52, 95% confidence interval [CI] 1.06–2.19) as compared with women without FVL (absolute risk 3.2%). There was no significant association between FVL and pre-eclampsia (OR?=?1.23, 95% CI 0.89–1.70) or between FVL and SGA (OR?=?1.0, 95% CI 0.80–1.25). PGM was not associated with pre-eclampsia (OR?=?1.25, 95% CI 0.79–1.99) or SGA (OR 1.25, 95% CI 0.92–1.70). Conclusions Women with FVL appear to be at a small absolute increased risk of late pregnancy loss. Women with FVL and PGM appear not to be at increased risk of pre-eclampsia or birth of SGA infants. Please see later in the article for the Editors' Summary

Rodger, Marc A.; Betancourt, Marisol T.; Clark, Peter; Lindqvist, Pelle G.; Dizon-Townson, Donna; Said, Joanne; Seligsohn, Uri; Carrier, Marc; Salomon, Ophira; Greer, Ian A.

2010-01-01

120

Liver abnormalities in pregnancy.  

PubMed

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

Than, Nwe Ni; Neuberger, James

2013-08-01

121

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

PubMed Central

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

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

2013-01-01

122

Effects of smoking during pregnancy  

Microsoft Academic Search

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

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

1999-01-01

123

Syncytin-1 and Glial Cells Missing a: Hypoxia-Induced Deregulated Gene Expression along with Disordered Cell Fusion in Primary Term Human Trophoblasts  

Microsoft Academic Search

Background\\/Aims: Pre-eclampsia, a major cause of perinatal morbidity, is characterized by alterations in placental oxygen availability and trophoblast differentiation. We investigated how different levels of hypoxia alter the expression of syncytin-1, glial cells missing a (GCMa) and syncytin-1 receptor ASCT2 and affect syncytialization in primary term human trophoblasts. Methods: Cells were incubated at 1, 3, 6 and 21% O2 for

C. Wich; S. Kausler; J. Dotsch; W. Rascher; I. Knerr

2009-01-01

124

Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin  

Microsoft Academic Search

Objective. SSc is a CTD characterized by early generalized microangiopathy with disturbed angiogenesis. Soluble endoglin (sENG), a serum anti-angiogenic protein, has recently been described as a major actor in pre-eclampsia, another severe vascular disease with abnormal angiogenesis. The aim of this study was to investigate, in a cross-sectional study, sENG levels together with other serum vascular markers. Methods. Serum levels

J. Wipff; J. Avouac; D. Borderie; D. Zerkak; H. Lemarechal; A. Kahan; C. Boileau; Y. Allanore

2008-01-01

125

Effect of asymmetric dimethyl arginine on nitric oxide synthase activity in normal and pre-eclamptic placentae.  

PubMed

An endogenous inhibitor of nitric oxide synthase (NOS), NG,NG dimethylarginine (asymmetric dimethylarginine, ADMA), which is present in human plasma and urine, has been reported to be elevated in the plasma of women with pre-eclampsia. As ADMA inhibition may contribute to reduced placental NOS activity observed in pre-eclampsia, the aim of this study was to compare the effects of ADMA on placental NOS activity from pre-eclamptic and normal pregnancies (gestational ages 38.4 +/- 0.9 and 38.3 +/- 0.3 weeks respectively). NOS activity was determined by measuring the conversion of [3H]L-arginine to [3H]L-citrulline in homogenates of normal and pre-eclamptic placentae in the absence and presence of increasing concentrations of ADMA (1-100 microM). The IC50 for ADMA for the pre-eclamptic placentae (22.1 +/- 2.1 microM, n = 6) was not significantly different from that for the normal placentae (18.8 +/- 1.4 microM, n = 6). When ADMA and L-arginine in homogenates was removed by ion exchange chromatography and exogenous L-arginine replaced (32 microM), the IC50 for the pre-eclamptic placentae (19.5 +/- 1.8 microM, n = 6) was not significantly different than that for the normal placentae (20.9 +/- 1.0 microM, n = 6), and NOS activity in the absence of endogenous and exogenous ADMA was still reduced in pre-eclamptic placentae. These results provide no evidence that the sensitivity of placental NOS to ADMA is affected by pre-eclampsia, or that placental ADMA contributes to the reduction of placental NOS in pre-eclampsia. PMID:8743168

King, R G; Di Iulio, J L; Gude, N M; Brennecke, S P

1995-01-01

126

Costs of maternal conditions attributable to smoking during pregnancy  

Microsoft Academic Search

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

E. Kathleen Adams; Cathy L. Melvin

1998-01-01

127

Epidermal growth factor rescues trophoblast apoptosis induced by reactive oxygen species  

Microsoft Academic Search

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

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

2007-01-01

128

Cerebrovascular disease in pregnancy  

Microsoft Academic Search

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

Michael A. Sloan; Barney J. Stern

2003-01-01

129

Extreme Hypertension, Eclampsia and Critical Care Seizures  

Microsoft Academic Search

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

Errol Gordon; Michel T. Torbey

130

Endoglin: a critical mediator of cardiovascular health  

PubMed Central

Endoglin (CD105) is a type III auxiliary receptor for the transforming growth factor beta (TGF?) superfamily. Several lines of evidence suggest that endoglin plays a critical role in maintaining cardiovascular homeostasis. Seemingly disparate disease conditions, including hereditary hemorrhagic telangiectasia, pre-eclampsia, and cardiac fibrosis, have now been associated with endoglin. Given the central role of the TGF? superfamily in multiple disease conditions, this review provides a detailed update on endoglin as an evolving therapeutic target in the management of cardiovascular disease.

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

2013-01-01

131

Antihypertensive therapy in pregnancy  

Microsoft Academic Search

Human pregnancy, normally characterized by systemic vasodilation and modest hypotension, can be complicated by underlying\\u000a maternal hypertension and several unique hypertensive disorders, including pre-eclampsia. Although well-designed and adequately\\u000a powered clinical trials are critically needed, there have been several recent meta-analyses of this large literature, along\\u000a with consensus statements and treatment guidelines from three distinct multidisciplinary groups of clinicians and investigators.

Jason G. Umans; Marshall D. Lindheimer

2001-01-01

132

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

PubMed Central

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

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

2013-01-01

133

Evidence for Fatty Acid Oxidation in Human Placenta, and the Relationship of Fatty Acid Oxidation Enzyme Activities with Gestational Age  

Microsoft Academic Search

Fetal disorders of mitochondrial fatty acid oxidation have recently been associated with obstetric complications including pre-eclampsia, Hemolysis, Elevated Liver enzymes, Low Platelets (HELLP) syndrome, placental floor infarct, and Acute Fatty Liver of Pregnancy (AFLP). These diseases occur in about a third of the mothers who are heterozygous for a defect in long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) enzyme and who bear

D. Rakheja; M. J. Bennett; B. M. Foster; R. Domiati-Saad; B. B. Rogers

2002-01-01

134

Cushing’s Syndrome in Pregnancy Secondary to Adrenal Adenoma  

Microsoft Academic Search

We describe a case of Cushing’s syndrome complicating pregnancy presented with acute heart failure, hypertension and glucose intolerance. A left adrenal adenoma was removed at 24 weeks of gestation. The pregnancy was ended with an emergency lower-segment Caesarean section at 31 weeks of gestation because of severe pre-eclampsia and HELLP syndrome. The case is reported not only because of its

Keith Wing-Kit Lo; Tze-Kin Lau

1998-01-01

135

Maternal Adaptation to High-altitude Pregnancy: An Experiment of Nature—A Review  

Microsoft Academic Search

A long and productive history of studies at high altitude has demonstrated that chronic hypoxia plays a key role in the aetiology of intrauterine growth restriction (IUGR) and pre-eclampsia. Susceptibility to altitude-associated IUGR varies among high-altitude populations in relation to their duration of altitude exposure, with multigenerational residents demonstrating one-third the birth weight fall present in shorter-resident groups. Higher uteroplacental

L. G. Moore; M. Shriver; L. Bemis; B. Hickler; M. Wilson; T. Brutsaert; E. Parra; E. Vargas

2004-01-01

136

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

PubMed

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

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

2012-10-01

137

On the potential of metformin to prevent preterm delivery in women with polycystic ovary syndrome - an epi-analysis.  

PubMed

Our aim was to re-evaluate whether metformin may reduce late miscarriage/preterm delivery, pre-eclampsia and gestational diabetes in women with polycystic ovary syndrome (PCOS). We performed an epi-analysis of two randomized controlled trials. The participants were 313 women aged 18-42 years with PCOS who had singleton pregnancies. They were randomized to metformin or placebo treatment from first trimester until delivery. We analysed the prevalence of late miscarriage/preterm delivery, pre-eclampsia and gestational diabetes according to both the intention-to-treat principle and per protocol analysis. The metformin-treated patients had less late miscarriage/preterm delivery; five (3%) vs. 18 (11%) in the placebo group (p < 0.01). There was no difference in the prevalence of gestational diabetes and pre-eclampsia between the metformin and the placebo group. In this epi-analysis, metformin treatment during pregnancy seems to reduce early delivery in women with PCOS. We believe that further randomized studies should be performed before firm conclusions can be drawn. PMID:23006146

Vanky, Eszter; DE Zegher, Francis; Díaz, Marta; Ibáñez, Lourdes; Carlsen, Sven M

2012-12-01

138

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

PubMed Central

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

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

2013-01-01

139

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/

2013-01-01

140

The novel inflammatory cytokine high mobility group box protein 1 (HMGB1) is expressed by human term placenta  

PubMed Central

High mobility group box protein 1 (HMGB1) was previously considered a strict nuclear protein, but lately data are accumulating on its extranuclear functions. In addition to its potent proinflammatory capacities, HMGB1 has a prominent role in a number of processes of specific interest for the placenta. Our overall aim was to investigate the expression of HMGB1 in human term placenta and elucidate a potential difference in HMGB1 expression comparing vaginal deliveries with elective Caesarean sections. In addition, placentas from normal pregnancies were compared with placentas from pregnancies complicated by pre-eclampsia. Twenty-five placentas, 12 from normal term pregnancies and 13 from pregnancies complicated by pre-eclampsia were analysed with immunohistochemistry for HMGB1 and its putative receptors; receptor for advanced glycation end-products (RAGE), Toll-like receptor 2 (TLR2) and TLR4. We present the novel finding that in addition to a strong nuclear HMGB1 expression in almost all cells in investigated placentas, an individual variation of cytoplasmic HMGB1 expression was detected in the syncytiotrophoblast covering the peripheral chorionic villi, by cells in the decidua and in amnion. Production of HMGB1 was confirmed by in situ hybridization. Although labour can be described as a controlled inflammatory-like process no differences in HMGB1 expression could be observed comparing active labour and elective Caesarean sections. However, a tendency towards a higher expression of cytoplasmic HMGB1 in the decidua from women with pre-eclampsia was demonstrated. The abundant expression of the receptors RAGE, TLR2 and TLR4 implicates a local capability to respond to HMGB1, although the precise role in the placenta remains to be elucidated.

Holmlund, Ulrika; Wahamaa, Heidi; Bachmayer, Nora; Bremme, Katarina; Sverremark-Ekstrom, Eva; Palmblad, Karin

2007-01-01

141

The use and misuse of animal analog models of human pregnancy disorders.  

PubMed

It has been suggested that the differences between placentation in humans and rodents, such as mice, are sufficient to render human pregnancy unique and to justify ignoring data generated using mice. Detailed examination of the placenta-decidua interaction and decidual NK cell composition in humans, and mice, show that the principles are the same. Indeed, the rat placenta is useful in showing an intermediary arrangement between humans and mice. This is consistent with the thesis of Darwin that structures of older species evolve with development of new species to provide a survival advantage. Molecular details may differ between species, but also between individuals given gene polymorphisms. Human data on interaction of HLA-C2 with NK cell KIR receptors has been used to suggest that human pregnancy problems such as recurrent miscarriage, fetal growth retardation, and pre-eclampsia are due to lack of activation of true uterine NK cell (TuNK) functions that promote trophoblast cell growth and invasion which prevents such problems. But when TuNKs bear certain KIR phenotypes, pathology results. It is shown that such mechanisms could only be pertinent in less than one-third of recurrent miscarriage patients. Activated blood-type NK cells that enter the uterus (BuNKs) remain the major effector of pregnancy loss in humans, and this is consistent with data from the mouse. The importance of activated BuNKs in pre-eclampsia and fetal growth retardation merits further investigation as pre-eclampsia and fetal growth restriction are also manifest in the CBAxDBA/2 mouse model where activated NK cells are the initiator of abortions. PMID:24725995

Clark, David A

2014-06-01

142

Renal markers in normal and hypertensive disorders of pregnancy in Indian women: a pilot study  

PubMed Central

Background Altered renal function is an essential component of the pathophysiological process in pre-eclampsia. Kidneys play an important role in the turnover of low molecular weight substances such as creatinine, uric acid and cystatin C. The present study was undertaken if these serum markers were characteristically altered in Indian pregnant women. Methods Serum levels were therefore determined in samples from 69 healthy women at term as well as in 27 samples of patients with Pregnancy induced hypertension (PIH) and in 20 patients with pre-eclampsia (PE). Results The levels of all three components were significantly higher in pre-eclamptic patients when compared to healthy controls with the mean ± SD being 1.47 ± 0.9 vs. 1.06 ± 0.2 for cystatin C, 0.95 ± 0.2 vs. 0.67 ± 0.1 for creatinine and 6.13 ± 1.8 vs. 4.28 ±1.1 for uric acid respectively. In PIH cystatin C was significantly higher, 1.25 ± 0.9 unlike creatinine, 0.67 ± 0.14 and uric acid, 4.30 ± 1.0. Receiver operating characteristic (ROC) plots demonstrated that the diagnostic accuracy of serum creatinine was superior to serum uric acid and serum cystatin C and serum uric acid was better than serum cystatin C. Conclusion The maternal serum cystatin C, creatinine and uric acid were all significantly elevated at the end of pregnancy in pre-eclampsia compared to those of healthy pregnant women. If this rise in the above markers during early pregnancy could predict the onset of PIH/PE, needs to be investigated.

Padma, Y; Aparna, V B; Kalpana, B; Ritika, V; Sudhakar, P R

2014-01-01

143

Postpartum HELLP syndrome--the case of lost battle  

PubMed Central

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

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

2013-01-01

144

Caesarean section in a case of systemic lupus erythematosus  

PubMed Central

Systemic lupus erythematosus (SLE) is an autoimmune disease most frequently found in women of child bearing age and may co-exist with pregnancy. Disease exacerbation, increased foetal loss, neonatal lupus and an increased incidence of pre-eclampsia are the major challenges. Its multisystem involvement and therapeutic interventions like anticoagulants, steroids and immunosuppressive agents pose a high risk for both surgery and anaesthesia. We describe successful management of an antinuclear antibody (ANA) positive parturient with bad obstetric history who underwent elective caesarean section under spinal anaesthesia.

Vyas, Varsha; Shukla, Deepika; Patil, Surekha; Mohite, Shubha

2014-01-01

145

Histological features of uteroplacental vessels in normal and hypertensive patients in relation to birthweight.  

PubMed

Placental bed biopsies were obtained during caesarean section from normal, pre-eclamptic and hypertensive pregnancies. Of the 14 biopsies from normal pregnancies 13 showed normal vascular physiological changes in the decidua and in the myometrium. Biopsies from 24 pregnancies complicated by pre-eclampsia showed acute atherosis in 18 and physiological changes limited to the decidua in six; none had normal physiological changes. Biopsies from five hypertensive patients showed all three types of histological changes. The mean birthweight centile was lower in the group with atherosis than in the group with limited and the group with normal physiological changes. PMID:2765429

Frusca, T; Morassi, L; Pecorelli, S; Grigolato, P; Gastaldi, A

1989-07-01

146

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.

2014-01-01

147

Perinatal neuroblastoma: a hidden bullet in the chest.  

PubMed

A neonate with antenatally diagnosed intrathoracic mass by ultrasound scan was delivered uneventfully at 35 weeks gestation by caesarean section due to pre-eclampsia and fluctuating hypertension in the mother. The intrathoracic mass was echogenic and the diagnosis was inconclusive. At 12 h of life the baby deteriorated acutely, in terms of increased oxygen requirement, ventilatory care, heart rate fluctuation, hypotension requiring inotropic support and died despite intensive care support. The parents were counselled that an autopsy would be invaluable in providing a diagnosis given the antenatal finding of an intrathoracic mass. The final diagnosis of neuroblastoma was performed at postmortem. PMID:24827646

Venkatesh, Harohalli Iyer; Mohanty, Pankaj Kumar; Razak, Abdul; Nagesh, N Karthik

2014-01-01

148

A case of HELLP syndrome: an immuno-"logical" approach.  

PubMed

We report on a 27-year-old woman who developed severe arterial hypertension on a background of general malaise within 48 hours after vaginal delivery, suggesting severe acute-onset pre-eclampsia. Concomitant biochemical observations of haemolysis, elevated liver tests and low platelets lead to the diagnosis of (post-partum) HELLP syndrome. Our patient was transferred immediately to the intensive care unit (ICU), where she underwent plasmapheresis in combination with intravenous glucocorticoids, nicardipine and labetalol. Our patient recovered fully after three plasmapheresis sessions. Genetic testing of mutations responsible for complement deficits was negative. PMID:23189549

Heggermont, W A; Verhelst, C; De Wilde, K; De Paepe, M; Lacquet, F; Vonck, A

2012-01-01

149

[Hypertensive emergencies in adults: a practical review].  

PubMed

Hypertensive emergencies must be distinguished from severe blood pressure elevations without acute target organ damage. Clinical examination (chest pain, dyspnoea, neurological disorders, ECG, retinal examination) and laboratory tests (blood and urine tests, cerebral imaging in case of neurological disorders) have to be immediately performed. Immediate referral to an intensive care unit is indicated, and an intravenous antihypertensive therapy has to be implemented. Blood pressure objectives depend on the associated acute pathology (myocardial infarction, pulmonary oedema, aortic dissection, severe pre-eclampsia and eclampsia of pregnancy, hypertensive encephalopathy, retinopathy, subarachnoid hemorrhage, cerebral hemorrhage, ischemic stroke treated or not with thrombolysis). PMID:20547034

Sosner, Philippe; Plouin, Pierre-François; Herpin, Daniel

2010-10-01

150

Modern management of eclampsia  

PubMed Central

Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains an important cause of maternal mortality and morbidity. Despite being recognised since antiquity, consistent management practices are still lacking. Given that the aim of good care is to prevent seizures, it is disappointing that in the majority of cases the first eclamptic convulsion occurs after admission to hospital. This indicates that either the women who are likely to have a convulsion were not identified accurately, or the treatment given was ineffective. The answer to poor management of eclampsia lies in better education and training of all obstetricians, anaesthetists, midwives, and general practitioners in the diagnosis and treatment of severe pre-eclampsia and eclampsia. Protocols for the management of fluid balance, antihypertensive and anticonvulsant therapies should be available and reviewed regularly. The universal adoption of such guidelines in all obstetric units would substantially reduce elements of substandard care which have repeatedly been identified in the triennial reports of the confidential enquiries into maternal deaths in the UK.???Keywords: pregnancy; hypertension; eclampsia

Salha, O.; Walker, J.

1999-01-01

151

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

PubMed Central

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

Tabatabaei, Mozhgan

2011-01-01

152

Placental Apoptosis in Health and Disease  

PubMed Central

Apoptosis, programmed cell death, is an essential feature of normal placental development but is exaggerated in association with placental disease. Placental development relies upon effective implantation and invasion of the maternal decidua by the placental trophoblast. In normal pregnancy, trophoblast apoptosis increases with placental growth and advancing gestation. However, apoptosis is notably exaggerated in the pregnancy complications, hydatidiform mole, pre-eclampsia, and intra-uterine growth restriction (IUGR). Placental apoptosis may be initiated by a variety of stimuli, including hypoxia and oxidative stress. In common with other cell-types, trophoblast apoptosis follows the extrinsic or intrinsic pathways culminating in the activation of caspases. In contrast, the formation of apoptotic bodies is less clearly identified, but postulated by some to involve the clustering of apoptotic nuclei and liberation of this material into the maternal circulation. In addition to promoting a favorable maternal immune response, the release of this placental-derived material is thought to provoke the endothelial dysfunction of pre-eclampsia. Widespread apoptosis of the syncytiotrophoblast may also impair trophoblast function leading to the reduction in nutrient transport seen in IUGR. A clearer understanding of placental apoptosis and its regulation may provide new insights into placental pathologies, potentially suggesting therapeutic targets.

