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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 in second pregnancy.

    PubMed

    Campbell, D M; MacGillivray, I; Carr-Hill, R

    1985-02-01

    A total population of pregnant women from Aberdeen City District 1967-1978 has been studied. There were 29 851 pregnancies and 6637 women had a first recorded pregnancy between 1967 and 1978 and had two or more pregnancy events. As expected the incidence of pre-eclampsia in a second pregnancy was less than that in a first pregnancy, but it was dependent on the outcome of the first pregnancy. If the first pregnancy was complicated by proteinuric pre-eclampsia than the incidence of the condition in the second pregnancy was similar to that in a first pregnancy, but women who were normotensive in the first pregnancy had a reduced incidence of the condition in the second pregnancy. The incidence of proteinuric pre-eclampsia after early abortion (less than 13 weeks), either spontaneous or induced was similar to the population incidence in a first pregnancy, but after a late spontaneous abortion the risk of proteinuric pre-eclampsia was significantly reduced. Change of civil status of the offspring from first to second pregnancy did not affect the incidence of pre-eclampsia in a second pregnancy. There was an effect of birthweight in that women who had proteinuric pre-eclampsia in conjunction with a low-birthweight baby (less than 2500 g) in their first pregnancy had double the incidence of proteinuric pre-eclampsia in their second pregnancy. Only a pregnancy of 37 weeks or more is likely to offer protection or 'immunity' to pre-eclampsia in a second pregnancy and even then the effect is moderated by the development of pre-eclampsia in the first pregnancy. PMID:3970893

  3. Copper and zinc in pre-eclampsia.

    PubMed

    Kiilholma, P; Paul, R; Pakarinen, P; Grönroos, M

    1984-01-01

    Twenty uncomplicated pregnancies, 10 parturients with mild and 10 parturients with severe pre-eclampsia, all with uncomplicated deliveries, were studied. Maternal and umbilical cord serum were checked for copper and zinc by the proton-induced X-ray emission (PIXE) method; maternal serum protein, hemoglobin and estriol were determined as well. Maternal zinc and copper values were lower, whereas the umbilical cord serum copper level was higher in the group with severe pre-eclampsia as compared with the controls. Maternal zinc was also lower in mild pre-eclampsia than in the controls. The possible causes of these changes are discussed in view of the hormonal, metabolic and enzymatic changes in pre-eclampsia. PMID:6097088

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

    PubMed Central

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

    2011-01-01

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

  5. Pre-eclampsia and cardiovascular disease

    PubMed Central

    Chen, Christina W.; Jaffe, Iris Z.; Karumanchi, S. Ananth

    2014-01-01

    Heart disease is the leading cause of death in women in all countries. A history of pre-eclampsia, one of the most deadly hypertensive complications of pregnancy, increases cardiovascular risk by two to four times, which is comparable with the risk induced by smoking. Substantial epidemiological data reveal that pregnancy-related hypertensive complications are associated with a predisposition to chronic hypertension, premature heart attacks, strokes, and renal complications. In this review, we summarize clinical studies that demonstrate this relationship and also discuss the pathogenesis of these long-term complications of pre-eclampsia. Future studies should focus on strategies to prevent the progression of cardiovascular disease in women exposed to pre-eclampsia, thereby improving long-term cardiovascular health in women. PMID:24532051

  6. Update on genetics of pre-eclampsia.

    PubMed

    Morgan, Linda

    2013-04-01

    Over half of the familial predisposition to pre-eclampsia can be attributed to genetic factors in the mother and/or fetus. The search for genetic susceptibility variants has progressed through candidate gene studies, family-based linkage studies, and most recently genome-wide association studies (GWAS). It is unlikely that any single variant has a large effect on pre-eclampsia susceptibility; studies involving thousands of samples are required to detect variants with small effect size. These exceed the resources of most individual research groups, and collaborative approaches are likely to be more fruitful. Collaboration has included meta-analysis of existing data, and recent publications offer some support to a role for thrombophilic polymorphisms in pre-eclampsia. A small number of GWAS have been published so far; the lack of replication of positive GWAS results in an independent population has been frustrating. This may be due to false positive results in the original GWAS, or lack of statistical power in the replication set. A further concern is that the pre-eclampsia syndrome is a common end-point to multiple pathologies with differing underlying genetic susceptibility, requiring ever larger sample sizes for their detection. In this climate, researchers should make every effort to record the phenotypic characteristics of their cohorts, to enable meta-analysis of independent GWAS results. The InterPregGen consortium of groups from Europe and Central Asia is conducting GWAS analysis of maternal and fetal genes in 13,000 pre-eclamptic pregnancies. This study will provide the opportunity to analyse maternal-fetal gene interactions in addition to their individual effects. Developments arising from the ever-falling costs of DNA sequencing include deep sequencing to identify rare variants with large effect sizes. The era of whole genome sequencing is likely to supplant the GWAS approach, creating challenges for data analysis, but with the potential to provide greater insights into the genetic basis of pre-eclampsia. PMID:26105842

  7. 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 or INS]-[NOS3]-[pre-eclampsia]; [INS]-[HSPA4 or CLU]-[pre-eclampsia]; [ACE]-[MTHFR]-[pre-eclampsia]. Conclusions For pre-eclampsia, diabetes mellitus, gestational diabetes and obesity, we showed that the size and connectivity of the associative molecular genetic networks, which describe interactions between comorbid diseases, statistically exceeded the size and connectivity of those built for randomly chosen pairs of diseases. Recently, we have shown a similar result for inversely comorbid diseases. This suggests that comorbid and inversely comorbid diseases have common features concerning structural organization of associative molecular genetic networks. PMID:25879409

  8. Association between Asymptomatic Bacteriuria and Pre-Eclampsia.

    PubMed

    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

  9. 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

  10. 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

  11. Prediction and primary prevention of pre-eclampsia.

    PubMed

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

    2011-08-01

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

  12. Antiphospholipid syndrome and pre-eclampsia.

    PubMed

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

    2011-03-01

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

  13. Pre-eclampsia in low and middle income countries.

    PubMed

    Firoz, Tabassum; Sanghvi, Harshad; Merialdi, Mario; von Dadelszen, Peter

    2011-08-01

    Pre-eclampsia and eclampsia are leading causes of maternal and perinatal morbidity and mortality worldwide. The exact prevalence, however, is unknown. The majority of pre-eclampsia related deaths in LMIC occur in the community and therefore, interventions must be focused at this level. There are a number of unique challenges facing LMIC but the principles of care for women with pre-eclampsia remain the same as in well resourced settings. Three primary delays lead to an increased incidence of maternal mortality from pre-eclampsia- delays in triage, transport and treatment. There are a number of other challenges facing LMIC and the health care worker shortage is particularly significant. Task shifting is a potential strategy to address this challenge. Community health care workers, specifically lady health care workers, are an integral part of the health care force in many LMIC and can be employed to provide timely care to women with pre-eclampsia. Prevention strategies should be applied to every pregnant woman since we cannot predict who will develop pre-eclampsia given the limitation in resources. Aspirin and calcium are the only two recommended therapies at this time. Measuring blood pressure and proteinuria is challenging in LMIC due to financial cost and lack of training. A detection tool that is affordable and can be easily applied is needed. Magnesium sulfate is the drug of choice for the prevention and treatment of eclampsia but it is underutilized due to barriers on multiple levels. PMID:21592865

  14. Monocytes and Macrophages in Pregnancy and Pre-Eclampsia

    PubMed Central

    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

  15. Telomere length, pre-eclampsia, and gestational diabetes

    PubMed Central

    2010-01-01

    Background Telomere length is a marker of cumulative damage to the cell, and has been associated with cardiovascular disease, hypertension, and diabetes. Findings The association of telomere length with pre-eclampsia and gestational diabetes mellitus (GDM) was examined in a nested case-control study. Circulating leukocyte telomere length was measured by Quantitative-PCR. Mean and median telomere length among cases and controls was compared, and logistic regression was used to model the outcomes as a function of tertile telomere length, with control for effects of potential confounders. Mean telomere length in pre-eclampsia cases was 0.77 (SD 0.14), in GDM cases was 0.73 (SD 0.10), and in controls was 0.74 (SD 0.14). The adjusted odds ratio comparing the highest tertile to the lowest for pre-eclampsia was 0.92 (0.15-5.46), and for gestational diabetes was 0.65 (0.13-3.34). Conclusions Further study is necessary to determine if telomere length is associated with these pregnancy complications. PMID:20416088

  16. Pre-eclampsia: evidence of altered ventricular repolarization by standard ECG parameters and QT dispersion.

    PubMed

    Raffaelli, Ricciarda; Prioli, Maria Antonia; Parissone, Francesca; Prati, Daniele; Carli, Michela; Bergamini, Corinna; Cacici, Giuseppe; Balestreri, Debora; Vassanelli, Corrado; Franchi, Massimo

    2014-11-01

    Pre-eclampsia complicates approximately 6-8% of all pregnancies. Epidemiologic studies have demonstrated a relationship between pre-eclampsia and cardiac morbidity and mortality later in life, but the effect of pre-eclampsia on electrical cardiac activity during the acute phase has not yet been understood. The aim of this study was to investigate ECG alterations during pre-eclampsia. Prepartum ECGs of 76 consecutive pre-eclamptic women were compared with those of 76 healthy pregnant women. All of the routine ECG parameters were considered, and ventricular repolarization was assessed by QT interval and QT dispersion (QTd). Pregnancies complicated by pre-eclampsia showed a significant alteration of ventricular repolarization compared with the control group. Among ECG parameters, QT and QTc intervals and QTd were more prolonged in pre-eclamptic women. Multivariate analysis also showed that pre-eclampsia was the only independent determinant of QTd. In conclusion, pre-eclampsia has a significant effect on ventricular repolarization. This alteration could, in part, explain the increased cardiovascular risk of women with a history of pre-eclampsia. Further studies are necessary to confirm the relationship between ventricular repolarization abnormalities and increased cardiovascular risk later in life. PMID:24965173

