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Sample records for pre-eclampsia

  1. [Pre-eclampsia].

    PubMed

    Post Uiterweer, E D; Veerbeek, J H W; Franx, A

    2015-02-01

    Pre-eclampsia or toxaemia of pregnancy is a multi-organ disorder in the second half of pregnancy. Approximately 1-3% of all pregnancies in the Netherlands are complicated by this condition. The disease is characterised by vascular damage resulting in hypertension and proteinuria with high morbidity for both mother and child. The underlying cause is a poorly developed placenta. To date the only real treatment comprises medicinal protection against complications and the disorder can be cured only through termination of pregnancy. Complications range from severe hypertension to maternal mortality due to cerebral haemorrhage. Long-term consequences can be severe for both mother and child. For instance, the risk of cardiovascular disease in mothers in later life is significantly increased. Many risk factors have been identified, including diabetes, BMI and an age of above 40. The association between periodontal disease and pre-eclampsia emphasises the importance of good oral hygiene in the periconceptional period. PMID:26193106

  2. Pre-eclampsia: pathophysiology, diagnosis, and management.

    PubMed

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

    2011-01-01

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

  3. Pre-eclampsia: pathophysiology, diagnosis, and management

    PubMed Central

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

    2011-01-01

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

  4. Immunological aspects of pre-eclampsia.

    PubMed

    Redman, C W

    1992-09-01

    The first pregnancy preponderance and apparent partner specificity of pre-eclampsia suggest that it might have an immune aetiology. The pathogenesis of pre-eclampsia is undefined although it is clear that it is a placental disorder. The maternal syndrome appears to be mediated by placental ischaemia secondary to spiral artery insufficiency. This leads to a hypothesis that pre-eclampsia is a two-stage disease. The first comprises processes that limit the size of the spiral arteries (poor placentation) or obstruct them (acute atherosis). Either or both may have immunological causes although there is no direct evidence. Factors limiting placentation could involve maternal immune intolerance of the fetal allograft, which in their most extreme expression could lead to immunologically mediated abortion. Thus pre-eclampsia may be part of a wider spectrum of pregnancy loss secondary to poor maternal immune accommodation of her genetically disparate fetus. The second stage involves the consequences of the ensuing placental ischaemia. The syndrome is currently tentatively ascribed to diffuse maternal endothelial dysfunction. There is less reason to invoke immunological mechanisms in the second stage although neutrophil activation could explain generalized endothelial damage. It should be clear that these conclusions are provisional and that the greatest need is for more investigation to eliminate the uncertainty which clouds our concepts.

  5. First trimester screening for pre-eclampsia.

    PubMed

    Kane, Stefan C

    2016-09-01

    The commercial availability of tests in the first trimester of pregnancy that predict the later development of pre-eclampsia has prompted considerable debate regarding their clinical utility and the degree to which they fulfil the longstanding principles of screening. Such tests have been shown to achieve detection rates for early pre-eclampsia (requiring delivery prior to 34 weeks) of over 90%, for a false positive rate of 10%. However, their capacity to predict later onset pre-eclampsia, which accounts for the bulk of the disease burden, is much more limited. The relatively few studies validating the performance of these tests in different populations have demonstrated significant variations in performance. Moreover, prospective research confirming that the administration of aspirin to those screened to be high risk reduces the incidence of pre-eclampsia is yet to be completed, and there may be harms in restricting aspirin therapy to this group, given its broader beneficial effect. In light of these limitations, further development of these tests is recommended prior to their introduction to clinical practice. PMID:27630745

  6. First trimester screening for pre-eclampsia.

    PubMed

    Kane, Stefan C

    2016-09-01

    The commercial availability of tests in the first trimester of pregnancy that predict the later development of pre-eclampsia has prompted considerable debate regarding their clinical utility and the degree to which they fulfil the longstanding principles of screening. Such tests have been shown to achieve detection rates for early pre-eclampsia (requiring delivery prior to 34 weeks) of over 90%, for a false positive rate of 10%. However, their capacity to predict later onset pre-eclampsia, which accounts for the bulk of the disease burden, is much more limited. The relatively few studies validating the performance of these tests in different populations have demonstrated significant variations in performance. Moreover, prospective research confirming that the administration of aspirin to those screened to be high risk reduces the incidence of pre-eclampsia is yet to be completed, and there may be harms in restricting aspirin therapy to this group, given its broader beneficial effect. In light of these limitations, further development of these tests is recommended prior to their introduction to clinical practice.

  7. Stress responses and pre-eclampsia.

    PubMed

    Redman, C W G

    2013-04-01

    Biological stress may affect individual cells, tissues or whole organisms, arising from disturbed homoeostasis of any cause. Stress is rarely localised. Because biological systems are closely integrated, it spreads to involve other systems. Stress responses are highly integrated and work to restore homoeostasis. Different response pathways overlap and interlink. If the responses fail or decompensate, distress ensues, of which the end-stage is death. Pre-eclampsia results from a series of biological stresses, possibly from conception, which become established by abnormal placentation and affect the mother, her foetus and her placenta. The stresses involve dialogue between mother and placenta. Even a normal placenta imposes substantial stress on maternal systems. When placental growth and perfusion is abnormal (poor placentation) then the placenta, particularly its outer trophoblast layer, becomes stressed - loosely denoted hypoxic damage or oxidative stress. Signals from the placenta spread the stress to the mother, who develops signs of pre-eclampsia. Cellular stress sensors initiate stress responses. Different stresses may trigger similar responses in specific cell types. The first cell response is reduced protein synthesis. However some synthetic pathways are spared or activated to produce stress signals. In relation to pre-eclampsia and the placenta, an excessive release of sFlt-1 a soluble decoy receptor for vascular endothelial growth factor (VEGF) is a trophoblast related stress signal. SFlt1 perturbs the angiogenic balance in the maternal circulation and is considered to cause many of the specific features of the maternal syndrome in pre-eclampsia. Three key points will be emphasised. First, multiple stressors, not simply hypoxia, stimulate the release of sFlt-1 from trophoblast. Second, sFlt-1 is only one of the group of stress signals delivered by trophoblast to the mother. Third, sFlt-1 is not the only trophoblast derived factor to perturb the maternal

  8. Molecular association of pathogenetic contributors to pre-eclampsia (pre-eclampsia associome)

    PubMed Central

    2015-01-01

    Background Pre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point. Results The use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA

  9. Fluid management in pre-eclampsia

    PubMed Central

    Schoeman, Leann K

    2013-01-01

    Intravenous fluid given to women with pre-eclampsia may be a necessary form of treatment; however, intravenous fluid therapy can also cause iatrogenic pulmonary oedema. The indications for the use of intravenous fluids, the titration of the amount of fluid given and the use of invasive monitoring have not been subject to adequate examination in randomised studies. Clinical experience, combined with available evidence and a reasoned approach are the basis for a suggested management algorithm. PMID:27708700

  10. Pre-eclampsia part 2: prediction, prevention and management.

    PubMed

    Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Korzeniewski, Steven J; Yeo, Lami; Romero, Roberto

    2014-09-01

    An antiangiogenic state might constitute a terminal pathway for the multiple aetiologies of pre-eclampsia, especially those resulting from placental abnormalities. The levels of angiogenic and antiangiogenic proteins in maternal blood change prior to a diagnosis of pre-eclampsia, correlate with disease severity and have prognostic value in identifying women who will develop maternal and/or perinatal complications. Potential interventions exist to ameliorate the imbalance of angiogenesis and, hence, might provide opportunities to improve maternal and/or perinatal outcomes in pre-eclampsia. Current strategies for managing pre-eclampsia consist of controlling hypertension, preventing seizures and timely delivery of the fetus. Prediction of pre-eclampsia in the first trimester is of great interest, as early administration of aspirin might reduce the risk of pre-eclampsia, albeit modestly. Combinations of biomarkers typically predict pre-eclampsia better than single biomarkers; however, the encouraging initial results of biomarker studies require external validation in other populations before they can be used to facilitate intervention in patients identified as at increased risk. Angiogenic and antiangiogenic factors might also be useful in triage of symptomatic patients with suspected pre-eclampsia, differentiating pre-eclampsia from exacerbations of pre-existing medical conditions and performing risk assessment in asymptomatic women. This Review article discusses the performance of predictive and prognostic biomarkers for pre-eclampsia, current strategies for preventing and managing the condition and its long-term consequences.

  11. Apolipoprotein E alleles in women with severe pre-eclampsia.

    PubMed Central

    Nagy, B; Rigó, J; Fintor, L; Karádi, I; Tóth, T

    1998-01-01

    This study investigated the frequency of apolipoprotein E (apoE) alleles among women with severe pre-eclampsia. The presence of the three most common apoE alleles (epsilon 2, epsilon 3, epsilon 4) was determined by polymerase chain reaction-restriction fragment length polymorphism in three groups of white women: non-pregnant healthy (n = 101), pregnant healthy (n = 52), and pregnant with a diagnosis of severe pre-eclampsia (n = 54). The frequency of apo epsilon 2 was highest among women with severe pre-eclampsia (16.6%) followed by non-pregnant women (12.9%), and those experiencing a healthy pregnancy (10.6%). The higher frequency of the apo epsilon 2 allele detected among women with severe pre-eclampsia suggests that apoE may play a role in the development of pre-eclampsia. PMID:9659248

  12. Potential role of folate in pre-eclampsia.

    PubMed

    Singh, Mansi Dass; Thomas, Philip; Owens, Julie; Hague, William; Fenech, Michael

    2015-10-01

    Dietary deficiencies of folate and other B vitamin cofactors involved in one-carbon metabolism, together with genetic polymorphisms in key folate-methionine metabolic pathway enzymes, are associated with increases in circulating plasma homocysteine, reduction in DNA methylation patterns, and genome instability events. All of these biomarkers have also been associated with pre-eclampsia. The aim of this review was to explore the literature and identify potential knowledge gaps in relation to the role of folate at the genomic level in either the etiology or the prevention of pre-eclampsia. A systematic search strategy was designed to identify citations in electronic databases for the following terms: folic acid supplementation AND pre-eclampsia, folic acid supplementation AND genome stability, folate AND genome stability AND pre-eclampsia, folic acid supplementation AND DNA methylation, and folate AND DNA methylation AND pre-eclampsia. Forty-three articles were selected according to predefined selection criteria. The studies included in the present review were not homogeneous, which made pooled analysis of the data very difficult. The present review highlights associations between folate deficiency and certain biomarkers observed in various tissues of women at risk of pre-eclampsia. Further investigation is required to understand the role of folate in either the etiology or the prevention of pre-eclampsia.

  13. Potential role of folate in pre-eclampsia.

    PubMed

    Singh, Mansi Dass; Thomas, Philip; Owens, Julie; Hague, William; Fenech, Michael

    2015-10-01

    Dietary deficiencies of folate and other B vitamin cofactors involved in one-carbon metabolism, together with genetic polymorphisms in key folate-methionine metabolic pathway enzymes, are associated with increases in circulating plasma homocysteine, reduction in DNA methylation patterns, and genome instability events. All of these biomarkers have also been associated with pre-eclampsia. The aim of this review was to explore the literature and identify potential knowledge gaps in relation to the role of folate at the genomic level in either the etiology or the prevention of pre-eclampsia. A systematic search strategy was designed to identify citations in electronic databases for the following terms: folic acid supplementation AND pre-eclampsia, folic acid supplementation AND genome stability, folate AND genome stability AND pre-eclampsia, folic acid supplementation AND DNA methylation, and folate AND DNA methylation AND pre-eclampsia. Forty-three articles were selected according to predefined selection criteria. The studies included in the present review were not homogeneous, which made pooled analysis of the data very difficult. The present review highlights associations between folate deficiency and certain biomarkers observed in various tissues of women at risk of pre-eclampsia. Further investigation is required to understand the role of folate in either the etiology or the prevention of pre-eclampsia. PMID:26359215

  14. Platelet function in pre-eclampsia.

    PubMed

    Kazmi, Rashid S; Cooper, Alan J; Lwaleed, Bashir A

    2011-03-01

    Pronounced hemostatic changes occur during pregnancy, and the balance shifts markedly in favor of hypercoagulability. Although primarily a result of a marked rise in the levels of several procoagulants and a fall in some natural anticoagulants, platelet activation also contributes to this prothrombotic tendency. Several studies have confirmed the accentuation of platelet activation in pre-eclampsia (P-EC), which remains an important obstetric complication affecting ~2 to 4% of pregnancies. Although there is still a long way to go, significant inroads have been made in the understanding of this enigmatic condition. Whereas the pathogenesis of P-EC is protean and involves a complex interplay of placental and maternal tissues, platelet activation is likely to contribute to several clinical features. Several techniques have been used to assess platelet activation in P-EC. Detection of aberrations of platelet function and activation appear to have predictive value for its diagnosis. The findings also lend support to the use of antiplatelet agents as prophylaxis in those women with a high risk of developing the condition.

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

    PubMed

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

    2014-08-01

    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.

  16. Endothelin-1: a key pathological factor in pre-eclampsia?

    PubMed

    Jain, Arjun

    2012-11-01

    Endothelin (ET)-1 has been implicated in a diverse range of signalling events in a wide variety of target tissues. Given its potent vasoactive function and the prevalence of hypertension in pre-eclampsia, there has been extensive research on the role of ET-1 in this disorder. Indeed, ET-1 has been suggested to contribute to hypertension in pre-eclampsia. Recently, ET-1 has also been implicated in the induction of both oxidative stress and endoplasmic reticulum stress in pre-eclampsia; each of which has been proposed to contribute to many of the clinical manifestations of this disorder. ET-1 has been shown to activate key signalling molecules that lead to induction of these stress pathways. The use of ET-receptor antagonists could block oxidative and endoplasmic reticulum stress. Hence, further research into the role of ET-1 in pre-eclampsia may lead to the development of possible strategies to circumvent these stress pathways and the associated pathology that occurs in pre-eclampsia. Endothelin (ET)-1 has been implicated in a diverse range of signalling events in a wide variety of target tissues. Given its potent vasoactive function and the prevalence of hypertension in pre-eclampsia, there has been extensive research on the role of ET-1 in this disorder. Indeed, ET-1 has been suggested to contribute to hypertension in pre-eclampsia. Recently, ET-1 has also been implicated in the induction of both oxidative stress and endoplasmic reticulum stress in pre-eclampsia, each of which has been proposed to contribute to many of the clinical manifestations of this disorder. ET-1 has been shown to activate key signalling molecules that lead to induction of these stress pathways. The use of ET-receptor antagonists could block oxidative and endoplasmic reticulum stress. Hence, further research into the role of ET-1 in pre-eclampsia may lead to the development of possible strategies to circumvent these stress pathways and the associated pathology that occurs in pre-eclampsia

  17. A case of recurrent severe pre-eclampsia associated with essential cryofibrinogenaemia

    PubMed Central

    Henderson, Christopher; Adno, Alan; Spicer, Timothy; Cleland, Bruce; Makris, Angela

    2013-01-01

    Essential cryofibrinogenaemia is a rare disorder characterized by cryofibrinogens without cryoglobulins. Connective tissue disorders and thrombophilia are known to increase risk of pre-eclampsia, but pre-eclampsia has not previously been reported in association with cryofibrinogenaemia. We report the case of a 32-year-old woman with recurrent severe pre-eclampsia diagnosed with essential cryofibrinogenaemia.

  18. Pre-eclampsia and the hypertensive disorders of pregnancy.

    PubMed

    Duley, Lelia

    2003-01-01

    Pre-eclampsia is a multisystem disorder, of unknown aetiology, usually associated with raised blood pressure and proteinuria. Although outcome for most women and their babies is good, it remains a major cause of morbidity and mortality. A wide range of interventions for prevention and treatment of pre-eclampsia have been evaluated in randomized trials. This evidence provides the basis for a rational approach to care. Overall, there is insufficient evidence for any firm conclusion about the effects of any aspect of diet or lifestyle during pregnancy. Antiplatelet agents are associated with a 19% reduction in the risk of pre-eclampsia (relative risk 0.81; 95% CI 0.75, 0.88), a 7% reduction in the risk of preterm birth (RR 0.93; 95% CI 0.89, 0.98), a 16% reduction in the risk of stillbirth or neonatal death (RR 0.84; 95% CI 0.74, 0.96) and an 8% reduction in the risk of a small for gestational age baby (RR 0.92; 95% CI 0.85, 1.00). For mild to moderate hypertension, trials evaluating bed rest are too small for reliable conclusions about the potential benefits and hazards. Antihypertensive agents halve the risk of progression to severe hypertension (RR 0.52; 95% CI 0.41, 0.64), but with no clear effect on pre-eclampsia (RR 0.99; 95% CI 0.84, 1.18), or any other substantive outcome. For severe hypertension, there is no good evidence that one drug is any better than another. Plasma volume expansion for severe pre-eclampsia seems unlikely to be beneficial, although the trials are small. The optimum timing of delivery for pre-eclampsia before 34 weeks is unclear. Magnesium sulphate more than halves the risk of eclampsia (RR 0.41; 95% CI 0.29, 0.58) and probably reduces the risk of maternal death (RR 0.54; 95% CI 0.26, 1.10). It is also the drug of choice for treatment of eclampsia.

  19. Hypoxia-inducible factor-1α as a predictive marker in pre-eclampsia

    PubMed Central

    AKHILESH, MEENAKSHI; MAHALINGAM, VIVEKANANDA; NALLIAH, SIVALINGAM; ALI, ROSALINA MOHD; GANESALINGAM, MURALI; HALEAGRAHARA, NAGARAJA

    2013-01-01

    The aim of this study was to determine whether or not the increased levels of hypoxia-inducible factor-1α (HIF-1α) could be used to demonstrate failed placentation in pre-eclamptic mothers. Twenty pregnant females with (pre-eclampsia group) or without pre-eclampsia (control group) were included in the present study. Antenatal and post-delivery HIF-1α transcription factor levels were measured. A significant increase was observed in the HIF-1α levels in the pre- and post-natal pre-eclampsia mothers. The findings suggest that the levels of HIF-1α in the blood of mothers with pre-eclampsia decrease after delivery of the placenta. The results confirm that there is increased HIF-1α in pre-eclampsia and a steady increase in the levels of HIF-1α could be commensurate with the possibility of a patient developing pre-eclampsia at a later trimester. PMID:24648931

  20. The Pre-Eclampsia Ontology: A Disease Ontology Representing the Domain Knowledge Specific to Pre-Eclampsia

    PubMed Central

    Mizuno, Satoshi; Ogishima, Soichi; Nishigori, Hidekazu; Jamieson, Daniel G.; Verspoor, Karin; Tanaka, Hiroshi; Yaegashi, Nobuo; Nakaya, Jun

    2016-01-01

    Pre-eclampsia (PE) is a clinical syndrome characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation, and is a leading cause of maternal and perinatal morbidity and mortality. Previous studies have gathered abundant data about PE such as risk factors and pathological findings. However, most of these data are not semantically structured. Clinical data on PE patients are often generated with semantic heterogeneity such as using disparate terminology to describe the same phenomena. In clinical studies, interoperability of heterogenic clinical data is required in various situations. In such a situation, it is necessary to develop an interoperable and standardized semantic framework to research the pathology of PE more comprehensively and to achieve interoperability of heterogenic clinical data of PE patients. In this study, we developed an ontology representing clinical features, treatments, genetic factors, environmental factors, and other aspects of the current knowledge in the domain of PE. We call this pre-eclampsia ontology “PEO”. To achieve interoperability with other ontologies, the core structure of PEO was compliant with the hierarchy of the Basic Formal Ontology (BFO). The PEO incorporates a wide range of key concepts and terms of PE from clinical and biomedical research in structuring the knowledge base that is specific to PE; therefore, PEO is expected to enhance PE-specific information retrieval and knowledge discovery in both clinical and biomedical research fields. PMID:27788142

  1. The management of severe pre-eclampsia and eclampsia.

    PubMed

    Hibbard, B M; Rosen, M

    1977-01-01

    With improving standards of antenatal care, severe pre-eclampsia dn eclampsia are becoming less common and experience in the management of these conditions is lessening. Co-ordinated plans for the care of patients should be established by obstetricians and anaesthetists working as a team. A suitable regime for drug therapy in severe pre-eclampsia or eclampsia is the following: Initial management Diazepam 10 mg slowly i.v. Pethidine 100-150 mg i.m. or i.v. in incremental dosage, or extradural blocks, if analgesia is also required. Hydrallazine 20 mg i.v. initially, followed by 5 mg at intervals of 20 min until the diastolic pressure is less than 110 mm Hg. Then, preferably by syringe pump in a concentration of 2 mg/ml, at a rate of 2-20 mg/h. If vomiting occurs this can be controlled by administration of atropine. Subsequent management Sedation and anticonvulsant therapy. Continue diazepam and, in severe cases, institute chlormethiazole infusion. Continue analgesia with pethidine or extradural block. Control of hypertension by adjusting the dose of hydrallazine. If tachycardia exceeds 120 beat/min give propanolol 2-4 mg i.v. Plasma protein depletion with groww oedema is treated by administration of salt-free albumin or plasma protein fraction. Diuretic therapy is indicated if there is gross oedema or signs suggestive of acute renal failure. Oliguria associated with increased blood urea may be a result of renal failure or dehydration. The latter should be evident from the patient's condition and central venous pressure, but i.v. fluids and frusemide 20-40 mg can be used as a therapeutic test. Mannitol reduces cerebral oedema and may be given if diuresis has been first produced with frusemide. Potassium chloride is given if the plasma potassium decreases to less than 3 mmol/litre. Heparin therapy is considered if there is clinical evidence of disseminated intravascular coagulation. PMID:831744

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

    PubMed Central

    Williams, Paula Juliet; Morgan, Linda

    2012-01-01

    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

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

    PubMed

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

    2015-02-01

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

  4. Community-based home-care program for the management of pre-eclampsia: an alternative.

    PubMed Central

    Helewa, M; Heaman, M; Robinson, M A; Thompson, L

    1993-01-01

    OBJECTIVE: To evaluate the safety, acceptability and cost of a community-based home-care program for the management of mild pre-eclampsia. DESIGN: A descriptive study of outcomes between Apr. 1, 1985, and Dec. 31, 1989. SETTING: St. Boniface General Hospital, Winnipeg. PATIENTS: Urban Winnipeg residents between 27 and 40 weeks' gestation with mild pre-eclampsia who demonstrated acceptance and compliance with home-care management; 321 patients of 1330 were enrolled in the program. INTERVENTIONS: Bed rest at home with daily biochemical and biophysical follow-up protocol and weekly clinic visits; patient education; hospital admission for labour, induction, worsening pre-eclampsia or noncompliance with rest at home. OUTCOME MEASURES: Patterns of referral to the program; clinical, biochemical and biophysical profiles; incidence of severe complications; reduction in total hospital stay and cost analysis. RESULTS: As many women were referred from physicians' offices as were referred from the hospital's antepartum unit, the average gestational age at referral being 36 weeks. Most (205 [64%]) of the women were nulliparous. The average length of stay in the program was 11.5 days. The program's availability resulted in a reduction of 2 days (from 5.7 days to 3.7 days) on average in the length of hospital stay when analysed for all 1330 women with pre-eclampsia. Of the 321 patients in the program 137 (43%) were admitted to hospital for worsening pre-eclampsia; severe pre-eclampsia developed 4 days after admission in 9. No patient suffered eclampsia, disseminated intravascular coagulopathy, abruption or fetal loss related to pre-eclampsia while in the program. The estimated cost saving in the management of pre-eclampsia was over $700,000 over the study period. CONCLUSION: The community-based home-care program is a safe, feasible and less costly alternative to hospital admission in the management of mild pre-eclampsia. PMID:8374846

  5. Magnesium sulfate in eclampsia and pre-eclampsia: pharmacokinetic principles.

    PubMed

    Lu, J F; Nightingale, C H

    2000-04-01

    Magnesium sulfate (MgSO4) is the agent most commonly used for treatment of eclampsia and prophylaxis of eclampsia in patients with severe pre-eclampsia. It is usually given by either the intramuscular or intravenous routes. The intramuscular regimen is most commonly a 4 g intravenous loading dose, immediately followed by 10 g intramuscularly and then by 5 g intramuscularly every 4 hours in alternating buttocks. The intravenous regimen is given as a 4 g dose, followed by a maintenance infusion of 1 to 2 g/h by controlled infusion pump. After administration, about 40% of plasma magnesium is protein bound. The unbound magnesium ion diffuses into the extravascular-extracellular space, into bone, and across the placenta and fetal membranes and into the fetus and amniotic fluid. In pregnant women, apparent volumes of distribution usually reach constant values between the third and fourth hours after administration, and range from 0.250 to 0.442 L/kg. Magnesium is almost exclusively excreted in the urine, with 90% of the dose excreted during the first 24 hours after an intravenous infusion of MgSO4. The pharmacokinetic profile of MgSO4 after intravenous administration can be described by a 2-compartment model with a rapid distribution (a) phase, followed by a relative slow beta phase of elimination. The clinical effect and toxicity of MgSO4 can be linked to its concentration in plasma. A concentration of 1.8 to 3.0 mmol/L has been suggested for treatment of eclamptic convulsions. The actual magnesium dose and concentration needed for prophylaxis has never been estimated. Maternal toxicity is rare when MgSO4 is carefully administered and monitored. The first warning of impending toxicity in the mother is loss of the patellar reflex at plasma concentrations between 3.5 and 5 mmol/L. Respiratory paralysis occurs at 5 to 6.5 mmol/L. Cardiac conduction is altered at greater than 7.5 mmol/L, and cardiac arrest can be expected when concentrations of magnesium exceed 12.5 mmol

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

    PubMed

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

    2014-01-09

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

  7. Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies

    PubMed Central

    Marder, Wendy; Knight, Jason S; Kaplan, Mariana J; Somers, Emily C; Zhang, Xu; O'Dell, Alexander A; Padmanabhan, Vasantha; Lieberman, Richard W

    2016-01-01

    Objective Systemic lupus erythematosus (SLE) is associated with increased risk of adverse pregnancy outcomes, including pre-eclampsia, particularly in association with antiphospholipid antibody syndrome (APS). While significant placental abnormalities are expected in pre-eclampsia, less is known about how lupus activity and APS in pregnancy affect the placenta. We describe placental pathology from a population of lupus pregnancies, several of which were complicated by APS-related thromboses, in which pre-eclampsia and other complications developed. We performed standard histopathological placental review and quantified neutrophils and neutrophil extracellular traps (NETs) in the intervillous space, given the recognised association of NETs with lupus, APS and pre-eclampsia. Methods Pre-eclampsia, SLE and control placentas were scored for histological features, and neutrophils were quantified on H&E and immunohistochemical staining for the granular protein myeloperoxidase. NETs were identified by extracellular myeloperoxidase staining in the setting of decondensed nuclei. Non-parametric analysis was used to evaluate differences in netting and intact neutrophils between groups, with Kruskal–Wallis testing for associations between histological findings and neutrophils. Results Placentas were evaluated from 35 pregnancies: 10 controls, 11 pre-eclampsia, 4 SLE+pre-eclampsia and 10 SLE, including one complicated by catastrophic APS and one complicated by hepatic and splenic vein thromboses during pregnancy. Intrauterine growth restriction and oligohydramnios were observed in lupus cases but not controls. Significantly more NETs were found infiltrating placental intervillous spaces in pre-eclampsia, SLE+pre-eclampsia and all 10 SLE non-pre-eclampsia cases. The ratio of NETs to total neutrophils was significantly increased in all case groups compared with controls. When present, NETs were associated with maternal vasculitis, laminar decidual necrosis, maternal

  8. Exome sequencing in pooled DNA samples to identify maternal pre-eclampsia risk variants.

    PubMed

    Kaartokallio, Tea; Wang, Jingwen; Heinonen, Seppo; Kajantie, Eero; Kivinen, Katja; Pouta, Anneli; Gerdhem, Paul; Jiao, Hong; Kere, Juha; Laivuori, Hannele

    2016-01-01

    Pre-eclampsia is a common pregnancy disorder that is a major cause for maternal and perinatal mortality and morbidity. Variants predisposing to pre-eclampsia might be under negative evolutionary selection that is likely to keep their population frequencies low. We exome sequenced samples from a hundred Finnish pre-eclamptic women in pools of ten to screen for low-frequency, large-effect risk variants for pre-eclampsia. After filtering and additional genotyping steps, we selected 28 low-frequency missense, nonsense and splice site variants that were enriched in the pre-eclampsia pools compared to reference data, and genotyped the variants in 1353 pre-eclamptic and 699 non-pre-eclamptic women to test the association of them with pre-eclampsia and quantitative traits relevant for the disease. Genotypes from the SISu project (n = 6118 exome sequenced Finnish samples) were included in the binary trait association analysis as a population reference to increase statistical power. In these analyses, none of the variants tested reached genome-wide significance. In conclusion, the genetic risk for pre-eclampsia is likely complex even in a population isolate like Finland, and larger sample sizes will be necessary to detect risk variants. PMID:27384325

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

    PubMed

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

    2012-07-01

    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.

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

    PubMed

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

    2012-05-01

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

  11. Transforming growth factor-beta 1 does not relate to hypertension in pre-eclampsia.

    PubMed

    Hennessy, A; Orange, S; Willis, N; Painter, D M; Child, A; Horvath, J S

    2002-11-01

    1. Pre-eclampsia is a human disease of pregnancy characterized by high blood pressure, proteinuria and end-organ damage, if severe. Pre-eclampsia is thought to be related to changes in early placental development, with the formation of a shallower than normal placental bed. 2. Transforming growth factor (TGF)-beta1 is a multifunctional fibrogenic growth factor involved in immune regulation that is elevated in some populations with a high risk of hypertensive end-organ disease related to increases in endothelin release. Transforming growth factor-beta1 is also an important factor in placental implantation. Alterations in TGF-beta1 may be related to abnormal placental development in early pregnancy and, thus, are a candidate for the development of hypertension in pre-eclampsia. 3. The aim of the present study was to examine the placental distribution and serum concentration of TGF-beta1 in patients with pre-eclampsia compared with normal pregnancy. 4. Patients with pre-eclampsia (n = 12) were compared with patients with normal pregnancy (n = 14). Transforming growth factor-beta1 was determined by TGF-beta1 Max ELISA (Promega, Madsion, WI, USA) after serum dilution (1/150) and acid activation. Placental distribution was determined by immunostaining with TGF-beta1 (Santa Cruz, Santa Cruz, CA, USA; 20 ng/mL) and the villi and decidual trophoblast were scored for intensity and extent of staining. 5. Patients with pre-eclampsia had a mean gestational age of 36 weeks, whereas those with a normal pregnancy had a mean gestational age of 39.0 +/- 0.4 weeks. There was no difference in TGF-beta1 concentration between the two groups (mean (+/-SEM) 27.1 +/- 1.0 vs 26.4 +/- 0.7 pg/mL for normal pregnancy and pre-eclampsia, respectively; P = 0.73, Mann-Whitney U-test). There was no correlation between systolic or diastolic blood pressure and TGF-beta1 concentration (regression analysis P = 0.4 and 0.2). Immunostaining was absent in the villous trophoblast cells and endovascular and

  12. Who let the dogs in: a canine trophoblast invasion model for pre-eclampsia.

    PubMed

    Kutzler, M; Sahlfeld, L; Fellows, E

    2012-12-01

    Pre-eclampsia affects 2-8% of pregnant women worldwide and is the third leading cause of maternal mortality in the United States, accounting for 20% of maternal deaths, for which the only known cure is delivery of the placenta. It is known that pre-eclampsia results from defects within the trophoblast invasion of the endometrium and myometrium. At a morphological level within the pre-eclamptic human placenta, trophoblast invasion is shallow, and this results in hypoperfusion, which is a life-threatening condition for both the mother and the foetus. Pre-eclampsia has been intensively investigated for over 50 years, and yet the causes are largely unknown. Despite a large body of data, it is still unknown exactly which mechanisms regulate trophoblast invasion. An effective animal model may be crucial to understanding the underlying causes of pre-eclampsia. A canine model is a proposed improvement on the current efforts to investigate disorders of shallow trophoblast invasion throughout gestation and to improve understanding of the factors that regulate trophoblast invasion. The objectives of this research were to elucidate and compare cellular and molecular similarities between normal canine trophoblasts with those from recently published reports on pre-eclampsia in women.

  13. Disentangling fetal and maternal susceptibility for pre-eclampsia: a British multicenter candidate-gene study.

    PubMed

    2005-07-01

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

  14. [Angiogenic factors can be used when pre-eclampsia is suspected].

    PubMed

    Andrea, Mille Kyhn; Lykke, Jacob Alexander

    2015-05-25

    Pre-eclampsia complicates 7% of pregnancies. The heterogeneity of the syndrome makes it difficult to assess its development and complications, and the current models have low predictive values. Studies indicate a significant difference in the levels of the angiogenic factors: placental growth factor (PlGF) and soluble fms-like tyrosin kinase 1 (sFlt-1), as well as the sFlt-1/PlGF ratio in women with pre-eclampsia compared to women without pre-eclampsia. These angiogenic factors can also be used to help find the women at risk for complications. However, before implementing PlGF and sFlt-1/PlGF ratio in the diagnosis and risk assessment, establishment and further validation of cut-offs are needed.

  15. Association between risk for pre-eclampsia and HLA DR4

    SciTech Connect

    Not Available

    1990-03-17

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

  16. Bell's palsy in pregnancy: underlying HELLP syndrome or pre-eclampsia?

    PubMed Central

    Neau, J-P; Pierre, F

    2013-01-01

    Bell's palsy is not uncommon during pregnancy. An association with pre-eclampsia (PE) has been reported previously. Furthermore, it has even been suggested that Bell's palsy could be a predictor of PE. We report three cases illustrating various possible aspects of this association, one of them including the features of HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome.

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

    PubMed Central

    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

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

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

    PubMed

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

    2014-02-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    Ahmed, Asif; Ramma, Wenda

    2015-01-01

    Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the ‘two-stage model’ of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the ‘accelerator’. The ‘braking system’ includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-γ-lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator–brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti-angiogenic factors sFlt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 PMID:25303561

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

    PubMed Central

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

    2014-01-01

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

  2. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis

    PubMed Central

    Bellamy, Leanne; Casas, Juan-Pablo; Hingorani, Aroon D

    2007-01-01

    Objective To quantify the risk of future cardiovascular diseases, cancer, and mortality after pre-eclampsia. Design Systematic review and meta-analysis. Data sources Embase and Medline without language restrictions, including papers published between 1960 and December 2006, and hand searching of reference lists of relevant articles and reviews for additional reports. Review methods Prospective and retrospective cohort studies were included, providing a dataset of 3 488 160 women, with 198 252 affected by pre-eclampsia (exposure group) and 29 495 episodes of cardiovascular disease and cancer (study outcomes). Results After pre-eclampsia women have an increased risk of vascular disease. The relative risks (95% confidence intervals) for hypertension were 3.70 (2.70 to 5.05) after 14.1 years weighted mean follow-up, for ischaemic heart disease 2.16 (1.86 to 2.52) after 11.7 years, for stroke 1.81 (1.45 to 2.27) after 10.4 years, and for venous thromboembolism 1.79 (1.37 to 2.33) after 4.7 years. No increase in risk of any cancer was found (0.96, 0.73 to 1.27), including breast cancer (1.04, 0.78 to 1.39) 17 years after pre-eclampsia. Overall mortality after pre-eclampsia was increased: 1.49 (1.05 to 2.14) after 14.5 years. Conclusions A history of pre-eclampsia should be considered when evaluating risk of cardiovascular disease in women. This association might reflect a common cause for pre-eclampsia and cardiovascular disease, or an effect of pre-eclampsia on disease development, or both. No association was found between pre-eclampsia and future cancer. PMID:17975258

  3. Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model.

    PubMed

    Li, Heng; Ohta, Hidenobu; Tahara, Yu; Nakamura, Sakiko; Taguchi, Kazuaki; Nakagawa, Machiko; Oishi, Yoshihisa; Goto, Yu-Ichi; Wada, Keiji; Kaga, Makiko; Inagaki, Masumi; Otagiri, Masaki; Yokota, Hideo; Shibata, Shigenobu; Sakai, Hiromi; Okamura, Kunihiro; Yaegashi, Nobuo

    2015-10-16

    Pre-eclampsia affects approximately 5% of all pregnant women and remains a major cause of maternal and fetal morbidity and mortality. The hypertension associated with pre-eclampsia develops during pregnancy and remits after delivery, suggesting that the placenta is the most likely origin of this disease. The pathophysiology involves insufficient trophoblast invasion, resulting in incomplete narrow placental spiral artery remodeling. Placental insufficiency, which limits the maternal-fetal exchange of gas and nutrients, leads to fetal intrauterine growth restriction. In this study, in our attempt to develop a new therapy for pre-eclampsia, we directly rescued placental and fetal hypoxia with nano-scale size artificial oxygen carriers (hemoglobin vesicles). The present study is the first to demonstrate that artificial oxygen carriers successfully treat placental hypoxia, decrease maternal plasma levels of anti-angiogenic proteins and ameliorate fetal growth restriction in the pre-eclampsia rat model.

  4. Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model

    PubMed Central

    Li, Heng; Ohta, Hidenobu; Tahara, Yu; Nakamura, Sakiko; Taguchi, Kazuaki; Nakagawa, Machiko; Oishi, Yoshihisa; Goto, Yu-ichi; Wada, Keiji; Kaga, Makiko; Inagaki, Masumi; Otagiri, Masaki; Yokota, Hideo; Shibata, Shigenobu; Sakai, Hiromi; Okamura, Kunihiro; Yaegashi, Nobuo

    2015-01-01

    Pre-eclampsia affects approximately 5% of all pregnant women and remains a major cause of maternal and fetal morbidity and mortality. The hypertension associated with pre-eclampsia develops during pregnancy and remits after delivery, suggesting that the placenta is the most likely origin of this disease. The pathophysiology involves insufficient trophoblast invasion, resulting in incomplete narrow placental spiral artery remodeling. Placental insufficiency, which limits the maternal-fetal exchange of gas and nutrients, leads to fetal intrauterine growth restriction. In this study, in our attempt to develop a new therapy for pre-eclampsia, we directly rescued placental and fetal hypoxia with nano-scale size artificial oxygen carriers (hemoglobin vesicles). The present study is the first to demonstrate that artificial oxygen carriers successfully treat placental hypoxia, decrease maternal plasma levels of anti-angiogenic proteins and ameliorate fetal growth restriction in the pre-eclampsia rat model. PMID:26471339

  5. Effect of Sildenafil on Pre-Eclampsia-Like Mouse Model Induced By L-Name.

    PubMed

    Motta, C; Grosso, C; Zanuzzi, C; Molinero, D; Picco, N; Bellingeri, R; Alustiza, F; Barbeito, C; Vivas, A; Romanini, M C

    2015-08-01

    N(omega)-nitro-L-arginine methyl ester (L-NAME) decreases the vasodilator effect of nitric oxide (NO) and induces pre-eclampsia in mouse. Sildenafil inhibits the degradation of nitric oxide and increases vasodilation. This study aimed to determine the effects of sildenafil citrate on angiogenesis and oxidative stress at the maternal foetal interface on pre-eclampsia-like mouse model induced by L-NAME. Twenty pregnant mice were divided into four groups: (i) vehicle control; (ii) L-NAME; (iii) sildenafil; (4) L-NAME+sildenafil. L-NAME was administered from day 7 of pregnancy and sildenafil from day 8 until day 16; animals were euthanized on day 17. Placental and foetal sizes and weights were measured; lipid peroxide levels and catalase activity in placental homogenates were determined, and placental vascular endothelia were identified by lectin-histochemistry using BSA-I lectin. Western blot analysis was used to determine VEGF expression in placental homogenates. No changes were seen in placental and foetal development in mice with normal pregnancies treated with sildenafil. Treatments with L-NAME reduced significantly the placental weight and average height and decreased the percentage of the endothelial surface. These alterations may be mediated by the reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L-NAME on nitric oxide synthase (NOS) synthesis. This effect was offset by the treatment with sildenafil, with an increase in the percentage of the endothelial surface. In conclusion, our results indicate that treatment with sildenafil on pre-eclampsia mouse model can be used without adverse effects on the concept and its use in the treatment of pre-eclampsia is promising.

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    1997-01-01

    During human placental development, cytotrophoblast stem cells differentiate and invade the uterus. Simultaneously, the cells modulate their expression of several classes of stage-specific antigens that mark transitions in the differentiation process and play a role in either uterine invasion (integrin cell-extracellular matrix receptors and matrix metalloproteinase-9) or immune interactions (HLA-G). The pregnancy disease pre-eclampsia is associated with shallow cytotrophoblast invasion. Previously we showed, by immunofluorescence localization on placental tissue, that in pre-eclampsia invasive cytotrophoblasts fail to properly modulate their integrin repertoire. This finding suggests possible abnormalities in the differentiation pathway that leads to uterine invasion. Here we used a culture system that supports this differentiation process to compare the differentiative and invasive potential of cytotrophoblasts obtained from control (n = 8, 22 to 38 weeks) and pre-eclamptic (n = 9, 24 to 38 weeks) placentas. In culture, the cells from pre-eclamptic placentas failed to properly modulate alpha1 integrin and matrix metalloproteinase-9 expression at the protein and mRNA levels. Their invasive potential was also greatly reduced. Likewise, the cells failed to up-regulate HLA-G protein and mRNA expression. These results suggest that defective cytotrophoblast differentiation/invasion can have significant consequences to the outcome of human pregnancy (ie, development of pre-eclampsia) and that, by the time delivery becomes necessary, the defect is not reversed by removing the cells from the maternal environment. Images Figure 1 Figure 2 Figure 5 Figure 6 Figure 9 PMID:9403732

  9. Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth

    PubMed Central

    Law, Kai P.; Han, Ting-Li; Tong, Chao; Baker, Philip N.

    2015-01-01

    Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered. PMID:26006232

  10. Mass spectrometry-based proteomics for pre-eclampsia and preterm birth.

    PubMed

    Law, Kai P; Han, Ting-Li; Tong, Chao; Baker, Philip N

    2015-01-01

    Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered. PMID:26006232

  11. Pre-eclampsia renamed and reframed: Intra-abdominal hypertension in pregnancy.

    PubMed

    Sawchuck, Diane J; Wittmann, Bernd K

    2014-11-01

    This hypothesis proposes pre-eclampsia is caused by intra-abdominal hypertension in pregnancy. Sustained or increasing intra-abdominal pressure ⩾12mmHg causes impaired venous return to the heart, systemic vascular resistance, ischemia reperfusion injury, intestinal permeability, translocation of lipopolysaccharide endotoxin to the liver, cytotoxic immune response, systemic inflammatory response, pressure transmission to thoracic and intra-cranial compartments, and multi-organ dysfunction. This hypothesis is predicated on Pascal's law, evidence founded in the intra-abdominal hypertension literature, and the adapted equation ΔIAP-P=ΔIAVF/Cab, where ΔIAP-P=change in intra-abdominal pressure in pregnancy, ΔIAVF=change in intra-abdominal vector force (volume and force direction) and Cab=abdominal compliance. Factors causing increased intra-abdominal pressure in pregnancy include: progressive uterine expansion, obstetrical factors that increase intra-uterine volume excessively or acutely, maternal anthropometric measurements that affect intra-abdominal pressure thresholds, maternal postures that increase abdominal force direction, abdominal compliance that is decreased, diminished with advancing gestation, or has reached maximum expansion, habitation at high altitude, and rapid drops in barometric pressure. We postulate that the threshold for lipopolysaccharide translocation depends on the magnitude of intra-abdominal pressure, the intestinal microbiome complex, and the degree of intestinal permeability. We advance that delivery cures pre-eclampsia through the mechanism of abdominal decompression.

  12. Risk factors for pre-eclampsia/eclampsia among working women in Mexico City.

    PubMed

    Cerón-Mireles, P; Harlow, S D; Sánchez-Carrillo, C I; Núñez, R M

    2001-01-01

    This study examined risk factors for pre-eclampsia/eclampsia in a population-based sample of pregnant working women in Mexico City. Over a 3-month period, all women who gave birth at three major hospitals and who had worked for at least 3 months during pregnancy were interviewed. After excluding mothers with multiple gestations or infants with birth defects, and previous diagnoses of hypertension, chronic renal disease or diabetes, 131 of 2,436 women (5.4%) had been diagnosed with pre-eclampsia and/or eclampsia. The frequency was much higher among women of low socio-economic status: 12% of uninsured women (SSA) compared with 4.2% of private sector employees (IMSS) and 1.3% of public sector employees (ISSSTE). After adjusting for education, women working in services (OR = 1.68, 95% CI = 1.01, 2.81) and in retail (OR = 1.99, 95% CI = 1.18, 3.37), primiparae (OR = 2.64, 95% CI = 1.65, 4.21) and women whose pregestational weight was > or = 55 kg (OR = 2.02, 95% CI = 1.34, 3.04) were at increased risk. Efforts to develop and evaluate intervention programmes should target hospitals serving the uninsured (SSA) if reduction in the number of preventable maternal deaths in Mexico is to be achieved. Such programmes should also target service and retail workers and identify women with poor glycaemic control early in pregnancy.

  13. Immunological analogy between allograft rejection, recurrent abortion and pre-eclampsia - the same basic mechanism?

    PubMed

    Wilczyński, Jacek R

    2006-07-01

    There are still controversies concerning the role of immunological mechanisms engaged both in recurrent abortions (RA) and pre-eclampsia (PE). According to some opinions, recurrent miscarriage is comparable to organ-specific autoimmune disease. Analysis of immune reactions shows that graft rejection shares many similar mechanisms with RA and PE. This fact allows us to conclude that rejection of transplanted alloantigenic organs and pregnancy loss have probably the same evolutionary origin. Subsets and functions of immunocompetent cells (T CD4, suppressor gammadeltaT, cytotoxic T CD8, Treg, Tr1, uterine NK cells), over-activation of innate immunity (activation of NK cytotoxic cells, macrophages, neutrophils and complement), changes of Th1/Th2 cytokine balance (IL-2, IL-12, IL-15, IL-18, IFNgamma, TNFalpha vs. IL-4, IL-10, TGFbeta), importance of HLA-G molecule, CD200/CD200R interaction, over-expression of adhesion molecules, fgl2 prothrombinase activation and stimulation of IDO and HO expression, all suggest that RA and PE are syndromes of fetal allograft rejection, and not organ-specific autoimmune diseases. According to that supposition, an analogy might exist between acute graft rejection and recurrent abortion, and between chronic graft rejection and pre-eclampsia. PMID:16829304

  14. Reduced Heart Rate Variability and Altered Cardiac Conduction after Pre-Eclampsia

    PubMed Central

    Murphy, Malia S. Q.; Seaborn, Geoffrey E. J.; Redfearn, Damian P.; Smith, Graeme N.

    2015-01-01

    Pre-eclampsia is a hypertensive disorder of pregnancy that is associated with elevated maternal risk for cardiovascular disease. The aims of this study were to determine the effect of normal pregnancy on postpartum parameters of the electrocardiogram, and furthermore to determine how a history of pre-eclampsia may affect these parameters. Ten-minute high-resolution (1000 Hz) orthogonal Holter electrocardiogram (ECG) recordings were used to measure heart rate variability (HRV). Signal-averaged P-wave and QRS complex durations were determined. Participants included non-pregnant controls, normotensive parous controls and women with a recent history of PE. While reductions in HRV induced by uncomplicated pregnancy returned to non-pregnant levels by 6–8 months postpartum HRV remained reduced in women with a history of PE compared to control groups. In addition, P-Wave and QRS complex durations were prolonged in PE subjects at 6–8 months postpartum compared to control groups. Only QRS duration was independent of differences in blood pressure. These results suggest increased sympathetic cardiac activity, and delayed myocardial conduction in women after PE; alterations consistent with cardiac remodeling and increased risk for arrhythmia. In examining the association between PE and cardiovascular disease, identification of ECG abnormalities soon after pregnancy in women with a history of PE highlights a unique opportunity for early identification and screening in this population before other risk factors become apparent. PMID:26407294

  15. Pre-eclampsia renamed and reframed: Intra-abdominal hypertension in pregnancy.

    PubMed

    Sawchuck, Diane J; Wittmann, Bernd K

    2014-11-01

    This hypothesis proposes pre-eclampsia is caused by intra-abdominal hypertension in pregnancy. Sustained or increasing intra-abdominal pressure ⩾12mmHg causes impaired venous return to the heart, systemic vascular resistance, ischemia reperfusion injury, intestinal permeability, translocation of lipopolysaccharide endotoxin to the liver, cytotoxic immune response, systemic inflammatory response, pressure transmission to thoracic and intra-cranial compartments, and multi-organ dysfunction. This hypothesis is predicated on Pascal's law, evidence founded in the intra-abdominal hypertension literature, and the adapted equation ΔIAP-P=ΔIAVF/Cab, where ΔIAP-P=change in intra-abdominal pressure in pregnancy, ΔIAVF=change in intra-abdominal vector force (volume and force direction) and Cab=abdominal compliance. Factors causing increased intra-abdominal pressure in pregnancy include: progressive uterine expansion, obstetrical factors that increase intra-uterine volume excessively or acutely, maternal anthropometric measurements that affect intra-abdominal pressure thresholds, maternal postures that increase abdominal force direction, abdominal compliance that is decreased, diminished with advancing gestation, or has reached maximum expansion, habitation at high altitude, and rapid drops in barometric pressure. We postulate that the threshold for lipopolysaccharide translocation depends on the magnitude of intra-abdominal pressure, the intestinal microbiome complex, and the degree of intestinal permeability. We advance that delivery cures pre-eclampsia through the mechanism of abdominal decompression. PMID:25189485

  16. The Prognostic Role of Angiotensin II Type 1 Receptor Autoantibody in Non-Gravid Hypertension and Pre-eclampsia

    PubMed Central

    Lei, Jinghui; Li, Yafeng; Zhang, Suli; Wu, Ye; Wang, Pengli; Liu, Huirong

    2016-01-01

    Abstract Angiotensin II type 1 receptor autoantibody (AT1-AA) is found in patients with non-gravid hypertension or pre-eclampsia, but the relationship is uncertain. The aim of the present study was to assess the association between AT1-AA and high blood pressure using meta-analysis, and to evaluate the prognosis value of AT1-AA for hypertensive diseases. Literature search from PubMed, Embase, and Cochrane databases were conducted using keywords “hypertension” or “pre-eclampsia,” “angiotensin II receptor type 1 autoantibody,” and its aliases from April 1999 to December 2015. Studies evaluating the association between AT1-AA and non-gravid hypertension or pre-eclampsia were included in this analysis. The quality of the eligible studies was assessed based on the Newcastle–Ottawa Scale with some modifications. Two researchers then independently reviewed all included studies and extracted all relevant data. Association between AT1-AA and hypertension was tested with pooled odds ratios (ORs) and 95% confidence intervals (CIs). Finally, we evaluated whether AT1-AA predicted the prognosis of hypertension by using a summary receiver-operating characteristic (ROC) curve and sensitivity analysis. Ten studies were finally included in this meta-analysis. AT1-AA showed more significant association with pre-eclampsia than that with non-gravid hypertension (pooled OR 32.84, 95% CI 17.19–62.74; and pooled OR 4.18, 95% CI 2.20–7.98, respectively). Heterogeneity among studies was also detected probably due to different hypertensive subtypes and AT1-AA measuring methods. Area under summary ROC curve (AUC) of pre-eclampsia was 0.92 (sensitivity 0.76; specificity 0.86). Area under the ROC curve of overall hypertensive diseases or non-gravid hypertension was lower than that of pre-eclampsia (0.86 and 0.72, respectively) with lower sensitivities (0.46 and 0.26, respectively). The major limitation of this analysis was the publication bias due to lack of unpublished data

  17. TH17- and IL-17- mediated autoantibodies and placental oxidative stress play a role in the pathophysiology of pre-eclampsia

    PubMed Central

    CORNELIUS, D. C.; LAMARCA, B.