Sharp, Andrew N.; Heazell, Alexander E.P.; Crocker, Ian P.; Mor, Gil

2011-01-01

153

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.

Lateef, Aisha; Petri, Michelle

2013-01-01

154

Effect of maternal body mass index on pregnancy outcome and newborn weight  

PubMed Central

Background Maternal obesity has been associated with adverse pregnancy outcomes, such as pre-eclampsia, eclampsia, pre- and post-term delivery, induction of labor, macrosomia, increased rate of caesarean section, and post-partum hemorrhage. The objective of this study was to determine the effect of maternal Body Mass Index (BMI) on pregnancy outcomes. Methods 1000 pregnant women were enrolled in the study. In order to explore the relationship between maternal first trimester Body Mass Index and pregnancy outcomes, participants were categorized into five groups based on their first trimester Body Mass Index. The data were analyzed using Pearson Chi-square tests in SPSS 18. Differences were considered significant if p < 0.05. Results Women with an above-normal Body Mass Index had a higher incidence of pre-eclampsia, induction of labor, caesarean section, pre-term labor, and macrosomia than women with a normal Body Mass Index (controls). There was no significant difference in the incidence of post-term delivery between the control group and other groups. Conclusion Increased BMI increases the incidence of induction of labor, caesarean section, pre-term labor and macrosomia. The BMI of women in the first trimester of pregnancy is associated with the risk of adverse pregnancy outcome.

2012-01-01

155

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.

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

156

The risk of adverse pregnancy outcomes in women who are overweight or obese  

PubMed Central

Background The prevalence of obesity amongst women bearing children in Australia is rising and has important implications for obstetric care. The aim of this study was to assess the prevalence and impact of mothers being overweight and obese in early to mid-pregnancy on maternal, peripartum and neonatal outcomes. Methods A secondary analysis was performed on data collected from nulliparous women with a singleton pregnancy enrolled in the Australian Collaborative Trial of Supplements with antioxidants Vitamin C and Vitamin E to pregnant women for the prevention of pre-eclampsia (ACTS). Women were categorized into three groups according to their body mass index (BMI): normal (BMI 18.5-24.9 kg/m2); overweight (BMI 25-29.9 kg/m2) and; obese (BMI 30-34.9 kg/m2). Obstetric and perinatal outcomes were compared by univariate and multivariate analyses. Results Of the 1661 women included, 43% were overweight or obese. Obese women were at increased risk of pre-eclampsia (relative risk (RR) 2.99 [95% confidence intervals (CI) 1.88, 4.73], p < 0.0001) and gestational diabetes (RR 2.10 [95%CI 1.17, 3.79], p = 0.01) compared with women with a normal BMI. Obese and overweight women were more likely to be induced and require a caesarean section compared with women of normal BMI (induction - RR 1.33 [95%CI 1.13, 1.57], p = 0.001 and 1.78 [95%CI 1.51, 2.09], p < 0.0001, caesarean section - RR 1.42 [95%CI 1.18, 1.70], p = 0.0002 and 1.63 [95%CI 1.34, 1.99], p < 0.0001). Babies of women who were obese were more likely to be large for gestational age (LFGA) (RR 2.08 [95%CI 1.47, 2.93], p < 0.0001) and macrosomic (RR 4.54 [95%CI 2.01, 10.24], p = 0.0003) compared with those of women with a normal BMI. Conclusion The rate of overweight and obesity is increasing amongst the Australian obstetric population. Women who are overweight and obese have an increased risk of adverse pregnancy outcomes. In particular, obese women are at increased risk of gestational diabetes, pregnancy induced hypertension and pre-eclampsia. Effective preventative strategies are urgently needed. Trial Registration Current Controlled Trials ISRCTN00416244

2010-01-01

157

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

PubMed Central

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

Chaturvedi, Sarika; Randive, Bharat

2013-01-01

158

Role of calcium supplementation during pregnancy in reducing risk of developing gestational hypertensive disorders: a meta-analysis of studies from developing countries  

PubMed Central

Background Hypertension in pregnancy stand alone or with proteinuria is one of the leading causes of maternal mortality and morbidity in the world. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy though the effect varies based on baseline calcium intake and pre-existing risk factors. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal mortality in developing countries. Methods A literature search was carried out on PubMed, Cochrane Library and WHO regional databases. Data were extracted into a standardized excel sheet. Identified studies were graded based on strengths and limitations of studies. All the included studies were from developing countries. Meta-analyses were generated where data were available from more than one study for an outcome. Primary outcomes were maternal mortality, eclampsia, pre-eclampsia, and severe preeclampsia. Neonatal outcomes like neonatal mortality, preterm birth, small for gestational age and low birth weight were also evaluated. We followed standardized guidelines of Child Health Epidemiology Reference Group (CHERG) to generate estimates of effectiveness of calcium supplementation during pregnancy in reducing maternal and neonatal mortality in developing countries, for inclusion in the Lives Saved Tool (LiST). Results Data from 10 randomized controlled trials were included in this review. Pooled analysis showed that calcium supplementation during pregnancy was associated with a significant reduction of 45% in risk of gestational hypertension [Relative risk (RR) 0.55; 95 % confidence interval (CI) 0.36-0.85] and 59% in the risk of pre-eclampsia [RR 0.41; 95 % CI 0.24-0.69] in developing countries. Calcium supplementation during pregnancy was also associated with a significant reduction in neonatal mortality [RR 0.70; 95 % CI 0.56-0.88] and risk of pre-term birth [RR 0.88, 95 % CI 0.78-0.99]. Recommendations for LiST for reduction in maternal mortality were based on risk reduction in gestational hypertensive related severe morbidity/mortality [RR 0.80; 95% CI 0.70-0.91] and that for neonatal mortality were based on risk reduction in all-cause neonatal mortality [RR 0.70; 95% CI 0.56-0.88]. Conclusion Calcium supplementation during pregnancy is associated with a reduction in risk of gestational hypertension, pre-eclampsia neonatal mortality and pre-term birth in developing countries.

2011-01-01

159

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

PubMed Central

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

Sharara, Hussein Attia

2012-01-01

160

Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands  

PubMed Central

Background In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear. Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open. The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae. Methods/Design This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information. We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis. Discussion The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes. Trial registration Italian trial: ClinicalTrials.gov Identifier: NCT01244347. Dutch trial: Dutch Trial Register ID: NTR3161.

2014-01-01

161

Helicobacter pylori and pregnancy-related disorders.  

PubMed

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

Cardaropoli, Simona; Rolfo, Alessandro; Todros, Tullia

2014-01-21

162

Endogenous digitalis  

PubMed Central

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

Bagrov, Alexei Y; Shapiro, Joseph I

2008-01-01

163

Dipping your feet in the water: podocytes in urine.  

PubMed

Podocyte injury and loss plays an important role in the pathogenesis and progression of many kidney diseases. Studies have shown that podocyte-related markers and products can be detected in the urine of patients with glomerular diseases such as focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis, diabetic nephropathy and pre-eclampsia. Therefore, detecting the loss of podocytes in the urine provides a useful noninvasive technique of gathering information about the disease type and/or activity of glomerular diseases. Currently, urine podocyte-related protein markers, mRNA, microRNA and exosomes have been used with varying degrees of success to study glomerular diseases. The determination of urinary podocyte loss may become an important noninvasive tool in the evaluation of glomerular diseases. PMID:24724555

Sir Elkhatim, Rashid; Li, Jordan Yz; Yong, Tuck Y; Gleadle, Jonathan M

2014-05-01

164

[Respiratory disorders during sleep in the pregnant woman].  

PubMed

Sleep disordered breathing can occur during pregnancy due to the development of hormonal changes and respiratory function abnormalities that perturb patency of the upper airways. Habitual snoring has been described in 25 p. 100 of the women during the third trimester of pregnancy. The incidence of sleep apnea hypopnea syndrome is unknown due to the lack of longitudinal epidemiological data, and results of the main studies are in favor of upper airway resistance syndrome. However, these sleep-related breathing disorders are more frequently associated with maternal and fetal complications such as maternal hypertension, pre eclampsia and intrauterine growth restriction. This article points out the importance of such associations because of the efficacy of continuous positive airway pressure on the regression of these nocturnal respiratory and vascular complications. PMID:14646807

Meurice, J C; Paquereau, J; Neau, J-P; Pourrat, O; Pierre, F

2003-11-01

165

Idiopathic subglottic stenosis in pregnancy: A deceptive laryngoscopic view  

PubMed Central

A 28-year-old lady with term gestation, pre-eclampsia and a vague history of occasional breathing difficulty, on irregular bronchodilator therapy, was scheduled for category 1 lower segment caesarean section in view of foetal distress. A Cormack-Lehane grade 1 direct laryngoscopic view was obtained following rapid sequence induction. However, it was not possible to insert a 7.0 or 6.0 size styleted cuffed tracheal tube in two attempts. Ventilation with a supraglottic device was inadequate. Airway was secured with a 4.0 size microlaryngeal surgery tube with difficulty. Computed tomography scan of the neck following tracheostomy for failed extubation revealed subglottic stenosis (SGS) with asymmetric arytenoid calcification. This report describes the management of a rare case of unrecognised idiopathic SGS in pregnancy.

Karippacheril, John George; Goneppanavar, Umesh; Prabhu, Manjunath; Revappa, Kiran Bada

2011-01-01

166

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

Walker, I.

2000-01-01

167

A Short History of Sonography in Obstetrics and Gynaecology  

PubMed Central

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

Campbell, S.

2013-01-01

168

Management of paroxysmal hypertension due to incidental pheochromocytoma in pregnancy  

PubMed Central

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

Lata, Indu; Sahu, Sandeep

2011-01-01

169

Posterior leukoencephalopathy syndrome as a cause of reversible blindness during pregnancy.  

PubMed

Cortical blindness is a rare and dramatic complication of pre-eclampsia. The precise nature of the pathogenesis of this condition has not previously been understood. Three preeclamptic patients with unremarkable previous medical history presented with acute blindness between the 28th and 33rd weeks of pregnancy. They were all diagnosed as posterior leukoencephalopathy syndrome (PLES). In all these patients, MRI study revealed the typical feature of gray-white matter edema localized to the temporo-parieto-occipital areas. Vision and MRI findings were restored in all patients after delivery. Although PLES has been described as a puerperal clinicoradiologic entity, it may be seen in preeclamptic-eclamptic patients during the pregnancy. Therefore neuro-imaging studies should be carried out in pregnant patients with visual disturbances in order to exclude PLES. Prompt diagnosis, immediate control of blood pressure, and elimination of possible causes resolves clinical and imaging findings. PMID:17688625

Onderoglu, Lutfu S; Dursun, Polat; Gultekin, Murat; Celik, Nilufer Y

2007-08-01

170

Adverse pregnancy outcome among teenagers: a reality?  

PubMed

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

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

2014-05-01

171

Thyroid dysfunction during pregnancy and in postpartum period: treatment and latest recommendations.  

PubMed

Thyroid dysfunction is the second most common endocrine disorder, only after diabetes mellitus, affecting females in reproductive age group. Pregnancy is associated with profound repercussions on the thyroid status of a lady. Thyroid dysfunctions such as hypothyroidism, thyrotoxicosis and thyroid nodules may develop during pregnancy leading to abortion, placental abruptions, pre-eclampsia, preterm delivery and reduced intellectual function in the offspring. Thus, maintenance of euthyroid state is of utmost important for maternal and fetal well being during pregnancy as well as after. The Endocrine Society has issued latest guidelines regarding the diagnosis and management of thyroid dysfunction related to pregnancy. All the clinicians should be well aware of the latest recommendations regarding management of thyroid dysfunction in pregnancy and in postpartum phase and practice them accordingly. PMID:24510157

Vandana; Kumar, Amit; Khatuja, Ritu; Mehta, Sumita

2014-05-01

172

[Pregnancy and adolescence].  

PubMed

The objective of this study was to verify the occurrence of pregnancy complications in adolescents and neonatal complications in their children. From 1980-1983, 88 pregnant adolescents under 16 years of age were treated at the Hospital das Clinicas of UFMG, Belo Horizonte, Brazil. The patients ranged in age from 13 to 16 years. There was an increased incidence of pregnancy complications in this group when compared to the incidence of complications presented by 552 patients over 17 years of age. The high percentage of unmarried adolescents indicates that a large number of their pregnancies were unplanned. There was a significant increase in the incidence of pre-eclampsia, urinary infection, and anemia in the group of pregnant adolescents. An increase in perinatal morbidity or mortality was not observed. Because of the obstetric problems detected, all pregnant adolescents should receive special attention in the prenatal period and during parturition. PMID:12267709

Cabra, A C; Peixoto, R M; Miranda, S P; Vieira, E

1985-01-01

173

Acute Cardiac Failure in a Pregnant Woman due to Thyrotoxic Crisis  

PubMed Central

Introduction. Cardiac failure during pregnancy is usually related to preeclampsia/eclampsia, rarely to hyperthyroidism. While hyperthyroidism can easily lead to hypertensive cardiac failure and may harm the fetus, it is sometimes difficult to distinguish hyperthyroidism from normal pregnancy. Case Presentation. We encountered a case of 41-year-old pregnant woman with hypertensive cardiac failure. Because we initially diagnosed as pre-eclampsia/eclampsia, Caesarian section was performed. However, her symptoms still persisted after delivery. After thyroid function test results taken on the day of admission were obtained on the fourth day, we could diagnose that her cardiac failure was caused by thyrotoxic crisis. Conclusions. Hypertensive cardiac failure due to hyperthyroidism during pregnancy is rare and difficult to diagnose because of similar presentation of normal pregnancy. However, physicians should be aware of the risks posed by hyperthyroidism during pregnancy.

Okuda, Nao; Onodera, Mutsuo; Tsunano, Yumiko; Nakataki, Emiko; Oto, Jun; Imanaka, Hideaki; Nishimura, Masaji

2012-01-01

174

Secondary headaches attributed to arterial hypertension  

PubMed Central

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

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

2013-01-01

175

Obesity and fetal-maternal outcomes  

PubMed Central

In women Obesity has a significant impact on every aspect of female reproductive life both in terms of infertility and early pregnancy complications. It is linked to a number of adverse obstetric outcomes as well as increased maternal and neonatal morbidity and mortality. These complications include miscarriage, congenital abnormalities, pre-eclampsia, gestational diabetes mellitus, iatrogenic preterm delivery, post-dates pregangy with increased rates of induction of labour, caesarian section and complications during and following operative procedures, post-partum haemorrhage, shoulder dystocia, infection, venous thromboembolism and increased hospital day. It is important to consider obese pregnant women as a high risk group with a linear increase in risk of complications associated with their degree of obesity.

Dinatale, Angela; Ermito, Santina; Fonti, Ilenia; Giordano, Rosalba; Cacciatore, Alessandra; Romano, Mattea; La Rosa, Beatrice

2010-01-01

176

[Use of magnesium sulfate in obstetrics].  

PubMed

Magnesium sulfate (MgSO(4)) is the best treatment of eclampsia, reduces the risk of recurrence better than other anticonvulsants and is recommended as first line in cases of eclampsia. In cases of severe pre-eclampsia and especially when prodromes are present, MgSO(4) reduces better than conventional anticonvulsants the risk of eclampsia. More recently, MgSO(4) was used in cases of preterm delivery to reduce the risk of cerebral palsy in premature infants. Three large randomized trials have obtained convergent results which all tended to show a neuroprotective effect of MgSO(4). These trials were included in three meta-analyzes that showed a 30% reduction in the incidence of cerebral palsy before 32 weeks gestation suggesting that this drug should be used in cases of preterm birth. A protocol using low doses associated with a well-conducted maternal surveillance reduces of maternal hypermagnesemia and the risk of maternal toxicity. PMID:22995056

Kayem, G; Mandelbrot, L; Haddad, B

2012-10-01

177

Clinical manifestations of obstructive sleep apnoea in pregnancy: more than snoring and witnessed apnoeas.  

PubMed

Sleep disordered breathing and its symptoms have been associated with a multitude of fetal and maternal complications including gestational hypertensive disorders, gestational diabetes and possibly pre-term labour and other markers of alterations in fetal wellbeing. The disease remains underdiagnosed in the general population but likely also in pregnancy, mostly because providers do not appropriately screen for the disorder. Sleep disordered breathing may manifest differently in women, since women report more fatigue and less snoring than men do. This paper discusses typical presentations of sleep disordered breathing but also reports some less obvious presentations to help providers recognise those manifestations and screen for the disorder when warranted. Our case series describes patients with diagnoses such as chronic hypertension, pre-eclampsia, pulmonary hypertension, nocturnal asthma and panic attacks, who were diagnosed with sleep disordered breathing and offered treatment with CPAP during pregnancy. PMID:22663313

Bourjeily, G; Barbara, N; Larson, L; He, M

2012-07-01

178

Unsuspected 34-week pregnancy presenting as acute hypoxaemic respiratory failure  

PubMed Central

An obese body habitus may interfere with diagnosis of potentially life?threatening conditions. This report describes an obese woman who presented with acute hypoxemic respiratory failure and diffuse infiltrates. Her body habitus disguised her parturient abdomen and she could not provide a history because she was intubated and paralysed. Only after a urine pregnancy test was undertaken did it become apparent that she was pregnant and the diagnosis of pre?eclampsia with pulmonary oedema was considered. Urine pregnancy tests are part of the standard work?up for abdominal pain in women of childbearing age, but are not viewed as part of the work?up for respiratory distress or diffuse radiographic infiltrates. This case illustrates the value of obtaining a pregnancy test in all women, particularly those with obese body habitus, who present with respiratory failure of unclear aetiology.

Luks, Andrew M

2007-01-01

179

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

PubMed Central

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

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

2012-01-01

180

How to manage hypertension in pregnancy effectively  

PubMed Central

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

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

2011-01-01

181

Impaired decidual natural killer cell regulation of vascular remodelling in early human pregnancies with high uterine artery resistance.  

PubMed

During human pregnancy, natural killer (NK) cells accumulate in the maternal decidua, but their specific roles remain to be determined. Decidual NK (dNK) cells are present during trophoblast invasion and uterine spiral artery remodelling. These events are crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Remodelling of spiral arteries is impaired in the dangerous pregnancy complication pre-eclampsia. We studied dNK cells isolated from pregnancies at 9-14 weeks' gestation, screened by uterine artery Doppler ultrasound to determine resistance indices which relate to the extent of spiral artery remodelling. dNK cells were able to promote the invasive behaviour of fetal trophoblast cells, partly through HGF. Cells isolated from pregnancies with higher resistance indices were less able to do this and secreted fewer pro-invasive factors. dNK cells from pregnancies with normal resistance indices could induce apoptotic changes in vascular smooth muscle and endothelial cells in vitro, events of importance in vessel remodelling, partly through Fas signalling. dNK cells isolated from high resistance index pregnancies failed to induce vascular apoptosis and secreted fewer pro-apoptotic factors. We have modelled the cellular interactions at the maternal-fetal interface and provide the first demonstration of a functional role for dNK cells in influencing vascular cells. A potential mechanism contributing to impaired vessel remodelling in pregnancies with a higher uterine artery resistance is presented. These findings may be informative in determining the cellular interactions contributing to the pathology of pregnancy disorders where remodelling is impaired, such as pre-eclampsia. PMID:22653829

Fraser, Rupsha; Whitley, Guy Stj; Johnstone, Alan P; Host, Amanda J; Sebire, Neil J; Thilaganathan, Baskaran; Cartwright, Judith E

2012-11-01

182

Pregnancy after renal transplantation: ten-year single-center experience.  