  17. Relationship between insulin resistance and circulating endothelial cells in pre-eclampsia.

    PubMed

    Anim-Nyame, Nick; Ghosh, Anshuman; Freestone, Nick; Arrigoni, Francesca I F

    2015-10-01

    Endothelial dysfunction and insulin resistance (IR) are established features of pre-eclampsia, however the cause and effect relationship between them remain unexplained. Circulating endothelial cells (CEC) are increased in pre-eclampsia and appear to correlate with the degree of endothelial dysfunction. We hypothesised that CEC count in pre-eclampsia would correlate with IR and might provide a simple measure of IR in pregnancies complicated by the disease. CEC count and IR were measured in 10 women with pre-eclampsia and 10 normal pregnant controls matched for maternal age, body mass index and gestational age during the third trimester. CEC count was determined using an established immunomagnetic bead separation method and IR was measured by the homeostasis model test. CEC count and IR were significantly increased in pre-eclampsia compared to normal pregnancy. However, there was no correlation between the CEC count and IR in pre-eclampsia. The data suggest that CEC count in pre-eclampsia is not a useful measure on its own of IR in pregnancies complicated by the disease. PMID:26172933

  18. KIR2DL4 expression rather than its single nucleotide polymorphisms correlates with pre-eclampsia

    PubMed Central

    Wang, Dandan; Tian, Yuan; Zhao, Yanhui; Liu, Lianlian; Liu, Xianying; Wu, Fuju

    2015-01-01

    Objective: To evaluate the single nucleotide polymorphisms and expression of KIR2DL4 (killer cell immunoglobulin-like receptors) gene in pre-eclampsia patients. Methods: KIR2DL4 gene polymorphisms were detected in 100 patients with pre-eclampsia and 100 healthy pregnant women, respectively, by using PCR-SS. Then, the expression of KIR2DL4 was measured in 5 cases of placentas tissues with pre-eclampsia and normal pregnancies by using qRT-PCR. Results: Compared with healthy controls, 16 loci of single nucleotide polymorphisms (SNP) were identified in pre-eclampsia patients, including 7 new polymorphisms loci. But, no significant difference was found in genotype distributions and allele frequencies in pre-eclampsia and controls (P>0.05). However, qRT-PCR results showed that KIR2DL4 mRNA in placenta tissues with pre-eclampsia was significantly lower than those with normal pregnancy, and the difference was statistically significant. Conclusion: Decreased level of KIR2DL4 rather than its SNP is correlated with the susceptibility of pre-eclampsia. PMID:26823774

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

    Williams, Paula Juliet; Morgan, Linda

    2012-01-01

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

  1. 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–fetal interface haemorrhage and non-occlusive fetal thrombotic vasculopathy. Conclusions In this pilot study of placental tissue from lupus pregnancies, outcomes were more complicated, particularly if associated with APS. Placental tissue revealed marked inflammatory and vascular changes that were essentially indistinguishable from placental tissue of pre-eclampsia pregnancies. PMID:27158525

  2. 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

  3. 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

  4. 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

  5. Diagnostic and predictive biomarkers for pre-eclampsia in patients with established hypertension and chronic kidney disease.

    PubMed

    Bramham, Kate; Seed, Paul T; Lightstone, Liz; Nelson-Piercy, Catherine; Gill, Carolyn; Webster, Philip; Poston, Lucilla; Chappell, Lucy C

    2016-04-01

    Women with chronic kidney disease (CKD) and chronic hypertension (CHT) frequently develop superimposed pre-eclampsia, but distinction from pre-existing disease is challenging. Plasma placental growth factor (PlGF), B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and serum relaxin concentrations were quantified in a longitudinal prospective cohort of 121 women with CKD: 44 with chronic hypertension, and 79 healthy controls. Biomarker concentrations were compared with 32 women with pre-eclampsia without pre-existing disease. Test performance was evaluated for diagnosis of superimposed pre-eclampsia requiring delivery within 14 days of sampling. PlGF was evaluated as a promising marker in a validation cohort of women with suspected pre-eclampsia (29 with CKD; 94 with chronic hypertension; 29 with superimposed pre-eclampsia requiring delivery within 14 days) and compared with women without pre-existing disease (290 with no pre-eclampsia and 176 with pre-eclampsia requiring delivery within 14 days). From 20 and up to 42 weeks of gestation, lower maternal PlGF concentrations had high diagnostic accuracy for superimposed pre-eclampsia requiring delivery within 14 days (receiver operator characteristic 0.85) and confirmed in the validation cohort. The other plasma and serum biomarkers were not discriminatory. Thus, plasma PlGF concentrations could potentially help guide clinical decision making regarding admission and delivery for superimposed pre-eclampsia. PMID:26924064

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

    PubMed

    Kutzler, M; Sahlfeld, L; Fellows, E

    2012-12-01

    Pre-eclampsia affects 2-8% of pregnant women worldwide and is the third leading cause of maternal mortality in the United States, accounting for 20% of maternal deaths, for which the only known cure is delivery of the placenta. It is known that pre-eclampsia results from defects within the trophoblast invasion of the endometrium and myometrium. At a morphological level within the pre-eclamptic human placenta, trophoblast invasion is shallow, and this results in hypoperfusion, which is a life-threatening condition for both the mother and the foetus. Pre-eclampsia has been intensively investigated for over 50 years, and yet the causes are largely unknown. Despite a large body of data, it is still unknown exactly which mechanisms regulate trophoblast invasion. An effective animal model may be crucial to understanding the underlying causes of pre-eclampsia. A canine model is a proposed improvement on the current efforts to investigate disorders of shallow trophoblast invasion throughout gestation and to improve understanding of the factors that regulate trophoblast invasion. The objectives of this research were to elucidate and compare cellular and molecular similarities between normal canine trophoblasts with those from recently published reports on pre-eclampsia in women. PMID:23279495

  7. Prediction of pre-eclampsia: a protocol for systematic reviews of test accuracy

    PubMed Central

    Cnossen, Jeltsje S; van der Post, Joris AM; Mol, Ben WJ; Khan, Khalid S; Meads, Catherine A; ter Riet, Gerben

    2006-01-01

    Background Pre-eclampsia, a syndrome of hypertension and proteinuria, is a major cause of maternal and perinatal morbidity and mortality. Accurate prediction of pre-eclampsia is important, since high risk women could benefit from intensive monitoring and preventive treatment. However, decision making is currently hampered due to lack of precise and up to date comprehensive evidence summaries on estimates of risk of developing pre-eclampsia. Methods/Design A series of systematic reviews and meta-analyses will be undertaken to determine, among women in early pregnancy, the accuracy of various tests (history, examinations and investigations) for predicting pre-eclampsia. We will search Medline, Embase, Cochrane Library, MEDION, citation lists of review articles and eligible primary articles and will contact experts in the field. Reviewers working independently will select studies, extract data, and assess study validity according to established criteria. Language restrictions will not be applied. Bivariate meta-analysis of sensitivity and specificity will be considered for tests whose studies allow generation of 2 × 2 tables. Discussion The results of the test accuracy reviews will be integrated with results of effectiveness reviews of preventive interventions to assess the impact of test-intervention combinations for prevention of pre-eclampsia. PMID:17052339

  8. 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.

  9. Post-splenectomy splenic artery aneurysm rupture in an atypical presentation of pre-eclampsia.

    PubMed

    Lembet, A; Saphier, C J; Gaddipati, S; Divino, C; Berkowitz, R L

    2001-10-01

    Splenic artery aneurysm rupture in pregnancy is an uncommon catastrophic event. We report a patient who presented at 15 3/7 weeks with atypical pre-eclampsia. After termination was recommended, the patient chose to continue the pregnancy. Reversal of clinical and laboratory abnormalities occurred and the patient was discharged. The patient presented again at 24 weeks with severe pre-eclampsia and residual splenic artery aneurysm rupture, at the site of a splenectomy that had been performed 24 years previously. PMID:11730503

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

    PubMed Central

    Gandhi, Sangeetha; Rao, Vishwas

    2014-01-01

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

  11. Anesthetic management of a case of severe pre-eclampsia with antepartum hemorrhage with pulmonary edema for caesarean section.

    PubMed

    Borkar, Sharmila; Barad, Deepa; Bharne, Sidhesh

    2012-01-01

    Pulmonary edema is a rare complication of pre-eclampsia. We report a case of severe pre-eclampsia with abruptio placentae with intra-uterine fetal demise, complicated by pulmonary edema, managed under general anesthesia for caesarean section. PMID:25885621

  12. Anesthetic management of a case of severe pre-eclampsia with antepartum hemorrhage with pulmonary edema for caesarean section

    PubMed Central

    Borkar, Sharmila; Barad, Deepa; Bharne, Sidhesh

    2012-01-01

    Pulmonary edema is a rare complication of pre-eclampsia. We report a case of severe pre-eclampsia with abruptio placentae with intra-uterine fetal demise, complicated by pulmonary edema, managed under general anesthesia for caesarean section. PMID:25885621

  13. 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

  14. The characteristic of Indonesia's pre-eclampsia: From obstetric intensive care with ventilator until epidemiologic and its molecular biology profile of pulmonary edema in severe pre-eclampsia.