    2016-01-01

    Pre-eclampsia is a multisystem disorder of pregnancy that affects 5–8% of pregnancies. The pathophysiologic mechanisms that lead to the development of pre-eclampsia are poorly understood. Higher than normal levels of circulating TH17 is observed in preeclamptic women compared to women with normal pregnancy. TH17 cells are a subset of CD4+ T helper cells that are characterized by their secretion of IL-17. Recent studies suggest a role for TH17 cells and IL-17 in the pathophysiology of pre-eclampsia. In this review, we will discuss the known function of TH17 cells and IL-17 in immunity and vascular function. We will then review the role of IL-17 and TH17 cells in normal pregnancy and their association with pre-eclampsia, followed by a discussion of the literature to examine a potential role for IL-17 and TH17 cells in mediating pathophysiology in pre-eclampsia. PMID:24971780

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

    PubMed

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

    2015-01-20

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

  19. Lack of platelet activation reflected by circulating soluble glycoprotein V in pre-eclampsia.

    PubMed

    Acar, K; Sucak, A; Beyazit, Y; Genc, G; Haznedaroglu, I C; Aksu, S; Danisman, N

    2007-01-01

    Pre-eclampsia (PE) is a human pregnancy-specific disorder of unknown aetiology. Although the quantitative relationship between platelet aggregation in PE is not clearly defined yet, we aimed to investigate the possible relationship between PE and platelet glycoprotein V (GPV), which is an integral platelet membrane protein involved in the function of the GPIb-V-IX receptor. Fifty patients with PE and 37 normotensive pregnant women (controls) were enrolled in this study. Fasting blood samples were collected and soluble GPV (sGPV) levels were determined using a commercially available enzyme immunoassay. No statistically significant difference in sGPV was found between PE patients and control subjects. There was no correlation between sGPV and platelet counts or between pregnancy duration and platelet counts. Further clinical and experimental investigations are needed to elucidate the pathological processes involved in the development of PE in complicated pregnancies.

  20. Association of single nucleotide polymorphisms in the human tumor necrosis factor-α and interleukin 1-β genes in patients with pre-eclampsia.

    PubMed

    Mohajertehran, Farnaz; Tavakkol Afshari, Jalil; Rezaieyazdi, Zahra; Ghomian, Nayereh

    2012-09-01

    Pre-eclampsia is a pregnancy-specific syndrome that may be dangerous especially to the fetus. Different cytokines have been found to be elevated in women with pre-eclampsia and may have possible roles in the development of this disorder. Alleles of the interleukin-l-beta (IL-lβ) and tumor necrosis factor alpha (TNF-α) genes are associated with pr-eeclampsia in several studies in different populations. The aim of the present study was to investigate the relationship between IL-lβ (C+3954T) and TNF-α (G-308A) gene polymorphisms with pre-eclampsia in north east of Iran (Khorasan province).This study included 54 diagnosed patients with pre-eclampsia and 50 normal pregnant women as control group. DNA was extracted from peripheral blood and the polymorphisms were determined by PCR-RFLP method. Data was analyzed using chi-square and Fisher's exact tests.There was significant association between TNF-α (G-308A) genotype and pre-eclampsia (p=0.001) but we did not find any significant association between IL-lβ (C+3954T) genotype and pre-eclampsia (p=0.39).The present study might suggest a role for TNF-α in the development of pre-eclampsia; however, IL-lβ (C+3954T) polymorphism could not be considered as a marker of susceptibility to preeclampsia in our population.

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

    PubMed

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

    2006-01-01

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

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

    SciTech Connect

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

    1982-01-01

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

  3. Placental expression of eNOS, iNOS and the major protein components of caveolae in women with pre-eclampsia.

    PubMed

    Smith-Jackson, K; Hentschke, M R; Poli-de-Figueiredo, C E; Pinheiro da Costa, B E; Kurlak, L O; Broughton Pipkin, F; Czajka, A; Mistry, H D

    2015-05-01

    Caveolae regulate many cardiovascular functions and thus could be of interest in relation to pre-eclampsia, a pregnancy specific disorder characterised by hypertension and proteinuria. We examined placental mRNA and protein expression/localisation of the caveolae components Caveolin 1-3, Cavin 1-4 as well as eNOS/iNOS in normotensive control (n = 24) and pre-eclamptic pregnancies (n = 19). Placental mRNA expression of caveolin-1, cavin 1-3, was lower and eNOS expression was increased in pre-eclampsia (P < 0.05 for all). Additionally Caveolin-1 protein expression was also reduced in pre-eclampsia (P = 0.007); this could be an adaptive response in pre-eclampsia, possibly to attenuate the oxidative stress/inflammation. PMID:25707739

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Elliot, Michael G.; Crespi, Bernard J.

    2015-01-01

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

  6. Restraint of Trophoblast Invasion of the Uterus by Decorin: Role in Pre-eclampsia.

    PubMed

    Nandi, Pinki; Siddiqui, Mohammad Fyyaz; Lala, Peeyush K

    2016-03-01

    Decorin (DCN) is a leucine-rich, TGF-β binding proteoglycan produced by mesenchymal cells including chondrocytes, dermal fibroblasts, and uterine decidual cells. It exerts multiple physiological functions including collagen fibrillogenesis, myogenesis, angiostasis, and restraining placental invasiveness. We discovered that decidua-derived DCN restrains proliferation, migration, and invasion of extravillous trophoblast (EVT) cells of the human placenta in a TGF-β-independent manner. These functions were differentially mediated by binding of DCN to multiple tyrosine kinase receptors (TKR) including EGFR, IGFR1, and VEGFR2. DCN blocked VEGFR-2 dependent EVT cell migration and endovascular differentiation by inhibiting P38MAPK and ERK1/2 pathways.We identified the avid VEGFR2 binding site in DCN protein as a 12 amino acids (LGTNPLKSSGIE) span in the Leucine-rich-repeat (LRR) 5 region of domain III. A single amino acid mutation (substitution of K to A) of DCN at this site abrogated VEGFR-2- dependent DCN actions. Also, DCN mRNA expression, measured with in situ hybridization, was selectively upregulated in decidual cells in placentas from mothers suffering from pre-eclampsia (PE), whereas the expression levels remained unchanged in chorionic villus mesenchymal cells. This difference between PE and control placentas was present at all gestational ages, indicating the pathogenic role of DCN in PE. We hypothesize that increased blood DCN levels could be a candidate biomarker for PE. PMID:26554635

  7. Polymorphisms of the IL27 gene in a Chinese Han population complicated with pre-eclampsia

    PubMed Central

    Liu, Bin; Li, Yuan; Yao, Yuan; Li, Hua; Liang, Hongda; Xin, Miaomiao; Wang, Liqin; Zhao, Lei; Lin, Jizheng; Liu, Shiguo

    2016-01-01

    IL-27 could inhibit the development of Th17 cells, and the Th17/regulatory T-cell imbalance may reverse maternal tolerance in pre-eclampsia (PE). The aim of this study was to investigate the association between genetic polymorphisms in IL27 with PE. Three SNPs in IL27 (rs153109, rs17855750, and rs181206) were genotyped in a Chinese Han cohort of 1040 PE patients and 1247 normal pregnant women using the TaqMan allelic discrimination real-time PCR method. The CC genotypic distribution of rs153109 was significantly higher among cases than controls (19.1% versus 13.3%, odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.23–1.93, p < 0.001), and the CT genotype was found to be significantly lower in cases than controls (41.7% versus 49.0%, OR: 0.74, 95% CI: 0.63–0.88, p < 0.001), disputing existing reports indicating the allele frequency of rs153109 is not significantly different between PE patients and controls. Additionally, the CC genotype of rs153109 was significantly more prevalent in PE cases than controls using a recessive model (p < 0.001). The allelic and genotypic frequencies of rs17855750 and rs181206 were not significantly different between two groups. Our results reveal that IL27 polymorphisms may be involved in the development of PE in Chinese Han population. PMID:26971578

  8. Pre-eclampsia has an adverse impact on maternal and fetal health.

    PubMed

    Lin, Saunders; Leonard, Dean; Co, Mary A M; Mukhopadhyay, Dhriti; Giri, Badri; Perger, Lena; Beeram, Madhava R; Kuehl, Thomas J; Uddin, Mohammad N

    2015-04-01

    Pre-eclampsia (preE) is a multifaceted complication found uniquely in the pregnant patient and one that has puzzled scientists for years. PreE is not a single disorder, but a complex syndrome that is produced by various pathophysiological triggers and mechanisms affecting about 5% of obstetrical patients. PreE is a major cause of premature delivery and maternal and fetal morbidity and mortality. PreE is characterized by de novo development of hypertension and proteinuria after 20 weeks of gestation and affects nearly every organ system, with the most severe consequences being eclampsia, pulmonary edema, intrauterine growth restriction, and thrombocytopenia. PreE alters the intrauterine environment by modulating the pattern of hormonal signals and activating the detrimental cellular signaling that has been transported to the fetus. The fetus has to adapt to this intrauterine environment with detrimental signals. The adaptive changes increase the risk of disease later in life. This review defines the predisposition and causes of preE and the cellular signaling detrimental to maternal health during preE. Moreover, the risk factors for diseases that are transmitted to the offspring have been addressed in this review. The detrimental signaling molecules that have been overexpressed in preE patients raises the possibility that those signals could be therapeutically blocked one day. PMID:25468481

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

    PubMed

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

    2012-09-01

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

  10. Polymorphisms of the IL27 gene in a Chinese Han population complicated with pre-eclampsia.

    PubMed

    Liu, Bin; Li, Yuan; Yao, Yuan; Li, Hua; Liang, Hongda; Xin, Miaomiao; Wang, Liqin; Zhao, Lei; Lin, Jizheng; Liu, Shiguo

    2016-01-01

    IL-27 could inhibit the development of Th17 cells, and the Th17/regulatory T-cell imbalance may reverse maternal tolerance in pre-eclampsia (PE). The aim of this study was to investigate the association between genetic polymorphisms in IL27 with PE. Three SNPs in IL27 (rs153109, rs17855750, and rs181206) were genotyped in a Chinese Han cohort of 1040 PE patients and 1247 normal pregnant women using the TaqMan allelic discrimination real-time PCR method. The CC genotypic distribution of rs153109 was significantly higher among cases than controls (19.1% versus 13.3%, odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.23-1.93, p < 0.001), and the CT genotype was found to be significantly lower in cases than controls (41.7% versus 49.0%, OR: 0.74, 95% CI: 0.63-0.88, p < 0.001), disputing existing reports indicating the allele frequency of rs153109 is not significantly different between PE patients and controls. Additionally, the CC genotype of rs153109 was significantly more prevalent in PE cases than controls using a recessive model (p < 0.001). The allelic and genotypic frequencies of rs17855750 and rs181206 were not significantly different between two groups. Our results reveal that IL27 polymorphisms may be involved in the development of PE in Chinese Han population. PMID:26971578

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

    PubMed Central

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

    2013-01-01

    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. PMID:23507553

  12. Hypomethylation of the LEP gene in placenta and elevated maternal leptin concentration in early onset pre-eclampsia.

    PubMed

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

    2013-03-10

    In pre-eclampsia, placental leptin is up-regulated and leptin is elevated in maternal plasma. To investigate potential epigenetic regulation of the leptin (LEP) gene in normal and complicated pregnancy, DNA methylation was assessed at multiple reported regulatory regions in placentae from control pregnancies (n=111), and those complicated by early onset pre-eclampsia (EOPET; arising <34 weeks; n=19), late onset pre-eclampsia (LOPET; arising ≥34 weeks; n=18) and normotensive intrauterine growth restriction (nIUGR; n=13). The LEP promoter was hypomethylated in EOPET, but not LOPET or nIUGR placentae, particularly at CpG sites downstream of the transcription start site (-10.1%; P<0.0001). Maternal plasma leptin was elevated in EOPET and LOPET (P<0.05), but not nIUGR, compared with controls. EOPET cases showed a trend towards biallelic LEP expression rather than skewed allelic expression observed in control placentae, suggesting that loss of normal monoallelic expression at the LEP locus is associated with hypomethylation, leading to increased overall LEP expression.

  13. Prospective assessment of neurodevelopment in children following a pregnancy complicated by severe pre-eclampsia

    PubMed Central

    Warshafsky, Chelsie; Walker, Mark; Wen, Shi-Wu; Smith, Graeme N

    2016-01-01

    Objective To prospectively examine whether children of women with a pregnancy affected by severe pre-eclampsia (PE), compared to children of women without a PE-affected pregnancy, have differences in neurodevelopmental performance up to 5 years of age. Design Prospective cohort study. Setting Tertiary care centre. Participants Women were recruited following a PE-affected pregnancy. After each PE participant was recruited, the next normotensive woman without a prior history of PE and matched by parity, maternal age and race was invited to participate. Women with a history of chronic hypertension, diabetes or renal disease were excluded. Total enrolment included 129 PE-affected and 140 normotensive mothers. Outcome measures The primary outcome measure was failure of the Ages and Stages Questionnaire (ASQ). The ASQ was completed yearly, until age 5. Results A significant difference was found in the proportion of ASQ categories failed in year 3 (p<0.05), and this approached significance in years 1 and 4 (p<0.10 and p<0.15, respectively). At year 1, the number of ASQ categories failed was significantly greater among children born to PE mothers. A subgroup analysis revealed that a significant proportion of PE children born preterm (<37 weeks) failed the ASQ in years 3 and 4 (p<0.05), and when failed, those who were preterm failed significantly more categories (p<0.05). A trend towards increased failure in the gross motor category was found. There was a significant positive correlation between maternal lifetime CVD risk score and number of ASQ categories failed at years 1 and 3 (p<0.05). Conclusions Severe PE is associated with other adverse pregnancy outcomes, including intrauterine growth restriction and preterm birth, all of which are associated with increased neurodevelopment delays. Thus, PE indicates a need for early screening and intervention at the neurodevelopmental level to improve children's long-term health, with larger studies required to tease out

  14. Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis

    PubMed Central

    Wu, Pensée; van den Berg, Caroline; Alfirevic, Zarko; O’Brien, Shaughn; Röthlisberger, Maria; Baker, Philip Newton; Kenny, Louise C.; Kublickiene, Karolina; Duvekot, Johannes J.

    2015-01-01

    Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE. PMID:26404264

  15. Mechanism of vascular dysfunction due to circulating factors in women with pre-eclampsia.

    PubMed

    Kao, Cindy K; Morton, Jude S; Quon, Anita L; Reyes, Laura M; Lopez-Jaramillo, Patricio; Davidge, Sandra T

    2016-04-01

    Circulating factors have been proposed to play a major role in the pathophysiology of endothelial dysfunction in pre-eclampsia (PE), which is defined as new-onset hypertension with proteinuria after 20 weeks of gestation. However, the mechanisms leading to altered vascular reactivity remain unclear. We hypothesized that circulating factors lead to endothelial dysfunction by increasing oxidative stress and reducing nitric oxide (NO) and prostaglandin (PG) bioavailability. Pregnant rat uterine and mesenteric arteries were incubated overnight with 3% normotensive (NP) or PE plasma collected from women upon admission to hospital. Responses to methacholine (MCh) were obtained using wire myography to assess endothelial function pathways. Vascular superoxide level was measured via dihydroethidium staining and nitric oxide synthase (NOS) expression via Western blots. PE plasma significantly increased superoxide levels and impaired endothelial dysfunction in uterine arteries (Emax 79.9±5.6% compared with 44.9±6.3%, P=0.0004), which was restored in the presence of oxidant scavengers or PG synthesis inhibition. Uterine artery vasodilation was abolished in the presence of pan-NOS inhibitor (P<0.0001) in both NP- and PE-treated vessels, but inducible nitric oxide synthase (iNOS)-dependent vasodilation was present only in NP-treated arteries. Uterine arteries exposed to PE plasma exhibit an increased endothelial NOS expression and a decreased iNOS expression. PE plasma did not alter endothelial function in mesenteric arteries, suggesting that the effect of circulating factors was vascular-bed-specific. We have shown that circulating factors lead to endothelial dysfunction via altered oxidative stress and vasodilator pathways. The present study contributes to our understanding of the pathophysiology and finding a potential target for intervention in PE.

  16. Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis.

    PubMed

    Wu, Pensée; van den Berg, Caroline; Alfirevic, Zarko; O'Brien, Shaughn; Röthlisberger, Maria; Baker, Philip Newton; Kenny, Louise C; Kublickiene, Karolina; Duvekot, Johannes J

    2015-01-01

    Pre-eclampsia (PE) complicates 2%-8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39-0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE. PMID:26404264

  17. Pre-eclampsia (PE) and Chorionicity in Women with Twin Gestations

    PubMed Central

    Singh, Anupama; Singh, Arati; Surapaneni, Tarakeswari; Nirmalan, Praveen Kumar

    2014-01-01

    Background: Pre-Eclampsia (PE) affects 6-31% of pregnant women with multiple gestations. There are conflicting reports on the association of PE with Chorionicity and zygosity; however, there is a lack of information on this potential association in a population of pregnant Asian Indian women. Aim: To determine as to whether chorionicity and zygosity were associated with PE in a population of Asian Indian women with twin gestations. Settings and Design: A retrospective observational study was done at a single tertiary care centre in Southern India. Material and Methods: The study included pregnant women with twin gestations, who was delivered at the study institute in 2012. Hypertension in pregnancy was categorized, based on the criteria of the International Society for the Study of Hypertension in Pregnancy. Chorionicity was determined by using ultrasonography and zygosity was determined, based on clinical criteria. Point estimates and the 95% Confidence Intervals (CI) around point estimates of PE and associations of chorionicity and zygosity with PE were determined by using bivariate analysis, logistic regression models and area under Receiver Operator Characteristic (ROC) curves. Results: This study included 208 women with twin gestations. The incidence of PE in dichorionic twin gestations was 13.17% (n=22, 95% CI: 8.66, 18.96), it was 4.87% (n=2, 95% CI: 0.83, 15.19) in monochorionic twin gestations, it was 16.36% (n=9, 95% CI: 8.29, 27.91) in dizygous twin gestations and it was 4.88% (n=2, 95% CI: 0.83, 15.19) in monozygous twin gestations. Neither chorionicity (adjusted OR: 2.59, 95% CI: 0.55, 12.19) nor zygosity (adjusted OR 2.72, 95% CI: 0.49, 15.13) were associated with PE In a multivariate logistic regression model. Conclusion: Although it was not statistically significant, the clinical incidence of PE was higher in dichorionic and dizygous twin gestations. PMID:24596736

  18. Maternal ophthalmic artery Doppler velocimetry in pre-eclampsia in Southwestern Nigeria

    PubMed Central

    Olatunji, Richard Busayo; Adekanmi, Ademola Joseph; Obajimi, Millicent Olubunmi; Roberts, Olumuyiwa Adebola; Ojo, Temitope Olumuyiwa

    2015-01-01

    Background Pre-eclampsia (PE) poses a serious challenge to maternal and fetal health in Africa. It is associated with hemodynamic changes that may affect the internal carotid/ophthalmic artery circulation with consequent neuro-ophthalmic manifestations. Ophthalmic artery Doppler (OAD) ultrasound is an important tool that can be used to detect hemodynamic changes in PE and monitor its severity. In this study, we evaluated hemodynamic changes on OAD ultrasound in the ophthalmic arteries of pre-eclamptic women and compared these with values in healthy pregnant women. Methods OAD parameters, such as, peak systolic velocity, peak diastolic velocity, end diastolic velocity, pulsatility index, and peak ratio, were measured on transorbital triplex ultrasound scan with a 7–10 MHz multifrequency linear transducer in 42 consenting pre-eclamptic patients and 41 pregnant controls matched for maternal age, gestational age, and parity at the Department of Radiology, University College Hospital, Ibadan. Univariate, bivariate, and receiver operating characteristic curve data analyses were performed. P<0.05 was considered to be statistically significant. Results Mean resistivity index, pulsatility index, and peak systolic velocity were significantly lower in pre-eclamptic patients than in the controls. Mean peak diastolic velocity, end diastolic velocity, and peak ratio were significantly higher in the pre-eclamptic group. The receiver operating characteristic curve showed that the resistivity index (sensitivity 75%, specificity 77.8%) could distinguish mild from severe PE while the peak ratio (sensitivity 90.5%, specificity 81.3%) could accurately detect PE. Conclusion OAD ultrasound can be used to monitor patients with PE for early detection of progression to severe forms before cerebral complications develop. OAD screening of patients at high risk for PE can also detect early changes of hemodynamic derangement. PMID:26229508

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

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

    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.

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

    PubMed Central

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

    2013-01-01

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

  1. Placental Chemokine Receptor D6 Is Functionally Impaired in Pre-Eclampsia

    PubMed Central

    Maulucci, Giuseppe; Rolfo, Alessandro; Giuffrida, Domenica; Veglia, Manuela; De Spirito, Marco; Scambia, Giovanni; Todros, Tullia; Di Simone, Nicoletta

    2016-01-01

    Background Pre-eclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality worldwide. It is defined by new onset of hypertension and proteinuria after the 20th week of gestation and characterized by systemic exaggerated inflammatory response. D6 is a chemokines scavenger receptor that binds with high affinity CC chemokines, internalizes and targets the ligands for degradation. It is expressed in trophoblast-derived tissues and prevents excessive placenta leukocyte infiltration.The aim of this study was to investigate the expression and function of D6 in human placentae from pre-eclamptic and healthy pregnant women. Methods and Results Plasma levels of D6-binding CC chemokines (CCL-2, CCL-3, CCL-4, CCL-7, CCL-11) and pro-inflammatory cytokines (IL-6, TNF-α, CRP) were analyzed in 37 healthy pregnant women and 38 patients with PE by multiplex bead assay. Higher circulating levels of CCL7, CCL11, IL-6, (p<0.0001) and CRP (p<0.05) were observed in PE women compared to controls. Levels of circulating CCL4 were decreased in PE (p<0.001), while no significant differences of CCL2, CCL3 or TNF-α levels were detected. Immunofluorescent staining of placental sections showed higher expression of D6 receptor in the PE syncytiotrophoblast. Confocal and Western blot (WB) analyses revealed a prevalent distribution of D6 in trophoblast cells membranes in PE. Increased activation of D6 intracellular pathway was observed by Western blot analyses of p-LIMK and p-cofilin in trophoblast cell lysates. D6 functional assays showed reduced scavenging of CCL2 in PE cells compared to controls. Since actin filaments spatial assembling is essential for D6 intracellular trafficking and scavenging activity, we investigated by confocal microscopy trophoblast cytoskeleton organization and we observed a dramatic disarrangement in PE compared to controls. Conclusions our results suggest membrane distribution of D6 receptor on trophoblast cell membranes in PE, together with

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

    PubMed Central

    2013-01-01

    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 < 0.001). Most facilities had the drugs and supplies needed to treat severe PE/E, including the preferred anticonvulsant, magnesium sulfate (MgSO4). One-third of the smallest facilities and half of larger facilities reported administering a second-line drug, diazepam, in some cases. In the case scenario, 96% of doctors and 89% of midwives recognized that MgSO4 should be used to manage severe PE/E, but 42% of doctors and 58% of midwives also thought diazepam had a role to play. Providers who were trained on the use of MgSO4 scored significantly higher than untrained providers on six of 20 items in the case scenario. Providers at larger facilities significantly outscored those at smaller facilities on five items. There

  3. T594M mutation of the epithelial sodium channel beta-subunit gene in pre-eclampsia and eclampsia in Black South African women.

    PubMed

    Pegoraro, R J; Roberts, C B; Rom, L; Moodley, J

    2004-09-01

    The possible role of the beta-subunit of the epithelial sodium channel T594M polymorphism in hypertensive disorders of pregnancy has not been examined. This study compared Black South African women with pre-eclampsia (n= 204), early onset pre-eclampsia (n= 67), eclampsia (n= 120) and gestational hypertension (n= 78) with 338 women from the same ethnic group who had full-term normotensive pregnancies, for the presence of the T594M polymorphism. The variant allele was detected in 1.7% to 3.8% of the various patient groups and in 3.6% of the control group reflecting no significant difference. These results suggest that the T594M polymorphism in the sodium channel beta-subunit is not associated with the pathogenesis of pre-eclampsia or gestational hypertension. PMID:15327619

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

    PubMed Central

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

    2007-01-01

    CD4+ CD25bright regulatory T (Treg) cells have been identified as a principle regulator of tolerance during pregnancy. In the setting of pre-eclampsia, however, little is known about the dynamics of these cells. In the current study, we determined CD4+ CD25bright Treg cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3+) cells at the placental bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC) of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non-pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were included. We found the percentage of CD25bright cells within the CD4+ T cell population in PBMC was reduced significantly in both Japanese and Polish pre-eclamptic cases than in normal pregnancy subjects (P < 0·001) and non-pregnant healthy controls (P < 0·001). Also, the percentage of FoxP3+ cells within CD3+ T cells in the placental bed biopsy samples of pre-eclamptic cases were decreased compared to those in normal pregnancy subjects. These findings suggest that a decreased number of Treg cells was present in pre-eclampsia, and these changes might break the maternal tolerance to the fetus. PMID:17459078

  5. Clinical accuracy of a low cost portable blood pressure device in pregnancy and pre-eclampsia: the Nissei DS-400.

    PubMed

    de Greeff, Annemarie; Shennan, Andrew H

    2015-07-01

    Hypertensive disorders of pregnancy cause significant maternal morbidity and mortality worldwide, particularly in developing countries. This study evaluated the accuracy of the Nissei DS-400, a low cost blood pressure (BP) device, in pregnancy according to the British Hypertension Society protocol. Forty-five pregnant women (15 with pre-eclampsia), were recruited from a large teaching hospital. Nine sequential same-arm BP measurements were taken from each woman by trained observers, alternating between mercury sphygmomanometry and the device. The Nissei DS-400 achieved the highest accuracy grade (A/A) in all subjects (n = 45) and in pregnancy alone (n = 30). The mean difference ± standard deviation between the standard and the device in pregnancy were -1.0 ± 5.1 mmHg and -1.1 ± 5.0 mmHg for systolic and diastolic BP, respectively, and -2.6 ± 5.9 mmHg and -3.4 ± 5.8 mmHg in all subjects. The Nissei-DS 400 can be recommended for clinical use in pregnancy and has potential as a good screening tool for pre-eclampsia in low resource settings. PMID:25911652

  6. The Prognostic Role of Angiotensin II Type 1 Receptor Autoantibody in Non-Gravid Hypertension and Pre-eclampsia: A Meta-analysis and Our Studies.

    PubMed

    Lei, Jinghui; Li, Yafeng; Zhang, Suli; Wu, Ye; Wang, Pengli; Liu, Huirong

    2016-04-01

    Angiotensin II type 1 receptor autoantibody (AT1-AA) is found in patients with non-gravid hypertension or pre-eclampsia, but the relationship is uncertain.The aim of the present study was to assess the association between AT1-AA and high blood pressure using meta-analysis, and to evaluate the prognosis value of AT1-AA for hypertensive diseases.Literature search from PubMed, Embase, and Cochrane databases were conducted using keywords "hypertension" or "pre-eclampsia," "angiotensin II receptor type 1 autoantibody," and its aliases from April 1999 to December 2015.Studies evaluating the association between AT1-AA and non-gravid hypertension or pre-eclampsia were included in this analysis. The quality of the eligible studies was assessed based on the Newcastle-Ottawa Scale with some modifications.Two researchers then independently reviewed all included studies and extracted all relevant data. Association between AT1-AA and hypertension was tested with pooled odds ratios (ORs) and 95% confidence intervals (CIs). Finally, we evaluated whether AT1-AA predicted the prognosis of hypertension by using a summary receiver-operating characteristic (ROC) curve and sensitivity analysis.Ten studies were finally included in this meta-analysis. AT1-AA showed more significant association with pre-eclampsia than that with non-gravid hypertension (pooled OR 32.84, 95% CI 17.19-62.74; and pooled OR 4.18, 95% CI 2.20-7.98, respectively). Heterogeneity among studies was also detected probably due to different hypertensive subtypes and AT1-AA measuring methods. Area under summary ROC curve (AUC) of pre-eclampsia was 0.92 (sensitivity 0.76; specificity 0.86). Area under the ROC curve of overall hypertensive diseases or non-gravid hypertension was lower than that of pre-eclampsia (0.86 and 0.72, respectively) with lower sensitivities (0.46 and 0.26, respectively).The major limitation of this analysis was the publication bias due to lack of unpublished data and the language limitation during

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

    PubMed

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

    2008-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  9. Placental Growth Factor (PlGF) in Women with Suspected Pre-Eclampsia Prior to 35 Weeks’ Gestation: A Budget Impact Analysis

    PubMed Central

    Duckworth, Suzy; Seed, Paul T.; Mackillop, Lucy; Shennan, Andrew H.; Hunter, Rachael

    2016-01-01

    Objective To model the resource implications of placental growth factor (PlGF) testing in women with suspected pre-eclampsia prior to 35 weeks’ gestation as part of a management algorithm, compared with current practice. Methods Data on resource use from 132 women with suspected pre-eclampsia prior to 35 weeks’ gestation, enrolled in a prospective observational cohort study evaluating PlGF measurement within antenatal assessment units within two UK consultant-led maternity units was extracted by case note review. A decision analytic model was developed using these data to establish the budget impact of managing women with suspected pre-eclampsia for two weeks from the date of PlGF testing, using a clinical management algorithm and reference cost tariffs. The main outcome measures of resource use (numbers of outpatient appointments, ultrasound investigations and hospital admissions) were correlated to final diagnosis and used to calculate comparative management regimes. Results The mean cost saving associated with the PlGF test (in the PlGF plus management arm) was £35,087 (95% CI -£33,181 to -£36,992) per 1,000 women. This equated to a saving of £582 (95% CI -552 to -£613) per woman tested. In 94% of iterations, PlGF testing was associated with cost saving compared to current practice. Conclusions This analysis suggests PlGF used as part of a clinical management algorithm in women presenting with suspected pre-eclampsia prior to 35 weeks’ gestation could provide cost savings by reducing unnecessary resource use. Introduction of PlGF testing could be used to direct appropriate resource allocation and overall would be cost saving. PMID:27741259

  10. Prevalence of pre-eclampsia, pregnancy hypertension and gestational diabetes in population-based data: impact of different ascertainment methods on outcomes.

    PubMed

    Chen, Jian Sheng; Roberts, Christine L; Simpson, Judy M; Ford, Jane B

    2012-02-01

    This study investigated strategies for ascertaining pre-eclampsia, pregnancy hypertension and gestational diabetes mellitus from birth records and/or hospital discharge data. The results showed that ascertaining these conditions from a data set that linked birth records to the corresponding maternal hospital record for birth was sufficient for health outcomes research. Antenatal hospital records provided few extra cases and may be necessary only for the ascertainment when a very accurate estimate of the prevalence is required.

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

    PubMed

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

    2009-10-01

    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.

  12. Periconceptional folic acid fortification for the risk of gestational hypertension and pre-eclampsia: a meta-analysis of prospective studies.

    PubMed

    Yang, Xiaorong; Chen, Hui; Du, Yihui; Wang, Shuting; Wang, Zhiping

    2016-10-01

    Published literatures report controversial results about the association of folic acid-containing multivitamins with gestational hypertension and pre-eclampsia. A comprehensive search was performed to identify related prospective studies to assess the effect of folic acid fortification on gestational hypertension and pre-eclampsia. The Q test and I(2) statistic were used to examine between-study heterogeneity. Fixed or random effects models were selected based on study heterogeneity. A funnel plot and modified Egger linear regression test were used to estimate publication bias. Eleven studies conformed to the criteria. Pooled results indicated that folic acid fortification alone was not associated with the occurrence of gestational hypertension [relative risk (RR) = 1.03, 95% confidence interval (CI): 0.98-1.09, P = 0.267] and pre-eclampsia (RR = 0.99, 95% CI: 0.90-1.08, P = 0.738). However, supplementation of multivitamins containing folic acid could prevent gestational hypertension (RR = 0.57, 95% CI: 0.43-0.76, P < 0.001) and pre-eclampsia (RR = 0.64, 95% CI: 0.48-0.84, P = 0.001). The difference between folic acid fortification alone and multivitamins containing folic acid was significant. This meta-analysis suggests that periconceptional multivitamin supplementation with appropriate dose, not folic acid alone, is an appropriate recommendation for pregnant women. The effect should be further confirmed by conducting large-scale randomised controlled trials.

  13. Natural antisense LHCGR could make sense of hypogonadism, male-limited precocious puberty and pre-eclampsia.

    PubMed

    Chambers, Anne E; Banerjee, Subhasis

    2005-09-28

    The pleiotropic effects of human chorionic gonadotrophin (hCG), the key regulator of human pregnancy, are dependent upon cell surface expression of its functional cognate receptor LHCGR in the placental trophoblasts, corpus luteum, uterus, vascular endothelial and smooth muscle cells. Additionally, lutenizing hormone-mediated signalling failure has often been linked to activating/inactivating mutations in LHCGR. One of the intriguing aspects of these studies is that the mutations are most frequently located within C-terminal 200-350 residues of the receptor protein. In an attempt to reconcile the mechanistic basis of LHCGR regulation and mutations, we have carried out bioinformatic analyses to identify the CpG-rich regions and the major potential scaffold/matrix attachment sites (S/MARs) in LHCGR and neighbouring gene (ALF) at human chromosome 2p21. Based on these analyses, we propose a chromatin-loop model, which may explain the temporal regulation and susceptibility to mutation of the human LHCGR. One of the characteristic features of the model, is that the major potential S/MAR sequences of the human LHCGR gene (68 kb) are located at the 3' end of the gene, and unlike mouse, the transmembrane and C-terminal protein coding sequences at exon 11 are embedded in this S/MAR site. Moreover, this region is subject to antisense transcription from the neighbouring gene ALF, which is gonad-specific and is only activated in meiotic spermatocytes and oocytes. Together, these analyses suggest that exon 11 of human LHCGR could be more susceptible to mutation than the other 10 exons together and that activation of LHCGR, contingent to the somatic silencing of neighbouring ALF, could be linked to male-limited precocious puberty and pre-eclampsia. PMID:16087288

  14. Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre-eclampsia.

    PubMed

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

    2013-01-01

    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 CEBPα (p = 0.031). Luciferase reporter analysis confirmed the aberrant methylation of LEP promoter and CEBPα 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.

  15. Predictive value of miR-210 as a novel biomarker for pre-eclampsia: a systematic review protocol

    PubMed Central

    Nikuei, Pooneh; Davoodian, Nahid; Tahamtan, Iman; Keshtkar, Abbas Ali

    2016-01-01

    Introduction Pre-eclampsia (PE) is a serious condition affecting 3–5% of all pregnancies worldwide. However, underlying molecular pathogenesis of this disease has largely remained unknown. Recently, several studies have indicated the possibility role of microRNAs, especially miR-210, in the aetiology of PE. The aim of this systematic review is to assess the possible role of miR-210 as a novel biomarker for the prediction of PE. Methods and analysis Using a combination of mesh terms ‘preeclampsia’, ‘microRNA’ and their equivalents, an electronic search will be performed for all observational studies (cross sectional, case–control and cohort) in PubMed, Web of Science, Scopus, Embase, Cochrane, LILACS and OvidSP MEDLINE from January 2005 to December 2015. Furthermore, other sources are searched, including grey literature, reference lists of relevant primary studies as well as key journals. Study selection, data extraction and quality assessment of studies will be performed independently by 2 reviewers, and any disagreement will be resolved by consensus. If sufficient data are available, it will be combined by either fixed or random effects models. We will investigate the source)s(and degree of heterogeneity using ‘Heterogeneity χ2’ and I2. Heterogeneity would be investigated through either subgroup analysis or metaregression. Stata V.11.1 will be used for data analysis. Ethics and dissemination The results of this study are disseminated in peer-reviewed journal articles and academic presentations. Formal ethical approval is not required, since the secondary data will be collected. Trial registration number CRD42015032345. PMID:27683514

  16. Feasibility of nephrinuria as a screening tool for the risk of pre-eclampsia: prospective observational study

    PubMed Central

    Zhai, Tianyue; Furuta, Itsuko; Akaishi, Rina; Kawabata, Kosuke; Chiba, Kentaro; Umazume, Takeshi; Ishikawa, Satoshi; Yamada, Takahiro; Morikawa, Mamoru; Minakami, Hisanori

    2016-01-01

    Objectives To investigate the possibility of nephrinuria as a screening tool for the risk of pre-eclampsia (PE). Design Prospective observational study. Setting A single university hospital. Changes in urinary nephrin:creatinine ratio (NCR, ng/mg) and protein:creatinine ratio (PCR, mg/mg) in pregnancy were determined. Significant proteinuria in pregnancy (SPIP) was defined as PCR>0.27. PE was diagnosed in women with both SPIP and hypertension. Participants 89 pregnant women in whom neither hypertension nor SPIP was present at enrolment, providing 31, 125 and 93 random urine samples during first, second and third trimesters, respectively. Results PE developed in 14 of the 89 women. NCR increased with increasing PCR in 14 women with PE (correlation coefficient, 0.862; p<0.0001). In contrast, NCR did not change significantly despite significant increases in PCR in 75 women with normotensive pregnancies defined as neither SPIP nor hypertension, indicating that there was little increase in nephrinuria over the physiological range of proteinuria in pregnancy. Relative risk of later development of PE among asymptomatic second and third trimester women with NCR (ng/mg) >122 (95th centile value for 75 women with normotensive pregnancies) was 5.93 (95% CI 2.59 to 13.6; 60% (6/10) vs 10% (8/79)) and 13.5 (95% CI 3.31 to 55.0; 75% (6/8) vs 5.5% (2/36)), respectively, compared with women with NCR≤122 at that time. Conclusions Nephrinuria was unlikely to increase in normal pregnancy. A certain NCR cut-off may efficiently differentiate women at higher risk of PE. PMID:27486123

  17. Criteria-Based Audit of Quality of Care to Women with Severe Pre-Eclampsia and Eclampsia in a Referral Hospital in Accra, Ghana

    PubMed Central

    Srofenyoh, Emmanuel K.; Grobbee, Diederick E.; Klipstein-Grobusch, Kerstin

    2015-01-01

    Objectives Severe pre-eclampsia and eclampsia are one of the major causes of maternal mortality globally. Reducing maternal morbidity and mortality demands optimizing quality of care. Criteria-based audits are a tool to define, assess and improve quality of care. The aim of this study was to determine applicability of a criteria-based audit to assess quality of care delivered to women with severe hypertensive disorders in pregnancy, and to assess adherence to protocols and quality of care provided at a regional hospital in Accra, Ghana. Methods Checklists for management of severe preeclampsia, hypertensive emergency and eclampsia were developed in an audit cycle based on nine existing key clinical care protocols. Fifty cases were audited to assess quality of care, defined as adherence to protocols. Analysis was stratified for complicated cases, defined as (imminent) eclampsia, perinatal mortality and/or one or more WHO maternal near miss C-criteria. Results Mean adherence to the nine protocols ranged from 15–85%. Protocols for ‘plan for delivery’ and ‘magnesium sulphate administration’ were best adhered to (85%), followed by adherence to protocols for ‘eclampsia’ (64%), ‘severe pre-eclampsia at admission’ (60%), ‘severe pre-eclampsia ward follow-up’ (53%) and ‘hypertensive emergency’ (53%). Protocols for monitoring were least adhered to (15%). No difference was observed for severe disease. Increased awareness, protocol-based training of staff, and clear task assignment were identified as contributors to better adherence. Conclusion A criteria-based audit is an effective tool to determine quality of care, identify gaps in standard of care, and allow for monitoring and evaluation in a health facility, ultimately resulting in improved quality of care provided and reduced maternal morbidity and mortality. In our audit, good adherence was observed for plan for delivery and treatment with magnesium sulphate. Substandard adherence to a number of

  18. Health system barriers to access and use of magnesium sulfate for women with severe pre-eclampsia and eclampsia in Pakistan: evidence for policy and practice.

    PubMed

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

    2013-01-01

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

  19. Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts

    PubMed Central

    Silverwood, Richard J; de Stavola, Bianca L; Inskip, Hazel; Cooper, Cyrus; Godfrey, Keith M; Crozier, Sarah; Fraser, Abigail; Nelson, Scott M; Lawlor, Debbie A; Tilling, Kate

    2015-01-01

    Study question Can routine antenatal blood pressure measurements between 20 and 36 weeks’ gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes? Methods This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women’s Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks. Study answer and limitations The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice. What this study adds The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care. Funding, competing interests, data sharing UK Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. Other

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

    STUDY QUESTION Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). SUMMARY ANSWER Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls. WHAT IS KNOWN ALREADY Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known. STUDY DESIGN, SIZE, DURATION A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192. MAIN RESULTS AND THE ROLE OF CHANCE Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies. LIMITATIONS, REASONS FOR CAUTION The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues. WIDER IMPLICATIONS OF THE FINDINGS This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin

  2. Association Between Gene Polymorphisms on Chromosome 1 and Susceptibility to Pre-Eclampsia: An Updated Meta-Analysis

    PubMed Central

    Zhang, Guixin; Zhao, Jinheng; Yi, Jianping; Luan, Yuanyuan; Wang, Qian

    2016-01-01

    Background This meta-analysis enabled us to obtain a precise estimation of the association between gene polymorphisms on chromosome 1 (MTHFR, AGT, F5, IL-10, LEPR) and the susceptibility to pre-eclampsia (PE) in order to reach a uniform conclusion. Material/Methods Web of Science, PubMed, EMBASE, Cochran Library (CENTRAL), and Chinese databases (Chinese National Knowledge Infrastructure-CNKI and Wan Fang) were electronically searched to select relevant studies for this meta-analysis. We selected 95 case-control studies investigating 5 genes (MTHFR, AGT, F5, IL-10, and LEPR) with 8 SNPs. Odds ratios (OR) with their 95% confidence intervals (CI) were used for estimating the association. Results A total of 16 646 PE patients and 28 901 normal-pregnancy patients were included in this meta-analysis. The overall results suggested that rs1801133 of MTHFR (OR=1.17, 95% CI: 1.05–1.13) and rs6025 of F5 (OR=1.53, 95%CI: 1.07–2.20) are significantly associated with PE, whereas rs1801131 of MTHFR, rs699 and rs4762 of AGT, rs1800896 and rs1800871 of IL-10, and rs1137101 of LEPR have no significant association with PE. Subgroup analysis by ethnicity revealed that, except for MTHFR rs1801133 and F5 rs6025 in Caucasians, which were significantly associated with an increased risk of PE, none of these SNPs were significantly associated with PE. As suggested by a symmetric funnel plot in conjunction with the Egger’s test, there was no significant publication bias in MTHFR rs1801133 (P=0.318) and rs1801131 (P=0.204), F5 rs6025 (P=0.511), LEPR rs1137101 (P=0.511), AGT rs4762 (P=0.215) and rs699 (P=0.482), IL-10 rs1800871 (P=0.955), and rs1800896 (P=0.144). Conclusions This meta-analysis provides evidence that MTHFR rs1801133 and F5 rs6025 are associated with an increased risk of PE, especially in Caucasians. However, we do not have sufficient evidence to conclude there is a significant association between other gene polymorphisms and PE. PMID:27348238

  3. The Effect of Multi mineral-Vitamin D Supplementation on Pregnancy Outcomes in Pregnant Women at Risk for Pre-eclampsia

    PubMed Central

    Asemi, Zatollah; Esmaillzadeh, Ahmad

    2015-01-01

    Background: The objective of this study was to determine the favorable effects of multi mineral-Vitamin D supplementation on pregnancy outcomes among women at risk for pre-eclampsia. Methods: This randomized double-blind controlled clinical trial was conducted among 46 women at risk for pre-eclampsia at 27 weeks’ gestation with positive roll-over test. Pregnant women were randomly assigned to receive either the multi mineral-Vitamin D supplements (n = 23) or the placebo (n = 23) for 9-week. Multi mineral-Vitamin D supplements were containing 800 mg calcium, 200 mg magnesium, 8 mg zinc, and 400 IU Vitamin D3. Fasting blood samples were taken at baseline and after 9-week intervention to measure related factors. Newborn's outcomes were determined. Results: Although no significant difference was seen in newborn's weight and head circumference between the two groups, mean newborns’ length (51.3 ± 1.7 vs. 50.3 ± 1.2 cm, P = 0.03) was significantly higher in multi mineral-Vitamin D group than that in the placebo group. Compared to the placebo, consumption of multi mineral-Vitamin D supplements resulted in increased levels of serum calcium (+0.19 vs. −0.08 mg/dL, P = 0.03), magnesium (+0.15 vs. −0.08 mg/dL, P = 0.03), zinc (+8.25 vs. −21.38 mg/dL, P = 0.001) and Vitamin D (+3.79 vs. −1.37 ng/ml, P = 0.01). In addition, taking multi mineral-Vitamin D supplements favorably influenced systolic blood pressure (SBP) (−1.08 vs. 6.08 mmHg, P = 0.001) and diastolic blood pressure (DBP) (−0.44 vs. 3.05 mmHg, P = 0.02). Conclusions: Multi mineral-Vitamin D supplementation for 9-week in pregnant women at risk for pre-eclampsia resulted in increased newborn's length, increased circulating levels of maternal serum calcium, magnesium, zinc and Vitamin D, and led to decreased maternal SBP and DBP. PMID:26288706

  4. Genome-wide association study of pre-eclampsia detects novel maternal single nucleotide polymorphisms and copy-number variants in subsets of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study cohort.

    PubMed

    Zhao, Linlu; Bracken, Michael B; DeWan, Andrew T

    2013-07-01

    A genome-wide association study was undertaken to identify maternal single nucleotide polymorphisms (SNPs) and copy-number variants (CNVs) associated with pre-eclampsia. Case-control analysis was performed on 1070 Afro-Caribbean (n = 21 cases and 1049 controls) and 723 Hispanic (n = 62 cases and 661 controls) mothers and 1257 mothers of European ancestry (n = 50 cases and 1207 controls) from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. European ancestry subjects were genotyped on Illumina Human610-Quad and Afro-Caribbean and Hispanic subjects were genotyped on Illumina Human1M-Duo BeadChip microarrays. Genome-wide SNP data were analyzed using PLINK. CNVs were called using three detection algorithms (GNOSIS, PennCNV, and QuantiSNP), merged using CNVision, and then screened using stringent criteria. SNP and CNV findings were compared to those of the Study of Pregnancy Hypertension in Iowa (SOPHIA), an independent pre-eclampsia case-control dataset of Caucasian mothers (n = 177 cases and 116 controls). A list of top SNPs were identified for each of the HAPO ethnic groups, but none reached Bonferroni-corrected significance. Novel candidate CNVs showing enrichment among pre-eclampsia cases were also identified in each of the three ethnic groups. Several variants were suggestively replicated in SOPHIA. The discovered SNPs and copy-number variable regions present interesting candidate genetic variants for pre-eclampsia that warrant further replication and investigation. PMID:23551011

  5. Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review.

