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Sample records for pre-eclampsia

  1. Pre-eclampsia.

    PubMed

    Mol, Ben W J; Roberts, Claire T; Thangaratinam, Shakila; Magee, Laura A; de Groot, Christianne J M; Hofmeyr, G Justus

    2016-03-01

    Pre-eclampsia affects 3-5% of pregnancies and is traditionally diagnosed by the combined presentation of high blood pressure and proteinuria. New definitions also include maternal organ dysfunction, such as renal insufficiency, liver involvement, neurological or haematological complications, uteroplacental dysfunction, or fetal growth restriction. When left untreated, pre-eclampsia can be lethal, and in low-resource settings, this disorder is one of the main causes of maternal and child mortality. In the absence of curative treatment, the management of pre-eclampsia involves stabilisation of the mother and fetus, followed by delivery at an optimal time. Although algorithms to predict pre-eclampsia are promising, they have yet to become validated. Simple preventive measures, such as low-dose aspirin, calcium, and diet and lifestyle interventions, show potential but small benefit. Because pre-eclampsia predisposes mothers to cardiovascular disease later in life, pregnancy is also a window for future health. A collaborative approach to discovery and assessment of the available treatments will hasten our understanding of pre-eclampsia and is an effort much needed by the women and babies affected by its complications. PMID:26342729

  2. [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

  3. Update in pre-eclampsia.

    PubMed

    Chanprapaph, Pharuhas

    2004-10-01

    Pre-eclampsia, formerly called pregnancy-induced hypertension, refers to the new onset of hypertension (SBP > or = 140 mmHg or DBP > or = 90 mmHg) and proteinuria (> or = 0.3 g protein in a 24-hour urine specimen or 1+ on dipstick) after 20 weeks of gestation in a previously normotensive women. It is a life-threatening, multi-organ involvement disease and remains the leading cause of maternal death. Its clinical manifestations are the result of generalized vasospasm, activation of the coagulation system, and changes in several humoral and autoregulatory systems related to volume and blood pressure control. Pre-eclampsia is responsible for high perinatal mortality and morbidity rates, primarily due to early termination of pregnancy. Fetus growth restriction, oligohyrdramnios and non-reassuring fetal status are the consequences of chronic placental hypoperfusion. Pre-eclampsia does not appear to accelerate fetal maturation, as once believed. Delivery remains the definitive treatment of choice for pre-eclampsia and should be timely. Cesarean section is not necessary and reserved for the obstetrical indications only. The expectant management may be considered for women remote from term (< 32 to 34 weeks of gestation) with stable and uncomplicated severe disease. The supportive management such as blood pressure control, seizure prevention, and fetal well-being assessment are also important to ensure the satisfactory outcome. To date, no screening test has been proved to be reliable and cost-effective. The prevention of pre-eclampsia with antioxidant therapy (vitamin C, E) has shown promise, but large, randomized trials are needed. Although controversy exists, calcium supplementation has shown no benefit in large trials, and most evidence suggests little or no benefit for low-dose aspirin as prevention in women in the low-risk category. PMID:21213502

  4. Severe hyponatraemia associated with pre-eclampsia.

    PubMed

    Anglim, Breffini; Levins, Kirk; Bussmann, Neidin; Imcha, Mendinaro

    2016-01-01

    Pre-eclampsia is a multisystem disorder with incidence rates ranging from 2% to 5%. Hyponatraemia is a rare complication of pre-eclampsia. A 41-year-old, para 0+1 in vitro fertilisation monochorionic diamniotic triplet pregnancy woman presented at 25 weeks with dyspnoea and general malaise. Her antenatal course was complicated by the diagnosis of intrauterine growth restriction in triplet one at 27 weeks of gestation. At 27+3 weeks gestation, she was diagnosed as having pre-eclampsia. Subsequent biochemical analysis demonstrated hyponatraemia with serum sodium falling steadily to 117 mmol/L over the next 19 days. She was admitted to intensive care unit for stabilisation of fulminant pre-eclampsia and severe hyponatraemia at 30+5 weeks of gestation. Hypertonic saline and intravenous labetolol were administered prior to delivery by caesarean section. She recovered well postdelivery with stabilisation of her blood pressure and normalisation of her sodium level to 135 mmol/L. Awareness and frequent monitoring of hyponatraemia should become an integral part of monitoring women with pre-eclampsia. PMID:27558187

  5. 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

  6. Pre-eclampsia: its pathogenesis and pathophysiolgy.

    PubMed

    Gathiram, P; Moodley, J

    2016-01-01

    Pre-eclampsia is a pregnancy-specific disorder that has a worldwide prevalence of 5-8%. It is one of the main causes of maternal and perinatal morbidity and mortality globally and accounts for 50 000-60 00 deaths annually, with a predominance in the low- and middle-income countries. It is a multi-systemic disorder however its aetiology, pathogenesis and pathophysiology are poorly understood. Recently it has been postulated that it is a two-stage disease with an imbalance between angiogenic and anti-antigenic factors. This review covers the latest thoughts on the pathogenesis and pathology of pre-eclampsia. The central hypothesis is that pre-eclampsia results from defective spiral artery remodelling, leading to cellular ischaemia in the placenta, which in turn results in an imbalance between anti-angiogenic and pro-angiogenic factors. This imbalance in favour of anti-angiogenic factors leads to widespread endothelial dysfunction, affecting all the maternal organ systems. In addition, there is foetal growth restriction (FGR). The exact aetiology remains elusive. PMID:27213853

  7. 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. PMID:25003612

  8. Serum uric acid and pre-eclampsia: an update.

    PubMed

    Bellomo, Gianni

    2012-06-01

    The association between uric acid (UA) and pre-eclampsia has been known for years, but the prognostic value of UA has been debated. This article will review recent evidences, evaluating UA as a prognostic factor for pre-eclampsia, both in the general population and in women with gestational hypertension, and as a predictor of disease severity and adverse maternal-fetal outcome. Finally, studies investigating UA as a putative pathogenic factor for pre-eclampsia are briefly mentioned. PMID:22894626

  9. Perinatal outcome of pre-eclampsia in parous women.

    PubMed

    Jian-Ying, Y; Xia, X

    2013-08-01

    Women with a second and recurrent pre-eclampsia pregnancy have more adverse pregnancy outcomes compared with women with pre-eclampsia in the first pregnancy. A retrospective cohort study was performed to compare the clinical characteristics and perinatal outcomes of pre-eclampsia in parous women who had complicated pre-eclampsia in previous pregnancies (n = 69) and uncomplicated pre-eclampsia in previous pregnancies (n = 312) from 2006 to 2010, in the Fujian Maternity and Child Health Hospital. No statistical significant differences were observed between the two groups in terms of: maternal age, admission blood pressure and BMI; prenatal care times, hospitalisation time, laboratory results and incident rates of complications. The incident and delivery weeks were earlier and the renal injury, caesarean section and small for gestational age (SGA) incidence rates were higher in recurrent pre-eclampsia women. Women with recurrent pre-eclampsia had adverse perinatal outcomes when compared with parous women with pre-eclampsia who had not had pre-eclampsia in prior pregnancies. PMID:23919854

  10. Association between Asymptomatic Bacteriuria and Pre-Eclampsia

    PubMed Central

    Rezavand, Negin; Veisi, Firooze; Zangane, Mrayam; Amini, Roghaye; Almasi, Afshin

    2016-01-01

    Asymptomatic bacteriuria is one of the most common and important bacterial infections during pregnancy and can result in progressive infections and endanger maternal as well as fetal health. In this study, we assessed the relationship between asymptomatic bacteriuria and pre-eclampsia. In this case-control study, pregnant women who presented to Imam Reza Hospital in Kermanshah in 2013-14 were studied. The minimum sample size was calculated as 125 pregnant women in each group with a total of 250 subjects. There were 125 women with pre-eclampsia and 125 women without pre-eclampsia (control group). Matching was done for age, gestational age, and parity between case and control groups. Matching was verified by a P value of 0.061 for maternal age and gestational age and 0.77 for parity. The statistical analyses were done by applying the chi-squared test and determining odds ratio (OR) for having bacteriuria in univariate logistic regression as well as multivariate regression with adjusting the effect of maternal age, gestational age, and parity. Pyuria and bacteriuria were significantly more common in pre-eclampsia group than in control group. The results showed that a significant association existed between asymptomatic bacteriuria and pre-eclampsia. The rate of asymptomatic bacteriuria was 6.8 times higher in women with pre-eclampsia compared to those without pre-eclampsia. Further studies are required for better clarification of association between asymptomatic bacteriuria and pre-eclampsia. PMID:26925912

  11. Assessment of Coagulation and Fibrinolysis in Pre-eclampsia

    PubMed Central

    Wood, S. M.; Burnett, D.; Picken, A. M.; Farrell, G. W.; Wolf, P.

    1974-01-01

    A method is described for distinguishing coagulation from fibrinolysis by three estimates of fibrinogen. This “fibrinogen series” together with plasma antithrombin and urinary urokinase have been compared in pregnant patients with venous thrombosis and pre-eclampsia. Evidence is presented for active coagulation during deterioration of the pre-eclampsia state and for enhanced fibrinolysis during improvement. PMID:4596483

  12. 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

  13. Combined Screening for Early Detection of Pre-Eclampsia

    PubMed Central

    Park, Hee Jin; Shim, Sung Shin; Cha, Dong Hyun

    2015-01-01

    Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers. PMID:26247944

  14. 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

  15. Monocytes and macrophages in pregnancy and pre-eclampsia.

    PubMed

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

    2014-01-01

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

  16. Pre-eclampsia and long-term maternal health

    PubMed Central

    Williams, David

    2012-01-01

    Pre-eclampsia is a syndrome of pregnancy, defined by the gestational-onset of hypertension and proteinuria, which resolves postpartum. This definition does not consider the variable multiorgan involvement of a syndrome that can include seizures, fulminating hepatic necrosis and a consumptive coagulopathy. These disparate clinical features are a consequence of an accelerated but transient metabolic syndrome with widespread maternal endothelial dysfunction and inflammation. A trigger to this maternal state is the relatively ischaemic placenta. As pregnancy progresses, the concentration of vaso-toxic factors released by the relatively ischaemic placenta gradually builds up in the maternal circulation. Those predisposed to endothelial dysfunction, e.g. women with risk factors for cardiovascular disease, are more sensitive to these placental derived factors and will develop pre-eclampsia before natural onset of labour. A woman's vulnerability to pre-eclampsia is therefore composed of a unique balance between her pre-existing maternal endothelial and metabolic health and the concentration of placental derived factors toxic to maternal endothelium. Delivery of the placenta remains the only cure. Years later, women who had pre-eclampsia are at increased risk of chronic hypertension, ischaemic heart disease, cerebrovascular disease, kidney disease, diabetes mellitus, thromboembolism, hypothyroidism and even impaired memory. This article describes how a brief, usually single episode of this acute pregnancy syndrome might both identify those vulnerable to chronic disease in later life and in some cases initiate chronic disease.

  17. Mitochondrial [dys]function; culprit in pre-eclampsia?

    PubMed

    McCarthy, Cathal Michael; Kenny, Louise Clare

    2016-07-01

    Mitochondria are extensively identified for their bioenergetic capacities; however, recently these metabolic hubs are increasingly being appreciated as critical regulators of numerous cellular signalling systems. Mitochondrial reactive oxygen species have evolved as a mode of cross-talk between mitochondrial function and physiological systems, to sustain equipoise and foster adaption to cellular stress. Redox signalling mediated by exaggerated mitochondrial-ROS (reactive oxygen species) has been incriminated in a plethora of disease pathologies. Excessive production of mitochondrial ROS is intrinsically linked to mitochondrial dysfunction. Furthermore, mitochondrial dysfunction is a key facilitator of oxidative stress, inflammation, apoptosis and metabolism. These are key pathogenic intermediaries of pre-eclampsia, hence we hypothesize that mitochondrial dysfunction is a pathogenic mediator of oxidative stress in the pathophysiology of pre-eclampsia. We hypothesize that mitochondrial-targeted antioxidants may restrain production of ROS-mediated deleterious redox signalling pathways. If our hypothesis proves correct, therapeutic strategies directly targeting mitochondrial superoxide scavenging should be actively pursued as they may alleviate maternal vascular dysfunction and dramatically improve maternal and fetal health worldwide. PMID:27252404

  18. Improving placental blood flow in pre-eclampsia with prostaglandin A1.

    PubMed

    Toppozada, M; Medhat, I; Sallam, H; Ismail, A A; el-Badawy, E S; Abd Rabbo, S

    1992-01-01

    Prostaglandin A1 is a potent hypotensive, peripheral vasodilator, a weak oxytocic, antiplatelet aggregator. It improves the renal hemodynamics. Its effect on placental circulation was evaluated (expressed as systolic/diastolic ratio and umbilical artery resistance index) in 20 women with severe pre-eclampsia and 10 normotensive pregnant women, by using the Doppler technique. Moreover, another 10 women with severe pre-eclampsia received dextrose 5% as a placebo for comparative purposes. Significant improvements in both parameters studied were observed in the women with severe pre-eclampsia. The beneficial changes differed significantly from the recorded values when using dextrose in pre-eclampsia or prostaglandin A1 in normotensive subjects. Such promising data add another important perspective to prostaglandin A1 in severe pre-eclampsia and may open up new avenues for its use in other situations with compromised placental flow. PMID:1315092

  19. [Gravidaprotective action of phenibut in experimental pre-eclampsia].

    PubMed

    Tiurenkov, I N; Perfilova, V N; Karamysheva, V I; Popova, T A; Lebedeva, S A; Mikhaĭlova, L I; Zhakupova, G A

    2014-01-01

    It was established that the replacement of drinking water by 1.8% NaCl solution in female rats during pregnancy causes experimental pre-eclampsia (EP), as evidenced by an increase in the blood pressure, proteinuria, and edema in the control group as compared to pregnant female rats with normal drinking regime. Animals with EP exhibited disturbance of vasodilating endothelial function, microcirculation disorder, and increased coagulation and thrombogenic potential of blood. In addition, the group with EP showed evidence of the activation of lipid peroxidation (LPO) due to lower activity of antioxidant enzymes. Daily oral administration ofphenibut (25 mg/kg) in female rats with EP during pregnancy prevents the increase in blood pressure and the severity of proteinuria and edemation. Phenibut improves the vasodilator and antithrombotic endothelial functions, increases uterine blood flow, improves microcirculation, limits LPO, and increases the activity of antioxidant enzymes. PMID:25668940

  20. Intrauterine device use and the risk of pre-eclampsia: a case–control study

    PubMed Central

    Parker, SE; Jick, SS; Werler, MM

    2016-01-01

    Objective To determine the association between intrauterine device (IUD) use, timing of removal prior to pregnancy, and the risk of pre-eclampsia. Design A case–control study within the Clinical Practice Research Datalink, UK. Setting Medical record database in the UK. Sample Cases of pre-eclampsia (n = 2744) were identified among pregnancies resulting in singleton deliveries from 1993 to 2010. Four controls, or pregnancies unaffected by pre-eclampsia, were matched to each case on maternal age, general practice, and year of delivery. Methods Data on IUD use were obtained from patient records. The odds ratios (ORs) for the association between IUD and pre-eclampsia were adjusted for covariates identified a priori, and analyses were stratified by BMI and number of prior deliveries. Main outcome measures Odds ratios (95% confidence intervals, 95% CIs) of pre-eclampsia in pregnancies among women with a history of IUD use, compared with women without a history of IUD use. Results Prior IUD use was associated with a reduced risk of pre-eclampsia (OR 0.76; 95% CI 0.58–0.98). The timing of removal in relation to the start of pregnancy showed an inverse association, with shorter intervals associated with a larger decrease in risk of pre-eclampsia. IUD removal within a year prior to pregnancy had an OR of 0.68 (95% CI 0.46–1.00). Among women with a prior delivery, the association between IUD use and pre-eclampsia was null. Conclusions Intrauterine device use is associated with a small decreased risk of pre-eclampsia, specifically if removed within the year prior to conception. PMID:25854682

  1. Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia.

    PubMed

    Southcombe, J H; Redman, C W G; Sargent, I L; Granne, I

    2015-09-01

    Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/β/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother. PMID:25693732

  2. 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

  3. Understanding Pre-Eclampsia Using Alzheimer's Etiology: An Intriguing Viewpoint.

    PubMed

    Cheng, Shi-Bin; Nakashima, Akitoshi; Sharma, Surendra

    2016-03-01

    Characterized by hypertension and proteinuria after the 20th week of gestation, pre-eclampsia (PE) is a major cause of maternal, fetal, and neonatal morbidity and mortality. Despite being recognized for centuries, PE still lacks a reliable, early means of diagnosis or prediction, and a safe and effective therapy. We have recently reported that the event of toxic protein misfolding and aggregation is a critical etiological manifestation in PE. Using comparative proteomic analysis of gestational age-matched sera from PE and normal pregnancy, we identified several proteins that appeared to be dysregulated in PE. Our efforts so far have focused on transthyretin (TTR), a transporter of thyroxine and retinol, and amyloid precursor protein whose aggregates were detected in the PE placenta. Based on these results and detection of TTR aggregates in sera from PE patients, we proposed that PE could be a disease of protein misfolding and aggregation. Protein misfolding and aggregation have long been linked with many neurodegenerative diseases such as Alzheimer's disease. However, linkage of protein misfolding and aggregation with the PE pathogenesis is a new and novel concept. This review aims to understand the roles of aggregated proteins in PE using the cues from the Alzheimer's etiology. PMID:26585303

  4. Pre-eclampsia and Cardiovascular Disease Risk Assessment in Women.

    PubMed

    Murphy, Malia S Q; Smith, Graeme N

    2016-07-01

    The underlying contributors of many cardiovascular events are often present decades before the onset of clinical symptoms, and the presence of risk factors in early life significantly influences risk of premature cardiovascular disease (CVD). The considerable burden of CVD in women and on health care resources necessitates an emphasis on prevention and early risk screening in women, before the development of the disease itself. The 2011 update to the American Heart Association's Effectiveness-Based Guidelines for the prevention of CVD acknowledges the contribution of the common pregnancy-related medical complications to a woman's cardiovascular risk, identifying pre-eclampsia (PE), gestational hypertension, and gestational diabetes mellitus as risk factors for heart disease and stroke. The aims of this review are to examine risk factors in young women and their role in the development of premature CVD, with particular attention paid to PE as a marker of a woman's cardiovascular risk. Current screening practices will be discussed, as will their influences on identifying and reducing cardiovascular risk and subsequent disease in younger women. PMID:27031056

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

    PubMed Central

    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

  6. 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

  7. Is Xanthine Oxidase, a Marker in Pre-eclampsia? A Case-Control Study

    PubMed Central

    Bambrana, Vanishree; Kotur, Pushpa P

    2015-01-01

    Introduction Pre-eclampsia is an obstetrics problem that affects multiple systemic functions and leads to the increased maternal and fetal morbidity and mortality. The objective of the study was to evaluate the plasma levels of Xanthine oxidase (XO) activity, uric acid and Nitric oxide (NO) levels in women with pre-eclampsia and normal pregnancy during antenatal and postpartum period. Materials and Methods A case control study was conducted in women with normal pregnancy (n=50) and pre-eclampsia (n=50) before and after delivery. XO activity, uric acid and NO levels were determined from samples at 30-39 weeks of gestation. The current study was conducted in association with Obstetrics and Gynecology Department of R.L. Jalappa Hospital and Research Center. The blood samples were analysed for assay of XO, uric acid and NO. The results were analysed by using SPSS software version 2013. P-value < 0.05 was considered as statistically significant. Results The plasma XO activity was elevated (p<0.001) in the pre-eclampsia compared to normotensive pregnant women before delivery and decreased after delivery (p<0.001) significantly. Uric acid level showed a significant increase in pre-eclampsia when compared to the control before delivery (p<0.001) however values were non-significant after delivery. Conclusion Placenta plays a key role in the pathophysiology of pre-eclampsia. Placenta removal leads to decrease trend of xanthine oxidase activity, uric acid and elevation of Nitric oxide as reversible changes in pre-eclampsia patients within 48 hours after delivery. PMID:26557508

  8. Maternal and fetal outcome in pre-eclampsia in a secondary care hospital in South India

    PubMed Central

    Aabidha, Parveen M.; Cherian, Anne G.; Paul, Emmanuel; Helan, Jasmin

    2015-01-01

    Background: Hypertensive disorders in pregnancy are one of the common causes for perinatal and maternal morbidity and mortality in developing countries. Pre-eclampsia is a condition which typically occurs after 20 weeks of gestation and has high blood pressure as the main contributing factor. The aim was to study the effects of pre-eclampsia on the mother and the fetus in rural South Indian population. Materials and Methods: This was a descriptive study conducted in a secondary level hospital in rural South India. A total of 1900 antenatal women were screened for pre-eclampsia during the period August 2010 to July 2011 to study the effects on the mother and fetus. Results: Of the 1900 women screened 93 were detected with pre-eclampsia in the study. Among these, 46.23% were primigravida, 30.1% belonged to socio-economic class 4 and 48.8% were among those with BMI 26–30. The incidence of severe pre-eclampsia was higher in the unregistered women. The most common maternal complication was antepartum hemorrhage (13.9%) and the most common neonatal complication was prematurity (23.65%). Conclusions: Treating anemia and improving socioeconomic status will improve maternal and neonatal outcome in pre-eclampsia. Antenatal care and educating women on significance of symptoms will markedly improve perinatal morbidity and mortality. Prematurity, growth restriction and low birth weight are neonatal complications to be anticipated and dealt with when the mother has pre-eclampsia. A good neonatal intensive care unit will help improve neonatal outcomes. PMID:25949977

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

    PubMed

    Pettit, Franziska; Brown, Mark A

    2012-01-01

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

  10. [Uric acid and purine plasma levels as plausible markers for placental dysfunction in pre-eclampsia].

    PubMed

    Escudero, Carlos; Bertoglia, Patricio; Muñoz, Felipe; Roberts, James M

    2013-07-01

    Uric acid is the final metabolite of purine break down, such as ATP, ADP, AMP, adenosine, inosine and hypoxanthine. The metabolite has been used broadly as a renal failure marker, as well as a risk factor for maternal and neonatal morbidity during pre-eclamptic pregnancies. High purine levels are observed in pre-eclamptic pregnancies, but the sources of these purines are unknown. However, there is evidence that pre-eclampsia (mainly severe pre-eclampsia) is associated with an increased release of cellular fragments (or microparticles) from the placenta to the maternal circulation. These in fact could be the substrate for purine metabolism. Considering this background, we propose that purines and uric acid are part of the same physiopathological phenomenon in pre-eclampsia (i.e., placental dysfunction) and could become biomarkers for placental dysfunction and postnatal adverse events. PMID:24356738

  11. 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.

  12. Uric acid: is it time to give up routine testing in management of pre-eclampsia?

    PubMed Central

    Talaulikar, Vikram Sinai; Shehata, Hassan

    2012-01-01

    Ever since it was first linked with the pathophysiology of pre-eclampsia, uric acid has been a routine test requested by many care-givers managing pregnant women with hypertensive disease of pregnancy for almost 100 years. Existing evidence however suggests that it has no definitive role in prediction, diagnosis or management of pre-eclampsia. We argue against routine uric acid testing in pregnancies complicated by hypertension not only because it has become a fruitless academic exercise but also because ceasing its routine use will ensure cost-savings for the health services.

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

    PubMed Central

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

    2014-01-01

    Introduction Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Methods Pre-eclampsia, which is more prevalent in resource-limited settings, contributes significantly to maternal, fetal and neonatal morbidity and mortality. However, the factors associated with these adverse outcomes are poorly understood in low resource settings. In this paper we examine the risk factors for adverse neonatal outcomes among women with pre-eclampsia at Mulago Hospital in Kampala, Uganda. Resuls Predictors of adverse neonatal outcomes were: preterm delivery (OR 5.97, 95% CI: 2.97-12.7) and severe pre-eclampsia (OR 5.17, 95% CI: 2.36-11.3). Conclusion Predictors of adverse neonatal outcomes among women with pre-eclampsia were preterm delivery and severe pre-eclampsia. Health workers need to identify women at risk, offer them counseling and, refer them if necessary to a hospital where they can be managed successfully. This may in turn reduce the neonatal morbidity and mortality associated with pre-eclampsia. PMID:24643210

  14. Differential Gene Expression Analysis of Placentas with Increased Vascular Resistance and Pre-Eclampsia Using Whole-Genome Microarrays

    PubMed Central

    Centlow, M.; Wingren, C.; Borrebaeck, C.; Brownstein, M. J.; Hansson, S. R.

    2011-01-01

    Pre-eclampsia is a pregnancy complication characterized by hypertension and proteinuria. There are several factors associated with an increased risk of developing pre-eclampsia, one of which is increased uterine artery resistance, referred to as “notching”. However, some women do not progress into pre-eclampsia whereas others may have a higher risk of doing so. The placenta, central in pre-eclampsia pathology, may express genes associated with either protection or progression into pre-eclampsia. In order to search for genes associated with protection or progression, whole-genome profiling was performed. Placental tissue from 15 controls, 10 pre-eclamptic, 5 pre-eclampsia with notching, and 5 with notching only were analyzed using microarray and antibody microarrays to study some of the same gene product and functionally related ones. The microarray showed 148 genes to be significantly altered between the four groups. In the preeclamptic group compared to notch only, there was increased expression of genes related to chemotaxis and the NF-kappa B pathway and decreased expression of genes related to antigen processing and presentation, such as human leukocyte antigen B. Our results indicate that progression of pre-eclampsia from notching may involve the development of inflammation. Increased expression of antigen-presenting genes, as seen in the notch-only placenta, may prevent this inflammatory response and, thereby, protect the patient from developing pre-eclampsia. PMID:21490790

  15. Maternal adiposity as an independent risk factor for pre-eclampsia: a meta-analysis of prospective cohort studies.

    PubMed

    Wang, Z; Wang, P; Liu, H; He, X; Zhang, J; Yan, H; Xu, D; Wang, B

    2013-06-01

    Studies investigating the association between maternal adiposity and risk of pre-eclampsia showed contradictory results. Therefore, we performed a meta-analysis of prospective cohort studies to estimate the effect of maternal adiposity on pre-eclampsia. We reviewed 1,286 abstracts and finally included 29 prospective cohort studies with 1,980,761 participants and 67,075 pre-eclampsia events. We pooled data with a random-effects model, and obtained risk estimates for five predetermined bodyweight groups: low, normal-weight (reference), overweight, obese and severely obese. In the cohort studies that unadjusted for pre-eclampsia risk factors, the pooled unadjusted relative risks (RR) with 95% confidence intervals (95%CI) for pre-eclampsia of overweight, obese and severely obese women were 1.58 (95% CI 1.44-1.72, P < 0.001), 2.68 (95% CI 2.39-3.01, P < 0.001) and 3.12 (95% CI 2.24-4.36, P < 0.001), respectively. In those cohorts that adjusted for pre-eclampsia risk factors, the pooled unadjusted RRs for pre-eclampsia of overweight, obese and severely obese women were 1.70 (95% CI 1.60-1.81, P < 0.001), 2.93 (95% CI 2.58-3.33, P < 0.001) and 4.14 (95% CI 3.61-4.75, P < 0.001), respectively. Sensitivity analysis showed maternal adiposity was associated with increased risk of pre-eclampsia in both nulliparous and multiparas women. In conclusion, overweight or obese pregnant women have a substantially increased risk of pre-eclampsia, and maternal adiposity is an independent risk factor of pre-eclampsia. PMID:23530552

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2011-10-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. S-Nitrosoglutathione improves haemodynamics in early-onset pre-eclampsia

    PubMed Central

    Everett, Thomas R; Wilkinson, Ian B; Mahendru, Amita A; McEniery, Carmel M; Garner, Stephen F; Goodall, Alison H; Lees, Christoph C

    2014-01-01

    Aims To determine the effects of in vivo S-nitrosoglutathione (GSNO) infusion on cardiovascular function, platelet function, proteinuria and biomarker parameters in early-onset pre-eclampsia. Methods We performed an open-label dose-ranging study of GSNO in early-onset pre-eclampsia. Six women underwent GSNO infusion whilst receiving standard therapy. The dose of GSNO was increased incrementally to 100 μg min−1 whilst maintaining blood pressure of >140/80 mmHg. Aortic augmentation index, aortic pulse wave velocity, blood pressure and maternal–fetal Doppler parameters were measured at each dose. Platelet P-selectin, protein-to-creatinine ratio and soluble anti-angiogenic factors were measured pre- and postinfusion. Results Augmentation index fell at 30 μg min−1 S-nitrosoglutathione (−6%, 95% confidence interval 0.6 to 13%), a dose that did not affect blood pressure. Platelet P-selectin expression was reduced [mean (interquartile range), 6.3 (4.9–7.6) vs. 4.1 (3.1–5.7)% positive, P = 0.03]. Soluble endoglin levels showed borderline reduction (P = 0.06). There was a borderline significant change in pre-to-postinfusion protein-to-creatinine ratio [mean (interquartile range), 0.37 (0.09–0.82) vs. 0.23 (0.07–0.49) g mmol−1, P = 0.06]. Maternal uterine and fetal Doppler pulsatility indices were unchanged. Conclusions In early-onset pre-eclampsia, GSNO reduces augmentation index, a biomarker of small vessel tone and pulse wave reflection, prior to affecting blood pressure. Proteinuria and platelet activation are improved at doses that affect blood pressure minimally. These effects of GSNO may be of therapeutic potential in pre-eclampsia, a condition for which no specific treatment exists. Clinical studies of GSNO in early-onset pre-eclampsia will determine whether these findings translate to improvement in maternal and/or fetal outcome. PMID:24627995

  5. 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

  6. 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

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

    PubMed

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

    2014-07-14

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

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

    PubMed

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

    2014-11-01

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

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

    PubMed Central

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

    2014-01-01

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

  10. Remifentanil in emergency caesarean section in pre-eclampsia complicated by thrombocytopenia and abnormal liver function.