PubMed

There has been an increase in the number of pregnancies among renal transplant recipients. Our experience included 61 pregnancies in 53 patients from January 1997 to April 2007, with 6 patients having multiple pregnancies. Patients were studied for clinical, obstetrical, and perinatal outcomes. The mean patient age was 24.5 years (range, 19-38). They all received living donor kidneys. The mean transplantation-pregnancy interval was 2.7 years (range, 1.7-5.3 years). Immunosuppressive drugs consisted of cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone (pred) in 38 patients (72%); CsA, azathioprine (AZA), plus pred were used in 15 patients (28%). Pregnancy complications were chronic hypertension in 21 patients (40%), anemia in 28 (52.6%), and urinary tract infection in 18 (34%). Twelve patients (22.6%) received blood transfusions. Pre-eclampsia was diagnosed in 14 cases (26.4%) and renal dysfunction in 11 (20.7%) with pre-eclampsia assumed to be the main cause. Three patients (5.6%) had graft losses as a result of hemorrhagic shock, sepsis, and eclampsia. Premature rupture of membranes occurred in 6 cases (11.3%), and preterm delivery occurred in 14 cases (26.4%). Eleven (20.7%) newborns were small for gestational age. One club foot and one large facial hemangioma occurred in 2 infants, respectively. One case of neonatal death was registered as a result of excessive prematurity. One mother died due to sepsis. Cesarean section was performed in 24 patients (45.2%), the main indications being related to hypertension and fetal distress. There were no significant differences between MMF-treated and AZA-treated patients with respect to clinical, obstetrical, and perinatal outcomes. This group of patients was characterized by a wide range of antenatal and perinatal problems that must be managed in specialized tertiary units to achieve the best results. MMF may be as safe as AZA in pregnancy. PMID:18261600

Ghafari, A; Sanadgol, H

2008-01-01

183

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

PubMed Central

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

2011-01-01

184

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

PubMed Central

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

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

2014-01-01

185

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

PubMed Central

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

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

2001-01-01

186

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

187

Risk Factors for Type 1 Diabetes Mellitus among Children and Adolescents in Basrah  

PubMed Central

Objectives Environmental factors play an important role in the pathogenesis of type 1 diabetes mellitus, many of these factors have been uncovered despite much research. A case-control study was carried out to determine the potential maternal, neonatal and early childhood risk factors for type 1 diabetes mellitus in children and adolescents in Basrah. Methods A total of 96 diabetic patients who have been admitted to the pediatric wards at 3 main hospitals in Basrah, and those who have visited primary health care centers over the period from the 4th of November 2006 to the end of May 2007 were recruited. In addition, 299 non-diabetic children were included, their age ranged from 18 months to 17 years. Results Family history of type 1 diabetes mellitus and thyroid diseases in first and second degree relatives was found to be an independent risk factor for type 1 diabetes mellitus, (p<0.001). Regarding maternal habits and illnesses during pregnancy, the study has revealed that tea drinking during pregnancy is a risk factor for type 1 diabetes mellitus in their offspring, (p<0.05). In addition, maternal pre-eclampsia and infections were found to be significant risk factor for type 1 diabetes mellitus, (p<0.001). Neonatal infections, eczema and rhinitis during infancy were also significantly associated with development of type 1 diabetes mellitus. Moreover, the results revealed that duration of <6 months breast feeding is an important trigger of type 1 diabetes mellitus. Conclusion Exposure to environmental risk factors during pregnancy (tea drinking, pre-eclampsia, and infectious diseases), neonatal period (respiratory distress, jaundice and infections) and early infancy are thought to play an important role in triggering the immune process leading to B-cell destruction and the development of type 1 diabetes mellitus.

Majeed, Athar Abdul Samad; Hassan, Kadhum

2011-01-01

188

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.

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

2009-01-01

189

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

PubMed

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

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

2014-01-01

190

Antidepressant use during pregnancy and the risk of pregnancy-induced hypertension  

PubMed Central

AIM Due to their effect on altering physiological interactions between vasodilator and vasoconstrictor autacoids in normal pregnancies, antidepressants may be associated with the risk of pregnancy-induced hypertension. We evaluated the impact of antidepressant use during pregnancy on the risk of pregnancy-induced hypertension. METHODS We conducted a nested case–control study within the Quebec Pregnancy Registry, built by linkage of provincial medical, pharmaceutical, hospital and birth databases. We identified 1216 women with a diagnosis of pregnancy-induced hypertension with or without pre-eclampsia and with no history of hypertension before pregnancy. We randomly selected 10 controls for each case, matched on case index date (date of diagnosis) and gestational age. Odds ratios (OR) were calculated using conditional logistic regression models, adjusting for sociodemographic characteristics, maternal depression, anxiety, other chronic conditions, medication use and health service utilization. RESULTS Among cases, 45 (3.7%) had used antidepressants during pregnancy compared with 300 (2.5%) in the control group (OR 1.52, 95% CI 1.10, 2.09). After adjusting for potential confounders, use of antidepressants during pregnancy was significantly associated with increased risk of pregnancy-induced hypertension (OR 1.53, 95% CI 1.01, 2.33). In stratified analyses, use of selective serotonin re-uptake inhibitors (OR 1.60, 95% CI 1.00, 2.55), and more specifically, paroxetine (OR 1.81, 95% CI 1.02, 3.23) was associated with risk of pregnancy-induced hypertension. CONCLUSIONS Women who use antidepressants during pregnancy are at increased risk of pregnancy-induced hypertension with or without pre-eclampsia above and beyond the risk that could be attributed to their depression or anxiety disorders.

De Vera, Mary A.; Berard, Anick

2012-01-01

191

Hypertensive crisis during pregnancy and postpartum period.  

PubMed

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

Too, Gloria T; Hill, James B

2013-08-01

192

Incidence and predictors of severe obstetric morbidity: case-control study  

PubMed Central

Objective To estimate the incidence and predictors of severe obstetric morbidity. Design Development of definitions of severe obstetric morbidity by literature review. Case-control study from a defined delivery population with four randomly selected pregnant women as controls for every case. Setting All 19 maternity units within the South East Thames region and six neighbouring hospitals caring for pregnant women from the region between 1 March 1997 and 28 February 1998. Participants 48?865 women who delivered during the time frame. Results There were 588 cases of severe obstetric morbidity giving an incidence of 12.0/1000 deliveries (95% confidence interval 11.2 to 13.2). During the study there were five maternal deaths attributed to conditions studied. Disease specific morbidities per 1000 deliveries were 6.7 (6.0 to 7.5) for severe haemorrhage, 3.9 (3.3 to 4.5) for severe pre-eclampsia, 0.2 (0.1 to 0.4) for eclampsia, 0.5 (0.3 to 0.8) for HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, 0.4 (0.2 to 0.6) for severe sepsis, and 0.2 (0.1 to 0.4) for uterine rupture. Age over 34 years, non-white ethnic group, past or current hypertension, previous postpartum haemorrhage, delivery by emergency caesarean section, antenatal admission to hospital, multiple pregnancy, social exclusion, and taking iron or anti-depressants at antenatal booking were all independently associated with morbidity after adjustment. Conclusion Severe obstetric morbidity and its relation to mortality may be more sensitive measures of pregnancy outcome than mortality alone. Most events are related to obstetric haemorrhage and severe pre-eclampsia. Caesarean section quadruples the risk of morbidity. Development and evaluation of ways of predicting and reducing risk are required with particular emphasis paid on the management of haemorrhage and pre-eclampsia. What is already known on this topicMaternal mortality is used internationally as a measure of the quality of obstetric intervention, although it is now rare in the developed worldHospital based series estimating the incidence of severe obstetric morbidity have used different definitionsEstimated incidence of severe obstetric morbidity ranges from 0.05 to 1.09What this study addsWith clear definitions and population based estimates of some severe obstetric morbidities this study estimated the overall incidence of severe obstetric morbidity as 1.2 % of deliveriesTwo thirds of the cases are related to severe haemorrhage, one third to hypertensive disordersRisk factors for severe maternal morbidity include maternal age >34, social exclusion, non-white, hypertension, previous postpartum haemorrhage, induction of labour, and caesarean section

Waterstone, Mark; Bewley, Susan; Wolfe, Charles

2001-01-01

193

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

PubMed Central

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

2013-01-01

194

Peripartum cardiomyopathy - case series  

PubMed Central

Objectives To study the pattern of presentation, course of disease and outcome of pregnancy in Peripartum Cardiomyopathy. Methods A prospective study of sixteen cases of PPCM was conducted at Apple Saraswati Multispecialty Hospital and Dr. D.Y. Patil Medical College and Hospital, Kolhapur, Maharashtra, India from January 2006 to December 2012. Data included age distribution, parity, gestational age, symptoms and risk factors. Medical management and pregnancy outcome were documented. Serial echocardiography data was compiled for a period of one year. Results In our study 9/16 (56%) were primigravidae, 4/16 (25%) had pre-eclamsia and 6/16 (35%) had co-existing hypertension. The difference in Echocardiography parameters observed between recovered and non-recovered patients was significant: Left Ventricular End diastolic dimension (5.6 cm vs 6.06 cm), Left Ventricular Ejection Fraction (28.7% vs 22.4%) and Left Ventricular fractional shortening (17.5% vs 13.4%). Thirteen out of sixteen patients were followed up for a period of one year out of which 61% (8/13) patients recovered completely. There was one mortality. Conclusion PPCM is a diagnosis of exclusion. Majority were young primigravidae presenting postnatally. Pre-eclampsia and hypertension were risk factors. ECHO parameters were reliable predictors of recovery. Future pregnancies are better avoided.

Prasad, Gowri Sayi; Bhupali, Ashok; Prasad, Sayi; Patil, Ajit N.; Deka, Yashodhan

2014-01-01

195

Ethnic differences in perinatal mortality--a challenge.  

PubMed Central

The perinatal mortality rates of mothers who delivered at St. Thomas's Hospital from 1969 to 1976 have been examined. The rate in the West Indian population was significant higher than in the United Kingdom white population. The increased West Indian mortality was confined to infants with a birth weight of more than 2.0 kg and a gestational age of more than 37 weeks. The relative risk of perinatal death for West Indian mothers compared with UK white mothers was 1.4 at birth weights of 2.5 kg to 2.9 kg, rising to 4.3 at 4.0 + kg. West Indian perinatal mortality in term babies of normal birth weight was higher in all maternal age and parity groups except parity 3, but the difference was greatest in women aged 30 or over. The African perinatal mortality rate was not significantly greater than the UK white rate although it followed the West Indian trends. Pre-eclampsia and forceps delivery were associated with a greatly increased perinatal mortality in West Indian babies. The excess West Indian mortality could not be explained completely by differences in the proportions of stillbirths and early neonatal deaths nor by the distribution of births by parity, maternal age, or social class. Possible explanations for the differences in mortality are discussed.

Robinson, M J; Palmer, S R; Avery, A; James, C E; Beynon, J L; Taylor, R W

1982-01-01

196

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.

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

2014-01-01

197

The use of fetal fibronectin testing in the management of a triplet pregnancy with a short cervix  

PubMed Central

Following in vitro fertilisation treatment, a 40-year-old woman was expecting trichorionic, triamniotic triplets. Her cervix shortened from 34 mm at 16+5 weeks to 16 mm at 20+5 weeks, a risk reported with 100% delivery before 28 weeks gestation. She was admitted to hospital and at 24+1 weeks was given corticosteroids. From 21+5 weeks her cervical length remained below 16 mm. However, weekly fetal fibronectin (fFN) tests were negative from 22+5 weeks to delivery at 35+5 weeks. This, along with an absence of symptoms, gave her doctors confidence to manage her as an outpatient from 28 weeks. At 33+5 weeks she was diagnosed as having pre-eclampsia and three live births were delivered by prelabour caesarean section. Prior to delivery her cervical length was 10 mm and fFN test remained negative. There are no reports of outcome following a negative fFN with a short cervix in triplet pregnancies but fFN could be a useful tool, in conjunction with cervical length measurement, in the management of triplets.

Morriss, Alexandra Karin; Smout, Elizabeth; Shennan, Andrew

2011-01-01

198

The use of fetal fibronectin testing in the management of a triplet pregnancy with a short cervix.  

PubMed

Following in vitro fertilisation treatment, a 40-year-old woman was expecting trichorionic, triamniotic triplets. Her cervix shortened from 34 mm at 16(+5) weeks to 16 mm at 20(+5) weeks, a risk reported with 100% delivery before 28 weeks gestation. She was admitted to hospital and at 24(+1) weeks was given corticosteroids. From 21(+5) weeks her cervical length remained below 16 mm. However, weekly fetal fibronectin (fFN) tests were negative from 22(+5) weeks to delivery at 35(+5) weeks. This, along with an absence of symptoms, gave her doctors confidence to manage her as an outpatient from 28 weeks. At 33(+5) weeks she was diagnosed as having pre-eclampsia and three live births were delivered by prelabour caesarean section. Prior to delivery her cervical length was 10 mm and fFN test remained negative. There are no reports of outcome following a negative fFN with a short cervix in triplet pregnancies but fFN could be a useful tool, in conjunction with cervical length measurement, in the management of triplets. PMID:22689723

Morriss, Alexandra Karin; Smout, Elizabeth; Shennan, Andrew

2011-01-01

199

Endothelial-derived hyperpolarization factor (EDHF) contributes to PlGF-induced dilation of mesenteric resistance arteries from pregnant rats.  

PubMed

The aim of this study was to investigate the cellular mechanism involved in the potent vasodilatory action of PlGF on mesenteric resistance arteries from pregnant rats. PlGF (3 nM) induced a vasodilation of 64 ± 3.8% that was completely abolished by endothelial denudation. Significant dilation (28 ± 4.0%) remained, however, in the presence of nitric oxide synthase and cyclooxygenase inhibition, and was associated with significant reductions in vascular smooth muscle cell calcium. Absence of dilation in potassium-depolarizing solution (30 mM) confirmed its dependence on endothelial-derived hyperpolarization factor. Subsequent studies established that vasodilation was abolished by pharmacologic inhibition of SK(Ca) (apamin) and BK(Ca) (iberiotoxin) but not IK(Ca) (tram-34) potassium channels. In summary, PlGF acts through the release of a combination of endothelium-derived relaxation factors. Based on the results of potassium channel blockade, we suggest that it induces endothelial hyperpolarization via SK(Ca) channel activation; this, in turn, leads to the release of a diffusible mediator that activates vascular smooth muscle BK(Ca) channels, hyperpolarization and vasodilation. This is the first study to identify the mechanism for PlGF/VEGFR-1 resistance artery dilation in the pregnant state, whose attenuation likely contributes to the systemic hypertension characteristic of pre- eclampsia. PMID:21985802

Mandalà, Maurizio; Gokina, Natalia; Barron, Carolyn; Osol, George

2012-01-01

200

Pregnancy outcomes and the effect of metformin treatment in women with polycystic ovary syndrome: an overview.  

PubMed

This article is a review of the literature assessing pregnancy outcomes and the effect of metformin treatment among women with polycystic ovary syndrome (PCOS). A review of research published in English was undertaken using PubMed and MEDLINE databases. The weight of the available evidence suggests that pregnant women with PCOS are at an increased risk of developing gestational diabetes, hypertensive disorders of pregnancy, preterm birth and early pregnancy loss. Obesity is a contributory factor for the increased risk of gestational diabetes in this group of women and is estimated to affect 5-40% of pregnant women with PCOS. The prevalence of other obstetric complications is estimated at 10-30% for gestational hypertension, 8-15% for pre-eclampsia and 6-15% for preterm birth. The association between PCOS and early pregnancy loss may not be direct, wherein the presence of PCOS-associated hyperinsulinemia, leading to hyperandrogenemia, has been implicated in the pathophysiology of early pregnancy loss. Apart from the role of metformin in improving the metabolic consequences accompanying PCOS, it has been shown to improve pregnancy rates in women with PCOS who are resistant to clomiphene citrate. In conclusion, pregnancy in women with PCOS is associated with adverse obstetric outcomes (multiple adverse obstetric risk). Whether metformin should be administered throughout pregnancy still remains controversial. Further prospective studies that foster a larger number of participants and adjust for all potentially confounding factors are needed. PMID:22375613

Ghazeeri, Ghina S; Nassar, Anwar H; Younes, Zeina; Awwad, Johnny T

2012-06-01

201

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

202

Liver diseases unique to pregnancy: a 2010 update.  

PubMed

Liver disorders occurring during pregnancy may be specifically pregnancy-related, or may be due to an intercurrent or chronic liver disease, which may present in anyone, pregnant or not. This review focuses on the liver diseases unique to pregnancy. Hyperemesis gravidarum, which occurs during early pregnancy, may be associated with liver dysfunction. Intrahepatic cholestasis of pregnancy typically occurs during the second or third trimester. Pruritus and the associated biological signs of cholestasis improve rapidly after delivery. Mutations in gene encoding biliary transporters, especially ABCB4 encoding the multidrug resistance 3 protein, have been found to be associated with this complex disease. Ursodeoxycholic acid is currently the most effective medical treatment in improving pruritus and liver tests. Pre-eclampsia, which presents in late pregnancy frequently involves the liver, and HELLP syndrome (Hemolysis-Elevated Liver enzymes-Low Platelets) is a life-threatening complication. Prognosis of acute fatty liver of pregnancy has been radically transformed by early delivery, and clinicians must have a high index of suspicion for this condition when a woman presents nausea or vomiting, epigastric pain, jaundice, or polyuria-polydipsia during the third trimester. Acute fatty liver of pregnancy has been found to be associated with a defect of long-chain 3-hydroxyacyl coenzyme A dehydrogenase in the fetus, and mothers and their offspring should undergo DNA testing at least for the main associated genetic mutation (c.1528G>C). PMID:21310683

Bacq, Yannick

2011-03-01

203

[Treatment experience with metformin in polycystic ovary syndrome].  

PubMed

Based on the favourable international experience with metformin in the most common female endocrine disease, the polycystic ovary syndrome, which has insulin resistance in the background, the author's treatment advice has been this in such cases since early 2002: for sexually active women who do not want to become pregnant for the time being, anti-androgenic contraceptive pill; for those who do not want to take contraceptives, contraceptives are contraindicated, or who do want to conceive, metformin. 44/71 non-diabetic patients opted for metformin treatment. A 3 to 30 month follow-up period of 25 patients could be evaluated. Seven patients had transient vertigo, diarrhoea or abdominal discomfort at the beginning of the treatment. The severity of acne of 21 patients diminished significantly by three months and the acne score fell close to the half value by six months. Body hair of 17 women with hypertrichosis diminished significantly by six months. Menstrual cycles of 8/13 patients became regular by three months; a further woman became pregnant and continued metformin throughout pregnancy. Her blood pressure remained normal despite suffering from pre-eclampsia during all of her previous pregnancies. The average body mass index and waist-to-hip ratio did not change significantly during the follow-up. Apart from few initial, transient side effects, disadvantages of the treatment were not found. Long-term metformin treatment resulted in significant improvement of the symptoms of patients with polycystic ovary syndrome. PMID:15991679

Petrányi, Gyula

2005-05-22

204

A rare manifestation of neonatal alloimmune thrombocytopaenia.  

PubMed

Neonatal alloimmune thrombocytopaenia (NAIT) results from a fetomaternal incompatibility with maternal sensitisation against a fetal human platelet antigen (HPA) and antibodies transfer to the fetal circulation, leading to platelet destruction. The clinical presentation is variable and isolated intraocular haemorrhage is rare. We present the case of a male newborn, with intrauterine growth restriction, born at 29?weeks due to pre-eclampsia. He presented proptosis of the left eye, hyphaema and elevated intraocular pressure, with no other signs of haemorrhage. Severe thrombocytopaenia was found (27×10(9)/L). Perinatal infection and maternal thrombocytopaenia were excluded. Positive anti-HPA-1a and antihuman leucocyte antigen class I alloantibodies were found in the mother. Platelet crossmatch between the father's platelets and mother's plasma was positive. Platelet transfusions and intravenous immunoglobulin were given with favourable response. This case highlights an unusual presentation of NAIT, which should be suspected in the presence of severe thrombocytopaenia in the first 24-72?h of life. PMID:24891486

Jerónimo, Monica; Azenha, Cátia; Mesquita, Joana; Pereira, Dolores Faria

2014-01-01

205

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

PubMed Central

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

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

2008-01-01

206

[Hyperhomocysteinemia and pregnancy complications].  

PubMed

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

Sztenc, S?awomir

2004-04-01

207

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

208

The science of implantation emerges blinking into the light.  

PubMed

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

Sharkey, Andrew M; Macklon, Nick S

2013-11-01

209

Salicylate and cocaine: interactive toxicity during chicken mid-embryogenesis.  