    PubMed

    Ray, J G; Laskin, C A

    1999-09-01

    Placental infarction or abruption, recurrent pregnancy loss and pre-eclampsia are thought to arise due to defects within the placental vascular bed. Deficiencies of vitamin B12 and folate, or other abnormalities within the methionine-homocyst(e)ine pathway have been implicated in the development of such placental diseases. We conducted a systematic literature review to quantify the risk of placental disease in the presence of these metabolic defects. Studies were identified through OVID Medline between 1966 and February 1999. Terms relating to the measurement of vitamin B12, folic acid, methylenetetrahydrofolate reductase or homocyst(e)ine were combined with those of pre-eclampsia, placental abruption/infarction or spontaneous and habitual abortion. Human studies comprising both cases and controls and published in the English language were accepted. Their references were explored for other publications. Data were abstracted on the matching of cases with controls, the mean levels of folate, B12 or homocyst(e)ine in each group or the frequency of the homozygous state for the thermolabile variant of methylenetetrahydrofolate reductase. The definition of 'abnormal' for each exposure was noted and the presence or absence of the exposure of interest for each outcome was calculated as an absolute rate with a 95 per cent confidence interval. The crude odds ratios were calculated for each study and then pooled using a random effects model. Eighteen studies were finally included. Eight studies examined the risk of placental abruption/infarction in the presence of vitamin B12 or folate deficiency, or hyperhomocyst(e)inaemia. Folate deficiency was a prominent risk factor for placental abruption/infarction among four studies, though not statistically significant (pooled odds ratio 25.9, 95 per cent CI 0.9-736.3). Hyperhomocyst(e)inaemia was also associated with placental abruption/infarction both without (pooled odds ratio 5.3, 95 per cent CI 1.8-15.9) and with methionine

  6. Acute presentation of gestational diabetes insipidus with pre-eclampsia complicated by cerebral vasoconstriction: a case report and review of the published work.

    PubMed

    Mor, Amir; Fuchs, Yael; Zafra, Kathleen; Haberman, Shoshana; Tal, Reshef

    2015-08-01

    Gestational diabetes insipidus (GDI) is a rare, self-limited complication of pregnancy. As it is related to excess placental vasopressinase enzyme activity, which is metabolized in the liver, GDI is more common in pregnancies complicated by conditions associated with liver dysfunction. We present a case of a 41-year-old woman at 38 weeks' gestation who presented with pre-eclampsia with severe features, including impaired liver function and renal insufficiency. Following cesarean section she was diagnosed with GDI, which was further complicated by cerebral vasoconstriction as demonstrated by magnetic resonance angiography. This case raises the possibility that cerebral vasoconstriction may be related to the cause of GDI. A high index of suspicion of GDI should be maintained in patients who present with typical signs and symptoms, especially in the setting of pregnancy complications associated with liver dysfunction.

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

    PubMed

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

    2015-02-01

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

  8. The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats

    PubMed Central

    Tian, Mei; Zhang, Yonghong; Liu, Zhaozhao; Sun, Guoqiang; Mor, Gil; Liao, Aihua

    2016-01-01

    The programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis by promoting regulatory T (Treg) development and inhibiting effector T (such as Th17) cell responses. However, the association between the PD-1/PD-L1 pathway and the Treg/Th17 imbalance has not been fully investigated in pre-eclampsia (PE). In this study, we observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 on the two subsets also changed in PE compared with normal pregnancy. We further explored their relationship in vivo using the L-NG-Nitroarginine Methyl Ester (L-NAME) induced PE-like rat models, also characterized by Treg/Th17 imbalance. Administration of PD-L1-Fc protein provides a protective effects on the pre-eclamptic models, both to the mother and the fetuses, by reversing Treg/Th17 imbalance through inhibiting PI3K/AKT/m-TOR signaling and enhancing PTEN expression. In addition, we also observed a protective effect of PD-L1-Fc on the placenta by reversing placental damages. These results suggested that altered PD-1/PD-L1 pathway contributed to Treg/Th17 imbalance in PE. Treatment with PD-L1-Fc posed protective effects on pre-eclamptic models, indicating that the use of PD-L1-Fc might be a potential therapeutic target in PE treatment. PMID:27277012

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

    PubMed Central

    Gangooly, Subrata; Jauniaux, Eric

    2014-01-01

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

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

    PubMed

    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

    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.

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

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

    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

    2012-01-01

    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

  13. Systematic Review of Micro-RNA Expression in Pre-Eclampsia Identifies a Number of Common Pathways Associated with the Disease

    PubMed Central

    Sheikh, Adam M.; Currie, Gemma; Delles, Christian

    2016-01-01

    Background Pre-eclampsia (PE) is a complex, multi-systemic condition of pregnancy which greatly impacts maternal and perinatal morbidity and mortality. MicroRNAs (miRs) are differentially expressed in PE and may be important in helping to understand the condition and its pathogenesis. Methods Case-control studies investigating expression of miRs in PE were collected through a systematic literature search. Data was extracted and compared from 58 studies to identify the most promising miRs associated with PE pathogenesis and identify areas of methodology which could account for often conflicting results. Results Some of the most frequently differentially expressed miRs in PE include miR-210, miR-223 and miR-126/126* which associate strongly with the etiological domains of hypoxia, immunology and angiogenesis. Members of the miR-515 family belonging to the imprinted chromosome 19 miR cluster with putative roles in trophoblast invasion were also found to be differentially expressed. Certain miRs appear to associate with more severe forms of PE such as miR-210 and the immune-related miR-181a and miR-15 families. Patterns of miR expression may help pinpoint key pathways (e.g. IL-6/miR-223/STAT3) and aid in untangling the heterogeneous nature of PE. The detectable presence of many PE-associated miRs in antenatal circulatory samples suggests their usefulness as predictive biomarkers. Further progress in ascertaining the clinical value of miRs and in understanding how they might contribute to pathogenesis is predicated upon resolving current methodological challenges in studies. These include differences in diagnostic criteria, cohort characteristics, sampling technique, RNA isolation and platform-dependent variation in miR profiling. Conclusion Reviewing studies of PE-associated miRs has revealed their potential as informants of underlying target genes and pathways relating to PE pathogenesis. However, the incongruity in results across current studies hampers their

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

    PubMed Central

    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

    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

  15. Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review.

    PubMed

    Kawasaki, Kaoru; Kondoh, Eiji; Minamiguchi, Sachiko; Matsuda, Fumihiko; Higasa, Koichiro; Fujita, Kohei; Mogami, Haruta; Chigusa, Yoshitsugu; Konishi, Ikuo

    2016-08-01

    A partial molar pregnancy almost always ends in miscarriage due to a triploid fetus. We describe a rare case of a singleton, partial molar pregnancy with a seemingly huge placenta, which continued to delivery of a live-born diploid baby. A 27-year-old primigravida suffered from severe pre-eclampsia and progressive anemia. The uterus was enormously enlarged for the gestational age. A cesarean section was performed because of deterioration of maternal status at 25 weeks' gestation, when more than 3000 mL blood spouted concurrently with the delivery of the placenta. The histological examination showed congestion in the decidua, which indicated disturbance of maternal venous return from the intervillous space. The chromosome complement of the placenta and the neonate were 69,XXX and 46,XX, respectively. We also reviewed all published cases of a singleton, partial molar pregnancy. A literature search yielded 18 cases of a singleton, diploid fetus with partial molar pregnancy. The mean gestational age at delivery was 24.5 ± 6.2 weeks, and fetuses survived outside the uterus in only four cases (22.2%). Intriguingly, previous reports numbered 10 cases with diploid placenta as well as five cases with no karyotyping of the placenta, indicating that they may have included a complete mole in a twin pregnancy or placental mesenchymal dysplasia. In conclusion, this was the first case of placentomegaly that presented manifestations of excessive abdominal distension and maternal severe anemia, and the second case of a singleton, partial molar pregnancy confirmed by chromosome analysis resulting in a diploid living baby.

  16. Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review.

    PubMed

    Kawasaki, Kaoru; Kondoh, Eiji; Minamiguchi, Sachiko; Matsuda, Fumihiko; Higasa, Koichiro; Fujita, Kohei; Mogami, Haruta; Chigusa, Yoshitsugu; Konishi, Ikuo

    2016-08-01

    A partial molar pregnancy almost always ends in miscarriage due to a triploid fetus. We describe a rare case of a singleton, partial molar pregnancy with a seemingly huge placenta, which continued to delivery of a live-born diploid baby. A 27-year-old primigravida suffered from severe pre-eclampsia and progressive anemia. The uterus was enormously enlarged for the gestational age. A cesarean section was performed because of deterioration of maternal status at 25 weeks' gestation, when more than 3000 mL blood spouted concurrently with the delivery of the placenta. The histological examination showed congestion in the decidua, which indicated disturbance of maternal venous return from the intervillous space. The chromosome complement of the placenta and the neonate were 69,XXX and 46,XX, respectively. We also reviewed all published cases of a singleton, partial molar pregnancy. A literature search yielded 18 cases of a singleton, diploid fetus with partial molar pregnancy. The mean gestational age at delivery was 24.5 ± 6.2 weeks, and fetuses survived outside the uterus in only four cases (22.2%). Intriguingly, previous reports numbered 10 cases with diploid placenta as well as five cases with no karyotyping of the placenta, indicating that they may have included a complete mole in a twin pregnancy or placental mesenchymal dysplasia. In conclusion, this was the first case of placentomegaly that presented manifestations of excessive abdominal distension and maternal severe anemia, and the second case of a singleton, partial molar pregnancy confirmed by chromosome analysis resulting in a diploid living baby. PMID:27225660

  17. Effectiveness and safety of 1 vs 4 h blood pressure profile with clinical and laboratory assessment for the exclusion of gestational hypertension and pre-eclampsia: a retrospective study in a university affiliated maternity hospital

    PubMed Central

    McCarthy, Elizabeth Anne; Carins, Thomas A; Hannigan, Yolanda; Bardien, Nadia; Shub, Alexis; Walker, Susan P

    2015-01-01

    Objective We asked whether 60 compared with 240 min observation is sufficiently informative and safe for pregnancy day assessment (PDAC) of suspected pre-eclampsia (PE). Design A retrospective study of 209 pregnant women (475 PDAC assessments, 6 months) with routinely collected blood pressure (BP), symptom and laboratory information. We proposed a 60 min screening algorithm comprising: absence of symptoms, normal laboratory parameters and ≤1high-BP reading (systolic blood pressure, SBP 140 mm Hg or higher or diastolic blood pressure, DBP 90 mm Hg or higher). We also evaluated two less inclusive screening algorithms. We determined short-term outcomes (within 4 h): severe hypertension, proteinuric hypertension and pregnancy-induced hypertension, as well as long-term outcome: PE-related diagnoses up to the early puerperium. We assessed performance of alternate screening algorithms performance using 2×2 tables. Results 1 in 3 women met all screen negative criteria at 1 h. Their risk of hypertension requiring treatment in the next 3 h was 1.8% and of failing to diagnose proteinuric hypertensive PE at 4 h was 5.1%. If BP triggers were 5 mm Hg lower, 1 in 6 women would be screen-negative of whom 1.1% subsequently develops treatment-requiring hypertension and 4.5% demonstrate short-term proteinuric hypertension. We present sensitivity, specificity, negative and positive likelihood ratios for alternate screening algorithms. Conclusions We endorse further research into the safest screening test where women are considered for discharge after 60 min. Safety, patient and staff satisfaction should be assessed prospectively. Any screening test should be used in conjunction with good clinical care to minimise maternal and perinatal hazards of PE. PMID:26582404

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

    PubMed Central

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

    2015-01-01

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

  19. Pre-Eclampsia, Birth Weight, and Autism Spectrum Disorders

    ERIC Educational Resources Information Center

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

    2010-01-01

    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…

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Wilczyński, Jacek R; Tchórzewski, Henryk; Głowacka, Ewa; Banasik, Małgorzata; Lewkowicz, Przemyslaw; Szpakowski, Marian; Zeman, Krzysztof; Wilczyński, Jan

    2002-01-01

    BACKGROUND: Transient hypertension (TH) and preeclampsia (PE) are believed to have different pathophysiology. However, 15-25% of pregnant women initially diagnosed as having TH develop PE. To clarify the immuno-pathogenetical connections between the two syndromes, we studied the pattern of T helper cell (Th)1/Th2 cytokine balance disturbances existing inside maternal decidua in normal pregnancy (NP) and pregnancies complicated with TH and PE. METHODS: Third-trimester decidual tissue was obtained by curettage of uterine cavity during elective caesarean sections in NP (n = 11), TH (n = 17) and PE (n = 21) patients. Cell suspensions were prepared by an electromechanical dispersal method and centrifugated using a standard gradient sedimentation technique. Isolated lymphocytes were placed in medium (RPMI 1640, 10% fetal calf serum, L-glutamine, penicillin, streptomycin) and cultured for 72 h with or without mitogen phytohaemaglutinine (PHA). The enzyme-linked immunosorbent assay method was used for estimation of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and interferon-gamma (IFN-gamma) in culture supernatant. STATISTICAL ANALYSIS: The Kruskal-Wallis and the Mann-Whitney U tests were used (p < 0.05). RESULTS: Both spontaneous and PHA-stimulated secretion of Th2-type cytokines IL-6 and IL-10 was decreased in PE patients compared with TH and NP patients. The concentration of Th1-type cytokine IFN-gamma was increased in patients suffering both from TH and PE. CONCLUSION: On the base of decidual cytokine secretion, both PE and TH are syndromes of local Th1/Th2 cytokine balance disturbances as compared with NP, and TH seems to be an intermediate step to PE. PMID:12061422

  2. Folic Acid Supplementation in Pregnancy and the Risk of Pre-Eclampsia-A Cohort Study.

    PubMed

    Wen, Shi Wu; Guo, Yanfang; Rodger, Marc; White, Ruth Rennicks; Yang, Qiuying; Smith, Graeme N; Perkins, Sherry L; Walker, Mark C

    2016-01-01

    This prospective cohort study designed to assess the effect of folic acid supplementation in pregnancy on the risk of preeclampsia (PE) took place in Ottawa, ON and Kingston, ON, Canada, from September 1, 2002 to August 31, 2008. Pregnant women, less than 20 weeks gestational age were recruited and delivered in the Ottawa region and the Kingston General Hospital. Demographic characteristics of the study participants and the patterns of supplementation of folic acid were described and occurrence of PE between women with folic acid supplementation during pregnancy and women without were compared. Multiple logistic regression was used in the estimation of the independent effect of supplementation of folic acid. Additional analyses assessing the effect of low RBC and serum folate and dose-response relationship were performed. Analyses were performed in all study participants, and then in high risk and low risk sub-groups, respectively. A total of 7,669 participants were included in the final analysis. Ninety five percent of the study participants were taking folic acid supplementation in early second trimester. The rate of PE was lower in the supplementation group than in the no supplementation group, and the difference was statistically significant in high risk women. Similar patterns of associations were observed in analysis by RBC and serum folate levels and in dose-response analysis. Folic acid supplementation in pregnancy may reduce PE risk in pregnant women, especially in those women with increased risk of developing PE.

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

    ERIC Educational Resources Information Center

    Mann, Joshua R.; McDermott, Suzanne

    2011-01-01

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

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

    ClinicalTrials.gov

    2013-12-11

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

  5. Precision test for precision medicine: opportunities, challenges and perspectives regarding pre-eclampsia as an intervention window for future cardiovascular disease

    PubMed Central

    Zhou, Xin; Niu, Jian-Min; Ji, Wen-Jie; Zhang, Zhuoli; Wang, Peizhong P; Ling, Xue-Feng B; Li, Yu-Ming

    2016-01-01

    Hypertensive disorders of pregnancy (HDP) comprise a spectrum of syndromes that range in severity from gestational hypertension and pre-eclamplsia (PE) to eclampsia, as well as chronic hypertension and chronic hypertension with superimposed PE. HDP occur in 2% to 10% of pregnant women worldwide, and impose a substantial burden on maternal and fetal/infant health. Cardiovascular disease (CVD) is the leading cause of death in women. The high prevalence of non-obstructive coronary artery disease and the lack of an efficient diagnostic workup make the identification of CVD in women challenging. Accumulating evidence suggests that a previous history of PE is consistently associated with future CVD risk. Moreover, PE as a maladaptation to pregnancy-induced hemodynamic and metabolic stress may also be regarded as a “precision” testing result that predicts future cardiovascular risk. Therefore, the development of PE provides a tremendous, early opportunity that may lead to changes in maternal and infant future well-being. However, the underlying pathogenesis of PE is not precise, which warrants precision medicine-based approaches to establish a more precise definition and reclassification. In this review, we proposed a stage-specific, PE-targeted algorithm, which may provide novel hypotheses that bridge the gap between Big Data-generating approaches and clinical translational research in terms of PE prediction and prevention, clinical treatment, and long-term CVD management. PMID:27347303

  6. Preeclampsia in low and middle income countries-health services lessons learned from the PRE-EMPT (PRE-Eclampsia-Eclampsia Monitoring, Prevention and Treatment) project.

    PubMed

    von Dadelszen, Peter; Firoz, Tabassum; Donnay, France; Gordon, Rebecca; Hofmeyr, G Justus; Lalani, Shifana; Payne, Beth A; Roberts, James M; Teela, Katherine C; Vidler, Marianne; Sawchuck, Diane; Magee, Laura A

    2012-10-01

    The hypertensive disorders of pregnancy, in particular preeclampsia, matter because adverse events occur in women with preeclampsia and, to a lesser extent, in women with the other hypertensive disorders. These adverse events are maternal, perinatal, and neonatal and can alter the life trajectory of each individual, should that life not be ended by complications. In this review we discuss a number of priorities and dilemmas that we perceive to be facing health services in low and middle income countries as they try to prioritize interventions to reduce the health burden related to preeclampsia. These priorities and dilemmas relate to calcium for preeclampsia prevention, risk stratification, antihypertensive and magnesium sulphate therapy, and mobile health. Significant progress has been and is being made to reduce the impact of preeclampsia in low and middle income countries, but it remains a priority focus as we attempt to achieve Millennium Development Goal 5.

  7. Precision test for precision medicine: opportunities, challenges and perspectives regarding pre-eclampsia as an intervention window for future cardiovascular disease.

    PubMed

    Zhou, Xin; Niu, Jian-Min; Ji, Wen-Jie; Zhang, Zhuoli; Wang, Peizhong P; Ling, Xue-Feng B; Li, Yu-Ming

    2016-01-01

    Hypertensive disorders of pregnancy (HDP) comprise a spectrum of syndromes that range in severity from gestational hypertension and pre-eclamplsia (PE) to eclampsia, as well as chronic hypertension and chronic hypertension with superimposed PE. HDP occur in 2% to 10% of pregnant women worldwide, and impose a substantial burden on maternal and fetal/infant health. Cardiovascular disease (CVD) is the leading cause of death in women. The high prevalence of non-obstructive coronary artery disease and the lack of an efficient diagnostic workup make the identification of CVD in women challenging. Accumulating evidence suggests that a previous history of PE is consistently associated with future CVD risk. Moreover, PE as a maladaptation to pregnancy-induced hemodynamic and metabolic stress may also be regarded as a "precision" testing result that predicts future cardiovascular risk. Therefore, the development of PE provides a tremendous, early opportunity that may lead to changes in maternal and infant future well-being. However, the underlying pathogenesis of PE is not precise, which warrants precision medicine-based approaches to establish a more precise definition and reclassification. In this review, we proposed a stage-specific, PE-targeted algorithm, which may provide novel hypotheses that bridge the gap between Big Data-generating approaches and clinical translational research in terms of PE prediction and prevention, clinical treatment, and long-term CVD management. PMID:27347303

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

    PubMed

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

    2014-02-01

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

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

    PubMed

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

    2014-02-01

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

  10. 32 CFR 732.16 - Emergency care requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... pregnancy in a manner that a delay, caused by referral to a USMTF or USTF, would jeopardize the welfare of... delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy...

  11. 32 CFR 732.16 - Emergency care requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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...

  12. 32 CFR 732.16 - Emergency care requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... pregnancy in a manner that a delay, caused by referral to a USMTF or USTF, would jeopardize the welfare of... delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy...

  13. 32 CFR 732.16 - Emergency care requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... pregnancy in a manner that a delay, caused by referral to a USMTF or USTF, would jeopardize the welfare of... delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy...

  14. 32 CFR 732.16 - Emergency care requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pregnancy in a manner that a delay, caused by referral to a USMTF or USTF, would jeopardize the welfare of... delivery. (4) Severe pre-eclampsia. (5) Hemorrhage, second and third trimester. (6) Ectopic pregnancy...

  15. Estrogen Receptor Alpha (ESR1) Gene Polymorphisms in Pre-eclamptic Saudi Patients

    PubMed Central

    El-Beshbishy, Hesham A.; Tawfeek, Manal A.; Al-Azhary, Nevin M.; Mariah, Reham A.; Habib, Fawzia A.; Aljayar, Lamya; Alahmadi, Abrar F.

    2015-01-01

    Objectives: Pre-eclampsia causes maternal mortality worldwide. Estrogen receptor alpha (ESR1) gene polymorphisms were responsible for cardiovascular diseases. This case control study was conducted to investigate whether 2 polymorphic genes of ESR1 are associated with pre-eclampsia among Saudi women in Madina city, Saudi Arabia. Methods: Blood samples from 97 pre-eclamptic and 94 healthy pregnant women were analyzed using restriction fragment length polymorphism-polymerase chain reaction method. All the subjects were recruited randomly from outpatient clinics of Madina Maternity Children Hospital (MMCH), Madina, Saudi Arabia, between Dec. 2012 and Jan. 2014. Results: There was no association between pre-eclampsia and PvuII and XbaI ESR1 gene polymorphisms individually. TT/AA and TT/AG genotype combination existed significantly in pre-eclamptic patients compared to control. The frequency of PvuII and XbaI combined TT/AA genotypes between pre-eclamptic women was 36.1% vs 9.6%, however, frequency of PvuII and XbaI combined TT/AG genotypes between pre-eclamptic women was 3.1% vs 17%, compared to control. The homozygous T-A haplotype carriers showed high pre-eclampsia risk, independent of pregnancy, BMI and smoking status (adjusted odds ratio (OR): 3.26, 95% confidence interval (CI):1.71-9.21). The heterozygous T-A haplotype carriers did not differ from that of non-carriers (adjusted OR: 1.12, 95% CI: 0.47-2.75). No association was observed between pre-eclampsia and T-G, C-G and C-A haplotype of PvuII and XbaIESR1 gene polymorphisms. Conclusions: T-A haplotype of homozygous associated with pre eclampsia not heterozygous carriers of ESR 1 PvuII and XbaI gene polymorphisms elicited high risk of pre-eclampsia. GG genotype of XbaI polymorphism decreased pre-eclampsia risk. Further studies using larger sample size are recommended to investigate the ESR 1 gene polymorphisms associated with pre-eclampsia. PMID:26430422

  16. Overview of randomised trials of diuretics in pregnancy.

    PubMed Central

    Collins, R; Yusuf, S; Peto, R

    1985-01-01

    Over the past 20 years at least 11 randomised trials of the prevention with diuretics of pre-eclampsia and its sequelae have been undertaken. Nine of these were reviewed. Reliable data from the remaining two were not available. The nine reviewed had investigated a total of nearly 7000 people. Significant evidence of prevention of "pre-eclampsia" was overwhelming, even when oedema was not included as a diagnostic criterion. But as the definitions of pre-eclampsia that had been used depended heavily on increases in blood pressure this evidence may simply have reflected the well known ability of diuretics to reduce blood pressure. When the data on perinatal death were reviewed a little difference was seen in postnatal survival. The incidence of stillbirths was reduced by about one third with treatment, but, perhaps owing to small numbers (only 37 stillbirths), the difference was not significant. Thus these randomised trials failed to provide reliable evidence of either the presence or the absence of any worthwhile effects of treatment with diuretics on perinatal mortality. The implications of this for current and future trials of beta blockers and other agents in the prevention of pre-eclampsia and its sequelae are that extremely large, ultra simple randomised trials are needed, of a size sufficient to permit direct assessment of the effects of treatment not on pre-eclampsia but on perinatal mortality itself. This may require the study of tens of thousands of pregnancies. PMID:3917318

  17. [Prognostic Value of Central Aortic Pressure in Pregnant Women With Hypertension].

    PubMed

    Chulkov, V S; Sinitsin, S P; Vereina, N K

    2015-01-01

    Prognostic value of central aortic pressure and peripheral blood pressure in relation to the development of pre-eclampsia was assessed in pregnant women with different forms of hypertension. It was shown that development of pre-eclampsia was associated with higher mean 24-hour systolic blood pressure (BP), time index of systolic BP, variability of diastolic BP, and pulse BP measured on weeks 16-22 of gestation. Pregnant women with hypertension, especially those with pre-eclampsia were characterized by absence of proper nocturnal BP lowering or BP elevation during night hours (non-dippers and night-peakers). Critical values for prediction of preeclampsia were daily average central (aortic) systolic BP higher than 115 mm Hg and a mean daily brachial systolic BP above 131 mm Hg.

  18. Hypertension in diabetic pregnancy: impact and long-term outlook.

    PubMed

    Colatrella, Antonietta; Loguercio, Valentina; Mattei, Luca; Trappolini, Massimo; Festa, Camilla; Stoppo, Michela; Napoli, Angela

    2010-08-01

    Hypertensive disorders in pregnancy can be chronic, pregestational or just diagnosed before the 20th week, or newly diagnosed in the second half of pregnancy. Any type of hypertension is more frequent in diabetic pregnancies with a different distribution among different types of diabetes. Most of the evidence is for pre-eclampsia associated with a marked increase in primary caesarean section, preterm birth and more need for neonatal intensive care. Different risk factors and pregnancy outcomes would support the hypothesis that pre-eclampsia and gestational hypertension might be largely separate entities, but this position is not unanimously accepted. Chronic hypertension increases with age and duration of diabetes, predicting increased rates of prematurity and neonatal morbidity, especially when associated with superimposed pre-eclampsia. Long-term consequences are observed in women whose pregnancy was complicated by hypertension such as chronic hypertension and cardiovascular diseases. PMID:20832742

  19. The hypertensive disorders of pregnancy (29.3).

    PubMed

    Magee, Laura A; Pels, Anouk; Helewa, Michael; Rey, Evelyne; von Dadelszen, Peter

    2015-07-01

    Hypertensive disorders are the most common medical complication of pregnancy. As such, a large part of antenatal care is dedicated to the detection of pre-eclampsia, the most dangerous of the hypertensive disorders. The highlights of this chapter include progress in the use of out-of-office blood pressure measurement as an adjunct to office blood pressure measurement, pre-eclampsia defined as proteinuria or relevant end-organ dysfunction, antihypertensive therapy for severe and non-severe hypertension and post-partum follow-up to mitigate the increased cardiovascular risk associated with any of the hypertensive disorders of pregnancy.

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

    PubMed Central

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

    2006-01-01

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

  1. [Pericardial effusion and pleural serositis in patients with severe preeclampsia and HELLP syndrome].

    PubMed

    Quiroz, María Nayeli Salas; Rodríguez, Héctor Xavier Alfaro; Lara, Daniel S Zúñiga

    2009-11-01

    The syndrome pre-eclampsia/eclampsia is a frequent entity in the obstetrical pathology and acquires interest to take to the patients to a critical state. It has repercussion in all the organism by his complications. The definitive treatment of pre-eclampsia/eclampsia is the interruption of the pregnancy. The pericardial effussion as severe complication of pre-eclampsia and Sx de HELLP is a little frequent entity. Few cases reported in Literature exists. In the Hospital Angeles Pedregal, two cases of patients embarrassed without antecedents of previous picture hypertensive, complicated are reported with severe pre-eclampsia and HELLP syndrome class II of Martin which developed pericardial effussion without presence of tamponade. The knowledge of the behavior of this cardiovascular complication as well as the multidisciplinary and integral handling, are without a doubt the best form to modify the evolution and to avoid the appearance of tamponade. The acute pericardial effussion can get to mean a medical urgency that puts in danger the life. Mainly when the intrapericardic pressure so is lifted that the heart is compressed and the diastolic pressures ventricular lefts and right are increased and in the absence of preexisting cardiac pathology, these pressures get to equal itself. This complication little frequents must be had in mind like more of the haemodynamic complications.

  2. Hypertensive disorders of pregnancy, respiratory outcomes and atopy in childhood.

    PubMed

    Shaheen, Seif O; Macdonald-Wallis, Corrie; Lawlor, Debbie A; Henderson, A John

    2016-01-01

    Few epidemiological studies have investigated the role of hypertensive disorders of pregnancy in the aetiology of childhood respiratory and atopic outcomes.In the Avon Longitudinal Study of Parents and Children we examined associations of maternal gestational hypertension, hypertension before pregnancy and pre-eclampsia with wheezing at 18 months, wheezing and asthma at 7 years and lung function at 8-9 years, after controlling for potential confounders (n=5322-8734, depending on outcome).Gestational hypertension was not associated with any of the outcomes. There was weak evidence for a positive association between pre-eclampsia and early wheezing (adjusted OR 1.31, 95% CI 0.94-1.82, compared to normotensive pregnancies) and for negative associations between pre-eclampsia and forced expiratory volume in 1 s (adjusted mean difference in sd score -0.14, 95% CI -0.33-0.06) and maximal mid-expiratory flow (-0.15, 95% CI -0.34-0.04). Hypertension before pregnancy was positively associated with wheezing (OR 1.63, 95% CI 1.16-2.31) and asthma (OR 1.34, 95% CI 1.00-1.79).Gestational hypertension is unlikely to be a risk factor for childhood respiratory disorders; hypertension before pregnancy may be a risk factor for childhood wheezing and asthma, but this finding needs replication. Larger studies are needed to confirm whether pre-eclampsia is associated with impaired childhood lung function.

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

    PubMed Central

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

    2010-01-01

    Problem Emerging evidence suggests that metabolism influences immune cell signaling and immunoregulation. To examine the immunoregulatory role of glycolysis in pregnancy, we evaluated the properties of pyruvate kinase in leukocytes from non-pregnant women and those with normal pregnancy and pre-eclampsia. Method of study We evaluated pyruvate kinase expression in lymphocytes and neutrophils from non-pregnant, pregnant, and pre-eclampsia patients using fluorescence microscopy and flow cytometry. Leukocyte pyruvate kinase activity and pyruvate concentrations were also evaluated. To study pyruvate’s effect on signaling, we labeled Jurkat T cells with Ca2+ dyes and measured cell responses in the presence of agents influencing intracellular pyruvate. Results The expression of pyruvate kinase is reduced in lymphocytes and neutrophils from normal pregnant women in comparison to those of non-pregnant women and pre-eclampsia patients. Similarly, the activity of pyruvate kinase and the intracellular pyruvate concentration are reduced in leukocytes of normal pregnant women in comparison to non-pregnant women and women with pre-eclampsia. Using Jurkat cells as a model of leukocyte signaling, we have shown that perturbations of intracellular pyruvate influence Ca2+ signals. Conclusion Normal pregnancy is characterized by reduced pyruvate kinase expression within lymphocytes and neutrophils. We speculate that reduced pyruvate kinase expression modifies immune cell responses due to reduced pyruvate concentrations. PMID:20560913

  4. Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice.

    PubMed

    Chatterjee, Piyali; Chiasson, Valorie L; Pinzur, Lena; Raveh, Shani; Abraham, Eytan; Jones, Kathleen A; Bounds, Kelsey R; Ofir, Racheli; Flaishon, Liat; Chajut, Ayelet; Mitchell, Brett M

    2016-04-01

    Pre-eclampsia, the development of hypertension and proteinuria or end-organ damage during pregnancy, is a leading cause of both maternal and fetal morbidity and mortality, and there are no effective clinical treatments for pre-eclampsia aside from delivery. The development of pre-eclampsia is characterized by maladaptation of the maternal immune system, excessive inflammation and endothelial dysfunction. We have reported that detection of extracellular RNA by the Toll-like receptors (TLRs) 3 and 7 is a key initiating signal that contributes to the development of pre-eclampsia. PLacental eXpanded (PLX-PAD) cells are human placenta-derived, mesenchymal-like, adherent stromal cells that have anti-inflammatory, proangiogenic, cytoprotective and regenerative properties, secondary to paracrine secretion of various molecules in response to environmental stimulation. We hypothesized that PLX-PAD cells would reduce the associated inflammation and tissue damage and lower blood pressure in mice with pre-eclampsia induced by TLR3 or TLR7 activation. Injection of PLX-PAD cells on gestational day 14 significantly decreased systolic blood pressure by day 17 in TLR3-induced and TLR7-induced hypertensive mice (TLR3 144-111 mmHg; TLR7 145-106 mmHg; both P<0.05), and also normalized their elevated urinary protein:creatinine ratios (TLR3 5.68-3.72; TLR7 5.57-3.84; both P<0.05). On gestational day 17, aortic endothelium-dependent relaxation responses improved significantly in TLR3-induced and TLR7-induced hypertensive mice that received PLX-PAD cells on gestational day 14 (TLR3 35-65%; TLR7 37-63%; both P<0.05). In addition, markers of systemic inflammation and placental injury, increased markedly in both groups of TLR-induced hypertensive mice, were reduced by PLX-PAD cells. Importantly, PLX-PAD cell therapy had no effects on these measures in pregnant control mice or on the fetuses. These data demonstrate that PLX-PAD cell therapy can safely reverse pre-eclampsia-like features during

  5. Classification of hypertension in pregnancy.

    PubMed

    Brown, M A; de Swiet, M

    1999-03-01

    In many ways there should be no need to classify hypertensive disorders in clinical practice. The very presence of rising blood pressure should alert the clinician to seek evidence for the development of pre-eclampsia and whether there are any emerging abnormalities of fetal growth and/or maternal renal, cerebral, hepatic or coagulation functions which may necessitate specific treatment, including delivery. While such a view may be appropriate for experienced clinicians with an understanding of the pathophysiology of the hypertensive disorders of pregnancy, it is of little help to junior or less experienced medical staff. Moreover, without an agreed international classification system it is impossible to compare truly clinical outcome, intervention or basic research studies from different units as entry criteria to these studies may differ considerably across individual units and certainly across countries. In this chapter we highlight the limitations of the existing classification systems and propose a system that is based on our present understanding of the pathophysiology of pre-eclampsia. The proposed system is not a radical departure from previous classifications, with grouping of hypertensive subjects into gestational hypertension, pre-eclampsia and chronic (usually essential) hypertension. Proteinuria, while remaining a hallmark of pre-eclampsia, is no longer considered a 'sine qua non' for this disorder to be diagnosed, reflecting our greater understanding of the maternal and fetal abnormalities in pre-eclampsia since previous classification systems were developed. This classification system has been compared with the traditional system of diagnosing proteinuric pre-eclampsia in a study of 1183 women with hypertension in pregnancy: diagnosing pre-eclampsia in this new manner still stratifies a high-risk group of pregnant women and the proposed diagnosis of gestational hypertension in this system stratifies a group of women at low maternal and fetal risk

  6. Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice.

    PubMed

    Chatterjee, Piyali; Chiasson, Valorie L; Pinzur, Lena; Raveh, Shani; Abraham, Eytan; Jones, Kathleen A; Bounds, Kelsey R; Ofir, Racheli; Flaishon, Liat; Chajut, Ayelet; Mitchell, Brett M

    2016-04-01

    Pre-eclampsia, the development of hypertension and proteinuria or end-organ damage during pregnancy, is a leading cause of both maternal and fetal morbidity and mortality, and there are no effective clinical treatments for pre-eclampsia aside from delivery. The development of pre-eclampsia is characterized by maladaptation of the maternal immune system, excessive inflammation and endothelial dysfunction. We have reported that detection of extracellular RNA by the Toll-like receptors (TLRs) 3 and 7 is a key initiating signal that contributes to the development of pre-eclampsia. PLacental eXpanded (PLX-PAD) cells are human placenta-derived, mesenchymal-like, adherent stromal cells that have anti-inflammatory, proangiogenic, cytoprotective and regenerative properties, secondary to paracrine secretion of various molecules in response to environmental stimulation. We hypothesized that PLX-PAD cells would reduce the associated inflammation and tissue damage and lower blood pressure in mice with pre-eclampsia induced by TLR3 or TLR7 activation. Injection of PLX-PAD cells on gestational day 14 significantly decreased systolic blood pressure by day 17 in TLR3-induced and TLR7-induced hypertensive mice (TLR3 144-111 mmHg; TLR7 145-106 mmHg; both P<0.05), and also normalized their elevated urinary protein:creatinine ratios (TLR3 5.68-3.72; TLR7 5.57-3.84; both P<0.05). On gestational day 17, aortic endothelium-dependent relaxation responses improved significantly in TLR3-induced and TLR7-induced hypertensive mice that received PLX-PAD cells on gestational day 14 (TLR3 35-65%; TLR7 37-63%; both P<0.05). In addition, markers of systemic inflammation and placental injury, increased markedly in both groups of TLR-induced hypertensive mice, were reduced by PLX-PAD cells. Importantly, PLX-PAD cell therapy had no effects on these measures in pregnant control mice or on the fetuses. These data demonstrate that PLX-PAD cell therapy can safely reverse pre-eclampsia-like features during

  7. Serum levels of interleukin-6, interleukin-1beta and human chorionic gonadotropin in pre-eclamptic and normal pregnancy.

    PubMed

    Casart, Ysabel C; Tarrazzi, Katiuska; Camejo, María I

    2007-05-01

    Studies in placentas from the first trimester and in vitro models indicate that interleukin (IL)-1beta and IL-6 induce the release of human chorionic gonadotropin (hCG). During pre-eclampsia there is an increase of pro-inflammatory cytokines; however, its relationship with hCG levels during the third trimester of pregnancy has not been determined. The aim of the present study was to evaluate the relationship between blood levels of IL-6, IL-1beta and hCG in normal pregnancy and pre-eclampsia. Blood samples during the third trimester of pregnancy from women with severe pre-eclampsia (n = 20) or normal pregnancy (n = 20) were assayed for hCG by immunoassay, IL-6 and IL-1beta by enzyme-linked immunosorbent assay. Serum level of IL-6 was significantly higher in pre-eclamptic than in normal women (16.5 +/- 2.1 vs. 4.9 +/- 1.1 pg/ml); however, IL-1beta was similar in both groups. Although hCG was higher in pre-eclampsia than normal pregnancy, the difference was not statistically significant. Furthermore, IL-1beta in normal pregnancy was correlated negatively with hCG (r = -0.69, p < 0.001). In conclusion, serum levels of IL-6 were increased in pre-eclampsia but were not correlated with hCG or IL-1beta; however, in normal pregnancy there was a negative correlation between IL-1beta and hCG. The interaction between IL-1beta and hCG at the third trimester needs to be investigated.

  8. HELLP syndrome: a diagnostic conundrum with severe complications.

    PubMed

    Rao, Devika; Chaudhari, Nikulkumar Kumar; Moore, Robert Michael; Jim, Belinda

    2016-01-01

    The HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome is believed to be part of the spectrum of pre-eclampsia, which falls within the category of hypertensive disorders of pregnancy. Maternal and fetal complications are more severe in HELLP as opposed to pre-eclampsia alone. We describe a 26-year-old primigravida woman with no medical history who presents with signs of HELLP with marked transaminitis and mild disseminated intravascular coagulation at 35 weeks of gestation who required emergent delivery of the fetus; the patient also sustained acute kidney injury requiring continuous veno-venous hemodiafiltration and a prolonged intensive care unit admission. Remarkably, with supportive care, all laboratory derangements, including renal function, normalised after 4 weeks. We discuss the diagnostic conundrum when faced with the possible diagnosis of HELLP in discriminating from its many imitators in order to assume proper treatment. PMID:27535735

  9. Inadequate vitamin D status in pregnancy: evidence for supplementation.

    PubMed

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

    2012-02-01

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

  10. [Up-to-date on the HELLP syndrome (Hemolysis, Elevated Liver enzymes and Low Platelets)].

    PubMed

    Medhioub Kaaniche, F; Chaari, A; Turki, O; Rgaieg, K; Baccouch, N; Zekri, M; Bahloul, M; Chelly, H; Ben Hamida, Ch; Bouaziz, M

    2016-06-01

    HELLP syndrome is an acronym for Hemolysis, Elevated Liver enzymes and Low Platelets. It is generally considered in the literature as a particular clinical form of pre-eclampsia, a severe complication of the second half of pregnancy. However, this syndrome can occur in isolation in the absence of pre-eclampsia symptoms. Its pathophysiology remains still unclear. The clinical picture is often incomplete and fruste at first. To date, its diagnosis and management is still the subject of much controversy. Associated or not with a vascular and renal manifestations, the HELLP syndrome is a high-risk maternal disorder. The objective of this article is to review the pathophysiological and clinical data and current treatment.

  11. Moving beyond silos: How do we provide distributed personalized medicine to pregnant women everywhere at scale? Insights from PRE-EMPT.

    PubMed

    von Dadelszen, Peter; Magee, Laura A; Payne, Beth A; Dunsmuir, Dustin T; Drebit, Sharla; Dumont, Guy A; Miller, Suellen; Norman, Jane; Pyne-Mercier, Lee; Shennan, Andrew H; Donnay, France; Bhutta, Zulfiqar A; Ansermino, J Mark

    2015-10-01

    While we believe that pre-eclampsia matters-because it remains a leading cause of maternal and perinatal morbidity and mortality worldwide-we are convinced that the time has come to look beyond single clinical entities (e.g. pre-eclampsia, postpartum hemorrhage, obstetric sepsis) and to look for an integrated approach that will provide evidence-based personalized care to women wherever they encounter the health system. Accurate outcome prediction models are a powerful way to identify individuals at incrementally increased (and decreased) risks associated with a given condition. Integrating models with decision algorithms into mobile health (mHealth) applications could support community and first level facility healthcare providers to identify those women, fetuses, and newborns most at need of facility-based care, and to initiate lifesaving interventions in their communities prior to transportation. In our opinion, this offers the greatest opportunity to provide distributed individualized care at scale, and soon. PMID:26433496

  12. Management of hypertensive disorders in pregnancy.

    PubMed

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

    2014-07-01

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

  13. Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy

    PubMed Central

    Oudejans, Cees; Poutsma, Ankie; Michel, Omar; Mulders, Joyce; Visser, Allerdien; van Dijk, Marie; Nauta, Tessa; Bokslag, Anouk; Paulus, Walter; de Haas, Andreas; Koolwijk, Pieter; de Groot, Christianne J. M.

    2016-01-01

    Background The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia. Findings We assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters. Conclusion The current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies. PMID:26870946

  14. Assessing perinatal depression as an indicator of risk for pregnancy-associated cardiovascular disease.

    PubMed

    Nicholson, Lauren; Lecour, Sandrine; Wedegärtner, Sonja; Kindermann, Ingrid; Böhm, Michael; Sliwa, Karen

    2016-01-01

    Cardiovascular conditions associated with pregnancy are serious complications. In general, depression is a well-known risk indicator for cardiovascular disease (CVD). Mental distress and depression are associated with physiological responses such as inflammation and oxidative stress. Both inflammation and oxidative stress have been implicated in the pathophysiology of CVDs associated with pregnancy. This article discusses whether depression could represent a risk indicator for CVDs in pregnancy, in particular in pre-eclampsia and peripartum cardiomyopathy (PPCM). PMID:27213860

  15. Capgras' syndrome with organic disorders.

    PubMed Central

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

    1990-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. Acute renal failure after treatment with sunitinib in a patient with multiple myeloma.

    PubMed

    Leung, Nelson; Saucier, Nathan A; Zeldenrust, Steven R; Gunderson, Heidi D; Cornell, Lynn D

    2009-08-01

    Sunitinib is a multiple tyrosine kinase receptors inhibitor that is approved for the treatment of advanced renal cell carcinoma. Amongst its targets are fetal liver tyrosine kinase receptor 3 (FLT 3) and vascular endothelial growth factor receptor (VEGFR). Renal toxicity has not been reported from the trials, but several patients have been reported to develop a pre-eclampsia-like syndrome. We report the first case of acute tubular necrosis in a patient with multiple myeloma following treatment with sunitinib.

  18. Why is there a modifying effect of gestational age on risk factors for cerebral palsy?

    PubMed Central

    Greenwood, C; Yudkin, P; Sellers, S; Impey, L; Doyle, P

    2005-01-01

    Objective: To investigate risk factors for cerebral palsy in relation to gestational age. Design: Three case-control studies within a geographically defined cohort. Setting: The former Oxfordshire Health Authority. Participants: A total of 235 singleton children with cerebral palsy not of postnatal origin, born between 1984 and 1993, identified from the Oxford Register of Early Childhood Impairment; 646 controls matched for gestation in three bands: ⩽32 weeks; 33–36 weeks; ⩾37 weeks. Results: Markers of intrapartum hypoxia and infection were associated with an increased risk of cerebral palsy in term and preterm infants. The odds ratio (OR) for hypoxia was 12.2 (95% confidence interval 1.2 to 119) at ⩽32 weeks and 146 (7.4 to 3651) at ⩾37 weeks. Corresponding ORs for neonatal sepsis were 3.1 (1.8 to 5.4) and 10.6 (2.1 to 51.9). In contrast, pre-eclampsia carried an increased risk of cerebral palsy at ⩾37 weeks (OR 5.1 (2.2 to 12.0)) but a decreased risk at ⩽32 weeks (OR 0.4 (0.2 to 1.0)). However, all infants ⩽32 weeks with maternal pre-eclampsia were delivered electively, and their risk of cerebral palsy was no lower than that of other electively delivered ⩽32 week infants (OR 0.9 (0.3 to 2.7)). Nearly 60% of ⩽32 week controls were delivered after spontaneous preterm labour, itself an abnormal event. Conclusion: Inflammatory processes, including pre-eclampsia, are important in the aetiology of cerebral palsy. The apparent reduced risk of cerebral palsy associated with pre-eclampsia in very preterm infants is driven by the characteristics of the gestation matched control group. Use of the term "protective" in this context should be abandoned. PMID:15724038

  19. Uterine Receptivity to Human Embryonic Implantation: Histology, Biomarkers, and Transcriptomics

    PubMed Central

    Aghajanova, L; Hamilton, AE; Giudice, LC

    2008-01-01

    Embryonic implantation is a dynamic process of paracrine interactions between the maternal compartment and the conceptus and involves a receptive endometrium and a developmentally competent blastocyst. Herein, we review histology, clinical approaches, and the promise of transcriptomics in elucidating mechanisms underlying implantation and development of biomarkers of uterine receptivity - with an eye to diagnose and treat implantation-based disorders of miscarriage, fetal growth restriction, pre-eclampsia, and infertility. PMID:18035563

  20. Thrombophilia and Pregnancy Complications

    PubMed Central

    Simcox, Louise E.; Ormesher, Laura; Tower, Clare; Greer, Ian A.

    2015-01-01

    There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question. PMID:26633369

  1. Defective implantation and placentation: laying the blueprint for pregnancy complications.

    PubMed

    Norwitz, Errol R

    2006-10-01

    Normal implantation and placentation is critical for pregnancy success. Many pregnancy-related complications that present late in gestation (such as pre-eclampsia and preterm labour) appear to have their origins early in pregnancy with abnormalities in implantation and placental development. Implantation is characterized by invasion of the maternal tissues of the uterus by fetal trophoblast, and the degree to which trophoblast invades these tissues appears to be a major determinant of pregnancy outcome. Excessive invasion can lead to abnormally firm attachment of the placenta to the myometrium (placenta accreta) with increased maternal and perinatal morbidity. Inadequate invasion, specifically restricted endovascular invasion, has been implicated in the pathophysiology of such conditions as pre-eclampsia (gestational proteinuric hypertension), preterm premature rupture of membranes, preterm labour, and intrauterine growth restriction. The molecular and cellular mechanisms responsible for implantation remain enigmatic. This review will include an overview of implantation followed by a discussion of a number of molecular mechanisms implicated in defective implantation and placentation including the role of decidual prostaglandins and haemorrhage in regulating trophoblast invasion. An improved understanding of the molecular mechanisms responsible for abnormal implantation and placentation will likely improve clinicians' abilities to treat disorders that occur along this continuum, including infertility, recurrent pregnancy loss, pre-eclampsia, and preterm birth.

  2. Defective implantation and placentation: laying the blueprint for pregnancy complications.

    PubMed

    Norwitz, Errol R

    2007-01-01

    Normal implantation and placentation is critical for pregnancy success. Many pregnancy-related complications that present late in gestation (such as pre-eclampsia and preterm labour) appear to have their origins early in pregnancy with abnormalities in implantation and placental development. Implantation is characterized by invasion of the maternal tissues of the uterus by fetal trophoblast, and the degree to which trophoblast invades these tissues appears to be a major determinant of pregnancy outcome. Excessive invasion can lead to abnormally firm attachment of the placenta to the myometrium (placenta accreta) with increased maternal and perinatal morbidity. Inadequate invasion, specifically restricted endovascular invasion, has been implicated in the pathophysiology of such conditions as pre-eclampsia (gestational proteinuric hypertension), preterm premature rupture of membranes, preterm labour, and intrauterine growth restriction. The molecular and cellular mechanisms responsible for implantation remain enigmatic. This review will include an overview of implantation followed by a discussion of a number of molecular mechanisms implicated in defective implantation and placentation including the role of decidual prostaglandins and haemorrhage in regulating trophoblast invasion. An improved understanding of the molecular mechanisms responsible for abnormal implantation and placentation will likely improve clinicians' abilities to treat disorders that occur along this continuum, including infertility, recurrent pregnancy loss, pre-eclampsia, and preterm birth.