    PubMed

    Johannsen, E K; Munro, A J

    1999-10-01

    We describe the use of remifentanil in a woman with severe pre-eclampsia who presented for emergency caesarean section. Remifentanil was effective in obtunding the hypertensive response to laryngoscopy and intubation. Previous studies have found no significant adverse effects of remifentanil on the neonate. With its short duration of action, the use of this new opioid has several potential advantages in the above setting. Further studies are required to explore the use of remifentanil as an adjunct to obstetric general anaesthesia. PMID:10520397

  11. Management of late preterm and early-term pregnancies complicated by mild gestational hypertension/pre-eclampsia.

    PubMed

    Sibai, Baha M

    2011-10-01

    Gestational hypertension/pre-eclampsia is the most frequent obstetrical complication, complicating 26%-29% of all gestations in nulliparous women. In general, the diagnosis of mild gestational hypertension/pre-eclampsia is made at 38 weeks or more in approximately 80% of cases. For many years, the optimal timing of delivery for patients with mild gestational hypertension/pre-eclampsia at 37-0/7 to 39-6/7 weeks was unclear. Recently, investigators of the HYPITAT (Pregnancy-induced hypertension and pre-eclampsia after 36 weeks: induction of labor versus expectant monitoring: A comparison of maternal and neonatal outcome, maternal quality of life and costs) randomized trial evaluated maternal and neonatal complications in patients at 36-40 weeks' gestation who were randomized to either induction of labor or expectant monitoring. The results of this trial revealed that induction of labor at or after 37-0 weeks was associated with lower rate of maternal complications without increased rates of either cesarean delivery or neonatal complications. In contrast, the optimum management for those with mild hypertension/pre-eclampsia with stable maternal and fetal conditions at 34-0/7 to 36-6/7 weeks remains uncertain. Therefore, there is urgent need for research to evaluate the reasons for late preterm birth in such women as well as for a randomized trial to evaluate the optimal timing for delivery in such patients. PMID:21962629

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

    PubMed

    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

  13. 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

  14. 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

  15. 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

  16. Comparison of serum trace element levels in patients with or without pre-eclampsia

    PubMed Central

    Farzin, Leila; Sajadi, Fattaneh

    2012-01-01

    Objective: In developing countries, nutritional deficiency of essential trace elements is a common health problem, particularly among pregnant women because of increased requirements of various nutrients. Accordingly, this study was initiated to compare trace elements status in women with or without pre-eclampsia. Materials and Methods: In this study, serum trace elements including zinc (Zn), selenium (Se), copper (Cu), calcium (Ca) and magnesium (Mg) were determined by using atomic absorption spectrometry (AAS) in 60 patients and 60 healthy subjects. Results: There was no significant difference in the values of Cu between two groups (P > 0.05). A significant difference in Zn, Se, Ca and Mg levels were observed between patients with pre-eclampsia and control group (P < 0.001, P<0.01, P<0.01 and P<0.001, respectively). Zn, Se, Ca and Mg levels were found to be 76.49 ± 17.62 μg/ dl, 8.82 ± 2.10 μg/ dl, 8.65 ± 2.14 mg/dl and 1.51 ± 0.34 mg/dl in Pre-eclamptic cases, and these values were found statistically lower compared to the controls (100.61 ± 20.12 μg/dl, 10.47 ± 2.78 μg/dl, 9.77 ± 3.02 mg/dl and 1.78 ± 0.27 mg/dl, respectively). While Cu levels were 118.28 ± 16.92 and 116.55 ± 15.23 μg/dl in the patients and the healthy subjects, respectively. In addition, no significant difference was found between two groups with respect to Hemoglobin Concentration (HbC) and Total White Blood Cell Count (TWBC) (P>0.05). Conclusion: Our findings indicate that the levels of Zn, Se, Ca and Mg are significantly altered in pregnant women with pre-eclampsia. This research shows that these deficiencies can not due to hemodilution. PMID:23825993

  17. Cord compression may rapidly influence the expression of placental angiogenic genes in pre-eclampsia.

    PubMed

    Järvenpää, J; Vuoristo, J T; Ukkola, O; Hirvikoski, P; Savolainen, E-R; Raudaskoski, T; Ryynänen, M

    2008-05-01

    Gene expression studies have demonstrated the altered expression level of placental angiogenesis related genes in severe pre-eclampsia (PE). In cord compression, the transportation of oxygen from the placenta to the fetus is blocked, and it is speculated that during blockade the originally hypoxic placenta may become hyperoxic. We compared the placental gene expression profiles of one pre-eclamptic patient with cord compression (the index patient) to the profiles of patients with PE and those of normal pregnancy controls (including one woman with cord compression). The gene expression of the cord compression PE patient resembled that observed in the normal pregnancies. We hypothesize that umbilical blockade may in a short period of time lead to placental hyperoxia, which in turn has an effect on angiogenic gene expression profile. PMID:18387671

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

    PubMed Central

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

    1998-01-01

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

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

    PubMed Central

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

    2006-01-01

    Background Pre-eclampsia is thought to have an important genetic component. Recently, pre-eclampsia has been associated in some studies with carriage of a common eNOS gene Glu298Asp polymorphism, a variant that leads to the replacement of glutamic acid by aspartic acid at codon 298. Method Healthy women with singleton pregnancies were recruited from 7 district general hospitals in London, UK. Women at high risk of pre-eclampsia were screened by uterine artery Doppler velocimetry at 22–24 weeks of gestation and maternal blood was obtained to genotype the eNOS Glu298Asp polymorphism. Odds ratios (OR) and 95%CI, using logistic regression methods, were obtained to evaluate the association between the Glu298Asp polymorphism and pre-eclampsia. A meta-analysis was then undertaken of all published studies up to November 2005 examining the association of eNOS Glu298Asp genotype and pre-eclampsia. Results 89 women with pre-eclampsia and 349 controls were included in the new study. The Glu298Asp polymorphism in a recessive model was not significantly associated with pre-eclampsia (adjusted-OR: 0.83 [95%CI: 0.30–2.25]; p = 0.7). In the meta-analysis, under a recessive genetic model (1129 cases & 2384 controls) women homozygous for the Asp298 allele were not at significantly increased risk of pre-eclampsia (OR: 1.28 [95%CI: 0.76–2.16]; p = 0.34). A dominant model (1334 cases & 2894 controls) was associated with no increase of risk of pre-eclampsia for women carriers of the Asp298 allele (OR: 1.12 [95%CI: 0.84–1.49]; p = 0.42). Conclusion From the data currently available, the eNOS Glu298Asp polymorphism is not associated with a significant increased risk of pre-eclampsia. However, published studies have been underpowered, much larger studies are needed to confirm or refute a realistic genotypic risk of disease, but which might contribute to many cases of pre-eclampsia in the population. PMID:16542455

  20. 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

  1. 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

  2. Endocan of the maternal placenta tissue is increased in pre-eclampsia

    PubMed Central

    Chang, Xinwen; Bian, Yiding; Wu, Yanming; Huang, Yajing; Wang, Kai; Duan, Tao

    2015-01-01

    Purpose: Pre-eclampsia (PE) is associated with intravascular inflammation and endothelial dysfunction. Interestingly, endocan plays a predominant role in the vascular inflammation and is considered as a biomarker of endothelial dysfunction. The aim of this study was to explore whether the endocan levels in serum and placenta were different between pregnant women with PE and the normal pregnancies. Methods: Total 22 patients, including 10 normal pregnant women and 12 patients with PE, were included in this study. Immunohistochemistry was used to evaluate the location of endocan. Then, the mRNA and protein levels of endocan in placenta were detected using qRT-PCR and western blotting. Serum endocan concentration was measured by ELISA. Results: Endocan protein was present in the human placenta, and the mRNA and protein levels of placenta tissues were elevated (P < 0.05) in the normal pregnancy with third trimester than those with first trimester. Furthermore, the expression of endocan mRNA and protein were increased in the placenta tissues of PE compared with in the normal pregnancy (P < 0.05); however, the endocan concentration of maternal serum did not have significant differences. Conclusion: Endocan may play a role in the progression of pregnancy and has a potential to be a new marker for the detective of PE. PMID:26823798

  3. 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

  4. Twin Chorionicity and the Risk of Hypertensive Disorders: Gestational Hypertension and Pre-eclampsia.

    PubMed

    Bartnik, Pawel; Kosinska-Kaczynska, Katarzyna; Kacperczyk, Joanna; Ananicz, Wojciech; Sierocińska, Aleksandra; Wielgos, Miroslaw; Szymusik, Iwona

    2016-08-01

    Twin gestation is known to be a risk factor for hypertensive disorders of pregnancy. However, the relationship between hypertensive disorders (pre-eclampsia (PE) and gestational hypertension (GH)) and chorionicity of twin pregnancy is unclear, and published data is conflicting. We decided to analyze the relationship between placentation and prevalence of hypertensive disorders. It was a retrospective cohort study. 312 twin pregnancies delivered between 2009 and 2014 were analyzed, 79 of which were monochorionic and 233 dichorionic. The occurrence of PE and GH was established according to American College of Obstetricians and Gynecologists' (ACOG) guidelines. Hypertensive disorders were diagnosed significantly more often in dichorionic than in monochorionic twin pregnancies (19.7% vs. 8.9%; OR = 2.53 95% CI 1.04-6.45; p = .03). PE occurred more frequently in DCP (13.3% vs. 3.8%; OR = 3.88 95% CI 1.09-16.46; p = .02). There were no differences between those two groups in the prevalence of GH (6.4% vs. 5.1%; p = .79). The logistic regression model for the occurrence of PE included chorionicity, mother's age lower than 18 or higher than 40, pre-gestational obesity, in vitro fertilization, primiparity, gestational age at delivery, gestational diabetes, and active smoking. It showed that dichorionicity remained an independent risk factor for PE (adjusted OR = 4.97.0 95% CI 1.06-23.38; p = .04). Dichorionicity seems to be a risk factor for PE but not for GH development. PMID:27160962

  5. Pre-eclampsia and the vascular endothelial growth factor: a new aspect.

    PubMed

    Liberis, A; Stanulov, G; Ali, E Chafouz; Hassan, A; Pagalos, A; Kontomanolis, E N

    2016-01-01

    Pre-eclampsia (PE) is a multi-system disorder of human gestation characterized by hypertension, proteinuria, and edema, which resolves with placental delivery. This disease affects 3-14% of all pregnancies worldwide and 5-8% in the USA. Furthermore PE remains one of the leading causes of maternal and neonatal mortality and morbidity worldwide. One of the most important goals in obstetrics is the early identification of the patient with an increased risk for PE. This paper unifies the essential and validated findings of past and current scientific investigation which encompass the relationship between PE and the vascular endothelial growth factor (VEGF). VEGF and its receptors have acquired great interest due to their vital role in neovascularization (vasculogenesis and angiogenesis) in a variety of physical and pathological processes such as the female reproductive cycle, PE, and tumorigenesis. VEGF is secreted in response to tissue hypoxia and endothelial cell damage. Alterations in the circulating levels of this factor may therefore identify those pregnancies with a high possibility of developing PE. This review will summarize the present authors' current understanding of the role of circulating VEGF in the pathogenesis, clinical diagnosis, and prediction of PE. PMID:27048010

  6. Early serum markers of pre-eclampsia: are we stepping forward?

    PubMed

    Laganà, Antonio Simone; Favilli, Alessandro; Triolo, Onofrio; Granese, Roberta; Gerli, Sandro

    2016-09-01

    Pre-eclampsia (PE) is a multisystemic disorder of human pregnancy, clinically characterized by hypertension, proteinuria, oedema and platelet aggregation; the syndrome includes vasoconstriction, resulting in maternal hypertension, reduced uterine blood flow, impairment of placenta-vascular endothelial integrity with increased permeability and activation of the coagulation cascade. The aetiopathogenesis of PE remains still unknown, although the central role played by the placenta seems to be crucial. To date, increasing efforts are trying to create an unique and robust biochemical pattern in serum to predict PE. Although the recent data, the definition of an early biochemical pattern in serum to predict PE is still far from reaching the final shape. This stalemate could be due, at least in part, to lack of robust and reproducible methodology (inclusion/exclusion criteria during enrolment, period and type of sample collection, type of sample analysis and interpretation of results) across the different studies. Considering these assumptions, the aim of the current paper is to review the available data about early serum markers of PE. PMID:26512423

  7. Association of anemia, pre-eclampsia and eclampsia with seasonality: a realist systematic review.

    PubMed

    Hlimi, Tina

    2015-01-01

    Seasonal patterns influencing maternal health have been documented globally and are of particular importance for women in developing countries who disproportionately suffer from anemia, pre-eclampsia and eclampsia. This paper adopts a realist systematic approach to investigate the maternal outcome of anemia and eclampsia in relation to seasonality. A review of 23 published studies shows a statistically significant link between these maternal disorders and seasonality in developing countries in Sub-Saharan Africa and Central and South Asia. Anemia and eclampsia tend to decrease during the dry season, only to increase with greater rainfall, low and cold temperatures. Numerous studies suggest that the seasonality of anemia and eclampsia is associated with changes in malaria transmission. This was observed during the rainy season, suggesting a potential seasonal relationship with malaria as a driver of these disorders in Sub-Saharan Africa. Anemia and eclampsia were principally exacerbated among primigravidae and young women. Food insecurity, access to antenatal care, poverty, and environmental factors may also play a crucial role in the predisposition to these disorders. More research is required to identify the seasonal link between malaria and eclampsia particularly as climate change may exacerbate the rate of the disorders in tropical and sub-tropical areas. PMID:25555235

  8. 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

  9. Syncytiotrophoblast Extracellular Vesicles from Pre-Eclampsia Placentas Differentially Affect Platelet Function

    PubMed Central

    Tannetta, Dionne S.; Hunt, Kathryn; Jones, Chris I.; Davidson, Naomi; Coxon, Carmen H.; Ferguson, David; Redman, Christopher W.; Gibbins, Jonathan M.; Sargent, Ian L.; Tucker, Katherine L.

    2015-01-01

    Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition. PMID:26551971

  10. 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

  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. The use of pulse wave velocity in predicting pre-eclampsia in high-risk women.

    PubMed

    Katsipi, Irene; Stylianou, Kostas; Petrakis, Ioannis; Passam, Andrew; Vardaki, Eleftheria; Parthenakis, Fragkiskos; Makrygiannakis, Antonios; Daphnis, Eugene; Kyriazis, John

    2014-08-01

    In this study, we evaluated the diagnostic utility of pulse wave velocity (PWV) alone or in combination with other diagnostic markers in predicting pre-eclampsia (PE) in high-risk women. Pregnant women at high risk for PE were recruited between 22 and 26 weeks of gestation and were assessed for (a) PWV, (b) serum levels of the placental soluble fms-like tyrosine kinase 1 (sFlt-1) protein and uric acid and (c) 24-h urinary protein and calcium excretion. Sensitivities and specificities were derived from receiver operating characteristic curves. Of 118 women recruited, 11 and 10 women developed early-onset PE (<34 weeks) and late-onset PE (≥34 weeks), respectively. Of the five diagnostic markers tested, PWV showed the highest detection rate for all cases (21) of PE (81%) and for early-onset PE (82%) at a fixed 10% false-positive rate (FPR), and when combined with sFlt-1, these figures increased to 90% and 92%, respectively. Despite the reduced ability of PWV to predict late-onset PE (detection rate 20%), the combination of PWV with sFlt-1 achieved a detection rate of 50% at a fixed 10% FPR. A suggested cutoff value of 9 m/s for PWV resulted in optimal sensitivity (91%) and specificity (86%) for predicting early-onset PE. This study is the first to show that PWV may be a potentially promising predictor of early-onset PE in women at high risk for PE. The combination of PWV with sFlt-1 may further improve the screening efficacy for predicting PE. PMID:24621469

  13. 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. PMID:26733722

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Placental microRNA expression in pregnancies complicated by superimposed pre-eclampsia on chronic hypertension

    PubMed Central

    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.

    2016-01-01

    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

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

    PubMed

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

    2013-03-01

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

  1. 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

  2. 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

  3. 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

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

    PubMed Central

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

    2014-01-01

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

  5. Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

    PubMed Central

    Bartsch, Emily; Medcalf, Karyn E; Park, Alison L

    2016-01-01

    Objective To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design Systematic review and meta-analysis of cohort studies. Data sources PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy. PMID:27094586

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

    PubMed Central

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

    2011-01-01

    Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. Design Randomised, blinded, placebo controlled clinical trial. Setting Tertiary public hospital in Mexico City. Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy. Main outcome measure Development of pre-eclampsia/eclampsia. Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14). Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be

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

    PubMed Central

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

    2013-01-01

    Introduction Pre-eclampsia is a common pregnancy condition affecting between 3% and 7% of women. Unfortunately, the exact pathophysiology of the disease is unknown and as such there are no effective treatments that exist notwithstanding prompt delivery of the fetus and culprit placenta. As many cases of pre-eclampsia occur in preterm pregnancies, it remains a significant cause of maternal and perinatal morbidity and mortality. Recently, in vitro and animal studies have highlighted the potential role of antioxidants in mitigating the effects of the disease. Melatonin is a naturally occurring antioxidant hormone and provides an excellent safety profile combined with ease of oral administration. We present the protocol for a phase I pilot clinical trial investigating the efficacy and side effects of maternal treatment with oral melatonin in pregnancies affected by preterm pre-eclampsia. Methods and analysis We propose undertaking a single-arm open label clinical trial recruiting 20 women with preterm pre-eclampsia (24+0–35+6 weeks). We will take baseline measurements of maternal and fetal well-being, levels of oxidative stress, ultrasound Doppler studies and other biomarkers of pre-eclampsia. Women will then be given oral melatonin (10 mg) three times daily until delivery. The primary outcome will be time interval between diagnosis and delivery compared to historical controls. Secondary outcomes will compare the baseline measurements previously mentioned with twice-weekly measurements during treatment and then 6 weeks postpartum. Ethics and dissemination Ethical approval has been obtained from Monash Health Human Research Ethics Committee B (HREC 13076B). Data will be presented at international conferences and published in peer-reviewed journals. Trial registration number ACTRN12613000476730 (ANZCTR). PMID:24056493

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

    PubMed Central

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

    2008-01-01

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

  11. Usability and Feasibility of PIERS on the Move: An mHealth App for Pre-Eclampsia Triage

    PubMed Central

    Cloete, Garth; Dunsmuir, Dustin T; Payne, Beth A; von Dadelszen, Peter; Dumont, Guy A; Ansermino, J Mark

    2015-01-01

    Background Pre-eclampsia is one of the leading causes of maternal death and morbidity in low-resource countries due to delays in case identification and a shortage of health workers trained to manage the disorder. Pre-eclampsia Integrated Estimate of RiSk (PIERS) on the Move (PotM) is a low cost, easy-to-use, mobile health (mHealth) platform that has been created to aid health workers in making decisions around the management of hypertensive pregnant women. PotM combines two previously successful innovations into a mHealth app: the miniPIERS risk assessment model and the Phone Oximeter. Objective The aim of this study was to assess the usability of PotM (with mid-level health workers) for iteratively refining the system. Methods Development of the PotM user interface involved usability testing with target end-users in South Africa. Users were asked to complete clinical scenario tasks, speaking aloud to give feedback on the interface and then complete a questionnaire. The tool was then evaluated in a pilot clinical evaluation in Tygerberg Hospital, Cape Town. Results After ethical approval and informed consent, 37 nurses and midwives evaluated the tool. During Study 1, major issues in the functionality of the touch-screen keyboard and date scroll wheels were identified (total errors n=212); during Study 2 major improvements in navigation of the app were suggested (total errors n=144). Overall, users felt the app was usable using the Computer Systems Usability Questionnaire; median (range) values for Study 1 = 2 (1-6) and Study 2 = 1 (1-7). To demonstrate feasibility, PotM was used by one research nurse for the pilot clinical study. In total, more than 500 evaluations were performed on more than 200 patients. The median (interquartile range) time to complete an evaluation was 4 min 55 sec (3 min 25 sec to 6 min 56 sec). Conclusions By including target end-users in the design and evaluation of PotM, we have developed an app that can be easily integrated into health

  12. Effect of calcium-vitamin D supplementation on metabolic profiles in pregnant women at risk for pre-eclampsia: a randomized placebo-controlled trial.

    PubMed

    Asemi, Zatollah; Tabassi, Zohreh; Heidarzadeh, Zahra; Khorammian, Hassan; Sabihi, Sima-Sadat; Samimi, Mansooreh

    2012-04-01

    Increased metabolic profiles during pregnancy are associated with an increased risk of maternal and neonatal morbidity and remain a significant medical challenge. To our knowledge, no reports are available indicating the effects of calcium-vitamin D supplementation on metabolic profiles among pregnant women at risk for pre-eclampsia. This study was designed to determine the effects of consumption calcium-vitamin D supplements on metabolic profiles among Iranian pregnant women at risk for pre-eclampsia. This randomized single-blind controlled clinical trial was performed among 49 pregnant women at risk for pre-eclampsia, primigravida, aged 18-35 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to consume the placebo (n = 25) or calcium-vitamin D supplements (n = 24) for 9 weeks. Calcium-vitamin D supplements were containing 500 mg carbonate calcium plus 200 IU vitamin D3. Fasting blood samples were taken at baseline and after 9 week intervention to measures of Fasting Plasma Glucose (FPG) and serum lipid profiles. Consumption of calcium-vitamin D supplements resulted in decreased FPG and serum triglycerides levels as compared to the placebo (-9.1 vs. 0.5 mg dL(-1); p = 0.03, -11.7 vs. 49.9 mg dL(-1); p = 0.001, respectively). No significant differences were found comparing calcium-vitamin D supplements and the placebo in terms of their effect on serum total-, HDL-, LDL-cholesterol levels. Within-group differences in the placebo group revealed a significant increase in serum triglycerides levels (+49.9 mg dL(-1), p < 0.0001). In conclusion, consumption of calcium-vitamin D supplements for 9 weeks during pregnancy among pregnant women at risk for pre-eclampsia resulted in decreased FPG and serum triglycerides levels as compared to the placebo group, but could not affect serum total-, HDL-, LDL-cholesterol levels. PMID:24163957

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

    PubMed

    Johnson, Matthew P; Brennecke, Shaun P; East, Christine E; Dyer, Thomas D; Roten, Linda T; Proffitt, J Michael; Melton, Phillip E; Fenstad, Mona H; Aalto-Viljakainen, Tia; Mäkikallio, Kaarin; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K

    2013-07-01

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

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

    PubMed

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

    2015-01-01

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

  15. A pre-eclampsia-associated Epstein-Barr virus antibody cross-reacts with placental GPR50.

    PubMed

    Elliott, Serra E; Parchim, Nicholas F; Kellems, Rodney E; Xia, Yang; Soffici, Alex R; Daugherty, Patrick S

    2016-07-01

    To characterize antibody specificities associated with pre-eclampsia (PE), bacterial displayed peptide library screening and evolution was applied to identify peptide epitopes recognized by plasma antibodies present in women with PE near the time of delivery. Pre-eclamptic women exhibited elevated IgG1 titers towards a peptide epitope KRPSCIGCK within the Epstein-Barr virus nuclear antigen 1 (EBNA-1). EBNA-1 epitope antibodies cross-reacted with a similar epitope within the extracellular N-terminus of the human G protein-coupled receptor, GPR50, expressed in human placental tissue and immortalized placental trophoblast cells. We observed increased antibody binding activity to epitopes from EBNA-1 and GPR50 among women with PE (n=42) compared to healthy-outcome pregnancies (n=43) and nulligravid samples (n=21). The EBNA-1 peptide potently blocked binding of the PE-associated antibody to the GPR50 epitope (IC50=58-81pM). These results reveal the existence of molecular mimicry between EBNA-1 and placental GPR50, supporting a mechanism for IgG1 deposition in the pre-eclamptic placenta. PMID:27181993

  16. Innate and adaptive immune interactions at the fetal-maternal interface in healthy human pregnancy and pre-eclampsia.

    PubMed

    Hsu, Peter; Nanan, Ralph Kay Heinrich

    2014-01-01

    Maternal immune tolerance of the fetus is indispensable for a healthy pregnancy outcome. Nowhere is this immune tolerance more important than at the fetal-maternal interface - the decidua, the site of implantation, and placentation. Indeed, many lines of evidence suggest an immunological origin to the common pregnancy-related disorder, pre-eclampsia. Within the innate immune system, decidual NK cells and antigen presenting cells (including dendritic cells and macrophages) make up a large proportion of the decidual leukocyte population, and are thought to modulate vascular remodeling and trophoblast invasion. On the other hand, within the adaptive immune system, Foxp3(+) regulatory T cells are crucial for ensuring immune tolerance toward the semi-allogeneic fetus. Additionally, another population of CD4(+)HLA-G(+) suppressor T cells has also been identified as a potential player in the maintenance of immune tolerance. More recently, studies are beginning to unravel the potential interactions between the innate and the adaptive immune system within the decidua, that are required to maintain a healthy pregnancy. In this review, we discuss the recent advances exploring the complex crosstalk between the innate and the adaptive immune system during human pregnancy. PMID:24734032

  17. Ultrasound Microbubble-Mediated Delivery of Integrin-Linked Kinase Gene Improves Endothelial Progenitor Cells Dysfunction in Pre-Eclampsia

    PubMed Central

    Cui, Kai; Yan, Ting; Luo, Qingqing; Zheng, Yanfang; Liu, Xiaoxia; Huang, Xiaoyu

    2014-01-01

    Pre-eclampsia (PE) is a specific vascular complication in pregnancy whose precise mechanism is still unclear. We hypothesized that endothelial progenitor cells (EPCs), the precursor of endothelial cells, might be impaired in patients with PE and hold a great promise for the treatment of PE. In the present study, we analyzed the EPCs number and expression of integrin-linked kinase (ILK) in PE patients. We confirmed that both EPCs number and ILK expression were diminished in PE patients. Next, we transfected EPCs with ILK gene using ultrasonic microbubble technique (UMT) for the first time, as UMT is a novel type of gene transfer technology showing promising applications in stem cells apart from EPCs. To further investigate the transfection efficiency of UMT, RT-PCR analysis and western blot were used to examine the messenger RNA (mRNA) and protein level of ILK. After transfection of the ILK gene, EPCs function was tested to illustrate the role of ILK in cell proliferation, apoptosis, migration, and secretion. The results of the in vitro study suggested that UMT, a novel gene delivery system, could be considered a potent physical method for EPCs transfection. Moreover, the growth and angiogenetic properties of EPCs are enhanced by introducing ILK. This study may afford a new trend for EPCs transfection and gene therapy in PE. PMID:24564279

  18. Placental hypoxia, endoplasmic reticulum stress and maternal endothelial sensitisation by sFLT1 in pre-eclampsia

    PubMed Central

    Charnock-Jones, D. Stephen

    2016-01-01

    The human placenta is a multifunctional organ that grows and adapts to increasing fetal demand and fluctuations in the intrauterine environment. It is subjected to physiological and pathological changes in local oxygenation, both of which induce adaptive changes. In early pregnancy a low PO2 is the normal physiological state and this is not hypoxic—there is no perturbation of ATP/ADP ratios and, if the placenta is sampled very rapidly, little HIF1α is detected in human first-trimester placental villi. Nonetheless, HIF1α can be increased and activated by culture. However, the placenta does show evidence of stress under pathological conditions. For example, in cases of pre-eclampsia where delivery by caesarean section is necessitated for maternal well-being before 34 weeks’ gestation, placental endoplasmic reticulum stress is evident. Cases delivered ≥34 weeks are indistinguishable from normal term controls. One consequence of placental stress, whether oxidative, related to the endoplasmic reticulum or immunological, is that factors are released into the maternal circulation, which affects the endothelium, leading to the maternal syndrome. Soluble FLT1 may contribute directly to this and the most likely mechanism is direct action on the maternal endothelium. sFLT1 is able to form a heterodimer with cell surface VEGF receptors and is therefore able to have a dominant negative effect (in addition to acting as a competitive inhibitor by simply binding vascular endothelial growth factor A [VEGFA] and placental growth factor [PlGF]). This leads in vitro to the sensitisation of endothelial cells to low levels of TNFα. PMID:26228018

  19. 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

  20. Placental hypoxia, endoplasmic reticulum stress and maternal endothelial sensitisation by sFLT1 in pre-eclampsia.

    PubMed

    Charnock-Jones, D Stephen

    2016-04-01

    The human placenta is a multifunctional organ that grows and adapts to increasing fetal demand and fluctuations in the intrauterine environment. It is subjected to physiological and pathological changes in local oxygenation, both of which induce adaptive changes. In early pregnancy a low PO2 is the normal physiological state and this is not hypoxic-there is no perturbation of ATP/ADP ratios and, if the placenta is sampled very rapidly, little HIF1α is detected in human first-trimester placental villi. Nonetheless, HIF1α can be increased and activated by culture. However, the placenta does show evidence of stress under pathological conditions. For example, in cases of pre-eclampsia where delivery by caesarean section is necessitated for maternal well-being before 34 weeks' gestation, placental endoplasmic reticulum stress is evident. Cases delivered ≥34 weeks are indistinguishable from normal term controls. One consequence of placental stress, whether oxidative, related to the endoplasmic reticulum or immunological, is that factors are released into the maternal circulation, which affects the endothelium, leading to the maternal syndrome. Soluble FLT1 may contribute directly to this and the most likely mechanism is direct action on the maternal endothelium. sFLT1 is able to form a heterodimer with cell surface VEGF receptors and is therefore able to have a dominant negative effect (in addition to acting as a competitive inhibitor by simply binding vascular endothelial growth factor A [VEGFA] and placental growth factor [PlGF]). This leads in vitro to the sensitisation of endothelial cells to low levels of TNFα. PMID:26228018

  1. 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

  2. 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

  3. 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

  4. Differentiation of ICOS+ and ICOS- recent thymic emigrant regulatory T cells (RTE T regs) during normal pregnancy, pre-eclampsia and HELLP syndrome.

    PubMed

    Wagner, M I; Jöst, M; Spratte, J; Schaier, M; Mahnke, K; Meuer, S; Zeier, M; Steinborn, A

    2016-01-01

    Two different subsets of naturally occurring regulatory T cells (nTregs), defined by their expression of the inducible co-stimulatory (ICOS) molecule, are produced by the human thymus. To examine the differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) recent thymic emigrant (RTE) T regs during normal pregnancy and in the presence of pre-eclampsia or haemolysis elevated liver enzymes low platelet (HELLP)-syndrome, we used six-colour flow cytometric analysis to determine the changes in the composition of the ICOS(+) and ICOS(-) T reg pools with CD45RA(+) CD31(+) RTE T regs, CD45RA(+) CD31(-) mature naive (MN) T regs, CD45RA(-) CD31(+) and CD45RA(-) CD31(-) memory Tregs. With the beginning of pregnancy until term, we observed a strong differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE, but not CD45RA(+) CD31(-) MN T regs, into CD45RA(-) CD31(-) memory T regs. At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS(+) CD45RA(-) CD31(-) memory T regs. However, in the presence of pre-eclampsia, there was a significantly increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs into CD45RA(-) CD31(+) memory T regs, wherein the lacking differentiation into CD45RA(-) CD31(-) memory T regs was partially replaced by the increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(-) MN Tregs into CD45RA(-) CD31(-) memory T regs. In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA(-) CD31(-) MN T regs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS(+) and ICOS(-) T regs, which were shown to be significantly less suppressive in pre-eclampsia patients, but not in HELLP syndrome patients. Hence, our findings propose that the regular differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs ensures a healthy pregnancy course, while their disturbed differentiation is

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

    PubMed

    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 AND 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

  6. 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

  7. 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

  8. Predicting the risk of pre-eclampsia between 11 and 13 weeks gestation by combining maternal characteristics and serum analytes, PAPP-A and free β-hCG

    PubMed Central

    GOETZINGER, Katherine R.; SINGLA, Ashima; GERKOWICZ, Sabrina; DICKE, Jeffrey M.; GRAY, Diana L.; ODIBO, Anthony O.