PubMed

Increased free radical production, due to ischemia and reperfusion, has been postulated as a cause of cocaine's (COC) developmental toxicity. Salicylate reacts with hydroxyl free radicals (*OH) to form stable, quantifiable reaction products, which can be measured with high-pressure liquid chromatography (HPLC). To determine if chicken embryos' brains and hearts were exposed to increased *OH concentrations after injection of COC, an injection of a nontoxic dose of sodium salicylate (NaSAL, 100 mg/kg egg, or 5 mg/egg), followed by 5 injections of COC (13.5 mg/kg or 0.675 mg/egg, every 1.5 h), was administered to eggs containing embryos on the 12th day of embryogenesis (E12). In addition to finding increased *OH concentrations in E12 embryonic hearts and brains, we observed that the developmental toxicity of COC, manifest as vascular disruption (hemorrhage) and lethality, was enhanced by NaSAL injection. These results confirm and extend results of similar experiments performed upon older embryos (E18), and indicate that increased &z.rad;OH concentration in embryonic tissues after COC exposure and toxic interactions of COC and NaSAL can also occur at an earlier stage of development. The results are discussed in light of possible exposure of human fetuses to both COC and salicylates, since COC-abusing pregnant women can be misdiagnosed with pre-eclampsia and aspirin is used to treat this syndrome. PMID:11163537

Venturini, L; Sparber, S B

2001-01-15

210

[Role of the genetic factors, detoxication systems and oxidative stress in the pathogenesis of endometriosis and infertility (review)].  

PubMed

The aim of this paper is to provide a systematic review of the role of the genetic factors, detoxication systems and oxidative stress in the pathogenesis of endometriosis and infertility. Endometriosis and infertility are still both the most uncommon diseases in gynecology. Many aspects of female reproductive function are strongly influenced by genetic factors, and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as polycystic ovary syndrome, endometriosis, fibroids, cancer (ovarian, vulvar, cervical), premature ovarian failure, recurrent pregnancy loss and pre-eclampsia. The most solid evidence linking specific polymorphisms to endometriosis is showed by the studies investigating a phase II detoxification enzyme. No data were found concerning influences of the genetic factors on the female infertility. Contrary, a lot of studies devoted to the genetic factors of male infertility are presented. It's known that endometriosis associated with increased systemic oxidative stress. The implication of increased systemic oxidative stress in disease progression or the association with other oxidative stress-related pathologic conditions needs to be addressed in further studies. The majority of studies suggest a reduced antioxidant capacity in infertile wome with endometriosis. In the present review we discussed the role of the genetic factors in the pathogenesis of endometriosis and infertility. NAT2 polimorphism, xenobiotic methabolism and exogenous factors are somehow related with these diseases. An altered balance between pro-oxidant antioxidant activities may have an impact on folliculogenesis and adequate embryo development. PMID:24340639

Dubinskaia, E D; Gasparov, A S; Fedorova, T A; Lapteva, N V

2013-01-01

211

Cardiology for gynecologists--a minireview.  

PubMed

Despite cardiovascular disease (CVD) being by far the most common cause of death in women worldwide, awareness is low. Myocardial infarction occurs 10 years later in women than in men. Symptoms may be atypical: dyspnea rather than chest pain. Also more women than men have myocardial infarction with normal coronary angiography, probably due to microvascular disease or coronary spasm. The prognosis of non-obstructive disease is now recognized to be the same than for obstructive disease. The conventional risk factors for CVD are the same for both genders but have a different impact for women. One example is psychosocial stress and angina pectoris can more often be induced by mental stress in women than in men. Also there are risk factors specific to women such as a history of pre-eclampsia, gestational hypertension or diabetes and polycystic ovary syndrome (PCOS). Furthermore atrial fibrillation increases the risk of stroke more in women than in men. However, 6 out of 10 deaths from CVD can be prevented by a healthy life style and dealing with preexisting risk factors. Hence it is important that gynecologists who start seeing women at an earlier age than cardiologists should be aware of cardiovascular disease. PMID:23727147

Schenck-Gustafsson, Karin; Rees, Margaret

2013-08-01

212

Hypoxia-inducible regulation of placental BOK expression.  

PubMed

BOK (BCL-2-related ovarian killer) is a member of the pro-apoptotic BCL-2 family that is highly expressed in the human placenta. BOK excess causes increased trophoblast autophagy and apoptosis in pre-eclampsia, a pathological condition of hypoxia and oxidative stress. In the present study, we identified an HRE (hypoxia-response element) at the junction of exon-1 and intron-1 (+229 to +279) in the human BOK gene, as well as an antisense transcript driven by a promoter located in intron-2. The isolated BOK-HRE bound hypoxia-inducible HIF (hypoxia-inducible factor) proteins in vitro as well as in trophoblastic JEG3 cells and was functional in its natural position as well as in front of a heterologous promoter. Being a reverted repeat, the BOK-HRE functioned in both orientations. This directionless feature of the BOK-HRE facilitates hypoxia regulation via HIF of both BOK and its antisense transcript as demonstrated by RNAi knockdown of the HIF system. Although the antisense transcript was expressed in several human carcinoma cell lines, including choriocarcinoma-derived JEG3 cells, no antisense-regulated mechanism for BOK expression was noted. Taken together, these findings indicate that hypoxia-induced expression of BOK in placental cells is regulated via HIF and is not affected by its antisense transcript. PMID:24806027

Luo, Daochun; Caniggia, Isabella; Post, Martin

2014-08-01

213

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

PubMed

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

Yang, Zhenyu; Huffman, Sandra L

2011-10-01

214

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

PubMed

TNF-? (tumor necrosis factor-?) is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-? is elevated (> 1 pg/mL) in several pathologies, including rheumatoid arthritis, atherosclerosis, cancer, pre-eclampsia; in obese individuals; and in trauma patients. To test whether circulating TNF-? could induce similar alterations in different districts along the vascular system, three endothelial cell lines, namely HUVEC, HPMEC, and HCAEC, were characterized in terms of 1) mechanical properties, employing atomic force microscopy; 2) cytoskeletal organization, through fluorescence microscopy; and 3) membrane overexpression of adhesion molecules, employing ELISA and immunostaining. Upon stimulation with TNF-? (10 ng/mL for 20 h), for all three endothelial cells, the mechanical stiffness increased by about 50% with a mean apparent elastic modulus of E ~5 ± 0.5 kPa (~3.3 ± 0.35 kPa for the control cells); the density of F-actin filaments increased in the apical and median planes; and the ICAM-1 receptors were overexpressed compared with controls. Collectively, these results demonstrate that sufficiently high levels of circulating TNF-? have similar effects on different endothelial districts, and provide additional information for unraveling the possible correlations between circulating pro-inflammatory cytokines and systemic vascular dysfunction. PMID:21499414

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

2011-01-01

215

"Near miss" obstetric morbidity in an inner city hospital in Saudi Arabia.  

PubMed

A defined "near-miss" end-point, e.g. peripartum hysterectomy, is a more useful measure of obstetric care in a modern inner-city hospital than maternal mortality. Thus, indication(s), type of operation, risk factors and surgical morbidity of all cases of peripartum hysterectomy conducted over a period of 85 months at King Abdul Aziz Hospital, Jeddah were reviewed. The incidence of hysterectomy was 1.22 per 1000 deliveries. Atonic postpartum haemorrhage was the most common reason (43.5%), followed by ruptured uterus (30.4%) and placenta accreta (26.1%). Of the atonic group, five patients were primigravidae, three of whom had severe pre-eclampsia. Abnormally prolonged labour was noted in this group. In the uterine rupture group, only two patients had had previous caesarean sections. In the placenta accreta group, three patients had placenta praevia, two of whom had scars from previous caesarean sections. One maternal death was attributed to amniotic fluid embolism. PMID:11338695

Nasrat, H A; Youssef, M H; Marzoogi, A; Talab, F

1999-07-01

216

'Near-miss' obstetric enquiry.  

PubMed

A near-miss maternal mortality enquiry was performed at University College Obstetric Hospital, London, by reviewing retrospectively all 30 obstetric admissions to the intensive care unit (ITU) over a two-year period. The obstetric admission rate to ITU was 0.5 (95% CI 0.32-0.67%), or one per 200 women delivered. Haemorrhage and severe pre-eclampsia were the two commonest causes of admission. Sub-standard care was identified in 52% of cases. Blood loss was often massive ( 2000 ml), underestimated and required large volume transfusions (mean transfusion 6.4 units, range 1-24). Although there are problems with definitions, ascertainment and validity, 'near-miss' review is feasible. It is worthwhile for every hospital to carry out its own 'near-miss' enquiry using appropriate local criteria to identify potential areas for improvements. 'Near-misses' are more prevalent than deaths and are dominated by conditions that are amenable to treatment. They may be even more sensitive to improvement or deterioration in obstetric services than mortality data. PMID:15511759

Bewley, S; Creighton, S B

1997-01-01

217

Urinary tract infection (UTI) in newborns: risk factors, identification and prevention of consequences.  

PubMed

The aim of the study is identification of urinary tract infections (UTI) and urinary tract anomalies (UTA) already in the perinatal period. The authors attempted to prevent serious consequences of the above conditions in the examined children. Family history data, certain conditions in pregnancy and appertaining symptoms in children were elaborated to specify selective distinctive criteria for children at risk. Newborns (1200) were selected for potential existence of a UTI. All the examined newborns underwent a urinalysis. Those with significant bacteriuria were taken urine specimens, C-reactive protein (RVP), Complete Blood Count (CBC) and bilirubin. The newborns with a UTI and a suspected UTA were sent to ultrasound examination, direct radio nuclide cystography and Tc99m MAG3 dynamic scanning. The frequency of a UTI in the perinatal period amounted to 4.5%. A UTA was found in 29.6% of the examinees. The infection was more likely to appear among newborns with a UTA in their families, a UTI, pre-eclampsia and a febrile infection in mother, intrauterine growth retardation, premature rupture of membranes (RVP), umbilical cord strangulation, jaundice, cyanosis, breathing difficulties, seizures and asphyxia. PMID:24308231

Milas, Vesna; Puselji?, Silvija; Stimac, Maja; Dobri?, Hana; Luki?, Gordana

2013-09-01

218

New horizons in platelets flow cytometry.  

PubMed

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

2013-03-01

219

The proprotein convertase furin is required for trophoblast syncytialization  

PubMed Central

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

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

2013-01-01

220

B-1a B cells regulate T cell differentiation associated with pregnancy disturbances.  

PubMed

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, Damián Oscar; Soldati, Rocío; Rolle, Luise; Zygmunt, Marek; Zenclussen, Ana Claudia; Jensen, Federico

2014-01-01

221

Renal function in normal and disordered pregnancy  

PubMed Central

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

Hussein, Wael; Lafayette, Richard A.

2014-01-01

222

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

PubMed

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

Liu, X; Gu, W; Li, X

2013-11-01

223

Comparison of maternal and newborn outcomes of Tibetan and Han Chinese delivering in Lhasa, Tibet  

PubMed Central

Aim To compare maternal and neonatal outcomes of Tibetan and Han Chinese women delivering vaginally at high altitude (3650 meters) in Lhasa, Tibet Autonomous Region, People’s Republic of China. Method Comparative analysis of data from a prospective observational study of Tibetan (n = 938) and Han Chinese (n = 146) women delivering at three hospitals between January 2004 and May 2005. Results Han Chinese women had higher rates of pre-eclampsia/gestational hypertension than Tibetan women, (10.3% vs 5.9%, P = 0.04). There was no difference in rates of postpartum hemorrhage between Tibetan and Han women (12.8% vs 17.1%, P = 0.15). Han newborns weighed significantly less than Tibetan newborns (P < 0.01), and were twice as likely to be small for gestational age, (24.5% vs 11.6%, P < 0.01). Tibetan newborns were less likely to have poor neonatal outcomes than Han newborns (P < 0.01). Conclusion In high altitude deliveries in Tibet, adverse outcomes were significantly more common among Han Chinese.

Miller, Suellen; Tudor, Carrie; Thorsten, Vanessa; Nyima; Sonam; Droyoung; Wright, Linda; Varner, Michael

2009-01-01

224

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

PubMed

The aim of this study was to evaluate whether a new low-cost strategy for the introduction of magnesium sulphate (MgSO4) for preeclampsia and eclampsia in low-resource areas will result in improved maternal and perinatal outcomes. Doctors and midwives from ten hospitals in Kano, Nigeria, were trained on the use of MgSO4. The trained health workers later conducted step-down training at their health facilities. MgSO4, treatment protocol, patella hammer, and calcium gluconate were then supplied to the hospitals. Data was collected through structured data forms. The data was analyzed using SPSS software. From February 2008 to January 2009, 1,045 patients with severe preeclampsia and eclampsia were treated. The case fatality rate for severe preeclampsia and eclampsia fell from 20.9 % (95 % CI 18.7-23.2) to 2.3 % (95 % CI 1.5-3.5). The perinatal mortality rate was 12.3 % as compared to 35.3 % in a center using diazepam. Introduction of MgSO4 in low-resource settings led to improved maternal and fetal outcomes in patients presenting with severe pre-eclampsia and eclampsia. Training of health workers on updated evidence-based interventions and providing an enabling environment for their practice are important components to the attainment of the Millennium Development Goals (MDG) in developing countries. PMID:22956402

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

2013-09-01

225

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

PubMed Central

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

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

2013-01-01

226

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

PubMed Central

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

2013-01-01

227

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.

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

2009-01-01

228

The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes.  

PubMed

Factor V Leiden (FVL) and ABO(H) blood groups are the common influences on haemostasis and retrospective studies have linked FVL with pregnancy complications. However, only one sizeable prospective examination has taken place. As a result, neither the impact of FVL in unselected subjects, any interaction with ABO(H) in pregnancy, nor the utility of screening for FVL is defined. A prospective study of 4250 unselected pregnancies was carried out. A venous thromboembolism (VTE) rate of 1.23/1000 was observed, but no significant association between FVL and pre-eclampsia, intra-uterine growth restriction or pregnancy loss was seen. No influence of FVL and/or ABO(H) on ante-natal bleeding or intra-partum or postpartum haemorrhage was observed. However, FVL was associated with birth-weights >90th centile [odds ratio (OR) 1.81; 95% confidence interval (CI(95)) 1.04-3.31] and neonatal death (OR 14.79; CI(95) 2.71-80.74). No association with ABO(H) alone, or any interaction between ABO(H) and FVL was observed. We neither confirmed the protective effect of FVL on pregnancy-related blood loss reported in previous smaller studies, nor did we find the increased risk of some vascular complications reported in retrospective studies. PMID:18028481

Clark, Peter; Walker, Isobel D; Govan, Lindsay; Wu, Olivia; Greer, Ian A

2008-01-01

229

Thyroid autoantibodies and associated complications during pregnancy.  

PubMed

This study was undertaken to determine the presence of thyroid autoantibodies and associated pregnancy complications from 49 pregnant women with thyroid disease. There were 31 (63%) women with Graves' disease (GD) and 18 (37%) with primary hypothyroidism (PHT). A total of 26 (53.1%) women, 19 (61%) with GD and seven (39%) with PHT, had positive antibodies. Six had thyroid peroxidase antibodies (TPO), one with thyroglobulin antibody (TG) and eight had TSH receptor antibodies (TR). Two had a mixture of antibodies involving TG/TPO (one GD vs one PHT), four with TG/TPO/TR (all had GD) and five with TPO/TR (four with GD vs one with PHT). There were associations in women with positive thyroid antibodies and pre-eclampsia (15.4%), abruptio placenta (4%), caesarean deliveries (31%), postpartum thyroiditis (19.2%) and abnormal neonatal thyroid function (15.4%). Women with positive thyroid antibodies in pregnancy need close care during and after pregnancy, as they can develop complications affecting both mother and fetus. PMID:20925608

Nor Azlin, M I; Bakin, Y D; Mustafa, N; Wahab, N A; Johari, M J M; Kamarudin, N A; Jamil, M A

2010-01-01

230

Recurrent pregnancy loss in patients with thyroid dysfunction  

PubMed Central

Purpose of the Review: Thyroid disturbances are common in women during their reproductive years. Thyroid dysfunction interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy outcome, thus becoming relevant in the algorithm of reproductive dysfunction. This review highlights the gap in knowledge regarding the contribution of thyroid dysfunction in reproduction. Literature Reviewed: Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. It is estimated that approximately 8-12% of all pregnancy losses are the result of endocrine factors. Autoimmune thyroid disease is present in around 4% of young females and up to 15% are at risk because they are thyroid antibody-positive. There is a strong relationship between thyroid immunity on one hand and infertility, miscarriage, and thyroid disturbances in pregnancy and postpartum, on the other hand. Even minimal hypothyroidism can increase rates of miscarriage and fetal death and may also have adverse effects on later cognitive development of the offspring. Hyperthyroidism during pregnancy may also have adverse consequences. Summary: Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality, and miscarriage. Universal screening for thyroid hormone abnormalities is not routinely recommended at present, but thyroid function must be examined in female with fetal loss or menstrual disturbances. Practitioners providing health care for women should be alert to thyroid disorders as an underlying etiology for recurrent pregnancy loss.

Sarkar, Debanjali

2012-01-01

231

Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester  

PubMed Central

Objective To analyse data from a randomised, controlled study of prandial insulin aspart versus human insulin, both with NPH insulin, in pregnant women with type 1 diabetes for potential factors predicting poor pregnancy outcomes. Research design/method Post hoc analysis including 91 subjects randomised prior to pregnancy with known outcome in early pregnancy and 259 subjects randomised prior to pregnancy/during pregnancy of <10 weeks’ gestation with known late-pregnancy outcomes. Poor early-pregnancy outcomes included fetal loss <22 gestational weeks and/or congenital malformation (n?=?18). Poor late-pregnancy outcomes included: composite endpoint including pre-eclampsia, preterm delivery and perinatal death (n?=?78); preterm delivery (n?=?63); and excessive fetal growth (n?=?88). Results 18 patients experienced a malformed/lost fetus in early pregnancy – none preceded by severe hypoglycaemia. Albuminuria in early pregnancy was a significant predictor of poor late-pregnancy outcome (composite endpoint; p?=?0.012). In the third trimester, elevated HbA1c,???1 plasma glucose (PG) measurement >11?mmol/L (198?mg/dL) and %PG values outside 3.9–7.0?mmol/L (70–126?mg/dL) were significant predictors of poor late-pregnancy outcomes (all p?

Mersebach, Henriette; Rastam, Jacob; Kaaja, Risto; Hod, Moshe; McCance, David R.; Mathiesen, Elisabeth R.

2014-01-01

232

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

PubMed Central

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

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

2007-01-01

233

[Clinical usefulness of inhibin assays in gynecology and obstetrics].  

PubMed

The main source of inhibin B in women is the growing follicle granulosa cells, while inhibin A is mainly produced by the corpus luteum and the placenta. In infertile women submitted to therapies of assisted reproduction, inhibin B has shown to be useful to predict a poor ovulatory response, though it has not yet overcome the performance of other markers. In the pre-natal screening of the Down syndrome, inhibin A has been repeatedly confirmed as useful in the second trimester and has also started to be considered in the first trimester test battery. Besides the two applications above, the dosage of total inhibin may contribute to the identification of cases of autoimmune ovarian insufficiency. Total inhibin may also be an auxiliary marker in the diagnosis of ovarian epithelial tumors, while the amount of inhibin B helps in the diagnosis of granulosa cells tumors. The use of inhibin A may be extended to the evaluation of pregnant women with risk of abortion, with a history of repeated abortion, with increased risk of pre-eclampsia, or even in the first days of follow-up of hydatiform mole post-emptying. All those applications are still under study, but with a real possibility of helping to extend the diagnostic spectrum of inhibin dosage in gynecology and obstetrics. PMID:20101378

Dos Reis, Fernando Marcos; De Rezende, Carolina Passos

2009-12-01

234

Obstetric nephrology: pregnancy in women with diabetic nephropathy--the role of antihypertensive treatment.  