    PubMed

    Hermanto; Adityawarman; Sulistyono; Ardian, M; Dachlan, E G

    2014-07-01

    Pulmonary edema is among the least frequently diagnosed criteria for severe pre-eclampsia. A higher incidence of pulmonary edema was noted in older patients, multigravidas, and patients with underlying chronic hypertension that developed prior to delivery. The development of pulmonary edema was also associated with the administration of excess colloid or crystaloid infusion. Two hundreds and thirty millions people occupying Indonesia as tropical and coastal country gave rise the problem of highly maternal mortality rate of 225/100,000 deliveries where pre-eclampsia and eclampsia as most possible cause. Over 5years from the year 2005 through 2009 our 160 eclampsia study observed about significantly correlation between typical estafet referred case and maternal mortality (Odds ratio 19.1 and P=0.065). Specifically those referred eclampsia cases arriving lately to our tertiary hospital, complication of pulmonary edema also apparently became determinant factor to uphold the increased maternal mortality (Odds ratio 6.1 and P=0.083) We found at our teaching hospital Dr. Soetomo Surabaya as referral center along the year 2012, 477 pre-eclampsia-eclampsia cases which complicated by 27 cases of pulmonary from which we apply obstetric intensive care unit for tightly monitoring treatment. The majority use of ventilator were applied on 22 cases (81.4%), that most approximately 16 cases (72%) need 48h under ventilator use and the remaining 6 cases was not untill 5days of extubation. The etiology of pulmonary edema in preeclamptic patients involves multi-factors; abnormal COP-PWCP gradient, increased pulmonary capillary permeability, and left ventricular failure were identified causes. It has been well known that the pathogenesis of pulmonary edema in severe pre-eclampsia-eclampsia initiated by capillary alveolar leakage that leading increased capillary permeability and extravascular fluid oncotic as well as decreased plasma oncotic pressure. In severe pre-eclampsia appear that another circumstance directing its worst state of inhibited angiogenesis related pulmonary edema. The study confirmed that the decreased serum albumin of ⩽3g% and its content of amino acid essentiale acitvate endoplasmic reticulum stress response in which indicated by increasingly produced GRP (Glucose Related-Protein) 78. It may affect the decreased VEGFR and may also be inhibiting angiogenesis and hypoxia as well. At such moment apparently pulmonary edema patient get worsening clinical sign. PMID:26104647

  15. Pre-eclampsia and future cardiovascular risk among women: a review.

    PubMed

    Ahmed, Raheel; Dunford, Joseph; Mehran, Roxana; Robson, Stephen; Kunadian, Vijay

    2014-05-13

    Cardiovascular disease continues to be the leading cause of death in the western world. Due to advancements in diagnosis, prevention, and treatment, cardiovascular mortality has fallen in recent years. Previous studies have evaluated the impact of traditional risk factors such as hypercholesterolemia and smoking. However, limited studies have been conducted to evaluate sex discrepancies among patients with cardiovascular disease. Pre-eclampsia is a multisystem placentally mediated disease, which usually arises after 32 weeks of gestation and classically presents with hypertension and proteinuria. Pre-eclampsia affects 2% to 8% of all pregnancies worldwide and is often complicated by fetal growth restriction. Women with a history of pre-eclampsia are at increased risk of future cardiovascular complications. Therefore, this topic is of significance to the cardiovascular health of over 300 million women worldwide. The goal of this review is to determine the association of pre-eclampsia and future cardiovascular risk and to explore the potential management options for these high-risk women. PMID:24613324

  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. 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

  18. 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

  19. Development of mHealth applications for pre-eclampsia triage.

    PubMed

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

    2014-11-01

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

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

    PubMed

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

    2015-08-01

    N(omega)-nitro-L-arginine methyl ester (L-NAME) decreases the vasodilator effect of nitric oxide (NO) and induces pre-eclampsia in mouse. Sildenafil inhibits the degradation of nitric oxide and increases vasodilation. This study aimed to determine the effects of sildenafil citrate on angiogenesis and oxidative stress at the maternal foetal interface on pre-eclampsia-like mouse model induced by L-NAME. Twenty pregnant mice were divided into four groups: (i) vehicle control; (ii) L-NAME; (iii) sildenafil; (4) L-NAME+sildenafil. L-NAME was administered from day 7 of pregnancy and sildenafil from day 8 until day 16; animals were euthanized on day 17. Placental and foetal sizes and weights were measured; lipid peroxide levels and catalase activity in placental homogenates were determined, and placental vascular endothelia were identified by lectin-histochemistry using BSA-I lectin. Western blot analysis was used to determine VEGF expression in placental homogenates. No changes were seen in placental and foetal development in mice with normal pregnancies treated with sildenafil. Treatments with L-NAME reduced significantly the placental weight and average height and decreased the percentage of the endothelial surface. These alterations may be mediated by the reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L-NAME on nitric oxide synthase (NOS) synthesis. This effect was offset by the treatment with sildenafil, with an increase in the percentage of the endothelial surface. In conclusion, our results indicate that treatment with sildenafil on pre-eclampsia mouse model can be used without adverse effects on the concept and its use in the treatment of pre-eclampsia is promising. PMID:25959785

  2. First trimester multivitamin/mineral use is associated with reduced risk of pre-eclampsia among overweight and obese women.

    PubMed

    Vanderlelie, Jessica; Scott, Rani; Shibl, Rania; Lewkowicz, Jessica; Perkins, Anthony; Scuffham, Paul A

    2016-04-01

    The use of pregnancy-specific multivitamin supplements is widely recommended to support maternal homeostasis during pregnancy. Our objective was to investigate whether multivitamin use during pregnancy is associated with a reduced risk of pre-eclampsia. The effect of multivitamin use on incidence of pre-eclampsia in lean and overweight/obese women was analysed using data collected between 2006 and 2011 as part of the Environments for Healthy Living Project, Griffith University, Australia. A total of 2261 pregnancies were included in the analysis with pre-eclampsia reported in 1.95% of subjects. Body mass index (BMI) ≥ 25 was associated with a 1.97-fold [95% confidence interval (CI): 0.93, 4.16] increase in pre-eclampsia risk. First trimester multivitamin use was reported by 31.8% of women and after adjustment, was associated with a 67% reduction in pre-eclampsia risk (95%CI: 0.14, 0.75). Stratification by BMI demonstrated a 55% reduction in pre-eclampsia risk (95%CI: 0.30, 0.86) in overweight (BMI: 25-29.9) and 62% risk reduction (95%CI: 0.16, 0.92) in obese (BMI: ≥30) cohorts that supplemented with multivitamins in the first trimester of pregnancy. This finding may be particular to the Australian population and reflect inherent nutritional deficits. First trimester folate supplementation was found to reduce pre-eclampsia incidence [adjusted odds ratios (AOR) 0.42 95%CI: 0.13, 0.98] and demonstrated significance upon stratification by overweight status for women with BMI >25 (AOR 0.55 95%CI: 0.31, 0.96). These results support the hypothesis that multivitamin supplementation may be beneficial in reducing the incidence of pre-eclampsia during pregnancy and be of particular importance for those with a BMI ≥25. PMID:24847942

  3. Serum Calcium Status among Pregnancies Complicated By Pre-Eclampsia in Bangladesh.

    PubMed

    Akhter, S; Hoque, M R; Paul, U K; Hossain, M M

    2015-10-01

    This case control cross sectional study was carried out in the department of biochemistry, Mymensingh medical college in collaboration with the outpatient department, family planning model clinic and antenatal obstetric ward of Mymensingh medical college hospital, Mymensingh during the period of July 2003 to June 2004. The aim of the study was to explore the status of serum calcium among pregnancies complicated by pre-eclampsia in Bangladesh as a means to monitor the possibility of management of these patients. A total of 82 subjects were selected and were grouped as Group I (32 healthy women with uncomplicated pregnancy as control subjects) and Group II (50 pregnant women with pre-eclampsia as cases). Serum calcium was estimated by colorimetric method from each sample. Statistical analysis was done by using SPSS windows package. Among the groups, meanSD (Standard Deviation) of Group I and Group II serum calcium were 8.711.00 and 10.781.44 mg/dl respectively. By comparing Group I with Group II highly significant difference were found in case of serum calcium (P<0.001). It is evident from the study that serum calcium level significantly increases among pregnancies complicated by pre-eclampsia in Bangladesh. PMID:26619999

  4. [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

  5. 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

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

    PubMed

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

    2014-08-01

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

  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 ?g/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0039). 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. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. 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

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

    PubMed Central

    Hawfield, Amret; Freedman, Barry I.

    2009-01-01

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

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

    PubMed Central

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

    2014-01-01

    Background Epidemiological data link low dietary calcium with pre-eclampsia. Current recommendations are for 1.52g/day calcium supplementation for low-intake pregnant women, based on randomised controlled trials of ?1g/day calcium supplementation from 20weeks of gestation. This is problematic logistically in low-resource settings; excessive calcium may be harmful; and 20weeks may be too late to alter outcomes. Objectives To review the impact of lower dose calcium supplementation on pre-eclampsia risk. Search strategy and selection criteria We searched PubMed and the Cochrane Pregnancy and Childbirth Group trials register. Data collection and analysis Two authors extracted data from eligible randomised and quasi-randomised trials of low-dose calcium (LDC, <1g/day), with or without other supplements. Main results Pre-eclampsia was reduced consistently with LDC with or without co-supplements (nine trials, 2234 women, relative risk [RR] 0.38; 95% confidence interval [95% CI] 0.280.52), as well as for subgroups: LDC alone (four trials, 980 women, RR 0.36; 95% CI 0.230.57]); LDC plus linoleic acid (two trials, 134 women, RR 0.23; 95% CI 0.090.60); LDC plus vitamin D (two trials, 1060 women, RR 0.49; 0.310.78) and a trend for LDC plus antioxidants (one trial, 60 women, RR 0.24; 95% CI 0.061.01). Overall results were consistent with the single quality trial of LDC alone (171 women, RR 0.30; 95% CI 0.061.38). LDC plus antioxidants commencing at 812weeks tended to reduce miscarriage (one trial, 60 women, RR 0.06; 95% CI 0.001.04). Conclusions These limited data are consistent with LDC reducing the risk of pre-eclampsia; confirming this in sufficiently powered randomised controlled trials would have implications for current guidelines and their global implementation. PMID:24621141