  3. Gene expression profiling of pre-eclamptic placentae by RNA sequencing

    PubMed Central

    Kaartokallio, Tea; Cervera, Alejandra; Kyllönen, Anjuska; Laivuori, Krista; Laivuori, Hannele; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli

    2015-01-01

    Pre-eclampsia is a common and complex pregnancy disorder that often involves impaired placental development. In order to identify altered gene expression in pre-eclamptic placenta, we sequenced placental transcriptomes of nine pre-eclamptic and nine healthy pregnant women in pools of three. The differential gene expression was tested both by including all the pools in the analysis and by excluding some of the pools based on phenotypic characteristics. From these analyses, we identified altogether 53 differently expressed genes, a subset of which was validated by qPCR in 20 cases and 19 controls. Furthermore, we conducted pathway and functional analyses which revealed disturbed vascular function and immunological balance in pre-eclamptic placenta. Some of the genes identified in our study have been reported by numerous microarray studies (BHLHE40, FSTL3, HK2, HTRA4, LEP, PVRL4, SASH1, SIGLEC6), but many have been implicated in only few studies or have not previously been linked to pre-eclampsia (ARMS2, BTNL9, CCSAP, DIO2, FER1L4, HPSE, LOC100129345, LYN, MYO7B, NCMAP, NDRG1, NRIP1, PLIN2, SBSPON, SERPINB9, SH3BP5, TET3, TPBG, ZNF175). Several of the molecules produced by these genes may have a role in the pathogenesis of pre-eclampsia, and some could qualify as biomarkers for prediction or detection of this pregnancy complication. PMID:26388242

  4. Thrombophilia and Pregnancy Complications.

    PubMed

    Simcox, Louise E; Ormesher, Laura; Tower, Clare; Greer, Ian A

    2015-01-01

    There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question.

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

    PubMed

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

    2012-12-01

    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.

  6. Gene expression profiling of pre-eclamptic placentae by RNA sequencing.

    PubMed

    Kaartokallio, Tea; Cervera, Alejandra; Kyllönen, Anjuska; Laivuori, Krista

    2015-01-01

    Pre-eclampsia is a common and complex pregnancy disorder that often involves impaired placental development. In order to identify altered gene expression in pre-eclamptic placenta, we sequenced placental transcriptomes of nine pre-eclamptic and nine healthy pregnant women in pools of three. The differential gene expression was tested both by including all the pools in the analysis and by excluding some of the pools based on phenotypic characteristics. From these analyses, we identified altogether 53 differently expressed genes, a subset of which was validated by qPCR in 20 cases and 19 controls. Furthermore, we conducted pathway and functional analyses which revealed disturbed vascular function and immunological balance in pre-eclamptic placenta. Some of the genes identified in our study have been reported by numerous microarray studies (BHLHE40, FSTL3, HK2, HTRA4, LEP, PVRL4, SASH1, SIGLEC6), but many have been implicated in only few studies or have not previously been linked to pre-eclampsia (ARMS2, BTNL9, CCSAP, DIO2, FER1L4, HPSE, LOC100129345, LYN, MYO7B, NCMAP, NDRG1, NRIP1, PLIN2, SBSPON, SERPINB9, SH3BP5, TET3, TPBG, ZNF175). Several of the molecules produced by these genes may have a role in the pathogenesis of pre-eclampsia, and some could qualify as biomarkers for prediction or detection of this pregnancy complication. PMID:26388242

  7. 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

    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

    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 PMID:20563311

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

    PubMed

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

    2009-01-01

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

  9. Pregnancy outcomes associated with viral hepatitis.

    PubMed

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

    2011-07-01

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

  10. A novel exonic variant (221delT) in the LGALS13 gene encoding placental protein 13 (PP13) is associated with preterm labour in a low risk population.

    PubMed

    Gebhardt, S; Bruiners, N; Hillermann, R

    2009-11-01

    Predicting adverse pregnancy outcome in low risk patients in a community with poor socio-economic circumstances is difficult, yet about 5% of these pregnancies will result in preterm labour or severe pre-eclampsia. In this study we aimed to identify markers in pro- and anti-inflammatory genes that may contribute to disease and possibly disease prediction in a low risk community setting. A prospective study was undertaken on 450 consecutive low risk primigravid patients. Blood obtained at first booking was screened for known immunological gene variants (IL4 -590, IL1B +3953, IL1RN, IL10 -1082; -819; -592 and TNFA -308; -238; +488) as well as for novel variants in the LGALS13 gene coding for placental protein 13 (PP13). The incidence of preterm labour and pre-eclampsia was 7.1% and 6.8% respectively. A novel exonic variant (221delT) in the LGALS13 gene increased the risk for preterm labour in the total study group (relative risk RR 2.27). Maternal carriage of the interleukin-1 RN*2 allele was associated with an increased risk of hypertension in pregnancy in the Coloured subgroup of the study cohort (RR 2.53). There was an increased risk for preterm labour in the same subgroup with carriage of the TNFA -308 A-allele (TNF2) (RR 2.53). No significance was found for the other variants examined. We conclude that single nucleotide polymorphisms (SNPs) in certain genes regulating implantation and inflammation may contribute to the complex etiology of pre-eclampsia and preterm labour. The association between the 221delT deletion and adverse pregnancy outcome needs to be confirmed in different populations.

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

    PubMed Central

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

    1996-01-01

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

  12. Pregnancy close to the edge: an immunosuppressive infiltrate in the chorionic plate of placentas from uncomplicated egg cell donation.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

    2013-01-01

    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

  14. Managing pregnancy with HIV, HELLP syndrome and low platelets.

    PubMed

    Onyangunga, O A; Moodley, J

    2012-02-01

    Management of pregnancies with human immunodeficiency virus, haemolytic anaemia, elevated liver enzymes, low platelets (HELLP) syndrome, and low platelets presents complexities in investigations and treatments, because these conditions and their treatment affect the mother and baby. Low platelets in severe pre-eclampsia, eclampsia and HELLP syndrome are relatively common, and should be detected early once the diagnosis of pre-eclampsia, HELLP syndrome, or both, are made. The mainstay of treatment is lowering of high blood pressure with rapid-acting antihypertensive agents, prevention of convulsions or further seizures with MgSO(4), use of steroids for fetal lung maturity if necessary, followed by delivery of the baby. The use of high-dose steroids for the rapid recovery of maternal platelet counts is controversial, and should not be used routinely in women with HELLP syndrome. The use of platelet transfusion in women with severe pre-eclampsia, eclampsia and HELLP syndrome is a temporising measure, and should only be justified if the clinical circumstances warrant their use (e.g. before caesarean section when the woman has a low platelet count with evidence of bruising or bleeding from venepuncture sites). Low platelets may be an isolated finding in asymptomatic pregnant women and warrant the offer of a human immunodeficiency virus test, as it may be the first sign of this infection. Isolated low platelets may also indicate gestational thrombocytopaenia or idiothrombocytopaenic purpura. Gestational thrombocytopaenia is a benign condition and a diagnosis of exclusion. All clinicians should be aware that low platelets warrant further investigations because of the above-mentioned issues.

  15. Diagnosis of a Myeloproliferative Disorder in Late Pregnancy

    PubMed Central

    Okoli, S; Wilkins, B; Robinson, S; Harrison, C

    2013-01-01

    A 38-year-old primiparous woman presented with pre-eclampsia at 36 weeks gestation with an abnormal full blood count and leukoerythroblastic blood film. JAK2 V617F was negative and splenomegaly was noted on abdominal ultrasound. Delivery was at 37 weeks gestation by emergency caesarean section due to abnormal cardiotocography. Bone marrow aspirate and trephine confirmed a diagnosis of myelofibrosis. The case highlights a rare presentation of primary myelofibrosis in pregnancy, the difficulties in management, and the UK Obstetric Surveillance System who are collecting epidemiological data on uncommon disorders in pregnancy.

  16. [Hypertension: is the actual definition adapted to women?].

    PubMed

    Wuerzner, G; Bochud, M; Jaunin-Stalder, N; Pechère-Bertschi, A

    2010-07-28

    The control of blood pressure in men and women differs due to different physiological pathways. Moreover, conditions increasing the risk of hypertension, such as pre-eclampsia, exposure to oral contraceptives are specific to women. Men have a higher blood pressure than women from pubertal growth to advanced age. However, the definition of hypertension (blood pressure--140/90 mmHg) is the same for adult men and women. The management of hypertension should be based not only on the level of blood pressure, but also on the global cardiovascular risk. Sex is included in the global evaluation of the cardiovascular risk.

  17. Antithrombin deficiency in pregnancy.

    PubMed

    Durai, Shivani; Tan, Lay Kok; Lim, Serene

    2016-01-01

    We present a case of a 39-year-old, gravida 3 para 2, Chinese female with a history of inherited type 1 Antithrombin deficiency and multiple prior episodes of venous thromboembolism. She presented at 29+4 weeks' gestation with severe pre-eclampsia complicated by haemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. She subsequently underwent an emergency caesarean section for non-reassuring fetal status, which was complicated by postpartum haemorrhage secondary to uterine atony, requiring a B-Lynch suture intraoperatively. PMID:27207982

  18. Does pre-pregnancy BMI determine blood pressure during pregnancy? A prospective cohort study

    PubMed Central

    Zuithoff, Peter; Browne, Joyce L; Amelia, Dwirani; Baharuddin, Mohammad; Grobbee, Diederick E; Uiterwaal, Cuno S P M

    2016-01-01

    Objectives To evaluate if pre-pregnancy body mass index (BMI) determines blood pressure throughout pregnancy and to explore the role of gestational weight gain in this association. In addition, the effects of pre-pregnancy BMI and gestational weight gain on the occurrence of gestational hypertension and pre-eclampsia were investigated. Design Prospective cohort study. Setting Maternal and child health primary care referral centre, Jakarta, Indonesia. Population and measurements 2252 pregnant women visiting Budi Kemuliaan Hospital and its branch for regular antenatal care visits from July 2012 to April 2015. Pre-pregnancy BMI (kg/m2) was based on self-reported pre-pregnancy weight and measured height at first visit. Gestational weight gain was calculated as weight at the day of delivery minus the pre-pregnancy weight. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured during pregnancy at every visit. Linear mixed models were used to analyse this relation with repeated blood pressure measures as the outcome and pre-pregnancy BMI as the predictor. When looking at gestational hypertension and pre-eclampsia as outcomes, (multiple) logistic regression was used in the analysis. Results Independent of pre-pregnancy BMI, SBP and DBP increased by 0.99 mm Hg/month and 0.46 mm Hg/month, respectively. Higher pre-pregnancy BMI was associated with higher pregnancy SBP (0.25 mm Hg/kg/m2; 95% CI 0.17 to 0.34; p<0.01) and DBP (0.18 mm Hg/kg/m2; 0.13 to 0.24; p<0.01) in adjusted analysis. Every 1 kg/m2 higher pre-pregnancy BMI was associated with 6% and 9% higher odds for gestational hypertension (adjusted OR (aOR) 1.06; 95% CI 1.03 to 1.09; p<0.01) and pre-eclampsia (aOR 1.09; 1.04 to 1.14; p<0.01). Accounting for gestational weight gain did not attenuate these associations. Conclusions Pre-pregnancy BMI determines the level, but not the change, of blood pressure in pregnancy and is linked to higher odds for gestational hypertension and

  19. Successful angioplasty during pregnancy for renal artery stenosis.

    PubMed

    Margueritte, François; Velasco, Stephane; Pourrat, Olivier; Pierre, Fabrice

    2016-03-01

    Renal artery stenosis can be diagnosed during pregnancy and treated at the same time. A 30-year-old woman had a sudden, severe but asymptomatic hypertensive crisis at 21 weeks of gestation. The diagnosis of renal artery stenosis suspected on Doppler ultrasonography was confirmed and treated by renal angioplasty, which reduced her blood pressure. At 27 weeks of gestation, her blood pressure increased again, associated with significant proteinuria, suggesting pre-eclampsia. A cesarean section was performed giving birth to a healthy 940-g child. Renal artery stenosis should be considered when sudden and early-onset hypertension appears during pregnancy.

  20. Maternal complications in pregnancy with diabetes.

    PubMed

    Kulshrestha, Vidushi; Agarwal, Nutan

    2016-09-01

    Maternal complications of diabetes in pregnancy include obstetric complications such as pre-eclampsia, preterm labour, polyhydramnios, increased operative delivery and increased infective morbidity. These can be minimized with optimal glycaemic control. Additionally, pregnancies with overt/pregestational diabetes may have diabetes related complications such as hypoglycaemia, worsening of retinopathy, nephropathy and diabetic ketoacidosis. Women with pre-existing diabetic vasculopathy should be managed with multi-disciplinary approach with maternal and foetal surveillance to detect any deterioration. Such patients have a poor pregnancy outcome. Gastropathy and coronary artery disease in diabetics is a contraindication to pregnancy. PMID:27582159

  1. Cardiovascular disease screening.

    PubMed

    Duffy, Jennifer Y; Hameed, Afshan B

    2015-06-01

    Cardiovascular disease is the leading cause of death amongst women worldwide. Cardiovascular risk assessment and primary prevention are important strategies to improve morbidity and mortality. In additional to the traditional risk factors, pregnancy complications such as pre-eclampsia and gestational diabetes increment future risk of developing cardiovascular complications. Additionally, several serum biomarkers are valuable measures for both risk assessment and predictors of clinical outcomes in women. The purpose of this review is to describe current risk stratification schemes as well as outline the role of obstetric history and serum biomarkers in adjusting risk stratification in women. PMID:26143091

  2. Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators.

    PubMed

    Pourrat, O; Coudroy, R; Pierre, F

    2015-06-01

    Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe consequences for maternal health, and this can be fatal when thrombotic thrombocytopenic purpura is misdiagnosed as severe HELLP syndrome. The aim of this paper is to propose relevant markers to differentiate pre-eclampsia complicated by severe HELLP syndrome from its imitators, even in the worrying situation of apparently indistinguishable conditions, and thereby assist clinical decision-making regarding whether or not to commence plasma exchange. Relevant identifiers to establish the most accurate diagnosis include the frequency of each disease and anamnestic data. Frank hemolysis, need for dialysis, neurological involvement and absence of disseminated intravascular coagulation are indicative of thrombotic microangiopathy. The definitive marker for thrombotic thrombocytopenic purpura is undetectable ADAMTS 13 activity. PMID:25879992

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

    PubMed Central

    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

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

  4. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome

    PubMed Central

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-01-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome. PMID:26229389

  5. ENDOCRINOLOGY IN PREGNANCY: Influence of maternal vitamin D status on obstetric outcomes and the fetal skeleton.

    PubMed

    Moon, Rebecca J; Harvey, Nicholas C; Cooper, Cyrus

    2015-08-01

    Vitamin D status has been increasingly associated with wide-ranging clinical outcomes. There is now a wealth of observational studies reporting on its associations with obstetric complications, including pre-eclampsia, gestational diabetes and the mode and timing of delivery. The findings are inconsistent, and currently there is a lack of data from high-quality intervention studies to confirm a causal role for vitamin D in these outcomes. This is similarly true with regards to fetal development, including measures of fetal size and skeletal mineralisation. Overall, there is an indication of possible benefits of vitamin D supplementation during pregnancy for offspring birthweight, calcium concentrations and bone mass as well as for reduced maternal pre-eclampsia. However, for none of these outcomes is the current evidence base conclusive, and the available data justify the instatement of high-quality randomised placebo controlled trials in a range of populations and health care settings to establish the potential efficacy and safety of vitamin D supplementation to improve particular outcomes. PMID:25862787

  6. Reducing morbidity and mortality among pregnant obese.

    PubMed

    Harper, Ann

    2015-04-01

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

  7. Adverse Pregnancy Outcomes and Cardiovascular Risk Factor Management

    PubMed Central

    Mehta, Puja K.; Minissian, Margo; Merz, C. Noel Bairey

    2015-01-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to established risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman’s risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia be evaluated for hypertension and other CVD risk factors within 6 months to 1 year post-partum. Given the burden and impact of CVD on women our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors. PMID:26159741

  8. Pre-oxygenation and apnoea in pregnancy: changes during labour and with obstetric morbidity in a computational simulation.

    PubMed

    McClelland, S H; Bogod, D G; Hardman, J G

    2009-04-01

    Using the Nottingham Physiology Simulator, we investigated the effects on pre-oxygenation and apnoea during rapid sequence induction of labour, obesity, sepsis, pre-eclampsia, maternal haemorrhage and multiple pregnancy in term pregnancy. Pre-oxygenation with 100% oxygen was followed by simulated rapid sequence induction when end-tidal nitrogen tension was less than 1 kPa, and apnoea. Labour, morbid obesity and sepsis accelerated pre-oxygenation and de-oxygenation during apnoea. Fastest pre-oxygenation was in labour, with 95% of the maximum change in expired oxygen tension occurring in 47 s, compared to 97 s in a standard pregnant subject. The labouring subject with a body mass index of 50 kg x m(-2) demonstrated the fastest desaturation, the time taken to fall to an arterial saturation < 90% being 98 s, compared to 292 s in a standard pregnant subject. Pre-eclampsia prolonged pre-oxygenation and tolerance to apnoea. Maternal haemorrhage and multiple pregnancy had minor effects. Our results inform the risk-benefit comparison of the anaesthetic options for Caesarean section.

  9. Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome.

    PubMed

    Vaught, Arthur J; Gavriilaki, Eleni; Hueppchen, Nancy; Blakemore, Karin; Yuan, Xuan; Seifert, Sara M; York, Sarah; Brodsky, Robert A

    2016-05-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome.

  10. Adverse pregnancy outcomes and cardiovascular risk factor management.

    PubMed

    Mehta, Puja K; Minissian, Margo; Bairey Merz, C Noel

    2015-06-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to establish risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman's risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia can be evaluated for hypertension and other CVD risk factors within 6 months to 1-year post-partum. Given the burden and impact of CVD on women in our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors. PMID:26159741

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

    PubMed

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

    2015-03-01

    As the age of pregnant women and prevalence of obesity and diabetes are increasing, so is the prevalence of medical disorders during pregnancy, particularly hypertension and the associated CKD. Pregnancy can worsen kidney function in women with severe disease, and hypertension puts them at risk for pre-eclampsia and the associated complications. There are no specific guidelines for hypertension management in this population, and tight control will not prevent pre-eclampsia. Women with end-stage kidney disease should be placed on intense dialysis regimens to improve obstetric outcomes, and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are best avoided. This article will review the rationale for a management plan that includes a multidisciplinary team to discuss risks and develop a plan before conception, antepartum monitoring for maternal and fetal morbidity, individualization of medical management using medications with established records during pregnancy, and balancing the level of blood pressure control proved to protect kidney function against the potential effects that aggressive blood pressure control could have on the fetal-placental unit.

  12. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome.

    PubMed

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-07-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome. PMID:26229389

  13. ENDOCRINOLOGY IN PREGNANCY: Influence of maternal vitamin D status on obstetric outcomes and the fetal skeleton.

    PubMed

    Moon, Rebecca J; Harvey, Nicholas C; Cooper, Cyrus

    2015-08-01

    Vitamin D status has been increasingly associated with wide-ranging clinical outcomes. There is now a wealth of observational studies reporting on its associations with obstetric complications, including pre-eclampsia, gestational diabetes and the mode and timing of delivery. The findings are inconsistent, and currently there is a lack of data from high-quality intervention studies to confirm a causal role for vitamin D in these outcomes. This is similarly true with regards to fetal development, including measures of fetal size and skeletal mineralisation. Overall, there is an indication of possible benefits of vitamin D supplementation during pregnancy for offspring birthweight, calcium concentrations and bone mass as well as for reduced maternal pre-eclampsia. However, for none of these outcomes is the current evidence base conclusive, and the available data justify the instatement of high-quality randomised placebo controlled trials in a range of populations and health care settings to establish the potential efficacy and safety of vitamin D supplementation to improve particular outcomes.

  14. Intergenerational exchange and perinatal risks: a note on interpretation of generational recurrence risks.

    PubMed

    Lie, Rolv T

    2007-07-01

    Population-based data that cover reproductive health outcomes across two complete generations have recently become available in the Nordic countries. Such data enable estimation of recurrence risks from one generation to the next of different conditions such as birth defects or pre-eclampsia. Risks related to a singleton pregnancy involve the contribution of three individuals: the mother, the father and the fetus. A paternal contribution is mainly through the father's contribution of half of the alleles of the fetus. A maternal contribution may occur in three fundamentally different ways. First, the mother provides half of the genomic alleles to the fetus, with contribution of paternal alleles completing the whole genome. Second, the mother provides the fetal environment and possible susceptibility to complications during pregnancy which she may have inherited from her mother. Finally, she provides the fetal mitochondria. Because of these different contributions, recurrence from mother to offspring is fundamentally different from recurrence from father to offspring. How recurrence risks reflect and shape the underlying contributions to overall perinatal risk is illustrated through a review of published data from Norway on gestational age, pre-eclampsia and birth defects.

  15. Maternal body mass index and risk of birth and maternal health outcomes in low- and middle-income countries: a systematic review and meta-analysis.

    PubMed

    Rahman, M M; Abe, S K; Kanda, M; Narita, S; Rahman, M S; Bilano, V; Ota, E; Gilmour, S; Shibuya, K

    2015-09-01

    We conducted a systematic review and meta-analysis of population-based cohort studies of maternal body mass index (BMI) and risk of adverse birth and health outcomes in low- and middle-income countries. PubMed, Embase, CINAHL and the British Nursing Index were searched from inception to February 2014. Forty-two studies were included. Our study found that maternal underweight was significantly associated with higher risk of preterm birth (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01-1.27), low birthweight (OR, 1.66; 95% CI, 1.50-1.84) and small for gestational age (OR, 1.85; 95% CI, 1.69-2.02). Compared with mothers with normal BMI, overweight or obese mothers were at increased odds of gestational diabetes, pregnancy-induced hypertension, pre-eclampsia, caesarean delivery and post-partum haemorrhage. The population-attributable risk (PAR) indicated that if women were entirely unexposed to overweight or obesity during the pre-pregnancy or early pregnancy period, 14% to 35% fewer women would develop gestational diabetes, pre-eclampsia or pregnancy-induced hypertension in Brazil, China, India, Iran or Thailand. The highest PAR of low birthweight attributable to maternal underweight was found in Iran (20%), followed by India (18%), Thailand (10%) and China (8%). Treatment and prevention of maternal underweight, overweight or obesity may help reduce the burden on maternal and child health in developing countries.

  16. Malignant hypertensive retinopathy as a presenting sign of an occult dead fetus

    PubMed Central

    Araújo, Joana; Tavares-Ferreira, João; Penas, Susana; Figueira, Luís; Paiva, Flávio Prézia; Falcão-Reis, Fernando

    2015-01-01

    We report one case of malignant hypertensive retinopathy as a presenting sign of fetal death in utero. Ophthalmic examination (including intravenous fluorescein angiography and optical coherence tomography) and obstetric and systemic evaluation were performed, providing a multidisciplinary approach. A 33-year-old overweight woman (body mass index 47 kg/m2) with no systemic or ocular known disease was admitted to our emergency department with a one-week history of bilateral vision loss and no systemic complaints. On examination, best corrected visual acuity was 1/10 in the right eye and 1/10 in the left eye. Anterior segment examination of both eyes was unremarkable. Ophthalmoscopic fundus findings included bilateral optic disc edema, diffuse cotton wool spots, intraretinal exudates, retinal hemorrhages, and multiple serous retinal detachments involving both maculae. Physical examination revealed a blood pressure of 220/110 mmHg. Further systemic workup revealed a previously unknown 35-week pregnancy with a dead fetus. An emergency cesarean section was performed. Pre-eclampsia is a life-threatening disorder for both mother and fetus. This case highlights the need to rule out pre-eclampsia in all women of childbearing age presenting with ocular signs of malignant hypertension, even without external signs of pregnancy. PMID:26082609

  17. Adverse pregnancy outcomes and cardiovascular risk factor management.

    PubMed

    Mehta, Puja K; Minissian, Margo; Bairey Merz, C Noel

    2015-06-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to establish risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman's risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia can be evaluated for hypertension and other CVD risk factors within 6 months to 1-year post-partum. Given the burden and impact of CVD on women in our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors.

  18. Relationship between ABO blood group and pregnancy complications: a systematic literature analysis

    PubMed Central

    Franchini, Massimo; Mengoli, Carlo; Lippi, Giuseppe

    2016-01-01

    Given the expression of ABO blood group antigens on the surface of a wide range of human cells and tissues, the putative interplay of the ABO system in human biology outside the area of transfusion and transplantation medicine constitutes an intriguing byway of research. Thanks to evidence accumulated over more than 50 years, the involvement of the ABO system in the pathogenesis of several human diseases, including cardiovascular, infectious and neoplastic disorders, is now acknowledged. However, there is controversial information on the potential association between ABO blood type and adverse pregnancy outcomes, including pre-eclampsia and related disorders (eclampsia, HELLP syndrome and intrauterine growth restriction), venous thromboembolism, post-partum haemorrhage and gestational diabetes. To elucidate the role of ABO antigens in pregnancy-related complications, we performed a systematic review of the literature published in the past 50 years. A meta-analytical approach was also applied to the existing literature on the association between ABO status and pre-eclampsia. The results of this systematic review are presented and critically discussed, along with the possible pathogenic implications. PMID:27177402

  19. Maternal body mass index and risk of birth and maternal health outcomes in low- and middle-income countries: a systematic review and meta-analysis.

    PubMed

    Rahman, M M; Abe, S K; Kanda, M; Narita, S; Rahman, M S; Bilano, V; Ota, E; Gilmour, S; Shibuya, K

    2015-09-01

    We conducted a systematic review and meta-analysis of population-based cohort studies of maternal body mass index (BMI) and risk of adverse birth and health outcomes in low- and middle-income countries. PubMed, Embase, CINAHL and the British Nursing Index were searched from inception to February 2014. Forty-two studies were included. Our study found that maternal underweight was significantly associated with higher risk of preterm birth (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01-1.27), low birthweight (OR, 1.66; 95% CI, 1.50-1.84) and small for gestational age (OR, 1.85; 95% CI, 1.69-2.02). Compared with mothers with normal BMI, overweight or obese mothers were at increased odds of gestational diabetes, pregnancy-induced hypertension, pre-eclampsia, caesarean delivery and post-partum haemorrhage. The population-attributable risk (PAR) indicated that if women were entirely unexposed to overweight or obesity during the pre-pregnancy or early pregnancy period, 14% to 35% fewer women would develop gestational diabetes, pre-eclampsia or pregnancy-induced hypertension in Brazil, China, India, Iran or Thailand. The highest PAR of low birthweight attributable to maternal underweight was found in Iran (20%), followed by India (18%), Thailand (10%) and China (8%). Treatment and prevention of maternal underweight, overweight or obesity may help reduce the burden on maternal and child health in developing countries. PMID:26094567

  20. Association of Gestational Hypertensive Disorders with Retinopathy of prematurity: A Systematic Review and Meta-analysis

    PubMed Central

    Chan, Priscilla Y. L.; Tang, Shu-Min; Au, Sunny C. L.; Rong, Shi-Song; Lau, Henry H. W.; Ko, Simon T. C.; Ng, Danny S. C.; Chen, Li Jia; Yam, Jason C. S.

    2016-01-01

    The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed. PMID:27491726

  1. The importance of being a regulatory T cell in pregnancy.

    PubMed

    Clark, David A

    2016-08-01

    Natural Foxp3(+) regulatory T cells (nTregs) defined by expression of the Foxp3 marker generated in the thymus against self autoantigens prevent systemic autoimmune and inflammatory disease. A second population of Tregs induced by exogenous antigens in the periphery (iTregs) are currently thought to play a key role in preventing infertility, recurrent pregnancy loss (occult and clinically-evident), pre-eclampsia, fetal growth restriction, and premature birth in outbred matings where the father is histoincompatible with the mother. Curiously, when iTregs are ablated in mice, fertility is usually not impaired and resorption rates in matings with allogeneic males can range from 0% to 100% in individual females. Analysis of possible explanations suggest iTregs prevent abortions by countering effects of environmental stressors. Depletion of iTregs at mid-pregnancy in mice only causes abortions in an artificial transgenic model. Effects of iTreg depletion on pre-eclampsia, fetal growth restriction, and premature birth remain to be tested. Tregs induced during pregnancy may also affect the health of offspring in post natal life as well as the health of the mother.

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

    PubMed

    Toda, Noboru; Toda, Hiroshi; Okamura, Tomio

    2013-08-15

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

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

    PubMed Central

    2011-01-01

    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

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

    PubMed Central

    2010-01-01

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

  5. Clinical and Preclinical Use of LOX-1-Specific Antibodies in Diagnostics and Therapeutics.

    PubMed

    De Siqueira, Jonathan; Abdul Zani, Izma; Russell, David A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan; Homer-Vanniasinkam, Shervanthi

    2015-11-01

    Lectin-like oxidized low-density lipoprotein receptor-1 (SR-E1, LOX-1, OLR1) was first discovered as a vascular receptor for modified lipoprotein particles nearly 20 years ago. Since then, in vitro and in vivo studies have demonstrated an association between LOX-1, a soluble form (sLOX-1) and a number of diseases including atherosclerosis, arthritis, hypertension and pre-eclampsia. However, converting such discoveries into tools and drugs for routine clinical use is dependent on translational preclinical and clinical studies but such studies have only begun to emerge in the past decade. In this review, we identify the key clinical applications and corresponding criteria that need to be addressed for the effective use of LOX-1-related probes and molecules for patient benefit in different disease states. PMID:26385009

  6. Oxidative stress in pregnancy and reproduction.

    PubMed

    Duhig, Kate; Chappell, Lucy C; Shennan, Andrew H

    2016-09-01

    Oxidative stress is implicated in the pathophysiology of many reproductive complications including infertility, miscarriage, pre-eclampsia, fetal growth restriction and preterm labour. The presence of excess reactive oxygen species can lead to cellular damage of deoxyribonucleic acids, lipids and proteins. Antioxidants protect cells from peroxidation reactions, limiting cellular damage and helping to maintain cellular membrane integrity. There is overwhelming evidence for oxidative stress causing harm in reproduction. However, there is sparse evidence that supplementation with commonly used antioxidants (mostly vitamins C and E) makes any difference in overcoming oxidative stress or reversing disease processes. There may be potential for antioxidant therapy to ameliorate or prevent disease, but this requires a thorough understanding of the mechanism of action and specificity of currently used antioxidants. PMID:27630746

  7. Impact of maternal obesity on perinatal and childhood outcomes.

    PubMed

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

    2015-04-01

    Maternal obesity is of major consequence, affecting every aspect of maternity care including both short- and long-term effects on the health of the offspring. Obese mothers are at a higher risk of developing gestational diabetes and pre-eclampsia, potentially exposing the foetus to an adverse intrauterine environment. Maternal obesity is linked to foetal macrosomia, resulting in increased neonatal and maternal morbidity. Foetal macrosomia is a result of a change in body composition in the neonate with an increase in both percentage fat and fat mass. Maternal obesity and gestational weight gain are associated with childhood obesity, and this effect extends into adulthood. Childhood obesity in turn increases chances of later life obesity, thus type 2 diabetes, and cardiovascular disease in the offspring. Further clinical trials of lifestyle and, potentially, pharmacological interventions in obese pregnant women are required to determine whether short- and long-term adverse effects for the mother and child can be reduced.

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

    PubMed

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

    2015-01-01

    Placental endoplasmic reticulum (ER) stress has been postulated in the pathophysiology of pre-eclampsia (PE) and intrauterine growth restriction (IUGR), but its activation remains elusive. Oxidative stress induced by ischaemia/hypoxia-reoxygenation activates ER stress in vitro. Here, we explored whether exposure to labour represents an in vivo model for the study of acute placental ER stress. ER stress markers, GRP78, P-eIF2α and XBP-1, were significantly higher in laboured placentas than in Caesarean-delivered controls localised mainly in the syncytiotrophoblast. The similarities to changes observed in PE/IUGR placentas suggest exposure to labour can be used to investigate induction of ER stress in pathological placentas.

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

    PubMed Central

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

    2013-01-01

    4-hydroxynonenal (HNE) is a lipid hydroperoxide end product formed from the oxidation of n-6 polyunsaturated fatty acids. The relative abundance of HNE within the vasculature is dependent not only on the rate of lipid peroxidation and HNE synthesis but also on the removal of HNE adducts by phase II metabolic pathways such as glutathione-S-transferases. Depending on its relative concentration, HNE can induce a range of hormetic effects in vascular endothelial and smooth muscle cells, including kinase activation, proliferation, induction of phase II enzymes and in high doses inactivation of enzymatic processes and apoptosis. HNE also plays an important role in the pathogenesis of vascular diseases such as atherosclerosis, diabetes, neurodegenerative disorders and in utero diseases such as pre-eclampsia. This review examines the known production, metabolism and consequences of HNE synthesis within vascular endothelial and smooth muscle cells, highlighting alterations in mitochondrial and endoplasmic reticulum function and their association with various vascular pathologies. PMID:24024167

  10. The Role of Decidual Macrophages During Normal and Pathological Pregnancy.

    PubMed

    Ning, Fen; Liu, Huishu; Lash, Gendie E

    2016-03-01

    Macrophages perform many specific functions including host defense, homeostasis, angiogenesis, and tissue development. Macrophages are the second most abundant leukocyte population in the non-pregnant endometrium and pregnant decidua and likely play a central role in the establishment and maintenance of normal pregnancy. Importantly, aberrantly activated uterine macrophages can affect trophoblast function and placental development, which may result in various adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth restriction or demise. Only by fully understanding the roles of macrophage in pregnancy will we be able to develop interventions for the treatment of these various pregnancy complications. This review discusses the general origin and classification of monocytes and macrophages and focuses on the phenotype and functional roles of decidual macrophage at the maternal-fetal interface in normal pregnancy, as well as discussing the potential contribution of the abnormal state of these cells to various aspects of pregnancy pathologies. PMID:26750089

  11. Antiphospholipid Antibodies and Antiphospholipid Syndrome during Pregnancy: Diagnostic Concepts

    PubMed Central

    Levy, Roger A.; dos Santos, Flavia Cunha; de Jesús, Guilherme R.; de Jesús, Nilson R.

    2015-01-01

    Antiphospholipid syndrome (APS) comprises of a wide spectrum of clinical and obstetric manifestations linked to the presence of antiphospholipid antibodies (aPL). APS was described in the context of lupus, and later as an isolated syndrome or primary APS. The presence of aPL, especially the lupus anticoagulant test, is associated with adverse pregnancy outcomes, such as fetal death, recurrent early miscarriages, pre-eclampsia, and placental insufficiency, but does not seem to influence infertility. High quality scientific data to support these associations, however, are lacking, and controversies arise about the definition of positive aPL (low vs medium-high titers) or even the definition of the adverse events. This review discusses APS classification criteria and the current debate about it. PMID:25999948

  12. A Short History of Sonography in Obstetrics and Gynaecology

    PubMed Central

    Campbell, S.

    2013-01-01

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

  13. Study on Serum Albumin in Third Trimester of Pregnancy.

    PubMed

    Sufrin, S; Nessa, A; Islam, M T; Das, R K; Rahman, M H

    2015-07-01

    Various hormones can cause marked changes in pregnant woman's appearance. Decreased level of serum albumin occurs in third trimester of pregnancy, which may be associated with increased maternal and infant mortality and morbidity. So, this study was carried out to evaluate and assess the level of serum albumin in third trimester of pregnancy. This cross-sectional study was carried out in the Department of Physiology Mymensingh Medical College, Mymensingh. This study enrolled 100 pregnant women of third trimester of pregnancy and 100 aged matched non-pregnant women from Mymensingh district. In this study serum albumin level in study group were 33.41 ± 4.62gm/l and in control group were 37.09 ± 4.21 gm/l, which was statistically decreased. The lower level of serum albumin in third trimester of pregnancy is the major concern of development of physiological edema during pregnancy and may be associated with pre-eclampsia.

  14. Asymptomatic spontaneous complete uterine rupture in a term pregnancy after uterine packing during previous caesarean section: a case report.

    PubMed

    Zhang, J; Chen, S F; Luo, Y E

    2014-01-01

    Uterine rupture is a life-threatening obstetrical complication with significant neonatal and maternal morbidity. The authors report a 36-year-old woman with a history of previous caesarean section because of pre-eclampsia and antepartum haemorrhage at 31 gestational weeks during her first pregnancy. Postpartum haemorrhage occurred and the uterine cavity was packed with gauze for reducing blood loss. After two years, she underwent elective, repeat caesarean section at 38+1 gestational weeks with no abdominal pain or vaginal bleeding. During the operation, a six- to seven-cm-long defect was found in the lower uterine segment, with complete separation of the uterine scar and disruption of the visceral peritoneum. A live baby was delivered. The postoperative course was uneventful. Uterine dehiscence and rupture should be suspected in the presence of risk factors such as previous caesarean section, especially uterine packing involved. Spontaneous silent rupture can occur in women without any alarming symptoms.

  15. Disease-Modifying Drug Possibly Linked to Placental Insufficiency: Severe placental complications in a pregnant woman with multiple sclerosis.

    PubMed

    Salahudheen, Sultan M; Begam, Muzibunnisa A

    2016-08-01

    Disease-modifying drugs (DMDs) such as interferon (IFN)-β and glatiramer acetate are often prescribed to slow disability progression in patients with multiple sclerosis (MS). However, adverse pregnancy outcomes have been reported with these medications. We report the rare occurrence of severe placental complications in a 30-year-old pregnant woman with MS who continued to take IFN-β during her first trimester. She presented at the Tawam Hospital, Al Ain, United Arab Emirates, in 2013 with early-onset fetal growth restriction. At 30 gestational weeks, she developed severe pre-eclampsia. The baby was delivered via emergency Caesarean section and was discharged at the age of two months. Continuation of IFN-β during pregnancy may have contributed to the development of placental insufficiency in this patient. Increased education regarding the risks of DMDs for pregnant patients with MS is very important to ensure successful pregnancy outcomes. PMID:27606121

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

    PubMed Central

    Lalitha, Rejani; Opio, Christopher Kenneth

    2013-01-01

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

  17. Exacerbations of asthma during pregnancy: Impact on pregnancy complications and outcome.

    PubMed

    Ali, Z; Hansen, A V; Ulrik, C S

    2016-05-01

    Asthma is common among pregnant women, and the incidence of asthma exacerbations during pregnancy is high. This literature review provides an overview of the impact of exacerbations of asthma during pregnancy on pregnancy-related complications. The majority of published retrospective studies reveal that asthma exacerbations during pregnancy increase the risk of pre-eclampsia, gestational diabetes, placental abruption and placenta praevia. Furthermore, these women also have higher risk for breech presentation, haemorrhage, pulmonary embolism, caesarean delivery, maternal admission to the intensive care unit and longer postpartum hospital stay. Asthma has been associated with increased risk of intrauterine growth retardation, small-for-gestational age, low birth weight, infant hypoglycaemia and preterm birth, but more recent prospective studies have not revealed significant associations with regard to these outcomes. In conclusion, asthma exacerbations during pregnancy are associated with complications of pregnancy, labour and delivery. Prevention of exacerbations is essential to reduce the risk of complications and poor outcome.

  18. [Bariatric surgery and pregnancy: literature review].

    PubMed

    Ferrand Miranda, Pedro; Contreras Rivas, Tomas; Leigh Pacciarini, Stephanie

    2014-02-14

    Obesity has currently reached epidemic proportions, both in Chile and in the world. This condition is associated to a variety of maternal complications in all stages of the vital cycle and during pregnancy. Medical treatment has not proved successful thus resulting in an increase in bariatric surgery in recent years, even when it is not first line treatment. This literature review aims to report updated results of surgical treatment for obesity before and during pregnancy with respect to fertility, gestational diabetes, pre-eclampsia and pregnancy-induced hypertension. It also looks into the possible effects of surgery on fetal development, and its relation to premature delivery, fetal macrosomy, low birth weight and neural tube defects, as well as effects on maternal and fetal outcomes, mainly in nutrition. Lastly, we suggest some recommendations that arise from this review on the role of contraception, nutrition and time between surgery and pregnancy.

  19. [Peripartum cardiomyopathy].

    PubMed

    Bouabdallaoui, Nadia; de Groote, Pascal; Mouquet, Frédéric

    2009-06-01

    The peripartum cardiomyopathy is a rare form of dilated cardiomyopathy. Its etiology remains unclear and is likely multifactorial. The diagnosis is based on the association of clinical heart failure and systolic dysfunction assessed by echocardiography or magnetic resonance imaging. Diagnosis to rule out are myocardial infarction, myocarditis, inherited cardiomyopathy, history of treatment by anthracycline. Risk factors are advance maternal age (> 30), multiparity, twin pregnancy, african origin, obesity, pre-eclampsia, gestational hypertension, and prolonged tocolytic therapy. Treatment of acute phase is identical to usual treatment of acute systolic heart failure. Angiotensin converting enzyme inhibitor and VKA are contra indicated during pregnancy. After delivery, VKA treatment should be discussed in case of systolic function < 25 % because of higher risk of thrombus. Complete recovery of systolic function is observed in 50 % of the case. The mortality risk is low. Subsequent pregnancy should be discouraged, especially if systolic function did not recover.

  20. Diabetes and obesity in pregnancy.

    PubMed

    Simmons, David

    2011-02-01

    An epidemic of obesity is affecting growing numbers of women in their childbearing years increasing their risk of obstetric complications including diabetes, hypertension, pre-eclampsia, some malformations, macrosomia and the need for obstetric intervention. There is growing evidence that maternal obesity may increase the risk of obesity and diabetes in the offspring. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require management during pregnancy. Management of obesity including weight loss and physical activity prior to pregnancy is likely to be beneficial for mother and baby, although the benefits of bariatric surgery remain unclear at this time. Limiting gestational weight gain to 5-9 kg among pregnant obese women is likely to improve obstetric outcomes, but how to achieve this remains an active area of research. If gestational diabetes develops, there is good evidence that clinical management reduces the risk of adverse pregnancy outcomes.

  1. Vitamin supplementation in pregnancy.

    PubMed

    2016-07-01

    Ensuring that a woman is well-nourished, both before and during pregnancy, is crucial for the health of the woman and that of the unborn child.(1) Maternal deficiency in key nutrients has been linked to pre-eclampsia, restricted fetal growth, neural tube defects, skeletal deformity and low birth weight.(1,2) Many nutritional supplements containing vitamins, minerals and other micronutrients are heavily marketed to women for all stages of pregnancy. However, much of the evidence for vitamin supplementation in pregnancy comes from studies carried out in low-income countries,(3) where women are more likely to be undernourished or malnourished than within the UK population. The challenges lie in knowing which supplements are beneficial and in improving uptake among those at most need. Here we summarise current UK guidance for vitamin supplementation in pregnancy and review the evidence behind it. PMID:27405305

  2. Keap1-Nrf2 regulated redox signaling in utero: Priming of disease susceptibility in offspring.

    PubMed

    Chapple, Sarah J; Puszyk, William M; Mann, Giovanni E

    2015-11-01

    Intrauterine exposure to gestational diabetes, pre-eclampsia or intrauterine growth restriction alters the redox status of the developing fetus. Such pregnancy-related diseases in most cases do not have a readily identifiable genetic cause, and epigenetic 'priming' mechanisms in utero may predispose both mother and child to later-life onset of cardiovascular and metabolic diseases. The concept of 'fetal programing' or 'developmental priming' and its association with an increased risk of disease in childhood or adulthood has been reviewed extensively. This review focuses on adaptive changes in the in utero redox environment during normal pregnancy and the consequences of alterations in redox control associated with pregnancies characterized by oxidative stress. We evaluate the evidence that the Keap1-Nrf2 pathway is important for protecting the fetus against adverse conditions in utero and may itself be subject to epigenetic priming, potentially contributing to an increased risk of vascular disease and insulin resistance in later life. PMID:26279476

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

    PubMed

    Blickstein, Dorith; Hod, Moshe; Bar, Jacob

    2003-12-01

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

  4. Management of inherited thrombophilia in pregnancy.

    PubMed

    Ormesher, Laura; Simcox, Louise; Tower, Clare; Greer, Ian A

    2016-07-01

    Adverse pregnancy outcomes, such as pregnancy loss and pre-eclampsia, are associated with thrombotic mechanisms and thrombophilia. Antithrombotic interventions, particularly low-molecular-weight heparin, have been investigated in women identified by previous pregnancy outcome; however, the results have been inconsistent. This may reflect heterogeneity of both the study groups and the disease processes resulting in inadequate stratification to guide antithrombotic interventions. Furthermore, the variation in gestation at initiation of low-molecular-weight heparin treatment might be important. Despite limited evidence of efficacy, low-molecular-weight heparin is often used in an attempt to prevent these complications, owing to the lack of other effective treatments and its perceived safety in pregnancy. Research is required to better understand the disease processes, identify possible biomarkers and thereby more homogeneous groups for targeted treatment. PMID:27638899

  5. Recruiting American Indian Women for a Genetic Epidemiology Study

    PubMed Central

    Nadeau, M.; Best, L.

    2010-01-01

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

  6. Microparticles in physiological and in pathological conditions.

    PubMed

    Roos, Maria Augusta; Gennero, Luisa; Denysenko, Tetyana; Reguzzi, Stefano; Cavallo, Giovanni; Pescarmona, Gian Piero; Ponzetto, Antonio

    2010-10-01

    Chronic diseases pose a severe burden to modern National Health Systems. Individuals nowadays have a far more extended lifespan than in the past, but healthy living was only scantily extended. As much as longer life is desirable, it is saddened by chronic diseases and organ malfunctions. One contributor to these problems was recognized to be represented by microparticles (MPs). Our purpose is to better understand MPs, to contrast their ominous threat and possible clinical importance. For this intent we correlated MPs with thrombotic pathologies, hemophilia, malaria, diabetes, cardiovascular diseases, endothelial dysfunctions, pulmonary hypertension, ischemic stroke, pre-eclampsia, rheumatologic diseases-rheumatoid arthritis, polymyositis-dermatomyositis, angiogenesis and tumor progression-cancer; we listed the possibilities of using them to improve transfusion methods, as a marker for acute allograft rejection, in stem cell transplantation, as neuronal biomarkers, to understand gender-specific susceptibility for diseases and to improve vaccination methods and we presented some methods for the detection of MPs. PMID:20941744

  7. Maternal arterial elasticity in the first trimester as a predictor of birthweight.

    PubMed

    O'Connor, Clare; O'Higgins, Amy; Segurado, Ricardo; Turner, Michael J; Stuart, Bernard; Kennelly, Máireád M

    2016-07-01

    The early detection of foetal growth restriction and macrosomia is an important goal of modern obstetric care. Aberrant foetal growth is an important cause of perinatal morbidity and mortality. Current modalities for detecting the abnormal foetal growth are often inadequate. Pulse wave analysis using applanation tonometry is a simple and non-invasive test that provides information about the cardiovascular system. Arterial elasticity has previously been implicated in the pathophysiology of pre-eclampsia and cardiovascular disease. Our study examined the relationship between maternal arterial elasticity and birthweight by using pulse wave analysis. We discovered that increased large artery elasticity predicted a larger baby at birth. Large artery elasticity therefore has the potential to act as a useful screening tool which may help in the prediction of women who are at risk of aberrant foetal growth. PMID:26800380

  8. The valuation of prenatal life in economic evaluations of perinatal interventions.

    PubMed

    Simon, Judit; Petrou, Stavros; Gray, Alastair

    2009-04-01

    Perinatal interventions delivered during the prenatal period have the potential to directly impact prenatal life. The decision on when to begin 'counting' the life of an infant in the calculus has received little attention in previous economic evaluations of perinatal interventions. We illustrate, using data from a recent trial-based economic evaluation of magnesium sulphate given to women with pre-eclampsia to prevent eclampsia, how different definitions of when human life commences can have a significant impact upon cost-effectiveness estimates based on composite outcome measures such as life years or quality-adjusted life years gained or disability-adjusted life years averted. Further, we suggest ways in which methods in this area can be improved.

  9. Disease-Modifying Drug Possibly Linked to Placental Insufficiency

    PubMed Central

    Salahudheen, Sultan M.; Begam, Muzibunnisa A.

    2016-01-01

    Disease-modifying drugs (DMDs) such as interferon (IFN)-β and glatiramer acetate are often prescribed to slow disability progression in patients with multiple sclerosis (MS). However, adverse pregnancy outcomes have been reported with these medications. We report the rare occurrence of severe placental complications in a 30-year-old pregnant woman with MS who continued to take IFN-β during her first trimester. She presented at the Tawam Hospital, Al Ain, United Arab Emirates, in 2013 with early-onset fetal growth restriction. At 30 gestational weeks, she developed severe pre-eclampsia. The baby was delivered via emergency Caesarean section and was discharged at the age of two months. Continuation of IFN-β during pregnancy may have contributed to the development of placental insufficiency in this patient. Increased education regarding the risks of DMDs for pregnant patients with MS is very important to ensure successful pregnancy outcomes. PMID:27606121

  10. Acute Cardiac Failure in a Pregnant Woman due to Thyrotoxic Crisis

    PubMed Central

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

    2012-01-01

    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. PMID:24804110

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

    PubMed Central

    Samra, Khawla Abu

    2013-01-01

    Pregnancy represents a real challenge to all body systems. Physiological changes can involve any of the body organs including the eye and visual system. The ocular effect of pregnancy involves a wide spectrum of physiologic and pathologic changes. The latter might be presenting for the first time during pregnancy such as corneal melting and corneal ectasia, or an already existing ocular pathologies that are modified by pregnancy such as diabetic retinopathy and glaucoma. In addition, pregnancy can affect vision through systemic disease that are either specific to the pregnant state itself such as the pre-eclampsia/eclampsia and Sheehan's syndrome, or systemic diseases that occur more frequently in relation to pregnancy such as Graves’ disease, idiopathic intracranial hypertension, anti-phospholipid syndrome, and disseminated intravascular coagulation. PMID:24082665

  12. Disease-Modifying Drug Possibly Linked to Placental Insufficiency

    PubMed Central

    Salahudheen, Sultan M.; Begam, Muzibunnisa A.