PubMed

This review highlights factors of importance for the clinical care of pregnant women with pregestational diabetes and microalbuminuria or diabetic nephropathy with particular focus on the role of intensive antihypertensive treatment during pregnancy. Most information in the literature comes from women with type 1 diabetes and diabetic nephropathy, but this is probably also valid for women with type 2 diabetes. Careful counseling of women with diabetic nephropathy before pregnancy with estimation of the risk for the mother and fetus is important. Pregnancy does not result in worsening of kidney function in women with diabetic nephropathy and normal serum creatinine, but pregnancy complications such as pre-eclampsia and preterm delivery are common. Intensive metabolic control before and during pregnancy, low-dose aspirin from 12 gestational weeks onward, and intensive antihypertensive treatment are important. Methyldopa, labetalol, and nifedipine are regarded safe in pregnancy, whereas angiotensin converting enzyme inhibitors, AngII antagonists, or statins should be paused before pregnancy. Case series and pathophysiological studies support the use of a stringent goal for BP and albumin excretion in pregnant women with diabetic nephropathy. Screening for diabetic retinopathy before and during pregnancy is mandatory and laser treatment should be performed if indicated. Pregnancy outcome in women with diabetic nephropathy has improved considerably with a take-home-baby rate of approximately 95%. Further research on the benefits and risks of intensive antihypertensive treatment in this population is needed. PMID:22917698

Mathiesen, Elisabeth R; Ringholm, Lene; Feldt-Rasmussen, Bo; Clausen, Peter; Damm, Peter

2012-12-01

235

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

236

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

PubMed

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

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

2012-08-01

237

Concise guidance: Pregnancy - occupational aspects of management  

PubMed Central

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

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

2013-01-01

238

Intravenous Infusion of Magnesium Sulphate During Subarachnoid Anaesthesia in Hip Surgery and Its Effect on Postoperative Analgesia: Our Experience  

PubMed Central

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

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

2013-01-01

239

Meta-analysis of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications.  

PubMed

A 35-year-old woman with recurrent severe placenta-mediated pregnancy complications in her 2 pregnancies asks: Will low-molecular-weight heparin help prevent recurrent placenta-mediated pregnancy complications in my next pregnancy? We performed a meta-analysis of randomized controlled trials (RCTs) comparing low-molecular-weight heparin (LMWH) vs no LMWH for the prevention of recurrent placenta-mediated pregnancy complications. We identified six RCTs that included a total of 848 pregnant women with prior placenta-mediated pregnancy complications. The primary outcome was a composite of pre-eclampsia (PE), birth of a small-for-gestational-age (SGA) newborn (<10th percentile), placental abruption, or pregnancy loss >20 weeks. Overall, 67 (18.7%) of 358 of women being given prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction, 0.52; 95% CI, 0.32 to 0.86; P = .01; I(2), 69%, indicating moderate heterogeneity). We identified similar relative risk reductions with LMWH for individual outcomes, including any PE, severe PE, SGA <10th percentile, SGA <5th percentile, preterm delivery <37 weeks, and preterm delivery <34 weeks with minimal heterogeneity. LMWH may be a promising therapy for recurrent, especially severe, placenta-mediated pregnancy complications, but further research is required. PMID:24357725

Rodger, Marc A; Carrier, Marc; Le Gal, Grégoire; Martinelli, Ida; Perna, Annalisa; Rey, Evelyne; de Vries, J I P; Gris, Jean-Christophe

2014-02-01

240

Cardiovascular risk in women: focus on hypertension.  

PubMed

Hypertension is a major concern in women, contributing to the risk for morbidity and mortality and the development of cardiovascular disease (CVD), heart attack, and stroke. A woman's risk for the development of hypertension increases with age. Although it also affects younger women, hypertension is prevalent in approximately 60% of women >65 years of age. In addition to age, there are specific risk factors and lifestyle contributors for the development of hypertension in women, including obesity, ethnicity, diabetes, and chronic kidney disease. Risk reduction strategies need to be used to help reduce hypertension; maintaining a healthy body weight through diet and exercise, reduced sodium intake, and lower alcohol intake are a few of the approaches for hypertension risk reduction in women. There are several proposed mechanisms for the development of hypertension that are unique to women and pertain to the aging-related elevated risk for hypertension resulting from falling estrogen levels during menopause. Oral contraceptives, pre-eclampsia and polycystic ovary syndrome are special considerations concerning the development and progression of hypertension in women. There are significant awareness issues and care gaps in the treatment of hypertension in women. Therefore, these problems must be faced and efforts need to be taken to resolve the issues surrounding the treatment and control of hypertension in women. PMID:24786446

Abramson, Beth L; Melvin, Rochelle G

2014-05-01

241

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

242

The protean manifestations of pheochromocytoma.  

PubMed

The treacherous and deceptive nature of pheochromocytoma makes it crucial to detect and treat it promptly; otherwise it will almost certainly be fatal from cardiovascular complications or metastases. Hypertension occurring in patients with pheochromocytomas is sustained in about 50% and paroxysmal in the remainder; however, many patients remain normotensive. Hypertension attacks may be precipitated by physical activity, postural changes, anxiety, certain foods or wine, some drugs, operative procedures, etc. Cardinal manifestations are paroxysmal hypertension, headache, palpitations +/- tachycardia, inappropriate sweating; anxiety, tremulousness, pallor (rarely flushing), chest and abdominal pains; nausea and vomiting often occur. Hypercatecholaminemia manifestations are more common and pronounced when paroxysmal hypertension occurs, but persons with familial pheochromocytoma may be asymptomatic. Protean manifestations of pheochromocytoma may simulate many conditions, some of which may have elevated plasma and urine catecholamines and their metabolites. Baro-reflex failure, postural tachycardia syndrome, sleep apnea, carcinoid, renal failure, and pseudopheochromocytoma may be diagnostic challenges. The history, physical examination, biochemical testing (after eliminating interfering drugs, when possible) for plasma and urinary metanephrines can usually establish or exclude presence of pheochromocytomas. Occasionally a clonidine suppression test is needed to differentiate neurogenic from pheochromocytic hypertension. Manifestations suggesting hypercatecholaminemia without hypertension are highly atypical of pheochromocytoma. Pheochromocytoma may present as panic attacks, pre-eclampsia, cardiomyopathy, infection with fever and leucocytosis, diabetes, migraine, shock, Cushing's syndrome, multiple organ failure with lactic acidosis, neurological manifestations, transitory electrocardiogram abnormalities, constipation, intestinal obstruction, visual impairment, convulsions, etc. The key to diagnosis is always to think of pheochromocytoma in the differential diagnosis of hypertension. PMID:19242899

Manger, W M

2009-09-01

243

Clinical implications of the ovarian/endometrial renin-angiotensin-aldosterone system.  

PubMed

New organ-specific functions of angiotensin II have recently been described: the importance of its role in the regulation of secretory epithelial function in many tissues including components of the reproductive tract has been documented. The source of angiotensin II in these tissues is the reproductive tract itself, and there is considerable evidence to suggest a distinct renin-angiotensin-aldosterone system in the ovary and uterus. Two main subtypes of angiotensin II receptors are recognized as angiotensin-receptor I and II, according to their sensitivity to the angiotensin II antagonists. However, the presence of angiotensin II receptors in the male and female reproductive tract suggests a multiplicity of roles that are unrelated to their primary functions or to each other. The renin-angiotensin-aldosterone system is a major determinant of sodium balance in pregnancy. More recently RT-PCR methods have revealed angiotensinogen transcription in the smooth muscle of spiral anteries of the decidua; a specific allele of this gene may be associated with hypertension in pregnancy as well as in pre-eclampsia. We investigated the evolution of plasma renin activity and aldosterone levels during normal and hypertensive pregnancy. Both were found to increase progressively during all three trimesters of normotensive pregnancy. Plasma renin activity in hypertensive women remained unchanged during all three trimesters of pregnancy. Plasma aldosterone levels in hypertensive women increased progressively during all three trimesters of pregnancy. However, plasma aldosterone levels remained significantly lower than the ones of normotensive pregnant women. These increased aldosterone levels were noticed despite unchanged renin levels. Further clinical studies investigating the renin-angiotensin-aldosterone system in the pathogenesis of pregnancy hypertension are needed. A renin-independent role of aldosterone in this pathological entity is suggested. PMID:10818397

Hassan, E; Creatsas, G; Mastorakos, G; Michalas, S

2000-01-01

244

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.

2011-01-01

245

Alterations in Polyadenylation and Its Implications for Endocrine Disease  

PubMed Central

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

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

2013-01-01

246

Neonatal Resuscitation in the Delivery Room from a Tertiary Level Hospital: Risk Factors and Outcome  

PubMed Central

Objective Timely identification and prompt resuscitation of newborns in the delivery room may cause a decline in neonatal morbidity and mortality. We try to identify risk factors in mother and fetus that result in birth of newborns needing resuscitation at birth. Methods Case notes of all deliveries and neonates born from April 2010 to March 2011 in Mahdieh Medical Center (Tehran, Iran), a Level III Neonatal Intensive Care Unit, were reviewed; relevant maternal, fetal and perinatal data was extracted and analyzed. Findings During the study period, 4692 neonates were delivered; 4522 (97.7%) did not require respiratory assistance. One-hundred seven (2.3%) newborns needed resuscitation with bag and mask ventilation in the delivery unit, of whom 77 (1.6%) babies responded to bag and mask ventilation while 30 (0.65%) neonates needed endotracheal intubation and 15 (0.3%) were given chest compressions. Epinephrine/volume expander was administered to 10 (0.2%) newborns. In 17 patients resuscitation was continued for >10 mins. There was a positive correlation between the need for resuscitation and following risk factors: low birth weight, preterm labor, chorioamnionitis, pre-eclampsia, prolonged rupture of membranes, abruptio placentae, prolonged labor, meconium staining of amniotic fluid, multiple pregnancy and fetal distress. On multiple regression; low birth weight, meconium stained liquor and chorioamnionitis revealed as independent risk factors that made endotracheal intubation necessary. Conclusion Accurate identification of risk factors and anticipation at the birth of a high-risk neonate would result in adequate preparation and prompt resuscitation of neonates who need some level of intervention and thus, reducing neonatal morbidity and mortality.

Afjeh, Seyyed-Abolfazl; Sabzehei, Mohammad-Kazem; Esmaili, Fatemeh

2013-01-01

247

Lack of exercise is a major cause of chronic diseases.  

PubMed

Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause versus treatment; physical activity and inactivity mechanisms differ; gene-environment interaction (including aerobic training adaptations, personalized medicine, and co-twin physical activity); and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, nonalcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, pre-eclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life. PMID:23798298

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

2012-04-01

248

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.

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

2014-01-01

249

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.

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

2013-01-01

250

One-year experience in the retinopathy of prematurity: frequency and risk factors, short-term results and follow-up  

PubMed Central

AIM As a result of the increase in premature births and the advances in neonatal intensive care, retinopathy of prematurity (ROP) remains one of the most important causes of childhood blindness worldwide. The main factors in the development of ROP are gestational age, birth weight and oxygen therapy. ROP continues to gain importance due to the increasing survival rates of more immature babies. METHODS Between January 2007 and October 2008, 203 premature infants treated at the Neonatal Intensive Care Unit (NNICU) were prospectively enrolled and the relationship between known risk factors and the occurance of ROP was studied. RESULTS ROP in various stages developed in 86 cases (42.4%). Statistically significant correlations were found between the development of ROP and birth weight (P<0.0001) gestational age (P<0.0001), oxygen treatment and its duration (P<0.0001 and P=0.002), mechanical ventilation (MV) and its duration (P=0,0001 and P=0.0001), apnea (P=0.001), intraventricular hemorrhage (IVH) (P=0.046), sepsis (P=0.0001), use of erythropoietin (EPO) (P=0.003), the number of blood transfusions and frequency (P=0.0001 and P=0.0001), surfactant application (P=0.0001), the presence of patent ductus arteriosus (PDA) (P=0.001) or bronchopulmonary dysplasia (BPD) (P=0.0001). No significant correlations were found between the occurance of ROP and maternal pre-eclampsia (P=0.293), multiple pregnancy (P=0.218), or hyperbilirubinemia (P=0.494). Severity of ROP was related significantly with birth weight (P=0.0001), but no significant correlation between severity of ROP and gestational age was present. CONCLUSION Early description and reduction of the risk factors related with the occurance of ROP with the help of routine screening programs may warrant the prevention of visual loss, however early ophthalmic diagnosis and treatment are still mandatory to provide better visual rehabilitation.

Mehmet, Sariaydin; Fusun, Atlihan; Sebnem, Calkavur; Ozgur, Olukman; Gulten, Ercan; Taylan, Ozturk Arif; Fatma, Kaya Kilic; Filiz, Gokaslan; Derya, Altinyaprak; Rana, Malatyali

2011-01-01

251

New-Onset Maternal Gestational Hypertension and Risk of Retinopathy of Prematurity  

PubMed Central

Purpose. To evaluate associations between conditions of maternal new-onset gestational hypertension (mHTN) and the features imparting risk of severe retinopathy of prematurity (ROP) in preterm infants. Methods. Hospital databases and charts of all preterm inborn infants at the University of North Carolina from 1996 to 2007 were retrospectively reviewed. The presence or absence of mHTN (e.g., pre-eclampsia) and infant factors (birthweight, gestational age, erythropoietin use, and zone and stage of ROP) were analyzed for independence of association. Results. Of the 5143 infants, 323 had ROP and 76 had mothers with mHTN. Infants with ROP were more likely to have mothers with mHTN and to be younger and smaller at birth. At initial examination, more infants of mothers with mHTN had vascularization into the lower zones than did infants of mothers without mHTN (P < 0.001). However, at the examination in which the most severe ROP was present, there was no association between mHTN and ROP stage (P = 0.2342). Analysis of stage and zone together showed that infants born to mothers with mHTN were more likely to have ROP at initial examination, after adjustment for gestational age, but not for birth weight. The use of erythropoietin was not associated with ROP zone or stage, even after adjustment for maternal condition, infant birth weight, or gestational age. Conclusions. Although larger avascular areas or higher severity scores were associated with mHTN after adjustment for gestational age at initial examination, no associations were found between mHTN and ROP severity score at the examination when ROP was most severe. There were no associations between ROP severity and treatment with erythropoietin.

Zayed, Mohamed A.; Uppal, Abhineet

2010-01-01

252

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

PubMed Central

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

2013-01-01

253

Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA).  

PubMed

Elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are found in various clinical settings, including renal failure, coronary heart disease, hypertension, diabetes and pre-eclampsia. In healthy people acute infusion of ADMA promotes vascular dysfunction, and in mice chronic infusion of ADMA promotes progression of atherosclerosis. Thus, ADMA may not only be a marker but also an active player in cardiovascular disease, which makes it a potential target for therapeutic interventions. This review provides a summary and critical discussion of the presently available data concerning the effects on plasma ADMA levels of cardiovascular drugs, hypoglycemic agents, hormone replacement therapy, antioxidants, and vitamin supplementation. We assess the evidence that the beneficial effects of drug therapies on vascular function can be attributed to modification of ADMA levels. To develop more specific ADMA-lowering therapies, mechanisms leading to elevation of plasma ADMA concentrations in cardiovascular disease need to be better understood. ADMA is formed endogenously by degradation of proteins containing arginine residues that have been methylated by S-adenosylmethionine-dependent methyltransferases (PRMTs). There are two major routes of elimination: renal excretion and enzymatic degradation by the dimethylarginine dimethylaminohydrolases (DDAH-1 and -2). Oxidative stress causing upregulation of PRMT expression and/or attenuation of DDAH activity has been suggested as a mechanism and possible drug target in clinical conditions associated with elevation of ADMA. As impairment of DDAH activity or capacity is associated with substantial increases in plasma ADMA concentrations, DDAH is likely to emerge as a prime target for specific therapeutic interventions. PMID:16444869

Maas, Renke

2005-07-01

254

PMM.06?Five-year experience of maternal cardiac disease in a district general hospital 2008-2012.  

PubMed

: CMACE 2008 has shown that the overall rate of mortality from cardiac disease has tripled over the last two decades being, the largest cause of indirect maternal death; mainly due to acquired heart disease. With the current increase in older mothers, obesity, immigration and survival of babies operated on for congenital heart disease, the need to identify women at risk of heart disease and to plan their careful management is crucial. Early identification of risk factors include hypertension, pre-eclampsia, diabetes, smoking, obesity and hyperlipidaemia and a multidisciplinary management improves maternal and foetal outcomes. General principles include a MDT approach with obstetrician, physician and regular monitoring. A 5-year retrospective survey of 31 women with cardiac disease was carried out in a Joint clinic. (3200 deliveries annually). Data included demographics, type of heart disease, medical, drug history, pregnancy management, delivery place, outcomes. 19 primigravida,14 multipara; all except one were all Caucasian. The most frequent reasons for referral were congenital heart disease or surgery for it, (n = 13) valve disease (n = 9) and arrhythmias (n = 8). Also, chemotherapy induced cardiomyopathy, pericarditis and neurocardiogenic syncope. All women were booked into the clinic by 12 weeks. 24 (73%) had ECG, 25 (76%) echocardiography. 10 women had foetal echocardiogram in pregnancy (all normal). 79% women had cardiology referral, 34% anaesthetic referral. 29 (93%) pregnancies were delivered locally while 4 delivered in a tertiary unit. 19 women delivered vaginally, 7 had emergency CS while 4 planned CS. 1 had a PPH and 1 admission to NNU. Maternal cardiac disease management in a joint clinic shows good outcomes. PMID:25021003

Old, A; Arya, R; Macleod, K; Verma, A; Chattington, P

2014-06-01

255

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

PubMed Central

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

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

2013-01-01

256

Multicolor flow cytometry and nanoparticle tracking analysis of extracellular vesicles in the plasma of normal pregnant and pre-eclamptic women.  

PubMed

Excessive release of syncytiotrophoblast extracellular vesicles (STBMs) from the placenta into the maternal circulation may contribute to the systemic inflammation that is characteristic of pre-eclampsia (PE). Other intravascular cells types (platelets, leukocytes, red blood cells [RBCs], and endothelium) may also be activated and release extracellular vesicles (EVs). We developed a multicolor flow cytometry antibody panel to enumerate and phenotype STBMs in relation to other EVs in plasma from nonpregnant (NonP) and normal pregnant (NormP) women, and women with late-onset PE. Nanoparticle tracking analysis (NTA) was used to determine EV size and concentration. In vitro-derived STBMs and EVs from platelets, leukocytes, RBCs, and endothelial cells were examined to select suitable antibodies to analyze the corresponding plasma EVs. Flow cytometry analysis of plasma from NonP, NormP, and PE showed that STBMs comprised the smallest group of circulating EVs, whereas most were derived from platelets. The next most abundant group comprised unidentified orphan EVs (which did not label with any of the antibodies in the panel), followed by EVs from RBCs and leukocytes. NTA showed that the total number of EVs in plasma was significantly elevated in NormP and late-onset PE women compared to NonP controls, and that EVs were smaller in size. In general, EVs were elevated in pregnancy plasma apart from platelet EVs, which were reduced. These studies did not show any differences in EVs between NormP and PE, probably because late-onset PE was studied. PMID:24227753

Dragovic, Rebecca A; Southcombe, Jennifer H; Tannetta, Dionne S; Redman, Christopher W G; Sargent, Ian L

2013-12-01

257

Soluble VEGFR-1 in pathophysiology of pregnancies complicated by hypertensive disorders: the Indian scenario.  

PubMed

An imbalance between angiogenic and anti-angiogenic factors has been hypothesized to have a major role in hypertensive disorders during pregnancy, which account for significant morbidity and mortality for the mother and neonate in India. There is a paucity of information on soluble vascular endothelial growth factor receptor-1 (sVEGFR-1, anti-angiogenic factor) concentrations in different subgroups of pregnancy-induced hypertensive (PIH) disorders particularly in gestational hypertension (GH) and eclampsia during pregnancy. This cross-sectional study was conducted in order to test the above hypothesis and to get more insight into the role of sVEGFR-1 in these disorders. The concentrations of sVEGFR-1 in serum were measured from women with 22-39 weeks of gestation in the control (n=180) and gestationally matched hypertensive (n=360) pregnant mothers by ELISA. These sVEGFR-1 concentrations were found to be significantly elevated in the study groups as the severity of disease increases from GH to eclampsia (24 076 pg ml(-1); 42000 pg ml(-1), P=0.0001) as compared with controls (3360 pg ml(-1)). According to Receiver operating characteristic curve analysis, at ? 34 weeks, the concentration cutoff, sensitivity, specificity for sVEGFR-1 in differentiating GH, pre-eclampsia and eclampsia were ? 7619.2 pg ml(-1), 75%, 75%; ? 16726.6 pg ml(-1), 89.1%, 89.1%; ? 26222.8 pg ml(-1), 91.6%, 91.6%, respectively. The gradual upregulation of sVEGFR-1 concentrations in these groups may be due to its intimate involvement in the etiopathogenesis of severity of various hypertensive disorders by antagonizing effects of VEGF during the placental development. These observations indicate the clinical utility of sVEGFR-1 in differentiating PIH disorders and also will be helpful for the evaluation of increased monitoring system for successful pregnancy. PMID:22357551

Tripathi, R; Ralhan, R; Saxena, S; Salhan, S; Rath, G

2013-02-01

258

Investigation on the suitability of the International Association of Diabetes and Pregnancy Study Group diagnostic criteria for gestational diabetes mellitus in China.  