  15. Severe pre-eclampsia and infants of very low birth weight.

    PubMed Central

    Szymonowicz, W; Yu, V Y

    1987-01-01

    The effect of severe pre-eclampsia on the outcome of infants of very low birth weight was studied in a prospective case control study of 35 pairs of infants of comparable gestation. Significantly more infants were delivered before the onset of labour and by caesarean section in the group with pre-eclampsia. These babies tended to be smaller and had a higher incidence of hyaline membrane disease, patent ductus arteriosus, pulmonary air leak, and hypotension. They also required more intensive treatment with oxygen and mechanical ventilation. The significant difference in birth weight was still apparent at 2 years of age. Although the mean psychomotor developmental index and the incidence of specific neurodevelopmental impairments were not significantly different between the two groups, survivors in the group born to pre-eclamptic mothers had a significantly lower mean mental developmental index, and significantly more of these children had one or more impairments compared with the control group at 2 years of age. PMID:3632019

  16. The renin-angiotensin-aldosterone system in pre-eclampsia: the delicate balance between good and bad.

    PubMed

    Verdonk, Koen; Visser, Willy; Van Den Meiracker, Anton H; Danser, A H Jan

    2014-04-01

    Pregnancy demands major changes of the cardiovascular system, and this involves, among others, activation of the RAAS (renin-angiotensin-aldosterone system), allowing an aldosterone-dependent increase in volume. Remarkably, a relative resistance to the pressor response of AngII (angiotensin II) develops simultaneously to prevent the increase in blood pressure that would normally accompany RAAS activation. The increase in volume, the degree of RAAS activation and the diminished pressor response to AngII are less pronounced in pre-eclampsia. However, animal models displaying excessive RAAS activation also result in a pre-eclampsia-like syndrome, and the aldosterone/renin ratio is elevated in pre-eclampsia compared with a normal pregnancy. New insights into the pathogenesis of pre-eclampsia have revealed a major role for VEGF (vascular endothelial growth factor), VEGF-inactivating sFlt-1 (soluble fms-like tyrosine kinase-1) and AT1 (angiotensin II type 1) receptor autoantibodies. The last mentioned activate AT(1) receptors, thereby potentially suppressing circulating renin and aldosterone. VEGF, both directly and indirectly (by increasing capillary density), affects adrenal aldosterone synthesis. The present review summarizes all of the recent findings regarding RAAS regulation in pre-eclampsia compared with normal pregnancy, concluding that factors such as sFlt-1 and AT(1) receptor autoantibodies disturb the delicate balance that normally results in a volume increase and a diminished vasoconstrictor response to AngII in pregnant women. It is possible that there are non-parallel changes in the circulating and renal RAAS in pre-eclampsia, which are potentially reflected by the urinary levels of renin. PMID:24400721

  17. Promising biomarkers for superimposed pre-eclampsia in pregnant women with established hypertension and chronic kidney disease.

    PubMed

    Acharya, Anjali

    2016-04-01

    The incidence of pre-eclampsia is high in women with chronic kidney disease and hypertension and the diagnosis is particularly challenging. Bramham et al. (2016) studied various biomarkers with the primary aim of predicting superimposed pre-eclampsia requiring delivery within 14 days of sampling. Their findings of the utility of a single biomarker for diagnosis in this high-risk group is a major advance that has significant implications and holds promise for the future. PMID:26994571

  18. 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

  19. Transthoracic echocardiographic assessment of haemodynamics in severe pre-eclampsia and HIV in South Africa.

    PubMed

    Dennis, A T; Dyer, R A; Gibbs, M; Nel, L; Castro, J M; Swanevelder, J L

    2015-09-01

    Haemodynamic and cardiac structural changes in severe pre-eclampsia and in pregnant women with human immunodeficiency virus (HIV) infection have not been clearly established. We performed transthoracic echocardiography on 105 women. Women with pre-eclampsia demonstrated (mean (SD), untreated vs treated) preserved fractional shortening (40 (7.1)% vs. 41 (8.6)%), a non-dilated left ventricle (4.5 (0.49) cm vs. 4.4 (0.44) cm), increased mitral valve E/septal e' (10.5 (3.3) vs. 10.6 (2.8)), and preserved tricuspid annular plane systolic exertion (2.6 (0.36) cm vs. 2.4 (0.51) cm). Women with HIV infection demonstrated (mean (SD), HIV-positive vs healthy) a reduced cardiac index (2.8 (0.64) ml.min(-1) .m(-2) vs. 3.1 (0.7) ml.min(-1) .m(-2) , p = 0.029), reduced septal s' tissue Doppler velocity (8.5 (1.5) cm.s(-1) vs. 9.3 (1.7) cm.s(-1) , p = 0.042), increased left ventricular end-diastolic area (7.6 (2.1) cm2 vs. 6.3 (1.7) cm2 , p = 0.004), and reduced right ventricular s' and e' velocity (s' velocity 14.7 (3.1) cm.s(-1) vs. 7.0 (2.9) cm.s(-1) p = 0.001, e' velocity 16.3 (4.1) cm.s(-1) vs. 18.7 (3.4) cm.s(-1) , p = 0.013). The mitral value E/septal e' was > 8 in 39% of patients with HIV. Fractional shortening (< 28%) was reduced in 10% of healthy women, and mitral valve E/septal e' ratios were > 8 in 38% of that group. Women with pre-eclampsia demonstrated preserved systolic function, with diastolic dysfunction. Women with HIV demonstrated reduced left and right ventricular systolic function, with increased ventricular dilatation. PMID:25891669

  20. TH17 cells in human recurrent pregnancy loss and pre-eclampsia

    PubMed Central

    Fu, Binqing; Tian, Zhigang; Wei, Haiming

    2014-01-01

    T helper 17 (TH17) cells have been identified as a new lineage of helper T cells and have been shown to be important in host defense against extracellular infectious agents, autoimmune disease and chronic inflammatory diseases. Recently, TH17 cells have also been shown to participate in successful pregnancy, as well as in the pathogenesis of diseases of pregnancy, such as recurrent spontaneous abortion (RSA) and pre-eclampsia (PE). Here, we review our current knowledge of TH17 cells in human RSA and PE. We also discuss how the local uterine microenvironment affects the differentiation of TH17 cells and the mechanisms that regulate TH17 cells during pregnancy. Research into TH17 cells will not only advance our understanding of TH17-related pregnancy complications, but will also facilitate the design of novel therapies for reproductive diseases. PMID:25027967

  1. 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

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

    PubMed

    Elliot, Michael G; Crespi, Bernard J

    2015-03-01

    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

  3. 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

  4. 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

  5. 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

  6. Candidate biochemical markers for screening of pre-eclampsia in early pregnancy.

    PubMed

    Forest, Jean-Claude; Charland, Marc; Massé, Jacques; Bujold, Emmanuel; Rousseau, François; Lafond, Julie; Giguère, Yves

    2012-06-01

    Pre-eclampsia (PE) and other hypertensive disorders of pregnancy (HDP) are a leading cause of adverse outcomes. Their pathophysiology remains elusive, hampering the development of efficient prevention. The onset of HDP and PE and the severity of their clinical manifestations are heterogeneous. The advent of preventive measures, such as low-dose aspirin that targets high-risk women, emphasizes the need of better prediction. Until recently, only environmental information and maternal risk factors were considered, with equivocal predictive value. No validated screening procedures were available to identify at-risk women despite the emergence of Doppler ultrasonography parameters for the uterine artery (e.g., pulsatility index and bilateral notching) and pathophysiological biochemical markers (e.g., angiogenesis, inflammation, and endothelial dysfunction). Owing to its heterogeneity and lack of specific, sensitive markers among those studied so far (>200), PE is unlikely to be detected early by a single predictive parameter. Systematic reviews have concluded that no single test fulfilling World Health Organization criteria for biomarker selection can diagnose/predict a disease. However, by combining antenatal risk factors, clinical parameters, as well as biophysical and biochemical markers into multivariate algorithms, the risk of PE can be estimated with performance levels that could reach clinical utility. Performance characteristics of selected algorithms will be presented and discussed with respect to transferability to different geographic and healthcare environments. PMID:22706239

  7. 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

  8. 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

  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. Factors associated with pre-eclampsia and quality care of affected teenagers during labour within health region H. in Kwa-Zulu Natal.

    PubMed

    Dlamini, N J

    1997-12-01

    This is a descriptive, exploratory study which aimed at identifying the factors that are associated with pre-eclampsia in teenagers. The study also aimed at assessing the quality of midwifery care during labour in teenagers with pre-eclampsia so that recommendations can be made based on empirical findings. The study was done within Health Region H of KwaZulu-Natal Province in South Africa. A structured interview schedule was designed to tap information from pre-eclamptic teenagers in an attempt to identify factors associated with pre-eclampsia. A checklist was also designed and administered to assess the care of a pre-eclamptic teenager during labour. The study revealed that factors like age, nulliparity and socio-economic status were associated with pre-eclampsia. In as far as the rest of the factors, there was no relationship as indicated in previous studies. The study also revealed that teenagers affected by pre-eclampsia delayed in attending the antenatal clinic resulting in the control of the disease being difficult. In as far as midwifery care, the study revealed that psychological and social care, as well as the hygienic state of patients was not satisfactory. Based on the findings of the study, it is recommended that health education on prevention of pre-eclampsia should be done on an ongoing process, while carers for teenage mothers should be given inservice education programmes on psychosocial care. The physical environment for maternity units must be improved. PMID:9538699

  12. 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

  13. 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

  14. 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.