    2011-01-01

    Objective To determine if a simplified model for predicting pre-eclampsia can be developed by combining first trimester serum analytes, PAPP-A and free β-hCG, and maternal characteristics. Methods A retrospective cohort study of patients seen for first-trimester aneuploidy screening from 2003–2009. The 5th, 10th, 90th and 95th percentiles for the analyte-MoMs for our population were determined and evaluated for association with pre-eclampsia. Univariate and backward stepwise logistic regression analyses were performed and the area under the ROC curves (AUC) used to determine the best models for predicting pre-eclampsia. Results Among 4,020 women meeting the inclusion criteria, outcome data was available for 3,716 (93%). There were 293 cases of pre-eclampsia. The final model identified a history of pre-gestational diabetes (aOR 2.6, 95% CI 1.7–3.9), chronic hypertension (aOR 2.6, 95% CI 1.7–3.9), maternal BMI >25 (aOR 2.5, 95% CI 1.9–3.4), African American race (aOR 1.8, 95% CI 1.3–2.6), and PAPP-A MoM <10th percentile (aOR 1.6, 95% CI 1.1–2.4) to be significant predictors of pre-eclampsia. (AUC= 0.70, 95% CI 0.65–0.72) Conclusion Low first-trimester PAPP-A levels are associated with the development of pre-eclampsia; however, the model was only modestly efficient in its predictive ability. PMID:20936638

  9. Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol

    PubMed Central

    Cluver, Catherine A; Walker, Susan P; Mol, Ben W; Theron, Gerard B; Hall, David R; Hiscock, Richard; Hannan, N; Tong, S

    2015-01-01

    Introduction Pre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than delivery. A drug that can quench the disease process could be useful to treat early onset pre-eclampsia, as it could allow pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have generated preclinical data to show esomeprazole, a proton pump inhibitor used for gastric reflux, has potent biological effects that makes it a worthwhile therapeutic candidate. Esomeprazole potently decreases soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin secretion from placenta and endothelial cells, and has biological actions to mitigate endothelial dysfunction and oxidative stress. Methods and analysis We propose undertaking a phase II, double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. We will recruit 120 women (gestational age of 26+0 to 31+6 weeks) who will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. Secondary outcomes include maternal, fetal and neonatal composite and individual outcomes. Maternal outcomes include maternal death, eclampsia, pulmonary oedema, severe renal impairment, cerebral vascular events and liver haematoma or rupture. Neonatal outcomes include neonatal death within 6 weeks after the due date, intraventricular haemorrhage, necrotising enterocolitis and bronchopulmonary dysplasia. We will examine whether esomeprazole can decrease serum sFlt-1 and soluble endoglin levels and we will record the safety of esomeprazole in these pregnancies. Ethics and dissemination This study has ethical approval (Protocol V.2.4, M14/09/038, Federal Wide assurance Number 00001372, IRB

  10. 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

  11. 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

  12. 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. PMID:25832854

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

    PubMed

    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

  14. 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

  15. The Effect of High Dose Folic Acid throughout Pregnancy on Homocysteine (Hcy) Concentration and Pre-Eclampsia: A Randomized Clinical Trial

    PubMed Central

    Sayyah-Melli, Manizheh; Ghorbanihaghjo, Amir; Alizadeh, Mahasti; Kazemi-Shishvan, Maryamalsadat; Ghojazadeh, Morteza; Bidadi, Sanam

    2016-01-01

    Pre-eclampsia is a pregnancy-related multi-systemic hypertensive disorder and affects at least 5% of pregnancies. This randomized clinical trial aimed at assessing the effect of low doses and high doses of folic acid on homocysteine (Hcy) levels, blood pressure, urea, creatinine and neonatal outcome. A randomized clinical trial was done at Alzahra Teaching Hospital, Tabriz University of Medical Sciences from April 2008 to March 2013. Four-hundred and sixty nulliparous pregnant women were randomly assigned into two groups. Group 1 (n = 230) received 0.5 mg of folic acid and group 2 (n = 230) received 5 mg of folic acid per daily. They were followed until delivery. Blood pressure and laboratory changes, including plasma Hcy levels, were measured and compared between the groups. Homocysteine concentrations were significantly higher at the time of delivery in group 1 (13.17±3.89 μmol/l) than in group 2 (10.31±3.54, μmol/l) (p<0.001). No statistically significant differences were observed in systolic and diastolic blood pressure (p = 0.84 and 0.15, respectively). Birth weight was significantly higher in group 2 (p = 0.031) and early abortion was significantly higher in group 1 than group 2 (p = 0.001). This study has provided evidence that a high dosage of folic acid supplements throughout pregnancy reduces Hcy concentrations at the time of delivery. Trial Registration: Iranian Registry of Clinical Trials IRCT201402175283N9 PMID:27166794

  16. 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

  17. 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

  18. Fish Oil Supplementation does not Reduce Risks of Gestational Diabetes Mellitus, Pregnancy-Induced Hypertension, or Pre-Eclampsia: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Chen, Bing; Ji, Xinran; Zhang, Lei; Hou, Zhaohui; Li, Chundong; Tong, Ying

    2015-01-01

    Background The effects of gestational supplementation with fish oil on risks for gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and pre-eclampsia (PE) have not been confirmed. In this study, a meta-analysis was performed to evaluate the effect of fish oil supplementation on these gestational complications. Material/Methods Randomized controlled human trials that investigated the effects of fish oil supplementation in pregnant women were identified by a systematic search of Medline, Embase, and Cochrane’s Library, and references of related reviews and studies up to December 2014. Relative risks (RRs) for GDM, PIH, and PE were the outcomes of interest. Fixed-effects or random-effects models were applied according to the heterogeneity. Results Thirteen comparisons from 11 published articles, including more than 5000 participants, were included. The results showed that fish oil supplementation was not associated with reduced risks for GDM (RR=1.06, 95% confidence interval [CI]: 0.85–1.32, p=0.60), PIH (RR=1.03, 95% CI: 0.89–1.20, p=0.66), or PE (RR=0.93, 95% CI: 0.74–1.16, p=0.51). No statistically significant heterogeneity was detected for the comparison of each outcome. The effects of fish oil on these gestational complications were consistent between women with low-risk and high-risk pregnancies. Conclusions Gestational supplementation with fish oil during the second or third trimester of pregnancy is not associated with reduced risks for GDM, PIH, or PE. Other possible benefits of fish oil supplementation during pregnancy warrant further evaluation. PMID:26256041

  19. 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

  20. 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

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

    PubMed Central

    Daniels, Karen; Lewin, Simon

    2008-01-01

    Background Few empirical studies of research utilisation have been conducted in low and middle income countries. This paper explores how research information, in particular findings from randomised controlled trials and systematic reviews, informed policy making and clinical guideline development for the use of magnesium sulphate in the treatment of eclampsia and pre-eclampsia in South Africa. Methods A qualitative case-study approach was used to examine the policy process. This included a literature review, a policy document review, a timeline of key events and the collection and analysis of 15 interviews with policy makers and academic clinicians involved in these policy processes and sampled using a purposive approach. The data was analysed thematically and explored theoretically through the literature on agenda setting and the policy making process. Results Prior to 1994 there was no national maternal care policy in South Africa. Consequently each tertiary level institution developed its own care guidelines and these recommended a range of approaches to the management of pre-eclampsia and eclampsia. The subsequent emergence of new national policies for maternal care, including for the treatment of pre-eclampsia and eclampsia, was informed by evidence from randomised controlled trials and systematic reviews. This outcome was influenced by a number of factors. The change to a democratic government in the mid 1990s, and the health reforms that followed, created opportunities for maternal health care policy development. The new government was open to academic involvement in policy making and recruited academics from local networks into key policy making positions in the National Department of Health. The local academic obstetric network, which placed high value on evidence-based practice, brought these values into the policy process and was also linked strongly to international evidence based medicine networks. Within this context of openness to policy development

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

    PubMed Central

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

    2014-01-01

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

  3. 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

  4. 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

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

    PubMed

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

    2014-10-01

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

  6. 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

  7. The global impact of pre-eclampsia and eclampsia.

    PubMed

    Duley, Lelia

    2009-06-01

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

  8. 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…

  9. [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. PMID:25600462

  10. 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…

  11. Genome-Wide Transcriptome Directed Pathway Analysis of Maternal Pre-Eclampsia Susceptibility Genes

    PubMed Central

    Yong, Hannah E. J.; Melton, Phillip E.; Johnson, Matthew P.; Freed, Katy A.; Kalionis, Bill; Murthi, Padma; Brennecke, Shaun P.; Keogh, Rosemary J.; Moses, Eric K.

    2015-01-01

    Background Preeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associated with PE. We have thus taken a novel integrative bioinformatics approach of analysing pathways common to the susceptibility genes and the PE transcriptome. Methods Using Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. The R software package libraries lumi and limma were used to preprocess transcript data for pathway analysis. Pathways were analysed and constructed using Pathway Studio. We examined ten candidate genes, which are from these functional groups: activin/inhibin signalling—ACVR1, ACVR1C, ACVR2A, INHA, INHBB; structural components—COL4A1, COL4A2 and M1 family aminopeptidases—ERAP1, ERAP2 and LNPEP. Results/Conclusion Major common regulators/targets of these susceptibility genes identified were AGT, IFNG, IL6, INHBA, SERPINE1, TGFB1 and VEGFA. The top two categories of pathways associated with the susceptibility genes, which were significantly altered in the PE decidual transcriptome, were apoptosis and cell signaling (p < 0.001). Thus, susceptibility genes from distinct functional groups share similar downstream pathways through common regulators/targets, some of which are altered in PE. This study contributes to a better understanding of how susceptibility genes may interact in the development of PE. With this knowledge, more targeted functional analyses of PE susceptibility genes in these key pathways can be performed to examine their contributions to the pathogenesis and severity of PE. PMID:26010865

  12. [The hormonal factors regulating water-electrolyte exchange in the pathogenesis of the hemodynamic disorders in pre-eclampsia].

    PubMed

    Zaporozhan, V M; Hozhenko, A I; Svirs'kyĭ, O O; Zalins'kyĭ, O O

    2000-01-01

    Study of indices of different endocrine links of female organisms with gestosis of the 2nd half of pregnancy with the search of degree of taking part of this hormones in the forming of basic syndromes of hestosis and guiding line to fundamental approach in medicinal practice with gestosis. Decrease of natrium content in CBV at the same time with decrease of intravascular volume of it and decrease of excretion of it with urine in the dynamics of gestosis confirms hestosis development and retention of natrium in the expectorant women's organism with primary delay of it in tissues. Energization of renin-angiotensin-aldosterone-tromboxane system, changes of prostaglandin-tromboxane link in blood contributed to forming of arterial hypertension and edema. With taking into account revealed changes of hormonal levels at the background of progressive hypovolemia, decrease of speed of excretion of natrium with urine and speed of glomerular filtration, differentiate approach in prescription for hypotensive and diuretic agents is recommended for the avoidance of possible hardening of state of expectorant woman with gestosis. PMID:10867862

  13. 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

  14. 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

  15. Hemodynamic and hemorheological profiles in women with proteinuric hypertension of pregnancy and in pregnant controls.

    PubMed

    Heilmann, L; Siekmann, U

    1989-01-01

    We obtained blood samples from 52 patients with pre-eclampsia and from 40 pregnant controls for measurement of plasma urate levels, hematocrit, white cell count and various hemorheological parameters. We also used impedance cardiography to measure cardiac output in both groups and from the results derived values for total peripheral resistance and oxygen transport. Central venous pressure was measured with a superior vena cava catheter in patients with pre-eclampsia but not in controls. Women with pre-eclampsia had significantly lower cardiac output and central venous pressure when compared with a control group. A modest correlation was observed between central venous pressure and cardiac output. The majority of pre-eclamptic patients had significantly raised hematocrit, leucocyte count, uric acid and red cell aggregation. Red cell deformability was significantly decreased in patients with pre-eclampsia. Most patients with severe pre-eclampsia (BP diast. greater than 100 mmHg) had a low Antithrombin III and colloid osmotic pressure level. The leucocyte count was raised when compared with the women with moderate pre-eclampsia. Oxygen delivery was reduced in patients with pre-eclampsia because of impaired rheological properties of their blood. PMID:2694970

  16. Spontaneous reversal of mirror syndrome in a twin pregnancy after a single fetal death.

    PubMed

    Pirhonen, Jouko P; Hartgill, Tom W

    2004-09-10

    The case report illustrates that pre-eclampsia like symptoms can arise as a consequence of pathological changes in a single feto-placental unit of a twin pregnancy and may resolve spontaneously when the cause is removed. PMID:15294378

  17. Sulfamethoxazole/Trimethoprim (Bactrim or Septra) and Pregnancy

    MedlinePlus

    ... kidney infection for the mother, preterm birth and pre-eclampsia (dangerously high blood pressure). Are there any other ... a greater risk for pregnancy complications such as preeclampsia, placenta abruption (when the placenta breaks away from ...

  18. Coagulation problems in human pregnancy.

    PubMed Central

    Redman, C. W.

    1979-01-01

    Coagulation problems in pregnancy are primarily associated with overactivity of the intrinsic clotting system. This accounts for the increased incidence of thrombo-embolism during pregnancy. Where specific obstetric complications cause clotting problems the common underlying feature is usually placental pathology as in abruptio placentae, pre-eclampsia or hydatidiform mole. Abnormal activation of the clotting system is an early, and occasionally the first detectable feature of pre-eclampsia, but there is no evidence that this is a primary change. Therefore the role of anticoagulant treatment in the management of pre-eclampsia remains questionable. A new test for estimating factor VIII consumption is proving to be a sensitive index of early activation of the clotting system and can be used for the diagnosis of early pre-eclampsia. PMID:382170

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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

  4. Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy

    PubMed Central

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

    2012-01-01

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

  5. Role of adiponectin on antioxidant profile: evaluation during healthy and hypertensive disorders of pregnancy.

    PubMed

    Eleuterio, Níbia Mariana; Palei, Ana C T; Machado, Jackeline S Rangel; Tanus-Santos, Jose E; Cavalli, Ricardo C; Sandrim, Valeria C

    2016-08-01

    The study of adipokines and oxidative stress has aided in understanding pre-eclampsia physiopathology. Therefore, our group aimed to evaluate the correlation between the adipokines (adiponectin and leptin) and the oxidative stress marker malondialdehyde-thiobarbituric acid reactive substances (MDA-TBARS) and antioxidant activity of plasma [ferric reducing ability of plasma (FRAP)] in healthy pregnant women and patients with gestational hypertension and pre-eclampsia. We found a significant negative correlation between MDA-TBARS and adiponectin (r = -0.40, p = 0.0042), suggesting a relationship between antioxidant levels and this adipokine in healthy pregnancies which is altered in patients with gestational hypertension or pre-eclampsia. PMID:26935256

  6. 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

  7. Variability of arterial blood pressure in normal and hypertensive pregnancy.

    PubMed

    Oney, T; Meyer-Sabellek, W

    1990-12-01

    In normal pregnancy the circadian blood pressure rhythm is similar to that in the non-pregnant state, with the highest blood pressure values in the morning and the lowest at midnight. This rhythm is lost in patients with pre-eclampsia. Women with severe pre-eclampsia show a reversed circadian rhythm, with a nocturnal increase in blood pressure during the sleeping phase. Although the reasons for this nocturnal hypertension in severe pre-eclampsia are poorly understood, the results suggest that pre-eclamptic women are endangered by hypertensive emergencies, mostly at night. Therefore blood pressure measurement should be extended to the night, and antihypertensive treatment must be adapted to the demands of a reversed circadian rhythm in relevant subgroups of patients. PMID:2082002

  8. Do hypertensive diseases of pregnancy disrupt neurocognitive development in offspring?

    PubMed

    Whitehouse, Andrew J O; Robinson, Monique; Newnham, John P; Pennell, Craig E

    2012-03-01

    The current study sought to determine whether hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) are associated with neurocognitive outcomes in middle childhood. Participants were members of the Western Australian Pregnancy Cohort (Raine) Study. Data were available for 1389 children (675 females; mean age = 10.59 years; SD = 0.19). Twenty-five per cent of these participants were offspring of pregnancies complicated by either gestational hypertension (n = 279), or pre-eclampsia (n = 34). Verbal ability at age 10 years was assessed with the Peabody Picture Vocabulary Test - Revised (PPVT-R), and non-verbal ability with Ravens Colored Progressive Matrices (RCPM). Separate multivariable regression analyses, incorporating sociodemographic, antenatal, obstetric and postnatal covariates, investigated the effect of a two- (normotensive pregnancy vs. hypertensive pregnancy) and three-level (normotensive pregnancy vs. gestational hypertension vs. pre-eclampsia) predictor variable on PPVT-R and RCPM scores. Offspring of pregnancies complicated by maternal hypertension (gestational hypertension or pre-eclampsia) had a mean PPVT-R score that was 1.83 ([95% confidence interval (CI) -3.48, -0.17], P = 0.03) points lower than children from normotensive pregnancies. Multivariable regression analysis also identified a significant inverse association between the three-level predictor variable and offspring PPVT-R scores (P = 0.02). Gestational hypertension (without pre-eclampsia) reduced offspring PPVT-R scores by 1.71 points [95% CI -3.39, -0.03] and pre-eclampsia led to a reduction of 3.53 points [95% CI -8.41, 1.35], although this latter association did not achieve statistical significance. There was no effect of the two- (P = 0.99) or three-level (P = 0.92) predictor variable on RCPM scores. Maternal hypertensive diseases of pregnancy are a risk factor for a small reduction in offspring verbal ability. PMID:22324495

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

    PubMed

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

    2013-09-01

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

  10. Multiple concomitant cranial nerve palsies secondary to preeclampsia.

    PubMed

    Gilca, Marina; Luneau, Katie

    2015-06-01

    A 32-year-old primigravid woman developed pre-eclampsia after delivery of twins along with left fifth, sixth, and seventh cranial neuropathies. She also had evidence of hepatic and renal involvement. Results of patient evaluation were otherwise unremarkable, and the palsies completely resolved over 3 months after treatment with valacyclovir and systemic corticosteroids. PMID:25768245

  11. 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

  12. Urine protein concentration estimation for biomarker discovery.

    PubMed

    Mistry, Hiten D; Bramham, Kate; Weston, Andrew J; Ward, Malcolm A; Thompson, Andrew J; Chappell, Lucy C

    2013-10-01

    Recent advances have been made in the study of urinary proteomics as a diagnostic tool for renal disease and pre-eclampsia which requires accurate measurement of urinary protein. We compared different protein assays (Bicinchoninic acid (BCA), Lowry and Bradford) against the 'gold standard' amino-acid assay in urine from 43 women (8 non-pregnant, 34 pregnant, including 8 with pre-eclampsia). BCA assay was superior to both Lowry and Bradford assays (Bland Altman bias: 0.08) compared to amino-acid assay, which performed particularly poorly at higher protein concentrations. These data highlight the need to use amino-acid or BCA assays for unprocessed urine protein estimation. PMID:26103798

  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. [Antihypertensive treatment in pregnancy].

    PubMed

    Souza, Alex R; Amorim, Melania R; Costa, Aurélio A R; Neto, Carlos N

    2010-01-01

    Pregnancy hypertensive disorders represent a frequent gestational pathology. It is one of the most important causes of maternal demise and perinatal morbidity/mortality in the world. Antihypertensive treatment is part of a vast therapeutic arsenal used for prevention of severe complications. However, data from literature research have been controversial about benefits of antihypertensive treatment. We performed a literature review about antihypertensive treatment in severe pre-eclampsia, describing drugs' pharmacological particularities and scientific evidences about their efficacy and safety. It is not controversial that treatment of hypertensive emergency must be instituted. The ideal medication used in those cases is not defined, therefore the real benefits of maintenance antihypertensive treatment in pre-eclampsia remains unclear. PMID:20353709

  15. 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

  16. 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. PMID:25259900

  17. 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

  18. Systemic and uteroplacental renin–angiotensin system in normal and pre-eclamptic pregnancies

    PubMed Central

    Anton, Lauren

    2009-01-01

    Pregnancy is characterized by an increase in many of the different components of the circulating renin–angiotensin system [RAS]. However, the physiological mechanisms of stimulated RAS activity during pregnancy are unknown. Even less understood is how this system may be altered in pre-eclampsia, a hypertensive disorder of pregnancy. Additional studies have shown the presence of a local tissue specific RAS in the uteroplacental unit of normal and pre-eclamptic pregnancies. Differences in normal pregnant and pre-eclamptic RAS component regulation may provide insight into the mechanisms responsible for the clinical pathological features of pre-eclampsia. Specifically, this review summarizes the key findings in the circulating and uteroplacental RAS in normal and pre-eclamptic pregnancies. PMID:19124433

  19. 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

  20. Identification of the primary outcomes that result from deficient spiral arterial modification in pregnant mice

    PubMed Central

    Croy, B. Anne; Burke, Suzanne D.; Barrette, Valerie F.; Zhang, Jianhong.; Hatta, Kota; Smith, Graeme N.; Bianco, Juares; Yamada, Aureo T.; Adams, Michael A.

    2011-01-01

    Pre-eclampsia, an acute complication of human pregnancy, is associated within complete physiological modification of decidual spiral arteries. This is thought to promote oxidative stress from perfusion/reperfusion of the placenta and to restrict placental and fetal growth. Alymphoid (genotype Rag2−/−/Il2rg−/−) mice, sufficient in dendritic and myeloid cell functions, lack spiral arterial modification with individual spiral arteries having ~1.7x the vascular resistance and 0.66x the blood velocity of +/+ mice. Their placentae are measurably hypoxic yet neither placental growth nor fetal survival is impaired and gestational hypertension is not seen. Thus, lymphocytes rather than vascular adaptations appear to be the pivotal contributors to the clinical complications of pre-eclampsia. PMID:22279618

  1. Leptin receptor gene polymorphisms in severely pre-eclamptic women.

    PubMed

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

    2006-09-01

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

  2. 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

  3. Treatment with sildenafil prevents impairment of learning in rats born to pre-eclamptic mothers.

    PubMed

    Cauli, O; Herraiz, S; Pellicer, B; Pellicer, A; Felipo, V

    2010-12-01

    Pre-eclampsia is an important hypertensive pregnancy disorder and a main cause of maternal and fetal morbidity and mortality. Children born from mothers with pre-eclampsia may present cognitive deficits. The mechanisms leading to this cognitive impairment remain unclear and no treatments to improve it have been tested. Pre-eclampsia is associated with impaired regulation of the nitric oxide-3'-5'guanosine monophosphate cyclic (cGMP) pathway, which modulates some cognitive functions. We hypothesized that alterations in the NO-cGMP pathway would be involved in the mechanisms leading to cognitive impairment in rats born to pre-eclamptic mothers and that treatment with sildenafil, an inhibitor of the phosphodiesterase that degrades cGMP, could restore their cognitive function. To test these hypotheses, we used an animal model of pre-eclampsia in rats: pregnant rats treated with l-nitro-arginine methyl ester, an inhibitor of nitric oxide synthase. Using this model, we assessed: (1) whether rats born to pre-eclamptic mothers show reduced learning ability and/or altered motor activity or coordination when they are 2 months-old; (2) whether cognitive impairment is associated with reduced function of the glutamate-NO-cGMP pathway in brain in vivo; and (3) whether treatment of the mothers with sildenafil prevents this cognitive and motor alterations. The results reported show that the ability to learn a conditional discrimination task in a Y maze is reduced in rats born to pre-eclamptic mothers. This impairment was associated with reduced function of the glutamate-NO-cGMP pathway in brain in vivo, as assessed by microdialysis in freely moving rats. Treatment with sildenafil restores the function of this pathway and learning ability. PMID:20832451

  4. [Maternal refusal to consent to a cesarean delivery, stillbirth].

    PubMed

    Defline, A; Obadia, M; El Djerbi, A; Plevy, P; Lepercq, J

    2014-01-01

    The doctor-lawyer perspective that we discuss is a maternal refusal to consent to a cesarean delivery for a fetal indication in June 2011. Despite repeated information of the risks during a three-week hospitalization for pre-eclampsia, after being assured of the proper understanding of the seriousness of the situation by the patient and spouse, and after consideration to transfer to another hospital, the reiterated refusal led to a late fetal extraction resulting in term stillbirth. PMID:23972774

  5. 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

  6. 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

  7. Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

    PubMed Central

    Burke, Suzanne D.; Dong, Hongmei; Hazan, Aleah D.; Croy, B. Anne

    2010-01-01

    Objective Pregnancies in diabetic women are at 4–12 more risk for pre-eclampsia, an urgent, acute onset complication of mid to late gestation, than pregnancies in normal women. Hallmarks of pre-eclampsia are hypertension, proteinuria and incomplete modification of endometrial spiral arteries. Transient, pro-angiogenic lymphocytes called uterine Natural Killer (uNK) cells are implicated in human and rodent spiral artery modification. We studied mid to late gestations in spontaneously type 1 diabetic NOD mice to ask if diabetes alters uNK cell homing and/or function. Research design and method Normoglycemic, prediabetic and diabetic NOD mice and controls were mated. Lymphocytes and endometrial endothelium and decidua were studied histologically and in functional assays. Results Conception accelerated progression to overt diabetes in NOD females who had limited spiral artery development, heavier placentae and lighter fetuses displaying numerous birth defects compared with controls. UNK cell numbers were reduced in the decidua basalis of diabetic females while interferon-γ production was elevated. In diabetic NOD mice, decidual expression of the endothelial cell addressin MAdCAM-1 was aberrant in position while VCAM-1 expression was reduced. Assays of lymphocyte adhesion to tissue sections under shear forces indicated that diabetes compromises the potential homing functions of both endometrial endothelium and peripheral NK cells. Conclusions In diabetes, gestational endometrium has immune and vascular defects that likely to contribute to murine fetal loss and birth defects. Analogous problems and pre-eclampsia in diabetic women may involve similar mechanisms. PMID:17827401

  8. Pregnancy complications in polycystic ovary syndrome patients.

    PubMed

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

    2015-02-01

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

  9. 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

  10. 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

  11. 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

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

    PubMed

    Clark, David A

    2014-06-01

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

  13. Scientific basis for the content of routine antenatal care. I. Philosophy, recent studies, and power to eliminate or alleviate adverse maternal outcomes.

    PubMed

    Villar, J; Bergsjø, P

    1997-01-01

    Recent literature was reviewed to identify elements of antenatal care which are of proven benefit in preventing or ameliorating adverse outcomes in the mother such as bleeding, anemia, pre-eclampsia, sepsis and genitourinary infection, and obstructed labor. Recent trials indicate that while fewer routine visits for low-risk women do not jeopardize a positive pregnancy outcome, patients may be less satisfied. None of the many factors which can cause bleeding during pregnancy can be eliminated through antenatal care, although risk factors can be identified through history-taking. Counseling on what to do is the best option. Routine iron supplementation against anemia is not necessary in well-nourished populations, but circumstantial evidence suggests that iron and folate should be provided for every pregnant woman in areas of high anemia prevalence. Hemoglobin determination as a routine test is more important near week 30 of term rather than early in pregnancy. Recent trials do not support routine aspirin to prevent pre-eclampsia among low-risk women, nor is there evidence that anti-hypertensive treatment of mild pre-eclampsia will prevent more serious disease. Improved detection and care may, however, lead to better outcomes. Urine culture and dipstick for leucocyte esterase and nitrite with subsequent treatment of positive cases will reduce the risk of pyelonephritis and appear to be cost-effective. Serological screening and treatment of syphilis is inexpensive and cost-effective, while obstructed labor can be anticipated in multiparas based upon obstetrical history; hospital delivery should be secured. PMID:9033238

  14. 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

  15. 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

  16. 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

  17. Thrombophilia related issues in women and children.

    PubMed

    Hoffman, Ron; Brenner, Benjamin

    2005-02-01

    Women experience increased thrombotic risk at pregnancy and puerperium as well as during hormonal therapy with oral contraceptives or hormone replacement therapy. Physiological and anatomical changes in pregnancy contribute to the hypercoagulable situation. Women with thrombophilia have an increased risk for venous and arterial thromboembolism as well as for gestational vascular complications including fetal loss, pre-eclampsia, placental abruption, and fetal growth restriction. Children are at increased thrombotic risk, particularly at the neonatal period, and may express thrombosis often in association with thrombophilia. This article will focuses on the clinical association, pathogenesis, and treatment of thrombophilia-related issues in women and children. PMID:15706481

  18. Late postpartum eclampsia complicated with posterior reversible encephalopathy syndrome: a case report and a literature review

    PubMed Central

    Zhang, Lihong; Wang, Yacong; Shi, Liang; Cao, Jianhui

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare but serious clinical-neuroradiological entity characterized by headache, vomiting, visual disturbances, altered mental status, seizures, and unconsciousness associated with the characteristic imaging findings including sub-cortical vasogenic edema at the bilateral parietal and occipital lobes. We describe a case of 28-year-old PRES patient secondary to delayed maternal postpartum eclampsia. This patient was not initially diagnosed with pre-eclampsia and PRES. The diagnosis was established after magnetic resonance imaging. After treatment this patient’s PRES resolved. Early diagnosis and treatment are the keys to reverse PRES. A literature review for PRES is provided in this report. PMID:26807372

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

    PubMed Central

    Shahien, Radi; Bowirrat, Abdalla

    2011-01-01

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

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

    PubMed

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

    2012-04-01

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

  2. 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

  3. Perinatal neuroblastoma: a hidden bullet in the chest

    PubMed Central

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

    2014-01-01

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

  4. α-Methyldopa-induced hepatitis during the postpartum period

    PubMed Central

    Kashkooli, Soleiman; Baraty, Brandon; Kalantar, Jamshid

    2014-01-01

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

  5. The effects of deprivation of prostaglandin precursors on vascular sensitivity to angiotensin II and on the kidney in the pregnant rabbit.

    PubMed Central

    O'Brien, P M; Broughton Pipkin, F

    1979-01-01

    1 Pregnant rabbits were deprived of essential fatty acids from day ten of pregnancy, and results compared with a control group on a normal diet. 2 At term, cannulation of jugular and carotid vessels was performed under anaesthesia, to study the vascular sensitivity to angiotensin II and basal blood pressure. 3 Plasma renin levels, urinary electrolytes and protein were measured. 4 Placental and renal tissue was examined histologically. 5 Though no changes were found in tissues, blood or urine, a markedly significant increase in response to angiotensin II was found in the group deprived of essential fatty acids. This parallels the findings in vascular response in human pre-eclampsia. PMID:760889

  6. 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

  7. Managing pregnancy in inflammatory rheumatological diseases

    PubMed Central

    2011-01-01

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

  8. 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

  9. Further case of Rubinstein-Taybi syndrome due to a deletion in EP300.

    PubMed

    Foley, Patricia; Bunyan, David; Stratton, John; Dillon, Michelle; Lynch, Sally Ann

    2009-05-01

    Rubinstein-Taybi syndrome (RSTS) is a heterogeneous disorder with approximately 45-55% of patients showing mutations in the CREB binding protein and a further 3% of patients having mutations in EP300. We report a male child with a deletion of exons 3-8 of the EP300 gene who has RSTS. He has a milder skeletal phenotype, a finding that has been described in other cases with EP300 mutations. The mother suffered from pre-eclampsia and HELLP syndrome in the pregnancy. She subsequently developed a mullerian tumor of her cervix 6 years after the birth of her son. PMID:19353645

  10. [Hypertensive emergencies in adults: a practical review].

    PubMed

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

    2010-10-01

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

  11. [Hypertension in pregnancy with special reference to its treatment].