PubMed

The aim of this study was to compare pregnancy outcomes of Chinese women diagnosed with gestational hyperglycaemia by the well-established American Diabetes Association (ADA) criteria, with those women meeting the newer criteria established by International Association of Diabetes and Pregnancy Study Groups (IADPSG). The study subjects consisted of 6,201 pregnant Chinese women with a singleton pregnancy who had received prenatal care and delivered between December 2008 and December 2011. Women who were screened positive with 1 h glucose load of ? 7.8 mmol/l underwent a diagnostic 3 h oral glucose tolerance test. Gestational hyperglycaemia was diagnosed using the ADA criteria and re-diagnosed according to the IADPSG criteria. The correlation between the incidences of adverse pregnant outcomes with gestational hyperglycaemia was analysed. In total, 570 patients (9.19% of 6,201) met the ADA criteria and 676 (10.90% of 6,201) met the IADPSG criteria. The 518 patients who met both standards showed a reduced caesarean section rate, as compared with 158 patients who only met the IADPSG standard and received no intervention (71.2% vs 79.7%, p < 0.05). The IADPSG-only group also had a higher rate of macrosomia and pre-eclampsia than the control group. The IADPSG criteria identified a group of women previously classified as normal according to the ADA criteria, but revealing poor pregnancy outcomes and requiring management. Therefore, we conclude that the IADPSG criteria are more suitable for the diagnosis of gestational hyperglycaemia in China. PMID:24456434

Shang, M; Lin, L; Ma, L; Yin, L

2014-02-01

259

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.

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

2012-01-01

260

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.

Hill, Suzanne; Yang, Annie; Bero, Lisa

2012-01-01

261

The lost children.  

PubMed

Women who have lost children to perinatal complications, are subjected to pain and grief continuously; however their agony increases on remembrance days such as birthdate, or on Mother's Day. Fathers, siblings and grandparents suffer too. Common disorders of pregnancy, such as pregnancy-induced hypertension (PIH), or the more serious pre-eclampsia, HELLP syndrome, or eclampsia, can lead to devastating effects such as miscarriage, stillbirth, or neonatal death; or at the very least, a sick infant. With many of these consequences, the loss of the dreams, hopes and plans that parents have made is imminent. The investigation of the psychosocial aspects of 'high-risk' pregnancy has never been fully addressed. However, the threat of loss, or the actual experience, may provoke the onset of a potential psychological crisis during the perinatal period. Therefore, it is important that these issues be addressed by the nurse in order to aid the development of coping mechanisms to enable women and their families to deal with what may happen. This may be done by predicting the stages of the bereavement process experienced by these women and their family members, as outlined in the Kubler-Ross model of bereavement (1969), which is indicative of many types of grief reactions. Other issues including the restriction in activity, uncertainty of pregnancy outcomes, disruption in work or career activities, financial strains, and reduced labour and birthing options, become concerns for high-risk pregnant women. The way women deal with these issues and the pathways nurses can take to help these women develop effective coping strategies, will be addressed also. PMID:10514603

Smith, S

1999-03-01

262

IBC CARe Microarray Allelic Population Prevalences in an American Indian Population  

PubMed Central

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

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

2013-01-01

263

Assessment of the effects of endothelin-1 and magnesium sulphate on regional blood flows in conscious rats, by the coloured microsphere reference technique.  

PubMed

There is evidence to suggest that magnesium (Mg2+) is beneficial in the treatment of a number of conditions, including pre-eclampsia and acute myocardial infarction. The mode of action of Mg2+ in these conditions is not clear, although the vasodilator properties of Mg2+ are well documented both in vitro and in vivo. Previously, we demonstrated that i.v. infusion of magnesium sulphate (MgSO4) alone, or in the presence of vasoconstrictors, caused increases in flow and conductance in the common carotid, internal carotid and hindquarters vascular beds, in conscious rats. Therefore, the objective of the present study was to investigate the regional and subregional changes in haemodynamics in response to the vasoconstrictor peptide endothelin-1 (ET-1) and MgSO4 in more detail, using the coloured microsphere reference technique. Infusion of ET-1 and MgSO4 had similar effects on heart rate and mean arterial pressure as in our previous study. Infusion of ET-1 caused a rise in mean arterial pressure and a fall in heart rate, and infusion of MgSO4 returned mean arterial pressure to control levels with no effect on heart rate. The responses to MgSO4 in the presence of ET-1 showed considerable regional heterogeneity with blood flow increasing (e.g. skeletal muscle), decreasing (e.g. stomach) or not changing (e.g. kidney). Of particular interest was the finding that MgSO4 caused increases in flow in the cerebral and coronary vascular beds. This, and our previous studies, have shown that MgSO4 can reverse vasoconstriction in a number of vascular beds, and indicate that this compound may have therapeutic benefit in conditions associated with vasospasm. PMID:10188972

Kemp, P A; Gardiner, S M; March, J E; Rubin, P C; Bennett, T

1999-02-01

264

Obstetric complications in women with IVF conceived pregnancies and polycystic ovarian syndrome.  

PubMed

Polycystic ovarian syndrome (PCOS) is often accompanied by infertility that necessitates ovulation induction using clomiphene citrate, gonadotropins or even in vitro fertilization (IVF). These treatment methods are known to increase the incidence of multiple pregnancies as well as some negative consequences, including a rise in the risk for gestational diabetes mellitus, pre-eclampsia, etc., Furthermore, pregnancies established after IVF carry an increased risk for maternal complications. However, the increased risk of developing adverse obstetric complications has been suggested to occur independently of obesity as well as in populations without assisted reproductive techniques. Many studies have been performed to study the effect of PCOS on pregnancy and the effect of pregnancy on PCOS. The hormonal milieu that is exaggerated in PCOS women is quite well understood at the biochemical and genetic levels. The maternal and neonatal outcomes of PCOS women who have undergone in vitro fertilization-embryo transfer (IVF-ET) have not been widely studied till date. This review aims to evaluate the current evidence regarding adverse obstetric outcomes of PCOS women undergoing IVF-ET. The rationale of this review is to study whether the adverse obstetric outcomes are increased in PCOS women in general, or particularly in those PCOS women who are undergoing IVF-ET. It is also important to analyze via a literature review whether the increased adverse outcomes are due to infertility in general or PCOS per se. An attempt has been made to give evidence regarding preventive strategies for obstetric complications in PCOS women who have undergone IVF-ET. PMID:24829525

Tandulwadkar, Sunita R; Lodha, Pooja A; Mangeshikar, Nirzari T

2014-01-01

265

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

PubMed Central

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

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

2013-01-01

266

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

PubMed

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

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

2014-03-01

267

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

PubMed Central

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

King, Bridget; Bryan, Phil

2014-01-01

268

Obstetric complications in women with IVF conceived pregnancies and polycystic ovarian syndrome  

PubMed Central

Polycystic ovarian syndrome (PCOS) is often accompanied by infertility that necessitates ovulation induction using clomiphene citrate, gonadotropins or even in vitro fertilization (IVF). These treatment methods are known to increase the incidence of multiple pregnancies as well as some negative consequences, including a rise in the risk for gestational diabetes mellitus, pre-eclampsia, etc., Furthermore, pregnancies established after IVF carry an increased risk for maternal complications. However, the increased risk of developing adverse obstetric complications has been suggested to occur independently of obesity as well as in populations without assisted reproductive techniques. Many studies have been performed to study the effect of PCOS on pregnancy and the effect of pregnancy on PCOS. The hormonal milieu that is exaggerated in PCOS women is quite well understood at the biochemical and genetic levels. The maternal and neonatal outcomes of PCOS women who have undergone in vitro fertilization-embryo transfer (IVF-ET) have not been widely studied till date. This review aims to evaluate the current evidence regarding adverse obstetric outcomes of PCOS women undergoing IVF-ET. The rationale of this review is to study whether the adverse obstetric outcomes are increased in PCOS women in general, or particularly in those PCOS women who are undergoing IVF-ET. It is also important to analyze via a literature review whether the increased adverse outcomes are due to infertility in general or PCOS per se. An attempt has been made to give evidence regarding preventive strategies for obstetric complications in PCOS women who have undergone IVF-ET.

Tandulwadkar, Sunita R; Lodha, Pooja A; Mangeshikar, Nirzari T

2014-01-01

269

The role of obesity in the development of polycystic ovary syndrome.  

PubMed

Polycystic Ovary Syndrome (PCOS) is one of the common endocrine diseases that affects women in their reproductive age. PCOS has diverse clinical implications that include reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, cardiovascular diseases) and psychological features (increased anxiety, depression and worsened quality of life). The exact patho-physiology of PCOS is complex and remains largely unclear. The prevalence of PCOS is estimated at 4-18%, depending on diverse factors discussed ahead. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and body weight. During the last decades, obesity and excess weight are major chronic diseases all around the word. Obesity increases some features of PCOS such as hyperandrogenism, hirsutism, infertility and pregnancy complications. Both obesity and insulin resistance increase diabetes mellitus type 2 and cardiovascular diseases. Moreover, obesity impairs insulin resistance and exacerbates reproductive and metabolic features of PCOS. It is well known that obesity is associated with anovulation, pregnancy loss and late pregnancy complications (pre-eclampsia, gestational diabetes). Obesity in PCOS is also linked to failure or delayed response to the various treatments including clomiphene citrate, gonadotropins and laparoscopic ovarian diathermy. It has been reported that, after losing as little as 5 % of initial body weight obese women with PCOS improved spontaneous ovulation rates and spontaneous pregnancy. Therefore, the weight loss prior to conception improves live birth rate in obese women with or without PCOS. The treatment of obesity may include lifestyle therapy (diet and exercise), pharmacological treatment and bariatric surgery. In summary, weight loss is considered the first-line therapy in obese women with PCOS. In the present review, the consequence and treatment of obesity in women with PCOS are discussed. PMID:22376149

Motta, Alicia Beatriz

2012-01-01

270

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

PubMed Central

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

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

2014-01-01

271

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

PubMed Central

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

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

2012-01-01

272

Clinical review: Special populations--critical illness and pregnancy.  

PubMed

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

Neligan, Patrick J; Laffey, John G

2011-01-01

273

The consequences of obesity and excess weight gain in pregnancy.  

PubMed

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

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

2011-11-01

274

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

PubMed

Increasingly, placental DNA methylation is assessed as a factor in pregnancy-related complications, yet the transcriptional impact of such findings is not always clear. Using a proliferative in vitro placental model, the effect of DNA methylation loss on gene activation was evaluated at a number of genes selected for being differentially methylated in pre-eclampsia-associated placentae in vivo. We aimed to determine whether reduced DNA methylation at specific loci was associated with transcriptional changes at the corresponding gene, thus providing mechanistic underpinnings for previous clinical findings and to assess the degree of transcriptional response amongst our candidate genes. BeWo and JEG3 choriocarcinoma cells were exposed to 1 ?M 5-Aza-2'-deoxycytidine (5-Aza-CdR) or vehicle control for 48 h, and re-plated and cultured for a further 72 h in normal media before cells were harvested for RNA and DNA. Bisulphite pyrosequencing confirmed that DNA methylation was reduced by ?30-50% points at the selected loci studied in both cell lines. Gene activation, measured by qRT-PCR, was highly variable and transcript specific, indicating differential sensitivity to DNA methylation. Most notably, loss of DNA methylation at the leptin (LEP) promoter corresponded to a 200-fold and 40-fold increase in LEP expression in BeWo and JEG3 cells, respectively (P < 0.01). Transcripts of steroidogenic pathway enzymes CYP11A1 and HSD3B1 were up-regulated ?40-fold in response to 5-Aza-CdR exposure in BeWo cells (P < 0.01). Other transcripts, including aromatase (CYP19), HSD11B2, inhibin (INHBA) and glucocorticoid receptor (NR3C1) were more moderately, although significantly, affected by loss of associated DNA methylation. These data present a mixed effect of DNA methylation changes at selected loci supporting cautionary interpretation of DNA methylation results in the absence of functional data. PMID:24623739

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

2014-07-01

275

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

PubMed Central

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

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

2005-01-01

276

Circulating CD56+ Cells of Diabetic Women Show Deviated Homing Potential for Specific Tissues During and Following Pregnancy  

PubMed Central

Background Human uterine natural killer (uNK) cells, the dominant lymphocytes in early pregnancy decidua, are important for spiral arterial remodelling. UNK cells are thought to arise from circulating CD56bright NK cells that egress into decidualizing endometrium. Both incomplete spiral arterial modification and aberrant NK cell function have been linked with pre-eclampsia, a syndrome more prevalent in diabetic women. Previous in vitro studies showed that changes in decidual endothelium induced by type 1 diabetes reduce its interactions with circulating leukocytes. We hypothesized that diabetes additionally has direct effects on circulating CD56+ NK cells that impair their decidual homing potential. Methods Serial blood samples were collected from control, type 1 diabetic (T1D) and type 2 diabetic (T2D) pregnant women throughout and after pregnancy. In vitro adhesion under shear forces was used to assay the functional capacity of circulating leukocytes and of CD56+ cells to adhere to endothelium in cryostat sections of gestation day (gd)7 normal mouse decidua, pancreas and lymph node. Results Fewer CD56+ cells from diabetic versus control women adhered to normal decidual endothelium. The CD56+ cell/total cell adhesion ratio was also lower in diabetics. More diabetic CD56+ cells adhered to pancreatic endothelium and their proportion was greater than for controls. Neither absolute nor proportional adhesion of CD56+ cells to lymph node endothelium differed between diabetics and controls. Conclusions The CD56+ cell adhesion patterns of T1D and T2D women differ from those of non-diabetic women and support the hypothesis that diabetes impairs mechanisms that could be used by CD56+ cells for egress into decidua.

Seaward, A. V. C.; Burke, S. D.; Ramshaw, H.; Smith, G. N.; Croy, B. A.

2011-01-01

277

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.

2012-01-01

278

Maternal and neonatal risk factors for childhood type 1 diabetes: a matched case-control study  

PubMed Central

Background An interaction between genetic susceptibility and environmental factors is thought to be involved in the aetiology of type 1 diabetes. The aim of this study was to investigate maternal and neonatal risk factors for type 1 diabetes in children under 15 years old in Grampian, Scotland. Methods A matched case-control study was conducted by record linkage. Cases (n = 361) were children born in Aberdeen Maternity Hospital from 1972 to 2002, inclusive, who developed type 1 diabetes, identified from the Scottish Study Group for the Care of Diabetes in the Young Register. Controls (n = 1083) were randomly selected from the Aberdeen Maternity Neonatal Databank, matched by year of birth. Exposure data were obtained from the Aberdeen Maternity Neonatal Databank. Conditional logistic regression was used to evaluate the association between various maternal and neonatal factors and the risk of type 1 diabetes. Results There was no evidence of statistically significant associations between type 1 diabetes and maternal age, maternal body mass index, previous abortions, pre-eclampsia, amniocentesis, maternal deprivation, use of syntocinon, mode of delivery, antepartum haemorrhage, baby's sex, gestational age at birth, birth order, birth weight, jaundice, phototherapy, breast feeding, admission to neonatal unit and Apgar score (P > 0.05). A significantly decreased risk of type 1 diabetes was observed in children whose mothers smoked at the booking appointment compared to those whose mothers did not, with an adjusted OR of 0.67, 95% CI (0.46, 0.99). Conclusions This case-control study found limited evidence of a reduced risk of the development of type 1 diabetes in children whose mothers smoked, compared to children whose mothers did not. No evidence was found of a significant association between other maternal and neonatal factors and childhood type 1 diabetes.

2010-01-01

279

Heme oxygenase-1 in placental development and pathology.  

PubMed

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

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

2013-04-01

280

[Pregnancy and antiphospholipid syndrome].  

PubMed

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

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

2012-04-01

281

Predictors of ratio of placental weight to fetal weight in multiethnic community.  

PubMed Central

OBJECTIVE--To determine whether placental ratio is influenced by maternal ethnic origin, obesity, hypertension, and haematological indices of iron deficiency anaemia. DESIGN--Observational study. SETTING--District general hospital in Birmingham. SUBJECTS--692 healthy nulliparous pregnant women, of whom 367 were European, 213 Asian, 99 Afro-Caribbean, and 13 of other or undocumented ethnic origin. MAIN OUTCOME MEASURES--Placental ratio and maternal body mass index, blood pressure, and haematological indices. RESULTS--Though birth weight and placental weight were lower in Asian women than in other groups, mean placental ratio was similar in Asian (19.5% (SD 3.3%)), European (20.0% (4.0%)), and Afro-Caribbean women (20.4% (5.3%)). Gestational age at birth was the main predictor of placental ratio in the univariate analysis (r = -0.34, P < 0.001) and multivariate analysis. The only other significant predictor of placental ratio in multivariate analysis was maternal body mass index, which was positively associated with placental ratio (r = 0.1, P = 0.01). Mean (SD) placental ratio was not significantly higher in women who developed gestational hypertension (20.4% (4.5%)) and pre-eclampsia (23.3% (7.3%)) than in normal women (19.8% (3.8%)). No evidence of a relation between placental ratio and first antenatal visit haemoglobin concentration or mean cell volume was detected, and placental ratio was not associated with change in mean cell volume during pregnancy or with third trimester serum ferritin concentration. CONCLUSIONS--These data do not support the proposed association between poor maternal nutrition and increased placental ratio. The association between high placental ratio and adult hypertension may be confounded by genetic and environmental factors associated with maternal obesity (and possibly maternal hypertension).

Perry, I. J.; Beevers, D. G.; Whincup, P. H.; Bareford, D.

1995-01-01

282

Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients.  

PubMed

MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that involved in post-transcriptional gene regulation. Evidence indicates that miRNAs play essential roles in endometriosis, pre-eclampsia, infertility and other reproductive system diseases. However, whether miRNAs are involved in recurrent spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA expression profiles in six pairs of villus or decidua from RSA patients and normal pregnancy (NP) women using a human miRNA microarray. Some of the chip results were confirmed by RT-qPCR. In the villi of RSA patients, expression of hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly lower, comparing with those of NP control. As well, a total of five miRNAs (hsa-miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were upregulated in the decidua of RSA patients. The target genes of these differentially expressed miRNAs were predicted by miRWalk, and we speculate a network of miRNA regulating RSA by target genes function on adhesion, apoptosis and angiogenesis. Our study may help clarify the molecular mechanisms which are involved in the progression of RSA, and provide a reference for future research. PMID:24686457

Dong, Fulu; Zhang, Yuan; Xia, Fei; Yang, Yi; Xiong, Sidong; Jin, Liping; Zhang, Jinping

2014-07-01

283

Transcriptional regulation of human thromboxane synthase gene expression  

SciTech Connect

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

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

1994-09-01

284

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

2012-01-01

285

The underrated benefits of oral contraception: consequences of pregnancy and induced abortion in teenagers.  

PubMed

If complications occur within a pregnancy planned and brought to term, they often can be dealt with and accepted. They are even more traumatic when they occur in an unwanted pregnancy that could have been prevented through contraception. Teenagers, because of their physical and psychological immaturity and also because of their social environment, seem to suffer with undue frequency from the complications of induced abortion. Its result, for the teenager, is a handicapped future in comparison to other women. Hence, access to contraception is important for all women, and especially for teenagers, in order to avoid such prejudicial situations. It is important, then, to prescribe oral contraception for its efficacy and its short- and long-term innocuousness. Because of her immaturity, the pregnant teenager is at risk: of spontaneous abortion, pre-eclampsia, anemia, hemorrhage, and prematurity. She is also at risk because of the social difficulties she will be facing. This is particularly true in families from developing countries. From birth, the child is also at risk: of low birth weight for the term, mortality in the first year of life, and all risks linked to abandonment, or education by a third party. In a proportion of 13 to 30% in western countries and in a proportion of 3% in East Asia or in Northwest Africa (Maghreb), induced abortions are a reflection of the following: early sexual activity without contraception even if fertility is still low in very young teenagers, absence of social protection or social independence, refusal of forced marriage, and presence or absence of liberal legislation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1362187

Dreyfus, R

1992-01-01

286

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

PubMed Central

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

Yesayan, Maria N.; Kahn, Daniel A.