    2016-01-01

    Disease-modifying drugs (DMDs) such as interferon (IFN)-β and glatiramer acetate are often prescribed to slow disability progression in patients with multiple sclerosis (MS). However, adverse pregnancy outcomes have been reported with these medications. We report the rare occurrence of severe placental complications in a 30-year-old pregnant woman with MS who continued to take IFN-β during her first trimester. She presented at the Tawam Hospital, Al Ain, United Arab Emirates, in 2013 with early-onset fetal growth restriction. At 30 gestational weeks, she developed severe pre-eclampsia. The baby was delivered via emergency Caesarean section and was discharged at the age of two months. Continuation of IFN-β during pregnancy may have contributed to the development of placental insufficiency in this patient. Increased education regarding the risks of DMDs for pregnant patients with MS is very important to ensure successful pregnancy outcomes.

  13. Acute Onset Peripartum Cardiomyopathy in a Woman with Severe Pre-eclamptia: A Diagnostic Dilemma

    PubMed Central

    Basak, Sonela; Rudra, Pallab

    2013-01-01

    Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy that can present as acute life-threatening pulmonary oedema in late pregnancy or early puerperium, its diagnosis is mainly by exclusion of other causes. Morbidity is high due to the reduced physiological reserve in pregnancy. PPCM and severe pre-eclampsia can co-exist and their clinical presentation may overlap, making the diagnosis more difficult and often delayed, with potentially devastating consequences. Here, we would like to share our experience of such a case and present to the readers how we dealt with the challenge. As obstetricians we often do not resort to transthoracic echocardiography, which in our case prompted the diagnosis timely. Lateral thinking and a heightened suspicion does help. Proper diagnosis is extremely important not only for the immediate appropriate management but also for advising long-term lifestyle modifications to minimize risk and counselling for future pregnancy.

  14. Epidemiology of the hypertensive disorders of pregnancy*

    PubMed Central

    Davies, A. Michael

    1979-01-01

    Disorders associated with hypertension during pregnancy, which are often linked with oedema and/or proteinuria and are variously termed toxaemia of pregnancy, EPH gestosis, pre-eclampsia, and eclampsia, are of unknown etiology, although they have been known for a long time and many attempts have been made to classify and explain them. In this paper, the author draws attention to the problems of standardizing values for blood pressure, proteinuria, and oedema and of determining their value in the diagnosis of the disorder. Different classification schemes are described and the problems of comparison between them are stressed. The frequency of the hypertensive disorders of pregnancy in different countries and groups at special risk are discussed. Finally, recommendations are made on the types of research and health care needed to combat the problem. PMID:314351

  15. Idiopathic subglottic stenosis in pregnancy: A deceptive laryngoscopic view.

    PubMed

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

    2011-09-01

    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.

  16. Hypertensive crisis during pregnancy and postpartum period.

    PubMed

    Too, Gloria T; Hill, James B

    2013-08-01

    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.

  17. Knowledge of midwives about hypertensive disorders during pregnancy in primary healthcare

    PubMed Central

    Ngwekazi, Nompumelelo L.

    2016-01-01

    Background Many factors or medical conditions may influence the outcome of pregnancy, which in turn, may increase infant and maternal morbidity and mortality. One such condition is an increase in blood pressure (BP). Setting The study was conducted in maternity obstetrical units (MOUs) in primary healthcare clinics (PHCs) in the Eastern Cape, South Africa. Objectives To determine the knowledge about hypertensive disorders during pregnancy (HDPs) of registered midwives working in MOUs in PHCs. Methods A quantitative descriptive correlation research design was applied. A simple random sample of 43 (44%) rural and urban clinics was selected, and all registered midwives (n = 101) working in these clinics completed a self-administered questionnaire. Data were collected over a period of 1 month. The reliability and validity of the methodology were supported by experts and a pilot study. Descriptive statistics including various statistical tests to determine any associations between variables using a 95% confidence interval were applied. Results A gap in the knowledge of midwives about HDPs was identified. Only 56.4% of the participants correctly answered the questions on the clinical manifestations of severe pre-eclampsia and 68.3% on the factors affecting BP, whereas 27.7% had no understanding about pre-eclampsia. Significant statistical differences were identified in the knowledge of staff in clinics where doctors visit regularly versus those in clinics where there are no visits (p = 0.04), and between experience of midwives and management of HDPs (p = 0.02). Conclusion The knowledge of midwives is deficient regarding HDPs. Continuous professional development is critical in midwifery both in theory and in clinical practice. PMID:27247155

  18. Inter-pregnancy weight change impacts placental weight and is associated with the risk of adverse pregnancy outcomes in the second pregnancy

    PubMed Central

    2014-01-01

    Background The inter-pregnancy period is considered a teachable moment when women are receptive to weight- management guidance aimed at optimising pregnancy outcome in subsequent pregnancies. In population based studies inter-pregnancy weight change is associated with several adverse pregnancy outcomes but the impact on placental size is unknown. Methods The association between inter-pregnancy weight change and the primary risk of adverse pregnancy outcomes in the second pregnancy was investigated in 12,740 women with first two consecutive deliveries at a single hospital using logistic regression. Results Compared with women who were weight stable, weight loss (>1BMI unit) between pregnancies was associated with an increased risk of spontaneous preterm delivery, low placental weight and small for gestational age (SGA) birth, while weight gain (>3BMI units) increased the risk of pre-eclampsia, gestational hypertension, emergency caesarean section, placental oversize and large for gestational age (LGA) birth at the second pregnancy. The relationship between weight gain and pre-eclampsia risk was evident in women who were overweight at first pregnancy only (BMI ≥25 units), while that between weight loss and preterm delivery was confined to women with a healthy weight at first pregnancy (BMI <25 units). In contrast, the association between weight loss and SGA was independent of first pregnancy BMI. A higher percentage of women who were obese at first pregnancy were likely to experience a large weight gain (P < 0.01) or weight loss (P < 0.001) between consecutive pregnancies compared with the normal BMI reference group. Conclusion Inter-pregnancy weight change in either direction increases the risk of a number of contrasting pregnancy complications, including extremes of placental weight. The placenta may lie on the causal pathway between BMI change and the risk of LGA or SGA birth. PMID:24450357

  19. Impact of Janani Suraksha Yojana on institutional delivery rate and maternal morbidity and mortality: an observational study in India.

    PubMed

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

    2012-12-01

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

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

    SciTech Connect

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

    1984-04-01

    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).

  1. HBsAg positivity during pregnancy and adverse maternal outcomes: a retrospective cohort analysis.

    PubMed

    Tan, J; Liu, X; Mao, X; Yu, J; Chen, M; Li, Y; Sun, X

    2016-10-01

    Hepatitis B virus infection characterized by HBsAg positivity during pregnancy is a well-recognized issue in developing countries, but the association between HBsAg positivity and adverse maternal outcomes remains uncertain. To examine the association between HBsAg positivity during pregnancy and adverse maternal outcomes, a retrospective cohort study was conducted in Sichuan province, China. Deliveries were recorded from six hospitals between 1 January 2009 and 31 December 2010. Pre-eclampsia, gestational diabetes mellitus (GDM), postpartum haemorrhage (PPH), intrahepatic cholestasis, Caesarean section and placenta previa were prespecified adverse maternal outcomes. We used two multivariate logistic regression models to assess the association between HBsAg positivity and adverse maternal outcomes. In total, 948 (4.2%) pregnant women were HBsAg positive from 22 374 deliveries. Pregnant women with positive HBsAg had higher risk of GDM (aOR1.41, 95%CI 1.15-1.74), PPH (1.44, 1.13-1.83), intrahepatic cholestasis (1.74, 1.40-2.16) and Caesarean section (1.24, 1.06-1.45). No statistical associations were found between HBsAg positivity and pre-eclampsia (1.36, 0.94-1.97), and placenta previa (1.21, 0.87-1.67). HBsAg positivity during pregnancy was associated with higher risk of multiple adverse maternal outcomes. Although the causality has yet to be established, efforts may be warranted in routine care, particularly in those with high risk for adverse maternal outcomes, given the volume population infected with HBsAg. Future studies are needed to establish causality and examine the impact of HBeAg on the adverse outcomes. PMID:27167604

  2. Pregnancy in renal transplantation: Recipient and donor aspects in the Arab world

    PubMed Central

    Kukla, Aleksandra; Issa, Naim; Ibrahim, Hassan N.

    2012-01-01

    Objective There are many kidney transplant recipients and living donors of reproductive age, and the prevalence of pregnancies in kidney transplant recipients can reach 55% in the Middle Eastern countries. Living kidney donation is predominant in this region. As the risks and outcomes of pregnancy should be a part of counselling for both recipients and donors, we reviewed available reports on maternal and foetal outcomes in these particular populations. Methods Information was obtained from retrospective analyses of a large database, and from single-centre reports indexed in PubMed on pregnancy in donors and kidney transplant recipients. The keywords used for the search included ‘fertility’, ‘kidney disease’, ‘pregnancy’, ‘maternal/foetal outcomes’, ‘kidney transplant recipient’, ‘immunosuppression side-effects’, ‘living donor’ and ‘Arab countries’. Results Pregnancies in kidney transplant recipients are most successful in those with adequate kidney function and controlled comorbidities. Similarly to other regions, pregnant recipients in the Middle East had a higher risk of pre-eclampsia (26%) and gestational diabetes (7%) than in the general population. Caesarean section was quite common, with an incidence rate of 61%, and the incidence of pre-term birth reached 46%. Conclusions Most living donors can have successful pregnancies and should not be routinely discouraged. Women who had pregnancies before and after donation were more likely to have adverse maternal outcomes (gestational diabetes, hypertension, proteinuria, and pre-eclampsia) in the latter, but no adverse foetal outcomes were found after donation. The evaluation before donation should include a gestational history and counselling about the potential risks. PMID:26558022

  3. PCSK6-mediated corin activation is essential for normal blood pressure

    PubMed Central

    Chen, Shenghan; Cao, Pengxiu; Dong, Ningzheng; Peng, Jianhao; Zhang, Chunyi; Wang, Hao; Zhou, Tiantian; Yang, Junhua; Zhang, Yue; Martelli, Elizabeth E; Prasad, Sathyamangla V Naga; Miller, Rachel E; Malfait, Anne-Marie; Zhou, Yiqing; Wu, Qingyu

    2016-01-01

    Hypertension is the most common cardiovascular disease, afflicting >30% of adults1. The cause of hypertension in most individuals remains unknown2,3, suggesting that additional contributing factors have yet to be discovered. Corin is a serine protease that activates the natriuretic peptides, thereby regulating blood pressure4. It is synthesized as a zymogen that is activated by proteolytic cleavage. CORIN variants and mutations impairing corin activation have been identified in people with hypertension and pre-eclampsia5–9. To date, however, the identity of the protease that activates corin remains elusive. Here we show that proprotein convertase subtilisin/kexin-6 (PCSK6, also named PACE4; ref. 10) cleaves and activates corin. In cultured cells, we found that corin activation was inhibited by inhibitors of PCSK family proteases and by small interfering RNAs blocking PCSK6 expression. Conversely, PCSK6 overexpression enhanced corin activation. In addition, purified PCSK6 cleaved wild-type corin but not the R801A variant that lacks the conserved activation site. Pcsk6-knockout mice developed salt-sensitive hypertension, and corin activation and pro-atrial natriuretic peptide processing activity were undetectable in these mice. Moreover, we found that CORIN variants in individuals with hypertension and pre-eclampsia were defective in PCSK6-mediated activation. We also identified a PCSK6 mutation that impaired corin activation activity in a hypertensive patient. Our results indicate that PCSK6 is the long-sought corin activator and is important for sodium homeostasis and normal blood pressure. PMID:26259032

  4. Clinical and echocardiographic profile and outcomes of peripartum cardiomyopathy: the Philippine General Hospital experience

    PubMed Central

    Samonte, Vim I; Ngalob, Queenie G; Mata, Ghea Divina B; Aherrera, Jaime Alfonso M; Reyes, Eugene; Punzalan, Felix Eduardo R

    2013-01-01

    Background Peripartum cardiomyopathy (PPCM) is a rare disease entity of unknown aetiology. High rates of mortality or poor overall clinical outcome are reported in women with this condition. Certain characteristics are risk factors for this disease. In Asia, there are limited data, especially in the Southeast Asian region. In the Philippines, no data exist regarding the prevalence or risk factors. Objectives To determine the prevalence, profile and outcomes of PPCM in Philippine General Hospital and to describe their echocardiographic findings. Methods All patients diagnosed with PPCM in the period of 1 January 2009–31 December 2010 were seen and examined. Demographic data and echocardiogram of the patients were reviewed. Results 9 were diagnosed with PPCM during the study period. The prevalence is 1 in 1270 live births. Mean age was 29. 78% presented with moderate to severe heart failure symptoms in the prepartum period. Among purported risk factors for PPCM, obesity, multiparity and pre-eclampsia were seen in most. Conversely, only one patient admitted to having more than a single sexual partner. Only one patient had multifetal pregnancy. None were smokers. 44% underwent caesarean section for maternal indication. No mortality was seen. Fetal outcomes were good with all resulting in live births and most were appropriate for gestational age. Echocardiographic findings showed global wall motion abnormalities in the majority, mean ejection fraction of 34% and mean fractional shortening of 20%. Conclusions PPCM is rare in the Philippines. Compared with international data, our patients are younger with low percentages of promiscuity, multifetal pregnancy, smoking history and tocolytic use. Similar to previous studies, obesity, multiparity and pre-eclampsia were also present in our PPCM patients. Immediate maternal and fetal outcomes were generally good. Adherence to standard heart failure management is high. PMID:27326145

  5. MSX2 Induces Trophoblast Invasion in Human Placenta

    PubMed Central

    Lu, Junjie; Yang, Genling; Tian, Na; Wang, Xiaojie; Tan, Yi; Tan, Dongmei

    2016-01-01

    Normal implantation depends on appropriate trophoblast growth and invasion. Inadequate trophoblast invasion results in pregnancy-related disorders, such as early miscarriage and pre-eclampsia, which are dangerous to both the mother and fetus. Msh Homeobox 2 (MSX2), a member of the MSX family of homeobox proteins, plays a significant role in the proliferation and differentiation of various cells and tissues, including ectodermal organs, teeth, and chondrocytes. Recently, MSX2 was found to play important roles in the invasion of cancer cells into adjacent tissues via the epithelial-mesenchymal transition (EMT). However, the role of MSX2 in trophoblastic invasion during placental development has yet to be explored. In the present study, we detected MSX2 expression in cytotrophoblast, syncytiotrophoblast, and extravillous cytotrophoblast cells of first or third trimester human placentas via immunohistochemistry analysis. Furthermore, we found that the in vitro invasive ability of HTR8/SVneo cells was enhanced by exogenous overexpression of MSX2, and that this effect was accompanied by increased protein expression of matrix metalloproteinase-2 (MMP-2), vimentin, and β-catenin. Conversely, treatment of HTR8/SVneo cells with MSX2-specific siRNAs resulted in decreased protein expression of MMP-2, vimentin, and β-catenin, and reduced invasion levels in a Matrigel invasion test. Notably, however, treatment with the MSX2 overexpression plasmid and the MSX2 siRNAs had no effect on the mRNA expression levels of β-catenin. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may be associated

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

    PubMed Central

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

    2005-01-01

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

  7. A cohort evaluation on arterial stiffness and hypertensive disorders in pregnancy

    PubMed Central

    2012-01-01

    Background Hypertensive disorders in pregnancy are associated with systemic endothelial dysfunction leading to impaired physiological vasodilation. Recent evidence has shown central aortic pressures obtained through pulse wave analysis, at less than 14 weeks of gestation, to be predictive of pre-eclampsia. In light of this, we aimed to evaluate the role of central aortic stiffness in the prediction and discrimination of hypertensive disorders in pregnancy. Methods A cohort study of women with viable, singleton pregnancies at less than 14 weeks of amenorrhoea, and without multiple pregnancies, autoimmune or renal disease, diagnosed with aneuploidy or fetal anomaly will be recruited from a single maternity hospital and followed up till delivery and puerperium. A targeted sample size of 1000 eligible pregnant women will be enrolled into the study from antenatal clinics. Main exposure under study is central aortic pulse pressure using radial pulse wave recording, and the outcomes under follow-up are gestational hypertension and pre-eclampsia. Other measures include lifestyle factors such as smoking, physical exercise, psychometric evaluations, vasoactive factors, uterine artery pulsatility index, height and weight measurements. These measures will be repeated over 4 antenatal visits at 11-14, 18-22, 28-32 and above 34 weeks of gestation. Double data entry will be performed on Microsoft Access, and analysis of data will include the use of random effect models and receiver operating characteristic curves on Stata 11.2. Discussion The proposed study design will enable a longitudinal evaluation of the central aortic pressure changes as a marker for vascular compliance during pregnancy. As measures are repeated over time, the timing and severity of changes are detectable, and findings may yield important information on how aberrant vascular responses occur and its role in the early detection and prediction of hypertensive disorders. PMID:23268774

  8. Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.

    PubMed

    Hamilton, Mark J; Newbury-Ecob, Ruth; Holder-Espinasse, Muriel; Yau, Shu; Lillis, Suzanne; Hurst, Jane A; Clement, Emma; Reardon, William; Joss, Shelagh; Hobson, Emma; Blyth, Moira; Al-Shehhi, Maryam; Lynch, Sally A; Suri, Mohnish

    2016-10-01

    Rubinstein-Taybi syndrome (RTS) is an autosomal dominant neurodevelopmental disorder characterized by growth deficiency, broad thumbs and great toes, intellectual disability and characteristic craniofacial appearance. Mutations in CREBBP account for around 55% of cases, with a further 8% attributed to the paralogous gene EP300. Comparatively few reports exist describing the phenotype of Rubinstein-Taybi because of EP300 mutations. Clinical and genetic data were obtained from nine patients from the UK and Ireland with pathogenic EP300 mutations, identified either by targeted testing or by exome sequencing. All patients had mild or moderate intellectual impairment. Behavioural or social difficulties were noted in eight patients, including three with autistic spectrum disorders. Typical dysmorphic features of Rubinstein-Taybi were only variably present. Additional observations include maternal pre-eclampsia (2/9), syndactyly (3/9), feeding or swallowing issues (3/9), delayed bone age (2/9) and scoliosis (2/9). Six patients had truncating mutations in EP300, with pathogenic missense mutations identified in the remaining three. The findings support previous observations that microcephaly, maternal pre-eclampsia, mild growth restriction and a mild to moderate intellectual disability are key pointers to the diagnosis of EP300-related RTS. Variability in the presence of typical facial features of Rubinstein-Taybi further highlights clinical heterogeneity, particularly among patients identified by exome sequencing. Features that overlap with Floating-Harbor syndrome, including craniofacial dysmorphism and delayed osseous maturation, were observed in three patients. Previous reports have only described mutations predicted to cause haploinsufficiency of EP300, whereas this cohort includes the first described pathogenic missense mutations in EP300.

  9. Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.

    PubMed

    Hamilton, Mark J; Newbury-Ecob, Ruth; Holder-Espinasse, Muriel; Yau, Shu; Lillis, Suzanne; Hurst, Jane A; Clement, Emma; Reardon, William; Joss, Shelagh; Hobson, Emma; Blyth, Moira; Al-Shehhi, Maryam; Lynch, Sally A; Suri, Mohnish

    2016-10-01

    Rubinstein-Taybi syndrome (RTS) is an autosomal dominant neurodevelopmental disorder characterized by growth deficiency, broad thumbs and great toes, intellectual disability and characteristic craniofacial appearance. Mutations in CREBBP account for around 55% of cases, with a further 8% attributed to the paralogous gene EP300. Comparatively few reports exist describing the phenotype of Rubinstein-Taybi because of EP300 mutations. Clinical and genetic data were obtained from nine patients from the UK and Ireland with pathogenic EP300 mutations, identified either by targeted testing or by exome sequencing. All patients had mild or moderate intellectual impairment. Behavioural or social difficulties were noted in eight patients, including three with autistic spectrum disorders. Typical dysmorphic features of Rubinstein-Taybi were only variably present. Additional observations include maternal pre-eclampsia (2/9), syndactyly (3/9), feeding or swallowing issues (3/9), delayed bone age (2/9) and scoliosis (2/9). Six patients had truncating mutations in EP300, with pathogenic missense mutations identified in the remaining three. The findings support previous observations that microcephaly, maternal pre-eclampsia, mild growth restriction and a mild to moderate intellectual disability are key pointers to the diagnosis of EP300-related RTS. Variability in the presence of typical facial features of Rubinstein-Taybi further highlights clinical heterogeneity, particularly among patients identified by exome sequencing. Features that overlap with Floating-Harbor syndrome, including craniofacial dysmorphism and delayed osseous maturation, were observed in three patients. Previous reports have only described mutations predicted to cause haploinsufficiency of EP300, whereas this cohort includes the first described pathogenic missense mutations in EP300. PMID:27465822

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

    PubMed

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

    2014-12-01

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

  11. Does high-density lipoprotein protect vascular function in healthy pregnancy?

    PubMed

    Sulaiman, Wan N Wan; Caslake, Muriel J; Delles, Christian; Karlsson, Helen; Mulder, Monique T; Graham, Delyth; Freeman, Dilys J

    2016-04-01

    The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur.

  12. A cross-sectional study of platelet volume in healthy normotensive women with bilateral uterine artery notches.

    PubMed

    Lees, C C; Brown, A S; Harrington, K F; Beacon, H J; Martin, J F; Campbell, S

    1997-10-01

    High uterine artery resistance characterized by bilateral notches seen on Doppler ultrasound in the second half of pregnancy is associated with an increased risk of adverse outcome related to pre-eclampsia and intrauterine growth retardation. We sought to establish whether there was a difference in platelet volume in healthy, normotensive women with high-resistance uterine artery Doppler findings compared to those with normal uterine artery Doppler findings. Forty-seven women were allocated prospectively into 'bilateral notch' and 'no notch' groups at color Doppler imaging of the uterine arteries carried out at a mean of 26 weeks' gestation. The difference in platelet volume between the two groups and the relationship of adverse outcome with raised platelet volume and high-resistance uterine artery Doppler findings was investigated. Twenty-three women had no evidence of uterine artery notches and 24 had bilateral uterine artery notches. Platelet volume in the women with bilateral notches was greater than in those with no notches (8.28 fl vs. 7.46 fl; p = 0.01). However, unlike high-resistance uterine artery Doppler findings, increased platelet volume was not associated with adverse outcome. Uterine artery Doppler flow abnormalities have not previously been studied in combination with hematological or biochemical markers. Our findings show, for the first time, that women with bilateral uterine artery notches have an increased platelet volume compared to those with normal uterine artery Doppler findings many weeks before clinical signs of pre-eclampsia or fetal growth retardation are evident. Women with abnormal uterine artery flow at this gestation may have other cardiovascular and hematological differences compared to those with normal flow.

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

    PubMed Central

    Waterstone, Mark; Bewley, Susan; Wolfe, Charles

    2001-01-01

    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

  14. A New Look at Care in Pregnancy: Simple, Effective Interventions for Neglected Populations

    PubMed Central

    Hodgins, Stephen; Tielsch, James; Rankin, Kristen; Robinson, Amber; Kearns, Annie; Caglia, Jacquelyn

    2016-01-01

    Background Although this is beginning to change, the content of antenatal care has been relatively neglected in safe-motherhood program efforts. This appears in part to be due to an unwarranted belief that interventions over this period have far less impact than those provided around the time of birth. In this par, we review available evidence for 21 interventions potentially deliverable during pregnancy at high coverage to neglected populations in low income countries, with regard to effectiveness in reducing risk of: maternal mortality, newborn mortality, stillbirth, prematurity and intrauterine growth restriction. Selection was restricted to interventions that can be provided by non-professional health auxiliaries and not requiring laboratory support. Methods In this narrative review, we included relevant Cochrane and other systematic reviews and did comprehensive bibliographic searches. Inclusion criteria varied by intervention; where available randomized controlled trial evidence was insufficient, observational study evidence was considered. For each intervention we focused on overall contribution to our outcomes of interest, across varying epidemiologies. Results In the aggregate, achieving high effective coverage for this set of interventions would very substantially reduce risk for our outcomes of interest and reduce outcome inequities. Certain specific interventions, if pushed to high coverage have significant potential impact across many settings. For example, reliable detection of pre-eclampsia followed by timely delivery could prevent up to ¼ of newborn and stillbirth deaths and over 90% of maternal eclampsia/pre-eclampsia deaths. Other interventions have potent effects in specific settings: in areas of high P falciparum burden, systematic use of insecticide-treated nets and/or intermittent presumptive therapy in pregnancy could reduce maternal mortality by up to 10%, newborn mortality by up to 20%, and stillbirths by up to 25–30%. Behavioral

  15. Contemporary Reproductive Outcomes for Patients With Polycystic Ovary Syndrome: A Retrospective Observational Study

    PubMed Central

    Jenkins-Jones, Sara; Morgan, Christopher L.

    2016-01-01

    Context: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility and may be associated with adverse pregnancy and neonatal outcomes. However, it is difficult to establish how much of this risk is due to PCOS and how much to obesity. Objective: This study aimed to determine the effect of PCOS upon fertility, pregnancy, and neonatal outcomes. Design and Setting: Data were extracted from the Clinical Practice Research Datalink (CPRD), a longitudinal anonymized primary care research database in the United Kingdom. Patients with a diagnosis of PCOS were matched to controls (1:2) by age (±1 y), body mass index (± 3 U), and CPRD practice. Standardized fertility ratios before and after diagnosis (index date) were calculated. Rates of miscarriage, pre-eclampsia, gestational diabetes, premature delivery, delivery method, and neonatal outcomes were compared. Results: Nine thousand sixty-eight women with PCOS matched study criteria. Prior to index date the standardized fertility ratio for patients with PCOS was 0.80 (95% confidence interval, 0.77–0.83); following index date it was 1.16 (1.12–1.20). The adjusted odds ratios (95% CI) for miscarriage (1.70; 1.56–1.84), pre-eclampsia (1.32; 1.16–1.49), gestational diabetes (1.41; 1.2–1.66), and premature delivery (1.25; 1.1–1.43) were all increased compared with controls. Of PCOS births, 27.7% were by Caesarean section compared with 23.7% of controls (1.13; 1.05–1.21). Infants born to mothers with PCOS had an increased risk of neonatal jaundice (1.20; 1.03–1.39) and respiratory complications (1.20; 1.06–1.37). Conclusions: PCOS is associated with subfertility but fertility rates are restored to those of the background population following diagnosis. Pregnancy complications and adverse neonatal outcomes are more prevalent for women with PCOS independently of obesity. PMID:26859102

  16. Adverse obstetrical and perinatal outcome in adolescent mothers associated with first birth: a hospital-based case-control study in a tertiary care hospital in North-East India

    PubMed Central

    Medhi, Robin; Das, Banani; Das, Arpana; Ahmed, Mansur; Bawri, Sonika; Rai, Suditi

    2016-01-01

    Purpose To analyze the adverse obstetrical and perinatal outcome of adolescent mothers associated with first birth. Patients and methods This prospective case-control study was conducted in a tertiary care teaching hospital of North-East India between January 2014 and December 2014. All adolescent primigravidae completing 28 weeks of gestation with singleton pregnancy and delivered at our institution were included in the study group. Primigravidae aged between 20 and 25 years were taken as a control group. Mothers having pregnancy complicated with diabetes mellitus, renal disorder, thyroid disorders, and cardiac diseases were excluded from the study. Demographic data, maternal complications like severe anemia, pre-eclampsia, eclampsia, gestational age at delivery, mode of delivery, and postpartum complications were compared. Among fetal complications, low-birth weight, preterm birth, neonatal intensive care unit admission, still birth, and early neonatal death were compared. All the patients were interviewed regarding contraceptive knowledge and its use preceding the pregnancy. Results Quality antenatal care was received by 80.6% of adolescent mothers. The adolescent mothers had a higher incidence of pre-eclampsia (odds ratio [OR] 2.017 95% confidence interval [CI]: 1.045–3.894, P=0.03), preterm deliveries (OR: 1.655, 95% CI: 1.039–2.636, P=0.03). Among fetal outcomes, the low- birth weight babies (OR: 1.59, 95% CI: 1.016–2.478), low mean birth weight (2,544.4±622.09 g versus 2,701.6±582.51 g), and higher admission to neonatal intensive care unit (OR: 1.957, 95% CI: 1.120–3.417) were significantly associated with adolescent mothers. There was no significant difference found regarding the mode of delivery, still birth, and early neonatal death. Moreover, contraceptive knowledge and its use were found to be poor among adolescent mothers. Conclusion With quality antenatal, intranatal, and postnatal care, the obstetric risk of childbirth in adolescent mothers

  17. Thrombosis during pregnancy: Risks, prevention, and treatment for mother and fetus--harvesting the power of omic technology, biomarkers and in vitro or in vivo models to facilitate the treatment of thrombosis.

    PubMed

    Ornaghi, Sara; Mueller, Martin; Barnea, Eytan R; Paidas, Michael J

    2015-09-01

    Maternal thromboembolism and a spectrum of placenta-mediated complications including the pre-eclampsia syndromes, fetal growth restriction, fetal loss, and abruption manifest a shared etiopathogenesis and predisposing risk factors. Furthermore, these maternal and fetal complications are often linked to subsequent maternal health consequences that comprise the metabolic syndrome, namely, thromboembolism, chronic hypertension, and type II diabetes. Traditionally, several lines of evidence have linked vasoconstriction, excessive thrombosis and inflammation, and impaired trophoblast invasion at the uteroplacental interface as hallmark features of the placental complications. "Omic" technologies and biomarker development have been largely based upon advances in vascular biology, improved understanding of the molecular basis and biochemical pathways responsible for the clinically relevant diseases, and increasingly robust large cohort and/or registry based studies. Advances in understanding of innate and adaptive immunity appear to play an important role in several pregnancy complications. Strategies aimed at improving prediction of these pregnancy complications are often incorporating hemodynamic blood flow data using non-invasive imaging technologies of the utero-placental and maternal circulations early in pregnancy. Some evidence suggests that a multiple marker approach will yield the best performing prediction tools, which may then in turn offer the possibility of early intervention to prevent or ameliorate these pregnancy complications. Prediction of maternal cardiovascular and non-cardiovascular consequences following pregnancy represents an important area of future research, which may have significant public health consequences not only for cardiovascular disease, but also for a variety of other disorders, such as autoimmune and neurodegenerative diseases.

  18. Kiss1 mutant placentas show normal structure and function in the mouse

    PubMed Central

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

    2015-01-01

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

  19. Immunofluorescence confocal laser scanning microscopy and immuno-electron microscopic identification of keratins in human materno-foetal interaction zone

    PubMed Central

    Ahenkorah, J; Hottor, B; Byrne, S; Bosio, P; Ockleford, C D

    2009-01-01

    Abstract We show here that at least 5 keratin proteins are present in villous trophoblast and the same 5 in extravillous trophoblast. A further 14 tested were undetectable in these tissues. In contrast, 10 of the 19 keratins tested were present in amniotic epithelium. The marking of amniotic epithelium on the one hand, as distinct from villous and extravillous trophoblast on the other, can be achieved using 5 keratins (K4, 6, 13, 14 and 17) with a mixture of positive and negative discrimination that is expected, in combination, to be highly sensitive. All the specific keratins identified in trophoblast were apparently up-regulated on the pathway to extravillous trophoblast. Co-ordinated differentiation at the molecular expression level is indicated by this finding. The relevant keratins are K5, 7, 8, 18 and 19. Specific keratins have been identified that are down-regulated in villous trophoblast in pre-eclamptic pregnancy. This difference between healthy and pre-eclamptic chorionic villous trophoblast keratin expression was statistically significant in 4 out of the 5 keratins. This was not the case for the extravillous trophoblast at the immunofluorescence confocal level but significant differences were obtained using immunogold electron microscopy. We suggest that the villous trophoblast in pre-eclamptic placentae is cytoskeletally weaker with respect to the filaments made from these specific proteins and that this is one reason why, in pre-eclampsia, trophoblast is deported in greater quantity than in healthy placentae. PMID:18466353

  20. [Hyperhomocysteinemia and pregnancy complications].

    PubMed

    Sztenc, Sławomir

    2004-04-01

    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.

  1. Epidemiologic study of necrotizing enterocolitis among low-birth-weight infants. Absence of identifiable risk factors.

    PubMed

    Kliegman, R M; Hack, M; Jones, P; Fanaroff, A A

    1982-03-01

    Necrotizing enterocolitis has been associated with a variety of perinatal problems which have been purported to be risk factors predisposing the neonate to NEC. The present investigation compares the perinatal histories of 48 low-birth-weight infants (less than 1,500 gm) with NEC to those of 553 high-risk infants of equivalent birth weight who did not have NEC but who were present in the nursery during a four-year observation period. The two populations were equivalent with regard to maternal factors such as socioeconomic status, education, race, and age. Both the antenatal and intrapartum risk scores were similar, as were the position of presentation and mode of delivery. The incidence of pre-eclampsia, prolonged rupture of the membranes, and placenta previa was also equivalent. Birth weight and gestational age were identical, as well as intrauterine growth retardation and low Apgar scores. The placement of umbilical artery catheters or the performance of exchange transfusions were not more frequent among patients with NEC. Infants who developed NEC demonstrated significantly different incidences of only three variables. Mothers of these infants were usually married, and their infants had less respiratory distress syndrome; the only adverse factor present more frequently was abruptio placenta. These data raise further questions concerning the significance of previously reported risk factors of NEC.

  2. Peripartum cardiomyopathy – case series

    PubMed Central

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

    2014-01-01

    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. PMID:24814122

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

    SciTech Connect

    Villagra, R.; Tchernitchin, N.N.; Tchernitchin, A.N.

    1997-02-01

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

  4. Exposure analysis methods impact associations between maternal physical activity and cesarean delivery

    PubMed Central

    Bovbjerg, Marit L.; Siega-Riz, Anna Maria; Evenson, Kelly R.; Goodnight, William

    2015-01-01

    Background Previous studies report conflicting results regarding a possible association between maternal physical activity (PA) and cesarean delivery. Methods 7-day PA recalls were collected by telephone from n=1205 pregnant women from North Carolina, without prior cesarean, during two time windows: 17-22 weeks and 27-30 weeks completed gestation. PA was treated as a continuous, non-linear variable in binomial regressions (log-link function); models controlled for primiparity, maternal contraindications to exercise, pre-eclampsia, pregravid BMI, and percent poverty. We examined both total PA and moderate-to-vigorous PA (MVPA) at each time. Outcomes data came from medical records. Results The dose-response curves between PA or MVPA and cesarean risk at 17-22 weeks followed an inverse J-shape, but at 27-30 weeks the curves reversed and were J-shaped. However, only (total) PA at 27-30 weeks was strongly associated with cesarean risk; this association was attenuated when women reporting large volumes of PA (>97.5th percentile) were excluded. Conclusion We did not find evidence of an association between physical activity and cesarean birth. We did, however, find evidence that associations between PA and risk of cesarean may be non-linear and dependent on gestational age at time of exposure, limiting the accuracy of analyses that collapse maternal PA into categories. PMID:24509873

  5. [Prenatal care and risk factors associated with premature birth and low birth weight in the a capital in the Brazilian Northeast].

    PubMed

    Gonzaga, Isabel Clarisse Albuquerque; Santos, Sheila Lima Diogenes; Silva, Ana Roberta Vilarouca da; Campelo, Viriato

    2016-06-01

    The main determinants of the risk of mortality in the neonatal period are low birth weight and premature birth. The study sought to analyze the adequacy of prenatal care and risk factors associated with premature birth and low birth weight in a northeastern Brazilian capital. This is a case-control study. A model for adequacy of prenatal conditions composed of four indicators was created. Descriptive statistics for univariate analysis were used; as well as Wald linear trend tests, Student's t and chi-square test for bivariate analysis and multiple logistic regression for multivariate analysis with p <0.05. Multivariate analysis showed that poor education, not performing gainful activity, caesarean section, oligohydramnios, placental abruption and pre-eclampsia are independent factors associated with premature birth and/or low birth weight. For adequacy of prenatal care, variable indicator III remained significant, showing that mothers who had inadequate prenatal care had an increased chance for the occurrence of the outcome, highlighting the need for adequate public health policies of care for pregnant women in the municipality under scrutiny.

  6. Noncoding RNA-regulated gain-of-function of STOX2 in Finnish pre-eclamptic families

    PubMed Central

    Oudejans, Cees BM; Poutsma, Ankie; Michel, Omar J.; Thulluru, Hari K.; Mulders, Joyce; van de Vrugt, Henri J.; Sistermans, Erik A.; van Dijk, Marie

    2016-01-01

    The familial forms of early onset pre-eclampsia and related syndromes (HELLP) present with hypertension and proteinuria in the mother and growth restriction of the fetus. Genetically, these clinically similar entities are caused by different founder-dependent, placentally-expressed paralogous genes. All susceptibility genes (STOX1, lincHELLP, INO80B) identified so far are master control genes that regulate an essential trophoblast differentiation pathway, but act at different entry points. Many genes remain to be identified. Here we demonstrate that a long non-coding RNA (lncRNA) within intron 3 of the STOX2 gene on 4q35.1 acts as a permissive cis-acting regulator of alternative splicing of STOX2. When this lncRNA is mutated or absent, an alternative exon (3B) of STOX2 is included. This introduces a stop codon resulting in the deletion of a highly conserved domain of 64 amino acids in the C-terminal of the STOX2 protein. A mutation present within a regulatory region within intron 1 of STOX2 has the same effect after blocking with CRISPR technology: transcripts with exon 3B are upregulated. This proces appears related to transcriptional control by a chromatin-splicing adaptor complex as described for FGFR2. For STOX2, CHD5, coding for a chromodomain helicase DNA binding protein, qualifies as the chromatin modifier in this process. PMID:27555360

  7. Prognostic value of creatine kinase BB-isoenzyme in high risk newborn infants.

    PubMed Central

    Ruth, V J

    1989-01-01

    Serum creatine kinase BB-isoenzyme (CK-BB) activity was studied on the first day of life in 31 acutely asphyxiated infants, 70 infants born after high risk pregnancies (pre-eclampsia or intrauterine growth retardation, or both), and 47 very low birthweight infants. Neuro-developmental evaluation was carried out at 2.2-2.5 years. Eight infants died with, and eight without, hypoxic-ischaemic lesions of the brain, 14 had cerebral palsy, 16 had mild motor impairment, six had developmental delay without motor impairment, and 96 were normal at follow up. Infants who died with brain injury had significantly higher CK-BB activity than infants with normal outcomes (geometric mean 12 U/l); the mean difference was 82 U/l with a 95% confidence interval from 31 to 219 U/l. CK-BB in infants with cerebral palsy and mild motor impairment (geometric means 12 and 15 U/l, respectively) were similar to controls. CK-BB activity after birth is predictive of neonatal death but not of neurological damage in survivors. PMID:2751331

  8. Pregnancy-related issues in women with systemic lupus erythematosus.

    PubMed

    Singh, Abha G; Chowdhary, Vaidehi R

    2015-02-01

    While fertility is preserved in females with systemic lupus erythematosus (SLE), it is well established that pregnancy in these patients is associated with adverse maternal and fetal outcomes, including pregnancy loss, pre-eclampsia, preterm delivery and intrauterine growth retardation, as well as neonatal mortality. Mechanisms underlying these adverse outcomes are poorly understood, and better understanding of these would allow development of targeted and personalized treatment strategies. Established risk factors for adverse pregnancy outcomes include active disease within 6 months prior to conception and during pregnancy, active nephritis, maternal hypertension, antiphospholipid antibodies and hypocomplementemia. While intensive monitoring is recommended, the comparative effectiveness of appropriate management strategies is unclear. While current strategies are able to achieve live births in 85-90% of pregnancies, certain aspects such as prevention of preterm birth, treatment of congenital heart block due to neonatal lupus and recurrent pregnancy loss despite best management, remains challenging. Pregnancy is also associated with an increased risk of flare of lupus, particularly in patients with active disease at time of conception or within 6 months prior to conception. Pregnant patients with SLE should be followed in a high-risk obstetric clinic, and care should be closely coordinated between the obstetrician and rheumatologist. PMID:25545844

  9. Placental Nutrient Transport and Intrauterine Growth Restriction

    PubMed Central

    Gaccioli, Francesca; Lager, Susanne

    2016-01-01

    Intrauterine growth restriction refers to the inability of the fetus to reach its genetically determined potential size. Fetal growth restriction affects approximately 5–15% of all pregnancies in the United States and Europe. In developing countries the occurrence varies widely between 10 and 55%, impacting about 30 million newborns per year. Besides having high perinatal mortality rates these infants are at greater risk for severe adverse outcomes, such as hypoxic ischemic encephalopathy and cerebral palsy. Moreover, reduced fetal growth has lifelong health consequences, including higher risks of developing metabolic and cardiovascular diseases in adulthood. Numerous reports indicate placental insufficiency as one of the underlying causes leading to altered fetal growth and impaired placental capacity of delivering nutrients to the fetus has been shown to contribute to the etiology of intrauterine growth restriction. Indeed, reduced expression and/or activity of placental nutrient transporters have been demonstrated in several conditions associated with an increased risk of delivering a small or growth restricted infant. This review focuses on human pregnancies and summarizes the changes in placental amino acid, fatty acid, and glucose transport reported in conditions associated with intrauterine growth restriction, such as maternal undernutrition, pre-eclampsia, young maternal age, high altitude and infection. PMID:26909042

  10. Three-dimensional ultrasound evaluation of the placenta.

    PubMed

    Hata, T; Tanaka, H; Noguchi, J; Hata, K

    2011-02-01

    Conventional two-dimensional (2D) ultrasound has been widely used for the evaluation of the placenta during pregnancy. This 2D ultrasound evaluation includes the morphology, anatomy, location, implantation, anomaly, size, and color/power and pulsed Doppler sonographic assessment of the placenta. The introduction of three-dimensional (3D) ultrasound would facilitate the novel assessment of the placenta, such as surface-rendered imaging and volume measurement. With the recent advances in 3D power Doppler (3DPD) ultrasound as well as quantitative 3DPD histogram analysis, quantitative and qualitative assessments of the vascularization and blood flow of the placenta have become feasible. These novel techniques may assist in the evaluation of the feto-placental function, and offer potential advantages relative to conventional 2D sonographic assessments. 3D ultrasound may be an important modality in future placental research, in the evaluation of feto-placental insufficiency in clinical practice, and in the prediction of fetal growth restriction and pre-eclampsia, although some limitations regarding the assessment of the placenta employing 3D ultrasound still remain unresolved.

  11. Measurement of neonatal skinfold thickness--is it of any clinical relevance?

    PubMed

    Verma, M; Singh, D; Chhatwal, J; Jayaharan, S

    1991-11-01

    The skinfold thickness (SFT) was measured in 750 Punjabi newborns at triceps and subscapular sites using a Harpenden's Caliper. It was correlated with various maternal and neonatal factors. SFT increased with increasing gestation but showed a decline after 40 weeks. There was a positive correlation of SFT with birth weight and length of the baby in both sexes. The correlation co-efficient for all these parameters was 0.9. The female babies had a higher SFT at all weight and length groups. Increasing maternal age, parity, weight and height all influenced the neonatal SFT positively. Mothers with higher SFT produced babies with more skinfold thickness. Similar relationship was observed between birth weight and these maternal factors. While severe pre-eclampsia and eclampsia led to a significant fall in SFT, hypertension alone did not affect it. A higher than normal SFT was seen among infants of diabetic mothers. It was concluded that the SFT does not give any additional information than that provided by the commonly measured parameters like birth weight and length.

  12. Low birth weight incidence in Lundu, Sarawak.

    PubMed

    Yadav, H

    1994-06-01

    The overall mean birth weight of the total deliveries (1986-1988) in Lundu Hospital was 2.96 kg. The mean birth weight for the male babies was 2.94 kg. The Chinese babies had a significantly higher mean birth weight (3.12 kg) than the other ethnic groups (p < 0.05). The overall incidence of low birth weight (LBW) in this study was 11.84 per cent. The Chinese again had a lower incidence of LBW of 6.73 per cent compared to Ibans who had the highest incidence of LBW, 13.59 per cent, with the Bidayuhs 12.97 per cent and Malays, 12.45 per cent. It was also noticed that of the 14.9 per cent preterm deliveries, 37.5 per cent were LBW. The very young mothers (15-19 years) and older mothers (> 40 years) seem to have a higher incidence of LBW. Mothers who had medical conditions like anaemia, hypertension, pre-eclampsia also had a higher incidence of LBW when compared to mothers who did not have a medical condition. Special emphasis should be given to mothers who have medical conditions, and to very young and very old mothers during antenatal care, to prevent incidence of LBW. PMID:8090096

  13. [Smokeless tobacco].

    PubMed

    Underner, M; Perriot, J

    2011-10-01

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

  14. Peripartum Cardiomyopathy Treatment with Dopamine Agonist and Subsequent Pregnancy with a Satisfactory Outcome.

    PubMed

    Melo, Maria Adélia Medeiros E; Carvalho, Jordão Sousa; Feitosa, Francisco Edson de Lucena; Araujo Júnior, Edward; Peixoto, Alberto Borges; Costa Carvalho, Francisco Herlânio; Carvalho, Regina Coeli Marques

    2016-06-01

    Pathophysiological mechanisms of peripartum cardiomyopathy are not yet completely defined, although there is a strong association with various factors that are already known, including pre-eclampsia. Peripartum cardiomyopathy treatment follows the same recommendations as heart failure with systolic dysfunction. Clinical and experimental studies suggest that products of prolactin degradation can induce this cardiomyopathy. The pharmacological suppression of prolactin production by D2 dopamine receptor agonists bromocriptine and cabergoline has demonstrated satisfactory results in the therapeutic response to the treatment. Here we present a case of an adolescent patient in her first gestation with peripartum cardiomyopathy that evolved to the normalized left ventricular function after cabergoline administration, which was used as an adjuvant in cardiac dysfunction treatment. Subsequently, despite a short interval between pregnancies, the patient exhibited satisfactory progress throughout the entire gestation or puerperium in a new pregnancy without any cardiac alterations. Dopamine agonists that are orally used and are affordable in most tertiary centers, particularly in developing countries, should be considered when treating peripartum cardiomyopathy cases. PMID:27399926

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

    PubMed

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

    1999-07-01

    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.

  16. Lung ultrasound-guided management of acute breathlessness during pregnancy.

    PubMed

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

    2013-01-01

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

  17. Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression

    PubMed Central

    Sasahira, Tomonori; Nishiguchi, Yukiko; Fujiwara, Rina; Kurihara, Miyako; Kirita, Tadaaki; Bosserhoff, Anja Katrin; Kuniyasu, Hiroki

    2016-01-01

    Background Storkhead box protein 2 (STOX2) is a transcriptional factor associated with pre-eclampsia with fetal growth restriction. We recently reported that melanoma inhibitory activity (MIA) promotes oral squamous cell carcinoma (OSCC) progression. However, the relationship between STOX2 and MIA remains unknown in malignancies. Methods We used immunohistochemistry and PCR to investigate MIA and STOX2 expression in OSCC. We also performed functional analysis in human OSCC cells. Results MIA and STOX2 mRNA levels were higher in OSCCs than in normal oral epithelial cells, and upregulation of STOX2 was significantly correlated with overexpression of MIA. Immunostaining for STOX2 was associated with nodal metastasis (P = 0.0002) and MIA expression (P < 0.0001). Furthermore, MIA expression (P = 0.0035) and STOX2 expression (P = 0.0061) were associated with poor outcome in OSCCs. In vitro analysis using OSCC cells revealed that MIA increased expression of STOX2 by paracrine manner. Moreover, STOX2 accelerated OSCC cell growth, invasion, suppressed apoptosis, and enhanced resistance to paclitaxel, cisplatin, and 5-FU. Conclusions Our results suggest that MIA-STOX2 signaling may be a useful diagnostic and therapeutic target in OSCCs. PMID:27050375

  18. Cryptogenic postpartum stroke.

    PubMed

    Bereczki, Dániel; Szegedi, Norbert; Szakács, Zoltán; Gubucz, István; May, Zsolt

    2016-01-01

    An estimated 25-40% of ischemic strokes are classified as cryptogenic, which means the cause of the cerebral infarction remains unidentified. One of the potential pathomechanisms - especially among young patients with no cardiovascular risk factors - is paradoxical embolism through a patent foramen ovale. Pregnancy, cesarean delivery and the postpartum period are associated with an increased risk of cerebrovascular events. Factors that may contribute to ischemic strokes during gestation and puerperium include classic cardiovascular risk factors, changes in hemostaseology/hemodynamics, and pregnancy-specific disorders such as pre-eclampsia, eclampsia, postpartum cerebral angiopathy or peripartum cardiomyopathy. In this case report, we present a 36-year-old thrombolysis candidate undergoing mechanical thrombectomy 3 weeks after a cesarean section due to HELLP-syndrome. After evaluation of anamnestic and diagnostic parameters, closure of the patent foramen ovale has been performed. In the absence of specific guidelines, diagnostic work-up for cryptogenic stroke should be oriented after the suspected pathomechanism based on patient history and clinical picture. As long as definite evidences emerge, management of cryptogenic stroke patients with pathogenic right-to-left shunt remains individual based on the mutual decision of the patient and the multidisciplinary medical team. PMID:27591063

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

    PubMed

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

    2004-06-01

    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

  20. Advances in understanding and treating liver diseases during pregnancy: A review

    PubMed Central

    Kamimura, Kenya; Abe, Hiroyuki; Kawai, Hirokazu; Kamimura, Hiroteru; Kobayashi, Yuji; Nomoto, Minoru; Aoyagi, Yutaka; Terai, Shuji

    2015-01-01

    Liver disease in pregnancy is rare but pregnancy-related liver diseases may cause threat to fetal and maternal survival. It includes pre-eclampsia; eclampsia; haemolysis, elevated liver enzymes, and low platelets syndrome; acute fatty liver of pregnancy; hyperemesis gravidarum; and intrahepatic cholestasis of pregnancy. Recent basic researches have shown the various etiologies involved in this disease entity. With these advances, rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival. The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention. Therefore, correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis. Therefore, here we review and summarized recent advances in understanding the etiologies, clinical courses and management of liver disease in pregnancy. This information will contribute to physicians for diagnosis of disease and optimum management of patients. PMID:25954092

  1. Risk factors for small for gestational age infants.

    PubMed

    McCowan, Lesley; Horgan, Richard P

    2009-12-01

    There are many established risk factors for babies who are small for gestational age (SGA) by population birth weight centiles (usually defined as <10th centile). The confirmed maternal risk factors include short stature, low weight, Indian or Asian ethnicity, nulliparity, mother born SGA, cigarette smoking and cocaine use. Maternal medical history of: chronic hypertension, renal disease, anti-phospholipid syndrome and malaria are associated with increased SGA. Risk factors developing in pregnancy include heavy bleeding in early pregnancy, placental abruption, pre-eclampsia and gestational hypertension. A short or very long inter-pregnancy interval, previous SGA infant or previous stillbirth are also risk factors. Paternal factors including changed paternity, short stature and father born SGA also contribute. Factors associated with reduced risk of SGA or increased birth weight include high maternal milk consumption and high intakes of green leafy vegetables and fruit. Future studies need to investigate risk factors for babies SGA by customised centiles as these babies have greater morbidity and mortality than babies defined as SGA by population centiles.