    PubMed

    Ukleja-Adamowicz, M; Nartowicz, E; Adamowicz, A

    Definition and classification of the arterial hypertension in pregnancy are discussed. An emphasis is on the problems of differential diagnosis between pre-eclampsia and other forms of hypertension. Use of hypotensive drugs in pregnant patients with particular reference to emergencies is also discussed. The treatment of pregnant women with hypertension is still a problem which require close co-operation of both an obstetrician and internist. Follow-up after labour is GP duty to find out if the patient remains hypertensive. If so, etiology of the disease should be again searched. PMID:1488337

  12. Anaesthesia for lower-segment caesarean section: Changing perspectives

    PubMed Central

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

    2010-01-01

    The number of caesarean sections has increased over the last two decades, especially in the developed countries. Hence, it has increasingly become a greater challenge to provide care for the parturient, but this has given obstetric anaesthetists a greater opportunity to contribute to obstetric services. While caesarean deliveries were historically performed using general anaesthesia, there is a recent significant move towards regional anaesthesia. Unique problems that patients with obesity and pre-eclampsia present will be discussed in the present article. New medications and devices now used in obstetric anaesthesia will change the practice and perspectives of our clinical practice. PMID:21189878

  13. Obstetric nephrology: lupus and lupus nephritis in pregnancy.

    PubMed

    Stanhope, Todd J; White, Wendy M; Moder, Kevin G; Smyth, Andrew; Garovic, Vesna D

    2012-12-01

    SLE is a multi-organ autoimmune disease that affects women of childbearing age. Renal involvement in the form of either active lupus nephritis (LN) at the time of conception, or a LN new onset or flare during pregnancy increases the risks of preterm delivery, pre-eclampsia, maternal mortality, fetal/neonatal demise, and intrauterine growth restriction. Consequently, current recommendations advise that the affected woman achieve a stable remission of her renal disease for at least 6 months before conception. Hormonal and immune system changes in pregnancy may affect disease activity and progression, and published evidence suggests that there is an increased risk for a LN flare during pregnancy. The major goal of immunosuppressive therapy in pregnancy is control of disease activity with medications that are relatively safe for a growing fetus. Therefore, the use of mycophenolate mofetil, due to increasing evidence supporting its teratogenicity, is contraindicated during pregnancy. Worsening proteinuria, which commonly occurs in proteinuric renal diseases toward the end of pregnancy, should be differentiated from a LN flare and/or pre-eclampsia, a pregnancy-specific condition clinically characterized by hypertension and proteinuria. These considerations present challenges that underscore the importance of a multidisciplinary team approach when caring for these patients, including a nephrologist, rheumatologist, and obstetrician who have experience with these pregnancy-related complications. This review discusses the pathogenesis, maternal and fetal risks, and management pertinent to SLE patients with new onset or a history of LN predating pregnancy. PMID:22879437

  14. 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. PMID:27219894

  15. Role of nitric oxide in maternal hemodynamics and hormonal changes in pregnant rats.

    PubMed

    Salas, S P

    1998-01-01

    Normal pregnancy is characterized by a significant reduction in total peripheral vascular resistance and decreased pressor responsiveness to vasodilator agents. This review will consider whether nitric oxide (NO) contributes to these changes, and whether a deficiency of NO produces a preeclampsia like syndrome. The biosynthesis of NO increases in pregnant animals, as assessed by the raised plasma concentration, urinary excretion and metabolic production rate of guanosine 3',5'-cyclic monophosphate (cGMP), the second messenger of NO. In addition, urinary excretion of nitrate, the stable metabolites of NO, increases during pregnancy, paralleling the rise in cGMP. Several studies provide convincing evidence indicating that expression and activity of different NO synthases (NOS) are increased in gravid animals. Acute blockade of NOS causes a dose response increase in blood pressure and reverses the blunted vasopressor response to vasoconstrictor agents. Long-term NOS inhibition produces a pre-eclampsia like syndrome, characterized by maternal hypertension, proteinuria, thrombocytopenia, and renal damage, and lower litter size and fetal weight. Both acute and chronic responses are reduced when L-arginine, the substrate for NOS, is administered in high doses, indicating that these changes are specific to NO inhibition. In conclusion, present data suggest that a disturbance in NO release may contribute to the pathogenesis of pre-eclampsia. PMID:9830512

  16. 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

  17. 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

  18. 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

  19. 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

  20. Expression of prostacyclin and thromboxane synthases in placenta and placental bed after pre-eclamptic pregnancies.

    PubMed

    Wetzka, B; Charnock-Jones, D S; Viville, B; Cooper, J C; Nüsing, R; Zahradnik, H P; Smith, S K

    1996-11-01

    Prostacyclin and thromboxane are potent antagonistic regulators of vascular tone and platelet aggregation. In pre-eclampsia, the ratio of their metabolites is decreased. Little is known about the local regulation of intrauterine prostacyclin and thromboxane production in this condition. Placenta and placental bed biopsies were obtained from uncomplicated and pre-eclamptic pregnancies. Prostacyclin synthase (PCS) and thromboxane synthase (TXS) and their mRNA's were localized by immunohistochemistry using monoclonal antibodies and in situ hybridization. Protein and mRNA levels were quantified by immunoblot and RNase protection assay. PCS-like immunoreactivity was found in endothelial cells and leiomyocytes, whereas fetal and maternal macrophages showed positive staining for TXS. Their mRNA was localized to trophoblast and endothelium, and TXS mRNA could also be detected in macrophages. Quantitative analysis showed no significant difference in intrauterine protein or mRNA expression after pre-eclampsia. The prostacyclin and thromboxane production seems to be compartmentalized within the uteroplacental unit. The expression of their synthesizing enzymes might be regulated post-transcriptionally. Additional regulation of prostaglandin production could be metabolically or on the substrate level and requires further elucidation. PMID:8916205

  1. Cyclooxygenase-1 and -2 in human placenta and placental bed after normal and pre-eclamptic pregnancies.

    PubMed

    Wetzka, B; Nüsing, R; Charnock-Jones, D S; Schäfer, W; Zahradnik, H P; Smith, S K

    1997-10-01

    In pre-eclampsia, the ratio of prostacyclin:thromboxane production rate is decreased favouring the vasoconstrictive thromboxane. One of the rate-limiting steps in prostaglandin synthesis is cyclooxygenase (COX) activity. Therefore, we investigated the expression of COX-1 and COX-2 in human placenta and placental bed. Tissue specimens from the 29th to 40th week of pregnancy were obtained from Caesarean sections after uncomplicated and pre-eclamptic pregnancies before the onset of labour. COX-1 and COX-2 were localized immunohistochemically with the identification of positive cells by double immunofluorescence staining. The protein and mRNA levels were analysed by immunoblotting and quantitative reverse transcriptase-polymerase chain reaction. Expression of both COX-1 and COX-2 could be observed in placenta and placental bed. COX-1-like immunoreactivity was observed in most cell types with strongest staining in macrophages. Only macrophages, endothelium, vascular leiomyocytes and fibroblasts stained positively for COX-2. In placenta, COX-1 and -2 expression was unchanged after pre-eclampsia. In placental bed, protein and mRNA levels of COX-1 were increased in the pre-eclamptic group (P < 0.05), whereas COX-2 expression did not differ significantly from normal pregnancies. An increased expression of COX-1 could be involved in the pathophysiology of pre-eclamptic changes within the placental bed. A therapy with drugs inhibiting COX-1 might be beneficial in this condition. PMID:9402302

  2. Stroke in pregnancy.

    PubMed

    Feske, Steven K

    2007-11-01

    Although pregnancy-associated stroke is uncommon, the risk of stroke is greatly increased above the low baseline rate in young patients during late pregnancy and, even more so, during the puerperium. Stroke is a major contributor to the serious morbidity and mortality of pregnancy. The physiological hormonally mediated changes in circulation, vascular tissue structure, and coagulability, and the pathological state of pre-eclampsia-eclampsia contribute to this increased risk of stroke. Pregnancy-associated strokes are roughly evenly divided among hemorrhagic strokes, mainly from rupture of aneurysms and arteriovenous malformations (AVMs); ischemic strokes, mainly from late pregnancy and postpartum cerebral venous thrombosis; and strokes associated with pre-eclampsia-eclampsia, with a contribution from cardioembolism, especially in populations at risk from a high rate of underlying rheumatic valvular heart disease. Awareness of the types of stroke to expect during pregnancy will facilitate early diagnosis. This article discusses the pathogenesis of pregnancy-associated stroke, its epidemiology, and some diagnostic and therapeutic issues unique to pregnancy. PMID:17940923

  3. 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

  4. The Salivary Scavenger and Agglutinin (SALSA) in Healthy and Complicated Pregnancy

    PubMed Central

    Reichhardt, Martin Parnov; Jarva, Hanna; Lokki, Anna Inkeri; Laivuori, Hannele; Vuorela, Piia; Loimaranta, Vuokko; Glasner, Andreas; Siwetz, Monika; Huppertz, Berthold; Meri, Seppo

    2016-01-01

    Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. The etiology is not clear, but an immune attack towards components of placenta or fetus has been indicated. This involves activation of the complement system in the placenta. We have previously described the presence of the complement-regulating protein salivary scavenger and agglutinin (SALSA) in amniotic fluid. In this study we investigated the potential role of SALSA in pregnancy by analyzing its presence in amniotic fluid and placental tissue during healthy and complicated pregnancies. SALSA levels in amniotic fluid increased during pregnancy. Before 20 weeks of gestation the levels were slightly higher in patients who later developed pre-eclampsia than in gestation age-matched controls. In the placenta of pre-eclamptic patients syncytial damage is often followed by the formation of fibrinoid structures. SALSA was found clustered into these fibrinoid structures in partial co-localization with complement C1q and fibronectin. In vitro analysis showed direct protein binding of SALSA to fibronectin. SALSA binds also to fibrin/fibrinogen but did not interfere with the blood clotting process in vitro. Thus, in addition to antimicrobial defense and epithelial differentiation, the data presented here suggest that SALSA, together with fibronectin and C1q, may be involved in the containment of injured placental structures into fibrinoids. PMID:26828433

  5. 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

  6. 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

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

    PubMed Central

    Tabatabaei, Mozhgan

    2011-01-01

    Objective: The aim of this study was to evaluate associations between pregnancy outcomes and prepregnancy body mass index and gestational weight gain among pregnant women who regularly attended health centers of Kazerun, Fars, Iran. Methods: In this descriptive study records from 5172 pregnant women were considered in this study, based on the methodology criteria. Women were distributed across 4 prepregnancy categories according to the Institute of Medicine (IOM) (1990) classification of body mass index, and to 4 end-of-pregnancy categories according to median weekly gestational weight gain. Results: The risks for gestational diabetes, gestational hypertension, pre-eclampsia, and preterm premature rupture of membranes were higher for those who were overweight or obese before becoming pregnant (P < 0.05). Moreover, a gestational weight gain of 0.50 kg per week or greater was associated with a higher risk for gestational hypertension, preterm premature rupture of membranes, and fetal macrosomia (P < 0.05). Women in the highest quartile for weight gain (≥ 0.59 kg per week) were at higher risk for pre-eclampsia (P < 0.05). Discussion: The results seems to indicate that excessive gestational weight gain and high prepregnancy body mass index were associated with increased risks for adverse pregnancy outcomes. PMID:22439074

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

    PubMed Central

    2014-01-01

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

  9. Increased planned delivery contributes to declining rates of pregnancy hypertension in Australia: a population-based record linkage study

    PubMed Central

    Roberts, Christine L; Algert, Charles S; Morris, Jonathan M; Ford, Jane B

    2015-01-01

    Objective Since the 1990s, pregnancy hypertension rates have declined in some countries, but not all. Increasing rates of early planned delivery (before the due date) have been hypothesised as the reason for the decline. The aim of this study was to explore whether early planned delivery can partly explain the declining pregnancy hypertension rates in Australia. Design Population-based record linkage study utilising linked birth and hospital records. Setting and participants A cohort of 1 076 122 deliveries in New South Wales, Australia, 2001–2012. Outcome measures Pregnancy hypertension (including gestational hypertension, pre-eclampsia and eclampsia) was the main outcome; pre-eclampsia was a secondary outcome. Results From 2001 to 2012, pregnancy hypertension rates declined by 22%, from 9.9% to 7.7%, and pre-eclampsia by 27%, from 3.3% to 2.4% (trend p<0.0001). At the same time, planned deliveries increased: prelabour caesarean section by 43% (12.9–18.4%) and labour inductions by 10% (24.8–27.2%). Many maternal risk factors for pregnancy hypertension significantly increased (p<0.01) over the study period including nulliparity, age ≥35 years, diabetes, overweight and obesity, and use of assisted reproductive technologies; some risk factors decreased including multifetal pregnancies, age <20 years, autoimmune diseases and previous pregnancy hypertension. Given these changes in risk factors, the pregnancy hypertension rate was predicted to increase to 10.5%. Examination of annual gestational age distributions showed that pregnancy hypertension rates actually declined from 38 weeks gestation and were steepest from 41 weeks; at least 36% of the decrease could be attributed to planned deliveries. The risk factors for pregnancy hypertension were also risk factors for planned delivery. Conclusions It appears that an unanticipated consequence of increasing early planned deliveries is a decline in the incidence of pregnancy hypertension. Women with risk

  10. 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

  11. Obstetric management of obesity in pregnancy.

    PubMed

    Jarvie, Eleanor; Ramsay, Jane E

    2010-04-01

    Rates of obesity among the pregnant population have increased substantially and adiposity has a damaging effect on every aspect of female reproductive life. This review summarises epidemiological data concerning obesity-related complications of pregnancy. Obesity is linked to a number of adverse obstetric outcomes as well as increased maternal and neonatal morbidity and mortality. These complications include miscarriage, congenital abnormalities, pre-eclampsia, gestational diabetes mellitus, iatrogenic preterm delivery, postdates pregnancy with increased rates of induction of labour, caesarean section, postpartum haemorrhage, shoulder dystocia, infection, venous thromboembolism, and increased hospital stay. It is important to consider obese pregnant women as a high risk group with a linear increase in risk of complications associated with their degree of obesity. Their obstetric management should be consultant-led and involve a multidisciplinary team approach to improve outcome. PMID:19880362

  12. 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

  13. 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

  14. Current trends in the treatment of polycystic ovary syndrome with desire for children

    PubMed Central

    Sastre, Margalida E; Prat, Maria O; Checa, Miguel Angel; Carreras, Ramon C

    2009-01-01

    Polycystic ovary syndrome (PCOS), one of the most frequent endocrine diseases, affects approximately 5%–10% of women of childbearing age and constitutes the most common cause of female sterility regardless of the need or not for treatment, a change in lifestyle is essential for the treatment to work and ovulation to be restored. Obesity is the principal reason for modifying lifestyle since its reduction improves ovulation and the capacity for pregnancy and lowers the risk of miscarriage and later complications that may occur during pregnancy (gestational diabetes, pre-eclampsia, etc). When lifestyle modification is not sufficient, the first step in ovulation induction is clomiphene citrate. The second-step recommendation is either exogenous gonadotrophins or laparoscopic ovarian surgery. Recommended third-line treatment is in vitro fertilization. Metformin use in PCOS should be restricted to women with glucose intolerance. PMID:19536311

  15. Repeated dosing of digoxin-fragmented antibody in preterm eclampsia.

    PubMed

    Adair, C D; Buckalew, V M; Kipikasa, J; Torres, C; Stallings, S P; Briery, C M

    2009-02-01

    Early onset eclampsia has significant morbidity and mortality for both the mother and fetus. No effective treatment exists at present except delivery and seizure prophylaxis with magnesium sulfate. We report the novel use of a fragmented ovine antibody against digoxin for the treatment of eclampsia. A 16-year-old primagravida at 29 weeks 5/7 days gestation presented with clinical diagnosis of eclampsia and was treated with compassionate off-label use of digoxin-fragmented ovine antibody (Digibind Glaxo Smith Kline, Research Triangle Park, NC, USA). Improvement of her underlying disorder during a 48 h treatment window was noted without adverse maternal or neonatal outcome. We suggest digoxin-fragmented ovine antibody as a possible intervention in preterm pregnancies complicated by pre-eclampsia or eclampsia. PMID:19177044

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

    PubMed

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

    2014-12-01

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

  17. Role of Heme Oxygenase, Leptin, Coenzyme Q10 and Trace Elements in Pre-eclamptic Women.

    PubMed

    Abo-Elmatty, Dina M; Badawy, Ehsan A; Hussein, Jihan S; Elela, Somaya Abo; Megahed, Hoda A

    2012-10-01

    The objective of this study to evaluate heme oxygenase (COHb), leptin and coenzyme Q10 (CoQ10) in pre-eclamptic women. Also Zinc, copper, Iron, total iron binding capacity, Ferritin and uric acid were assessed. 120 female subjects were included in this study. They were divided into, 60 female with normal pregnancy attending the outpatient clinic, 60 pre-eclamptic patients were recruited from obstetrics and gynaecology department El-kasr El-Aini hospital. The results showed that in pre-eclampatic group, leptin level was significantly increased while COHb and CoQ10 was significantly decreased. It is concluded that hemeoxygenase, leptin and coenzyme CoQ10 can be considered as new markers for prediction of pre-eclampsia. PMID:24082464

  18. 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

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

    PubMed

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

    2014-01-01

    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. PMID:25192021

  20. Idiopathic intracranial hypertension presenting as postpartum headache.

    PubMed

    Mathew, Mariam; Salahuddin, Ayesha; Mathew, Namitha R; Nandhagopal, Ramachandiran

    2016-01-01

    Postpartum headache is described as headache and neck or shoulder pain during the first 6 weeks after delivery. Common causes of headache in the puerperium are migraine headache and tension headache; other causes include pre-eclampsia/eclampsia, post-dural puncture headache, cortical vein thrombosis, subarachnoid hemorrhage, posterior reversible leukoencephalopathy syndrome, brain tumor, cerebral ischemia, meningitis, and so forth. Idiopathic intracranial hypertension (IIH) is a rare cause of postpartum headache. It is usually associated with papilledema, headache, and elevated intracranial pressure without any focal neurologic abnormality in an otherwise healthy person. It is more commonly seen in obese women of reproductive age group, but rare during pregnancy and postpartum. We present a case of IIH who presented to us 18 days after cesarean section with severe headache and was successfully managed. PMID:26818168

  1. Smoking can be good for you.

    PubMed

    Wolf, R; Orion, E; Matz, H; Maitra, S; Rowland-Payne, C

    2004-04-01

    Smoking is without doubt one of the greatest causes of avoidable illness and death in the modern world. Most well known is the relationship between smoking and numerous cancers, cerebrovascular and cardiovascular disease. Smoking and most especially nicotine, are, however, sometimes beneficial in certain diseases, including Parkinson's, Alzheimer's, allergic alveolitis, nausea and vomiting of pregnancy, pre-eclampsia, fibroids, carcinoma of body of uterus, ulcerative colitis, pyoderma gangrenosum, aphthous stomatitis and ulceration, pemphigus, herpes simplex and acne. In the immensely justifiable enthusiasm to discredit this dangerous activity, the mechanisms behind these beneficial effects tend to have been un-discussed or ignored. It is the aim of this paper to spur interest in the reasons for these effects. If the mechanisms are elucidated, therapeutic advances may be possible. PMID:17147565

  2. A second delivery after heart transplantation – a case study

    PubMed Central

    Kalinka, Jarosław; Szubert, Maria; Zdziennicki, Andrzej; Chojnowski, Krzysztof; Maciejewski, Marek; Piestrzeniewicz, Katarzyna; Drożdż, Jarosław

    2014-01-01

    Pregnancy after organ transplantation is becoming relatively common. We present the case of a heart transplant recipient who gave birth to a second child. Despite the fact that the transplanted heart seems to adapt well to the changes caused by pregnancy, gestation in patients after heart transplantation may be complicated by hypertension, pre-eclampsia, or preterm labor. In this article, we consider the issues of preterm uterine contractions, anemia, thrombocytopenia, and several other complications in pregnant patients with transplanted hearts. We also present current opinions regarding the use of glucocorticoids as a form of preventing breathing disorders in neonates as well as breast-feeding by mothers receiving immunosuppressive agents. Pregnancies in heart transplant recipients should be considered high-risk. A second successful delivery of a healthy child remains a challenge for such patients and their doctors. PMID:26336446

  3. Pregnancy outcomes in Southeast Asian migrant workers at Southern Thailand.

    PubMed

    Hanprasertpong, T; Hanprasertpong, J

    2015-01-01

    This retrospective study was conducted to determine the pregnancy outcomes and identify predictive factors of adverse outcomes in pregnant migrant workers who delivered at Songklanagarind Hospital from January 2002 to December 2012. Two hundred and forty migrant worker pregnancies were enrolled. Pre-eclampsia, gestational diabetes mellitus, pre-term birth and foetal intrauterine growth restriction found were 15, 7.9, 13.7 and 3.7%, respectively. No stillbirth was found. Apgar score was

  4. Development of prenatal screening--A historical overview.

    PubMed

    Cuckle, Howard; Maymon, Ron

    2016-02-01

    The first prenatal screening test to be introduced was based on a single maternal serum marker of neural tube defects. Since then various prenatal screening concepts have been developed, the most successful being Down syndrome risk estimation using multiple serum and ultrasound markers. Today a completely new approach to aneuploidy screening is available based on maternal plasma cell-free DNA testing. This has the potential to markedly improve screening performance but routine testing is currently too expensive in a public health setting. However, it can be cost-effective when used in combination with existing multi-maker tests. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia that can be prevented using soluble low-dose aspirin treatment started before 16 weeks of gestation. Prenatal screening for cardiac abnormalities, fragile X syndrome and recessive genetic disorders is underutilized and public health planners should considered a more widespread application of available methods. PMID:26764253

  5. 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

  6. [Takayashu and pregnancy].

    PubMed

    Belyamani, L; Azendour, H; Elmoqadem, A; Kouach, J; Zidouh, S; Drissi Kamili, N

    2009-06-01

    Takayashu arteritis is a chronic inflammatory disease of the large arteries, usually affecting the aorta and its large branches and the pulmonary arteries, with a higher incidence during the childbearing years. We report the case of a 33-year-old patient, primigravida with Takayashu arteritis diagnosed three years ago. At 37 weeks of gestation, she was admitted for a pre-eclampsia and a left ventricular insufficiency. Elective caesarean section under general anesthesia after joint decision between the attending obstetrician and the medical and anesthetic consultants, and allowed the extraction of a hypotrophic baby. The association of pregnancy with Takayashu's arteritis is almost always uneventful. It is associated with high values of maternal blood pressure and severe intra-uterine growth retardation. PMID:18930177

  7. 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. PMID:26467747

  8. 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

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

    PubMed Central

    2013-01-01

    Introduction Advanced abdominal (extrauterine) pregnancy is a rare condition with high maternal and fetal morbidity and mortality. Because the placentation in advanced abdominal pregnancy is presumed to be inadequate, advanced abdominal pregnancy can be complicated by pre-eclampsia, which is another condition with high maternal and perinatal morbidity and mortality. Diagnosis and management of advanced abdominal pregnancy is difficult. Case presentation We present the case of a 33-year-old African woman in her first pregnancy who had a full-term advanced abdominal pregnancy and developed gross ascites post-operatively. The patient was successfully managed; both the patient and her baby are apparently doing well. Conclusion Because most diagnoses of advanced abdominal pregnancy are missed pre-operatively, even with the use of sonography, the cornerstones of successful management seem to be quick intra-operative recognition, surgical skill, ready access to blood products, meticulous post-operative care and thorough assessment of the newborn. PMID:23302289

  10. Racial Differences in C-Reactive Protein Levels During Normal Pregnancy

    PubMed Central

    Picklesimer, Amy H; Jared, Heather L.; Moss, Kevin; Offenbacher, Steven; Beck, James D; Boggess, Kim A

    2008-01-01

    Objective Characterization of serum C-Reactive Protein (CRP) levels in a diverse population of healthy pregnant women using a high sensitivity assay. Study Design Cross-sectional analysis of a cohort of 775 pregnant women. CRP measured on serum specimens drawn <26 weeks gestation using highly sensitive ELISA kits. Results Median CRP was 4.8 mg/L (inter-quartile range 0.63 – 15.7). Black women had higher median CRP values than whites (7.68 mg/L vs 2.59 mg/L, p<.001). Black women demonstrated higher levels of CRP even after controlling for known confounding factors such as smoking and maternal weight. Conclusion Pregnancy is an inflammatory stressor. The etiology of racial differences is unclear, but may be important for understanding racial disparities in the incidence inflammatory disorders such as preterm labor and pre-eclampsia. PMID:18539258

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

    PubMed

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

    2014-05-01

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

  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. Roles and regulation of the matrix metalloproteinase system in parturition.

    PubMed

    Geng, Junnan; Huang, Cong; Jiang, Siwen

    2016-04-01

    Significant tissue destruction, repair, and remodeling are involved in parturition, which involves fetal membrane rupture, cervical ripening, and uterine contraction and its subsequent involution. Extracellular matrix degradation and remodeling by proteolytic enzymes, such as matrix metalloproteinases (MMPs), are required for the final steps of parturition. MMPs participate in physiological degradation and remodeling through their proteolytic activities on specific substrates, and are balanced by the action of their inhibitors. Disruption to this balance can result in pathological stress that ends with preterm or post-term birth or pre-eclampsia. In this review, we examine the roles and regulation of the MMP system in physiological and pathological labor, and propose a model that illustrates the mechanisms by which the MMP system contributes to these processes. Mol. Reprod. Dev. 83: 276-286, 2016. © 2016 Wiley Periodicals, Inc. PMID:26888468

  14. Predicting the development of pregnancy-associated hypertension. The place of standardised blood-pressure measurement.

    PubMed

    Gallery, E D; Hunyor, S N; Ross, M; Györy, A Z

    1977-06-18

    82 initially normotensive pregnant women with no known history of renal disease were seen at monthly intervals from 16 weeks' amenorrhoea onwards, and their blood-pressure (B.P.) was measured sitting and lying on their left side. 15 developed hypertension (B.P. greater than 135/85 mm Hg lying on the left side) in late pregnancy. When these women were compared with the 67 who remained normotensive throughout, their B.P.s were found to be significantly higher even in early pregnancy, although individual patients were not always separable in this way. When B.P. measured in this rigidly standardised manner was compared with routine antenatal clinic values, it was apparent that the latter did not detect the difference between the two groups. Women who develop hypertension in the third trimester of pregnancy (pre-eclampsia) may represent a separate group from entirely normal pregnant women from the beginning of pregnancy. PMID:68380

  15. Successful pregnancy with autoimmune cirrhosis.

    PubMed

    Braga, António; Braga, Jorge

    2016-01-01

    Pregnancy with liver cirrhosis is a rare and dangerous event that exposes mother and fetus to potentially lethal risks. During pregnancy, hepatic decompensation could suffice and the development of hepatic failure and encephalopathy could occur. The incidence of obstetric complications is also increased with a high rate of pre-eclampsia, postpartum bleeding, preterm delivery and stillbirth. We report a case of a 27-year-old woman with autoimmune hepatitis and liver cirrhosis complicated by splenomegaly, oesophageal varices and severe thrombocytopaenia. During pregnancy, close clinical and analytical surveillance was performed. She was medicated with corticosteroids, azathioprine and propranolol. At the 25th week of gestation, an upper gastrointestinal endoscopy was performed to control oesophageal varices. This patient had an uneventful pregnancy until 37 weeks. At 37th week of gestation, after spontaneous rupture of membranes, signs of acute fetal distress were observed, and an urgent caesarean was performed. Good neonatal and maternal outcomes were achieved. PMID:26825934

  16. Human chronic gonadotropin concentrations in very early pregnancy and subsequent preeclampsia.

    PubMed

    Rabie, Nader Z; Magann, Everett F

    2014-09-01

    Evaluation of: Asvold BO, Vatten LJ, Tanbo TG, Eskild A. Concentrations of human chorionic gonadotrophin in very early pregnancy and subsequent pre-eclampsia: a cohort study. Hum. Reprod. 29(6), 1153-1160 (2014). A total of 2405 consecutive singleton pregnancies were followed to determine if early HCG levels were associated with the development of preeclampsia. All pregnancies were conceived by in vitro fertilization, which allowed very accurate gestational age dating. HCG levels were obtained on day 12, and grouped into 4 categories (<50, 50-99, 100-149, ≥ 150). HCG levels less than 50 were associated with an odds ratio of 2.3 (95% CI: 1.2-4.7) for preeclampsia and and odds ratio of 4.2 (95% CI: 1.4-12.2) for severe preeclampsia. Early HCG levels may serve as a marker for the detection of preeclampsia. PMID:25335537

  17. What are the roles of macrophages and monocytes in human pregnancy?

    PubMed

    Tang, Mao-Xing; Hu, Xiao-Hui; Liu, Zhao-Zhao; Kwak-Kim, Joanne; Liao, Ai-Hua

    2015-11-01

    During pregnancy, the maternal immune system is challenged by the semi-allogeneic fetus, which leads to systemic and local immunity. Systemic immunity, including enhanced innate immunity with increased activation of monocytes, is induced by various placental factors. Maternal immune adaptations are most evident at the feto-maternal interface, where macrophages are enriched and communicate with various decidual leukocytes. These cells are not only contributing to the protection of the growing fetus from microorganisms, but also aiding placental development by promoting trophoblast invasion and spiral artery remodeling, and the parturition process. Thus, monocytes and macrophages concurrently play important roles throughout the trimesters. Dysregulation of these cells may thus lead to pregnancy complications, such as pre-eclampsia and preterm labor. In this review, monocytes and macrophage subsets and their roles in normal and pathological pregnancies are reviewed. PMID:26340023

  18. 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

  19. Infertility today: the management of female medical causes.

    PubMed

    Tinneberg, Hans-Rudolf; Gasbarrini, Antonio

    2013-12-01

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

  20. Successful Pregnancy Following Assisted Reproduction in Woman With Systemic Lupus Erythematosus and Hypertension

    PubMed Central

    de Macedo, José Fernando; de Macedo, Gustavo Capinzaiki; Campos, Luciana Aparecida; Baltatu, Ovidiu Constantin

    2015-01-01

    Abstract Patients with systemic lupus erythematosus have a poor prognosis of pregnancy, since it is associated with significant maternal and fetal morbidity, including spontaneous miscarriage, pre-eclampsia, intrauterine growth restriction, fetal death and pre-term delivery. We report a case with successful pregnancy in a patient with systemic lupus erythematosus and hypertension. A 39-year-old nulliparous woman presented with systemic lupus erythematosus with antinuclear and antiphospholipid antibodies, hypertension and recurrent pregnancy loss presented for assisted reproduction. The patient responded well to enoxaparin and prednisone during both assisted reproduction and prenatal treatment. This case report indicates that prescription of immunosuppressant and blood thinners can be safely recommended throughout the whole prenatal period in patients with systemic lupus erythematosus. Enoxaparin and prednisone may be prescribed concurrently during pregnancy. PMID:26376400

  1. Extracellular vesicles and reproduction-promotion of successful pregnancy.

    PubMed

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

    2014-11-01

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

  2. 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

  3. Maternal deaths associated with eclampsia in South Africa: Lessons to learn from the confidential enquiries into maternal deaths, 2005 - 2007.

    PubMed

    Moodley, J

    2010-11-01

    Eclampsia is the commonest direct cause of maternal death in South Africa. The latest Saving Mothers Report (2005-2007) indicates that there were 622 maternal deaths due to hypertensive disorders of pregnancy. Of these, 334 (55.3%) were due to eclampsia; of the eclamptic deaths, 50 were over the age of 35 years and 83 were under 20 years old. Avoidable factors involved patient related factors (mainly delay in seeking help), administrative factors (mainly delay in transport) and health personnel issues (mainly due to delay in referring patients). The major causes of death were cerebrovascular accidents and cardiac failure. The majority of deaths due to cardiac failure were due to pulmonary oedema. To reduce deaths from eclampsia, more attention must be given to the detection of pre-eclampsia; the provision of information on the advantages of antenatal care to the population at large and training of health professions in the management of obstetric emergencies. PMID:21081020

  4. When a pregnancy required a neurological consultation: a case report.

    PubMed

    Ferraldeschi, M; Tari Capone, F; Di Lisi, F; Patella, R; Ceschim, V; Cao, M; Cannoni, S; Rasura, M

    2012-11-01

    Posterior reversible encephalopathy syndrome (PRES) is a transient clinical and neuroradiological syndrome characterized by clinical signs and symptoms including hypertension, seizures, altered mental status, headache, and vision changes and characteristic features on head computed tomography (CT) or magnetic resonance imaging (MRI) scan. PRES is most commonly reported in the literature in association with obstetric patients suffering from pre-eclampsia or eclampsia. In the acute setting, it is important to recognize the characteristics of PRES and immediately treat patients' emerging conditions that are hypertension and seizures. The following case report describes a pregnant patient who presented clinical characteristics of eclampsia with recurrent episodes of seizure and hypertension complicated by PRES. This case highlights the importance of early recognition and treatment of this condition that is usually transient and completely reversible, but can lead to ischemic injury and irreversible brain damage. PMID:23306742

  5. Pheochromocytoma in pregnancy: a case report and review of literature

    PubMed Central

    George, J; Tan, J Y L

    2010-01-01

    Hypertension is a common problem in pregnancy that can result in significant maternal and fetal morbidity and mortality. The common causes include pre-eclampsia, gestational hypertension and essential hypertension. Although phaeochromocytoma is a rare cause of hypertension in pregnancy, it can lead to potentially life-threatening cardiovascular complications for the mother and increased fetal mortality if left undiagnosed and untreated. The diagnosis can be confirmed by measurement of plasma and urinary catecholamines and their metabolities followed by radiological localization of the tumour. Surgical resection of the tumour after adequate pre-operative control of hypertension using sequential alpha- followed by beta-blockers is the definitive treatment. In pregnancy, depending on the gestation at which diagnosis is made, the optimal timing for surgery is during the late first or early second trimester. When the pregnancy is more advanced, medical management followed by combined caesarean section and tumour resection closer to term is preferred.

  6. A comparison between 24-hour and 2-hour urine collection for the determination of proteinuria.

    PubMed

    Somanathan, N; Farrell, T; Galimberti, A

    2003-07-01

    Proteinuria is one of the fundamental criteria for the diagnosis of pre-eclampsia with quantitative assessment based on the 24-hour urine protein estimation as the gold standard. This study was undertaken to determine whether a 2-hour protein estimation correlated with that of a formal 24-hour collection. Thirty women with proteinuric hypertension were recruited. There was significant correlation between the 2-hour and 24-hour urine protein levels (Pearson's correlation coefficient 0.76 (P 0.000). A positive 2-hour test was associated more closely with significant levels of 24-hour proteinuria than dipstick analysis alone. We conclude from this study that a random 2-hour sample could be used for the initial assessment of proteinuria and so avoid the delay associated with 24-hour quantification of urinary protein. PMID:12881076

  7. The effects of exposure to particulate matter and neighbourhood deprivation on gestational hypertension.

    PubMed

    Vinikoor-Imler, Lisa C; Gray, Simone C; Edwards, Sharon E; Miranda, Marie Lynn

    2012-03-01

    Gestational hypertension, pre-eclampsia and eclampsia are conditions that affect the health of both mothers and infants during and after pregnancy. Recent research indicates the importance of considering environmental, social and individual contributors to poor pregnancy outcomes. Our research examined particulate matter (PM) concentrations as one measure of environmental exposure and neighbourhood quality as one measure of the social environment. We used these measures, as well as maternal characteristics, to predict the risk of gestational hypertension (including pre-eclampsia and eclampsia). North Carolina Detailed Birth Record data for 2000-2003 were obtained and geocoded for all singleton births. Levels of PM(10) and PM(2.5) were determined using air quality data from the US Environmental Protection Agency. Information on a woman's residential neighbourhood was determined from 2000 Census data. Modified Poisson regression models clustered by tract were used to examine the associations between PM levels, neighbourhood deprivation and maternal characteristics with gestational hypertension. Analysis was restricted to women residing within 20 km of a PM monitor. Both PM(10) and PM(2.5) were associated with gestational hypertension; the risk ratios for an interquartile range (IQR) increase in exposure were 1.07 [95% confidence interval (CI) 1.04, 1.11] for PM(10) (IQR: 3.92 µg/m(3)) and 1.11 [95% CI 1.08, 1.15] for PM(2.5) (IQR: 2.24 µg/m(3)). Living in a neighbourhood with increased levels of deprivation was also associated with gestational hypertension. Any smoking during pregnancy, younger age and higher level of education were inversely associated with risk of gestational hypertension. Compared with non-Hispanic White women, non-Hispanic Black women were at higher risk of gestational hypertension, whereas Hispanic women were at lower risk. Increased levels of PM and neighbourhood deprivation, as well as certain individual characteristics, were associated with

  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. PMID:27465822

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

    PubMed

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

    2014-07-01

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

  10. 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

  11. 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).