2014-01-01

287

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

PubMed Central

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

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

2013-01-01

288

Chemokine scavenger D6 is expressed by trophoblasts and aids the survival of mouse embryos transferred into allogeneic recipients.  

PubMed

Proinflammatory CC chemokines are thought to drive recruitment of maternal leukocytes into gestational tissues and regulate extravillous trophoblast migration. The atypical chemokine receptor D6 binds many of these chemokines and is highly expressed by the human placenta. D6 is thought to act as a chemokine scavenger because, when ectopically expressed in cell lines in vitro, it efficiently internalizes proinflammatory CC chemokines and targets them for destruction in the absence of detectable chemokine-induced signaling. Moreover, D6 suppresses inflammation in many mouse tissues, and notably, D6-deficient fetuses in D6-deficient female mice show increased susceptibility to inflammation-driven resorption. In this paper, we report strong anti-D6 immunoreactivity, with specific intracellular distribution patterns, in trophoblast-derived cells in human placenta, decidua, and gestational membranes throughout pregnancy and in trophoblast disease states of hydatidiform mole and choriocarcinoma. We show, for the first time, that endogenous D6 in a human choriocarcinoma-derived cell line can mediate progressive chemokine scavenging and that the D6 ligand CCL2 can specifically associate with human syncytiotrophoblasts in term placenta in situ. Moreover, despite strong chemokine production by gestational tissues, levels of D6-binding chemokines in maternal plasma decrease during pregnancy, even in women with pre-eclampsia, a disease associated with increased maternal inflammation. In mice, D6 is not required for syngeneic or semiallogeneic fetal survival in unchallenged mice, but interestingly, it does suppress fetal resorption after embryo transfer into fully allogeneic recipients. These data support the view that trophoblast D6 scavenges maternal chemokines at the fetomaternal interface and that, in some circumstances, this can help to ensure fetal survival. PMID:20147628

Madigan, Judith; Freeman, Dilys J; Menzies, Fiona; Forrow, Steve; Nelson, Scott M; Young, Anne; Sharkey, Andrew; Moffett, Ashley; Graham, Gerard J; Greer, Ian A; Rot, Antal; Nibbs, Robert J B

2010-03-15

289

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

PubMed

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

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

2004-01-01

290

[Acute fatty liver of pregnancy. Report of a case and review of the literature].  

PubMed

Acute Fatty Liver of Pregnancy. The acute fatty liver of pregnancy (AFLP) is an uncommon entity, potentially fatal, which affects women during the last quarter of pregnancy. It is characterized by a prodromic period of symptoms followed by jaundice, hepatic failure, clotting disorders and fatty infiltration of the liver, evident through hepatic biopsy. The incidence ranks from 1 to 20 thousand births, and it is more frequent among women with multiple pregnancies. We report the case of a 29-year-old patient, with multiple pregnancy 33 to 34 weeks of gestation, blood pressure values of 140/90 mmHg, 160,000/dL platelets, PT 25.6 seconds, TPT 64.7 seconds, blood glucose 52 mL/dL, creatinine 2.1 mg/dL, uric acid 11.9 mg/dL, lactic dihydrogenase 1063 U/l, GPT 220 U/l, AF 1172 U/l, total bilirubin 8.4 mg/dL, proteinuria 30 mg/dL. A cesarean section was practiced after correcting the coagulation disorders. The first twin was a male with birth weight of 2,070 g, APGAR 8-9; the second twin was a female fetal death weighting 2,050 g. Hepatic biopsy confirmed the diagnosis. The cause of AFLP is unknown. The frequency among multiple pregnancies is higher. Almost half of the cases have hypertension and proteinuria. There are also high levels of both transaminases, phosphatase and bilirubins and hypoglycemia. The prothrombin time is enlarged. The differential diagnostic between pre-eclampsia and AFLP is not crucial since the obstetric management is the same. The main treatment is promptly deliverance and general measures. The obstetrician must be aware of this hepatic disease. PMID:11195962

Ibargüengoitia Ochoa, F; Plascencia, J L; Flores Villalon, A; Zambrana Castañeda, M

2000-12-01

291

Maternal and child health. Maternal mortality in the Americas.  

PubMed

Maternal health in Latin America and the Caribbean continues to be an important issue, which is significantly affected by access to appropriate health technology and quality care, which in turn may be dependent upon economic conditions. Although contraceptive knowledge was high, only 53% of couples used some method of contraception. About 32% and 37% of maternal mortality in Mexico and Colombia could have been averted if contraception had been used. One study of 240 maternal deaths in Mexico indicated that 85% were potentially preventable, and 70% could have been potentially avoided with better medical and institutional care. The table gave the number and rate of maternal mortality and risk by country. In 23 countries, maternal mortality was one of the ten leading causes of death among women. The five prominent causes tended to be abortion, hemorrhage, toxemia, complications of the puerperium, and indirect causes among women aged 15-49 years. Countries can be grouped by level of maternal mortality: 227/100,000 live births, 133/100,000, and 50/100,000. About 280,000 to 420,000 episodes of severe intercurrent obstetric problems potentially occurred annually among the 12 million women of reproductive age in the region. In the United States about 1 out of every 5 pregnancies involved pregnancy related hospitalization in 1987. In Mexico in 1989, of the 740,000 obstetric related discharges for obstetric reasons, 80.5% were related to delivery and 19.5%, to morbidity during pregnancy. During the prenatal period, the five leading causes of morbidity have been identified as premature rupture of membranes, urinary tract infection, potential premature delivery, pre-eclampsia, and pregnancy induced hypertension. Latin American is also a region with increasing numbers of cesarean section deliveries. Maternal deaths in Latin America and the Caribbean would be reduced 47 times and 85% of deaths could be avoided if the health systems paralleled those in Canada. PMID:8240944

1993-10-15

292

Normal human pregnancy results in maternal immune activation in the periphery and at the uteroplacental interface.  

PubMed

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

Loewendorf, Andrea I; Nguyen, Tina A; Yesayan, Maria N; Kahn, Daniel A

2014-01-01

293

Urinary lysosomal enzyme excretion in pregnant women with hypertensive disorders.  

PubMed

Background: The authors assessed proximal renal tubular dysfunction and/or damage in pregnant women with various types of hypertension by measuring the three urinary lysosomal enzyme levels: N-acetyl-?-d-glucosaminidase (NAG), arylsulfatase A and ?-glucuronidase. Methods: The study consisted of 120 pregnant women divided into four groups: 41 women in 20th week of gestation or more, with pregnancy-induced hypertension (PIH group), 28 pregnant women after 20 weeks of pregnancy with pre-eclampsia (PE group), 21 pregnant women with chronic hypertension, identified before 20th week of pregnancy (CH group) and 30 healthy, pregnant women (healthy controls (HC) group). Results: Statistical analysis showed significantly higher levels of all the three of lysosomal enzymes in the urine of patients with PE compared with the healthy pregnant women, pregnant women with PIH and the ones with chronic hypertension. Additionally, significantly higher values of NAG were found in the group of pregnant women with PIH compared with healthy pregnancies. No correlation was found between the concentration of enzymes in urine and values of blood pressure in any of the analyzed groups of pregnant women. Conclusions: The authors conclude that higher values of all the studied enzymes in PE group, in the comparison with the other groups, indicate proximal tubular damage at the cellular level. The lack of correlation between the concentration of lysosomal enzymes and blood pressure suggests that the damage to these parts of kidney is complex. In addition, mechanisms other than hypertension realizing intracellular enzymes may be involved in this process. PMID:24724946

Torbé, Andrzej; Ch?apowska, Ewelina; Szyma?ska-Pasternak, Jolanta; Sulecka, Aneta; Bober, Joanna; Kwiatkowska, Ewa; Kwiatkowski, Sebastian; Rzepka, Rafa?; Konstanty-Kurkiewicz, Wioletta; Torbé, Bogdan

2014-08-01

294

Comprehensive Analysis of Genes Expressed by Rare Microchimeric Fetal Cells in the Maternal Mouse Lung1  

PubMed Central

ABSTRACT During pregnancy, cells from each fetus travel into the maternal circulation and organs, resulting in the development of microchimerism. Identification of the cell types in this microchimeric population would permit better understanding of possible mechanisms by which they affect maternal health. However, comprehensive analysis of fetal cells has been hampered by their rarity. In this study, we sought to overcome this obstacle by combining flow cytometry with multidimensional gene expression microarray analysis of fetal cells isolated from the murine maternal lung during late pregnancy. Fetal cells were collected from the lungs of pregnant female mice. cDNA was amplified and hybridized to gene expression microarrays. The resulting fetal cell core transcriptome was interrogated using multiple methods including Ingenuity Pathway Analysis, the BioGPS gene expression database, principal component analysis, the Eurexpress gene expression atlas, and primary literature. Here we report that small numbers of fetal cells can be flow sorted from the maternal lung, facilitating discovery-driven gene expression analysis. We additionally show that gene expression data can provide functional information about fetal cells. Our results suggest that fetal cells in the murine maternal lung are a mixed population, consisting of trophoblasts, mesenchymal stem cells, and cells of the immune system. Detection of trophoblasts and immune cells in the maternal lung may facilitate future mechanistic studies related to the development of immune tolerance and pregnancy-related complications, such as pre-eclampsia. Furthermore, the presence and persistence of mesenchymal stem cells in maternal organs may have implications for long-term postpartum maternal health.

Pritchard, Stephanie; Wick, Heather C.; Slonim, Donna K.; Johnson, Kirby L.; Bianchi, Diana W.

2012-01-01

295

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

2014-01-01

296

A systems biology perspective on sVEGFR1: its biological function, pathogenic role & therapeutic use  

PubMed Central

Angiogenesis is the growth of new capillaries from pre-existent microvasculature. A wide range of pathological conditions, from atherosclerosis to cancer, can be attributed to either excessive or deficient angiogenesis. Central to the physiological regulation of angiogenesis is the vascular endothelial growth factor (VEGF) system – its ligands and receptors (VEGFRs) are thus prime molecular targets of pro-angiogenic and anti-angiogenic therapies. Of growing interest as a prognostic marker and therapeutic target in angiogenesis-dependent diseases is soluble VEGF receptor-1 (sVEGFR1, also known as sFlt-1) – a truncated version of the cell membrane-spanning VEGFR1. For instance, it is known that sVEGFR1 is involved in the endothelial dysfunction characterizing the pregnancy disorder of pre-eclampsia, and sVEGFR1’s therapeutic potential as an anti-angiogenic agent is being evaluated in pre-clinical models of cancer. This mini-review begins with an examination of the protein domain structure and biomolecular interactions of sVEGFR1 in relation to the full-length VEGFR1. A synopsis of known and inferred physiological and pathological roles of sVEGFR1 is then given, with emphasis on the utility of computational systems biology models in deciphering the molecular mechanisms by which sVEGFR1’s purported biological functions occur. Finally, we present the need for a systems biology perspective in interpreting circulating VEGF and sVEGFR1 concentrations as surrogate markers of angiogenic status in angiogenesis-dependent diseases.

Wu, Florence T.H.; Stefanini, Marianne O.; Mac Gabhann, Feilim; Kontos, Christopher D.; Annex, Brian H.; Popel, Aleksander S.

2011-01-01

297

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

PubMed

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

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

2011-01-01

298

Fatal atypical reversible posterior leukoencephalopathy syndrome: a case report  

PubMed Central

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

2013-01-01

299

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

PubMed

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

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

1995-12-01

300

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

PubMed Central

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

2012-01-01

301

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

PubMed Central

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

2012-01-01

302

The diagnostic and prognostic performance of a selective screening strategy for gestational diabetes mellitus according to ethnicity in europe.  

PubMed

Context: The performance of standard selective screening strategies for gestational diabetes mellitus (GDM) may vary according to ethnicity. Objective: We aimed to evaluate the diagnostic and prognostic performance of a selective screening tool to determine whether it accurately predicts GDM and events in women of different ethnicities. The tool selectively screens based on patients having one or more of the following risk factors (RFs): body mass index ?25 kg/m(2), age ?35 years, family history of diabetes, and personal history of GDM or macrosomia. Design and Setting: We conducted an observational prospective study at a university hospital. Participants: We included 17 344 women of European (30.9%), North African (29.6%), Sub-Saharan African (22.2%), Caribbean (8.7%), Indian-Pakistani-Sri Lankan (5.5%), and Asian (3.3%) ethnicities who were without pregravid diabetes and had singleton deliveries (2002-2010). Main Outcome Measures: We universally screened GDM and GDM-related events (pre-eclampsia, birth weight ?4000 g, or dystocia). Results: Independent of confounding factors, North African (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.21-1.52; P < .001) and Indian-Pakistani-Sri Lankan (OR, 2.52; 95% CI, 2.13-3.00; P < .001) women had more GDM than Europeans, whereas Sub-Saharan African women had less (OR, 0.82; 95% CI, 0.71-0.94; P < .01). Having one or more RFs was associated with GDM among Europeans (OR, 1.45; 95% CI, 1.22-1.76), North African (OR, 1.33; 95% CI, 1.13-1.55), Sub-Saharan African (OR, 1.48; 95% CI, 1.20-1.83), and Caribbean (OR, 1.55; 95% CI, 1.12-2.14) women. Having one or more RFs was also associated with GDM-related events only in European (P < .01) and North African (P < .05) women, with the following incidences in Europeans: no GDM/no RF, 6.9%; no GDM/RF, 9.0%; GDM/no RF, 14.7%; and GDM/RF, 12.6%. Conclusion: Standard selective screening criteria were not predictive of GDM in women from India-Pakistan-Sri Lanka and Asia and were associated with GDM-related events only in European and North African women. However, the women with GDM, who were routinely treated, had a poor prognosis, even for those free of RFs. These results support universal screening, irrespective of ethnicity. PMID:24423342

Cosson, Emmanuel; Cussac-Pillegand, Camille; Benbara, Amélie; Pharisien, Isabelle; Jaber, Yahya; Banu, Isabela; Nguyen, Minh Tuan; Valensi, Paul; Carbillon, Lionel

2014-03-01

303

Fetal programming: the perspective of single and twin pregnancies.  

PubMed

Multiple pregnancy is associated with increased risk of adverse consequences for both mother and fetus(es), including increased rates of maternal hypertension and pre-eclampsia, spontaneous abortion, Caesarean delivery, low birthweight, birth prematurity, perinatal mortality, admission to neonatal intensive care and extended length of care, respiratory distress, cerebral palsy, developmental delay, contact with disability services and mortality to age 5 years. Premature birth, which affects 97% of triplets and 53.3% of twins in Australia, is not the sole factor involved. The rate of multiple pregnancy in Australia is 1.7%. This compares to 22.1% for pregnancies resulting from assisted reproduction technology (ART). As a result, 21.8% of babies born from ART are from a multiple pregnancy, in comparison to the USA where the majority of babies born from ART are from a multiple pregnancy. Additionally, the population rate of multiple births is rising due to the more frequent use of ART and continued multi-embryo transfers, which is operating against a background of rising implantation rates within ART clinics. Twins have been of interest from a programming perspective. However, analysis of associations between crude birthweight and subsequent metabolic risk factors or mortality in adulthood from chronic disease indicate that adaptations in pregnancy to support multi-fetal growth are not identical to fetal growth restriction in singleton pregnancies. Indeed, the process of 'maternal constraint' is incompletely understood and confounds such comparisons. From a programming perspective, it is a challenge to identify in twin pregnancies the transition from physiological adaptation to pathological growth restriction. Growth disparity between twins has been more illuminating of subtle adverse effects for the smaller of twin pairs in both blood pressure and insulin resistance in adulthood. Interestingly, these effects can be observed in both dizygotic and to a lesser degree in monozygotic twins, which indicates a role for both genetic and environmental factors in these measures. This suggests that, consistent with experimental studies in other species, the relationship between impaired growth in utero and chronic disease in later life is not simply mediated by a common genetic pathway. PMID:15745646

Davies, Michael J

2005-01-01

304

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

SciTech Connect

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

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

2012-11-01

305

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

PubMed Central

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

2011-01-01

306

Acute renal failure in pregnancy: our experience.  

PubMed

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

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

2014-03-01

307

Circulating biomarkers of oxidative stress in complicated pregnancies.  

PubMed

Increased lipid peroxidation (LPO) and reduced antioxidant activity may contribute to the development of complications in pregnancy. The present study discusses the possibility of LPO and antioxidant activity in both maternal and umbilical cord blood as an indicator of oxygen radical activity. For this aim, pregnancies with hypertension and pre-eclampsia, diabetes mellitus (insulin dependent diabetes mellitus and gestational diabetes mellitus), oligohydramnios and abruptio placentae, as well as a healthy control group, were subjected in the present study. Simultaneous determination of glutathione S-transferase (GST), selenium dependent glutathione peroxidase (Se-GPx), catalase (CAT) activities and thiobarbituric acid reactive-substances (TBARs) levels were carried out in maternal erythrocyte and plasma in the antenatal period (in the third trimester) and immediately after the delivery. The same oxidative stress-related parameters were determined in umbilical cord blood as well. Erythrocyte GST activity was significantly increased in insulin-dependent diabetic pregnancy (IDDP) when compared to the control (P<0.05). Erythrocyte Se-GPx activity was found to be significantly increased in hypertensive preeclamptic pregnancy (HPP) (P<0.05) and in IDDP (P<0.05). Alterations in enzyme activities were accompanied by a simultaneous significant increase in the levels of TBARs in plasma samples of HPP (P<0.05), and IDDP (P<0.05). Enzyme activities were found to be significantly lower in cord blood samples than the maternal values, except GST. This enzyme represents about two- to threefold higher activity than those of the maternal activity in uncomplicated and complicated groups. Cord blood erythrocyte and plasma Se-GPx and CAT activities were decreased significantly in the HPP group when compared to the maternal value (P<0.05). Cord blood erythrocyte CAT activity was significantly decreased in the HPP group compared to the control (P<0.05). Cord blood TBARs levels were significantly lower than the before deliveries maternal value in the HPP group (P<0.05). No difference was detected between umbilical cord blood and maternal blood TBARs levels after delivery. The results of the present study suggest that oxidative stress and subsequent lipid peroxidation accompany the complications of hypertension, preeclampsia and diabetes mellitus in pregnancy. Maternal erythrocyte GST activity seems to be a sensitive indicator of oxidative stress in IDDP before delivery. The same enzyme can be used in cord blood as a biomarker of oxidative stress upon a sudden increase in oxygenation during delivery. These multiparameter biomarkers can also be used in monitoring the efficiency of antioxidant supplementation in complicated pregnant women, as has recently been suggested for diabetic and preeclamptic pregnancies. PMID:12592416

Orhan, Hilmi; Onderoglu, Lütfü; Yücel, Aykan; Sahin, Gönül

2003-02-01

308

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.

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

2009-01-01

309

Dialyzability and binding of digoxin-like immunoreactive factors (DLIF) with serum macromolecules in uremic patients on hemodialysis.  