  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. 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

  17. Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

    PubMed Central

    Myatt, L; Clifton, RG; Roberts, JM; Spong, CY; Wapner, RJ; Thorp, JM; Mercer, BM; Peaceman, AM; Ramin, SM; Carpenter, MW; Sciscione, A; Tolosa, JE; Saade, G; Sorokin, Y; Anderson, GD

    2014-01-01

    Objective To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. Design A nested case–control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. Setting A multicentre study in 16 academic medical centres in the USA. Population Low-risk nulliparous women. Methods Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9–12, 15–18 and 23–26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. Main outcome measures Change in PlGF, sFlt-1 and sEng. Results Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64–99%), 77% (95% CI 50–93%) and 77% (95%CI 50–93%) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. Conclusion Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia. PMID:23331974

  18. Genome-wide hypermethylation coupled with promoter hypomethylation in the chorioamniotic membranes of early onset pre-eclampsia

    PubMed Central

    Ching, Travers; Song, Min-Ae; Tiirikainen, Maarit; Molnar, Janos; Berry, Marla; Towner, Dena; Garmire, Lana X.

    2014-01-01

    Pre-eclampsia is the leading cause of fetal and maternal morbidity and mortality. Early onset pre-eclampsia (EOPE) is a disorder that has severe maternal and fetal outcomes, whilst its etiology is poorly understood. We hypothesize that epigenetics plays an important role to mediate the development of EOPE and conducted a case–control study to compare the genome-wide methylome difference between chorioamniotic membranes from 30 EOPE and 17 full-term pregnancies using the Infinium Human Methylation 450 BeadChip arrays. Bioinformatics analysis tested differential methylation (DM) at CpG site level, gene level, and pathway and network level. A striking genome-wide hypermethylation pattern coupled with hypomethylation in promoters was observed. Out of 385 184 CpG sites, 9995 showed DM (2.6%). Of those DM sites, 91.9% showed hypermethylation (9186 of 9995). Over 900 genes had DM associated with promoters. Promoter-based DM analysis revealed that genes in canonical cancer-related pathways such as Rac, Ras, PI3K/Akt, NFκB and ErBB4 were enriched, and represented biological functional alterations that involve cell cycle, apoptosis, cancer signaling and inflammation. A group of genes previously found to be up-regulated in pre-eclampsia, including GRB2, ATF3, NFKB2, as well as genes in proteasome subunits (PSMA1, PMSE1, PSMD1 and PMSD8), harbored hypomethylated promoters. Contrarily, a cluster of microRNAs, including mir-519a1, mir-301a, mir-487a, mir-185, mir-329, mir-194, mir-376a1, mir-486 and mir-744 were all hypermethylated in their promoters in the EOPE samples. These findings collectively reveal new avenues of research regarding the vast epigenetic modifications in EOPE. PMID:24944161

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

    PubMed Central

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

    2013-01-01

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

  20. The effect of sildenafil on the altered thoracic aorta smooth muscle responses in rat pre-eclampsia model.

    PubMed

    Turgut, Nergiz Hacer; Temiz, Tijen Kaya; Bagcivan, Ihsan; Turgut, Bulent; Gulturk, Sefa; Karadas, Baris

    2008-07-28

    The pathophysiology of pre-eclampsia is still unknown thus effective primary prevention is not possible at the stage. The present study was conducted to research the smooth muscle responses in the pre-eclampsia model with suramin treated rats and the effect of phosphodiesterase-5 (PDE5) inhibitor on these responses. Rats of three groups; control, suramin and suramin+sildenafil were given intraperitoneal injections of saline, suramin or sildenafil citrate. Suramin injections caused increased blood pressure, protein in urine and caused fetal growth retardation. The use of sildenafil citrate straightened significantly both blood pressure and average fetus weight, but did not reach to control values. At the end of pregnancy, thoracic aorta rings were exposed to contractile and relaxant agents. KCl contraction responses, sodium nitroprusside and papaverine relaxation responses were similar in three groups. Contraction responses of phenylephrine, increased significantly in suramin group. Relaxation responses of acethylcholine and bradykinin decreased in suramin group. The use of sildenafil citrate partially straightened both relaxation and contraction responses, but did not reach to control values. In all groups in the presence of L-nitromonomethylarginine (L-NAME), 1H-(1, 2, 4) oxadiazole (4, 3-a) guinoxalin-1-one (ODQ) and indomethacin decreased the relaxation responses of acetylcholine and bradykinin. The cyclic guanosine monophosphate (cGMP) content of thoracic aorta tissue was determined by radioimmunoassay technique. The content of cGMP in suramin group decreased and use of sildenafil citrate increased the cGMP content but did not reach to control values. We conclude that in pre-eclampsia, the increase of contraction responses, the decrease of relaxation responses and the decrease of cGMP content can depend on insufficiency about synthesis or release of relaxant factors which was released from the vessel endothelium. The results in this study show that in pre-eclampsia; PDE5 inhibitors enhance endothelial function and may be used for protection. Further studies are needed to clear the efficiency and safety of PDE5 inhibitors. PMID:18538317

  1. 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

  2. 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 literature search. Prospective study with large simple size and specific measuring data collection are needed to enhance our findings in the future.Our analysis confirms that elevated AT1-AA in serum is significantly associated with hypertensive disorder, especially pre-eclampsia. AT1-AA may be a valuable indicator for poorer prognosis of patients with pre-eclampsia, and could be used in patients with hypertensive disease for risk evaluation and making individual treatment decision. PMID:27124051

  3. 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 evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. Trial registration Clinical trials NCT00469846. PMID:21596735

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

    PubMed

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

    2008-01-01

    Catalase (antioxidant enzyme) activity in erythrocytes and serum levels of trace elements (copper, iron, zinc), heavy metals (cadmium, cobalt) and vitamins A (retinol), D (cholecalciferol) and E (alpha-tocopherol) were measured in 145 subjects comprising 47 pre-eclamptic pregnant women (PE), 48 healthy pregnant women (HP) and 50 healthy non-pregnant controls (NP). Catalase, vitamins A, D and E and levels of cobalt were significantly lower in the PE group compared with the HP and NP groups, whereas levels of copper, iron and cadmium were significantly higher in the PE group than in the HP and NP groups. Levels of zinc were significantly lower in both the PE and HP groups compared with the NP group. This assessment of oxidant/antioxidant imbalance in pregnant women could be useful in the early identification of pre-eclampsia and antioxidant supplementation in the early weeks of gestation might be useful. PMID:19094444

  5. Colour Doppler ultrasound of spiral artery blood flow in the prediction of pre-eclampsia and intrauterine growth restriction.

    PubMed

    Gebb, Juliana; Dar, Pe'er

    2011-06-01

    Pre-eclampsia and intrauterine growth restriction are responsible for significant maternal and fetal morbidity and mortality worldwide. Identifying pregnancies at highest risk for their development would allow increased surveillance in individual pregnancies and also allow therapeutic trials to decrease their incidences in the future. To date, multiple attempts to develop a screening test for these disorders have met with limited success. Proposed screening methods have included maternal serum biochemical parameters as well as ultrasonographic markers. Uterine artery Doppler, direct evaluation of the spiral arteries using colour and spectral Doppler, three-dimensional placental volume analysis and, most recently, three-dimensional power Doppler angiography have all been suggested. Although an adequate screening method remains elusive, advances in ultrasound technology have improved our ability to observe the pathophysiologic changes that occur with these conditions early in pregnancy, bringing us closer to a reproducible screening model. PMID:21377937

  6. 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

  7. Retinal Vein Occlusion and Pregnancy, Pre-Eclampsia, and Eclampsia: The Results from a Nationwide, Population-Based Study Using the National Claim Database

    PubMed Central

    Seo, Kyung Ha; Park, Kyu Hyung; Woo, Se Joon

    2015-01-01

    Objective To investigate the incidence of retinal vein occlusion (RVO) in pregnant women and in the subpopulation of pregnant women with pre-eclampsia/eclampsia compared to that in the age-matched general female population to determine if there is increased risk of RVO in pregnancy. Design Nationwide population-based retrospective study using data entered into the Korean national health claims database from 2007 to 2011. Setting and Participants Of the incident RVO cases in the database, RVO cases that occurred during the pregnancy-associated period, which spanned a 52-week period from 40-weeks-before to 12-weeks-after childbirth, were identified. Of these cases, the presence of pre-eclampsia/eclampsia was determined. Main Outcome and Measure The standardized incidence ratios (SIRs) of RVO in the general pregnant population and in the pregnant population with pre-eclampsia/eclampsia were determined with respect to the age-matched general female population. Results Pregnancy-related RVO was identified in 33 cases from the 1.8 million women who experience childbirth during the study period, while the expected number of cases calculated by the direct standardization to the age-matched general population was 113. Of the 33 patients, 12 patients (36.4%) had pre-eclampsia or eclampsia. The SIR for the general pregnant population in reference to the age-matched general female population was 0.29 (95% CI, 0.20–0.41). In contrast, the SIR for the pregnant population with pre-eclampsia/eclampsia in reference to the age-matched general female population and the age-matched general pregnant population was 67.50 (95% CI, 34.88–117.92) and 246.50 (95% CI, 127.37–430.59), respectively. Conclusions and Relevance The results suggest that pre-eclampsia/eclampsia is a risk factor for RVO, while pregnancy itself may not be a risk factor for RVO. PMID:25774513

  8. 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 care settings in low- and middle-income countries. Usability problems were often related to mobile phone features (eg, scroll wheels, touch screen use). Larger scale evaluation of the clinical impact of this tool is underway. PMID:25887292

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

    PubMed

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

    2009-10-01

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

  10. 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

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

    PubMed Central

    2007-01-01

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

  12. 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

  13. Improved Assay for Quantifying a Redox Form of Angiotensinogen as a Biomarker for Pre-Eclampsia: A Case-Control Study

    PubMed Central

    Rahgozar, Soheila; Amirian, Tayebeh; Qi, Miao; Shahshahan, Zahra; Entezar-E-Ghaem, Mansureh; Ghasemi Tehrani, Hatav; Miroliaei, Mehran