  12. Gestational and Pregestational Diabetes Mellitus in Omani Women

    PubMed Central

    Abu-Heija, Adel T.; Al-Bash, Majeda; Mathew, Mariam

    2015-01-01

    Objectives: The aim of this study was to assess the prevalence of gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM) among pregnant women in Oman and compare their obstetric and perinatal outcomes. Methods: This retrospective study assessed the obstetric and perinatal outcomes of pregnant Omani women with GDM or PGDM who delivered at the Sultan Qaboos University Hospital in Muscat, Oman, between January 2009 and December 2010. Results: There were a total of 5,811 deliveries during the study period. Of the 5,811 women who gave birth, 639 women were found to have diabetes mellitus (11.0%). A total of 581 of the diabetic women had GDM (90.9%) and only 58 (9.1%) had PGDM. Women with PGDM had a significantly higher incidence of pre-eclampsia (P = 0.022), preterm deliveries (P <0.001) and Caesarean sections (P <0.001). Neonatal complications, such as respiratory distress syndrome (RDS), neonatal hypoglycaemia, neonatal jaundice and subsequent admission to a neonatal intensive care unit (NICU) were significantly higher for neonates born to mothers with PGDM compared to those born to mothers with GDM (P <0.001). The corrected perinatal mortality rates for women with PGDM and GDM were 34.5 and 13.7 per 1,000 live births, respectively. Conclusion: In this Omani cohort, women with PGDM were at higher risk of developing obstetric and perinatal complications such as pre-eclampsia, preterm delivery and Caesarean delivery compared to women with GDM. In addition, neonates who had mothers with PGDM had higher rates of RDS, neonatal hypoglycaemia, neonatal jaundice and admission to the NICU. PMID:26629376

  13. Clinical cardiovascular risk during young adulthood in offspring of hypertensive pregnancies: insights from a 20-year prospective follow-up birth cohort

    PubMed Central

    Davis, Esther F; Lewandowski, Adam J; Aye, Christina; Williamson, Wilby; Boardman, Henry; Huang, Rae-Chi; Mori, Trevor A; Newnham, John; Beilin, Lawrence J; Leeson, Paul

    2015-01-01

    Objectives Offspring of hypertensive pregnancies have increased cardiovascular risk factors during childhood. We hypothesised that offspring of hypertensive pregnancies would demonstrate increased clinical levels of hypertension by young adult life, which would be proportional to the severity of the pregnancy complication. Design Prospective birth cohort study Setting Tertiary obstetric hospital. Participants 2868 young adult offspring of women enrolled during pregnancy into the Western Australia Pregnancy Cohort (Raine) Study. Main outcome measures Cardiovascular risk, including incidence of hypertension and metabolic disease, in those born to hypertensive compared to normotensive pregnancies. Results Young adult offspring of hypertensive pregnancies were 2.5 times (95% CI 1.32 to 4.56, p=0.004) more likely to have global lifetime risk (QRISK) scores above the 75th centile. Thirty per cent of 20 year olds with hypertensive blood pressures were born following a hypertensive pregnancy. Pre-eclampsia or hypertension resulting in preterm birth associated with a threefold (95% CI 1.3 to 7.0, p=0.01) greater risk of being hypertensive by age 20 years, with no differences in body mass index. Whereas pregnancy-induced hypertension associated with a smaller 3±1 mm Hg blood pressure rise (p=0.001) and a twofold (95% CI 1.5 to 2.8, p=0.001) greater risk of being obese or overweight. Risk factor associations were consistent throughout early life and independent of other birth-factors. Conclusions Incidence of offspring hypertension was significantly increased in those whose mothers had a more complicated pregnancy history, including preterm birth and pre-eclampsia. PMID:26105032

  14. 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

  15. 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. PMID:26888561

  16. Perinatal complications associated with maternal asthma during pregnancy

    PubMed Central

    Johnston, Stephanie; Said, Joanne

    2012-01-01

    Background Asthma is one of the most common medical illnesses occurring in pregnancy and its incidence amongst the obstetric population is increasing. Previous studies have suggested that asthma is not a benign illness in pregnancy, and can contribute towards increased rates of pregnancy complications. Methods We undertook a retrospective audit of 6458 deliveries during 2008 at The Royal Women's Hospital to determine the perinatal outcomes for women with a self-reported diagnosis of asthma. Results We found that 501 (7.8%) deliveries were to women who identified themselves as asthmatics. Of these, 15.6% reported exacerbations of their asthma symptoms during pregnancy, with the remainder reporting improvement or stabilization. There was an increased rate of preterm birth (12.9%) in the asthmatic population, compared to the non-asthmatic population (OR = 1.48, CI [1.12–1.95], P = 0.005). Asthma remained significantly associated with an increased risk of preterm birth after adjusting for maternal smoking status using logistic regression analysis (Adjusted OR 1.41, CI [1.07–1.86], P = 0.01). Women were also at increased risk of developing pre-eclampsia (OR 1.71, CI [1.09–2.67], P = 0.02) but not fetal growth restriction. Women identifying themselves as asthmatics were also more likely to deliver by caesarean section (OR 1.32, CI [1.09–1.6], P = 0.003). Conclusion These findings suggest that maternal asthma may be associated with an increased risk of preterm birth, pre-eclampsia and caesarean delivery.

  17. Amniotic mesenchymal cells from pre-eclamptic placentae maintain immunomodulatory features as healthy controls.

    PubMed

    Pianta, Stefano; Magatti, Marta; Vertua, Elsa; Bonassi Signoroni, Patrizia; Muradore, Ivan; Nuzzo, Anna Maria; Rolfo, Alessandro; Silini, Antonietta; Quaglia, Federico; Todros, Tullia; Parolini, Ornella

    2016-01-01

    Pre-eclampsia (PE) is one of the most severe syndromes in human pregnancy, and the underlying mechanisms of PE have yet to be determined. Pre-eclampsia is characterized by the alteration of the immune system's activation status, an increase in inflammatory Th1/Th17/APC cells, and a decrease in Th2/Treg subsets/cytokines. Moreover, inflammatory infiltrates have been detected in the amniotic membranes of pre-eclamptic placentae, and to this date limited data are available regarding the role of amniotic membrane cells in PE. Interestingly, we and others have previously shown that human amniotic mesenchymal stromal cells (hAMSC) possess anti-inflammatory properties towards almost all immune cells described to be altered in PE. In this study we investigated whether the immunomodulatory properties of hAMSC were altered in PE. We performed a comprehensive study of cell phenotype and investigated the in vitro immunomodulatory properties of hAMSC isolated from pre-eclamptic pregnancies (PE-hAMSC), comparing them to hAMSC from normal pregnancies (N-hAMSC). We demonstrate that PE-hAMSC inhibit CD4/CD8 T-cell proliferation, suppress Th1/Th2/Th17 polarization, induce Treg and block dendritic cells and M1 differentiation switching them to M2 cells. Notably, PE-hAMSC generated a more prominent induction of Treg and higher suppression of interferon-γ when compared to N-hAMSC, and this was associated with higher transforming growth factor-β1 secretion and PD-L2/PD-L1 expression in PE-hAMSC. In conclusion, for the first time we demonstrate that there is no intrinsic impairment of the immunomodulatory features of PE-hAMSC. Our results suggest that amniotic mesenchymal stromal cells do not contribute to the disease, but conversely, could participate in offsetting the inflammatory environment which characterizes PE. PMID:26515425

  18. MSX2 Induces Trophoblast Invasion in Human Placenta.

    PubMed

    Liang, Hao; Zhang, Qian; 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

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

    PubMed

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

    2014-11-01

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

  20. Trends in health facility based maternal mortality in Central Region, Kenya: 2008-2012

    PubMed Central

    Muchemi, Onesmus Maina; Gichogo, Agnes Wangechi; Mungai, Jane Githuku; Roka, Zeinab Gura

    2016-01-01

    Introduction WHO classifies Kenya as having a high maternal mortality. Regional data on maternal mortality trends is only available in selected areas. This study reviewed health facility maternal mortality trends, causes and distribution in Central Region of Kenya, 2008-2012. Methods We reviewed health records from July 2008 to June 2012. A maternal death was defined according to ICD-10 criterion. The variables reviewed included socio-demographic, obstetric characteristics, reasons for admission, causes of death and contributing factors. We estimated maternal mortality ratio for each year and overall for the four year period using a standard equation and used frequencies means/median and proportions for other descriptive variables. Results A total 421 deaths occurred among 344,191 live births; 335(80%) deaths were audited. Maternal mortality ratios were: 127/100,000 live births in 2008/09; 124/100,000 live births in 2009/2010; 129/100,000 live births in 2010/2011 and 111/100,000 live births in 2011/2012. Direct causes contributed majority of deaths (77%, n=234) including hemorrhage, infection and pre-eclampsia/eclampsia. Mean age was 30(±6) years; 147(71%) attended less than four antenatal visits and median gestation at birth was 38 weeks (IQR=9). One hundred ninety (59%) died within 24 hours after admission. There were 111(46%) caesarian births, 95(39%) skilled vaginal, 31(13%) unskilled 5(2%) vacuum deliveries and 1(<1%) destructive operation. Conclusion The region recorded an unsteady declining trend. Direct causes contributed to the majority deaths including hemorrhage, infection and pre-eclampsia/eclampsia. We recommend health education on individualized birth plan and mentorship on emergency obstetric care. Further studies are necessary to clarify and expand the findings of this study. PMID:27516824

  1. 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

  2. Chorangiosis: the potential role of smoking and air pollution.

    PubMed

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

    2009-01-01

    Chorangiosis is considered to be strongly associated with various fetal, maternal, and placental disorders, including pre-eclampsia, diabetes, hypertension, and major congenital anomalies, and has been found to correlate with increased fetal morbidity and mortality. In this study, we investigated the pathologic effects of maternal smoking and air pollution on the pathogenesis of chorangiosis. We investigated 92 placentas macroscopically and microscopically over a 3-month period (March 2006-May 2006) at Denizli State Hospital to identify the frequency of chorangiosis and the potential role of maternal smoking and air pollution. Placental changes were examined by light microscopy after hematoxylin and eosin (H&E) staining and immunohistochemical evaluation of CD 34 and CD 68; muscle-specific actin was used to confirm the diagnosis. Among the 92 mothers included in the study, 33 were smokers (group I), 31 were thought to have been exposed to air pollution (group II), and 28 were living in rural areas free of air pollution and maternal smoking (group III). Chorangiosis was found in 14% (13/92) of all placentas: 7 (53.8%) cases were assigned to group I, 5 (38.5%) to group II, and 1 (7.7%) to group III. Vascular changes were found mainly in the smoking and air pollution groups. There appeared to be no correlation of these vascular changes with placental weight, parity, gestational age, major congenital anomalies, and maternal factors, including diabetes and pre-eclampsia. We presume that smoking and air pollution may contribute to the development of chorangiosis. We suggest that chorangiosis may be an adaptive response to maternal hypoxia, and studies addressing the role of smoking and air pollution in chorangiosis may provide new insights into the pathogenesis of this condition. PMID:18635319

  3. 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

  4. 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. PMID:23916027

  5. 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

  6. 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

  7. 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.

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

    PubMed Central

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

    2014-01-01

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

  9. 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

  10. Differences in late fetal death rates in association with determinants of small for gestational age fetuses: population based cohort study

    PubMed Central

    Cnattingius, Sven; Haglund, Bengt; Kramer, Michael S

    1998-01-01

    Objective: To examine differences in late fetal death rates in association with determinants of small for gestational age fetuses. Design: Population based cohort study. Subjects: 1 026 249 pregnancies without congenital malformations. Setting: Sweden 1983-92. Main outcome measure: Late fetal death rate. Results: Depending on underlying determinants late fetal death rates were greatly increased in extremely small for gestational age fetuses (range 16 to 45 per 1000) compared with non-small for gestational age fetuses (1.4 to 4.6). In extremely small for gestational age fetuses late fetal death rates were increased from 31 per 1000 in mothers aged less than 35 years to 45 per 1000 in older mothers, and from 22 per 1000 in women <155 cm in height to 33 per 1000 in women ⩾175 cm tall. Late fetal death rates were also higher in extremely small for gestational age fetuses in singleton compared with twin pregnancies and in non-hypertensive pregnancies compared with pregnancies complicated by severe pre-eclampsia or other hypertensive disorders. Slightly higher late fetal death rates were observed in nulliparous compared with parous women and in non-smokers compared with smokers. Conclusions: Although the risk of late fetal death is greatly increased in fetuses that are extremely small for gestational age the risk is strongly modified by underlying determinants—for example, there is a lower risk of late fetal death in a small for gestational age fetus if the mother is of short stature, has a twin pregnancy, or has hypertension. Key messages Small for gestational age fetuses are at increased risk of late fetal death regardless of the underlying determinants The effect of birthweight ratio on risk of late fetal death is modified by underlying determinants, except maternal age Regardless of birthweight ratio the rates of late fetal death are higher among women aged 35 years or older compared with younger women In pregnancies of extremely small for gestational age

  11. 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

  12. 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

  13. 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

  14. Antiphospholipid syndrome.

    PubMed

    Ruiz-Irastorza, Guillermo; Crowther, Mark; Branch, Ware; Khamashta, Munther A

    2010-10-30

    The antiphospholipid syndrome causes venous, arterial, and small-vessel thrombosis; pregnancy loss; and preterm delivery for patients with severe pre-eclampsia or placental insufficiency. Other clinical manifestations are cardiac valvular disease, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, and cognitive impairment. Antiphospholipid antibodies promote activation of endothelial cells, monocytes, and platelets; and overproduction of tissue factor and thromboxane A2. Complement activation might have a central pathogenetic role. Of the different antiphospholipid antibodies, lupus anticoagulant is the strongest predictor of features related to antiphospholipid syndrome. Therapy of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thromboprophylaxis is recommended in patients with systemic lupus erythematosus and probably in purely obstetric antiphospholipid syndrome. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin. Hydroxychloroquine is a potential additional treatment for this syndrome. Possible future therapies for non-pregnant patients with antiphospholipid syndrome are statins, rituximab, and new anticoagulant drugs. PMID:20822807

  15. 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

  16. Antiphospholipid Syndrome during pregnancy: the state of the art.

    PubMed

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

    2011-04-01

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

  17. [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. PMID:17849803

  18. 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

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

    PubMed

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

    2009-12-01

    Anti-angiogenic VEGF (vascular endothelial growth factor) isoforms, generated from differential splicing of exon 8, are widely expressed in normal human tissues but down-regulated in cancers and other pathologies associated with abnormal angiogenesis (cancer, diabetic retinopathy, retinal vein occlusion, the Denys-Drash syndrome and pre-eclampsia). Administration of recombinant VEGF(165)b inhibits ocular angiogenesis in mouse models of retinopathy and age-related macular degeneration, and colorectal carcinoma and metastatic melanoma. Splicing factors and their regulatory molecules alter splice site selection, such that cells can switch from the anti-angiogenic VEGF(xxx)b isoforms to the pro-angiogenic VEGF(xxx) isoforms, including SRp55 (serine/arginine protein 55), ASF/SF2 (alternative splicing factor/splicing factor 2) and SRPK (serine arginine domain protein kinase), and inhibitors of these molecules can inhibit angiogenesis in the eye, and splice site selection in cancer cells, opening up the possibility of using splicing factor inhibitors as novel anti-angiogenic therapeutics. Endogenous anti-angiogenic VEGF(xxx)b isoforms are cytoprotective for endothelial, epithelial and neuronal cells in vitro and in vivo, suggesting both an improved safety profile and an explanation for unpredicted anti-VEGF side effects. In summary, C-terminal distal splicing is a key component of VEGF biology, overlooked by the vast majority of publications in the field, and these findings require a radical revision of our understanding of VEGF biology in normal human physiology. PMID:19909248

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

    PubMed Central

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

    2010-01-01

    Anti-angiogenic VEGF (vascular endothelial growth factor) isoforms, generated from differential splicing of exon 8, are widely expressed in normal human tissues but down-regulated in cancers and other pathologies associated with abnormal angiogenesis (cancer, diabetic retinopathy, retinal vein occlusion, the Denys-Drash syndrome and pre-eclampsia). Administration of recombinant VEGF165b inhibits ocular angiogenesis in mouse models of retinopathy and age-related macular degeneration, and colorectal carcinoma and metastatic melanoma. Splicing factors and their regulatory molecules alter splice site selection, such that cells can switch from the anti-angiogenic VEGFxxxb isoforms to the pro-angiogenic VEGFxxx isoforms, including SRp55 (serine/arginine protein 55), ASF/SF2 (alternative splicing factor/splicing factor 2) and SRPK (serine arginine domain protein kinase), and inhibitors of these molecules can inhibit angiogenesis in the eye, and splice site selection in cancer cells, opening up the possibility of using splicing factor inhibitors as novel anti-angiogenic therapeutics. Endogenous anti-angiogenic VEGFxxxb isoforms are cytoprotective for endothelial, epithelial and neuronal cells in vitro and in vivo, suggesting both an improved safety profile and an explanation for unpredicted anti-VEGF side effects. In summary, C-terminal distal splicing is a key component of VEGF biology, overlooked by the vast majority of publications in the field, and these findings require a radical revision of our understanding of VEGF biology in normal human physiology. PMID:19909248

  1. 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

  2. [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. PMID:27276545

  3. The protean manifestations of pheochromocytoma.

    PubMed

    Manger, W M

    2009-09-01

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

  4. 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

  5. Outcome assessment of pregnancy-related acute kidney injury in Morocco: A national prospective study.

    PubMed

    Kabbali, Nadia; Tachfouti, Nabil; Arrayhani, Mohammed; Harandou, Mustapha; Tagnaouti, Mounia; Bentata, Yassamine; Laouad, Inass; Ramdani, Benyounes; Bayahia, Rabia; Oualim, Zouhair; Houssaini, Tarik Sqalli

    2015-01-01

    Acute kidney injury (AKI) is a rare but life-threatening complication of pregnancy. The aim of this paper is to study the characteristics of acute AKI in pregnancy and to emphasize on its management modalities in Moroccan hospitals. This is a national prospective study performed over six months from July 1 to December 31 2010 on AKI developing in pregnant patients, both preand post-partum period. Patients with pre-existing kidney disease were excluded from the study. Outcome was considered unfavorable when complete recovery of renal function was not achieved and/or maternal death occurred. Forty-four patients were included in this study. They were 29.6 ± 6 years old and mostly illiterate (70.6%). Most AKI occurred in the post-partum period, with 66% of the cases occurring in those who did not receive antenatal care. The main etiologies were pre-eclampsia (28 cases), hemorrhagic shock (six cases) and septic events (five cases). We noted three cases of acute fatty liver, one case of obstructive kidney injury and one case of lupus nephritis. Hemodialysis was necessary in 17 (38.6%) cases. The outcome was favorable in 29 patients. The maternal mortality rate was 11.4%. Two poor prognostic factors were identified: Age over 38 years and sepsis. AKI is a severe complication of pregnancy in developing countries. Its prevention necessitates the improvement of the sanitary infrastructure and the establishment of the obligatory antenatal care. PMID:26022044

  6. Seasonal variation and hypertensive disorders of pregnancy in eastern Sudan.

    PubMed

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

    2015-02-01

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

  7. 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

  8. Association between World Health Organization categories of body mass index and relative risks for weight-related pregnancy outcomes: a retrospective cohort study

    PubMed Central

    Zaballa, Katrina; Liu, Anthony; Peek, Michael John; Mongelli, Max; Nanan, Ralph

    2012-01-01

    Objective To analyse the dose-dependent effect of body mass index (BMI) categories for common pregnancy outcomes. Methods A retrospective cohort study of all deliveries that occurred between 1 January 2005 and 31 December 2009 in a tertiary maternity centre, in Sydney Australia. Common pregnancy outcomes were analysed against World Health Organization (WHO) BMI categories using multiple logistic regression analysis. Results From a total of 18,304 pregnancies, 9087 singleton pregnancies with complete data-sets were identified. Of these pregnancies, 4000 (44%) had a normal BMI, 470 (5.2%) were underweight, 2293 (25.2%) were overweight, 1316 (14.5%) were obese class I, 630 (6.9%) were obese class II and 378 (4.2%) were obese class III. Using the normal BMI category as the reference, there was a clear dose effect of BMI categories for hypertension (P < 0.001), pre-eclampsia (P < 0.001), caesarean section (P < 0.001), macrosomia (P < 0.001), large for gestational age (P < 0.001), small for gestational age (P < 0.001) and neonatal respiratory distress (P = 0.039). In contrast, despite a significant association with BMI (P < 0.001), a dose-dependent effect was not found for gestational diabetes. Conclusion The results of our study have important clinical significance as the data, using WHO BMI categories, more accurately help stratify risk assessment in a clinically relevant dose-dependent relationship.

  9. 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

  10. 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

  11. 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

  12. 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

  13. A rare manifestation of neonatal alloimmune thrombocytopaenia

    PubMed Central

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

    2014-01-01

    Neonatal alloimmune thrombocytopaenia (NAIT) results from a fetomaternal incompatibility with maternal sensitisation against a fetal human platelet antigen (HPA) and antibodies transfer to the fetal circulation, leading to platelet destruction. The clinical presentation is variable and isolated intraocular haemorrhage is rare. We present the case of a male newborn, with intrauterine growth restriction, born at 29 weeks due to pre-eclampsia. He presented proptosis of the left eye, hyphaema and elevated intraocular pressure, with no other signs of haemorrhage. Severe thrombocytopaenia was found (27×109/L). Perinatal infection and maternal thrombocytopaenia were excluded. Positive anti-HPA-1a and antihuman leucocyte antigen class I alloantibodies were found in the mother. Platelet crossmatch between the father's platelets and mother's plasma was positive. Platelet transfusions and intravenous immunoglobulin were given with favourable response. This case highlights an unusual presentation of NAIT, which should be suspected in the presence of severe thrombocytopaenia in the first 24–72 h of life. PMID:24891486

  14. Adverse pregnancy and neo-natal outcomes after assisted reproductive treatment in patients with pelvic endometriosis: a case-control study.

    PubMed

    Jacques, Marianne; Freour, Thomas; Barriere, Paul; Ploteau, Stéphane

    2016-06-01

    To assess the impact of endometriosis on obstetric outcomes and to determine whether the severity, location and surgical treatment of the disease before the pregnancy had an impact on the prevalence of these disorders, a monocentric, case-control study was performed. In total, 113 pregnancies obtained by assisted reproductive treatment among patients with endometriosis were matched with control selected among assisted reproductive treatment pregnancies due to male infertility. The main result measures were pregnancy outcome at the obstetrical and neo-natal levels. The incidence of first trimester bleeding, pre-eclampsia, premature delivery threat, pelvic pain and Caesarean section was significantly higher (P < 0.05) in women with endometriosis. Except for gestational diabetes and intrauterine growth restriction (IUGR), the severity, location of lesions and surgical treatment of endometriosis did not have an impact on either pregnancy outcome or risk of obstetric complications. The IUGR is mainly due to deep locations and the revised American Fertility Society (rAFS) stages III-IV. Newborns with a mother suffering from endometriosis are at greater risk of being premature, smaller for their gestational age and more frequently hospitalized than the control group. Deep location of endometriosis is associated with more prematurity, hospitalization and smaller birthweight than ovarian locations. PMID:27068240

  15. Adenomyosis: new knowledge is generating new treatment strategies.

    PubMed

    Benagiano, Giuseppe; Brosens, Ivo; Carrara, Sabina

    2009-05-01

    In the early days, all mucosal invasions of abdominal organs were considered to be one pathological condition of uncertain origin, termed adenomyoma. It was only in the 1920s that endometriosis and adenomyosis were clearly separated and it took approximately 80 years to put forward a new theory reunifying their pathogenesis. Today, identification of adenomyosis is carried out exclusively through vaginal ultrasonography and MRI. These techniques have made a careful evaluation of a distinct anatomical structure and the inner myometrial layers underlying the endometrium, termed the junctional zone, possible. Adenomyosis is characterized by a homogeneous thickening of this portion of the myometrium. When this hyperplasia is associated to an alteration of spiral arterioles' angiogenesis, then both adenomyosis and endometriosis may develop. Evidence is being accumulated that pre-eclampsia, fetal growth restriction and premature delivery may be linked, together representing a new, major obstetrical syndrome characterized by a modified uterine environment around the time of nidation. A dozen different medical or surgical techniques are utilized for the treatment of adenomyosis and novel approaches are being tested. These include use of inhibitors of angiogenesis that have been shown to cause reduced neo-angiogenesis, a significant modification of gene expression and a decrease in the percentage of active lesions. Encouraging results have also been obtained with the levonorgestrel-releasing intrauterine system. PMID:19392615

  16. Biological Functions of Thyroid Hormone in Placenta

    PubMed Central

    Chen, Cheng-Yi; Chen, Chie-Pein; Lin, Kwang-Huei

    2015-01-01

    The thyroid hormone, 3,3,5-triiodo-l-thyronine (T3), modulates several physiological processes, including cellular growth, differentiation, metabolism, inflammation and proliferation, via interactions with thyroid hormone response elements (TREs) in the regulatory regions of target genes. Infection and inflammation are critical processes in placental development and pregnancy-related diseases. In particular, infection is the leading cause of neonatal mortality and morbidity worldwide. However, to date, no successful approach has been developed for the effective diagnosis of infection in preterm infants. Pre-eclampsia (PE) is a serious disorder that adversely affects ~5% of human pregnancies. Recent studies identified a multiprotein complex, the inflammasome, including the Nod-like receptor (NLR) family of cytosolic pattern recognition receptors, the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, which plays a vital role in the placenta. The thyroid hormone modulates inflammation processes and is additionally implicated in placental development and disease. Therefore, elucidation of thyroid hormone receptor-regulated inflammation-related molecules, and their underlying mechanisms in placenta, should facilitate the identification of novel predictive and therapeutic targets for placental disorders. This review provides a detailed summary of current knowledge with respect to identification of useful biomarkers and their physiological significance in placenta. PMID:25690032

  17. 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

  18. 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

  19. 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. PMID:27170927

  20. 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

  1. Epigenetics: new concepts of old phenomena in vascular physiology.

    PubMed

    Krause, Bernardo; Sobrevia, Luis; Casanello, Paola

    2009-10-01

    The hypothesis of 'Developmental Origins of Health and Disease' (DOHaD) relies on the presence of mechanisms sensing and signalling a diversity of stimuli during fetal development. The mechanisms that have been broadly suggested to be involved in these processes are the epigenetic modifications that could 'record' perinatal stimuli. Since the definition of epigenetic and the associated mechanisms are conflictive, in this review epigenetic was defined as 'chromosome-based mechanisms that can change the phenotypic plasticity in a cell or organism'. The most understood epigenetic mechanisms (i.e. DNA methylation, histone post-translational modifications (PTM), ATP-dependent chromatin modifications and non-coding RNAs) and reported evidence for their role in fetal programming were briefly reviewed. The development of the vascular system is strongly influenced by epigenetic mechanisms. For that reason vascular cells are good candidates to be explored regarding epigenetic programming since its proved susceptibility to be imprinted. This has been described in pregnancy diseases such as intra-uterine growth restriction, gestational diabetes and pre-eclampsia, where changes in vascular function are preserved in vitro. PMID:19485890

  2. Indications and outcome for obstetric patients' admission to intensive care unit: a 7-year review.

    PubMed

    Lataifeh, I; Amarin, Z; Zayed, F; Al-Mehaisen, L; Alchalabi, H; Khader, Y

    2010-05-01

    The objective of this retrospective study was to investigate the indications, interventions and clinical outcome of pregnant and newly delivered women admitted to the multidisciplinary intensive care unit at the King Abdullah University Hospital in Jordan over a 7-year period from January 2002 to December 2008. The collected data included demographic characteristics of the patients, mode of delivery, pre-existing medical conditions, reason for admission, specific intervention, length of stay and maternal outcome. A total of 43 women required admission to the intensive care unit (ICU), which represented 0.37% of all deliveries. The majority (95.3%) of patients were admitted to the ICU postpartum. The most common reasons for admissions were (pre)eclampsia (48.8%) and obstetric haemorrhage (37.2). The remainder included adult respiratory distress syndrome (6.9%), pulmonary embolism (2.3%) and neurological disorders (4.6%). Mechanical ventilation was required to support 18.6% of patients and transfusion of red blood cells was needed for 48.8% of patients. There were three maternal deaths (6.9%). A multidisciplinary team approach is essential to improve the management of hypertensive disorders and postpartum haemorrhage to achieve significant improvements in maternal outcome. A large, prospective study to know which women are at high risk of admission to the intensive care units and to prevent serious maternal morbidity and mortality is warranted. PMID:20455722

  3. 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.

  4. 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.

  5. PubMed Central

    Ménard, L; Gagnon, R

    1994-01-01

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

  6. 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

  7. 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

  8. Use of oral anti-diabetic agents in pregnancy: a pragmatic approach.

    PubMed

    Kalra, Bharti; Gupta, Yashdeep; Singla, Rajiv; Kalra, Sanjay

    2015-01-01

    Insulin is the gold standard for treatment of hyperglycemia during pregnancy, when lifestyle measures do not maintain glycemic control during pregnancy. However, recent studies have suggested that certain oral hypoglycemic agents (metformin and glyburide) may be safe and be acceptable alternatives. There are no serious safety concerns with metformin, despite it crossing the placenta. Neonatal outcomes are also comparable, with benefit of reductions in neonatal hypoglycemia, maternal hypoglycemia and weight gain, and improved treatment satisfaction. Glibenclamide is more effective in lowering blood glucose in women with gestational diabetes, and with a lower treatment failure rate than metformin. Although generally well-tolerated, some studies have reported higher rates of pre-eclampsia, neonatal jaundice, longer stay in the neonatal care unit, macrosomia, and neonatal hypoglycaemia. There is also paucity of long-term follow-up data on children exposed to oral agents in utero. This review aims to provide an evidence-based approach, concordant with basic and clinical pharmacological knowledge, which will help medical practitioners use oral anti-diabetic agents in a rational and pragmatic manner. Pubmed search was made using Medical Subject Headings (MESH) terms "Diabetes" and "Pregnancy" and "Glyburide"; "Diabetes" and "Pregnancy" and "Metformin". Limits were randomized controlled trials (RCTs) and meta-analysis. The expert reviews on the topic were also used for discussion. Additional information (studies/review) pertaining to discussion under sub-headings like safety during breastfeeding; placental transport; long-term safety data were searched (pubmed/cross-references/expert reviews). PMID:25709972

  9. Effects of Parity on Blood Pressure among African-American Women

    PubMed Central

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

    2010-01-01

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

  10. Long-term medical risks to the living kidney donor.

    PubMed

    Lam, Ngan N; Lentine, Krista L; Levey, Andrew S; Kasiske, Bertram L; Garg, Amit X

    2015-07-01

    Living kidney donation benefits recipients and society but carries short-term and long-term risks for the donor. This Review summarizes the studies that underlie our current understanding of these risks in the first decade after donation, with a view to improving the informed consent process. Two studies report a higher risk of end-stage renal disease (ESRD) among donors than among healthy nondonors; however, the absolute 15-year incidence of ESRD is <1%. All-cause mortality and the risk of cardiovascular events are similar among donors and healthy nondonors, although one study provides evidence for a 5% increase in all-cause mortality after 25 years that is attributable to donation. Some evidence suggests that the 20-year incidence of gout is slightly higher among donors than among healthy nondonors. The risks of gestational hypertension or pre-eclampsia seem to be 6% higher in pregnancies among donors than in pregnancies among healthy nondonors. The incidences of acute kidney injury, kidney stones that require surgical intervention, gastrointestinal bleeding and fractures seem no higher among donors than among healthy nondonors, although some of these conclusions are based on a small number of events. Future studies must clarify the lifetime incidence of long-term outcomes, particularly in relation to a donor's age, race, and history of comorbidities. PMID:25941060

  11. 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

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

    PubMed Central

    Effer, S. B.