PubMed

Digoxin-Like Immunoreactive Factors (DLIF) which cross-react with antidigoxin antibodies are present in elevated concentrations in patients on hemodialysis, uremia, hypertensives, liver failure, pre-eclampsia and premature birth. DLIF may have a potential role as a natriuretic hormone with a speculated low molecular weight (less than 1000). We studied the dialyzability and bindings of DLIF with serum components in hemodialysis patients. We analyzed DLIF concentrations in sera and protein free ultrafiltrates of 31 patients and 22 normal volunteers using a fluorescence polarization assay for digoxin. The DLIF concentrations were expressed as nmol/L Digoxin Equivalent. The gel filtration analysis was done using three different Bio-Gel columns with molecular weight cut-offs of 10,000, 20,000 and 40,000. Molecules with lower molecular weight than cut-off were absorbed in the column. Only 3 out of 22 normal volunteers (13.6%) showed measurable DLIF. However 23 out of 31 patients (74.2%) showed measurable DLIF. The concentrations of DLIF were significantly higher in patients with renal failure on hemodialysis (P less than 0.05) by both chi-squared and Fisher's exact test. We observed no statistically significant difference in the concentrations of DLIF in pre and post-dialysis sera, indicating that DLIF were not filtered during hemodialysis. We observed no DLIF activity in the protein free ultrafiltrates of any DLIF positive sera (patients and normal volunteers), indicating that unlike digoxin (where we observed 70-80% of total digoxin concentrations in ultrafiltrates), DLIF were strongly bound to serum components. With Bio-Gel filtration experiments (five different serum pools), we recovered all DLIF activities in the fraction equivalent to the void volume of the column with Bio-Gel P6 and P10 columns, indicating that DLIF were almost completely bound to serum components with molecular weight greater than 20,000. On the other hand, we recovered no DLIF activities in the void volume when the same serum pools were passed through the Bio-Gel P30 column, indicating that DLIF were strongly bound to serum macromolecules with molecular weight less than 40,000. In sharp contrast, when serum containing digoxin was subjected to the same series of experiments, we recovered only 20-30% of digoxin concentrations in void volume with all three columns as expected since digoxin is only 25% bound to albumin (MW 67,000). PMID:1943464

Dasgupta, A; Peng, Y

1991-01-01

310

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.

2014-01-01

311

Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids.  

PubMed

One of the key molecules promoting angiogenesis is the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF or VEGF-A), which acts through two high-affinity receptor tyrosine kinases (VEGFR), VEGFR-1 (or Flt-1) and VEGFR-2 (or KDR/Flk-1). It was shown before that a soluble variant of VEGFR-1 (sVEGFR-1) can be generated by differential splicing of the flt-1 mRNA. This soluble receptor is an antagonist to VEGF action, reducing the level of free, active VEGF-A, and therefore, plays a pivotal role in the generation of vascular diseases like pre-eclampsia or intra-uterine growth retardation. Here we show that sVEGFR-1 is produced by cultured human microvascular and macrovascular endothelial cells and a human melanoma cell line. The soluble receptor is mainly complexed with ligands; only 5-10% remains detectable as free, uncomplexed receptor protein. Furthermore, we show the time course of total and free sVEGFR-1 release together with its putative ligands, VEGF-A and placenta growth factor (PIGF), from macrovascular endothelial cells. The release of sVEGFR-1 was quantitatively measured in two different ELISA types. The release of sVEGFR-1 was strongly enhanced by phorbol-ester (PMA); the cells produced up to 22 ng/ml of sVEGFR-1 after 48 hours. The expression of VEGF-A and PIGF was moderately influenced by PMA. We also show a hypoxia-induced increase of sVEGFR-1 expression in cells cultured from placenta, a tissue that has a high flt-1 gene expression. Moreover, we demonstrate that sVEGFR-1 in amniotic fluids acts as a sink for exogenous VEGF165 and PIGF-2. Here, for the first time, to what extent recombinant ligands have to be added to compensate for the sink function of amniotic fluids was analyzed. In conclusion, human endothelial cells produce high levels of sVEGFR-1, which influences the availability of VEGF-A or related ligands. Therefore, sVEGFR-1 may reduce the ligand binding to transmembrane receptors and interfere with their signal transduction. PMID:10780661

Hornig, C; Barleon, B; Ahmad, S; Vuorela, P; Ahmed, A; Weich, H A

2000-04-01

312

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.

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

2014-01-01

313

Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta  

PubMed Central

Nodal, a secreted signaling protein from the transforming growth factor beta (TGF-?)-super family plays a vital role during early embryonic development. Recently, it was found that maternal decidua-specific Nodal knockout mice show intrauterine growth restriction (IUGR) and preterm birth. The chromosomal location of NODAL is in the same linkage area as the placental (fetal) pre-eclampsia (PE) susceptibility gene STOX1, which is associated with the familial form of early-onset, IUGR-complicated PE. As the STOX1 linkage was originally identified in women being born from a pre-eclamptic pregnancy as well as suffering from PE themselves, the linkage could in part be caused by NODAL, which is why the potential maternal–fetal interaction between STOX1 and NODAL was investigated. In the PE families with the STOX1 susceptibility allele carried by the children born from pre-eclamptic pregnancies, it was found that the pre-eclamptic mothers themselves all carried the NODAL H165R SNP, which causes a 50% reduced activity. Surprisingly, in decidua-specific Nodal knockout mice the fetal placenta showed up-regulation of STOX1 and NODAL expression. Conditioned media of human first trimester decidua and a human endometrial stromal cell line (T-HESC) treated with siRNAs against NODAL or carrying the H165R SNP were also able to induce NODAL and STOX1 expression when added to SGHPL-5 first trimester extravillous trophoblast cells. Finally, a human TGF-?/BMP signaling pathway PCR-array on decidua and the T-HESC cell line with Nodal knockdown revealed upregulation of Activin-A, which was confirmed in conditioned media by ELISA. We show that maternal decidua Nodal knockdown gives upregulation of NODAL and STOX1 mRNA expression in fetal extravillous trophoblast cells, potentially via upregulation of Activin-A in the maternal decidua. As both Activin-A and Nodal have been implicated in PE, being increased in serum of pre-eclamptic women and upregulated in pre-eclamptic placentas respectively, this interaction at the maternal–fetal interface might play a substantial role in the development of PE.

Thulluru, Hari Krishna; Park, Craig; Dufort, Daniel; Kleiverda, Gunilla; Oudejans, Cees; van Dijk, Marie

2013-01-01

314

Endogenous and exogenous cardiac glycosides and their mechanisms of action.  

PubMed

Cardiac glycosides have been used for decades to treat congestive heart failure. The recent identification of cardiotonic steroids such as ouabain, digoxin, marinobufagenin, and telocinobufagin in blood plasma, adrenal glands, and hypothalamus of mammals led to exciting new perspectives in the pathology of heart failure and arterial hypertension. Biosynthesis of ouabain and digoxin occurs in adrenal glands and is under the control of angiotensin II, endothelin, and epinephrine released from cells of the midbrain upon stimulation of brain areas sensing cerebrospinal Na(+) concentration and, apparently, the body's K(+) content. Rapid changes of endogenous ouabain upon physical exercise may favor the economy of the heart by a rise of intracellular Ca(2)(+) levels in cardiac and atrial muscle cells. According to the sodium pump lag hypothesis, this may be accomplished by partial inhibition of the sodium pump and Ca(2+) influx via the Na(+)/Ca(2+) exchanger working in reverse mode or via activation of the Na(+)/K(+)-ATPase signalosome complex, generating intracellular calcium oscillations, reactive oxygen species, and gene activation via nuclear factor-kappaB or extracellular signal-regulated kinases 1 and 2. Elevated concentrations of endogenous ouabain and marinobufagenin in the subnanomolar concentration range were found to stimulate proliferation and differentiation of cardiac and smooth muscle cells. They may have a primary role in the development of cardiac dysfunction and failure because (i) offspring of hypertensive patients evidently inherit elevated plasma concentrations of endogenous ouabain; (ii) such elevated concentrations correlate positively with cardiac dysfunction, hypertrophy, and arterial hypertension; (iii) about 40% of Europeans with uncomplicated essential hypertension show increased concentrations of endogenous ouabain associated with reduced heart rate and cardiac hypertrophy; (iv) in patients with advanced arterial hypertension, circulating levels of endogenous ouabain correlate with BP and total peripheral resistance; (v) among patients with idiopathic dilated cardiomyopathy, high circulating levels of endogenous ouabain and marinobufagenin identify those individuals who are predisposed to progressing more rapidly to heart failure, suggesting that endogenous ouabain (and marinobufagenin) may contribute to toxicity upon digoxin therapy. In contrast to endogenous ouabain, endogenous marinobufagenin may act as a natriuretic substance as well. It shows a higher affinity for the ouabain-insensitive alpha(1) isoform of Na(+)/K(+)-ATPase of rat kidney tubular cells and its levels are increased in volume expansion and pre-eclampsia. Digoxin, which is synthesized in adrenal glands, seems to counteract the hypertensinogenic action of ouabain in rats, as do antibodies against ouabain, for example, (Digibind) and rostafuroxin (PST 2238), a selective ouabain antagonist. It lowers BP in ouabain- and adducin-dependent hypertension in rats and is a promising new class of antihypertensive medication in humans. PMID:17610345

Schoner, Wilhelm; Scheiner-Bobis, Georgios

2007-01-01

315

Physical activity and pregnancy: cardiovascular adaptations, recommendations and pregnancy outcomes.  

PubMed

Regular physical activity is associated with improved physiological, metabolic and psychological parameters, and with reduced risk of morbidity and mortality. Current recommendations aimed at improving the health and well-being of nonpregnant subjects advise that an accumulation of > or =30 minutes of moderate physical activity should occur on most, if not all, days of the week. Regardless of the specific physiological changes induced by pregnancy, which are primarily developed to meet the increased metabolic demands of mother and fetus, pregnant women benefit from regular physical activity the same way as nonpregnant subjects. Changes in submaximal oxygen uptake (VO(2)) during pregnancy depend on the type of exercise performed. During maternal rest or submaximal weight-bearing exercise (e.g. walking, stepping, treadmill exercise), absolute maternal VO(2) is significantly increased compared with the nonpregnant state. The magnitude of change is approximately proportional to maternal weight gain. When pregnant women perform submaximal weight-supported exercise on land (e.g. level cycling), the findings are contradictory. Some studies reported significantly increased absolute VO(2), while many others reported unchanged or only slightly increased absolute VO(2) compared with the nonpregnant state. The latter findings may be explained by the fact that the metabolic demand of cycle exercise is largely independent of the maternal body mass, resulting in no absolute VO(2) alteration. Few studies that directly measured changes in maternal maximal VO(2) (VO(2max)) showed no difference in the absolute VO(2max) between pregnant and nonpregnant subjects in cycling, swimming or weight-bearing exercise. Efficiency of work during exercise appears to be unchanged during pregnancy in non-weight-bearing exercise. During weight-bearing exercise, the work efficiency was shown to be improved in athletic women who continue exercising and those who stop exercising during pregnancy. When adjusted for weight gain, the increased efficiency is maintained throughout the pregnancy, with the improvement being greater in exercising women. Regular physical activity has been proven to result in marked benefits for mother and fetus. Maternal benefits include improved cardiovascular function, limited pregnancy weight gain, decreased musculoskeletal discomfort, reduced incidence of muscle cramps and lower limb oedema, mood stability, attenuation of gestational diabetes mellitus and gestational hypertension. Fetal benefits include decreased fat mass, improved stress tolerance, and advanced neurobehavioural maturation. In addition, few studies that have directly examined the effects of physical activity on labour and delivery indicate that, for women with normal pregnancies, physical activity is accompanied with shorter labour and decreased incidence of operative delivery. However, a substantial proportion of women stop exercising after they discover they are pregnant, and only few begin participating in exercise activities during pregnancy. The adoption or continuation of a sedentary lifestyle during pregnancy may contribute to the development of certain disorders such as hypertension, maternal and childhood obesity, gestational diabetes, dyspnoea, and pre-eclampsia. In view of the global epidemic of sedentary behaviour and obesity-related pathology, prenatal physical activity was shown to be useful for the prevention and treatment of these conditions. Further studies with larger sample sizes are required to confirm the association between physical activity and outcomes of labour and delivery. PMID:20524714

Melzer, Katarina; Schutz, Yves; Boulvain, Michel; Kayser, Bengt

2010-06-01

316

In Vitro Fertilization and Multiple Pregnancies  

PubMed Central

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

2006-01-01

317

[Role of embolization in the management of uterine fibroids].  

PubMed

Uterine artery embolization using non spherical PVA particles or calibrated trisacryl microspheres above 500 ?m is effective to treat menorrhagia, bulk-related symptoms and pelvic pain in more than 90% of cases in the short-term. In the long-term, embolization is effective in 75% of cases at 5-7 years. At 6 months, uterine volume reduction and dominant fibroid volume reduction varies between 30-60% and 50-80% respectively. During hospital stay, the complication rate is 3%. Secondary hysterectomy for complication is less than 2% at 3 months. Definitive amenorrhea is reported in less than 5% of cases in women of less than 45 years of age. No significant impact of embolization on hormonal function has been reported in women less than 45 years with normal baseline function. Secondary hysterectomy for clinical failure or recurrence is reported in 14-28% of cases at 5 years. Non-spherical PVA particles are associated with more microcatheter occlusion than trisacryl microspheres. No difference between PVA particles and trisacryl microspheres was found in terms of post-embolization pain or analgesic doses. PVA microspheres (Contour SE et Bead Block) are associated with lower clinical success and lower fibroid devascularization using MRI than trisacryl microspheres. No difference between PVA particles and trisacryl microspheres was found in terms of clinical efficacy, uterine volume reduction and complication rate. Randomized studies comparing embolization to hysterectomy demonstrate that reinterventions are more frequently performed after embolization. Secondary hysterectomy is performed in 13 to 24% of cases at 2 years and in up to 28% of cases at 5 years. Hospital stay, duration of recovery and time off work are shorter after embolization compared to hysterectomy. Embolization is cheaper than hysterectomy at 12 and 24 months even taking into consideration the additional costs of imaging and reinterventions. Randomized studies comparing embolization to myomectomy demonstrate that in the short- and mid-term there is no difference in terms of control of menorrhagia and bulk-related symptoms. Uterine volume reduction and quality of life were not different at 6 months. Periprocedural and 30-day complication rates are not different. At 6 months, the rate of complications is higher after myomectomy. Reinterventions are more frequent after embolization compared to myomectomy. Hospital stay, duration of recovery and time off work are shorter after embolization compared to myomectomy. Embolization should be considered with caution in pregnancy-seeking women since there is still a lack of good quality data available in the specific group of patients. FSH level is more frequently elevated after embolization compared to myomectomy. Pregnancy rate and term pregnancy rate are higher after myomectomy compared to embolization. Spontaneous abortion is more frequent after embolization than after myomectomy. There is no difference between embolization and myomectomy for the rates of pre-term delivery, cesarean section, post-partum hemorrhage, pre-eclampsia or intra-uterine growth retardation. Embolization performed before myomectomy (preoperative or combined procedures) can be discussed for an individual patient but there is not enough data to support its routine use. PMID:22093440

Kahn, V; Fohlen, A; Pelage, J-P

2011-12-01

318

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.

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

2014-01-01

319

Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy: executive summary.  

PubMed

Objective: This executive summary presents in brief the current evidence assessed in the clinical practice guideline prepared by the Canadian Hypertensive Disorders of Pregnancy Working Group and published by Pregnancy Hypertension (http://www.pregnancyhypertension.org/article/S2210-7789(14)00004-X/fulltext) to provide a reasonable approach to the diagnosis, evaluation, and treatment of the hypertensive disorders of pregnancy. Evidence: Published literature was retrieved through searches of Medline, CINAHL, and The Cochrane Library in March 2012 using appropriate controlled vocabulary (e.g., pregnancy, hypertension, pre-eclampsia, pregnancy toxemias) and key words (e.g., diagnosis, evaluation, classification, prediction, prevention, prognosis, treatment, postpartum follow-up). Results were restricted to systematic reviews, randomized control trials, controlled clinical trials, and observational studies published in French or English between January 2006 and February 2012. Searches were updated on a regular basis and incorporated in the guideline to September 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values: The quality of evidence in the guideline summarized here was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1). Recommendations Chapter 1: Diagnosis and classification of the measurement of BP for HDPs ? BP Measurement: 1-10 ? Diagnosis of Hypertension: 11-17 ? Measurement of Proteinuria: 18-24 ? Classification of HDPs: 25-31 ? Investigations to Classify HDPs: 32-37 Chapter 2: Prediction and prevention ? Predicting Preeclampsia: 38-40 ? Preventing Preeclampsia and its Complications in Women at Low Risk: 41-46 ? Preventing Preeclampsia and its Complications in Women at Increased Risk: 47-54 Chapter 3: Treatment of the HDPs ? Dietary and Lifestyle Changes: 55-59 ? Place of Care: 60, 61 ? Antihypertensive Therapy for Severe Hypertension: 62-68 ? Antihypertensive Therapy for Non-Severe Hypertension Without Comorbid Conditions: 69-73 ? For Non-Severe Hypertension (BP of 140-159/90-109 mmHg) With Comorbid Conditions: 74-76 ? Corticosteroids for Acceleration of Fetal Pulmonary Maturity: 77-80 ? Timing of Delivery for Women With Preeclampsia: 81-88 ? Timing of Delivery for Women With Gestational Hypertension: 89, 90 ? Timing of Delivery for Women with Pre-existing Hypertension: 91 ? Mode of Delivery: 92-97 ? Anaesthesia: General Principles: 98-101 ? Anaesthesia: Fluid Administration: 102-105 ? Monitoring: 106-108 ? Coagulation: 109, 110 ? Aspects of Care Specific to Women Wth Pre-Existing Hypertension: 111-115 ? Aspects of Care for Women With Preeclampsia: Magnesium Sulphate for Preventing or Treating Eclampsia: 116-123 ? Aspects of Care for Women With Preeclampsia: Plasma Volume Expansion: 124 ? Therapies for HELLP Syndrome: 125-131 ? Care in the 6 Weeks Postpartum: 132-142 ? Care Beyond 6 Weeks Postpartum: 143-148 ? Effects of Maternal Hypertension and its Therapies on Child Neurobehavioural Development: 149, 150 Chapter 4: Patient Perspective: 151-153. PMID:24927294

Magee, Laura A; Pels, Anouk; Helewa, Michael; Rey, Evelyne; von Dadelszen, Peter; Magee, Laura A; Audibert, Francois; Bujold, Emmanuel; Côté, Anne-Marie; Douglas, Myrtle Joanne; Eastabrook, Genevieve; Firoz, Tabassum; Gibson, Paul; Gruslin, Andrée; Hutcheon, Jennifer; Koren, Gideon; Lange, Ian; Leduc, Line; Logan, Alexander G; MacDonell, Karen L; Moutquin, Jean-Marie; Sebbag, Ilana

2014-05-01

320

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

PubMed Central

STUDY QUESTION Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? SUMMARY ANSWER T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. WHAT IS KNOWN ALREADY Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. STUDY DESIGN, SIZE, DURATION This laboratory-based study used human decidua from first (8–11 weeks; n = 18) and second (12–16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10?) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel® was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TR?1, TR?1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different cell isolates were unaffected by T3 so changes in cell numbers could not account for any observed effects. In the first trimester, T3 decreased VEGF-A secretion by total decidual cells (P < 0.05) and increased angiopoietin-2 secretion by stromal-depleted cells (P < 0.05) but in the second trimester total decidual cells showed only increased angiogenin secretion (P < 0.05). In the first trimester, T3 reduced IL-10 secretion by total decidual cells (P < 0.05), and reduced granulocyte macrophage colony stimulating factor (P < 0.01), IL-8 (P < 0.05), IL-10 (P < 0.01), IL-1? (P < 0.05) and monocyte chemotactic protein -1 (P < 0.001) secretion by macrophages, but increased tumour necrosis factor-? secretion by stromal-depleted cells (P < 0.05) and increased IL-6 by uNK cells (P < 0.05). In contrast, in the second trimester T3 increased IL-10 secretion by total decidual cells (P < 0.01) but did not affect cytokine secretion by uNK cells and macrophages. Conditioned media from first trimester T3-treated total decidual cells and macrophages did not alter EVT invasion compared with untreated controls. Thus, treatment of decidual cells with T3 resulted in changes in both angiogenic growth factor and cytokine secretion in a cell type-specific and gestational age-dependent manner, with first trimester decidual macrophages being the most responsive to T3 treatment, but these changes in decidual cell secretome did not affect EVT invasion in vitro. LIMITATIONS, REASONS FOR CAUTION Our results are based on in vitro findings and we cannot be certain if a similar response occurs in human pregnancy in vivo. WIDER IMPLICATIONS OF THE FINDINGS Optimal maternal thyroid hormone concentrations could play a critical role in maintaining a balanced inflammatory response in early pregnancy to prevent fetal immune rejection and promote normal placental dev

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

2014-01-01