    2015-01-01

    Objective Angiotensinogen exists in two distinct redox forms in plasma, the oxidized sulfhydryl-bridge form and the reduced, unbridged, free thiol form. The oxidized form of angiotensinogen compared to the free thiol form preferentially interacts with renin resulting in increased generation of angiotensin. The predictive potential of the ratio of free-thiol to oxidized angiotensinogen in the plasma for pre-eclampsia was first suggested by the Read group in ref 10. We propose an improved method for determining the ratio and validate the method in a larger cohort of pregnant women. Methods Plasma samples from 115 individuals with pre-eclampsia and from 55 healthy pregnant control subjects were collected sequentially over a 2 year period. Using two distinct enzyme-linked immunosorbent assays (ELISAs) the plasma levels of total and free thiol angiotensinogen were quantified. The oxidized angiotensinogen plasma level is derived by subtracting the level of free thiol, reduced angiotensinogen from the total angiotensinogen levels in the plasma. Results The relative proportion of free thiol angiotensinogen, expressed as a percentage of that observed with an in-house standard, is significantly decreased in pre-eclamptic patients (70.85% ± 29.49%) (mean ± SD) as compared to healthy pregnant controls (92.98 ± 24.93%) (mean ± SD) p ≤ 0.0001. The levels of total angiotensinogen did not differ between the two groups. Conclusion Patients with pre-eclampsia had substantially lower levels of free thiol angiotensinogen compared to healthy pregnant controls, whilst maintaining similar total angiotensinogen levels in the plasma. Hence, elevated levels of plasma oxidized angiotensinogen may be a contributing factor to hypertension in the setting of pre-eclampsia. PMID:26312482

  14. Activities of some glycosaminoglycan- degrading enzymes in Wharton's jelly and their alteration in EPH-gestosis (Pre-eclampsia).

    PubMed

    Romanowicz, L; Bańkowski, E; Sobolewski, K; Jaworski, S

    1999-09-01

    Oedema, proteinuria, hypertension (EPH)-gestosis (pre-eclampsia) is associated with a premature replacement of hyaluronic acid by sulphated glycosaminoglycans (GAGs), both in the umbilical cord arteries and in Wharton's jelly. It may be concluded from our previous report that such a phenomenon may be the result of reduction in degradation of these compounds. In order to support such a conclusion the activities of GAG-degrading enzymes in normal umbilical cord arteries and those taken from newborns delivered by mothers with EPH-gestosis were compared. It was found that EPH-gestosis results in a significant reduction in the activities of neutral endoglycosidases degrading most of the sulphated GAGs (except keratan sulphate). In the case of acidic endoglycosidases, no characteristic alterations have been found. Only the activity of heparan sulphate-degrading endoglycosidase significantly decreased. In contrast to the above-mentioned endoglycosidases, the activities of arylsulphatase B and 6-sulphatase distinctly increased. The decrease in the activities of endoglycosidases are thought to be responsible for EPH-gestosis-associated accumulation of sulphated GAGs in extracellular matrix of Wharton's jelly. This leads to the suspicion that EPH-gestosis-induced changes in the GAGs composition may alter the fibrillogenesis conditions in Wharton's jelly. The sulphated GAGs accumulated in Wharton's jelly may interact with some growth factors which modify the myofibroblasts' proliferation, gene expression, protein biosynthesis and other processes. A significance of EPH-gestosis-induced alteration in Wharton's jelly is discussed. PMID:10460952

  15. Severe pre-eclampsia complicated by HELLP syndrome alterations in the structure of the umbilical cord (morphometric and immunohistochemical study)

    PubMed Central

    Balsak, Deniz; Togrul, Cihan; Ekinci, Cenap; Cavus, Yunus; Tahaoglu, Ali Emre; Deveci, Engin; Gül, Talip; Karaman, Evren; Ekinci, Aysun; Sakar, Nafi

    2015-01-01

    The aim of this study was to evaluate the morphometric and immunohistochemistry in umbilical cords from patients with severe pre-eclampsia with and without haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. The patient and control groups were similar according to baseline obstetric characteristics. White blood cell count in patients with HELLP syndrome and the control group was significantly increased among patients with HELLP syndrome (p < 0.001). Morphometric examination and endothelial core length were significantly different between the groups. In the umbilical cord cross-section of the HELLP group, endothelial cell degeneration in the vessel wall and basement membrane thickening were observed. In the muscle layer of blood vessels, the following disorders were found: increased collagen fibres in the muscle cell, hyperplasia and separation of muscle fibres as well as edema in the intermediate connective tissue. Immunohistochemical analysis showed that endothelial cells, basal membrane and fibroblast cells in the HELLP group expressed high levels of CD44. Vessel wall and amniotic epithelial basement membrane thickening were observed in the HELLP group. Matrix metalloproteinase 9 (MMP9) was expressed. Fibroblast and smooth muscle cells were fusiform and showed a positive reaction to immunohistochemical staining of α-actin smooth muscle. PMID:26019650

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  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. 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

  20. 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 funding sources for authors are detailed in the full online paper. With the exceptions of CM-W, HMI, and KMG there were no competing interests. PMID:26578347

  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. Ceruloplasmin and copper level in maternal and cord blood and in the placenta in normal pregnancy and in pre-eclampsia.

    PubMed

    Fattah, M M; Ibrahim, F K; Ramadan, M A; Sammour, M B

    1976-01-01

    Copper and ceruloplasmin were assayed in maternal and cord blood sera and in the placenta of 10 women with normal pregnancies, in 10 patients mild and 10 with severe pre-eclampsia. Copper and ceruloplasmin levels were significantly elevated in the maternal blood of pre-eclamptic patients as compared with normal pregnant women. The placental and cord blood concentrations of copper and ceruloplasmin showed non-significant changes, which indicates that their increase in the maternal blood is not of placental origin. PMID:998171

  3. 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 associated with the occurrence of pre-eclampsia and HELLP syndrome. PMID:26285098

  4. 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, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a well co-ordinated multidisciplinary collaboration of clinicians, basic scientists and mathematicians is vital. STUDY FUNDING/COMPETING INTEREST(S) No financial support was obtained for this project. There are no conflicts of interest. PMID:25351721

  5. 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

  6. 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, IRB0005239), and is registered with NHREC (ID 3649) and the Pan African Clinical Trial Registry (PACTR201504000771349). Data will be presented at international conferences and published in peer-reviewed journals. PMID:26510725

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

    PubMed

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

    2014-10-01

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

  8. 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

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2014-01-01

    Based on gestational age at diagnosis and/or delivery, pre-eclampsia (PE) is commonly divided into early-onset (<34 weeks) and late-onset (≥34 weeks) forms. Recently, the distinction between ‘placental’ and ‘maternal’ causation has been proposed, with ‘placental’ cases being more frequently associated with early-onset and intrauterine growth restriction. To test whether molecular placental pathology varies according to clinical presentation, we investigated stress-signalling pathways, including unfolded protein response (UPR) pathways, MAPK stress pathways, heat-shock proteins and AMPKα in placentae delivered by caesarean section for clinical indications at different gestational ages. Controls included second-trimester, pre-term and normal-term placentae. BeWo cells were used to investigate how these pathways react to different severities of hypoxia–reoxygenation (H/R) and pro-inflammatory cytokines. Activation of placental UPR and stress-response pathways, including P-IRE1α, ATF6, XBP-1, GRP78 and GRP94, P-p38/p38 and HSP70, was higher in early-onset PE than in both late-onset PE and normotensive controls (NTCs), with a clear inflection around 34 weeks. Placentae from ≥ 34 weeks PE and NTC were indistinguishable. Levels of UPR signalling were similar between second-trimester and term controls, but were significantly higher in pre-term ‘controls’ delivered vaginally for chorioamnionitis and other conditions. Severe H/R (1/20% O2) induced equivalent activation of UPR pathways, including P-eIF2α, ATF6, P-IRE1α, GRP78 and GRP94, in BeWo cells. By contrast, the pro-inflammatory cytokines TNFα and IL-1β induced only mild activation of P-eIF2α and GRP78. AKT, a central regulator of cell proliferation, was reduced in the < 34 weeks PE placentae and severe H/R-treated cells, but not in other conditions. These findings provide the first molecular evidence that placental stress may contribute to the pathophysiology of early-onset pre-eclampsia, whereas that is unlikely to be the case in the late-onset form of the syndrome. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:24931423

  11. 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

  12. Toll-like receptor 9 activation: a novel mechanism linking placenta-derived mitochondrial DNA and vascular dysfunction in pre-eclampsia.

    PubMed

    Goulopoulou, Styliani; Matsumoto, Takayuki; Bomfim, Gisele F; Webb, R Clinton

    2012-10-01

    Emerging evidence suggests that in addition to being the 'power houses' of our cells, mitochondria facilitate effector responses of the immune system. Cell death and injury result in the release of mtDNA (mitochondrial DNA) that acts via TLR9 (Toll-like receptor 9), a pattern recognition receptor of the immune system which detects bacterial and viral DNA but not vertebrate DNA. The ability of mtDNA to activate TLR9 in a similar fashion to bacterial DNA stems from evolutionarily conserved similarities between bacteria and mitochondria. mtDNA may be the trigger of systemic inflammation in pathologies associated with abnormal cell death. PE (pre-eclampsia) is a hypertensive disorder of pregnancy with devastating maternal and fetal consequences. The aetiology of PE is unknown and removal of the placenta is the only effective cure. Placentas from women with PE show exaggerated necrosis of trophoblast cells, and circulating levels of mtDNA are higher in pregnancies with PE. Accordingly, we propose the hypothesis that exaggerated necrosis of trophoblast cells results in the release of mtDNA, which stimulates TLR9 to mount an immune response and to produce systemic maternal inflammation and vascular dysfunction that lead to hypertension and IUGR (intra-uterine growth restriction). The proposed hypothesis implicates mtDNA in the development of PE via activation of the immune system and may have important preventative and therapeutic implications, because circulating mtDNA may be potential markers of early detection of PE, and anti-TLR9 treatments may be promising in the management of the disease. PMID:22671429

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

    PubMed Central

    2007-01-01

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

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

    PubMed Central

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

    2014-01-01

    Objective Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. Design Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. Setting Antenatal clinics. Population Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). Methods Maternal serum levels of sRAGE (total circulating pool), Nε-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. Main outcome measures Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE–). Results In DM PE+ versus DM PE–, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE : hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE : AGE and sRAGE : CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. Conclusions In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM. PMID:22900949

  15. 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 disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care. Please see later in the article for the Editors' Summary PMID:24465185

  16. 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 22 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

  17. 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 intake and iron and folic acid supplementation in pregnancy was associated with a reduced occurrence of symptoms suggestive of PE or E in Indian women. PMID:25785774

  18. 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.