    1969-01-01

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

  13. 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

  14. Modelling the type and timing of consecutive events: application to predicting preterm birth in repeated pregnancies

    PubMed Central

    Shih, Joanna H.; Albert, Paul S.; Mendola, Pauline; Grantz, Katherine L.

    2016-01-01

    Summary Predicting the occurrence and timing of adverse pregnancy events such as preterm birth is an important analytical challenge in obstetrical practice. Developing statistical approaches that can be used to assess the risk and timing of these adverse events will provide clinicians with tools for individualized risk assessment that account for a woman’s prior pregnancy history. Often adverse pregnancy outcomes are subject to competing events; for example, interest may focus on the occurrence of pre-eclampsia-related preterm birth, where preterm birth for other reasons may serve as a competing event. We propose modelling the type and timing of adverse outcomes in repeated pregnancies. We formulate a joint model, where types of adverse outcomes across repeated pregnancies are modelled by using a polychotomous logistic regression model with random effects, and gestational ages at delivery are modelled conditionally on the types of adverse outcome. The correlation between gestational ages conditional on the adverse pregnancies is modelled by the semiparametric normal copula function. We present a two-stage estimation method and develop the asymptotic theory for the estimators proposed. The model and estimation procedure proposed are applied to the National Institute of Child Health and Human Development consecutive pregnancies study data and evaluated by simulations.

  15. 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

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

    PubMed

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

    2015-06-01

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

  17. 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

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

    PubMed

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

    2012-12-01

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

  19. 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. PMID:26880019

  20. Ischemic Stroke during Pregnancy and Puerperium

    PubMed Central

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

    2011-01-01

    Ischemic stroke during pregnancy and puerperium represents a rare occurrence but it could be a serious and stressful event for mothers, infants, and also families. Whenever it does occur, many concerns arise about the safety of the mother and the fetus in relation to common diagnostic tests and therapies leading to a more conservative approach. The physiological adaptations in the cardiovascular system and in the coagulability that accompany the pregnant state, which are more significant around delivery and in the postpartum period, likely contribute to increasing the risk of an ischemic stroke. Most of the causes of an ischemic stroke in the young may also occur in pregnant patients. Despite this, there are specific conditions related to pregnancy which may be considered when assessing this particular group of patients such as pre-eclampsia-eclampsia, choriocarcinoma, peripartum cardiomiopathy, amniotic fluid embolization, and postpartum cerebral angiopathy. This article will consider several questions related to pregnancy-associated ischemic stroke, dwelling on epidemiological and specific etiological aspects, diagnostic issue concerning the use of neuroimaging, and the related potential risks to the embryo and fetus. Therapeutic issues surrounding the use of anticoagulant and antiplatelets agents will be discussed along with the few available reports regarding the use of thrombolytic therapy during pregnancy. PMID:21331336

  1. 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. PMID:26403978

  2. Born from pre-eclamptic pregnancies predisposes infants to altered cortisol metabolism in the first postnatal year

    PubMed Central

    Broughton Pipkin, Fiona; Mistry, Hiten D; Roy, Chandrima; Dick, Bernhard; Waugh, Jason; Chikhi, Rebecca; Kurlak, Lesia O; Mohaupt, Markus G

    2015-01-01

    Pre-eclampsia leads to disturbed fetal organ development, including metabolic syndrome, attributed to altered pituitary-adrenal feedback loop. We measured cortisol metabolites in infants born from pre-eclamptic and normotensive women and hypothesised that glucocorticoid exposure would be exaggerated in the former. Twenty-four hour urine was collected from infants at months 3 and 12. Cortisol metabolites and apparent enzyme activities were analysed by gas chromatography-mass spectrometry. From 3 to 12 months, excretion of THS, THF and pregnandiol had risen in both groups; THF also rose in the pre-eclamptic group. No difference was observed with respect to timing of the visit or to hypertensive status for THE or total F metabolites (P>0.05). All apparent enzymes activities, except 17α-hydroxylase, were lower in infants at 12 compared to 3 months in the normotensive group. In the pre-eclamptic group, only 11β-HSD activities were lower at 12 months.17α-hydroxylase and 11β-HSD activities of tetrahydro metabolites were higher in the pre-eclamptic group at 3 months (P<0.05). 11β-hydroxylase activity increased in the pre-eclamptic group at 12 months. Cortisol excretion, determined by increased 11β-hydroxylase, compensates for high 11β-HSD-dependent cortisol degradation at 3 months and at 12 months counterbalances the reduced cortisol substrate availability in infants born from pre-eclamptic mothers. PMID:26378058

  3. 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

  4. Fibrinogen, an endogenous ligand of Toll-like receptor 4, activates monocytes in pre-eclamptic patients.

    PubMed

    Al-ofi, Ebtisam; Coffelt, Seth B; Anumba, Dilly O

    2014-06-01

    Pre-eclampsia (PE) remains the leading cause of pregnancy-associated mortality and morbidity, urging the need for a better understanding of its aetiology and pathophysiological progression. A key characteristic of PE is a systemic, exaggerated, inflammatory condition involving abnormal cytokine levels in serum, altered immune cell phenotype and Th1/Th2-type immunological imbalance. However, it is unknown how this heightened inflammatory condition manifests. We previously reported increased expression of the lipopolysaccharide receptor, Toll-like receptor 4 (TLR4), on monocytes from PE patients compared with normotensive, pregnant patients (NP). This upregulation of TLR4 on PE monocytes was accompanied by a hyper-responsiveness to bacterial TLR4 ligands. To determine whether non-microbial, endogenous TLR4 ligands also activate monocytes from PE patients, we investigated the expression of host-derived TLR4 ligands and the response of monocytes to these endogenous ligands. Plasma levels of fibrinogen - but not fibronectin or heparan sulphate - were higher in PE patients than in NP. Exposure to fibrinogen was associated with significantly increased production of inflammatory cytokines by monocytes from PE patients. Interestingly, this effect was not observed with NP monocytes. Our findings suggest that the fibrinogen-TLR4 axis might play an important role in the atypical activation of monocytes observed in PE patients that may contribute to the exaggerated inflammatory condition. PMID:24661950

  5. Monocyte subpopulations from pre-eclamptic patients are abnormally skewed and exhibit exaggerated responses to Toll-like receptor ligands.

    PubMed

    Al-ofi, Ebtisam; Coffelt, Seth B; Anumba, Dilly O

    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 CD14(low)CD16(+) 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 CD14(high)CD16(+) and CD14(low)CD16(+) 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

  6. Urinary tract stones in pregnancy.

    PubMed

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

    1995-02-01

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

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

    PubMed

    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

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

    PubMed

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

    2011-11-01

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

  9. Implications of the angiotensin converting enzyme gene insertion/deletion polymorphism in health and disease: a snapshot review

    PubMed Central

    Gard, Paul R

    2010-01-01

    This review considers the 250+ papers concerning the association of the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (rs1799752) and various disease conditions published in 2009. The deletion allele occurs in approximately 55% of the population and is associated with increased activity of the ACE enzyme. It might be predicted that the D allele, therefore, might be associated with pathologies involving increased activity of the renin-angiotensin system. The D allele was seen to be associated with an increased risk of hypertension, pre-eclampsia, heart failure, cerebral infarct, diabetic nephropathy, encephalopathy, asthma, severe hypoglycaemia in diabetes, gastric cancer (in Caucasians) and poor prognosis following kidney transplant. On the positive side, the D allele appears to offer protection against schizophrenia and chronic periodontitis and confers greater up-per-body strength in old age. The I allele, meanwhile, offers improved endurance/athletic performance and aerobic capacity as determined by lung function tests, although it does increase the risk of oral squamous cell carcinoma and obstructive sleep apnoea in hypertensives. PMID:21537387

  10. 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

  11. 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

  12. [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. PMID:20605104

  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. PMID:26016557

  14. Acute pulmonary oedema in pregnant women.

    PubMed

    Dennis, A T; Solnordal, C B

    2012-06-01

    Acute pulmonary oedema in pregnant women is an uncommon but life-threatening event. The aims of this review are to address why pulmonary oedema occurs in pregnant women and to discuss immediate management. We performed a systematic literature search of electronic databases including MEDLINE, EMBASE and the Cochrane Library, using the key words obstetrics, pregnancy, acute pulmonary oedema, pregnancy complications, maternal, cardiac function and haemodynamics. We present a simple clinical classification of acute pulmonary oedema in pregnancy into pulmonary oedema occurring in normotensive or hypotensive women (i.e. without hypertension), and acute pulmonary oedema occurring in hypertensive women, which allows focused management. Pre-eclampsia remains an important cause of hypertensive acute pulmonary oedema in pregnancy and preventive strategies include close clinical monitoring and restricted fluid administration. Immediate management of acute pulmonary oedema includes oxygenation, ventilation and circulation control with venodilators. Pregnancy-specific issues include consideration of the physiological changes of pregnancy, the risk of aspiration and difficult airway, reduced respiratory and metabolic reserve, avoidance of aortocaval compression and delivery of the fetus. PMID:22420683

  15. Magnesium in disease

    PubMed Central

    Wanner, Christoph

    2012-01-01

    Although the following text will focus on magnesium in disease, its role in healthy subjects during physical exercise when used as a supplement to enhance performance is also noteworthy. Low serum magnesium levels are associated with metabolic syndrome, Type 2 diabetes mellitus (T2DM) and hypertension; consequently, some individuals benefit from magnesium supplementation: increasing magnesium consumption appears to prevent high blood pressure, and higher serum magnesium levels are associated with a lower risk of developing a metabolic syndrome. There are, however, conflicting study results regarding magnesium administration with myocardial infarction with and without reperfusion therapy. There was a long controversy as to whether or not magnesium should be given as a first-line medication. As the most recent trials have not shown any difference in outcome, intravenous magnesium cannot be recommended in patients with myocardial infarction today. However, magnesium has its indication in patients with torsade de pointes and has been given successfully to patients with digoxin-induced arrhythmia or life-threatening ventricular arrhythmias. Magnesium sulphate as an intravenous infusion also has an important established therapeutic role in pregnant women with pre-eclampsia as it decreases the risk of eclamptic seizures by half compared with placebo. PMID:26069818

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

    PubMed

    Jones, Karlie; Ballesteros, Angela; 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

  17. Pregnancy is not a risk factor for idiopathic sudden sensorineural hearing loss: A nationwide population-based study.

    PubMed

    Yen, Ting-Ting; Lin, Ching-Heng; Shiao, Jiun-Yih; Liang, Kai-Li

    2016-05-01

    Conclusion Sudden sensorineural hearing loss (SSNHL) in pregnancy is rare. It usually occurs in the third trimester. SSNHL in pregnancy does not increase risks during delivery or subsequent stroke. Objectives This study aimed to investigate the incidence and to determine the factors associated with SSNHL in pregnancy. Method Data were retrieved from Taiwan's National Health Insurance Database (NHIRD), covering the years 2000-2009. Patients admitted for SSNHL during pregnancy were enrolled. An age-matched controlled cohort was randomly selected from pregnant women without SSNHL in the NHIRD. The clinical characteristics of both cohorts were collected for further analyses. Results Thirty-three patients with SSNHL in pregnancy were enrolled. The estimated incidence of SSNHL in pregnancy in Taiwan was 2.71 per 100,000 pregnancies. The incidence of SSNHL in pregnancy was lower than that of the general female population. The incidence of SSNHL in the third trimester was higher compared to the other two. The incidence of SSNHL occurring in the 30-39 years old age group was higher than other groups. Women with better socioeconomic status had a higher incidence of SSNHL. There were no identified systemic diseases before SSNHL. Two patients had pre-eclampsia and one patient had premature delivery. Nevertheless, SSNHL in pregnancy did not increase the risk for stroke. PMID:27052963

  18. The proprotein convertase furin is required for trophoblast syncytialization

    PubMed Central

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

    2013-01-01

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

  19. New insights into the function of Cullin 3 in trophoblast invasion and migration.

    PubMed

    Zhang, Qian; Yu, Song; Huang, Xing; Tan, Yi; Zhu, Cheng; Wang, Yan-Ling; Wang, Haibin; Lin, Hai-Yan; Fu, Jiejun; Wang, Hongmei

    2015-08-01

    Cullin 3 (CUL3), a scaffold protein, assembles a large number of ubiquitin ligase complexes, similar to Skp1-Cullin 1-F-box protein complex. Several genetic models have shown that CUL3 is crucial for early embryonic development. Nevertheless, the role of CUL3 in human trophoblast function remains unclear. In this study, immunostaining revealed that CUL3 was strongly expressed in the villous cytotrophoblasts, the trophoblast column, and the invasive extravillous trophoblasts. Silencing CUL3 significantly inhibited the outgrowth of villous explant ex vivo and decreased invasion and migration of trophoblast HTR8/SVneo cells. Furthermore, CUL3 siRNA decreased pro-MMP9 activity and increased the levels of TIMP1 and 2. We also found that the level of CUL3 in the placental villi from pre-eclamptic patients was significantly lower as compared to that from their gestational age-matched controls. Moreover, in the lentiviral-mediated placenta-specific CUL3 knockdown mice, lack of CUL3 resulted in less invasive trophoblast cells in the maternal decidua. Taken together, these results suggest an essential role for CUL3 in the invasion and migration of trophoblast cells, and dysregulation of its expression may be associated with the onset of pre-eclampsia. PMID:26021998

  20. Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

    PubMed Central

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

    2009-01-01

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

  1. 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

  2. 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

  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. Does hypoxia play a role in infantile hemangioma?

    PubMed

    de Jong, Sophie; Itinteang, Tinte; Withers, Aaron H J; Davis, Paul F; Tan, Swee T

    2016-05-01

    Infantile hemangioma (IH), the most common tumor of infancy, is characterized by rapid growth during infancy, followed by spontaneous involution over 5-10 years. Certain clinical observations have led to the suggestion that IH is triggered and maintained by hypoxia. We review the literature on the possible role of hypoxia in the etiology of IH, in particular, (1) the role of hypoxia inducible factor-1α (HIF-1α) and its downstream targets including GLUT-1 and VEGF; (2) the pathophysiological link between IH and retinopathy of prematurity; (3) hypoxic events in the early life including placental insufficiency, pre-eclampsia and low birthweight that have the potential to promote hypoxic stress; and (4) the evidence supporting the development of IH independent of HIF-1α. We also discuss these observations in the context of recent evidence of the crucial role of stem cells and the cytokines niche that governs their proliferation and inevitable differentiation, offering novel insights into the biology of IH. We propose that various triggers may simultaneously up-regulate HIF-1α, which is downstream of the renin-angiotensin system, specifically angiotensin II, which promotes production of HIF-1α. These developments shed light to the understanding of this enigmatic condition. PMID:26940670

  5. Obstetric and long-term kidney outcomes in renal transplant recipients: a 40-yr single-center study.

    PubMed

    Stoumpos, Sokratis; McNeill, Susan H; Gorrie, Morag; Mark, Patrick B; Brennand, Janet E; Geddes, Colin C; Deighan, Christopher J

    2016-06-01

    Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case-cohort study was performed identifying 83 pairs of pregnant and non-pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre-eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of ≥20% loss of eGFR between immediately pre-pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non-pregnant controls and a pregnancy was not associated with poorer 10-yr transplant or 20-yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long-term transplant function. PMID:26992458

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

    PubMed Central

    Herington, Jennifer L.; Bany, Brent M.

    2010-01-01

    A critical period in establishing pregnancy occurs after the onset of implantation but before placental development. Evidence strongly suggests that abnormalities occurring during this period can result in pregnancy termination or in pre-eclampsia; the latter may lead to small-for-gestational-weight offspring that are likely to be unhealthy. Clearly, events occurring in the endometrium during the implantation process are crucial for proper fetal development and for optimal offspring health. In several mammalian species bi-directional communication between the conceptus and endometrium during implantation is required for successful pregnancy. Although different implantation and placentation modes occur in different mammalian species, common aspects of this bi-directional signaling may exist. The molecular signals from the trophoblast cells of the conceptus, which direct endometrial changes during implantation progression, are well known in some non-rodent species. Currently, we know little about such signaling in rodents during implantation progression, when the endometrium undergoes decidualization. This review focuses on data that support the hypothesis that paracrine signals from the rodent conceptus influence decidualization. Where possible, these findings are compared and contrasted to information currently known in other species that exhibit different implantation modes. PMID:19551814

  7. Managing type 1 diabetes mellitus in pregnancy--from planning to breastfeeding.

    PubMed

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

    2012-11-01

    Type 1 diabetes mellitus in pregnant women increases the risk of adverse outcomes for mother and offspring. Careful preconception counselling and screening is important, with particular focus on glycaemic control, indications for antihypertensive therapy, screening for diabetic nephropathy, diabetic retinopathy and thyroid dysfunction, as well as review of other medications. Supplementation with folic acid should be initiated before conception in order to minimize the risk of fetal malformations. Obtaining and maintaining tight control of blood glucose and blood pressure before and during pregnancy is crucial for optimizing outcomes; however, the risk of severe hypoglycaemia during pregnancy is a major obstacle. Although pregnancy does not result in deterioration of kidney function in women with diabetic nephropathy and normal serum creatinine levels, pregnancy complications such as pre-eclampsia and preterm delivery are more frequent in these women than in women with T1DM and normal kidney function. Rapid-acting insulin analogues are considered safe to use in pregnancy and studies on long-acting insulin analogues have provided reassuring results. Immediately after delivery the insulin requirement declines to approximately 60% of the prepregnancy dose, and remains 10% lower than before pregnancy during breastfeeding. PMID:22965164

  8. Trisomy 18: experience of a reference hospital from the south of Brazil.

    PubMed

    Rosa, Rafael F M; Rosa, Rosana C M; Lorenzen, Marina B; de Moraes, Felipe N; Graziadio, Carla; Zen, Paulo R G; Paskulin, Giorgio A

    2011-07-01

    Trisomy 18 is a chromosomal syndrome characterized by a broad clinical picture, as well as a very reserved prognosis. The aim of our study was to verify the clinical characteristics and survival of patients diagnosed in a referral hospital in southern Brazil. Our sample consisted of 31 patients, 22 were female (71%), ages ranging from 1 to 1,395 days (median 14 days). The majority had a single cell lineage with full trisomy of chromosome 18 (94%). Concerning pregnancy complications, pre-eclampsia was the main abnormality described (17%). Fetal ultrasound was performed in 23 cases, and the most frequent abnormalities were polyhydramnios (41%) and intrauterine growth retardation (27%). There were no reports of prenatal identification of the syndrome. Most patients were born by cesarean due to pregnancy and fetal complications and about half of the cases were premature. Congenital heart defects represented the main major malformation observed (94%). Thirty patients (97%) progressed to death (survival ranged from 2 to 780 days, and 87% died within the first 6 months of life). Trisomy 18 is a serious chromosomal disorder with limited survival. Abnormalities of pregnancy appear to be frequent, which can lead to complications for both fetus and mother. The prenatal identification of these patients in our country is still inadequate, resulting in important implications for genetic counseling and management of these patients and their families. And this makes the possibility of interruption of pregnancy, regardless of ethical factors involved, an unlikely option. PMID:21671399

  9. The endocrine function of human placenta: an overview.

    PubMed

    Costa, Mariana A

    2016-01-01

    During pregnancy, several tightly coordinated and regulated processes take place to enable proper fetal development and gestational success. The formation and development of the placenta is one of these critical pregnancy events. This organ plays essential roles during gestation, including fetal nourishment, support and protection, gas exchange and production of several hormones and other mediators. Placental hormones are mainly secreted by the syncytiotrophoblast, in a highly and tightly regulated way. These hormones are important for pregnancy establishment and maintenance, exerting autocrine and paracrine effects that regulate decidualization, placental development, angiogenesis, endometrial receptivity, embryo implantation, immunotolerance and fetal development. In addition, because they are released into maternal circulation, the profile of their blood levels throughout pregnancy has been the target of intense research towards finding potential robust and reliable biomarkers to predict and diagnose pregnancy-associated complications. In fact, altered levels of these hormones have been associated with some pathologies, such as chromosomal anomalies or pre-eclampsia. This review proposes to revise and update the main pregnancy-related hormones, addressing their major characteristics, molecular targets, function throughout pregnancy, regulators of their expression and their potential clinical interest. PMID:26615903

  10. 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. PMID:25602070

  11. Co-evolution of NK receptors and HLA ligands in humans is driven by reproduction.

    PubMed

    Moffett, Ashley; Colucci, Francesco

    2015-09-01

    Allogeneic individuals co-exist during pregnancy in eutherian mammals. Maternal and fetal cells intermingle at the site of placental attachment in the uterus, where the arteries are remodeled to supply the fetus with oxygen and nutrients. This access by placental cells to the maternal supply line determines the growth and birth weight of the baby and is subject to stabilizing selection. Invading placental trophoblast cells express human leukocyte antigen class I ligands (HLA-E, HLA-G, and HLA-C) for receptors on maternal uterine natural killer (NK) and myelomonocytic cells, CD94/NKG2, leukocyte immunoglobulin-like receptor (LILR), and killer immunoglobulin receptor (KIR). Of these, only the KIR/HLA-C system is highly polymorphic. Different combinations of maternal KIR and fetal HLA-C variants are correlated with low birth weight and pre-eclampsia or high birth weight and obstructed labor, the two extremes of the obstetric dilemma. This situation has arisen because of the evolution of bipedalism and subsequently, in the last million years, larger brains. At this point, the human system began to reach a balance between KIR A and KIR B haplotypes and C1 and C2 epitopes of HLA-C alleles that reflects a functional compromise between the competing demands of immunity and reproduction. PMID:26284484

  12. 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

  13. Fetal–maternal interface impedance parallels local NADPH oxidase related superoxide production

    PubMed Central

    Guedes-Martins, L.; Silva, E.; Gaio, A.R.; Saraiva, J.; Soares, A.I.; Afonso, J.; Macedo, F.; Almeida, H.

    2015-01-01

    Blood flow assessment employing Doppler techniques is a useful procedure in pregnancy evaluation, as it may predict pregnancy disorders coursing with increased uterine vascular impedance, as pre-eclampsia. While the local causes are unknown, emphasis has been put on reactive oxygen species (ROS) excessive production. As NADPH oxidase (NOX) is a ROS generator, it is hypothesized that combining Doppler assessment with NOX activity might provide useful knowledge on placental bed disorders underlying mechanisms. A prospective longitudinal study was performed in 19 normal course, singleton pregnancies. Fetal aortic isthmus (AoI) and maternal uterine arteries (UtA) pulsatility index (PI) were recorded at two time points: 20–22 and 40–41 weeks, just before elective Cesarean section. In addition, placenta and placental bed biopsies were performed immediately after fetal extraction. NOX activity was evaluated using a dihydroethidium-based fluorescence method and associations to PI values were studied with Spearman correlations. A clustering of pregnancies coursing with higher and lower PI values was shown, which correlated strongly with placental bed NOX activity, but less consistently with placental tissue. The study provides evidence favoring that placental bed NOX activity parallels UtA PI enhancement and suggests that an excess in oxidation underlies the development of pregnancy disorders coursing with enhanced UtA impedance. PMID:25912167

  14. The role of anti-phospholipid antibodies in autoimmune reproductive failure.

    PubMed

    Pantham, Priyadarshini; Abrahams, Vikki M; Chamley, Lawrence W

    2016-05-01

    Anti-phospholipid antibodies (aPL) are autoantibodies that are associated with thrombosis and a range of pregnancy complications including recurrent pregnancy loss and pre-eclampsia. The three clinically relevant, well-characterized aPL are anti-cardiolipin antibodies, lupus anticoagulant and anti-beta-2-glycoprotein I (β2GPI) antibodies. aPL do not bind directly to phospholipids but instead bind to a plasma-binding 'cofactor'. The most extensively studied cofactor is β2GPI, whose role in pregnancy is not fully elucidated. Although the pathogenicity of aPL in recurrent pregnancy loss is well established in humans and animal models, the association of aPL with infertility does not appear to be causative. aPL may exert their detrimental effects during pregnancy by directly binding trophoblast cells of the placenta, altering trophoblast signalling, proliferation, invasion and secretion of hormones and cytokines, and by increasing apoptosis. Heparin is commonly used to treat pregnant women with aPL; however, as thrombotic events do not occur in the placentae of all women with aPL, it may exert a protective effect by preventing the binding of aPL to β2GPI or by acting through non-thrombotic pathways. The aim of this review is to present evidence summarizing the current understanding of this field. PMID:26884418

  15. 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

  16. Acute hypertensive crisis in pregnancy.

    PubMed

    Silver, H M

    1989-05-01

    Severe pre-eclampsia is a state of acute afterload increase where compensation may be total by use of the Frank-Starling mechanism and/or increased adrenergic drive, or may be uncompensated in a patient with limited or exhausted preload reserve. As such, we are presented with a diverse group of patients and antihypertensive therapy ideally should be individualized. In reality we are dealing with a complex situation because of the presence of the fetus raising concerns about direct effects on the fetus as well as on uteroplacental blood flow. This limits our choice of agents to those with extensive use in pregnancy except in complicated or resistant cases. For these reasons, hydralazine is the antihypertensive agent of choice for treatment of acute hypertensive emergencies in pregnancy. In the complicated case other agents such as sodium nitroprusside or nitroglycerin may be more appropriate and, in these cases, hemodynamic monitoring should be performed to allow not only greater safety, but also to tailor therapy to the individual hemodynamic profile. PMID:2649760

  17. 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

  18. Posterior reversible encephalopathy syndrome (PRES) in a thirty-six-week gestation eclamptic.

    PubMed

    Powell, Emilie S; Goldman, Mitchell J

    2007-11-01

    Posterior reversible encephalopathy syndrome (PRES) is a transient clinical neuroradiological entity characterized by clinical signs and symptoms including hypertension, generalized seizure activity, altered mental status, headache, and vision changes; along with characteristic findings on head computed tomography or magnetic resonance imaging scan. Albeit a rare condition, PRES is most commonly reported in the literature in association with obstetric patients suffering from pre-eclampsia or eclampsia. In the acute setting, it is important to recognize the characteristics of PRES and immediately treat the inciting conditions: the patient's hypertension and seizures. Although this condition is usually transient and completely reversible, ischemic injury and irreversible damage have been reported. In the event of early and effective treatment, cognitive function may be completely restored. The following case report reviews a pregnant patient who presented to the Emergency Department with generalized seizure activity and a clinical picture characteristic of PRES. The case demonstrates how appropriate treatment in the acute setting allows complete restoration of cognitive function in the long term. PMID:17976748

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

    PubMed Central

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

    2007-01-01

    Matrix metalloproteinases (MMPs) have been shown to play significant roles in a number of physiological as well as pathological processes. Best known to proteolyse components of the extracellular matrix, MMPs have recently been discovered to also target a growing list of proteins apart from these, both inside and outside the cell. MMPs have also been traditionally thought of as enzymes involved in chronic processes such as angiogenesis, remodelling and atherosclerosis on a days-week time-scale. However they are now understood to also act acutely in response to oxidative stress on a minutes time-scale on non-extracellular matrix substrates. This review focuses on the acute actions and both extracellular and intracellular targets of two prominent MMP family members, MMP-2 and -9, in cardiovascular diseases including ischaemia/reperfusion injury, inflammatory heart disease, septic shock and pre-eclampsia. Also discussed are various ways of regulating MMP activity, including post-translational mechanisms, the endogenous tissue inhibitors of metalloproteinases and pharmacological inhibitors. A comprehensive understanding of MMP biology is necessary for the development of novel pharmacological therapies to combat the impact of cardiovascular disease. PMID:17592511

  20. Risk factors for cardiovascular disease in women: relationship to lipid peroxidation and oxidative stress.

    PubMed

    Castelao, J Esteban; Gago-Dominguez, Manuela

    2008-01-01

    Many risk factors that promote cardiovascular disease (CVD) have been identified. These include hypertension, hypercholesterolemia, diabetes, decreased estrogen in post-menopausal women, increased homocysteine, and cigarette smoking. It has recently become clear that a mechanism common to these risk factors is oxidative stress. CVD risk factors specific to women are parity, oophorectomy, pre-eclampsia, and menopause. There are several proposed mechanisms to explain these women-specific associations, such as reduced lifetime exposure to estrogen and insulin resistance, but the underlying mechanism is still unclear. One fact that did not receive much attention is the role of the oxidation hypothesis in these reproductive factors-CVD associations. In fact, pregnant, oophorectomized, and post-menopausal women exhibit higher levels of lipid peroxidation than non-pregnant, non-oophorectomized and pre-menopausal women, respectively. We propose that the increased levels of lipid peroxidation during these states are responsible, at least in part, for their increased risk of CVD. This review extends the concept of the oxidation hypothesis of CVD to reproductive risk factors in women. It also addresses the potential role of oxidative stress in the hyperthyroidism-CVD relationship, as hyperthyroidism is a common disorder that most frequently occurs in women. We also discuss how screening human populations for reactive oxygen species (ROS) levels could help identify groups with a high level of ROS that may be at risk of developing CVD. PMID:18308480

  1. 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

  2. [Hyperhomocysteinemia and pregnancy: a dangerous association].

    PubMed

    Aubard, Y; Darodes, N; Cantaloube, M; Aubard, V; Diallo, D; Teissier, M P

    2000-06-01

    Homocysteine results from the demethylation of the essential amino acid methionine. Its metabolism depends primarily on three enzymes and several vitamin cofactors (vit. B6, B9 and B12). Genetic abnormality in these enzymes or deficiency of these vitamins lead to Hyperhomocysteinemia. Hyperhomocysteinemia belongs among the congenital thrombophilies and is a long-known vascular disease risk factor. The discovery that hyperhomocysteinemia may also be responsible for several pregnancy complications has only recently been made. Studies in this area are still scarce and report on limited numbers of patients. It nevertheless appears clear that HHCh is associated with the syndromes of repeated miscarriage, pre-eclampsia, placenta abruptio, thromboembolic events, neural tube defects, and perhaps with fetal death-in-utero and intra-uterine growth retardation. Supplementation with vitamin B9 can reduce plasma HC levels, and is thus recommended in patients with HHCh. The prevention of thromboembolic events during pregnancy by anticoagulant treatment is also desirable in these patients. PMID:10844324

  3. 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

  4. 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.

  5. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview.