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

    PubMed

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

    2006-01-01

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

  3. A review of inter- and intraspecific variation in the eutherian placenta

    PubMed Central

    Gundling, William E.; Wildman, Derek E.

    2015-01-01

    The placenta is one of the most morphologically variable mammalian organs. Four major characteristics are typically discussed when comparing the placentas of different eutherian species: placental shape, maternal–fetal interdigitation, intimacy of the maternal–fetal interface and the pattern of maternal–fetal blood flow. Here, we describe the evolution of three of these features as well as other key aspects of eutherian placentation. In addition to interspecific anatomical variation, there is also variation in placental anatomy and function within a single species. Much of this intraspecific variation occurs in response to different environmental conditions such as altitude and poor maternal nutrition. Examinations of variation in the placenta from both intra- and interspecies perspectives elucidate different aspects of placental function and dysfunction at the maternal–fetal interface. Comparisons within species identify candidate mechanisms that are activated in response to environmental stressors ultimately contributing to the aetiology of obstetric syndromes such as pre-eclampsia. Comparisons above the species level identify the evolutionary lineages on which the potential for the development of obstetric syndromes emerged. PMID:25602076

  4. Thrombophilia in pregnancy

    PubMed Central

    Walker, I.

    2000-01-01

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

  5. A review of inter- and intraspecific variation in the eutherian placenta.

    PubMed

    Gundling, William E; Wildman, Derek E

    2015-03-01

    The placenta is one of the most morphologically variable mammalian organs. Four major characteristics are typically discussed when comparing the placentas of different eutherian species: placental shape, maternal-fetal interdigitation, intimacy of the maternal-fetal interface and the pattern of maternal-fetal blood flow. Here, we describe the evolution of three of these features as well as other key aspects of eutherian placentation. In addition to interspecific anatomical variation, there is also variation in placental anatomy and function within a single species. Much of this intraspecific variation occurs in response to different environmental conditions such as altitude and poor maternal nutrition. Examinations of variation in the placenta from both intra- and interspecies perspectives elucidate different aspects of placental function and dysfunction at the maternal-fetal interface. Comparisons within species identify candidate mechanisms that are activated in response to environmental stressors ultimately contributing to the aetiology of obstetric syndromes such as pre-eclampsia. Comparisons above the species level identify the evolutionary lineages on which the potential for the development of obstetric syndromes emerged. PMID:25602076

  6. [Premature newborn: a case presentation].

    PubMed

    Pastor Rodríguez, Jesús David; Pastor Bravo, María Del Mar; López García, Visitación; Cotes Teruel, María Isabel; Mellado, Jesús Eulogio; Cárceles, José Jara

    2010-01-01

    A case is presented of a premature newborn of 27 weeks gestation and weighing 420 grams who was delivered as a result of a maternal pre-eclampsia and retarded intra-uterine growth. During the 125 days of hospitalisation, an individual care plan based on the Virginia Henderson model was devised and applied to both the child and her parents using NANDA diagnostics, interventions according to the NIC classification, and the expected results according to the NOC classification. The Marjory Gordon functional patterns were used for the initial assessment. By applying the pre-term newborn (PTNB) plan, all their needs were provided and were modified throughout the hospital stay, with new needs that were added to the established ones. These required a continuous assessment with the subsequent adapting of the care plan. Likewise, the care required by the parents varied from the initial grief due to the possible loss of their child to learning the alarm signs and the home care that their child would need. The child was finally discharged weighing 2900 grams and with normal neurological and psychomotor development, although with a lower weight appropriate to her age. Currently, at 2 years old, the child has a normal neurological and psychomotor development, but with weight and size lower than the P(3) percentile. She requires speech therapy treatment due to paralysis of the right vocal cord.

  7. Training of midwives in advanced obstetrics in Liberia

    PubMed Central

    Dolo, Obed; Clack, Alice; Gibson, Hannah; Lewis, Naomi

    2016-01-01

    Abstract Problem The shortage of doctors in Liberia limits the provision of comprehensive emergency obstetric and neonatal care. Approach In a pilot project, two midwives were trained in advanced obstetric procedures and in the team approach to the in-hospital provision of advanced maternity care. The training took two years and was led by a Liberian consultant obstetrician with support from international experts. Local setting The training took place in CB Dunbar Maternity Hospital. This rural hospital deals with approximately 2000 deliveries annually, many of which present complications. In February 2015 there were just 117 doctors available in Liberia. Relevant changes In the first 18 months of training, the trainees were involved with 236 caesarean sections, 35 manual evacuations of products of conception, 25 manual removals of placentas, 21 vaginal breech deliveries, 14 vacuum deliveries, four repairs of ruptured uteri, the management of four cases of shoulder dystocia, three hysterectomies, two laparotomies for ruptured ectopic pregnancies and numerous obstetric ultrasound examinations. The trainees also managed 41 cases of eclampsia or severe pre-eclampsia, 25 of major postpartum haemorrhage and 21 of shock. Although, initially they only assisted senior doctors, the trainees subsequently progressed from direct to indirect supervision and then to independent management. Lessons learnt To compensate for a shortage of doctors able to undertake comprehensive emergency obstetric and neonatal care, experienced midwives can be taught to undertake advanced obstetric care and procedures. Their team work with doctors can be particularly valuable in rural hospitals in resource-poor countries. PMID:27147768

  8. Monocyte Subpopulations from Pre-Eclamptic Patients Are Abnormally Skewed and Exhibit Exaggerated Responses to Toll-Like Receptor Ligands

    PubMed Central

    Al-ofi, Ebtisam

    2012-01-01

    The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14lowCD16+ monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14highCD16+ and CD14lowCD16+ monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP controls. These data suggest that PE monocytes are hyper-responsive to TLR ligands and this may contribute to exacerbation of the disease. PMID:22848746

  9. Blood Pressure in Third Trimester of Pregnancy.

    PubMed

    Sufrin, S; Nessa, A; Islam, M T; Khatun, A A; Husain, M F; Khatun, N; Wahed, F; Das, R K; Zannat, M R

    2016-01-01

    Pregnancy is a great stressful physiological condition in women during their reproductive period. During pregnancy several hemodynamic, biochemical and hematological modifications occur as a part of the physiological adaptation of the body. Changes in blood pressure occur in third trimester of pregnancy, which may be associated with increased maternal and infant mortality and morbidity. This cross-sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, from July 2013 to June 2014. Study subjects were selected by following purposive sampling procedure and the protocol of this study was approved by Institutional Ethics Committee (IEC) of Mymensingh. This study enrolled 100 pregnant women of third trimester of pregnancy and 100 aged matched non-pregnant women from Mymensingh district. Mean systolic blood pressure in study group were 124.8±14.51 mm of Hg and in control group were 106.50±10.67 mm of Hg, which was statistically increased. Diastolic blood pressure in study group was 83.00±13.37 mm of Hg and in control group 71.05±7.12 mm of Hg, which was also statistically significant. The changes in blood pressure in third trimester of pregnancy is the major concern of developing the risk of pre-eclampsia & eclampsia, and increased prevalence of IUGR, pre-maturity and perinatal mortality. This study reveals significant changes of blood pressure during third trimester of pregnancy.

  10. Noncoding RNA-regulated gain-of-function of STOX2 in Finnish pre-eclamptic families.

    PubMed

    Oudejans, Cees Bm; Poutsma, Ankie; Michel, Omar J; Thulluru, Hari K; Mulders, Joyce; van de Vrugt, Henri J; Sistermans, Erik A; van Dijk, Marie

    2016-01-01

    The familial forms of early onset pre-eclampsia and related syndromes (HELLP) present with hypertension and proteinuria in the mother and growth restriction of the fetus. Genetically, these clinically similar entities are caused by different founder-dependent, placentally-expressed paralogous genes. All susceptibility genes (STOX1, lincHELLP, INO80B) identified so far are master control genes that regulate an essential trophoblast differentiation pathway, but act at different entry points. Many genes remain to be identified. Here we demonstrate that a long non-coding RNA (lncRNA) within intron 3 of the STOX2 gene on 4q35.1 acts as a permissive cis-acting regulator of alternative splicing of STOX2. When this lncRNA is mutated or absent, an alternative exon (3B) of STOX2 is included. This introduces a stop codon resulting in the deletion of a highly conserved domain of 64 amino acids in the C-terminal of the STOX2 protein. A mutation present within a regulatory region within intron 1 of STOX2 has the same effect after blocking with CRISPR technology: transcripts with exon 3B are upregulated. This proces appears related to transcriptional control by a chromatin-splicing adaptor complex as described for FGFR2. For STOX2, CHD5, coding for a chromodomain helicase DNA binding protein, qualifies as the chromatin modifier in this process. PMID:27555360

  11. Antiphospholipid syndrome and pregnancy.

    PubMed

    Zatti, Sonia; Rebaioli, Chiara Biasini; Lojacono, Andrea; Rovetto, Bettina; Barbolini, Edoardo; Taglietti, Marco; Nuzzo, Monica; Tincani, Angela

    2006-11-01

    Since the 1960s, antiphospholipid antibodies have been known to be associated with repeated miscarriages and fetal losses. Other complications of pregnancy, such as preterm birth, with pre-eclampsia or severe placental insufficiency were also frequently reported and are included in the current classification criteria of the antiphospholipid syndrome. The titer, isotype or antigen specificity of the antibodies may be important in risk determination. The pathogenesis of pregnancy failures is not only linked to the thrombophilic effect of antiphospholipid antibodies but also to a direct effect of antibodies on trophoblast differentiation and invasion. The study of experimental animal models provided sound evidence of the pathogenic role of antiphospholipid antibodies both in lupus-prone and -naive mice. The classification of pregnant antiphospholipid syndrome patients as being at a 'high risk' has completely changed their prognosis due to obstetric monitoring and the application of effective therapy. In fact, despite the high rates of complications and preterm delivery, a successful outcome can now be achieved in a large majority of cases.

  12. Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes.

    PubMed

    Tedeschi, Sara K; Guan, Hongshu; Fine, Alexander; Costenbader, Karen H; Bermas, Bonnie

    2016-07-01

    Systemic lupus erythematosus (SLE) is a disease of reproductive-age women, and thus questions regarding how disease influences pregnancy outcomes arise. We investigated whether five specific types of SLE activity during the 6 months before conception or during pregnancy (nephritis, cytopenias, skin disease, arthritis, serositis) were associated with adverse pregnancy outcomes. We performed a retrospective cohort study of pregnancy outcomes among women with SLE at the Brigham and Women's Hospital Lupus Center. Adverse pregnancy outcomes included pre-eclampsia, pre-term delivery, elective termination due to SLE, spontaneous miscarriage at weeks 12-20, and stillbirth. SLE and obstetric history, laboratories, and medications were obtained from electronic medical records. Generalized linear mixed models adjusting for potential confounders were used to identify predictors of any adverse pregnancy outcome. Most pregnancies resulted in a live term delivery (76.5 %). After adjustment for Hispanic ethnicity, prior adverse pregnancy outcome and medication use 6 months before conception, nephritis during pregnancy (odds ratio (OR) 3.6, 95 % confidence interval (CI) 1.0-12.8), cytopenias during pregnancy (OR 3.9, 95 % CI 1.3-11.4), and serositis during pregnancy (OR 5.9, 95 % CI 1.0-34.0) were significantly associated with adverse pregnancy outcome. Specific types of SLE disease activity during pregnancy were related to adverse pregnancy outcome. Nephritis, cytopenias, and serositis carried a higher risk of adverse pregnancy outcome, suggesting that these abnormalities should be carefully monitored during pregnancy. PMID:27166627

  13. Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews.

    PubMed

    Marchi, J; Berg, M; Dencker, A; Olander, E K; Begley, C

    2015-08-01

    Maternal obesity is linked with adverse outcomes for mothers and babies. To get an overview of risks related to obesity in pregnant women, a systematic review of reviews was conducted. For inclusion, reviews had to compare pregnant women of healthy weight with women with obesity, and measure a health outcome for mother and/or baby. Authors conducted full-text screening, quality assurance using the AMSTAR tool and data extraction steps in pairs. Narrative analysis of the 22 reviews included show gestational diabetes, pre-eclampsia, gestational hypertension, depression, instrumental and caesarean birth, and surgical site infection to be more likely to occur in pregnant women with obesity compared with women with a healthy weight. Maternal obesity is also linked to greater risk of preterm birth, large-for-gestational-age babies, foetal defects, congenital anomalies and perinatal death. Furthermore, breastfeeding initiation rates are lower and there is greater risk of early breastfeeding cessation in women with obesity compared with healthy weight women. These adverse outcomes may result in longer duration of hospital stay, with concomitant resource implications. It is crucial to reduce the burden of adverse maternal and foetal/child outcomes caused by maternal obesity. Women with obesity need support to lose weight before they conceive, and to minimize their weight gain in pregnancy.

  14. Position of the Academy of Nutrition and Dietetics: Obesity, Reproduction, and Pregnancy Outcomes.

    PubMed

    Stang, Jamie; Huffman, Laurel G

    2016-04-01

    It is the position of the Academy of Nutrition and Dietetics that all women of reproductive age receive education about maternal and fetal risks associated with prepregnancy obesity, excessive gestational weight gain, and significant postpartum weight retention, including potential benefits of lifestyle changes. Behavioral counseling to improve dietary intake and physical activity should be provided to overweight and obese women, beginning in the preconception period and continuing throughout pregnancy, for at least 12 to 18 months postpartum. Weight loss before pregnancy may improve fertility and reduce the risk of poor maternal-fetal outcomes, such as preterm birth, gestational diabetes, gestational hypertension, pre-eclampsia, assisted delivery, and select congenital anomalies. Lifestyle interventions that moderate gestational weight gain may reduce the risk of poor pregnancy outcomes, such as gestational diabetes, gestational hypertension, large for gestational age, and macrosomia, as well as lower the risk for significant postpartum retention. Postpartum interventions that promote healthy diet and physical activity behaviors may reduce postpartum weight retention and decrease obesity-related risks in subsequent pregnancies. Analysis of the evidence suggests that there is good evidence to support the role of diet, physical activity, and behavior changes in promoting optimal weight gain during pregnancy; however, there is currently a relative lack of evidence in other areas related to reproductive outcomes.

  15. Blood Pressure Mobile Monitoring for Pregnant Woman Based Android System

    NASA Astrophysics Data System (ADS)

    Supriyanti, Retno; Erfayanto, Uji; Ramadani, Yogi; Murdyantoro, Eko; Widodo, Haris B.

    2016-01-01

    Currently, at least 18,000 women die every year in Indonesia due to pregnancy or childbirth. It means that every half hour a woman dies due to pregnancy or childbirth. As a result, every year 36,000 children became orphans. The high maternal mortality rate was put Indonesia on top in ASEAN. The main causes of maternal mortality are high-risk pregnancy. Mothers who have diseases like high blood pressure, pre-eclampsia, diabetes, hyperthyroidism, and already over 40 years old and infectious diseases such as rubella, hepatitis and HIV can be factors that lead to high-risk pregnancy. This paper will discuss the development of a blood pressure monitoring device that is suitable for pregnant women. It is based on convenience for pregnant women to get the equipment that is flexible with her presence. Results indicate that the equipment is in use daily support for pregnant women therefore, one of the causes of maternal mortality can be detected earlier.

  16. Essential basic and emergency obstetric and newborn care: from education and training to service delivery and quality of care.

    PubMed

    Otolorin, Emmanuel; Gomez, Patricia; Currie, Sheena; Thapa, Kusum; Dao, Blami

    2015-06-01

    Approximately 15% of expected births worldwide will result in life-threatening complications during pregnancy, delivery, or the postpartum period. Providers skilled in emergency obstetric and newborn care (EmONC) services are essential, particularly in countries with a high burden of maternal and newborn mortality. Jhpiego and its consortia partners have implemented three global programs to build provider capacity to provide comprehensive EmONC services to women and newborns in these resource-poor settings. Providers have been educated to deliver high-impact maternal and newborn health interventions, such as prevention and treatment of postpartum hemorrhage and pre-eclampsia/eclampsia and management of birth asphyxia, within the broader context of quality health services. This article describes Jhpiego's programming efforts within the framework of the basic and expanded signal functions that serve as indicators of high-quality basic and emergency care services. Lessons learned include the importance of health facility strengthening, competency-based provider education, global leadership, and strong government ownership and coordination as essential precursors to scale-up of high impact evidence-based maternal and newborn interventions in low-resource settings. PMID:26115858

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

    PubMed

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

    2012-06-01

    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.

  18. A pilot study using laser-based technique for non-invasive diagnostics of hypertensive conditions in mice

    NASA Astrophysics Data System (ADS)

    Litvinova, Karina S.; Ahmad, Shakil; Wang, Keqing; Rafailov, Ilya E.; Sokolovski, Sergei G.; Zhang, Lin; Rafailov, Edik U.; Ahmed, Asif

    2016-02-01

    Endothelial dysfunction is directly linked to preeclampsia, a maternal hypertensive condition that is life threating for both the mother and the baby. Epidemiological studies show that women with a history of pre-eclampsia have an elevated risk for cardiovascular disease. Here we report a new non-invasive diagnostic test for preeclampsia in mice that allows us to non-invasively assess the condition of the animals during the experiment and treatment in established models of preeclampsia. A laser-based multifunctional diagnostics system (LAKK-M) was chosen to carry out non-invasive analysis of multiple parameters. The device was used to simultaneously record the microcirculatory blood flow and oxygen saturation, as well as fluorescence levels of endogenous fluorophores. Preliminary experiments were conducted on adenoviral (Ad-)- mediated overexpression of sFlt-1 (Ad-sFlt-1) to mimic preeclampsialike symptoms in mice. The recorded data displayed the ability of the LAKK-M diagnostics device to detect significant differences in perfusion measurements between the control and Ad-sFlt-1 treatment. Preliminary results provide a potential avenue to employ these diagnostics technology to monitor and aid in maintaining control of live animal conditions throughout the experiment and treatment.

  19. Systematic Analysis of the Molecular Mechanism Underlying Decidualization Using a Text Mining Approach

    PubMed Central

    Liu, Ji-Long; Wang, Tong-Song

    2015-01-01

    Decidualization is a crucial process for successful embryo implantation and pregnancy in humans. Defects in decidualization during early pregnancy are associated with several pregnancy complications, such as pre-eclampsia, intrauterine growth restriction and recurrent pregnancy loss. However, the mechanism underlying decidualization remains poorly understood. In the present study, we performed a systematic analysis of decidualization-related genes using text mining. We identified 286 genes for humans and 287 genes for mice respectively, with an overlap of 111 genes shared by both species. Through enrichment test, we demonstrated that although divergence was observed, the majority of enriched gene ontology terms and pathways were shared by both species, suggesting that functional categories were more conserved than individual genes. We further constructed a decidualization-related protein-protein interaction network consisted of 344 nodes connected via 1,541 edges. We prioritized genes in this network and identified 12 genes that may be key regulators of decidualization. These findings would provide some clues for further research on the mechanism underlying decidualization. PMID:26222155

  20. Maternal mortality in obstetrics and gynaecology in a tertiary care hospital.

    PubMed

    Khatun, K; Ara, R; Aleem, N T; Khan, S; Husein, S; Alam, S; Roy, A S

    2015-01-01

    Maternal mortality is the leading causes of death and disability of reproductive age in the developing countries. Bangladesh is one of the developing countries where maternal mortality is very high. The purpose of the present study was to see the causes of maternal deaths at Obstetrics and Gynaecology ward. This retrospective study was carried out in the Department of Obstetrics and Gynaecology at Dhaka Medical College Hospital (DMCH). All maternal deaths were included in this study from July 2003 to June 2004 for a period of one year. The incidence of maternal death was 18.5/1000 live birth. Hypertensive disorder of pregnancy (41.84%) was the most common cause of maternal death followed by unsafe abortions (21.4%), PPH (10.2%), obstructed labour (8.2%). Among 98 patients 36(36.7%) cases are died due to eclampsia. Death due to pre-eclampsia (5.1%), unsafe Abortion (21.4%), Obstetric haemorrhage (18.4%) and obstructed labour (8.3%) were commonly found in this study. The study permits to conclude that Hypertensive disorder of pregnancy is the leading cause of pregnancy related deaths followed by unsafe abortions and obstetric haemorrhage. Other causes include obstructed labour, anaesthetic complications and others.

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2012-01-01

    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.

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

    PubMed Central

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

    2013-01-01

    Objective Nuclear factor kappa B (NF-κB) 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-κB, 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-κB 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-κB 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-κB/IKK complex expression and oxidative stress reactions in the placenta. PMID:23772281

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

    PubMed

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

    2011-01-01

    TNF-α (tumor necrosis factor-α) is a potent pro-inflammatory cytokine that regulates the permeability of blood and lymphatic vessels. The plasma concentration of TNF-α 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-α 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-α (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-α 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

  5. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases

    PubMed Central

    Perrone, Serafina; Santacroce, Antonino; Picardi, Anna; Buonocore, Giuseppe

    2016-01-01

    Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity. PMID:27170927

  6. Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews.

    PubMed

    Marchi, J; Berg, M; Dencker, A; Olander, E K; Begley, C

    2015-08-01

    Maternal obesity is linked with adverse outcomes for mothers and babies. To get an overview of risks related to obesity in pregnant women, a systematic review of reviews was conducted. For inclusion, reviews had to compare pregnant women of healthy weight with women with obesity, and measure a health outcome for mother and/or baby. Authors conducted full-text screening, quality assurance using the AMSTAR tool and data extraction steps in pairs. Narrative analysis of the 22 reviews included show gestational diabetes, pre-eclampsia, gestational hypertension, depression, instrumental and caesarean birth, and surgical site infection to be more likely to occur in pregnant women with obesity compared with women with a healthy weight. Maternal obesity is also linked to greater risk of preterm birth, large-for-gestational-age babies, foetal defects, congenital anomalies and perinatal death. Furthermore, breastfeeding initiation rates are lower and there is greater risk of early breastfeeding cessation in women with obesity compared with healthy weight women. These adverse outcomes may result in longer duration of hospital stay, with concomitant resource implications. It is crucial to reduce the burden of adverse maternal and foetal/child outcomes caused by maternal obesity. Women with obesity need support to lose weight before they conceive, and to minimize their weight gain in pregnancy. PMID:26016557

  7. Systematic Analysis of the Molecular Mechanism Underlying Decidualization Using a Text Mining Approach.

    PubMed

    Liu, Ji-Long; Wang, Tong-Song

    2015-01-01

    Decidualization is a crucial process for successful embryo implantation and pregnancy in humans. Defects in decidualization during early pregnancy are associated with several pregnancy complications, such as pre-eclampsia, intrauterine growth restriction and recurrent pregnancy loss. However, the mechanism underlying decidualization remains poorly understood. In the present study, we performed a systematic analysis of decidualization-related genes using text mining. We identified 286 genes for humans and 287 genes for mice respectively, with an overlap of 111 genes shared by both species. Through enrichment test, we demonstrated that although divergence was observed, the majority of enriched gene ontology terms and pathways were shared by both species, suggesting that functional categories were more conserved than individual genes. We further constructed a decidualization-related protein-protein interaction network consisted of 344 nodes connected via 1,541 edges. We prioritized genes in this network and identified 12 genes that may be key regulators of decidualization. These findings would provide some clues for further research on the mechanism underlying decidualization. PMID:26222155

  8. Correlation of pregnancy outcome with quadruple screening test at second trimester

    PubMed Central

    Yazdani, Shahla; Rouholahnejad, Rahele; Asnafi, Nesa; Sharbatdaran, Majid; Zakershob, Marziihe; Bouzari, Zinatossadat

    2015-01-01

    Background: Abnormal levels of the markers AFP, hCG, and uE3 could be useful in predicting adverse pregnancy outcomes. This study was designed to determine the correlation between second trimester maternal serum markers and adverse pregnancy outcome (APO). Methods: In this historical cohort study, we randomly followed 231 obstetric patients with quadruple screening test in 14-18 weeks of gestation from March 2012 to March 2013 in a medical laboratory in Babol, Iran. We measured maternal serum levels of alphafetoprotein (AFP), human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin-A. The risk of adverse pregnancy outcomes (APOs) were then compared between patients with negative and positive test results. We used Chi-square and Fisher-exact tests for qualitative variables and t-test for quantitative variables. Demographic differences between the two groups were minimized by applying logistic regression. Results: The risk of having an APO such as pre-eclampsia (p=0.008), fetal growth restriction (p=0.028) and premature rupture of membrane (p=0.040) increased significantly in patients with abnormal markers. Conclusion: Abnormal results of quadruple screening test could be associated with APO in women with normal appearing fetus. PMID:26913244

  9. Position of the Academy of Nutrition and Dietetics: Obesity, Reproduction, and Pregnancy Outcomes.

    PubMed

    Stang, Jamie; Huffman, Laurel G

    2016-04-01

    It is the position of the Academy of Nutrition and Dietetics that all women of reproductive age receive education about maternal and fetal risks associated with prepregnancy obesity, excessive gestational weight gain, and significant postpartum weight retention, including potential benefits of lifestyle changes. Behavioral counseling to improve dietary intake and physical activity should be provided to overweight and obese women, beginning in the preconception period and continuing throughout pregnancy, for at least 12 to 18 months postpartum. Weight loss before pregnancy may improve fertility and reduce the risk of poor maternal-fetal outcomes, such as preterm birth, gestational diabetes, gestational hypertension, pre-eclampsia, assisted delivery, and select congenital anomalies. Lifestyle interventions that moderate gestational weight gain may reduce the risk of poor pregnancy outcomes, such as gestational diabetes, gestational hypertension, large for gestational age, and macrosomia, as well as lower the risk for significant postpartum retention. Postpartum interventions that promote healthy diet and physical activity behaviors may reduce postpartum weight retention and decrease obesity-related risks in subsequent pregnancies. Analysis of the evidence suggests that there is good evidence to support the role of diet, physical activity, and behavior changes in promoting optimal weight gain during pregnancy; however, there is currently a relative lack of evidence in other areas related to reproductive outcomes. PMID:27017177

  10. [Diabetes insipidus and pregnancy].

    PubMed

    Gutiérrez Cruz, Oswaldo; Careaga Benítez, Ricardo

    2007-04-01

    Diabetes insipidus is an uncommon pathology; its incidence varies from two to six cases in 100,000 pregnancies. It has multiple etiologies and it is classified in central and neurogenic. Patients with diabetes insipidus generally show intense thirst, polyuria, neurologic symptoms and hypernatremia. It does not seem to alter the patient's fertility. Diabetes insipidus is usually associated with pre-eclampsia, HELLP syndrome, and fatty liver disease of pregnancy. This is a report of a case seen at the Hospital General de Cholula, in Puebla, Mexico. A 19 year-old female, with 37.2 weeks of pregnancy, had a history of Langerhans cell histiocytosis since she was four years. Patient was treated with intranasal desmopressin until 2005. She went to an obstetric evaluation; laboratory and cabinet studies were obtained. A healthy 1900 g female was obtained through vaginal delivery, with a 7/9 Apgar score. We should be familiarized with this uncommon pathology because of its association with several obstetric emergencies.

  11. The placenta: a multifaceted, transient organ.

    PubMed

    Burton, Graham J; Fowden, Abigail L

    2015-03-01

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

  12. Utility of proteomics in obstetric disorders: a review

    PubMed Central

    Hernández-Núñez, Jónathan; Valdés-Yong, Magel

    2015-01-01

    The study of proteomics could explain many aspects of obstetric disorders. We undertook this review with the aim of assessing the utility of proteomics in the specialty of obstetrics. We searched the electronic databases of MEDLINE, EBSCOhost, BVS Bireme, and SciELO, using various search terms with the assistance of a librarian. We considered cohort studies, case-control studies, case series, and systematic review articles published until October 2014 in the English or Spanish language, and evaluated their quality and the internal validity of the evidence provided. Two reviewers extracted the data independently, then both researchers simultaneously revised the data later, to arrive at a consensus. The search retrieved 1,158 papers, of which 965 were excluded for being duplicates, not relevant, or unrelated studies. A further 86 papers were excluded for being guidelines, protocols, or case reports, along with another 64 that did not contain relevant information, leaving 43 studies for inclusion. Many of these studies showed the utility of proteomic techniques for prediction, pathophysiology, diagnosis, management, monitoring, and prognosis of pre-eclampsia, perinatal infection, premature rupture of membranes, preterm birth, intrauterine growth restriction, and ectopic pregnancy. Proteomic techniques have enormous clinical significance and constitute an invaluable weapon in the management of obstetric disorders that increase maternal and perinatal morbidity and mortality. PMID:25926758

  13. Sources and Determinants of Vitamin D Intake in Danish Pregnant Women

    PubMed Central

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

    2012-01-01

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

  14. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases.

    PubMed

    Perrone, Serafina; Santacroce, Antonino; Picardi, Anna; Buonocore, Giuseppe

    2016-05-01

    Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.

  15. Antioxidants and fetal protection against ethanol teratogenicity. I. Review of the experimental data and implications to humans.

    PubMed

    Cohen-Kerem, Raanan; Koren, Gideon

    2003-01-01

    Ethanol is the most common human teratogen, and heavy drinking during pregnancy can result in serious adverse outcomes to the fetus. The cellular mechanisms by which ethanol induces damage in utero are not well understood, while induction of oxidative stress is believed to be one putative mechanism. Our objective is to review the data of antioxidant effects in experimental models of fetal alcohol syndrome. Prior to the description of the available experimental data, we will briefly review the mechanisms leading to ethanol-induced oxidative stress. Ethanol-induced oxidative damage to the fetus could be attenuated by a variety of antioxidants as was documented in whole animal and tissue culture studies. Experiments, retrieved from the literature search, are described and criticized. Although experimental data are still limited, the application of a treatment strategy that includes antioxidants is justified since antioxidant treatment in human pregnancy for pre-eclampsia was demonstrated to be safe and effective. The available experimental evidence and the safety of vitamins C and E in pregnancy suggest that experimental use of antioxidants in alcohol-consuming mothers should be seriously considered to reduce fetal alcohol damage.

  16. Risk factors for small for gestational age infants.

    PubMed

    McCowan, Lesley; Horgan, Richard P

    2009-12-01

    There are many established risk factors for babies who are small for gestational age (SGA) by population birth weight centiles (usually defined as <10th centile). The confirmed maternal risk factors include short stature, low weight, Indian or Asian ethnicity, nulliparity, mother born SGA, cigarette smoking and cocaine use. Maternal medical history of: chronic hypertension, renal disease, anti-phospholipid syndrome and malaria are associated with increased SGA. Risk factors developing in pregnancy include heavy bleeding in early pregnancy, placental abruption, pre-eclampsia and gestational hypertension. A short or very long inter-pregnancy interval, previous SGA infant or previous stillbirth are also risk factors. Paternal factors including changed paternity, short stature and father born SGA also contribute. Factors associated with reduced risk of SGA or increased birth weight include high maternal milk consumption and high intakes of green leafy vegetables and fruit. Future studies need to investigate risk factors for babies SGA by customised centiles as these babies have greater morbidity and mortality than babies defined as SGA by population centiles. PMID:19604726

  17. [Treatment experience with metformin in polycystic ovary syndrome].

    PubMed

    Petrányi, Gyula

    2005-05-22

    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.

  18. Human leukocyte antigen-G in the male reproductive system and in seminal plasma.

    PubMed

    Larsen, Margit Hørup; Bzorek, Michael; Pass, Malene B; Larsen, Lise Grupe; Nielsen, Mette Weidinger; Svendsen, Signe Goul; Lindhard, Anette; Hviid, Thomas Vauvert F

    2011-12-01

    One of the non-classical human leukocyte antigen (HLA) class Ib proteins, HLA-G, is believed to exert important immunoregulatory functions, especially during pregnancy. The presence of HLA protein in paternal seminal fluid has been suggested to have an influence on the risk of developing pre-eclampsia. We have investigated whether HLA-G protein is present in human seminal plasma and in different tissue samples of the male reproductive system. Western blot technique and a soluble HLA-G (sHLA-G) assay were used to detect sHLA-G in human seminal plasma samples. Immunohistochemical staining was performed on paraffin-embedded tissue samples. We detected sHLA-G protein in seminal plasma, and HLA-G expression in normal testis and in epididymal tissue of the male reproductive system but not in the seminal vesicle. Furthermore, the results indicated a weak expression of HLA-G in hyperplastic prostatic tissue. In summary, several of the findings reported in this study suggest an immunoregulatory role of HLA-G in the male reproductive system and in seminal plasma.

  19. Blood Pressure in Third Trimester of Pregnancy.

    PubMed

    Sufrin, S; Nessa, A; Islam, M T; Khatun, A A; Husain, M F; Khatun, N; Wahed, F; Das, R K; Zannat, M R

    2016-01-01

    Pregnancy is a great stressful physiological condition in women during their reproductive period. During pregnancy several hemodynamic, biochemical and hematological modifications occur as a part of the physiological adaptation of the body. Changes in blood pressure occur in third trimester of pregnancy, which may be associated with increased maternal and infant mortality and morbidity. This cross-sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, from July 2013 to June 2014. Study subjects were selected by following purposive sampling procedure and the protocol of this study was approved by Institutional Ethics Committee (IEC) of Mymensingh. This study enrolled 100 pregnant women of third trimester of pregnancy and 100 aged matched non-pregnant women from Mymensingh district. Mean systolic blood pressure in study group were 124.8±14.51 mm of Hg and in control group were 106.50±10.67 mm of Hg, which was statistically increased. Diastolic blood pressure in study group was 83.00±13.37 mm of Hg and in control group 71.05±7.12 mm of Hg, which was also statistically significant. The changes in blood pressure in third trimester of pregnancy is the major concern of developing the risk of pre-eclampsia & eclampsia, and increased prevalence of IUGR, pre-maturity and perinatal mortality. This study reveals significant changes of blood pressure during third trimester of pregnancy. PMID:26931243

  20. Hypertensive diseases of pregnancy.

    PubMed

    1991-01-01

    A meeting in Singapore of principal investigators from 7 countries in a WHO collaborative study on hypertensive disease of pregnancy, also called pre-eclampsia or eclampsia, pointed out women at risk, suggested management guidelines, and summarized operations research projects involving administration of aspirin or calcium supplements. Hypertensive disease of pregnancy may ultimately end in fatal seizures. It is often marked by warning signs of severe headaches and facial and peripheral edema. A survey in Jamaica found that 0.72% of a group of 10,000 pregnant women had eclamptic seizures. These were the cause of almost one-third of all obstetric deaths in the period 1981-1983. 10.4% of the pregnant women had hypertension, and half of these had proteinuria. Associated risk factors were primigravida, age 30, abnormal weight gain, edema, 1+ proteinuria. A phased program of management guidelines for identifying and treating affected women is being instituted in half of Jamaica's parishes. An operations research project involves administration of low-dose aspirin vs. placebo. Another controlled trial, in Peru, is testing calcium supplements. A third trial in Argentina will compare 2 drug regimens.

  1. Living kidney donation: outcomes, ethics, and uncertainty.

    PubMed

    Reese, Peter P; Boudville, Neil; Garg, Amit X

    2015-05-16

    Since the first living-donor kidney transplantation in 1954, more than half a million living kidney donations have occurred and research has advanced knowledge about long-term donor outcomes. Donors in developed countries have a similar life expectancy and quality of life as healthy non-donors. Living kidney donation is associated with an increased risk of end-stage renal disease, although this outcome is uncommon (<0·5% increase in incidence at 15 years). Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. Many donors incur financial expenses due to factors such as lost wages, need for sick days, and travel expenses. Yet, most donors have no regrets about donation. Living kidney donation is practised ethically when informed consent incorporates information about risks, uncertainty about outcomes is acknowledged when it exists, and a donor's risks are proportional to benefits for the donor and recipient. Future research should determine whether outcomes are similar for donors from developing countries and donors with pre-existing conditions such as obesity. PMID:26090646

  2. PSG9 Stimulates Increase in FoxP3+ Regulatory T-Cells through the TGF-β1 Pathway

    PubMed Central

    Mentink-Kane, Margaret; Warren, James; Rattila, Shemona; Malech, Harry; Kang, Elizabeth; Dveksler, Gabriela

    2016-01-01

    The pregnancy-specific glycoproteins (PSGs) are a family of proteins secreted by the syncytiotrophoblast of the placenta and are the most abundant trophoblastic proteins in maternal blood during the third trimester. The human PSG family consists of 10 protein-coding genes, some of which have a possible role in maintaining maternal immune tolerance to the fetus. PSG9 was reported as a potential predictive biomarker of pre-eclampsia, a serious complication of pregnancy that has been related to immunological dysfunction at the fetal-maternal interface. Therefore, we hypothesized that PSG9 may have an immunoregulatory role during pregnancy. We found that PSG9 binds to LAP and activates the latent form of TGF-β1. In addition, PSG9 induces the secretion of TGF-β1 from macrophages but not from CD4+ T-cells. TGF-β1 is required for the ex vivo differentiation of regulatory T-cells and, consistent with the ability of PSG9 to activate this cytokine, we observed that PSG9 induces the differentiation of FoxP3+ regulatory T-cells from naïve murine and human T-cells. Cytokines that are associated with inflammatory responses were also reduced in the supernatants of T-cells treated with PSG9, suggesting that PSG9, through its activation of TGFβ-1, could be a potent inducer of immune tolerance. PMID:27389696

  3. Gene expression in term placentas is regulated more by spinal or epidural anesthesia than by late-onset preeclampsia or gestational diabetes mellitus

    PubMed Central

    Lekva, Tove; Lyle, Robert; Roland, Marie Cecilie Paasche; Friis, Camilla; Bianchi, Diana W.; Jaffe, Iris Z.; Norwitz, Errol R.; Bollerslev, Jens; Henriksen, Tore; Ueland, Thor

    2016-01-01

    Pre-eclampsia (PE) and gestational diabetes mellitus (GDM) are common complications of pregnancy, but the mechanisms underlying these disorders remain unclear. The aim was to identify the extent of altered gene expression in term placentas from pregnant women with late-onset PE and GDM compared to controls. RNAseq identified few significantly differentially regulated genes in placental biopsies between PE, GDM, or uncomplicated pregnancy (n = 10 each group). Five genes were altered in placentas from PE including 4 non-coding genes and Angiopoietin 2 (ANGPT2). No genes were significantly regulated by GDM. In contrast, many genes were significantly regulated by fetal, maternal and delivery-specific variables, particularly spinal and epidural anesthesia. We selected ANGPT2 and Chemokine (C-X-C motif) ligand 14 (CXCL14) to test with qPCR in a larger set of placentas (n = 475) and found no differences between the groups. However, regression analysis revealed a stronger association between placental ANGPT2 and CXCL14 mRNA expression and fetal, maternal and delivery-specific variables than diagnostic group. To conclude, the gene expression in term placentas are highly affected by fetal, maternal and delivery specific variables. Few regulated genes were found in late-onset PE and GDM placentas, which may suggest that these conditions could be more affected by maternal factors. PMID:27405415

  4. Dutch guideline for the management of hypertensive crisis -- 2010 revision.

    PubMed

    van den Born, B J H; Beutler, J J; Gaillard, C A J M; de Gooijer, A; van den Meiracker, A H; Kroon, A A

    2011-05-01

    Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.

  5. Living kidney donation: outcomes, ethics, and uncertainty.

    PubMed

    Reese, Peter P; Boudville, Neil; Garg, Amit X

    2015-05-16

    Since the first living-donor kidney transplantation in 1954, more than half a million living kidney donations have occurred and research has advanced knowledge about long-term donor outcomes. Donors in developed countries have a similar life expectancy and quality of life as healthy non-donors. Living kidney donation is associated with an increased risk of end-stage renal disease, although this outcome is uncommon (<0·5% increase in incidence at 15 years). Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. Many donors incur financial expenses due to factors such as lost wages, need for sick days, and travel expenses. Yet, most donors have no regrets about donation. Living kidney donation is practised ethically when informed consent incorporates information about risks, uncertainty about outcomes is acknowledged when it exists, and a donor's risks are proportional to benefits for the donor and recipient. Future research should determine whether outcomes are similar for donors from developing countries and donors with pre-existing conditions such as obesity.

  6. Acute liver failure in pregnancy: an overview.

    PubMed

    Jayanthi, V; Udayakumar, N

    2008-03-01

    Acute liver failure (ALF) in pregnancy is a common challenging clinical problem both in terms of correct diagnosis and management. Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute viral hepatitis is unaffected by pregnancy, except in patients with hepatitis E (HEV), particularly from endemic countries like India, where ALF carries a high mortality. In both HEV infection and herpes simplex infections, maternal and fetal mortality rates are significantly increased. ALF specific to pregnancy including pre-eclampsia, associated with hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, acute fatty liver of pregnancy, and hepatic infarction result in increased maternal and fetal mortality if not recognized and acted on early. Early recognition of possible causes and prompt treatment are crucial for successful outcome of ALF in pregnancy. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. This review article addresses the present understanding of ALF in pregnancy reviewing the common causes of ALF and their management in pregnancy. PMID:18299670

  7. The placenta: a multifaceted, transient organ

    PubMed Central

    Burton, Graham J.; Fowden, Abigail L.

    2015-01-01

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

  8. New Horizons in Platelets Flow Cytometry

    PubMed Central

    Saboor, Muhammad; Moinuddin, Moinuddin; Ilyas, Samina

    2013-01-01

    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

  9. Evidence for No Significant Impact of Müllerian Anomalies on Reproductive Outcomes of Twin Pregnancy in Korean Women.

    PubMed

    Shim, Sohyun; Hur, Yoon-Mi; Kim, Da Hee; Seong, Seok Ju; Kim, Mi-La; Shin, Joong Sik

    2016-04-01

    The present article aimed to evaluate the impact of congenital Müllerian anomalies (MA) on twin pregnancy after 24 gestational weeks in Korean women. All records of twin pregnancies in a large maternity hospital in Korea between January 2005 and July 2013 were analyzed. Patients with monochorionic monoamniotic (MCMA) twins, non-Korean patients, patients with twins delivered prior to 24 gestational weeks, and patients with miscarriage of one fetus or intrauterine fetal death (IUFD) before 24 gestational weeks were excluded from data analysis. In total, 1,422 women with twin pregnancy were eligible for data analysis, including 17 (1.2%) who had a known congenital MA (septate uterus, bicornuate uterus, arcuate uterus, and unicornuate uterus). Except for the mode of conception, baseline demographics were similar between women with MA and those without MA. No significant differences were found in pregnancy outcomes of gestational age at delivery (p = .86), birth weight of smaller and larger twins (p = .54 and p = .65), and number of twins with birth weight <5th percentile for gestational age (p = .43).The rates of obstetrical complications such as pre-eclampsia, gestational diabetes mellitus (GDM), placenta previa, cerclage, IUFD, and postpartum hemorrhage were not significantly different between the two groups either. We concluded that the presence of congenital MA may not increase obstetrical risks in outcomes of pregnancy of twins delivered after 24 gestational weeks.