    TOXLINE Toxicology Bibliographic Information

    Rahat B; Hamid A; Ahmad Najar R; Bagga R; Kaur J

    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 PE.

  19. Pre-eclampsia - The "uterine reinnervation" view.

    PubMed

    Quinn, M J

    2014-11-01

    Difficult vaginal deliveries, gynaecological surgery, and, persistent straining during defaecation injure uterine nerves. Cytokines released from injured, uterine nerves cause regeneration of new nerves with altered structures and functions. In structural terms, these new nerves proliferate in chaotic and dysfunctional patterns with abnormal, cross-sectional profiles. In functional terms they are particularly sensitive to "stretch" or mechanosensory transduction. Release of neural cytokines also causes hyperplasia of the walls of adjacent, denervated uterine arterioles that may reduce uteroplacental blood flow during pregnancy. In the "uterine reinnervation" view, "stretch" applied to injured uterine nerves triggers uterorenal nerves to cause vasoconstriction in the renal cortex, hypertension and proteinuria i.e. the key features of preeclampsia. There are two intrauterine mechanisms that stretch injured, uterine nerves (a) in the placental bed, (b) in the extraplacental myometrium, respectively. In "early-onset" preeclampsia (<34weeks), continuing increases in maternal plasma volume, increase blood flow through denervated, and, narrowed uterine arterioles in the placental bed, stretching injured perivascular nerves resulting in preeclampsia with a small-for-gestational-age fetus. In "late-onset" preeclampsia (>34weeks), nulliparity, multiple pregnancy, concealed abruption and polyhydramnios increase myometrial tension and results in preeclampsia with an appropriate-for-gestational-age fetus. Widespread activation of autonomic nerves results in multi-system features of these syndromes. Changes in placental site and circulatory compliance may contribute to different phenotypes of the preeclamptic syndromes in subsequent pregnancies. The "uterine reinnervation" view offers an explanation of the common clinical features of the preeclamptic syndromes through a single pathophysiological mechanism, namely, prepregnancy injury to uterine nerves. Importantly, it offers an explanation for resolution of the symptoms and signs of preeclampsia with delivery of the fetus, the "early" and "late-onset" preeclamptic syndromes, and, the established clinical associations of the condition including nulliparity, hydramnios, multiple pregnancy, molar pregnancy, concealed abruption, etc. Establishing the presence of injured nerves expressing mechanoreceptors in the uterus, and, neural cytokines in thickened, uterine arterioles, will assist in developing this view. However, myometrial hyperplasia during the second half of pregnancy separates injured uterine nerves from injured uterine arterioles ensuring that the key pathoanatomical relationship in preeclampsia will be difficult to demonstrate. PMID:25216751

  20. [Conservative management in severe pre-eclampsia].

    PubMed

    Romero Arauz, J F; Lara González, A L; Izquierdo Puente, C

    2000-02-01

    A total of 58 women with severe preeclampsia between 28-33 weeks of gestation were studied during the period from 1 October 1996 to 1 October 1997. Twenty-four women (42%) developed maternal or fetal indications necessitating early delivery within 48 hours, meanwhile the other 34 patients (58%) received expectant management. The average pregnancy prolongation period in the conservative management group was 6.4 days (range 3 to 18). The primary indications for delivery in this group were maternal indications 16 (47%), fetal compromise 13 (39%), 34 weeks of gestation 3 (8%), abruption placentae 1 (3%) and preterm labor 1 (3%). The mean birth weight and Apgar score at 5 minutes were 1520 +/- 310 g and 8, respectively. Expectant management was not associated with fetal death or maternal complications. The only neonatal death was related with sepsis and prematurity. The women in the early delivery group totaled two stillbirths and three neonatal deaths. PMID:10774104

  1. 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…

  2. Role of volume expansion in severe pre-eclampsia.

    PubMed

    Kirshon, B; Moise, K J; Cotton, D B; Longmire, S; Jones, M; Tessem, J; Joyce, T A

    1988-11-01

    Fifteen primigravid patients with severe pregnancy-induced hypertension were studied by catheterization of the right side of the heart. A hemodynamic protocol was implemented that required maintaining colloid osmotic pressure above 17 millimeters of mercury, pulmonary capillary wedge pressure below 15 millimeters of mercury and the mean arterial pressure in a very narrow range throughout labor and delivery and for 48 hours postpartum. The initial colloid osmotic pressures and pulmonary capillary wedge pressures were 18.0 +/- 2.6 and 10.5 +/- 4.0 millimeters of mercury, respectively, and remained essentially unchanged throughout the post partum period. The only benefit derived from volume expansion in these patients appeared to be the absence of acute fetal distress after the initiation of antihypertensive therapy. Six of 15 patients had late fetal stress develop during labor, suggesting that aggressive volume repletion and colloid osmotic pressure correction in pregnancy-induced hypertension does not effect the over-all incidence of fetal distress. We recommend that correction of colloid osmotic pressure be restricted to instances in which extremely low values (less than 12 millimeters of mercury) or a prolonged negative colloid osmotic pressure to pulmonary capillary wedge pressure gradient are identified. Finally, the benefit of volume expansion in pregnancy-induced hypertension appears to be the prevention of sudden and profound drops in blood pressure with antihypertensive therapy--not the prevention of fetal distress during labor. PMID:3140400

  3. 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

  4. 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…

  5. 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

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

    ClinicalTrials.gov

    2013-12-11

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

  7. Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion

    PubMed Central

    Na, Kyu-Hwan; Choi, Jong Ho; Kim, Chun-Hyung; Kim, Kwang-Soo

    2013-01-01

    Objective We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. Methods NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. Results NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. Conclusion NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development. PMID:23614111

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

    PubMed Central

    Seyhan, Tülay Özkan; Bezen, Olgaç; Sungur, Mukadder Orhan; Kalelioğlu, İbrahim; Karadeniz, Meltem; Koltka, Kemalettin

    2014-01-01

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

  9. Pregnant women with schizophrenia are at higher risk of pre-eclampsia, venous thromboembolism and adverse neonatal outcomes.

    PubMed

    Raimondi, Aubrey; Sheiner, Eyal

    2015-04-01

    Implications for practice and research: Higher rates of preterm delivery and small for gestational age (SGA) babies in schizophrenic mothers confirm previous findings in the context of newer antipsychotic drugs and treatment practices. Women with schizophrenia should be counselled about increased risks and followed by a provider specialising in high-risk pregnancies. Strategies to address modifiable risk factors during pregnancy and the perinatal period are necessary. Special attention should be given to smoking cessation and control of blood pressure. Novel findings include increased rates of thromboembolic disease in pregnancy and large for gestational age (LGA) infants in births involving schizophrenic mothers. Further studies should assess whether potential confounding factors such as body mass index (BMI), alcohol, tobacco and drug use, and the type of antipsychotic medications used, affect the novel findings reported. PMID:25179642

  10. 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

  11. 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...

  12. 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...

  13. 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...

  14. 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

  15. 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...

  16. 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 ...

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

    PubMed Central

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

    2013-01-01

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

  18. Acute pregnancy-associated hypertension treated with hypnosis: a case report.

    PubMed

    Smith, C H

    1989-01-01

    A 24-year-old patient was treated using hypnotic intervention for acute pregnancy-associated hypertension. The patient displayed evidence of secondary arrest of labor and acute onset of signs and symptoms of pre-eclampsia. Hypnotic intervention resulted in normal vaginal delivery without complications or further evidence of morbidity secondary to a hypertensive episode. Hypnosis as an adjunct in the treatment of pre-eclampsia should be investigated further. PMID:2919576

  19. Aortic stiffness in normal and hypertensive pregnancy.

    PubMed

    Avni, B; Frenkel, G; Shahar, L; Golik, A; Sherman, D; Dishy, V

    2010-02-01

    The objective of this study was to examine whether aortic stiffness, as assessed by pulse wave analysis, could reliably discriminate between normal and hypertensive pregnancies. One hundred pregnant women were studied: five with severe pre-eclampsia, 27 with gestational hypertension, 14 with chronic hypertension and 54 with normal pregnancy. Central hemodynamic parameters were obtained by an applanation tonometry and included central aortic systolic blood pressure (CSBP), central aortic diastolic blood pressure (CDBP), augmentation pressure (AP), augmentation index (AIx), AIx corrected to a heart rate of 75 (AIx@75) and time to reflection (Tr). All measures of aortic stiffness, including AP, AIx and AIx@75 were significantly higher in women with gestational hypertension and pre-eclampsia compared with normal pregnancies and women with chronic hypertension (p < 0.05 for all comparisons). There were no significant differences between normal pregnancies and women with chronic hypertension (p > 0.05 for all comparisons). Tr was significantly shorter in women with pre-eclampsia and gestational hypertension compared with normal pregnancies (p < 0.05). Aortic stiffness, as assessed by pulse wave analysis, is significantly increased in women with pre-eclampsia and gestational hypertension but not in treated women with chronic hypertension. Pulse wave analysis has a potential as a screening tool in women at high risk for pre-eclampsia. The final role of this method should be determined in prospective studies. PMID:20001391