    PubMed

    Herrmann, W

    2001-08-01

    Hyperhomocysteinemia is the result of a disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological studies have proven, that hyperhomocysteinemia is a risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Conflicting results come from prospective studies. Trials which are now in progress may clarify the "causality" of high homocysteine concentrations and will assess the value of homocysteine-lowering therapy. The induction of the atherogenic process by hyperhomocysteinemia seems to be associated with an alteration of endothelial and smooth muscle cell function leading to an accelerated formation of reactive oxygen species. An increased endothelial expression of adhesion molecules will then lead to an enhanced deposition of oxidized LDL in the vessel wall with the formation of foam cells. Additionally, hyperhomocysteinemia interferes with the coagulation system and thus also has prothrombotic effects. There is a high prevalence of hyperhomocysteinemia as a sign of a vitamin deficiency in elderly subjects which strongly increases with age. Elderly people have a high frequency of vitamin B12 deficiency which can be diagnosed more reliably by the measurement of serum methylmalonic acid (MMA) level than by serum vitamin B12. Subjects following a strict vegetarian diet also have a high prevalence of hyperhomocysteinemia caused by functional vitamin B12 deficiency (increased MMA level). Last but not least, hyperhomocysteinemia is a factor in the pathogenesis of neural tube defects and pre-eclampsia. An early diagnosis of vitamin B12 deficiency is important for the prevention of neurological damages. Homocysteine should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in obese subjects, in elderly people, in postmenopausal women, and in early pregnancy. A specific diagnosis

  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. Effects of an aquatic physical exercise program on glycemic control and perinatal outcomes of gestational diabetes: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Gestational diabetes mellitus (GDM) is increasing worldwide and has been associated with adverse perinatal outcomes and high risk for chronic disease both for the mother and for the child. Physical exercise is feasible for diabetic pregnant women and contributes to better glycemic control and to a decrease in adverse perinatal outcomes. However, there are no randomized controlled trials (RCT) assessing the effects of aquatic physical exercise on GDM control and adverse maternal and fetal outcomes. Methods/Design An RCT will be conducted at Instituto de Medicina Integral Prof Fernando Figueira (IMIP), Brazil. A total of 72 pregnant women will be studied; 36 gestational diabetics will undergo an aquatic physical exercise program in a thermal pool, 3 times per week over 2 months. The primary endpoint will be glucose level control and use of insulin; secondary endpoints will be the following maternal and fetal outcomes: weight gain during pregnancy, blood pressure, pre-eclampsia diagnosis, intrauterus growth restriction, preterm birth, Cesarean section, macrosomia and maternal or neonatal intensive care admission. Endpoints between intervention and control group will analyzed by t test for unpaired data and χ2 test, and the level of significance will set at <0.05. Discussion The physical proprieties of water make aquatic exercises ideal for pregnant women. An aquatic physical exercise program developed for GDM women will be trialed in a thermal pool and under the supervision of physiotherapist to ensure compliance. It is expected that this study will provide evidence as to the effect of aquatic physical exercise on GDM control. Trial registration ClinicalTrial.gov, NCT01940003. PMID:24245914

  8. 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. PMID:17196252

  9. Recorded pregnancy histories of the mothers of singletons and the mothers of twins: a longitudinal comparison.

    PubMed

    Croft, Maxine L; Morgan, Vera; Read, Anne W; Jablensky, Assen S

    2010-12-01

    A population-based record linkage case cohort of 239,995 births, to 119,214 women, born in Western Australia from 1980 to 2001 inclusive, was used to measure the recording of selected indicators of maternal health (current and prior) during pregnancy. We compared records of women with singleton pregnancies with that in twin pregnancies Mothers of first- and second-born singletons (n = 117,647) were compared with women with a first-born singleton followed by twins (n = 1,567). Binary indicators were used to calculate population prevalence of medical conditions, pregnancy complications and birth outcomes. Infant outcomes included stillbirth, low birthweight, preterm birth and birth defects. Women with twins were significantly older and taller, with similar rates of medical conditions and pregnancy complications during first singleton pregnancies compared with women with two consecutive singletons. However, during their second pregnancy, women with twins had significantly higher rates of essential hypertension, pre-eclampsia, threatened abortion, premature rupture of the membranes and ante partum hemorrhage with abruption than women with singletons. For both groups, maternal conditions in the first pregnancy were underreported in the second pregnancy, including diabetes, epilepsy, asthma, chronic renal dysfunction and essential hypertension. At the second birth, twins were 3 times more likely to be stillborn, 17 times more likely to be low birthweight and 4 times more likely to be delivered preterm compared with singletons. This research demonstrates the importance for epidemiologists and others, of having access to a complete maternal medical history for analyses of risks associated with maternal, infant and childhood morbidity. PMID:21142936

  10. 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

  11. 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

  12. A Grhl2-dependent gene network controls trophoblast branching morphogenesis.

    PubMed

    Walentin, Katharina; Hinze, Christian; Werth, Max; Haase, Nadine; Varma, Saaket; Morell, Robert; Aue, Annekatrin; Pötschke, Elisabeth; Warburton, David; Qiu, Andong; Barasch, Jonathan; Purfürst, Bettina; Dieterich, Christoph; Popova, Elena; Bader, Michael; Dechend, Ralf; Staff, Anne Cathrine; Yurtdas, Zeliha Yesim; Kilic, Ergin; Schmidt-Ott, Kai M

    2015-03-15

    Healthy placental development is essential for reproductive success; failure of the feto-maternal interface results in pre-eclampsia and intrauterine growth retardation. We found that grainyhead-like 2 (GRHL2), a CP2-type transcription factor, is highly expressed in chorionic trophoblast cells, including basal chorionic trophoblast (BCT) cells located at the chorioallantoic interface in murine placentas. Placentas from Grhl2-deficient mouse embryos displayed defects in BCT cell polarity and basement membrane integrity at the chorioallantoic interface, as well as a severe disruption of labyrinth branching morphogenesis. Selective Grhl2 inactivation only in epiblast-derived cells rescued all placental defects but phenocopied intraembryonic defects observed in global Grhl2 deficiency, implying the importance of Grhl2 activity in trophectoderm-derived cells. ChIP-seq identified 5282 GRHL2 binding sites in placental tissue. By integrating these data with placental gene expression profiles, we identified direct and indirect Grhl2 targets and found a marked enrichment of GRHL2 binding adjacent to genes downregulated in Grhl2(-/-) placentas, which encoded known regulators of placental development and epithelial morphogenesis. These genes included that encoding the serine protease inhibitor Kunitz type 1 (Spint1), which regulates BCT cell integrity and labyrinth formation. In human placenta, we found that human orthologs of murine GRHL2 and its targets displayed co-regulation and were expressed in trophoblast cells in a similar domain as in mouse placenta. Our data indicate that a conserved Grhl2-coordinated gene network controls trophoblast branching morphogenesis, thereby facilitating development of the site of feto-maternal exchange. This might have implications for syndromes related to placental dysfunction. PMID:25758223

  13. 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

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

    PubMed Central

    Poursafa, Parinaz; Kelishadi, Roya

    2011-01-01

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

  15. In utero imaging of the placenta: importance for diseases of pregnancy.

    PubMed

    Abramowicz, J S; Sheiner, E

    2007-04-01

    Maurice Panigel demonstrated by X-rays, almost 40 years ago, placental maternal blood jets in non-human primates. Although to researchers the importance of the placenta is evident, in clinical obstetrical imaging, the fetus takes precedence. The placenta is imaged almost as an after thought and mostly to determine its location in the uterus. In animal species, the placenta was imaged with techniques which would be considered too invasive (or too costly for routine use) in humans, many pioneered by Panigel: radioangiography, radioisotopes scintigraphy, thermography, magnetic resonance imaging (MRI) and spectroscopy, positive emission tomography (PET) and single photon emission computed tomography (SPECT). Ultrasound allows for detailed, and, as far as is known, safe analyses of not only placental structure in the human but also its function. Earlier, only 2-dimensional grey-scale was available and more than 20 years ago, placental grading was popular. Later, colour imaging and spectral Doppler analysis of blood velocity both in the umbilical artery and within the placenta as well as the uterus and fetal vessels became essential and, more recently, the use of ultrasound contrast agents has been described, albeit not yet in a clinical setting. Three-dimensional ultrasound permits evaluation of the placenta in several planes, more precise depiction of internal vasculature as well as more accurate volume assessment. Several medical disorders of the pregnant woman or her fetus begin or end in the placenta, and ultrasound is the optimal investigation method. Obvious examples include pre-eclampsia and other forms of hypertension in pregnancy, less than optimal fetal growth (i.e. intrauterine growth restriction), triploidy (and its placental manifestation: partial mole), non-immune hydrops as well as several infectious processes. Ultrasound is also particularly suited to evaluate specific placental conditions, such as abnormal placentation (placenta previa and accrete for

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

    PubMed Central

    Yesayan, Maria N.; Kahn, Daniel A.

    2014-01-01

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

  17. 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

  18. 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

  19. Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells.

    PubMed

    Djurisic, S; Teiblum, S; Tolstrup, C K; Christiansen, O B; Hviid, T V F

    2015-03-01

    The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy complications, partly explained by HLA-G polymorphisms which are associated with differences in the alternative splicing pattern and of the stability of HLA-G mRNA. Of special importance is a 14 bp insertion/deletion polymorphism located in the 3'-untranslated region of the HLA-G gene. In the current study, we present novel evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, using a very accurate and sensitive Digital droplet PCR technique. Allelic imbalance in heterozygous samples was observed as differential expression levels of 14 bp insertion/deletion allele-specific mRNA transcripts, which was further associated with low levels of HLA-G surface expression on primary trophoblast cells. Full gene sequencing of HLA-G allowed us to study correlations between HLA-G extended haplotypes and single-nucleotide polymorphisms and HLA-G surface expression. We found that a 1:1 expression (allelic balance) of the 14 bp insertion/deletion mRNA alleles was associated with high surface expression of HLA-G and with a specific HLA-G extended haplotype. The 14 bp del/del genotype was associated with a significantly lower abundance of the G1 mRNA isoform, and a higher abundance of the G3 mRNA isoform. Overall, the present study provides original evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, which influences HLA-G surface expression on primary trophoblast cells, considered to be important in the pathogenesis of pre-eclampsia and other pregnancy complications. PMID:25425608

  20. 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

  1. The morphometry of materno—fetal oxygen exchange barrier in a baboon model of obesity

    PubMed Central

    Samson, J.E.; Mari, G.; Dick, E.J.; Hubbard, G.B.; Ferry, R.J.; Schlabritz-Loutsevitch, N.E.

    2012-01-01

    Introduction More than one-fourth of U.S. women are overweight; more than one-third are obese. Maternal obesity has been linked to an increased incidence of stillbirths, fetal macrosomia, fetal intrauterine growth restriction and pre-eclampsia. The placenta plays a key role in the nutrients and oxygen supply to the fetus. The data about structural changes in the placental villous membrane (VM), a major component of the feto-maternal nutrient and oxygen exchange barrier, during obesity are sparse and inconsistent. Our objective was to evaluate the morphometric changes in the placental exchange barrier in a baboon model of obesity. Materials and methods The previously described baboon model of maternal obesity was studied. We compared 4 obese to 4 non-obese baboons. Placental stereology with the use of transmission electron microscopy was performed to estimate VM oxygen diffusing capacities and morphometry. Results The specific placental oxygen diffusing capacities per unit of fetal weight were similar in baboons and humans. Maternal leptin concentrations correlated negatively with placental basement membrane thickness (r = −0.78, p < 0.05), while fetal leptin levels correlated negatively with endothelial thickness of fetal capillaries (r = −0.78, p < 0.05). The total and specific villous membrane oxygen diffusing capacities were not different between the two groups. Conclusion To the best of our knowledge this is the first report of placental oxygen diffusing capacities and placental ultrastructural changes in a baboon model of obesity. Previously reported placental inflammation in maternal obesity is not associated with changes in the VM diffusing capacities and ultrastructure. PMID:21872927

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

    PubMed Central

    King, Bridget; Bryan, Phil

    2014-01-01

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

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

    PubMed Central

    Krieg, S.A.; Fan, X.; Hong, Y.; Sang, Q.-X.; Giaccia, A.; Westphal, L.M.; Lathi, R.B.; Krieg, A.J.; Nayak, N.R.

    2012-01-01

    Recurrent pregnancy loss (RPL) occurs in ∼5% of women. However, the etiology is still poorly understood. Defects in decidualization of the endometrium during early pregnancy contribute to several pregnancy complications, such as pre-eclampsia and intrauterine growth restriction (IUGR), and are believed to be important in the pathogenesis of idiopathic RPL. We performed microarray analysis to identify gene expression alterations in the deciduas of idiopathic RPL patients. Control patients had one antecedent term delivery, but were undergoing dilation and curettage for current aneuploid miscarriage. Gene expression differences were evaluated using both pathway and gene ontology (GO) analysis. Selected genes were validated using quantitative reverse transcription–polymerase chain reaction (qRT–PCR). A total of 155 genes were found to be significantly dysregulated in the deciduas of RPL patients (>2-fold change, P < 0.05), with 22 genes up-regulated and 133 genes down-regulated. GO analysis linked a large percentage of genes to discrete biological functions, including immune response (23%), cell signaling (18%) and cell invasion (17.1%), and pathway analysis revealed consistent changes in both the interleukin 1 (IL-1) and IL-8 pathways. All genes in the IL-8 pathway were up-regulated while genes in the IL-1 pathway were down-regulated. Although both pathways can promote inflammation, IL-1 pathway activity is important for normal implantation. Additionally, genes known to be critical for degradation of the extracellular matrix, including matrix metalloproteinase 26 and serine peptidase inhibitor Kazal-type 1, were also highly up-regulated. In this first microarray approach to decidual gene expression in RPL patients, our data suggest that dysregulation of genes associated with cell invasion and immunity may contribute significantly to idiopathic recurrent miscarriage. PMID:22505054

  4. Exercise guidelines in pregnancy: new perspectives.

    PubMed

    Zavorsky, Gerald S; Longo, Lawrence D

    2011-05-01

    In 2002, the American College of Obstetricians and Gynecologists published exercise guidelines for pregnancy, which suggested that in the absence of medical or obstetric complications, 30 minutes or more of moderate exercise a day on most, if not all, days of the week is recommended for pregnant women. However, these guidelines did not define 'moderate intensity' or the specific amount of weekly caloric expenditure from physical activity required. Recent research has determined that increasing physical activity energy expenditure to a minimum of 16 metabolic equivalent task (MET) hours per week, or preferably 28 MET hours per week, and increasing exercise intensity to ≥60% of heart rate reserve during pregnancy, reduces the risk of gestational diabetes mellitus and perhaps hypertensive disorders of pregnancy (i.e. gestational hypertension and pre-eclampsia) compared with less vigorous exercise. To achieve the target expenditure of 28 MET hours per week, one could walk at 3.2 km per hour for 11.2 hours per week (2.5 METs, light intensity), or preferably exercise on a stationary bicycle for 4.7 hours per week (∼6-7 METs, vigorous intensity). The more vigorous the exercise, the less total time of exercise is required per week, resulting in ≥60% reduction in total exercise time compared with light intensity exercise. Light muscle strengthening performed over the second and third trimester of pregnancy has minimal effects on a newborn infant's body size and overall health. On the basis of this and other information, updated recommendations for exercise in pregnancy are suggested. PMID:21510713

  5. 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

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

    PubMed

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

    2014-11-01

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

  7. Evaluation of a shorter methionine loading test.

    PubMed

    de Jonge, Robert; Griffioen, Pieter H; van Zelst, Bertrand; Brouns, R Montserrate; Visser, Willy; Lindemans, Jan

    2004-01-01

    We validated whether a shorter methionine loading test is as accurate as the original 6-h test in identifying hyperhomocysteinemic patients and investigated determinants of fasting and post-load homocysteine concentration. Plasma homocysteine was determined in EDTA-blood from women with a history of pre-eclampsia (n=106) after 12 h fasting and 3 and 6 h after an oral methionine load (0.1 g/kg body weight). The 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, vitamin B6, vitamin B12, folate and creatinine were measured as determinants of homocysteine concentration. Good correlation and agreement between 3-h and 6-h plasma concentration of post-load (r=0.93, Kendall's tau-b=0.85) and delta (post-load minus the fasting value; r=0.90, Kendall's tau-b=0.79) homocysteine was observed and gross misclassification did not occur after division of 3-h and 6-h homocysteine scores into quartiles. Multiple linear regression revealed MTHFR 677 TT (p=0.01), folate (p=0.04) and vitamin B12 (p=0.06) as determinants of fasting homocysteine concentration; only MTHFR 677TT was related to 3-h (p=0.04) and 6-h (p=0.004) post-load homocysteine concentration. The MTHFR 677TT genotype resulted in >30% higher fasting and 3-h and 6-h post-load homocysteine concentrations compared to the wild-type CC genotype. This study shows that the 3-h methionine loading test is as good as the 6-h methionine loading test in identifying hyperhomocysteinemic patients. Furthermore, remethylation parameters (MTHFR 677C>T) strongly affect both fasting and post-load homocysteine. PMID:15497468

  8. eNOS activation and NO function: pregnancy adaptive programming of capacitative entry responses alters nitric oxide (NO) output in vascular endothelium--new insights into eNOS regulation through adaptive cell signaling.

    PubMed

    Boeldt, D S; Yi, F X; Bird, I M

    2011-09-01

    In pregnancy, vascular nitric oxide (NO) production is increased in the systemic and more so in the uterine vasculature, thereby supporting maximal perfusion of the uterus. This high level of functionality is matched in the umbilical vein, and in corresponding disease states such as pre-eclampsia, reduced vascular responses are seen in both uterine artery and umbilical vein. In any endothelial cell, NO actually produced by endothelial NO synthase (eNOS) is determined by the maximum capacity of the cell (eNOS expression levels), eNOS phosphorylation state, and the intracellular [Ca(2+)](i) concentration in response to circulating hormones or physical forces. Herein, we discuss how pregnancy-specific reprogramming of NO output is determined as much by pregnancy adaptation of [Ca(2+)](i) signaling responses as it is by eNOS expression and phosphorylation. By examining the changes in [Ca(2+)](i) signaling responses from human hand vein endothelial cells, uterine artery endothelial cells, and human umbilical vein endothelial cells in (where appropriate) nonpregnant, normal pregnant, and pathological pregnant (pre-eclamptic) state, it is clear that pregnancy adaptation of NO output occurs at the level of sustained phase 'capacitative entry' [Ca(2+)](i) response, and the adapted response is lacking in pre-eclamptic pregnancies. Moreover, gap junction function is an essential permissive regulator of the capacitative response and impairment of NO output results from any inhibitor of gap junction function, or capacitative entry using TRPC channels. Identifying these [Ca(2+)](i) signaling mechanisms underlying normal pregnancy adaptation of NO output not only provides novel targets for future treatment of diseases of pregnancy but may also apply to other common forms of hypertension. PMID:21555345

  9. Sleep disordered breathing in pregnancy

    PubMed Central

    2015-01-01

    Key points Sleep disordered breathing (SDB) is common and the severity increases as pregnancy progresses. Frequent snoring, older age and high pre-pregnancy body mass index (>25 kg⋅m−2) could be reliable indicators for SDB in early pregnancy. SDB screening tools, including questionnaires, used in the nonpregnant population have poor predictive ability in pregnancy. Accumulating evidence suggests that SDB during pregnancy may be associated with increased risk of adverse pregnancy outcomes, including gestational diabetes and pre-eclampsia. However, the results should be interpreted cautiously because several studies failed to adjust for potential maternal confounders and have other study limitations. There are no pregnancy-specific practice guidelines for SDB treatment. Many clinicians and practices follow recommendations for the treatment in the general population. Women with pre-existing SDB might need to be reassessed, particularly after the sixth month of pregnancy, because symptoms can worsen with nasal congestion and weight gain. Educational aims To highlight the prevalence and severity of sleep disordered breathing (SDB) in the pregnant population. To inform readers about risk factors for SDB in pregnancy. To explore the impact of SDB on adverse maternal and fetal outcomes, and biological pathways for associated adverse maternal and fetal outcomes. To introduce current management options for SDB in pregnancy, including medical and behavioural approaches. Sleep disordered breathing (SDB) is very common during pregnancy, and is most likely explained by hormonal, physiological and physical changes. Maternal obesity, one of the major risk factors for SDB, together with physiological changes in pregnancy may predispose women to develop SDB. SDB has been associated with poor maternal and fetal outcomes. Thus, early identification, diagnosis and treatment of SDB are important in pregnancy. This article reviews the pregnancy-related changes affecting the

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

    PubMed

    Motta, Alicia Beatriz

    2012-01-01

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

  11. LOW PRETERM BIRTH RATE WITH DECREASING EARLY NEONATAL MORTALITY IN BOSNIA AND HERZEGOVINA DURING 2007-2014

    PubMed Central

    Hudic, Igor; Stray-Pedersen, Babill; Skokic, Fahrija; Fatusic, Zlatan; Zildzic-Moralic, Aida; Skokic, Maida; Fatusic, Jasenko

    2016-01-01

    The aim: of the study was to determine the situation of preterm births and early neonatal mortality during 2007-2014 in Tuzla Canton, Bosnia and Herzegovina. Methods: The study covers a 8-year period and is based on the protocols at the Tuzla Clinic for Gynecology and Obstetrics that covers all birth in Tuzla Canton area. We analyzed the gestational age of all newborns and recorded the number of neonatal deaths in the first week after birth. Demographics, pregnancy and birth characteristics were collected from the maternal records. Results: The total number of births in the period was 32738. Preterm birth was identified in 2401 (7.3%) cases with 12,5% occurring before 32 gestational weeks and 64% in 35-36 gestational weeks. The mothers of the 24-31 gws preterm group were significantly younger that those in the 32-36 group. In the 32-36 group there were significantly greater proportions of mothers with assisted reproductive technology and pre-eclampsia and 16.7% was medical induced preterm births versus 11.4 % in the 24-31 PTB group, p<0.05. The incidence of PTB did no vary significantly during the period, the lowest rate was found in 2010 (6.4%). A total of 221 children died giving a early mortality rate of 6.8 per 1000 live born over the 8 years. The majority 156 dying infants (70.6%) were preterm, only 5.7% died being born in the 35-36 gestational week (5.9 per 1000). Overall the preterm early mortality (7.3 per 1000) has shown a decreasing tendency during the latter years. Conclusion: During the last 8 years there have been no significant decline in preterm birth in the Tuzla region while a decline in early neonatal death has been registered. PMID:27047264

  12. 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

  13. 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

  14. The majority of murine γδ T cells at the maternal-fetal interface in pregnancy produce IL-17.

    PubMed

    Pinget, Gabriela V; Corpuz, Theresa M; Stolp, Jessica; Lousberg, Erin L; Diener, Kerrilyn R; Robertson, Sarah A; Sprent, Jonathan; Webster, Kylie E

    2016-08-01

    Compared with lymphoid tissues, the immune cell compartment at mucosal sites is enriched with T cells bearing the γδ T-cell receptor (TCR). The female reproductive tract, along with the placenta and uterine decidua during pregnancy, are populated by γδ T cells predominantly expressing the invariant Vγ6(+)Vδ1(+) receptor. Surprisingly little is understood about the function of these cells. We found that the majority of γδ T cells in the non-pregnant uterus, pregnant uterus, decidua and placenta of mice express the transcription factor RORγt and produce interleukin-17 (IL-17). In contrast, IFNγ-producing γδ T cells were markedly reduced in gestational tissues compared with uterine-draining lymph nodes and spleen. Both uterine-resident invariant Vγ6(+) and Vγ4(+) γδ T cells which are more typically found in lymphoid tissues and circulating blood, were found to express IL-17. Vγ4(+) γδ T cells were particularly enriched in the placenta, suggesting a pregnancy-specific recruitment or expansion of these cells. A small increase in IL-17-producing γδ T cells was observed in allogeneic compared with syngeneic pregnancy, suggesting a contribution to regulating the maternal response to paternally-derived alloantigens. However, their high proportions also in non-pregnant uteri and gestational tissues of syngeneic pregnancy imply a role in the prevention of intrauterine infection or quality control of fetal development. These data suggest the need for a more rigorous evaluation of the role of IL-17 in sustaining normal pregnancy, particularly as emerging data points to a pathogenic role for IL-17 in pre-eclampsia, pre-term birth, miscarriage and maternal immune activation-induced behavioral abnormalities in offspring. PMID:27241697

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

    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. PMID:25429364

  17. 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

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

    PubMed

    Shalom, Erez; Shahar, Yuval; Lunenfeld, Eitan

    2013-05-01

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

  19. 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

  20. 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) PMID:1362187

  1. NADPH- and iron-dependent lipid peroxidation inhibit aromatase activity in human placental microsomes.

    PubMed

    Milczarek, Ryszard; Sokołowska, Ewa; Hallmann, Anna; Kaletha, Krystian; Klimek, Jerzy

    2008-06-01

    During pregnancy placenta is the most significant source of lipid hydroperoxides and other reactive oxygen species (ROS). The increased production of lipid peroxides and other ROS is often linked to pre-eclampsia. It is already proved that placental endoplasmic reticulum may be an important place of lipid peroxides and superoxide radical production. In the present study we revealed that NADPH- and iron-dependent lipid peroxidation in human placental microsomes (HPM) inhibit placental aromatase--a key enzyme of estrogen biosynthesis in human placenta. We showed that significant inhibition of this enzyme is caused by small lipid peroxidation (TBARS (thiobarbituric acid-reactive substances)<4nmol/mg microsomal protein (m.p.)). More intensive lipid peroxidation (TBARS>9nmol/mg microsomal protein) diminishes aromatase activity to value being less than 5% of initial value. NADPH- and iron-dependent lipid peroxidation also causes disappearance of cytochrome P450 parallel to observed aromatase activity inhibition. EDTA, alpha-tocopherol, MgCl(2) and superoxide dismutase (SOD) prevent aromatase activity inhibition and cytochrome P450(AROM) degradation. Mannitol and catalase have not effect on TBARS synthesis, aromatase activity and cytochrome P450 degradation. In view of the above we postulate that the inhibition of aromatase activity observed is mainly a consequence of cytochrome P450(AROM) degradation induced by lipid radicals. The role of hydroxyl radical in cytochrome P450 degradation is negligible in our experimental conditions. The results presented here also suggest that the inhibition of aromatase activity can also take place in placenta at in vivo conditions. PMID:18499441

  2. 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. PMID:23410822

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

    PubMed

    Neligan, Patrick J; Laffey, John G

    2011-01-01

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

  4. 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

  5. Effects of Lipopolysaccharide on Human First Trimester Villous Cytotrophoblast Cell Function In Vitro.

    PubMed

    Li, Liping; Tu, Jiaoqin; Jiang, Yao; Zhou, Jie; Yabe, Shinichiro; Schust, Danny J

    2016-02-01

    It has been shown that adverse obstetrical outcomes such as pre-eclampsia and intrauterine growth retardation correlate with maternal infection. In this study, we investigated mechanisms involved in infection-associated abnormalities in cytotrophoblast function. Primary human first trimester cytotrophoblast cells were isolated and treated with lipopolysaccharide (LPS). Levels of the cytokines and chemokines were measured and cytotrophoblast invasion was investigated. In addition, first trimester decidual macrophages were isolated and treated with the conditioned medium from LPS-treated cytotrophoblast cells, and macrophage migration was assessed. Coculturing decidual macrophages with cytotrophoblast cells was conducted to investigate macrophage costimulatory molecule and receptor expression and intracellular cytokine production. We found that LPS exposure increased cytotrophoblast production of pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, and chemokines IL-8, macrophage inflammatory protein (MIP)-1alpha, and CXCL12 in a dose-dependent manner. In addition, LPS decreased cytotrophoblast invasion, and its effect was Toll-like receptor 4 (TLR4)-dependent and partly TNF-alpha-dependent. Conditioned medium from LPS-stimulated cytotrophoblast cells increased decidual macrophage migration and this effect was partly TLR4-dependent. Furthermore, coculturing decidual macrophages with LPS-exposed cytotrophoblast cells up-regulated macrophage CD80 and CD86 expression and intracellular TNF-alpha and IL-12p40 production, while down-regulating macrophage CD206 and CD209 expression and intracellular IL-10 secretion. LPS-stimulated macrophages also inhibited cytotrophoblast invasion. In conclusion, our results indicate that LPS increases the production of a subset of proinflammatory cytokines and chemokines by human first trimester cytotrophoblast cells, decreases cytotrophoblast invasion, and alters the cross talk between

  6. 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

  7. [Indications for cesarean section and their outcome at the Hospital Center in Libreville].

    PubMed

    Picaud, A; Nlome-Nze, A R; Kouvahe, V; Faye, A; Ondo-Mve, R

    1990-06-01

    Over a 16-year period and 113,739 deliveries, the rate of caesarean sections in the Department of Gynecology-Obstetrics of the Centre Hospitalier of Libreville (Gabon) reaches 1.79 p. cent. Since 1985, there is a highly significant (p less than 0.001) of that rate reaching 2.33 p. cent. A comparative study of two 4-year periods (1981-1984 and 1985-1988) permits to analyze the evolution of caesarean sections. The increase is the result of an improved diagnosis of the pathology during pregnancy, especially pre-eclampsia (6.2 p. cent of indications), a better obstetrical monitoring in pelvic deliveries (7 p. cent) and screening of fetal distress (11 p. cent). The indications remain stable in mechanical dystocias and placenta praevia (40 p. cent) and for scarred uterus (19 p. cent) the rate of which remains at 1 p. cent of the deliveries. The decreased rate of perinatal mortality which has benefited from the improvement of the quality of care is not directly related to the increased rate of caesarean sections: in Africa, caesarean sections are still performed in harmful conditions for saving the mother. Maternal mortality remains high (160 of 100,000 NB) and the mortality of caesarean sections is 9 for 1,000, with only 4 p. 1,000 related to the C. section itself and not to the pathology requiring the procedure. The mortality of caesarean section is 5 times higher than that of vaginal deliveries. Caesarean sections results in uterine ruptures during subsequent pregnancies (2 p. cent of scarred uterus). The increased of caesarean sections may only be considered within the scope of concomitant improvement of prenatal monitoring, obstetrical monitoring and neonatal medicine. PMID:2202041

  8. 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

  9. 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

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

    PubMed

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

    2011-12-01

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

  11. [Pregnancy and antiphospholipid syndrome].

    PubMed

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

    2012-04-01

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

  12. [Thrombocytopenia and pregnancy].