  10. Vitamin D supplementation for women during pregnancy

    PubMed Central

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

    2013-01-01

    Background Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse gestational outcomes. Objectives To examine whether supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011), the International Clinical Trials Registry Platform (ICTRP) (31 October 2011), the Networked Digital Library of Theses and Dissertations (28 October 2011) and also contacted relevant organisations (8 April 2011). Selection criteria Randomised and quasi-randomised trials with randomisation at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy. Data collection and analysis Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy. Main results The search strategy identified 34 potentially eligible references. We included six trials assessing a total of 1023 women, excluded eight studies, and 10 studies are still ongoing. Five trials involving 623 women compared the effects of vitamin D alone versus no supplementation/placebo and one trial with 400 women compared the effects of vitamin D and calcium versus no supplementation. Only one trial with 400 women reported on pre-eclampsia: women who received 1200 IU vitamin D along with 375 mg of elemental calcium per day were as likely to develop pre-eclampsia as women who received no supplementation (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.33 to 1.35). Data from four trials

  11. Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy

    PubMed Central

    Woudstra, Douglas M; Chandra, Sue; Hofmeyr, G Justus; Dowswell, Therese

    2014-01-01

    Background Pre-eclampsia is a relatively common complication of pregnancy. HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a severe manifestation of pre-eclampsia with significant morbidity and mortality for pregnant women and their children. Corticosteroids are commonly used in the treatment of HELLP syndrome in the belief that they improve outcomes. Objectives To determine the effects of corticosteroids on women with HELLP syndrome and their children. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 June 2010). Selection criteria Randomized controlled trials comparing any corticosteroid with placebo, no treatment, or other drug; or comparing one corticosteroid with another corticosteroid or dosage in women with HELLP syndrome. Data collection and analysis Two review authors assessed trial quality and extracted data independently. Main results Eleven trials (550 women) compared corticosteroids with placebo or no treatment. There was no difference in the risk of maternal death (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.28 to 3.21), maternal death or severe maternal morbidity (RR 0.27, 95% CI 0.03 to 2.12), or perinatal/infant death (RR 0.64, 95% CI 0.21 to 1.97). The only clear effect of treatment on individual outcomes was improved platelet count (standardized mean difference (SMD) 0.67, 95% CI 0.24 to 1.10). The effect on platelet count was strongest for women who commenced treatment antenatally (SMD 0.80, 95% CI 0.25 to 1.35). Two trials (76 women) compared dexamethasone with betamethasone. There was no clear evidence of a difference between groups in respect to perinatal/infant death (RR 0.95, 95% CI 0.15 to 6.17) or severe perinatal/infant morbidity or death (RR 0.64, 95% CI 0.27 to 1.48). Maternal death and severe maternal morbidity were not reported. In respect to platelet count, dexamethasone was superior to betamethasone (MD 6.02, 95% CI 1.71 to 10.33), both when treatment was

  12. Animal models of human placentation--a review.

    PubMed

    Carter, A M

    2007-04-01

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

  13. Lack of exercise is a major cause of chronic diseases.

    PubMed

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

    2012-04-01

    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

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

    PubMed Central

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

    2014-01-01

    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

  15. The impact of an educational pamphlet on knowledge and anxiety in women with preeclampsia

    PubMed Central

    Sauvé, Nadine; Powrie, Raymond O; Larson, Lucia; Phipps, Maureen G; Weitzen, Sherry; Fitzpatrick, Donna; Rosene-Montella, Karen

    2008-01-01

    Objective: This study was undertaken to evaluate whether or not an educational pamphlet could improve knowledge without increasing anxiety in women with preeclampsia. Methods: One hundred women recruited from an inpatient setting with suspected or proven preeclampsia were asked to answer a questionnaire assessing demographics, knowledge (primary outcome), anxiety and satisfaction (secondary outcomes) after being randomized to an intervention group (who received a pamphlet) or a control group (who did not received a pamphlet). The pamphlet and questionnaire, both designed by a multidisciplinary team, were read and answered at the same time. Results: Baseline and demographic characteristics were similar between the two groups. Knowledge about the symptoms of pre-eclampsia was excellent in both groups (61% to 100% correct answers). Women in both groups were well aware that preeclampsia in the past (P = 0.22) and a family history of preeclampsia (P = 0.57) were risk factors. There was a significant difference in knowledge about the risk of some fetal complications, including death (90% versus 39%, P < 0.01) and all maternal complications (P < 0.05) favouring the intervention group. Despite increased knowledge about preeclampsia and its risks, anxiety was not greater in the intervention group. Overall, there was a trend towards less knowledge in vulnerable subgroups (non-white, low income and schooling levels), but the improvement of knowledge with the pamphlet was equivalent. Baseline anxiety was higher in the vulnerable groups, but was generally not increased by the pamphlet. Conclusion: An educational pamphlet for women with suspected preeclampsia was able to increase knowledge without increasing anxiety. PMID:27630740

  16. Lack of cardioprotection by single-dose magnesium prophylaxis on isoprenaline-induced myocardial infarction in adult Wistar rats

    PubMed Central

    Garson, Christie; Kelly-Laubscher, Roisin; Gwanyanya, Asfree; Blackhurst, Dee

    2015-01-01

    Summary Aim Magnesium (Mg2+) is effective in treating cardiovascular disorders such as arrhythmias and pre-eclampsia, but its role during myocardial infarction (MI) remains uncertain. In this study, we investigated the effects of Mg2+ pre-treatment on isoprenaline (ISO)-induced MI in vivo. Methods Rats divided into four groups were each pre-treated with either MgSO4 (270 mg/kg intraperitoneally) or an equivalent volume of physiological saline, prior to the ISO (67 mg/kg subcutaneously) or saline treatments. One day post-treatment, the electrocardiogram and left ventricular blood pressures were recorded. Infarcts were determined using 2,3,5-triphenyltetrazolium chloride staining, and serum markers of lipid peroxidation were measured with spectrophotometric assays. Results Mg2+ pre-treatment neither altered the ISO-induced infarct size compared with ISO treatment alone (p > 0.05), nor reversed the low-voltage electrocardiogram or the prominent Q waves induced by ISO, despite a trend to decreased Q waves. Similarly, Mg2+ did not prevent the ISO-induced decrease in peak left ventricular blood pressure or the decrease in minimal rate of pressure change. Mg2+ did not reverse the ISO-induced gain in heart weight or loss of body weight. Neither ISO nor Mg2+ altered the concentrations of lipid peroxidation markers 24 hours post MI induction. Conclusion Although Mg2+ had no detrimental effects on electrical or haemodynamic activity in ISO-induced MI, the lack of infarct prevention may detract from its utility in MI therapy. PMID:26212925

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

    PubMed Central

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

    2007-01-01

    Purpose To examine the association between birthweight in offspring and mortality in their parents. Distinguishing between risks of outcomes in mothers from fathers potentially provides clues as to the relative roles of genetic versus non-genetic mechanisms underlying these associations.. Methods We studied total and cause-specific mortality in a population-based cohort of 37,718 mothers and 38,002 fathers whose offspring were delivered in West Jerusalem during 1964–76, after an average follow-up of 34.12 years Results Hazard models controlling for socio-demographic and lifestyle characteristics indicated a U-shaped relationship between offspring’s birthweight and overall mortality, deaths from CHD, circulatory and other non-neoplastic causes in their mothers. Higher CHD mortality rates were observed among mothers who gave birth to babies with low (HR=2.13; 95%CI 1.40–3.25) and high birthweight (HR=1.98; 95%CI 1.36–2.88), as compared to mothers whose offspring weighed 2500–3999 gr at birth. Adjustment for maternal pre-eclampsia, slightly attenuated these results. Multivariate models indicated a negative linear relationship (HR=0.95, 95%CI 0.91–0.99) between offspring’s birthweight and overall mortality in their fathers. Unlike the association in mothers, the relation was noted primarily with deaths from “other causes”. Conclusions Birthweight of offspring is associated with parental mortality although the relation differs for fathers and mothers. These findings broaden previous observations that intra-uterine events have long-term consequences for adult health and support the need to explore genetic and/or environmental mechanisms underlying these associations. PMID:17855119

  18. Venlafaxine: more dangerous than most "selective" serotonergic antidepressants.

    PubMed

    2016-04-01

    Venlafaxine is a serotonergic and noradrenergic antidepressant. It shares the same serotonergic adverse effects as the "selective" serotonin reuptake inhibitor (SSRI) antidepressants while in addition provoking noradrenergic adverse effects, in particular cardiovascular disorders, yet offers no demonstrated advantages over SSRIs in terms of efficacy. Several cohort studies using data from a UK database have shown that venlafaxine overdoses are more frequently fatal than SSRI overdoses. Several meta-analyses of more than 70 published and unpublished randomised clinical trials, including about 7000 patients in total, have shown that treatment discontinuation due to adverse effects is more common with venlafaxine than with SSRI antidepressants. Venlafaxine can provoke dose-dependent blood pressure elevation, sometimes requiring treatment discontinuation. Exposure to venlafaxine during the second and third trimesters of pregnancy increases the risk of pre-eclampsia and eclampsia. A cohort study in about 50 elderly patients and analysis of several hundred reported suicide attempts by venlafaxine overdose demonstrated a risk of QT interval prolongation, which can lead to torsades de pointes, an unusual and potentially fatal type of ventricular tachycardia. Large British and Danish cohort studies found no increased risk of sudden cardiac death with venlafaxine compared with other antidepressants. However, since only 3.5% and 7% of the patients were using venlafaxine, the statistical power of these studies was relatively low. In practice, the data available as of mid-2015 from clinical trials and epidemiological studies confirm the harms foreseeable from venlafaxine's pharmacological properties: a higher risk of cardiovascular adverse effects and of fatal overdoses than with most SSRI antidepressants. Since venlafaxine and SSRI antidepressants have similar and limited efficacy, venlafaxine is best avoided. An SSRI anti-depressant is a more reasonable option, with the

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

    PubMed Central

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

    2015-01-01

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

  20. Biological mechanisms for nutritional regulation of maternal health and fetal development.

    PubMed

    Wu, Guoyao; Imhoff-Kunsch, Beth; Girard, Amy Webb

    2012-07-01

    This review paper highlights mechanisms for nutritional regulation of maternal health and fetal development. Malnutrition (nutrient deficiencies or obesity) in pregnant women adversely affects their health by causing or exacerbating a plethora of problems, such as anaemia, maternal haemorrhage, insulin resistance, and hypertensive disorders (e.g. pre-eclampsia/eclampsia). Maternal malnutrition during gestation also impairs embryonic and fetal growth and development, resulting in deleterious outcomes, including intrauterine growth restriction (IUGR), low birthweight, preterm birth, and birth defects (e.g. neural tube defects and iodine deficiency disorders). IUGR and preterm birth contribute to high rates of neonatal morbidity and mortality. Major common mechanisms responsible for malnutrition-induced IUGR and preterm birth include: (i) abnormal growth and development of the placenta; (ii) impaired placental transfer of nutrients from mother to fetus; (iii) endocrine disorders; and (iv) disturbances in normal metabolic processes. Activation of a series of physiological responses leading to premature and sustained contraction of the uterine myometrium also results in preterm birth. Recent epidemiologic studies have suggested a link between IUGR and chronic metabolic disease in children and adults, and the effects of IUGR may be carried forward to subsequent generations through epigenetics. While advanced medical therapies, which are generally unavailable in low-income countries, are required to support preterm and IUGR infants, optimal nutrition during pregnancy may help ameliorate many of these problems. Future studies are necessary to develop effective nutritional interventions to enhance fetal growth and development and alleviate the burden of maternal morbidity and mortality in low- and middle-income countries. PMID:22742599

  1. Placental microRNA expression in pregnancies complicated by superimposed pre‑eclampsia on chronic hypertension.

    PubMed

    Vashukova, Elena S; Glotov, Andrey S; Fedotov, Pavel V; Efimova, Olga A; Pakin, Vladimir S; Mozgovaya, Elena V; Pendina, Anna A; Tikhonov, Andrei V; Koltsova, Alla S; Baranov, Vladislav S

    2016-07-01

    Pre-eclampsia (PE) is a complication of pregnancy that affects 5‑8% of women after 20 weeks of gestation. It is usually diagnosed based on the de novo onset of hypertension and proteinuria. Preexisting hypertension in women developing PE, also known as superimposed PE on chronic hypertension (SPE), leads to elevated risk of maternal and fetal mortality. PE is associated with an altered microRNA (miRNA) expression pattern in the placenta, suggesting that miRNA deregulation is involved in the pathogenesis of PE. Whether and how the miRNA expression pattern is changed in the SPE placenta remains unclear. The present study analyzed the placental miRNA expression profile in pregnancies complicated by SPE. miRNA expression profiles in SPE and normal placentas were investigated using an Ion Torrent sequencing system. Sequencing data were processed using a comprehensive analysis pipeline for deep miRNA sequencing (CAP‑miRSeq). A total of 22 miRNAs were identified to be deregulated in placentas from patients with SPE. They included 16 miRNAs previously known to be associated with PE and 6 novel miRNAs. Among the 6 novel miRNAs, 4 were upregulated (miR‑518a, miR‑527, miR‑518e and miR‑4532) and 2 downregulated (miR‑98 and miR‑135b) in SPE placentas compared with controls. The present results suggest that SPE is associated with specific alterations in the placental miRNA expression pattern, which differ from alterations detected in PE placentas, and therefore, provide novel targets for further investigation of the molecular mechanisms underlying SPE pathogenesis. PMID:27176897

  2. Nutrition and maternal, neonatal, and child health.

    PubMed

    Christian, Parul; Mullany, Luke C; Hurley, Kristen M; Katz, Joanne; Black, Robert E

    2015-08-01

    This article reviews the central role of nutrition in advancing the maternal, newborn, and child health agenda with a focus on evidence for effective interventions generated using randomized controlled trials in low- and middle-income countries (LMIC). The 1000 days spanning from conception to 2 years of life are a critical period of time when nutritional needs must be ensured; failure to do so can lead to adverse impacts on short-term survival as well as long-term health and development [corrected]. The burden of maternal mortality continues to be high in many under-resourced settings; prenatal calcium supplementation in populations with low intakes can reduce the risk of pre-eclampsia and eclampsia morbidity and mortality and is recommended, and antenatal iron-folic acid use in many countries may reduce anemia, a condition that may be an underlying factor in postpartum hemorrhage. Sufficient evidence exists to promote multiple micronutrient supplementation during pregnancy to reduce fetal growth restriction and low birth weight. Early initiation of breastfeeding (within an hour), exclusive breastfeeding in the first 6 months of life, and vitamin A supplementation in the first few days of life in Asia (but not in Africa) reduce infant mortality. Biannual large-dose vitamin A supplements to children 6-59 months of age and zinc for treatment of diarrhea continue to be important strategies for improving child health and survival. Early nutrition and micronutrient status can influence child development but should be integrated with early responsive learning interventions. Future research is needed that goes beyond the 1000 days to ensure adequate preconceptional nutrition and health, with special emphasis on adolescents who contribute to a large proportion of first births in many LMIC. Thus, we make the case for integrating proven nutrition interventions with those for health in pregnant women, and with those for health and child development in neonates, infants, and

  3. Study protocol for the randomised controlled trial: combined multimarker screening and randomised patient treatment with ASpirin for evidence-based PREeclampsia prevention (ASPRE)

    PubMed Central

    O'Gorman, Neil; Wright, David; Rolnik, Daniel L; Nicolaides, Kypros H; Poon, Liona C

    2016-01-01

    Introduction Pre-eclampsia (PE) affects 2–3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. Prophylactic use of low-dose aspirin in women at risk for PE may substantially reduce the prevalence of the disease. Effective screening for PE requiring delivery before 37 weeks (preterm PE) can be provided by a combination of maternal factors, uterine artery Doppler, mean arterial pressure, maternal serum pregnancy-associated plasma protein A and placental growth factor at 11–13 weeks' gestation, with a detection rate of 75% at a false-positive rate of 10%. We present a protocol (V.6, date 25 January 2016) for the ASpirin for evidence-based PREeclampsia prevention (ASPRE) trial, which is a double-blinded, placebo-controlled, randomised controlled trial (RCT) that uses an effective PE screening programme to determine whether low-dose aspirin given to women from 11 to 13 weeks' gestation will reduce the incidence of preterm PE. Methods and analysis All eligible women attending for their first trimester scan will be invited to participate in the screening study for preterm PE. Those found to be at high risk of developing preterm PE will be invited to participate in the RCT. Further scans will be conducted for assessment of fetal growth and biomarkers. Pregnancy and neonatal outcomes will be collected and analysed. The first enrolment for the pilot study was in April 2014. As of April 2016, 26 670 women have been screened and 1760 recruited to the RCT. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. Trial registration number ISRCTN13633058. PMID:27354081

  4. Comparison of Normal and Pre-Eclamptic Placental Gene Expression: A Systematic Review with Meta-Analysis

    PubMed Central

    2016-01-01

    Pre-eclampsia (PE) is a serious multi-factorial disorder of human pregnancy. It is associated with changes in the expression of placental genes. Recent transcription profiling of placental genes with microarray analyses have offered better opportunities to define the molecular pathology of this disorder. However, the extent to which placental gene expression changes in PE is not fully understood. We conducted a systematic review of published PE and normal pregnancy (NP) control placental RNA microarrays to describe the similarities and differences between NP and PE placental gene expression, and examined how these differences could contribute to the molecular pathology of the disease. A total of 167 microarray samples were available for meta-analysis. We found the expression pattern of one group of genes was the same in PE and NP. The review also identified a set of genes (PE unique genes) including a subset, that were significantly (p < 0.05) down-regulated in pre-eclamptic placentae only. Using class prediction analysis, we further identified the expression of 88 genes that were highly associated with PE (p < 0.05), 10 of which (LEP, HTRA4, SPAG4, LHB, TREM1, FSTL3, CGB, INHA, PROCR, and LTF) were significant at p < 0.001. Our review also suggested that about 30% of genes currently being investigated as possibly of importance in PE placenta were not consistently and significantly affected in the PE placentae. We recommend further work to confirm the roles of the PE unique and associated genes, currently not being investigated in the molecular pathology of the disease. PMID:27560381

  5. Safety of bronchodilators and corticosteroids for asthma during pregnancy: what we know and what we need to do better.

    PubMed

    Gregersen, Thorbjørn Lomholt; Ulrik, Charlotte Suppli

    2013-01-01

    Asthma is a common medical condition complicating pregnancy with potentially serious effects on pregnancy outcome. The aim of this review is to provide an update on efficacy and safety of asthma medications, primarily bronchodilators and corticosteroids, used during pregnancy with focus on pregnancy outcome, and, furthermore, to discuss limitations of available studies and point to possible improvements in future studies. A planned series of systematic searches was conducted using the PubMed database. Use of short-acting β2-agonists has generally been established as safe, and the few studies stating otherwise appear to have, perhaps critical, methodological limitations. The safety of long-acting β2-agonists remains to be further investigated, and the few available studies have methodological limitations and, therefore, provide no definite answers, although a very recent study supports the safety of add-on long-acting β2-agonists to inhaled corticosteroids. Inhaled corticosteroids are generally found to be safe, although further research is needed to investigate both the efficacy and safety of high dose therapy with inhaled corticosteroids. Studies have reported associations between the use of systemic corticosteroids and adverse perinatal outcomes, such as preterm birth, low birth weight, and pre-eclampsia. This must, however, be weighed against the potential serious impact of severe, uncontrolled asthma itself on pregnancy outcome. The main obstacle to a valid interpretation of several of the available studies is the inadequate stratification for asthma severity and control. Overall, asthma in itself and not just poor asthma control poses a greater risk to pregnancy outcomes than asthma medication. Nonetheless, more studies focusing on disentangling the effects of asthma alone and asthma medications are needed. Increased use of stratified risk assessments, taking the concept of asthma severity into greater consideration, is much warranted in future studies.

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

    PubMed

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

    2009-04-27

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

  7. Tailoring systematic reviews to meet critical priorities in maternal health in the intrapartum period.

    PubMed

    Viswanathan, Meera

    2008-01-01

    Health care practitioners and researchers commonly call for greater reliance on evidence as a means to achieve improvement in quality of care. Systematic reviews provide a means to accelerate the use of evidence-based clinical interventions and public health practices. The extent to which these time- and resource-intensive systematic reviews currently address critical maternal health priorities in the intrapartum period is unclear. This analysis summarises key maternal health and research priorities, maps these priorities to existing reviews, identifies gaps in the literature that can be addressed with systematic reviews, and highlights key methodological concerns in conducting systematic reviews. The analysis draws on published data on maternal morbidities and an overview of 108 systematic reviews in Medline in the past 5 years using the MeSH terms 'Delivery, Obstetric,' to draw the links between health priorities, research priorities, existing evidence and missing evidence. Key causes of morbidity during labour and delivery in the United States include haemorrhage, pre-eclampsia and eclampsia, obstetric trauma and infection. Analyses of maternal morbidity and mortality suggest that key concerns include racial and ethnic disparities in health outcomes and the prevention of adverse events. Systematic reviews, however, generally tend to focus on the reduction of harms associated with interventions, are frequently limited to randomised designs, and do not address issues of health disparities. The results suggest that advances in evidence-based care in maternal health require that systematic reviews address issues of prevention of adverse events, include a larger variety of study designs when necessary and pay closer attention to health disparities.

  8. Biology of insulin-like factor 3 in human reproduction.

    PubMed

    Ivell, Richard; Anand-Ivell, Ravinder

    2009-01-01

    BACKGROUND Insulin-like factor 3 (INSL3) is a neohormone that has evolved to address specific mammalian traits, in particular, the first phase of testicular descent towards the scrotum during mid-gestation. METHODS A thorough literature search was made in PubMed using the terms INSL3, as well as the older synonyms RLF and Ley-IL. RESULTS INSL3 is a major secretory product of the testicular Leydig cells in the fetus and in adult men, and in rodent models, reduction in fetal INSL3 expression is an early marker of the testicular dysgenesis syndrome. In women, it is produced in lower amounts by ovarian theca and luteal cells, and circulating levels are increased in women with polycystic ovarian syndrome. During pregnancy, there is evidence for an interaction regulating the feto-placental unit. The presence of INSL3 in amniocentesis samples taken at 12-14 weeks gestation is absolutely specific for male gender, and levels are predictive of subsequent pre-eclampsia and/or birthweight. INSL3 is also involved in adult traits, such as spermatogenesis and bone metabolism. In adult men, INSL3 is constitutively expressed and secreted into the bloodstream at a constant level, reflecting the number and/or functional capacity of the Leydig cells. In complete contrast, testosterone is highly variable within individuals, is acutely responsive to fluctuations in the hypothalamic-pituitary-gonadal axis and appears to have marginal diagnostic value. INSL3 declines consistently with age in adult men. CONCLUSIONS INSL3 promises to become an important new diagnostic tool to characterize those men with late-onset hypogonadism and to add clinical diagnostic value at amniocentesis.

  9. The GPR54-Kisspeptin complex in reproductive biology: neuroendocrine significance and implications for ovulation induction and contraception.

    PubMed

    Sills, Eric Scott; Walsh, Anthony P H

    2008-12-01

    KISS1 encodes the kisspeptin (KP) family of peptides which were originally characterised as potent antimetastatic agents in breast cancer and malignant melanoma cells. One member of this family of arginine-phenylalanine amide peptides, KP-54, was subsequently identified as the natural ligand for the G-protein coupled receptor-54 (GPR54). In addition to its importance as a metastatic suppressor, KP has been found to play a major neuroregulatory role in governing endogenous gonadotropin release by its modulation of the hypothalamic-pituitary-gonadal (HPG) axis. In humans, KISS1 mRNA has been localised to the hypothalamic anteroventral periventricular nucleus and arcuate nucleus. Although GPR54 is expressed in human pituitary cells, it is not presently known if gonadotrope cells themselves are targets for significant KP activity. It was recently shown that full disruption of the KP/GPR54 complex resulted in hypogonadotropic hypogonadism. Indeed, evidence now suggests that KP/GPR54 signalling during gestation is necessary for sexual differentiation and implicates activation of the KP/GPR54 complex as the single most important upstream event regulating GnRH release. Several compelling studies have placed KP as the leading candidate molecule responsible for initiating puberty, making this receptor-ligand complex of fundamental importance to the neuroendocrinology of reproduction. Here, we discuss key KP/GPR54 discovery events and present an evolution of KP biology in the context of recent animal and human experimental work. With evidence pointing to proper KP/GPR54 signalling as the principal trigger for activation of GnRH neurons and subsequent ovulation, elucidation of how this pathway is modulated is likely to bring novel pharmacologic strategies for fertility treatment (and contraception) within reach. Because the physiological significance KP is now acknowledged to extend well beyond cancer biology (and may also contribute to the pathophysiology of pre-eclampsia

  10. [How to manage a patient with chronic arterial hypertension during pregnancy and the postpartum period].

    PubMed

    Pourrat, O

    2015-03-01

    The management of chronic arterial hypertension during pregnancy and postpartum requires first to estimate the risk of the pregnancy, linked with the severity of hypertension, with cardiac and renal involvement, with its cause as well as with the background (obesity, diabetes, possible history of placental vascular pathology). On a very practical approach, antihypertensive drug has to be started or increased if systolic pressure reaches or exceeds 160 mmHg or if diastolic pressure reaches or exceeds 105 mmHg. Below this level, there are no evidence-based medicine data, but it seems reasonable to treat if pressure increases over 150/100 mmHg (140/90 mmHg in case of ambulatory monitoring). Excessive pressure figures control must be avoided as much as insufficient ones: in practice, it is necessary to decrease the treatment dose if figures are below 130/80 mmHg. Three antihypertensive drugs are consensually recommended today: alphametyldopa, calcium-channel blockers and labetalol. Monotherapy is most often sufficient; if needed, two of these drugs can easily be associated, and even three if necessary. Converting enzyme inhibitors and angiotensin receptor II antagonists should not be prescribed to pregnant women. Betablockers and diuretics are not recommended. Whatever is the antihypertensive drug used, it is necessary to detect the signs of bad placenta blood circulation with uterine Doppler ultrasound and regular controls of fetal growth, and to check for appearance of proteinuria, defining then over-imposed pre-eclampsia needing immediate admission to the maternity. After delivery, lacatation suppresion with bromocriptin should not be prescribed.

  11. Isolation and purification of human placental plasma membranes from normal and pre-eclamptic pregnancies. a comparative study.

    PubMed

    Jimenez, V; Henriquez, M; Llanos, P; Riquelme, G

    2004-05-01

    Human placental syncytiotrophoblast is the main barrier for materno-fetal exchange. Analysis of transplacental transport involves the study of ion channels in both the maternal-facing microvillous membrane (MVM) and the fetal-facing basal membrane (BM). Difficulties in having access to intact placenta with conventional electrophysiological methods favour alternative methodologies, such as isolation and reconstitution of membranes in artificial lipid systems. Pre-eclampsia is a major health problem of human pregnancy. The search for altered physiological processes in pre-eclamptic placentae requires the investigation of events at both the microvillous and basal surfaces. The aim of this study was to obtain reliable syncytiotrophoblast plasma membranes from human normal (N) and pre-eclamptic (PE) pregnancies. We describe a protocol which allows for the simultaneous isolation of MVM and BM. The purity of the membranes isolated was evaluated using enzymatic assays, binding studies, Western blotting and immunohistochemistry. Enrichment of alkaline phosphatase activity for MVM was 17 to 21-fold, with 13-16 per cent protein recovery, for both N and PE. Enrichment of adenylate cyclase activity for BM was 9-fold for N, and enrichment of dihydroalprenolol binding to beta-adrenergic receptors was 12-fold for N and 6-fold for PE, with 14 per cent protein recovery for both N and PE. Cross contamination was low and mitochondrial membrane contamination was negligible. We conclude that MVM and BM isolated from placentae of pre-eclamptic women are similar in enrichment and purity to those of healthy women, thus allowing their use in comparative electrophysiological studies.

  12. The Return of Congenital Rickets, Are We Missing Occult Cases?

    PubMed

    Elidrissy, Abdelwahab T H

    2016-09-01

    Congenital rickets is the term given to fetus born with clinical features of rickets, but those born with biochemical evidence of rickets without obvious clinical features still can be considered occult congenital rickets. Some of the affected babies with this disease have the intrauterine rachitic environment, but a calcium trans-placental pump prevents the fetus from having clinical features of rickets. They may present with hypocalcemia few days after birth or later with more florid features of rickets. Congenital rickets cases born with florid features reported over the last 40 years are few and can be divided into two groups. The first due to severe maternal osteomalacia in which their bones were so decalcified to have enough calcium to be pumped to their fetus. Another group in which newborn babies were hypocalcemic due to other maternal diseases as malabsorption, celiac disease, pre-eclampsia, and prematurity. All inherited rickets cases per se, or as part of other syndromes can be considered congenital rickets. Most cases seen in our region are due to maternal vitamin D deficiency with symptoms becoming obvious when the infants are breastfed, or may present with hypocalcemic convulsions or craniotabes. This is a review of congenital rickets with the aim of shedding light on this potentially acute disease that needs more attention and awareness in the neonatal period to avoid rare serious complications as cardiomyopathy or myelofibrosis and the complications of hypocalcemic convulsions. Congenital rickets cases seen simulate a tip of an ice-burg and its prevention is an important issue, especially with the tremendous urbanization with tall buildings living in sun-deprived flats as the commonest type of residence leading to the increasing incidence of maternal osteomalacia and rickets. PMID:27245342

  13. Maternal death after oocyte donation at high maternal age: case report

    PubMed Central

    Schutte, Joke M; Schuitemaker, Nico WE; Steegers, Eric AP; van Roosmalen, Jos

    2008-01-01

    Background The percentage of women giving birth after the age of 35 increased in many western countries. The number of women remaining childless also increased, mostly due to aging oocytes. The method of oocyte donation offers the possibility for infertile older women to become pregnant. Gestation after oocyte-donation-IVF, however, is not without risks for the mother, especially at advanced age. Case presentation An infertile woman went abroad for oocyte-donation-IVF, since this treatment is not offered in The Netherlands after the age of 45. The first oocyte donation treatment resulted in multiple gestation, but was ended by induced abortion: the woman could not cope with the idea of being pregnant with twins. During the second pregnancy after oocyte donation, at the age of 50, she was mentally more stable. The pregnancy, again a multiple gestation, was uneventful until delivery. Immediately after delivery the woman had hypertension with nausea and vomiting. A few hours later she had an eclamptic fit. HELLP-syndrome was diagnosed. She died due to cerebral haemorrhage. Conclusion In The Netherlands, the age limit for women receiving donor oocytes is 45 years and commercial oocyte donation is forbidden by law. In other countries there is no age limit, the reason why some women are going abroad to receive the treatment of their choice. Advanced age, IVF and twin pregnancy are all risk factors for pre-eclampsia, the leading cause of maternal death in The Netherlands. Patient autonomy is an important ethical principle, but doctors are also bound to the principle of 'not doing harm', and do have the right to refuse medical treatment such as IVF-treatment. The discussion whether women above 50 should have children is still not closed. If the decision is made to offer this treatment to a woman at advanced age, the doctor should counsel her intensively about the risks before treatment is started. PMID:19116003

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

    PubMed

    Dreyfus, R

    1992-01-01

    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)

  15. Risk of preterm delivery and hypertensive disorders of pregnancy in relation to maternal co-morbid mood and migraine disorders during pregnancy.

    PubMed

    Cripe, Swee May; Frederick, Ihunnaya O; Qiu, Chunfang; Williams, Michelle A

    2011-03-01

    We evaluated the risks of preterm delivery and hypertensive disorders of pregnancy among pregnant women with mood and migraine disorders, using a cohort study of 3432 pregnant women. Maternal pre-pregnancy or early pregnancy (<20 weeks gestation) mood disorder and pre-pregnancy migraine diagnoses were ascertained from interview and medical record review. We fitted generalised linear models to derive risk ratios (RR) and 95% confidence intervals (CI) of preterm delivery and hypertensive disorders of pregnancy for women with isolated mood, isolated migraine and co-morbid mood-migraine disorders, respectively. Reported RR were adjusted for maternal age, race/ethnicity, marital status, parity, smoking status, chronic hypertension or pre-existing diabetes mellitus, and pre-pregnancy body mass index. Women without mood or migraine disorders were defined as the reference group. The risks for preterm delivery and hypertensive disorders of pregnancy were more consistently elevated among women with co-morbid mood-migraine disorders than among women with isolated mood or migraine disorder. Women with co-morbid disorders were almost twice as likely to deliver preterm (adjusted RR=1.87, 95% CI 1.05, 3.34) compared with the reference group. There was no clear evidence of increased risks of preterm delivery and its subtypes with isolated migraine disorder. Women with mood disorder had elevated risks of pre-eclampsia (adjusted RR=3.57, 95% CI 1.83, 6.99). Our results suggest an association between isolated migraine disorder and pregnancy-induced hypertension (adjusted RR=1.42, 95% CI 1.00, 2.01). This is the first study examining perinatal outcomes in women with co-morbid mood-migraine disorders. Pregnant women with a history of migraine may benefit from screening for depression during prenatal care and vigilant monitoring, especially for women with co-morbid mood and migraine disorders.

  16. The consequences of obesity and excess weight gain in pregnancy.

    PubMed

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

    2011-11-01

    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.

  17. Inter-Pregnancy Weight Change and the Risk of Recurrent Pregnancy Complications.

    PubMed

    Wallace, Jacqueline M; Bhattacharya, Sohinee; Campbell, Doris M; Horgan, Graham W

    2016-01-01

    Women with specific adverse pregnancy outcomes in their first pregnancy may be receptive to inter-pregnancy weight management guidance aimed at preventing these complications reoccurring in subsequent pregnancies. Thus the association between inter-pregnancy weight change and the risk of recurrent pregnancy complications at the second pregnancy was investigated in a retrospective cohort study of 24,520 women with their first-ever and second consecutive deliveries in Aberdeen using logistic regression. Compared with women who were weight stable, weight loss (>2BMI units) between pregnancies was associated with an increased risk of recurrent small for gestational age (SGA) birth and elective Cesarean-section, and was protective against recurrent pre-eclampsia, placental oversize and large for gestational age (LGA) birth. Conversely weight gain (>2BMI units) between pregnancies increased the risk of recurrent gestational hypertension, placental oversize and LGA birth and was protective against recurrent low placental weight and SGA birth. The relationships between weight gain, and placental and birth weight extremes were evident only in women with a healthy weight at first pregnancy (BMI<25units), while that between weight gain and the increased risk of recurrent gestational hypertension was largely independent of first pregnancy BMI. No relationship was detected between inter-pregnancy weight change and the risk of recurrent spontaneous preterm delivery, labour induction, instrumental delivery, emergency Cesarean-section or postpartum hemorrhage. Therefor inter-pregnancy weight change impacts the risk of recurrent hypertensive disorders, SGA and LGA birth and women with a prior history of these specific conditions may benefit from targeted nutritional advice to either lose or gain weight after their first pregnancy. PMID:27145132

  18. Nutrition and maternal, neonatal, and child health.

    PubMed

    Christian, Parul; Mullany, Luke C; Hurley, Kristen M; Katz, Joanne; Black, Robert E

    2015-08-01

    This article reviews the central role of nutrition in advancing the maternal, newborn, and child health agenda with a focus on evidence for effective interventions generated using randomized controlled trials in low- and middle-income countries (LMIC). The 1000 days spanning from conception to 2 years of life are a critical period of time when nutritional needs must be ensured; failure to do so can lead to adverse impacts on short-term survival as well as long-term health and development [corrected]. The burden of maternal mortality continues to be high in many under-resourced settings; prenatal calcium supplementation in populations with low intakes can reduce the risk of pre-eclampsia and eclampsia morbidity and mortality and is recommended, and antenatal iron-folic acid use in many countries may reduce anemia, a condition that may be an underlying factor in postpartum hemorrhage. Sufficient evidence exists to promote multiple micronutrient supplementation during pregnancy to reduce fetal growth restriction and low birth weight. Early initiation of breastfeeding (within an hour), exclusive breastfeeding in the first 6 months of life, and vitamin A supplementation in the first few days of life in Asia (but not in Africa) reduce infant mortality. Biannual large-dose vitamin A supplements to children 6-59 months of age and zinc for treatment of diarrhea continue to be important strategies for improving child health and survival. Early nutrition and micronutrient status can influence child development but should be integrated with early responsive learning interventions. Future research is needed that goes beyond the 1000 days to ensure adequate preconceptional nutrition and health, with special emphasis on adolescents who contribute to a large proportion of first births in many LMIC. Thus, we make the case for integrating proven nutrition interventions with those for health in pregnant women, and with those for health and child development in neonates, infants, and

  19. Pregnancy outcomes in myeloproliferative neoplasms: UK prospective cohort study.

    PubMed

    Alimam, Samah; Bewley, Susan; Chappell, Lucy C; Knight, Marian; Seed, Paul; Gray, Gabriella; Harrison, Claire; Robinson, Susan

    2016-10-01

    The reported higher risk of maternal and fetal complications in women with myeloproliferative neoplasms (MPN) poses challenge during pregnancy. A national prospective study of maternal and fetal outcomes of pregnant women with a diagnosis of MPN was undertaken via the United Kingdom Obstetric Surveillance System between January 2010 and December 2012. Fifty-eight women with a diagnosis of MPN were identified; 47 (81%) essential thrombocythaemia, five (9%) polycythaemia vera, five (9%) myelofibrosis and one (2%) MPN-unclassified. There were 58 live births. The incidence of miscarriage was 1·7/100 (95% confidence interval [CI]: 0·04-9·24) and the perinatal mortality rate was 17/1000 (95% CI: 0·44-92·36) live and stillbirths. Incidence of maternal complications was 9% (5/57) pre-eclampsia, 9% (5/57) post-partum haemorrhage and 3·5% (2/57) post-partum haematoma. There were no maternal deaths or thrombotic events. Delivery was induced in 45% (24/53) of women and the Caesarean section rate was 45% (24/53). The majority (85%, 45/53) delivered at term (>37 weeks gestation). Twenty-two percent (12/54) of neonates were below the 10% centile for growth and 13% (7/54) required admission to a neonatal care-unit; there were no neonatal deaths. The findings of this large, UK prospective study suggests women with MPN appear to have successful pregnancies with better outcomes than would be anticipated from the literature.

  20. A polymorphism in an autophagy-related gene, ATG16L1, influences time to delivery in women with an unfavorable cervix who require labor induction.

    PubMed

    Doulaveris, Georgios; Orfanelli, Theofano; Benn, Kiesha; Zervoudakis, Ioannis; Skupski, Daniel; Witkin, Steven S

    2013-07-01

    Autophagy is an intracellular process that maintains homeostasis by the removal of damaged organelles and proteins. A single nucleotide polymorphism (SNP) in the autophagy-related 16-like 1 (ATG16L1) gene results in decreased autophagy. We evaluated whether the ATG16L1 polymorphism influenced the time to delivery during labor induction in pregnant women with an unfavorable cervix. DNA from 69 women with an unfavorable cervix who required labor induction due to post-term (>294 days) (n=26), oligohydramnios (n=17), hypertension or pre-eclampsia (n=10), abnormal fetal heart rate (n=8), diabetes (n=3) or other reasons (n=5) was tested by gene amplification and endonuclease digestion for a SNP in ATG16L1 (rs2241880). The mean hours (SD) from induction to delivery was 20.8 (9.7) for women who were A,A homozygotes, 19.2 (8.8) for A,G heterozygotes and 14.3 (6.6) for homozygote carriers of the G,G variant (P=0.03 A,A vs. G,G, P=0.04 A,A/A,G vs. G,G). The G,G prevalence was 24.4% and 4.2% for those who delivered in ≤24 and >24 h, respectively (P=0.04). There was no difference in genotype distribution by indication for induction. A decreased genetic capacity for autophagy may be beneficial in women with an unfavorable cervix whose labor has to be induced. PMID:23633462

  1. Inter-Pregnancy Weight Change and the Risk of Recurrent Pregnancy Complications

    PubMed Central

    Wallace, Jacqueline M.; Bhattacharya, Sohinee; Campbell, Doris M.; Horgan, Graham W.

    2016-01-01

    Women with specific adverse pregnancy outcomes in their first pregnancy may be receptive to inter-pregnancy weight management guidance aimed at preventing these complications reoccurring in subsequent pregnancies. Thus the association between inter-pregnancy weight change and the risk of recurrent pregnancy complications at the second pregnancy was investigated in a retrospective cohort study of 24,520 women with their first-ever and second consecutive deliveries in Aberdeen using logistic regression. Compared with women who were weight stable, weight loss (>2BMI units) between pregnancies was associated with an increased risk of recurrent small for gestational age (SGA) birth and elective Cesarean-section, and was protective against recurrent pre-eclampsia, placental oversize and large for gestational age (LGA) birth. Conversely weight gain (>2BMI units) between pregnancies increased the risk of recurrent gestational hypertension, placental oversize and LGA birth and was protective against recurrent low placental weight and SGA birth. The relationships between weight gain, and placental and birth weight extremes were evident only in women with a healthy weight at first pregnancy (BMI<25units), while that between weight gain and the increased risk of recurrent gestational hypertension was largely independent of first pregnancy BMI. No relationship was detected between inter-pregnancy weight change and the risk of recurrent spontaneous preterm delivery, labour induction, instrumental delivery, emergency Cesarean-section or postpartum hemorrhage. Therefor inter-pregnancy weight change impacts the risk of recurrent hypertensive disorders, SGA and LGA birth and women with a prior history of these specific conditions may benefit from targeted nutritional advice to either lose or gain weight after their first pregnancy. PMID:27145132

  2. Comparison of Normal and Pre-Eclamptic Placental Gene Expression: A Systematic Review with Meta-Analysis.

    PubMed

    Brew, O; Sullivan, M H F; Woodman, A

    2016-01-01

    Pre-eclampsia (PE) is a serious multi-factorial disorder of human pregnancy. It is associated with changes in the expression of placental genes. Recent transcription profiling of placental genes with microarray analyses have offered better opportunities to define the molecular pathology of this disorder. However, the extent to which placental gene expression changes in PE is not fully understood. We conducted a systematic review of published PE and normal pregnancy (NP) control placental RNA microarrays to describe the similarities and differences between NP and PE placental gene expression, and examined how these differences could contribute to the molecular pathology of the disease. A total of 167 microarray samples were available for meta-analysis. We found the expression pattern of one group of genes was the same in PE and NP. The review also identified a set of genes (PE unique genes) including a subset, that were significantly (p < 0.05) down-regulated in pre-eclamptic placentae only. Using class prediction analysis, we further identified the expression of 88 genes that were highly associated with PE (p < 0.05), 10 of which (LEP, HTRA4, SPAG4, LHB, TREM1, FSTL3, CGB, INHA, PROCR, and LTF) were significant at p < 0.001. Our review also suggested that about 30% of genes currently being investigated as possibly of importance in PE placenta were not consistently and significantly affected in the PE placentae. We recommend further work to confirm the roles of the PE unique and associated genes, currently not being investigated in the molecular pathology of the disease. PMID:27560381

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

    PubMed

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

    2014-01-01

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

  4. Pregnancy-associated retinal diseases and their management.

    PubMed

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

    2013-01-01

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

  5. Autoimmune disease and pregnancy.

    PubMed

    Jones, W R

    1994-06-01

    Autoimmune diseases are relatively common in women, and tend to occur in the childbearing years. These disorders fall broadly into two groups: (i) Multisystem diseases such as systemic lupus erythematosus (SLE) and related connective tissue disorders (CTD). This group includes the 'pre-clinical' antiphospholipid or lupus obstetric syndrome which may first manifest itself as a pregnancy disorder causing recurrent abortion, fetal death, fetal growth retardation and early onset severe pre-eclampsia. (ii) Tissue- or organ-specific disorders such as autoimmune thrombocytopaenic purpura (ATP), autoimmune thyroid disease (Graves' disease, Hashimoto's autoimmune thyroiditis, and post-postum thyroiditis), autoimmune haemolytic anaemia, and the very rare myasthenia gravis. The study of autoimmune diseases against the background of pregnancy as an experimental system of nature has provided important insights into the nature of the disease processes and the relevance or otherwise of circulating autoantibodies to pathological effects. Thus, for example, if neonatal manifestations of adult disease are causally related to the transfer of autoantibodies across the placenta, they will disappear over a time course consistent with the catabolism of IgG, providing no permanent damage is produced. Conversely, if autoantibodies are demonstrable in the neonate, in the absence of clinical effects, they may only be an epiphenomenon of the maternal disease. In addition, on occasions, disease manifestations may be seen in the baby when the mother shows none. This may occur when the mother is in remission, but still has circulating antibodies, or when she has an occult form of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. The Return of Congenital Rickets, Are We Missing Occult Cases?

    PubMed

    Elidrissy, Abdelwahab T H

    2016-09-01

    Congenital rickets is the term given to fetus born with clinical features of rickets, but those born with biochemical evidence of rickets without obvious clinical features still can be considered occult congenital rickets. Some of the affected babies with this disease have the intrauterine rachitic environment, but a calcium trans-placental pump prevents the fetus from having clinical features of rickets. They may present with hypocalcemia few days after birth or later with more florid features of rickets. Congenital rickets cases born with florid features reported over the last 40 years are few and can be divided into two groups. The first due to severe maternal osteomalacia in which their bones were so decalcified to have enough calcium to be pumped to their fetus. Another group in which newborn babies were hypocalcemic due to other maternal diseases as malabsorption, celiac disease, pre-eclampsia, and prematurity. All inherited rickets cases per se, or as part of other syndromes can be considered congenital rickets. Most cases seen in our region are due to maternal vitamin D deficiency with symptoms becoming obvious when the infants are breastfed, or may present with hypocalcemic convulsions or craniotabes. This is a review of congenital rickets with the aim of shedding light on this potentially acute disease that needs more attention and awareness in the neonatal period to avoid rare serious complications as cardiomyopathy or myelofibrosis and the complications of hypocalcemic convulsions. Congenital rickets cases seen simulate a tip of an ice-burg and its prevention is an important issue, especially with the tremendous urbanization with tall buildings living in sun-deprived flats as the commonest type of residence leading to the increasing incidence of maternal osteomalacia and rickets.

  7. Safety of Tdap vaccine in pregnant women: an observational study

    PubMed Central

    Petousis-Harris, Helen; Walls, Tony; Watson, Donna; Paynter, Janine; Graham, Patricia; Turner, Nikki

    2016-01-01

    Objectives Actively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination. Design and settings A prospective observational study conducted in 2 New Zealand regions. Participants Women in their 28th–38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Tdap administration. Telephone interviews were conducted at 48 h and 4 weeks postvaccination. Main outcomes measures Outcomes were injection site reactions, systemic symptoms and serious adverse events (SAEs). Where available, data have been classified and reported according to Brighton Collaboration definitions. Results 793 women participated with 27.9% receiving trivalent inactivated influenza vaccine concomitantly. 79% of participants reported mild or moderate pain and 2.6% severe pain. Any swelling was reported by 7.6%, induration by 12.0% (collected from 1 site only, n=326), and erythema by 5.8% of participants. Fever was reported by 17 (2.1%) participants, 14 of these occurred within 24 h. Headache, dizziness, nausea, myalgia or arthralgia was reported by <4% of participants, respectively, and fatigue by 8.4%. During the study period, there were 115 adverse events in 113 participants, most of which were minor. At the end of the reporting period, 31 events were classified as serious (eg, obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia). All had variable onset time from vaccination. There were two perinatal deaths. Clinician assessment of all SAEs found none likely to be vaccine related. Conclusions Vaccination with Tdap in pregnant women was well tolerated with no SAE likely to be caused by the vaccine. Trial registration number ACTRN12613001045707. PMID:27091823

  8. Oxfordshire Women and Their Children's Health (OxWATCH): protocol for a prospective cohort feasibility study

    PubMed Central

    Harrison, S; Petrovic, G; Chevassut, A; Brook, L; Higgins, N; Kenworthy, Y; Selwood, M; Snelgar, T; Arnold, L; Boardman, H; Heneghan, C; Leeson, P; Redman, C; Granne, I

    2015-01-01

    Introduction Some specific pregnancy disorders are known to be associated with increased incidence of long-term maternal ill health (eg, gestational diabetes with late onset type 2 diabetes; pre-eclampsia with arterial disease). To what degree these later health conditions are a consequence of the woman's constitution prior to pregnancy rather than pregnancy itself triggering changes in a woman's health is unknown. Additionally, there is little prospective evidence for the impact of pre-pregnancy risk factors on the outcome of pregnancy. To understand the importance of pre-pregnancy health requires the recruitment of women into a long-term cohort study before their first successful pregnancy. The aim of this feasibility study is to test recruitment procedures and acceptability of participation to inform the planning of a future large-scale cohort study. Methods The prospective cohort feasibility study will recruit nulliparous women aged 18–40 years. Women will be asked to complete a questionnaire to assess the acceptability of our recruitment and data collection procedures. Baseline biophysical, genetic, socioeconomic, behavioural and psychological assessments will be conducted and samples of blood, urine, saliva and DNA will be collected. Recruitment feasibility and retention rates will be assessed. Women who become pregnant will be recalled for pregnancy and postpregnancy assessments. Ethics and dissemination The study protocol was approved by South Central Portsmouth REC (Ref: 12/SC/0492). The findings from the study will be disseminated through peer reviewed journals, national and international conference presentations and public events. Trial registration number http://www.clinicaltrials.gov; NCT02419898. PMID:26553837

  9. Transcriptional regulation of human thromboxane synthase gene expression

    SciTech Connect

    Lee, K.D.; Baek, S.J.; Fleischer, T

    1994-09-01

    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.

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

    PubMed

    Fischer, Claudia; Voss, Andreas

    2014-01-01

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

  11. Underestimating risk in women delays diagnosis of CVD.

    PubMed

    Keteepe-Arachi, Tracey; Sharma, Sanjay

    2016-03-01

    CVD remains the most common cause of mortality in women. In 2007, the annual mortality in women secondary to CAD was 4.7 times that of breast cancer. Around 2.8 million women are living with CVD in the UK. There has been an increase in the prevalence of MI in women aged 35 to 54, while a decline in prevalence was observed in age-matched men. Difficulty in evaluating symptoms of ischaemic heart disease in women is well documented and remains challenging because of their atypical nature. The main gender difference is that women tend to present less frequently with exertional symptoms of chest pain before an AMI. Although men and women share classic cardiovascular risk factors the relative importance of each risk factor may be gender specific. The impact of smoking is greater in women than men, especially in those under 50. Diabetes is a more potent risk factor for fatal CHD in women than men. Risk factors specific to women include postmenopausal status, hysterectomy and complications during pregnancy. Women who develop gestational diabetes mellitus or pre-eclampsia more than double their risk of CVD later in life. Transition to the menopause is associated with a worsening CHD risk profile. After the menopause women may experience an increase in weight, alteration in fat distribution and an increase in other CVD risk factors such as diabetes and a more adverse lipid profile. Pharmacological stress testing is preferred for diagnosing CAD in females with lower exercise capacity. Stress cardiomyopathy is triggered by intense, unexpected emotional or physical stress and is characterised by transient apical systolic dysfunction or ballooning of the left ventricle. The syndrome predominantly affects postmenopausal women. Women presenting with STEMI have worse outcomes compared with men. However, in those presenting with NSTEMI there were no differences in outcomes. PMID:27214974

  12. Therapeutics and anaesthesia.

    PubMed

    Magee, Laura A; Lowe, S; Douglas, M J; Kathirgamanathan, A

    2011-08-01

    Many aspects of hypertension care outside pregnancy may be applied in pregnancy, but little information is available on which to base decision-making. It would seem reasonable to continue previous dietary salt restriction and physical activity in women with pre-existing (and controlled) hypertension, encourage a heart-healthy diet in all women with a hypertension disorder of pregnancy, and take patient preference into account when deciding on place of care. Although bed rest has become a key part of obstetric practice and for care of women with a hypertension disorder of pregnancy, in particular, the evidence is lacking to support this practice. This may also increase thromboembolic risk. Antihypertensive treatment is strongly advised for women with severe hypertension. The most common agents are parenteral labetalol, hydralazine, or oral nifedipine capsules. Clinicians should familiarise themselves with multiple agents. Until the role of antihypertensive treatment for non-severe hypertension in pregnancy is clarified by ongoing research, clinicians should explicitly state an individual patient's blood pressure goal, which could reasonably be anywhere between 130/80 and 155/105 mmHg. Labetalol and methyldopa are used most commonly. Breastfeeding should be encouraged. Many risk factors for hypertension (e.g. obesity), as well as hospitalisation and pre-eclampsia, all increase the thromboembolic risk for pregnant women, and care providers should consider thromboprophylaxis in the appropriate setting. Finally, anaesthetists play a critical role in the management of women with a hypertension disorder of pregnancy, and should be involved earlier rather than later in the course of their care.

  13. Pregnancy outcomes in myeloproliferative neoplasms: UK prospective cohort study.

    PubMed

    Alimam, Samah; Bewley, Susan; Chappell, Lucy C; Knight, Marian; Seed, Paul; Gray, Gabriella; Harrison, Claire; Robinson, Susan

    2016-10-01

    The reported higher risk of maternal and fetal complications in women with myeloproliferative neoplasms (MPN) poses challenge during pregnancy. A national prospective study of maternal and fetal outcomes of pregnant women with a diagnosis of MPN was undertaken via the United Kingdom Obstetric Surveillance System between January 2010 and December 2012. Fifty-eight women with a diagnosis of MPN were identified; 47 (81%) essential thrombocythaemia, five (9%) polycythaemia vera, five (9%) myelofibrosis and one (2%) MPN-unclassified. There were 58 live births. The incidence of miscarriage was 1·7/100 (95% confidence interval [CI]: 0·04-9·24) and the perinatal mortality rate was 17/1000 (95% CI: 0·44-92·36) live and stillbirths. Incidence of maternal complications was 9% (5/57) pre-eclampsia, 9% (5/57) post-partum haemorrhage and 3·5% (2/57) post-partum haematoma. There were no maternal deaths or thrombotic events. Delivery was induced in 45% (24/53) of women and the Caesarean section rate was 45% (24/53). The majority (85%, 45/53) delivered at term (>37 weeks gestation). Twenty-two percent (12/54) of neonates were below the 10% centile for growth and 13% (7/54) required admission to a neonatal care-unit; there were no neonatal deaths. The findings of this large, UK prospective study suggests women with MPN appear to have successful pregnancies with better outcomes than would be anticipated from the literature. PMID:27612319

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

    PubMed Central

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

    2015-01-01

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

  15. Alterations in Polyadenylation and Its Implications for Endocrine Disease

    PubMed Central

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

    2013-01-01

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

  16. CYP3A variation and the evolution of salt-sensitivity variants.

    PubMed

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

    2004-12-01

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

  17. Lack of exercise is a major cause of chronic diseases.

    PubMed

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

    2012-04-01

    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.

  18. Hypertension, Snoring, and Obstructive Sleep Apnea During Pregnancy: A Cohort Study

    PubMed Central

    O’Brien, Louise M.; Bullough, Alexandra S.; Chames, Mark C.; Shelgikar, Anita V.; Armitage, Roseanne; Guilleminualt, Christian; Sullivan, Colin E.; Johnson, Timothy R. B.; Chervin, Ronald D.

    2014-01-01

    Objective To assess the frequency of obstructive sleep apnea among women with and without hypertensive disorders of pregnancy. Design Cohort study. Setting Obstetric clinics at an academic medical center. Population Pregnant women with hypertensive disorders (chronic hypertension, gestational hypertension, or pre-eclampsia) and normotensive women. Methods Women completed a questionnaire about habitual snoring and underwent overnight ambulatory polysomnography. Main Outcome Measures The presence and severity of obstructive sleep apnea. Results Obstructive sleep apnoea was found among 21 of 51 women with hypertensive disorders (41%), but in only three of 16 women who were normotensive (19%, chi-square test, P = 0.005). Non-snoring hypertensive women typically had mild obstructive sleep apnea but >25% of snoring hypertensive women had moderate-to-severe obstructive sleep apnea. Among the hypertensive women, the mean apnea/hypopnea index was substantially higher in snorers than non-snorers (19.9±34.1 vs. 3.4±3.1, p=0.013) and the oxyhemoglobin saturation nadir was significantly lower (86.4±6.6 vs. 90.2±3.5, p=0.021). Among hypertensive women, after stratification by obesity the pooled relative risk for obstructive sleep apnea in snoring women with hypertension compared to non-snoring hypertension was 2.0 [95%CI 1.4–2.8]. Conclusions Pregnant women with hypertension are at high risk for unrecognised obstructive sleep apnea. While longitudinal and intervention studies are urgently needed, it would seem pertinent given the known relationship between obstructive sleep apnea and hypertension in the general population, that hypertensive pregnant women who snore should be tested for obstructive sleep apnea, a condition believed to cause or promote hypertension. PMID:24888772

  19. In-depth Medical Nutrition Therapy for a Woman with Diabetes: From Pregnancy to Delivery

    PubMed Central

    2016-01-01

    Diabetes in pregnancy is associated with higher rates of miscarriage, pre-eclampsia, preterm labor, and fetal malformation. To prevent these obstetric and perinatal complications, women with diabetes have to control levels of blood sugar, both prior to and during pregnancy. Thus, individualized medical nutrition therapy for each stage of pregnancy is essential. We provided in-depth medical nutrition therapy to a 38-year-old pregnant woman with diabetes at all stages of pregnancy up to delivery. She underwent radiation therapy after surgery for breast cancer and was diagnosed with diabetes. At the time of diagnosis, her glycated hemoglobin level was 8.3% and she was planning her pregnancy. She started taking an oral hypoglycemic agent and received education regarding the management of diabetes and preconception care. She became pregnant while maintaining a glycated hemoglobin level of less than 6%. We provided education program for diabetes management during the pregnancy, together with insulin therapy. She experienced weight loss and ketones were detected; furthermore, she was taking in less than the recommended amount of foods for the regulation of blood sugar levels. By giving emotional support, we continued the counseling and achieved not only glycemic control but also instilled an appreciation of the importance of appropriate weight gain and coping with difficulties. Through careful diabetes management, the woman had a successful outcome for her pregnancy, other than entering preterm labor at 34 weeks. This study implicated that the important things in medical nutrition therapy for pregnant women with diabetes are frequent follow-up care and emotional approach through the pregnancy process. PMID:27812519

  20. Placental Microparticles and MicroRNAs in Pregnant Women with Plasmodium falciparum or HIV Infection

    PubMed Central

    Moro, Laura; Bardají, Azucena; Macete, Eusebio; Barrios, Diana; Morales-Prieto, Diana M.; España, Carolina; Mandomando, Inacio; Sigaúque, Betuel; Dobaño, Carlota; Markert, Udo R.; Benitez-Ribas, Daniel; Alonso, Pedro L.; Menéndez, Clara; Mayor, Alfredo

    2016-01-01

    Background During pregnancy, syncytiotrophoblast vesicles contribute to maternal tolerance towards the fetus, but also to pathologies such as pre-eclampsia. The aim of the study was to address whether Plasmodium falciparum and HIV infections in pregnancy affect the secretion, microRNA content and function of trophoblast microparticles. Methods Microparticles were isolated and characterized from 122 peripheral plasmas of Mozambican pregnant women, malaria- and/or HIV-infected and non-infected. Expression of placenta-related microRNAs in microparticles was analysed by qPCR and the effect of circulating microparticles on dendritic cells assessed by phenotype analysis and cytokine/chemokine measurement. Results Concentrations of total and trophoblast microparticles detected by flow cytometry were higher in HIV-positive (P = 0.005 and P = 0.030, respectively) compared to non-infected mothers, as well as in women delivering low birthweight newborns (P = 0.032 and P = 0.021, respectively). miR-517c was overexpressed in mothers with placental malaria (P = 0.034), compared to non-infected. Microparticles from HIV-positive induced a higher expression of MHCII (P = 0.021) and lower production of MCP1 (P = 0.008) than microparticles from non-infected women. Conclusions In summary, alterations in total and trophoblast microparticles associated with malaria and HIV in pregnant women may have an immunopathogenic role. The potential for placental-derived vesicles and microRNAs as biomarkers of adverse outcomes during pregnancy and malaria infection should be confirmed in future studies. PMID:26757431

  1. Heme oxygenase and the immune system in normal and pathological pregnancies

    PubMed Central

    Ozen, Maide; Zhao, Hui; Lewis, David B.; Wong, Ronald J.; Stevenson, David K.

    2015-01-01

    Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity. PMID

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

    PubMed Central

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

    2015-01-01

    Objective To evaluate the prognoses associated with psychosocial deprivation in women with gestational diabetes mellitus (GDM). Design Observational study considering the 1498 multiethnic women with GDM who gave birth between January 2009 and February 2012. Setting Four largest maternity units in the northeastern suburban area of Paris. Participants The 994 women who completed the Evaluation of Precarity and Inequalities in Health Examination Centers (EPICES) questionnaire. Main outcome measure Main complications of GDM (large infant for gestational age (LGA), shoulder dystocia, caesarean section, pre-eclampsia). Results Psychosocial deprivation (EPICES score ≥30.17) affected 577 women (56%) and was positively associated with overweight/obesity, parity and non-European origin, and negatively associated with family history of diabetes, fruit and vegetable consumption and working status. The psychosocially deprived women were diagnosed with GDM earlier, received insulin treatment during pregnancy more often and were more likely to have LGA infants (15.1% vs 10.6%, OR=1.5 (95% CI 1.02 to 2.2), p<0.05) and shoulder dystocia (3.1% vs 1.2%, OR=2.7 (0.97 to 7.2), p<0.05). In addition to psychosocial deprivation, LGA was associated with greater parity, obesity, history of GDM, ethnicity, excessive gestational weight gain and insulin therapy. A multivariate analysis using these covariates revealed that the EPICES score was independently associated with LGA infants (per 10 units, OR=1.12 (1.03 to 1.20), p<0.01). Conclusions In our area, psychosocial deprivation is common in women with GDM and is associated with earlier GDM diagnoses and greater insulin treatment, an increased likelihood of shoulder dystocia and, independently of obesity, gestational weight gain and other confounders with LGA infants. PMID:25748416

  3. IBC CARe Microarray Allelic Population Prevalences in an American Indian Population

    PubMed Central

    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

    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

  4. Heme oxygenase and the immune system in normal and pathological pregnancies.

    PubMed

    Ozen, Maide; Zhao, Hui; Lewis, David B; Wong, Ronald J; Stevenson, David K

    2015-01-01

    Normal pregnancy is an immunotolerant state. Many factors, including environmental, socioeconomic, genetic, and immunologic changes by infection and/or other causes of inflammation, may contribute to inter-individual differences resulting in a normal or pathologic pregnancy. In particular, imbalances in the immune system can cause many pregnancy-related diseases, such as infertility, abortions, pre-eclampsia, and preterm labor, which result in maternal/fetal death, prematurity, or small-for-gestational age newborns. New findings imply that myeloid regulatory cells and regulatory T cells (Tregs) may mediate immunotolerance during normal pregnancy. Effector T cells (Teffs) have, in contrast, been implicated to cause adverse pregnancy outcomes. Furthermore, feto-maternal tolerance affects the developing fetus. It has been shown that the Treg/Teff balance affects litter size and adoptive transfer of pregnancy-induced Tregs can prevent fetal rejection in the mouse. Heme oxygenase-1 (HO-1) has a protective role in many conditions through its anti-inflammatory, anti-apoptotic, antioxidative, and anti-proliferative actions. HO-1 is highly expressed in the placenta and plays a role in angiogenesis and placental vascular development and in regulating vascular tone in pregnancy. In addition, HO-1 is a major regulator of immune homeostasis by mediating crosstalk between innate and adaptive immune systems. Moreover, HO-1 can inhibit inflammation-induced phenotypic maturation of immune effector cells and pro-inflammatory cytokine secretion and promote anti-inflammatory cytokine production. HO-1 may also be associated with T-cell activation and can limit immune-based tissue injury by promoting Treg suppression of effector responses. Thus, HO-1 and its byproducts may protect against pregnancy complications by its immunomodulatory effects, and the regulation of HO-1 or its downstream effects has the potential to prevent or treat pregnancy complications and prematurity. PMID

  5. Predicting adverse obstetric outcome after early pregnancy events and complications: a review.

    PubMed

    van Oppenraaij, R H F; Jauniaux, E; Christiansen, O B; Horcajadas, J A; Farquharson, R G; Exalto, N

    2009-01-01

    BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited or small uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care. PMID:19270317

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

    PubMed Central

    2014-01-01

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

  7. Nitrotyrosine immunostaining correlates with increased extracellular matrix: evidence of postplacental hypoxia.

    PubMed

    Stanek, J; Eis, A L; Myatt, L

    2001-04-01

    Nitrotyrosine residues (NT), an index of oxidative stress arising from peroxynitrite formation and action, are found in placental vasculature of pregnancies complicated by pre-eclampsia (PE) or pregestational insulin-dependent diabetes mellitus (IDDM). This study correlates conventional placental pathology with NT immunostaining in 20 cases of perinatal mortality (13 stillbirths and seven cases of neonatal mortality) associated with PE, IDDM, amniotic fluid infection syndrome (AFIS), or from fetal/neonatal demise not related to these conditions (congenital anomalies) (n = five/group). Patients with PE have more decidual arteriolopathy and Tenney-Parker change, while patients with IDDM and ascending infection have more villous cytotrophoblastic hyperplasia. Archival paraffin-embedded placental sections were immunostained for NT for correlation with clinical features and H&E histological findings. The intensity of immunostaining for NT varied from absent (n = 7) to 1+ (n = 5) or 2+ (n = 8). All eight placentae with 2+ staining showed increased villous extracellular matrix (ECM), compared to none of five with 1+ staining and two of seven with no staining (chi2 = 14.3, P = 0.001). There was no statistically significant difference in the percentage of stem villi with luminal vascular abnormalities (5.7 vs 10 vs 35.7 per cent, F = 2.3, P = 0.1). Our data show that increased production of reactive oxygen species by placental tissue may be associated with increased extracellular matrix, itself produced by fibroblasts under the influence of oxygen. NT immunostaining may therefore help differentiate those cases of perinatal morbidity/mortality associated with post-placental hypoxia provided that the secondary impact of intrauterine fetal death can be excluded by future studies. PMID:11312630

  8. 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

    2014-01-01

    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

  9. Acute renal failure in pregnancy: our experience.

    PubMed

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

    2014-03-01

    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

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

    PubMed

    Thorne-Lyman, Andrew; Fawzi, Wafaie W

    2012-07-01

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

  11. Selenium status in U.K. pregnant women and its relationship with hypertensive conditions of pregnancy.

    PubMed

    Rayman, Margaret P; Bath, Sarah C; Westaway, Jacob; Williams, Peter; Mao, Jinyuan; Vanderlelie, Jessica J; Perkins, Anthony V; Redman, Christopher W G

    2015-01-28

    Dietary intake/status of the trace mineral Se may affect the risk of developing hypertensive conditions of pregnancy, i.e. pre-eclampsia and pregnancy-induced hypertension (PE/PIH). In the present study, we evaluated Se status in U.K. pregnant women to establish whether pre-pregnant Se status or Se supplementation affected the risk of developing PE/PIH. The samples originated from the SPRINT (Selenium in PRegnancy INTervention) study that randomised 230 U.K. primiparous women to treatment with Se (60 μg/d) or placebo from 12 weeks of gestation. Whole-blood Se concentration was measured at 12 and 35 weeks, toenail Se concentration at 16 weeks, plasma selenoprotein P (SEPP1) concentration at 35 weeks and plasma glutathione peroxidase (GPx3) activity at 12, 20 and 35 weeks. Demographic data were collected at baseline. Participants completed a FFQ. U.K. pregnant women had whole-blood Se concentration lower than the mid-range of other populations, toenail Se concentration considerably lower than U.S. women, GPx3 activity considerably lower than U.S. and Australian pregnant women, and low baseline SEPP1 concentration (median 3.00, range 0.90-5.80 mg/l). Maternal age, education and social class were positively associated with Se status. After adjustment, whole-blood Se concentration was higher in women consuming Brazil nuts (P= 0.040) and in those consuming more than two seafood portions per week (P= 0.054). A stepwise logistic regression model revealed that among the Se-related risk factors, only toenail Se (OR 0.38, 95% CI 0.17, 0.87, P= 0.021) significantly affected the OR for PE/PIH. On excluding non-compliers with Se treatment, Se supplementation also significantly reduced the OR for PE/PIH (OR 0.30, 95% CI 0.09, 1.00, P= 0.049). In conclusion, U.K. women have low Se status that increases their risk of developing PE/PIH. Therefore, U.K. women of childbearing age need to improve their Se status.

  12. Pregnancy outcomes of liver transplant recipients: a systematic review and meta-analysis.

    PubMed

    Deshpande, Neha A; James, Nathan T; Kucirka, Lauren M; Boyarsky, Brian J; Garonzik-Wang, Jacqueline M; Cameron, Andrew M; Singer, Andrew L; Dagher, Nabil N; Segev, Dorry L

    2012-06-01

    Approximately 14,000 women of reproductive age are currently living in the United States after liver transplantation (LT), and another 500 undergo LT each year. Although LT improves reproductive function in women with advanced liver disease, the associated pregnancy outcomes and maternal-fetal risks have not been quantified in a broad manner. To obtain more generalizable inferences, we performed a systematic review and meta-analysis of articles that were published between 2000 and 2011 and reported pregnancy-related outcomes for LT recipients. Eight of 578 unique studies met the inclusion criteria, and these studies represented 450 pregnancies in 306 LT recipients. The post-LT live birth rate [76.9%, 95% confidence interval (CI) = 72.7%-80.7%] was higher than the live birth rate for the US general population (66.7%) but was similar to the post-kidney transplantation (KT) live birth rate (73.5%). The post-LT miscarriage rate (15.6%, 95% CI = 12.3%-19.2%) was lower than the miscarriage rate for the general population (17.1%) but was similar to the post-KT miscarriage rate (14.0%). The rates of pre-eclampsia (21.9%, 95% CI = 17.7%-26.4%), cesarean section delivery (44.6%, 95% CI = 39.2%-50.1%), and preterm delivery (39.4%, 95% CI = 33.1%-46.0%) were higher than the rates for the US general population (3.8%, 31.9%, and 12.5%, respectively) but lower than the post-KT rates (27.0%, 56.9%, and 45.6%, respectively). Both the mean gestational age and the mean birth weight were significantly greater (P < 0.001) for LT recipients versus KT recipients (36.5 versus 35.6 weeks and 2866 versus 2420 g). Although pregnancy after LT is feasible, the complication rates are relatively high and should be considered during patient counseling and clinical decision making. More case and center reports are necessary so that information on post-LT pregnancy outcomes and complications can be gathered to improve the clinical management of pregnant LT recipients. Continued reporting to active

  13. Selenium status in U.K. pregnant women and its relationship with hypertensive conditions of pregnancy.

    PubMed

    Rayman, Margaret P; Bath, Sarah C; Westaway, Jacob; Williams, Peter; Mao, Jinyuan; Vanderlelie, Jessica J; Perkins, Anthony V; Redman, Christopher W G

    2015-01-28

    Dietary intake/status of the trace mineral Se may affect the risk of developing hypertensive conditions of pregnancy, i.e. pre-eclampsia and pregnancy-induced hypertension (PE/PIH). In the present study, we evaluated Se status in U.K. pregnant women to establish whether pre-pregnant Se status or Se supplementation affected the risk of developing PE/PIH. The samples originated from the SPRINT (Selenium in PRegnancy INTervention) study that randomised 230 U.K. primiparous women to treatment with Se (60 μg/d) or placebo from 12 weeks of gestation. Whole-blood Se concentration was measured at 12 and 35 weeks, toenail Se concentration at 16 weeks, plasma selenoprotein P (SEPP1) concentration at 35 weeks and plasma glutathione peroxidase (GPx3) activity at 12, 20 and 35 weeks. Demographic data were collected at baseline. Participants completed a FFQ. U.K. pregnant women had whole-blood Se concentration lower than the mid-range of other populations, toenail Se concentration considerably lower than U.S. women, GPx3 activity considerably lower than U.S. and Australian pregnant women, and low baseline SEPP1 concentration (median 3.00, range 0.90-5.80 mg/l). Maternal age, education and social class were positively associated with Se status. After adjustment, whole-blood Se concentration was higher in women consuming Brazil nuts (P= 0.040) and in those consuming more than two seafood portions per week (P= 0.054). A stepwise logistic regression model revealed that among the Se-related risk factors, only toenail Se (OR 0.38, 95% CI 0.17, 0.87, P= 0.021) significantly affected the OR for PE/PIH. On excluding non-compliers with Se treatment, Se supplementation also significantly reduced the OR for PE/PIH (OR 0.30, 95% CI 0.09, 1.00, P= 0.049). In conclusion, U.K. women have low Se status that increases their risk of developing PE/PIH. Therefore, U.K. women of childbearing age need to improve their Se status. PMID:25571960

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

    PubMed Central

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

    2014-01-01

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

  15. Looking to the future.

    PubMed

    Lamont, Ronald F

    2003-04-01

    Since the 7th and 13th Study Groups of the Royal College of Obstetricians and Gynaecologists met in 1977 and 1985, respectively, no meeting of this magnitude has convened to discuss the problems of spontaneous preterm labour and delivery and the associated fetomaternal mortality and morbidity. In the 17 years or so since that time, advances have been made in our understanding of the mechanisms of labour, the role of infection, the benefit of antepartum corticosteroids and the development of safer more specific tocolytics. In the future, an understanding of the genetic risk of spontaneous preterm labour and preterm birth is essential, particularly with respect to the predisposition to produce potentially damaging pro-inflammatory cytokines. The examination of the tissue damage will require pathologists specifically trained in perinatal pathology if the aetiology is to be ascertained and future management tailored to the risks. A greater understanding of fetomaternal immunology and response to antigen exposure in pregnancy may help us to understand which fetomaternal pairs are at greatest risk of responding by delivering preterm, with greater or lesser tissue damage than others with similar risk. Specifically, the relation between spontaneous preterm labour and proteinuric pre-eclampsia with their common immunology, inflammatory response and tissue damage leading to either spontaneous preterm labour or iatrogenic preterm birth will need to be addressed. This meeting has been very clinically and obstetrically orientated, in future we will need to involve epidemiologists, neonatologists, microbiologists, genito-urinary medicine physicians, immunologists, geneticists, biochemists, physiologists and endocrinologists. Although spontaneous preterm labour and preterm birth are the major causes of perinatal mortality and morbidity in the developed world, the definition and management protocols for spontaneous preterm labour varies from unit to unit and country to country. A

  16. Isolated elevation of IgA anti-beta2glycoprotein I antibodies with manifestations of antiphospholipid syndrome: a case series of five patients.

    PubMed

    Kumar, S; Papalardo, E; Sunkureddi, P; Najam, S; González, E B; Pierangeli, S S

    2009-10-01

    Current diagnostic classification criteria recommend elevated titres of anti-cardiolipin (aCL) and/or anti-beta(2)GPI antibody by ELISA IgG or IgM and/or lupus anticoagulant (LA) to confirm antiphospholipid syndrome (APS). Although IgA aPL antibodies have been shown to be pathogenic in animal models of APS, their clinical significance has remained elusive. We report four cases of exclusive IgA anti-beta(2)GPI antibody sero-positivity with concomitant clinical manifestations associated with APS. Four of the five patients were LA negative. 1) Thirty-eight-year-old African-American female with SLE presented with resolving digital ulcers. Serum IgA anti-beta(2)GPI antibody titres were 118.5 SAU (normal range: 0-20 SAU). 2) Twenty-seven-year-old African-American woman with SLE was evaluated for recent onset of severe headaches, unresponsive to analgesics and anti-migraine medications. MRI of the brain revealed hyper-intensities in the white matter in the frontal lobes. Serum IgA anti-beta(2)GPI antibody titres were 29.1 Standard A Units (SAU). 3) Thirty-two-year-old Hispanic female with history of two unexplained miscarriages and negative serologies for SLE. Serum IgA anti-beta(2)GPI antibody titres were 102.0 SAU. 4) Twenty-five-year-old white female with history of recent unexplained miscarriage in the 11th week of gestation and associated complaints of numbness and tingling in her hands. Her IgA anti-beta(2)GPI antibody titre was 62.0 SAU. 5) Twenty-five-year-old African-American woman with SLE, positive for anti-Ro antibodies with a history of ischemic fingers, a pregnancy loss and recent pregnancy complicated due to pre-eclampsia. Her LA was positive and her IgA anti-beta(2)GPI antibody titer was 186.0 SAU. This case series supports that elevated IgA anti-beta(2)GPI antibody titres may identify additional patients who have clinical features of APS but who do not meet current diagnostic criteria.

  17. Roll-to-roll, shrink-induced superhydrophobic surfaces for antibacterial applications, enhanced point-of-care detection, and blood anticoagulation

    NASA Astrophysics Data System (ADS)

    Nokes, Jolie McLane

    Superhydrophobic (SH) surfaces are desirable because of their unique anti-wetting behavior. Fluid prefers to bead up (contact angle >150°) and roll off (contact angle hysteresis <10°) a SH surface because micro- and nanostructure features trap air pockets. Fluid only adheres to the peaks of the structures, causing minimal adhesion to the surface. Here, shrink-induced SH plastics are fabricated for a plethora of applications, including antibacterial applications, enhanced point-of-care (POC) detection, and reduced blood coagulation. Additionally, these purely structural SH surfaces are achieved in a roll-to-roll (R2R) platform for scalable manufacturing. Because their self-cleaning and water resistant properties, structurally modified SH surfaces prohibit bacterial growth and obviate bacterial chemical resistance. Antibacterial properties are demonstrated in a variety of SH plastics by preventing gram-negative Escherichia coli (E. coli) bacterial growth >150x compared to flat when fluid is rinsed and >20x without rinsing. Therefore, a robust and stable means to prevent bacteria growth is possible. Next, protein in urine is detected using a simple colorimetric output by evaporating droplets on a SH surface. Contrary to evaporation on a flat surface, evaporation on a SH surface allows fluid to dramatically concentrate because the weak adhesion constantly decreases the footprint area. On a SH surface, molecules in solution are confined to a footprint area 8.5x smaller than the original. By concentrating molecules, greater than 160x improvements in detection sensitivity are achieved compared to controls. Utility is demonstrated by detecting protein in urine in the pre-eclampsia range (150-300microgmL -1) for pregnant women. Further, SH surfaces repel bodily fluids including blood, urine, and saliva. Importantly, the surfaces minimize blood adhesion, leading to reduced blood coagulation without the need for anticoagulants. SH surfaces have >4200x and >28x reduction of

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

    PubMed Central

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

    2014-01-01

    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

  19. Placental endoplasmic reticulum stress negatively regulates transcription of placental growth factor via ATF4 and ATF6β: implications for the pathophysiology of human pregnancy complications.

    PubMed

    Mizuuchi, Masahito; Cindrova-Davies, Tereza; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J; Yung, Hong Wa

    2016-03-01

    Low maternal circulating concentrations of placental growth factor (PlGF) are one of the hallmarks of human pregnancy complications, including fetal growth restriction (FGR) and early-onset pre-eclampsia (PE). Currently, PlGF is used clinically with other biomarkers to screen for high-risk cases, although the mechanisms underlying its regulation are largely unknown. Placental endoplasmic reticulum (ER) stress has recently been found to be elevated in cases of FGR, and to an even greater extent in early-onset PE complicated with FGR. ER stress activates the unfolded protein response (UPR); attenuation of protein translation and a reduction in cell growth and proliferation play crucial roles in the pathophysiology of these complications of pregnancy. In this study, we further identified that ER stress regulates release of PlGF. We first observed that down-regulation of PlGF protein was associated with nuclear localization of ATF4, ATF6α and ATF6β in the syncytiotrophoblast of placentae from PE patients. Transcript analysis showed a decrease of PlGF mRNA, and an increase from genes encoding those UPR transcription factors in placentae from cases of early-onset PE, but not of late-onset (>34 weeks) PE, compared to term controls. Further investigations indicated a strong correlation between ATF4 and PlGF mRNA levels only (r = - 0.73, p < 0.05). These results could be recapitulated in trophoblast-like cells exposed to chemical inducers of ER stress or hypoxia-reoxygenation. The stability of PlGF transcripts was unchanged. The use of small interfering RNA specific for transcription factors in the UPR pathways revealed that ATF4 and ATF6β, but not ATF6α, modulate PlGF transcription. To conclude, ATF4 and ATF6β act synergistically in the negative regulation of PlGF mRNA expression, resulting in reduced PlGF secretion by the trophoblast in response to stress. Therefore, these results further support the targeting of placental ER stress as a potential new therapeutic

  20. Angiotensin II activates the calcineurin/NFAT signaling pathway and induces cyclooxygenase-2 expression in rat endometrial stromal cells.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

    Ashworth, Ann; Feachem, R. G.

    1985-01-01

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

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

    SciTech Connect

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

    2012-11-01

    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

  5. Vitamin D depletion does not affect key aspects of the preeclamptic phenotype in a transgenic rodent model for preeclampsia.

    PubMed

    Andersen, Louise Bjørkholt; Golic, Michaela; Przybyl, Lukasz; Sorensen, Grith Lykke; Jørgensen, Jan Stener; Fruekilde, Palle; von Versen-Höynck, Frauke; Herse, Florian; Højskov, Carsten Schriver; Dechend, Ralf; Christesen, Henrik Thybo; Haase, Nadine

    2016-07-01

    Maternal vitamin D deficiency is proposed as a risk factor for preeclampsia in humans. We tested the hypothesis that vitamin D depletion aggravates and high supplementation ameliorates the preeclampsia phenotype in an established transgenic rat model of human renin-angiotensin system-mediated preeclampsia. Adult rat dams, transgenic for human angiotensinogen (hAGT) and mated with male rats transgenic for human renin (hREN), were fed either vitamin D-depleted chow (VDd) or enriched chow (VDh) 2 weeks before mating and during pregnancy. Mean blood pressure was recorded by tail-cuff, and 24-hour urine samples were collected in metabolic cages at days 6 and 18 of gestation. Rats were sacrificed at day 21 of gestation. Depleted dams (VDd) had negligible serum 25-hydroxyvitamin D2+3 levels (mean ± SEM; 2.95 ± 0.45 nmol/l vs. VDh 26.20 ± 2.88 nmol/l, P = .01), but in both groups, levels of 1,25(OH)2D3 remained below detection level of 25 pmol/l. Dietary vitamin D depletion did not aggravate hypertension (mean ± SEM BP, day 20 of gestation: 151.38 ± 5.65 mmHg VDd vs. 152.00 ± 4.10 mmHg VDh) or proteinuria. Fetal anthropometrics were similar between the groups, whereas VDd displayed lower placental:fetal weight ratios (0.15 vs. 0.16 g/g, P = .01) and increased sFlt-1/PlGF ratio. Expression of hREN was lower in placenta of VDd dams (0.82 ± 0.44 AU vs. 1.52 ± 0.15 AU, P = .04). Expression of key vitamin D metabolizing enzymes was unchanged. Dietary vitamin D intervention did not alter key aspects of the preeclampsia phenotype using the transgenic rodent model of human renin-angiotensin system-mediated pre-eclampsia, plausibly due to altered vitamin D metabolism or excretion in the transgenic rats. PMID:27450577

  6. Frequency of the CCR5-delta32 allele in Brazilian populations: A systematic literature review and meta-analysis.

    PubMed

    Silva-Carvalho, Wlisses Henrique Veloso; de Moura, Ronald Rodrigues; Coelho, Antonio Victor Campos; Crovella, Sergio; Guimarães, Rafael Lima

    2016-09-01

    The CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp deletion in the CCR5 gene (CCR5-delta32) that produces a truncated non-functional protein not expressed on the cell surface. This polymorphism, known to be associated with susceptibility to infectious and inflammatory diseases, such as osteomyelitis, pre-eclampsia, systemic lupus erythematous, juvenile idiopathic arthritis, rheumatoid arthritis and HIV/AIDS, is more commonly found in European populations with average frequency of 10%. However, it is also possible to observe a significant frequency in other world populations, such as the Brazilian one. We performed a systematic review and meta-analysis of CCR5-delta32 genetic association studies in Brazilian populations throughout the country to estimate the frequency of this polymorphism. We also compared CCR5-delta32 frequencies across Brazilian regions. The systematic literature reviewed studies involving delta32 allele in Brazilian populations published from 1995 to 2015. Among the reviewed literature, 25 studies including 30 Brazilian populations distributed between the North, Northeast, South and Southeast regions were included in our meta-analysis. We observed an overall allelic frequency of 4% (95%-CI, 0.03-0.05), that was considered moderate and, notably, higher than some European populations, such as Cyprus (2.8%), Italy (3%) and Greece (2.4%). Regarding the regional frequency comparisons between North-Northeast (N-NE) and South-Southeast (S-SE) regions, we observed an allelic frequency of 3% (95%-CI, 0.02-0.04) and 4% (95%-CI, 0.03-0.05), respectively. The populations from S-SE regions had a slightly higher CCR5-delta32 frequency than N-NE regions (OR=1.41, p=0.002). Although there are several studies about the CCR5-delta32 polymorphism and its effect on the immune response of some infectious diseases, this report is the first meta

  7. Reducing stillbirths: interventions during labour

    PubMed Central

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

    2009-01-01

    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

  8. The Impact of Macronutrients on Retinal Microvasculature among Singapore Pregnant Women during the Mid-Late Gestation

    PubMed Central

    Li, Ling-Jun; Ong, Peng Guan; Colega, Marjorelee T.; Han, Chad Yixian; Chen, Ling Wei; Man Eyn Kidd, Ryan; Lamoureux, Ecosse; Gluckman, Peter; Kwek, Kenneth; Chong, Yap Seng; Saw, Seang Mei; Godfrey, Keith M.; Wong, Tien Yin; Chong Foong-Fong, Mary

    2016-01-01

    Background Imbalanced macronutrient intakes can induce impairment of endothelial and vascular function, and further lead to metabolic and cardiovascular disease. However, little is known about the influence of such diets on endothelial and vascular dysfunction in pregnant women, even though high-fat diet is a known risk for pregnancy complications such as gestational diabetes and pre-eclampsia. Objective We aimed to assess the association between maternal macronutrient intakes (protein, fat and carbohydrates), dietary quality and retinal microvascular changes in a multi-ethnic Asian mother-offspring cohort. Methods Pregnant women (n = 614) with singleton pregnancies were recruited during their first trimester from June 2009 to Sep 2010. Maternal diet quality and macronutrient intakes, expressed as a percentage of total energy during pregnancy, were ascertained using 24 hr recalls and 3 d food diaries at 26–28 weeks gestation. Retinal examination was completed at the same clinic visit. Dietary quality was assessed and scored using the Health Eating Index in Asian Pregnant women (HEI-AP), while macronutrients intakes ware expressed as percentages of total energy and further log transformed for analysis. Associations were examined cross-sectionally by substitution models with the use of multiple linear regression. Results In adjusted model, each 20 points decrease in HEI-AP score was associated with a significant increase of 1.70 μm (p<0.05) in retinal venular calibre. Each 0.1 log increase in percentage of total fat intake was associated with a significant increment of 1.84 μm (p<0.05) in retinal venular caliber. Additionally, each 0.1 log increase in percentage of mono-unsaturated fat intake was associated with an increment of 1.84 μm (p<0.01) in retinal venular caliber. Conclusions In this cross-sectional study, we found that women with higher fat and lower protein intakes, and lower diet quality tended to have wider retinal venular caliber, which is

  9. The effects of vitamin D3 on lipogenesis in the liver and adipose tissue of pregnant rats.

    PubMed

    Kang, Eun-Jin; Lee, Jae-Eon; An, Sung-Min; Lee, Jae Ho; Kwon, Hyeog Soong; Kim, Byoung Chul; Kim, Seon Jong; Kim, Joo Man; Hwang, Dae Youn; Jung, Young-Jin; Yang, Seung Yun; Kim, Seung Chul; An, Beum-Soo

    2015-10-01

    Obesity is a worldwide individual and public health issue, and contributes to the development of numerous chronic diseases. In particular, maternal obesity has harmful effects on both the mother and child during and after pregnancy. The digestion and metabolism of food are controlled by endocrine factors, including insulin, glucagon and estrogen. These hormonal factors are differentially regulated during pregnancy due to the specialized hormonal environment during this period. In the present study, we examined the effects of 1,25-dihydroxyvitamin D3 (VD3), an active hormonal form of nutritional vitamin D3, on lipid metabolism in pregnant rats. The body weight of rats treated with VD3 was significantly reduced compared to that of the rats in the control group. In addition, histological analysis demonstrated that the amount of fat stored in adipocytes was reduced by treatment with VD3. To determine the role of VD3 in lipid metabolism, the expression levels of lipid metabolism‑associated genes were measured in the rat adipose tissue and liver. VD3 negatively regulated the expression of various lipogenic genes, including fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) and acetyl-CoA carboxylase 1 (ACC1), in both the adipose tissue and liver. However, the regulators of lipogenic enzymes such as, sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-γ (PPAR-γ) and insulin-induced gene 2 (INSIG2) were differentially regulated by VD3 in a tissue‑specific manner. On the whole, these findings suggest that VD3 regulates lipid metabolism and deposition in the liver and adipose tissue, and thereby reduces fat in pregnant animals, as well as body weight. Our results suggest that the alteration of lipogenesis through the administration of VD3 may help to reduce excessive weight gain during pregnancy and prevent obesity‑related pregnancy complications such as pre-eclampsia, gestational diabetes

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

    PubMed Central

    2010-01-01

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

  11. Glucocorticoid Metabolism in Hypertensive Disorders of Pregnancy: Analysis of Plasma and Urinary Cortisol and Cortisone

    PubMed Central

    Kosicka, Katarzyna; Siemiątkowska, Anna; Krzyścin, Mariola; Bręborowicz, Grzegorz H.; Resztak, Matylda; Majchrzak-Celińska, Aleksandra; Chuchracki, Marek; Główka, Franciszek K.

    2015-01-01

    Objectives The aim of the study was to analyze the plasma and urinary cortisol (F) and cortisone (E) levels in normotensive and hypertensive pregnant women. The parameters known to reflect the function of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) were calculated to verify the changes in glucocorticoid balance over the course of gestational hypertension (GH) and pre-eclampsia (PE). Materials and Methods This retrospective case-control study included women in the third trimester of pregnancy, diagnosed with: GH (n = 29), PE (n = 26), or chronic hypertension (CH; n = 22). Normotensive women in their third trimester of pregnancy were also included (controls; n = 43). The plasma and urinary F and E levels were measured with the HPLC-FLD method. The 11β-HSD2 function was estimated by calculating the following ratios: plasma F/E and urinary free F to urinary free E (UFF/UFE). A statistical analysis was performed based on case-control structure. Results and Discussion PE was characterized by lower plasma F levels (639.0 nmol/L), UFF/Cr levels (3.80 μg/mmol) and F/E ratio (3.46) compared with that of the controls (811.7 nmol/L, 6.28 μg/mmol and 5.19, respectively) with marked abnormalities observed in the changes of F/E and UFF/UFE ratios with advancing gestation. GH patients showed significant disparities in the urinary steroid profile with lower UFF/UFE ratio (0.330 vs. 0.401) compared with the normotensive controls and abnormal changes in the UFF/UFE throughout pregnancy. The observed tendency towards lower F/E and UFF/UFE ratios in PE and GH patients may reflect more intensive F metabolism over the course of those disorders. In the normal pregnancy group, the plasma F/E and UFF/UFE ratios tended to present inverse correlations with advancing gestation. This trend was much less marked in PE and GH patients, suggesting that the abnormalities in 11β-HSD2 functions progressed with the GA. The birth weights of neonates born from pre-eclamptic pregnancies were

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

    PubMed Central

    Thorne-Lyman, Andrew; Fawzi, Wafaie W.

    2013-01-01

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

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

    PubMed

    Thorne-Lyman, Andrew; Fawzi, Wafaie W

    2012-07-01

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

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

    PubMed Central

    2012-01-01

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

  15. Hypertensive disorders of pregnancy and risk of diabetes in Indian women: a cross-sectional study

    PubMed Central

    Agrawal, Sutapa; Fledderjohann, Jasmine

    2016-01-01

    Background Epidemiological data from high-income countries suggest that women with hypertensive disorders of pregnancy (HDP) are more likely to develop diabetes later in life. Objective We investigated the association between pre-eclampsia and eclampsia (PE&E) during pregnancy and the risk of diabetes in Indian women. Design Cross-sectional study. Setting India. Methods Data from India's third National Family Health Survey (NFHS-3, 2005–2006), a cross-sectional survey of women aged 15–49 years, are used. Self-reported symptoms suggestive of PE&E were obtained from 39 657 women who had a live birth in the 5 years preceding the survey. The association between PE&E and self-reported diabetes status was assessed using multivariable logistic regression models adjusting for dietary intake, body mass index (BMI), tobacco smoking, alcohol drinking, frequency of TV watching, sociodemographic characteristics and geographic region. Results The prevalence of symptoms suggestive of PE&E in women with diabetes was 1.8% (n=207; 95% CI 1.5 to 2.0; p<0.0001) and 2.1% (n=85; 95% CI 1.8 to 2.3; p<0.0001), respectively, compared with 1.1% (n=304; 95% CI 1.0 to 1.4) and 1.2% (n=426; 95% CI 1.1 to 1.5) in women who did not report any PE&E symptoms. In the multivariable analysis, PE&E was associated with 1.6 times (OR=1.59; 95% CI 1.31 to 1.94; p<0.0001) and 1.4 times (OR=1.36; 95% CI 1.05 to 1.77; p=0.001) higher risk for self-reported diabetes even after controlling for dietary intake, BMI and sociodemographic characteristics. Conclusions HDP is strongly associated with the risk of diabetes in a large nationally representative sample of Indian women. These findings are important for a country which is already tackling the burden of young onset of diabetes in the population. However, longitudinal medical histories and a clinical measurement of diabetes are needed in this low-resource setting. PMID:27496230

  16. THE IMPACT OF MATERNAL OBESITY ON MOTHER AND NEONATAL HEALTH: STUDY IN A TERTIARY HOSPITAL OF ASTANA, KAZAKHSTAN

    PubMed Central

    AIMUKHAMETOVA, GULZHAN; UKYBASOVA, TALSHYN; HAMIDULLINA, ZAITUNA; ZHUBANYSHEVA, KARLYGASH; HARUN-OR-RASHID, MD.; YOSHIDA, YOSHITOKU; KASUYA, HIDEKI; SAKAMOTO, JUNICHI

    2012-01-01

    ABSTRACT This study was aimed to investigate the impact of maternal obesity on mothers and their neonatal health. Our study population consisted of 157 women with completed singleton pregnancies, which included both obese (Body mass index, BMI≥30) and non-obese women (BMI<30). Data were collected from case histories, and ante- and postnatal records at the tertiary hospital in Astana, Kazakhstan between January and February of 2008. Associations between pregnancy and delivery-related complications, outcomes, and maternal obesity were estimated as odds ratios (ORs) and 95% confidence intervals (CIs) using a logistic regression model. Women aged 30 years or more were at higher risk of obesity (OR=3.1, 95% CI=0.8–11.6) than women less than 30 years old. Multiparous women were also at higher risk of obesity (OR=4.1, 95% CI=0.9–19.6) than primiparous ones. Obese women were also more likely to have longer hospital stays of more than 10 days (OR=2.2, 95% CI=0.8–6.2), and were more prone to eclampsia/pre-eclampsia (OR=24.7, 95% CI=2.2–44.8), cesarean sections (OR=2.1, 95% CI=0.7–6.2), and abnormal labor (OR=8.1, 95% CI=1.0–63.8) compared to non-obese women. Neonatal complications such as pneumonia (OR=3.4, 95% CI=0.6–20.2) and fetal macrosomia (OR=2.2, 95% CI=0.6–8.0) were also more common among babies born to obese mothers. Congenital baby birth defects were strongly associated with maternal obesity (P=0.016). We concluded that maternal obesity is associated with increased risks of both maternal and neonatal complications, and that such risks increase with advanced age and parity of the mother. Hence, medical practices must take these complications into account by ensuring an adaptable and early management in order to improve mothers and their neonatal health. PMID:22515114

  17. The effect of pH and ion channel modulators on human placental arteries.

    PubMed

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

    2014-01-01

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

  18. Study on the Expressions of PHD and HIF in Placentas from Normal Pregnant Women and Patients with Preeclampsia

    PubMed Central

    Liu, Wei; Wang, Shu-Jun; Lin, Qi-De

    2014-01-01

    Objective: To investigate the relationship between oxygen sensitivity of trophoblast and hypoxia in preeclamptic placenta by the study on the expressions of hypoxia-inducible factor prolyl 4-hydroxylase (PHD) and hypoxia-inducible factor (HIF) in placentas from normal pregnant women and patients with pre-eclampsia. Methods: Subjects were chosen from the in-patients or the out-patients from May 2003 to May 2004. They were divided into 5 groups: early pregnancy group (EP), 13 cases; middle pregnancy group (MP), 9 cases; late pregnancy group (LP, or control group), 12 cases; preeclampsia (PE) group, 20 cases; gestational hypertension group (GH), 10 cases. The mRNA expressions of PHD-1 and -2 and -3 in placentas from all the subjects were assessed by in situ hybridization and Real-time PCR. The expressions of HIF-1α and -2α in placentas from different groups were assessed by immunohistochemistry and western blot. Results: PHD-1,-2 and -3 mRNA were mainly expressed in cytoplasm of trophoblast, especially strongly expressed in extravillous trophoblast. During the progress of pregnancy, the expression of PHD-1 increased significantly (R=0.616, P<0.001). The PHD-1mRNA expression in placentas from PE group decreased significantly compared with that from control group, P<0.05. A significant direct correlation between the PHD-1 mRNA expression in placentas from PE group and their placenta weight was found (R=0.457, P<0.05). The HIF-2α, not the HIF-1α expression, from PE group was significantly higher than that from control group, P<0.01; The HIF-2α expression in trophoblast from PE was inversely correlated to the date of the onset of the disease (R=-0.730, P<0.01). Conclusions: PHD-1 played an important role in hypoxic response pathway of trophoblast through modulating the level of HIF-2α. The overly activated hypoxic response pathway of trophoblast in preeclamptic placenta, which is manifested as the result of HIF-2α over-expression, is the key point to hypoxic

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

    PubMed Central

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

    2014-01-01

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

  20. Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis

    PubMed Central

    Simmonds, Mark; Bryant, Maria; Sheldon, Trevor A; Tuffnell, Derek; Golder, Su; Dunne, Fidelma; Lawlor, Debbie A

    2016-01-01

    Objectives To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified. Design Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials. Data sources Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts. Eligibility criteria for selecting studies Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome. Appraisal and data extraction Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools. Results 25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of

  1. Uric Acid as a predictor of adverse maternal and perinatal outcomes in women hospitalized with preeclampsia.

    PubMed

    Livingston, Joel R; Payne, Beth; Brown, Mark; Roberts, James M; Côté, Anne-Marie; Magee, Laura A; von Dadelszen, Peter

    2014-10-01

    Objectif : Bien qu’un taux sérique élevé d’acide urique soit couramment constaté chez les femmes qui présentent une prééclampsie, son utilité pour ce qui est de la prévision des issues indésirables a récemment été remise en question. Nous avions pour objectif d’analyser les données issues d’une importante cohorte de femmes présentant une prééclampsie, afin de déterminer l’utilité du taux sérique d’acide urique pour ce qui est de la prévision des issues indésirables maternelles et périnatales. Méthodes : Les données ont été tirées d’une étude prospective internationale toujours en cours qui porte sur des femmes hospitalisées présentant une prééclampsie (Pre-eclampsia Integrated Estimate of RiSk). Une régression logistique univariée a été utilisée pour déterminer la relation entre la concentration sérique en acide urique (tant absolue que corrigée en fonction de l’âge gestationnel [score Z]) et les issues indésirables (maternelles et périnatales). Des analyses ont été menées pour comparer des cohortes de femmes présentant une prééclampsie définie par l’hypertension et la protéinurie à des cohortes de femmes présentant une prééclampsie définie par l’hypertension et l’hyperuricémie. Résultats : Le score Z quant à l’acide urique était associé à des issues périnatales indésirables (RC, 1,5; IC à 95 %, 1,4 - 1,7) et comptait une estimation ponctuelle > 0,7 (surface sous la courbe de la fonction d’efficacité de l’observateur, 0,72; IC à 95 %, 0,69 - 0,74). Une association significative a également été constatée entre la concentration sérique en acide urique et des issues indésirables maternelles; toutefois, l’estimation ponctuelle était < 0,7. Aucune différence significative n’a été constatée entre les groupes « prééclampsie définie par l’hypertension et la protéinurie » et « prééclampsie définie par l’hypertension et l

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

    PubMed

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

    2011-12-01

    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.

  3. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME - PART 2.

    PubMed

    Goodman, Neil F; Cobin, Rhoda H; Futterweit, Walter; Glueck, Jennifer S; Legro, Richard S; Carmina, Enrico

    2015-12-01

    . Assessment of a woman with PCOS for infertility involves evaluating for preconceptional issues that may affect response to therapy or lead to adverse pregnancy outcomes and evaluating the couple for other common infertility issues that may affect the choice of therapy, such as a semen analysis. Women with PCOS have multiple factors that may lead to an elevated risk of pregnancy, including a high prevalence of IGT--a clear risk factor for gestational diabetes--and MetS with hypertension, which increases the risk for pre-eclampsia and placental abruption. Women should be screened and treated for hypertension and diabetes prior to attempting conception. Women should be counseled about weight loss prior to attempting conception, although there are limited clinical trial data demonstrating a benefit to this recommendation. Treatment for women with PCOS and anovulatory infertility should begin with an oral agent such as clomiphene citrate or letrozole, an aromatase inhibitor. PMID:26642102

  4. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians.

    PubMed

    Vayssière, C; Sentilhes, L; Ego, A; Bernard, C; Cambourieu, D; Flamant, C; Gascoin, G; Gaudineau, A; Grangé, G; Houfflin-Debarge, V; Langer, B; Malan, V; Marcorelles, P; Nizard, J; Perrotin, F; Salomon, L; Senat, M-V; Serry, A; Tessier, V; Truffert, P; Tsatsaris, V; Arnaud, C; Carbonne, B

    2015-10-01

    caesarean deliveries for FGR are not recommended (Grade C). In cases of vaginal delivery, fetal heart rate must be monitored continuously during labour, and any delay before intervention must be faster than in low-risk situations (professional consensus). Regional anaesthesia is preferred in trials of vaginal delivery, as in planned caesareans. Morbidity and mortality are higher in SGA newborns than in normal-weight newborns of the same gestational age (LE3). The risk of neonatal mortality is two to four times higher in SGA newborns than in non-SGA preterm and full-term infants (LE2). Initial management of an SGA newborn includes combatting hypothermia by maintaining the heat chain (survival blanket), ventilation with a pressure-controlled insufflator, if necessary, and close monitoring of capillary blood glucose (professional consensus). Testing for antiphospholipids (anticardiolipin, circulating anticoagulant, anti-beta2-GP1) is recommended in women with previous severe FGR (below third percentile) that led to birth before 34 weeks of gestation (professional consensus). It is recommended that aspirin should be prescribed to women with a history of pre-eclampsia before 34 weeks of gestation, and/or FGR below the fifth percentile with a probable vascular origin (professional consensus). Aspirin must be taken in the evening or at least 8h after awakening (Grade B), before 16 weeks of gestation, at a dose of 100-160mg/day (Grade A). PMID:26207980

  5. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME - PART 2.

    PubMed

    Goodman, Neil F; Cobin, Rhoda H; Futterweit, Walter; Glueck, Jennifer S; Legro, Richard S; Carmina, Enrico

    2015-12-01

    . Assessment of a woman with PCOS for infertility involves evaluating for preconceptional issues that may affect response to therapy or lead to adverse pregnancy outcomes and evaluating the couple for other common infertility issues that may affect the choice of therapy, such as a semen analysis. Women with PCOS have multiple factors that may lead to an elevated risk of pregnancy, including a high prevalence of IGT--a clear risk factor for gestational diabetes--and MetS with hypertension, which increases the risk for pre-eclampsia and placental abruption. Women should be screened and treated for hypertension and diabetes prior to attempting conception. Women should be counseled about weight loss prior to attempting conception, although there are limited clinical trial data demonstrating a benefit to this recommendation. Treatment for women with PCOS and anovulatory infertility should begin with an oral agent such as clomiphene citrate or letrozole, an aromatase inhibitor.

  6. In Vitro Fertilization and Multiple Pregnancies

    PubMed Central

    2006-01-01

    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