    PubMed

    Khellaf, M; Loustau, V; Bierling, P; Michel, M; Godeau, B

    2012-08-01

    The occurrence of thrombocytopenia during pregnancy is frequent (about 10%). Etiologies of thrombocytopenia are dominated by the gestational thrombocytopenia (>75%), which requires no exploration and no specific treatment; it usually occurs during the last trimester of pregnancy and corrects itself spontaneously after delivery. Other etiologies are: (1) immune thrombocytopenia (ITP) either primary or associated with other pathologies; ITP may appear early in the first trimester of pregnancy, (2) thrombotic microangiopathy syndromes, and (3) obstetric thrombocytopenia: eclampsia and HELLP syndrome (hemolysis elevated liver enzymes, and low platelet count). Treatment of pre-eclampsia and HELLP syndrome is based on resuscitative measures and symptomatic fetal extraction that will be discussed according to the term and severity of the case. The treatment of microangiopathy is based on resuscitation and plasma exchange. For ITP, no specific action is needed during pregnancy and only symptomatic patients with a platelet count less than 30×10(9)/L must receive a treatment. It is important to prepare the childbirth that can be vaginally except if there is an obstetric contraindication. A platelet count of 50×10(9)/L is required for the delivery, and of 75×10(9)/L in case of spinal anesthesia. Treatment implies a short course of corticosteroids associated with infusion of immunoglobulins in the most severe forms or in case of steroids resistance. There is a risk of neonatal thrombocytopenia requiring a control of the blood count for the baby at birth and within 5 days, newborns have to be treated if the platelet count is less than 20×10(9)/L. PMID:22742709

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

    PubMed Central

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

    2011-01-01

    An imbalance in circulating pro-angiogenic and anti-angiogenic factors is postulated to play a causal role in pre-eclampsia (PE). We have described an inbred mouse strain, BPH/5, which spontaneously develops a PE-like syndrome including late-gestational hypertension, proteinuria, and poor feto-placental outcomes. Here we tested the hypothesis that an angiogenic imbalance during pregnancy in BPH/5 mice leads to the development of PE-like phenotypes in this model. Similar to clinical findings, plasma from pregnant BPH/5 showed reduced levels of free vascular endothelial growth factor (VEGF) and placental growth factor (PGF) compared to C57BL/6 controls. This was paralleled by a marked decrease in VEGF protein and Pgf mRNA in BPH/5 placentae. Surprisingly, antagonism by the soluble form of the FLT1 receptor (sFLT1) did not appear to be the cause of this reduction, as sFLT1 levels were unchanged or even reduced in BPH/5 compared to controls. Adenoviral-mediated delivery of VEGF121 (Ad-VEGF) via tail vein at e7.5 normalized both the plasma free VEGF levels in BPH/5 and restored the in vitro angiogenic capacity of serum from these mice. Ad-VEGF also reduced the incidence of fetal resorptions and prevented the late-gestational spike in blood pressure and proteinuria observed in BPH/5. These data underscore the importance of dysregulation of angiogenic factors in the pathogenesis of PE, and suggest the potential utility of early pro-angiogenic therapies in treating this disease. PMID:21079047

  14. 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

  15. Vitamin D3 alters Toll-like receptor 4 signaling in monocytes of pregnant women at risk for preeclampsia

    PubMed Central

    Qian, Lei; Wang, Hongyou; Wu, Fenghui; Li, Ming; Chen, Wei; LV, Lianzheng

    2015-01-01

    Vitamin D deficiency during pregnancy is thought to play a role in the development of preeclampsia; however, the underlying mechanism is not fully understood. In this study, a randomized double-blind placebo-controlled clinical trial was performed among 60 pregnant women at risk for pre-eclampsia according to abnormal uterine artery Doppler waveform. Subjects were randomly divided into 2 groups to receive a daily dose of 2000 IU vitamin D3 supplements (n=30) or receive placebo (n=30) between gestational weeks 20-32 for a total of 12 consecutive weeks. Because vitamin D3 supplementation can induce anti-inflammatory cytokine signaling, peripheral blood monocytes were investigated by flow cytometry for expression of toll-like receptor 4 (TLR4), an important mediator of innate immune response. The pro-inflammatory cytokines secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1 from monocytes, which are typically upregulated in preeclampsia, was also assessed. The incidence of preeclampsia was significantly lower in patients treated with vitamin D3 compared to the placebo group. Both the mean fluorescence intensity and the positive percentage of monocytes TLR4 in the vitamin D group were significantly lower compared to the placebo group, as well as the concentrations of secreted TNF-α, IL-6, and IL-1, while the concentration of IL-10 was higher. In the placebo group, the positive frequency of monocytes TLR4 was negatively correlated with the concentration of serum 25-hydroxyvitamin D in preeclampsia patients. Based on these results, we conclude that vitamin D3 supplementation for patients at risk of preeclampsia leads to a decrease in the expression of peripheral blood monocytes TLR4 and a subsequent decrease in pro-inflammatory cytokine secretion. Therefore, inhibiting the expression of monocytes TLR4 through vitamin D3 supplement may be a new approach to preeclampsia prevention. PMID:26770399

  16. Rare inflammatory and hereditary connective tissue diseases.

    PubMed

    Klipple, G L; Riordan, K K

    1989-05-01

    Polyarteritis nodosa developing during gestation has an extremely grave prognosis. To an uncertain extent, this results from a delay in recognition and therapy. The diagnosis of PAN is complicated by the expanded differential of common conditions associated with pregnancy such as pre-eclampsia and toxemia which can present with similar symptoms and signs. On the other hand, the pregnant woman with known, quiescent disease has a much better prognosis with only one of four women experiencing exacerbation. In women with Behcet's disease, convincing reports of both pregnancy-related flares and remissions involving primarily mucocutaneous manifestations are found in the literature. Gestational exacerbation of the more serious manifestations including chorioretinitis, vasculitis and CNS disease does not appear to be a problem. Also, a significant effect on fetal development or survival is not evident. The pregnant woman with the Marfan syndrome and pre-existing cardiovascular disease, particularly dilatation of the aortic root, has a substantially increased risk of developing a major complication during gestation most commonly aortic aneurysm, dissection, rupture or insufficiency. Echocardiographic determination of the aortic root diameter is prognostic with a decreased risk at a diameter of 40 mm or less. A diameter of greater than 40 to 45 mm constitutes a significant contraindication to pregnancy. All pregnancies in patients with the Marfan syndrome are considered high risk and frequent evaluations and echocardiograms are required. The EDS patient is subject to a wide range of gestational complications resulting from the basic connective tissue defect manifested clinically by hyperextensible skin, joint hypermobility, connective tissue and vascular fragility, and poor wound healing. The most serious complications occur in type I EDS (gravis) and type IV (ecchymotic) and include extensive perineal tears and hematoma after vaginal delivery, uterine prolapse and rupture

  17. A rare presentation of aplasia cutis congenita after feto-reduction in a trichorionic-triamniotic pregnancy.

    PubMed

    Vettori, D J; Jairath, P

    2015-01-01

    Aplasia cutis congenita (ACC) is rare skin disorder of newborns that has been linked to both assisted reproductive technology (ART) and feto-reduction procedures. ACC is characterized by well-demarcated lesions that are devoid of all skin layers. Group-V ACC presents with a distinctive and symmetrical distribution pattern. It is thought to result from an insult to the fetus after concomitant twin demise and is almost exclusively reported in monochorionic gestations.A 41-year-old female with an in vitro fertilization (IVF) assisted tri-chorionic gestation subsequently underwent selective feto-reduction of Fetus C. The patient delivered two pre-term neonates secondary to pre-eclampsia. The initial exam of Twin B showed extensive, well-demarcated, symmetrical areas devoid of any skin over the anterior and lateral trunk, extending up the lateral thoracic walls. Chest and abdominal viscera were visible through a thin fibrous membrane. The skin defects were managed conservatively with twice-daily dressings of Aquaphor, and Vaseline gauze. The areas of aplasia slowly contracted, though residual scarring was noted. After four weeks in the NICU, most of the areas were healed.ACC in multi-fetal pregnancies is a rare, but well-described complication. This is, to our knowledge, the first reported case in a tri-chorionic IVF gestation after feto-reduction. With increased incidence of ART-associated pregnancies and the use of feto-reduction for higher order gestations, this may become more common. Neonates often require specialized intensive care. Conservative management usually will suffice, although surgical grafting may be required. Physicians should be aware of this condition and counsel their feto-reduction patients of the risk. PMID:26485557

  18. Trends in Pre-Pregnancy Diabetes Among Deliveries in 19 U.S. States, 2000–2010

    PubMed Central

    Bardenheier, Barbara H.; Imperatore, Giuseppina; Devlin, Heather M.; Kim, Shin Y.; Cho, Pyone; Geiss, Linda S.

    2015-01-01

    Background Trends in state-level prevalence of pre-pregnancy diabetes mellitus (PDM; i.e., type 1 or type 2 diabetes diagnosed before pregnancy) among delivery hospitalizations are needed to inform healthcare delivery planning and prevention programs. Purpose To examine PDM trends overall, by age group, race/ethnicity, primary payer, and with comorbidities such as pre-eclampsia and pre-pregnancy hypertension, and to report changes in prevalence over 11 years. Methods In 2014, State Inpatient Databases from the Agency for Healthcare Research and Quality were analyzed to identify deliveries with PDM and comorbidities using diagnosis-related group codes and ICD-9-CM codes. General linear regression with a log-link and binomial distribution was used to assess the annual change. Results Between 2000 and 2010, PDM deliveries increased significantly in all age groups, all race/ethnicity groups, and in all states examined (p<0.01). The age-standardized prevalence of PDM increased from 0.65 per 100 deliveries in 2000 to 0.89 per 100 deliveries in 2010, with a relative change of 37% (p<0.01). Although PDM rates were highest in the South, some of the largest relative increases occurred in five Western states (≥9%). Non-Hispanic blacks had the highest PDM rates and the highest absolute increase (0.26 per 100 deliveries). From 2000 to 2010, the proportion of PDM deliveries with pre-pregnancy hypertension increased significantly (p<0.01) from 7.4% to 14.1%. Conclusions PDM deliveries are increasing overall and particularly among those with PDM who have hypertension. Effective diabetes prevention and control strategies for women of childbearing age may help protect their health and that of their newborns. PMID:25326417

  19. [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. PMID:24075628

  20. 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

  1. Obstetric Outcome in Early and Late Onset Gestational Diabetes Mellitus.

    PubMed

    Easmin, S; Chowdhury, T A; Islam, M R; Beg, A; Jahan, M K; Latif, T; Dhar, S; Alam, M N; Akhter, M

    2015-07-01

    Obstetric outcome in early onset and late onset GDM was compared in a prospective study conducted at the Department of Obstetrics & Gynecology in BIRDEM, Dhaka, Bangladesh. A total 120 pregnant women were recruited purposively for the study in which 60 were early onset GDM and 60 were late onset GDM during study period of January 2008 to December 2009. Patients were followed up in different periods of gestation, during delivery and early postpartum period & findings were compared between two groups. BMI & family history of diabetes were significantly higher in early GDM group (p<0.05). Evidence of increased glycaemia was observed in early GDM group & difference of glycaemic status was statistically significant (p<0.05). Insulin was needed in 85% of early onset GDM and 55% in late onset GDM. There was also significant difference (p<0.05). In this study, 23.3% of early onset GDM group developed pre-eclampsia while in late onset GDM it was 10% and was statistically significant (p<0.05). Regarding intrapartum & postpartum complications - perineal tear, PPH wound infection, puerperal sepsis were more in early onset than late onset GDM group with no significant difference. Regarding foetal outcome, 8.3% early GDM group delivered asphyxiated baby in comparison to 3.3% in late GDM group. Twenty percent (20%) of early onset GDM group had to admit their babies in neonatal unit while in late onset group it was 5%. There was significant difference between two groups (p<0.05). Neonatal hypoglycaemia was also statistically significantly (p<0.05) higher in early GDM group. Neonatal hyper-bilirubinaemia, RDS, perinatal death was more in early onset GDM subjects. Early onset GDM subjects are high risk subgroup & have significant deleterious effect on maternal and perinatal outcome than late GDM groups. PMID:26329938

  2. A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries

    PubMed Central

    Saleem, Sarah; Goudar, Shivaprasad S; Patel, Archana; Esamai, Fabian; Garces, Ana; Chomba, Elwyn; Althabe, Fernando; Moore, Janet; Kodkany, Bhalachandra; Pasha, Omrana; Belizan, Jose; Mayansyan, Albert; Derman, Richard J; Hibberd, Patricia L; Liechty, Edward A; Krebs, Nancy F; Hambidge, K Michael; Buekens, Pierre; Carlo, Waldemar A; Wright, Linda L; Koso-Thomas, Marion; Jobe, Alan H; Goldenberg, Robert L

    2014-01-01

    Abstract Objective To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths. Methods A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until six weeks postpartum. Findings Between 2010 and 2012, 214 070 of 220 235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100 000 live births, ranging from 69 per 100 000 in Argentina to 316 per 100 000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive six weeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.97–11.27), as were perinatal deaths (RR: 4.30; 95% CI: 3.26–5.67) and 7-day (RR: 3.94; 95% CI: 2.74–5.65) and 28-day neonatal deaths (RR: 7.36; 95% CI: 5.54–9.77). Conclusion Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality. PMID:25177075

  3. 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

  4. 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

  5. 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

  6. Thrombin Regulates Soluble fms-Like Tyrosine Kinase-1 (sFlt-1) Expression in First Trimester Decidua

    PubMed Central

    Lockwood, Charles J.; Toti, Paolo; Arcuri, Felice; Norwitz, Errol; Funai, Edmund F.; Huang, Se-Te J.; Buchwalder, Lynn F.; Krikun, Graciela; Schatz, Frederick

    2007-01-01

    The primary placental defect in preeclampsia is shallow trophoblast invasion of the decidua leading to incomplete vascular transformation and inadequate uteroplacental perfusion. Soluble fms-like tyrosine kinase-1 (sFlt-1) seems to interfere with these events by inhibiting local angiogenesis and/or by impeding trophoblast invasion. Preeclampsia is also associated with maternal thrombophilias and decidual hemorrhage, which form thrombin from decidual cell-expressed tissue factor. Although sFlt-1 is highly expressed by trophoblasts, sFlt-1 expression has not been studied in decidual cells, which are the predominant cell type encountered by invading trophoblasts. Here, we demonstrate that isolated decidual cells express sFlt-1 mRNA, suggesting that they can synthesize sFlt-1. Moreover, in first trimester decidual cells, thrombin enhanced sFlt-1 mRNA levels, as measured by quantitative reverse transcriptase-polymerase chain reaction, and levels of secreted sFlt-1 protein, as measured by enzyme-linked immunosorbent assay. The thrombin antagonist hirudin blocked this effect, demonstrating that active thrombin is required. Emphasizing the specificity of the thrombin response, neither interleukin-1β nor tumor necrosis factor-α affected sFlt-1 expression in the decidual cells. In contrast to first trimester decidual cells, thrombin did not affect sFlt-1 levels in cultured term decidual cells. In early pregnancy, thrombin may act as an autocrine/paracrine enhancer of sFlt-1 expression by decidual cells to promote pre-eclampsia by interfering with local vascular transformation. PMID:17392178

  7. Human placental renin-angiotensin system in normotensive and pre-eclamptic pregnancies at high altitude and after acute hypoxia-reoxygenation insult.

    PubMed

    Kurlak, Lesia O; Mistry, Hiten D; Cindrova-Davies, Tereza; Burton, Graham J; Broughton Pipkin, Fiona

    2016-03-01

    A functioning placental renin-angiotensin system (RAS) appears necessary for uncomplicated pregnancy and is present during placentation, which occurs under low oxygen tensions. Placental RAS is increased in pre-eclampsia (PE), characterised by placental dysfunction and elevated oxidative stress. We investigated the effect of high altitude hypoxia on the RAS and hypoxia-inducible factors (HIFs) by measuring mRNA and protein expression in term placentae from normotensive (NT) and PE women who delivered at sea level or above 3100 m, using an explant model of hypoxia-reoxygenation to assess the impact of acute oxidative stress on the RAS and HIFs. Protein levels of prorenin (P = 0.049), prorenin receptor (PRR; P = 0.0004), and angiotensin type 1 receptor (AT1R, P = 0.006) and type 2 receptor (AT2R, P = 0.002) were all significantly higher in placentae from NT women at altitude, despite mRNA expression being unaffected. However, mRNA expression of all RAS components was significantly lower in PE at altitude than at sea level, yet PRR, angiotensinogen (AGT) and AT1R proteins were all increased. The increase in transcript and protein expression of all the HIFs and NADPH oxidase 4 seen in PE compared to NT at sea level was blunted at high altitude. Experimentally induced oxidative stress stimulated AGT mRNA (P = 0.04) and protein (P = 0.025). AT1R (r = 0.77, P < 0.001) and AT2R (r = 0.81, P < 0.001) mRNA both significantly correlated with HIF-1β, whilst AT2R also correlated with HIF-1α (r = 0.512, P < 0.013). Our observations suggest that the placental RAS is responsive to changes in tissue oxygenation: this could be important in the interplay between reactive oxygen species as cell-signalling molecules for angiogenesis and hence placental development and function. PMID:26574162

  8. 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

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

    PubMed Central

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

    2016-01-01

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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

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

    PubMed Central

    Hill, Suzanne; Yang, Annie; Bero, Lisa

    2012-01-01

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

  20. 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

  1. 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

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

    PubMed Central

    2014-01-01

    commencement of treatment, and other patient characteristics available at baseline such as gestational age and estimated fetal weight. The secondary outcomes for mothers include co-incidence and severity of the maternal syndrome of pre-eclampsia, mortality, and other serious adverse events. Discussion Trials are expected to start in 2013–2014 and end in 2016–2017. Data analyses of individual trials are expected to finish in 2019. Given the pre-planned and agreed IPD protocol, these results should be available in 2020. PMID:24618418

  3. 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

  4. Results of the Recent Immigrant Pregnancy and Perinatal Long-term Evaluation Study (RIPPLES)

    PubMed Central

    Ray, Joel G.; Vermeulen, Marian J.; Schull, Michael J.; Singh, Gita; Shah, Rajiv; Redelmeier, Donald A.

    2007-01-01

    Background People who immigrate to Western nations may experience fewer chronic health problems than original residents of those countries, which raises concerns about long-term environmental or lifestyle factors in those countries. We tested whether the “healthy immigrant effect” extends to the risk of placental dysfunction during the short interval of pregnancy. Methods We conducted a population-based retrospective cohort study of data for 796 105 women who had a first documented obstetric delivery in Ontario between 1995 and 2005. Recency of immigration was determined for each woman as the time from her enrolment in universal health insurance to her date of delivery, classified as less than 3 months, 3–5 months, 6–11 months, 12–23 months, 24–35 months, 36–47 months, 48–59 months and 5 years or more (the referent). The primary composite outcome was maternal placental syndrome (defined as a diagnosis of pre-eclampsia or eclampsia, placental abruption or placental infarction). Results The mean age of the women was 28.8 years. Maternal placental syndrome occurred in 45 216 women (5.7%). The risk of this outcome was lowest among the women who had immigrated less than 3 months before delivery (3.8%) and highest among those living in Ontario at least 5 years (6.0%), for a crude odds ratio (OR) of 0.62 (95% confidence interval [CI] 0.54–0.71). After adjustment for maternal age, income status, pre-existing hypertension, diabetes mellitus, multiple gestation and receipt of prenatal ultrasonography, the risk of maternal placental syndrome was correlated with the number of months since immigration in a gradient manner (OR, 95% CI): less than 3 months (0.53, 0.47–0.61), 3–5 months (0.68, 0.61–0.76), 6–11 months (0.67, 0.63–0.71), 12–23 months (0.69, 0.66–0.73), 24–35 months (0.75, 0.70–0.79), 36–47 months (0.75, 0.70–0.80) and 48–59 months (0.82, 0.77–0.87). Interpretation There was a progressively lower risk of maternal placental

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

    PubMed Central

    2011-01-01

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

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

    PubMed

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

    2014-11-01

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

  7. 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

  8. The role of cytokines as inflammatory mediators in preeclampsia

    PubMed Central

    Udenze, Ifeoma; Amadi, Casimir; Awolola, Nicholas; Makwe, Christian Chigozie

    2015-01-01

    Introduction This study is to determine the concentrations of IL-6, TNF α, and C reactive protein (CRP) in women with severe preeclampsia, and compare with those of gestational age- matched normotensive pregnant women and to correlate CRP levels with markers of organ damage in women with preeclampsia. Methods This was a case control study of fifty women with severe preeclampsia and fifty gestational age matched pregnant women with normal blood pressure. The women were drawn from The Antenatal Clinic of The Lagos University Teaching Hospital. Severe pre eclampsia was defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110mmHg and ≥2+ of proteinuria. After obtaining an informed consent, each participant completed a structured questionnaire. The questionnaire sought information on socio-demographic and clinical data. From each participant, mid-stream urine was collected for urinalysis and culture, and blood sample was collected for biochemical analysis. Comparisons of continuous variables and categorical variables were done using the Student's t test and Chi square test respectively. Correlation analysis was used to determine the associations between variables. Statistical significance was set at P Results The women were similar in their socio demographic characteristics. There was a statistically significant difference in the systolic blood pressure (p < 0.0001), diastolic blood pressure ( p < 0.0001), uric acid ( p < 0.0001), AST ( p < 0.0001), ALP ( p < 0.0001), creatinine ( p < 0.0013), GGT ( p < 0.005), IL 6 ( p < 0.021), CRP ( p < 0.0002), and TNF α ( p < 0.023), between the group with severe preeclampsia and the group with normal blood pressure. This study also reports a significant association between CRP and systolic blood pressure, diastolic blood pressure, uric acid AST and ALP (p Conclusion The inflammatory cytokines, IL6, TNF α and CRP are elevated in severe preeclampsia and may mediate some of the clinical

  9. 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

  10. The WHO antenatal care randomised controlled trial: rationale and study design.

    PubMed

    Villar, J; Bakketeig, L; Donner, A; al-Mazrou, Y; Ba'aqeel, H; Belizán, J M; Carroli, G; Farnot, U; Lumbiganon, P; Piaggio, G; Berendes, H

    1998-10-01

    The World Health Organisation and collaborating institutions in developing countries are conducting a multicentre randomised controlled trial to evaluate a new antenatal care (ANC) programme, consisting of tests, clinical procedures and follow-up actions scientifically demonstrated to be effective in improving maternal and newborn outcomes. These activities are distributed, for practical reasons, over four visits during the course of pregnancy and are aimed at achieving predetermined goals. The study is taking place in four countries, Argentina, Cuba, Saudi Arabia and Thailand. Recruitment of study subjects started on 1 May 1996. All 53 ANC clinical units had been enrolled by December 1996. Clinics in each country were randomly allocated (cluster randomisation) to provide either the new programme or the traditional programme currently in use. Approximately 24,000 women presenting for ANC at these clinics over an average period of 18 months will have been recruited. As women attending the control clinics receive the 'best standard treatment' as currently offered in these clinics, individual informed consent is requested only from women attending the intervention clinics. Authorities of the corresponding health districts and all participating clinics have provided written institutional informed consent before randomisation. The primary outcome of the trial in relation to maternal conditions is the rate of a morbidity indicator index, defined as the presence of at least one of the following conditions for which ANC is relevant: (a) pre-eclampsia or eclampsia during pregnancy or within 24 h of delivery; (b) postpartum anaemia (haemoglobin < 90 g/L); or (c) severe urinary tract infection/pyelonephritis, defined as an episode requiring antibiotic treatment and/or hospitalisation. The primary fetal outcome is the rate of low birthweight (< 2500 g). Adverse maternal and fetal outcomes are expected for approximately 10% of the control group. Several maternal and perinatal

  11. 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

  12. Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial

    PubMed Central

    Turnbull, Deborah; McPhee, Andrew J; Deussen, Andrea R; Grivell, Rosalie M; Yelland, Lisa N; Crowther, Caroline A; Wittert, Gary; Owens, Julie A; Robinson, Jeffrey S

    2014-01-01

    Objective To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women. Design Multicentre randomised trial. We utilised a central telephone randomisation server, with computer generated schedule, balanced variable blocks, and stratification for parity, body mass index (BMI) category, and hospital. Setting Three public maternity hospitals across South Australia. Participants 2212 women with a singleton pregnancy, between 10+0 and 20+0 weeks’ gestation, and BMI ≥25. Interventions 1108 women were randomised to a comprehensive dietary and lifestyle intervention delivered by research staff; 1104 were randomised to standard care and received pregnancy care according to local guidelines, which did not include such information. Main outcome measures Incidence of infants born large for gestational age (birth weight ≥90th centile for gestation and sex). Prespecified secondary outcomes included birth weight >4000 g, hypertension, pre-eclampsia, and gestational diabetes. Analyses used intention to treat principles. Results 2152 women and 2142 liveborn infants were included in the analyses. The risk of the infant being large for gestational age was not significantly different in the two groups (lifestyle advice 203/1075 (19%) v standard care 224/1067 (21%); adjusted relative risk 0.90, 95% confidence interval 0.77 to 1.07; P=0.24). Infants born to women after lifestyle advice were significantly less likely to have birth weight above 4000 g (lifestyle advice 164/1075 (15%) v standard care 201/1067 (19%); 0.82, 0.68 to 0.99; number needed to treat (NNT) 28, 15 to 263; P=0.04). There were no differences in maternal pregnancy and birth outcomes between the two treatment groups. Conclusions For women who were overweight or obese, the antenatal lifestyle advice used in this study did not reduce the risk delivering a baby weighing above the 90th centile for gestational age and sex or improve maternal

  13. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results

    PubMed Central

    Yelnik, Cecile M; Laskin, Carl A; Porter, T Flint; Branch, D Ware; Buyon, Jill P; Guerra, Marta M; Lockshin, Michael D; Petri, Michelle; Merrill, Joan T; Sammaritano, Lisa R; Kim, Mimi Y; Salmon, Jane E

    2016-01-01

    Objective We previously reported that lupus anticoagulant (LAC) is the main predictor of poor pregnancy outcome in antiphospholipid antibody (aPL)-positive patients. We sought to confirm this finding in an independent group of patients who were subsequently recruited into the PROMISSE study. Methods The PROMISSE study is a multicentre, prospective, observational study of pregnancy outcomes in women with aPL and/or systemic lupus erythematosus (SLE) that enrolled patients from 2003 to 2015. All consecutive, aPL-positive patients from the PROMISSE study who completed their pregnancy between April 2011 and January 2015 (after the previous PROMISSE report) are included in the current report. Patients were followed monthly until delivery, and aPL was tested at first, second and third trimesters of pregnancy and at 12 weeks post partum. Adverse pregnancy outcomes (APOs) were defined as fetal death after 12 weeks of gestation, neonatal death, delivery prior to 36 weeks of gestation due to pre-eclampsia or placental insufficiency or small-for-gestational age (birth weight <5th percentile). Results Forty-four aPL-positive patients are included in this paper. Thirteen patients had APOs, which occurred in 80% of cases during the second trimester of pregnancy. LAC was present in 69% of patients with APOs compared with 27% of patients without APOs (p=0.01). No association was found between anticardiolipin antibodies (aCL) or anti-β2 glycoprotein I antibodies (aβ2GPI) IgG or IgM positivity and APOs. Definite antiphospholipid syndrome (history of thrombosis and/or pregnancy morbidity and aPL) was found in 92% of patients with any APOs compared with 45% of patients without APOs (p=0.004). Conversely, the frequency of SLE was not statistically different between those with and without APOs (30% vs 39%). Conclusions Our findings, in an independent group of aPL-positive patients from the PROMISSE study, confirm that LAC, but not aCL and aβ2GPI, is predictive of poor pregnancy

  14. Maternal obesity is associated with a reduction in placental taurine transporter activity

    PubMed Central

    Ditchfield, A M; Desforges, M; Mills, T A; Glazier, J D; Wareing, M; Mynett, K; Sibley, C P; Greenwood, S L

    2015-01-01

    Background/Objectives: Maternal obesity increases the risk of poor pregnancy outcome including stillbirth, pre-eclampsia, fetal growth restriction and fetal overgrowth. These pregnancy complications are associated with dysfunctional syncytiotrophoblast, the transporting epithelium of the human placenta. Taurine, a β-amino acid with antioxidant and cytoprotective properties, has a role in syncytiotrophoblast development and function and is required for fetal growth and organ development. Taurine is conditionally essential in pregnancy and fetal tissues depend on uptake of taurine from maternal blood. We tested the hypothesis that taurine uptake into placental syncytiotrophoblast by the taurine transporter protein (TauT) is lower in obese women (body mass index (BMI)⩾30 kg m−2) than in women of ideal weight (BMI 18.5–24.9 kg m−2) and explored potential regulatory factors. Subjects/Methods: Placentas were collected from term (37–42-week gestation), uncomplicated, singleton pregnancies from women with BMI 19–49 kg m−2. TauT activity was measured as the Na+-dependent uptake of 3H-taurine into placental villous fragments. TauT expression in membrane-enriched placental samples was investigated by western blot. In vitro studies using placental villous explants examined whether leptin or IL-6, adipokines/cytokines that are elevated in maternal obesity, regulates TauT activity. Results: Placental TauT activity was significantly lower in obese women (BMI⩾30) than women of ideal weight (P<0.03) and inversely related to maternal BMI (19–49 kg m−2; P<0.05; n=61). There was no difference in TauT expression between placentas of ideal weight and obese class III (BMI⩾40) subjects. Long-term exposure (48 h) of placental villous explants to leptin or IL-6 did not affect TauT activity. Conclusions: Placental TauT activity at term is negatively related to maternal BMI. We propose that the reduction in placental TauT activity in maternal obesity

  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. 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

  17. The effects of angiogenic growth factors on extravillous trophoblast invasion and motility.

    PubMed

    Lash, G E; Cartwright, J E; Whitley, G S; Trew, A J; Baker, P N

    1999-11-01

    There is accumulating evidence that deficient trophoblast invasion of the placental bed spiral arteries is crucial to the pathogenesis of pre-eclampsia and intrauterine growth restriction. However, the factors which regulate the process of trophoblast invasion remain unclear. We have investigated whether extravillous trophoblast invasion and motility are mediated by the angiogenic growth factors, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). The SGHPL-4 extravillous trophoblast cell line was utilized. Expression of mRNA for the receptors of VEGF and PlGF (KDR and flt-1) was determined using the reverse transcriptase polymerase chain reaction. An in vitro model of invasion assessed the number and length of trophoblast processes invading into an extracellular matrix. The motility of cells under standard culture conditions was also quantified. The effect of the addition of VEGF and PlGF (+/-heparin) on trophoblast invasion and motility was determined. The effect of VEGF and PlGF (+/-heparin) on SGHPL-4 cell proliferation was assessed by cell counts at 24, 48 and 72 h post-addition of growth factor. The SGHPL-4 cells expressed mRNA for the flt-1 but not the KDR receptor. The addition of VEGF resulted in a significant decrease in the number of trophoblast processes formed (P< 0.02); this effect was not influenced by the addition of heparin. However, there was no effect on the length of processes formed in response to VEGF (+/-heparin). The addition of PlGF had no effect on either the number or the length of processes formed. The addition of VEGF increased the motility of the SGHPL-4 cells (P< 0.002); the addition of heparin prevented this VEGF-induced increase in motility. The addition of PlGF had no effect on SGHPL-4 motility (+/-heparin). Neither growth factor had any effect on the proliferative ability of SGHPL-4 cells. Contrary to our hypothesis, we did not find that the angiogenic growth factors, VEGF and PlGF, mediated the in vitro

  18. Fab fragment glycosylated IgG may play a central role in placental immune evasion

    PubMed Central

    Gu, Jiang; Lei, Yu; Huang, Yuanping; Zhao, Yingying; Li, Jing; Huang, Tao; Zhang, Junjun; Wang, Juping; Deng, Xiaodong; Chen, Zhengshan; Korteweg, Christine; Deng, Ruishu; Yan, Meiling; Xu, Qian; Dong, Shengnan; Cai, Monghong; Luo, Lili; Huang, Guowei; Wang, Yun; Li, Qian; Lin, Changmei; Su, Meng; Yang, Chunzhang; Zhuang, Zhengping

    2015-01-01

    glycosylated IgG can react to certain leukocytes in the membrane and cytoplasm, while symmetric IgG from the placenta does not have this property. LIMITATIONS, REASONS FOR CAUTION Most of the experiments were performed in vitro. The proposed mechanism calls for verification in normal and abnormal pregnancy. WIDER IMPLICATIONS OF THE FINDINGS This study identified a number of new phenomena suggesting that aIgG produced by the placenta would be able to react to detrimental antibodies and leukocytes and interfere with their immune reactions against the placenta and the fetus. This opens a new dimension for further studies on pregnancy physiology and immunology. Should the mechanism proposed here be confirmed, it will have a direct impact on our understanding of the physiology and pathology of human reproduction and offer new possibilities for the treatment of many diseases including spontaneous abortion, infertility and pre-eclampsia. It also sheds light on the mechanism of immune evasion in general including that of cancer. STUDY FUNDING/COMPETING INTEREST(S) Funded by the Li KaShing Foundation and the National Natural Science Foundation to Jiang Gu, grant no. 30971150 and 81030033. There is no competing interest. Trial registration number: N/A. PMID:25505012

  19. [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. PMID:22093440

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

    PubMed Central

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

    2014-01-01

    Background Endothelial injury, which may present clinically as hypertension, proteinuria and increased von Willebrand Factor (vWF) level, is a common manifestation in IgA nephropathy (IgAN). However, causal factors for endothelial injury in IgAN are not completely understood. An imbalance of vascular endothelial growth factor/Soluble fms-like tyrosine kinase-1 (VEGF/sFlt-1) has been observed in many diseases with endothelial dysfunction, including pre-eclampsia and diabetic retinopathy, but whether it contributes to endothelial injury in IgAN requires further exploration. Methods Initially, 96 IgAN patients and 22 healthy volunteers were enrolled as a discovery cohort. VEGF/sFlt-1, sFlt-1 and VEGF levels were compared between patients with IgAN and healthy volunteers to explore the underlying factors that contribute to endothelial injury in IgAN. The identified contributor (sFlt-1) was further confirmed in a replication cohort, which included 109 IgAN patients and 30 healthy volunteers. Correlations of sFlt-1 with hypertension, proteinuria, Oxford-E score and plasma vWF were further evaluated in the combined 205 patients with IgAN. Results VEGF/sFlt-1 levels were significantly lower in IgAN patients than healthy volunteers (0.33±0.27 vs. 0.43±0.22, p = 0.02) in the discovery cohort. Within the ratio, plasma sFlt-1 levels were significantly elevated (101.18±25.19 vs. 79.73±18.85 pg/ml, p<0.001), but plasma VEGF levels showed no significant differences. Elevated sFlt-1 levels in the replication cohort were confirmed in IgAN patients (93.40±39.78 vs. 71.92±15.78 pg/ml, p<0.001). Plasma sFlt-1 levels in IgAN patients correlated with proteinuria (severe (>3.5 g/d) vs. moderate (1–3.5 g/d) vs. mild (<1 g/d) proteinuria: 115.95±39.09 vs. 99.89±28.55 vs. 83.24±33.92 pg/ml; severe vs. mild: p<0.001, moderate vs. mild p = 0.001, severe vs. moderate: p = 0.014), hypertension (with vs. without hypertension: 107.87±31.94 vs. 87.32±32.76 pg/ml, p = 0

  1. 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