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

    PubMed

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

    2014-11-01

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

  1. 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

  2. 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 pregnancy and have a potential therapeutic role in pre-eclampsia treatment. PMID:26685104

  3. Pheochromocytoma and pregnancy: a difficult and dangerous ordeal.

    PubMed

    Mohamed Ismail, Nor Azlin; Abd Rahman, Rahana; Abd Wahab, Norasyikin; Muhammad, Rohaizak; Nor Azmi, Kamaruddin

    2012-01-01

    Pheochromocytoma during pregnancy is potentially disastrous to the mother and fetus. Its ambiguous presentation is often mistaken for pre-eclampsia, although it may imitate other problems during pregnancy. Early diagnosis and timely, appropriate management reduces possible maternal and fetal complications. We identified a case of pheochromocytoma during pregnancy; the condition was initially diagnosed as pre-eclampsia complicated with gestational diabetes. Surgical intervention via left adrenalectomy was successfully performed in the second trimester. After surgery, all of the patient's medical problems nearly subsided and she did not require further treatment. However, her fetus displayed restricted intrauterine growth, and the patient eventually had premature delivery via a caesarean section. A multidisciplinary team to identify and treat pheochromocytoma is mandatory to ensure optimal conditions for tumour removal and to anticipate any possible catastrophic events. PMID:22977377

  4. 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

  5. Elevated copper and lowered zinc in the placentae of pre-eclamptics.

    PubMed

    Brophy, M H; Harris, N F; Crawford, I L

    1985-01-15

    Selected cations (Ca, Co, Cu, Mg, Zn, Si, and K) were determined in the placentae of 18 women. Between pre-eclamptic and normal subjects there were significant (p less than 0.05) differences in copper and zinc concentrations and borderline significant differences in cobalt concentration. In the placentae of the ten women with a normal pregnancy, the average concentrations of copper and zinc were 53 and 192 micrograms atoms/kg placenta, respectively. In the placentae of 8 women with pre-eclampsia, the concentrations were 124 and 134 micrograms atoms/kg placenta for copper and zinc, respectively. Elevation of copper and decrease in zinc may be an exaggeration of normal pregnancy physiology that occurs in pre-eclampsia. PMID:3978817

  6. 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

  7. 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

  8. 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

  9. 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

  10. Prenatal Screening Using Maternal Markers

    PubMed Central

    Cuckle, Howard

    2014-01-01

    Maternal markers are widely used to screen for fetal neural tube defects (NTDs), chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening. PMID:26237388

  11. [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

  12. Is birth weight determined genetically?

    PubMed

    Carr-Hill, R; Campbell, D M; Hall, M H; Meredith, A

    1987-09-19

    Birthweight correlations were analysed among 505 intergenerational pairs of first births to women aged 18-25 identified from a large obstetric data bank. After standardisation for fetal sex, maternal height, gestational age, and proteinuric pre-eclampsia residual correlations of between 0.1402 and 0.1725 were found, suggesting only a small genetic effect. It is concluded that genetic factors play only a small part in determining birth weight. PMID:3117303

  13. 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

  14. 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

  15. Differential localization of superoxide dismutase isoforms in placental villous tissue of normotensive, pre-eclamptic, and intrauterine growth-restricted pregnancies.

    PubMed

    Myatt, L; Eis, A L; Brockman, D E; Kossenjans, W; Greer, I A; Lyall, F

    1997-10-01

    Several isoforms of superoxide dismutase (SOD), including copper/zinc (cytosolic) and manganese (mitochondrial), exist. In the human placenta, SOD may prevent excessive superoxide accumulation and any potential deleterious oxidative effects. In pre-eclampsia, increased levels of lipid peroxide and decreased SOD activity have been described in the placenta. Oxidative stress such as occurs in pre-eclampsia can alter expression of SOD isoforms. The objective of this study was to localize the copper/zinc and manganese SOD isoforms in the placenta using immunohistochemistry and to compare localization and intensity of immunostaining in tissues from normotensive pregnancies with those from pregnancies complicated by pre-eclampsia and/or intrauterine growth restriction (IUGR). Western blotting with specific antibodies recognized a 17-kD copper/zinc and a 23-kD manganese SOD subunit in placental homogenates. Intense immunostaining for the manganese SOD isoform was seen in villous vascular endothelium, but only faint staining was found in the syncytiotrophoblast or villous stroma. In serial sections, intense immunostaining for copper/zinc SOD was seen in certain cells of the villous stroma but only faint immunostaining in syncytiotrophoblast and vascular endothelium. No apparent differences in localization or intensity of immunostaining for either isoform were seen between tissues of normotensive or pre-eclamptic pregnancies, with or without IUGR. The different cellular localizations of the SOD isoforms suggest that they fulfill different functional roles within the placenta. PMID:9313805

  16. 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

  17. Oocyte donation is an independent risk factor for pregnancy complications: the implications for women of advanced age.

    PubMed

    Younis, Johnny S; Laufer, Neri

    2015-02-01

    Maternal age at first pregnancy and age-related infertility are steadily increasing, and the demand for assisted reproductive technologies (ART) to treat age-related infertility is also on the rise. The latest registry findings from Europe and the United States show that the meager results of ART in women above 43 years of age have not improved much over the past 10 years. The latest evidence shows that the demand for oocyte donation (OD) is steadily increasing. Contrary to previous belief-attributing increased perinatal complications in OD recipients to advanced maternal age and multifetal pregnancy-accumulating evidence from the past few years suggests that OD itself is a significant and independent risk factor for pregnancy complications, mostly for pre-eclampsia. The increased rate of chronic maternal disease and medical complications in pregnancy observed in advanced maternal age, coupled with the growing demand for OD, with its independent association with pre-eclampsia, create an urgent need to adopt a clear policy taking these risks into account. We present recent evidence showing that OD is an independent risk factor for pre-eclampsia and suggest recommendations for women approaching OD treatment in advanced age. PMID:25646636

  18. Antiphospholipid antibodies internalised by human syncytiotrophoblast cause aberrant cell death and the release of necrotic trophoblast debris.

    PubMed

    Viall, Chez A; Chen, Qi; Liu, Bonnia; Hickey, Anthony; Snowise, Saul; Salmon, Jane E; Stone, Peter R; Chamley, Lawrence W

    2013-12-01

    Antiphospholipid antibodies (aPL) are the strongest maternal risk factor for pre-eclampsia, a hypertensive disease of human pregnancy. Pre-eclampsia is triggered by a toxic factor released from the placenta that activates the maternal endothelium. Antiphospholipid antibodies cause the release of necrotic trophoblast debris from the placental syncytiotrophoblast and this debris can activate endothelial cells. In this study, we investigated how aPL affects syncytiotrophoblast death and production of necrotic trophoblast debris by examining the interaction between aPL and human first trimester placental explants. Human polyclonal and murine monoclonal aPL, but not control antibodies, were rapidly internalised by the syncytiotrophoblast. Inhibitors of endocytosis or the low-density lipoprotein receptor (LDLR) family, but not toll-like receptors, decreased the internalisation of aPL and prevented the release of necrotic trophoblast debris from the syncytiotrophoblast. Once internalised, aPL increased inner mitochondrial membrane leak and Cytochrome c release while depressing oxidative flux through Complex IV of the electron transport system in syncytiotrophoblast mitochondria. These data suggest that the human syncytiotrophoblast internalises aPL by antigen-dependent endocytosis involving LDLR family members. Once internalised by the syncytiotrophoblast, aPL affects the death-regulating mitochondria, causing extrusion of necrotic trophoblast debris which can activate maternal endothelial cells thereby contributing to the pathogenesis of pre-eclampsia. PMID:24035196

  19. Influence of mineral and vitamin supplements on pregnancy outcome.

    PubMed

    Hovdenak, Nils; Haram, Kjell

    2012-10-01

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

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

    PubMed

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

    2009-01-01

    Plasma volume expansion of more than 1.5 l and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.e. pre-eclampsia commonly coincide with hemo concentration and over activation of blood coagulation both of which alter blood rheology. On the basis of 4,985 consecutively recorded singleton pregnancies values range of blood rheological parameters in women with normal and complicated outcome of pregnancy at the time of their delivery were compared. Plasma viscosity (pv) was determined using KSPV 1 Fresenius and RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. Seventy-nine point four percent (n=3,959) had normal pregnancy outcome and 1,026 with adverse outcome of pregnancy had pre-eclampsia (8.4%; n=423), had newborn with a birth-weight < 2,500 g (9.5%; n=473), had early-birth before week 37 (9.3%; n=464), and/or were diagnosed with intra uterine growth retardation (IUGR) (5.0%; n=250). In women with normal pregnancy outcome mean (+/-SD) of pv was 1.31+/-0.09 mPa s, of E0 was 21.6+/-5.3, and of E1 was 38.4+/-7.9 while in women with adverse outcome means for rheological parameters were statistically significantly different i.e. pv: 1.32+/-0.08 mPa s; p=0.006, E0: 22.1+/-5.5; p=0.002 and E1: 39.5+/-8.5; p=0.0006. Subgroup analysis revealed statistical significant lower pv in women who either had pre term delivery or a low birth-weight child (p<0.005) as compared to women who had normal pregnancy outcome while patients with pre-eclampsia had markedly higher low shear and stasis RBC aggregation (p<0.0001). None of the rheological results at term were correlated with either maternal age (r<0.04), BMI (r<0.09), maternal weight gain until delivery (r<0.04), or fetal outcome such as APGAR-score (r<0.09) art. pH in the umbilical cord (-0.05pre-eclampsia hemo concentration and increased fibrinogen turnover due to enhanced coagulation activation are weighty co factors of pv but were associated with lower pv in patients with pre-eclampsia. However, coincidental increased RBC aggregation and hemo concentration may potentially derogate blood flow in the materno-fetal unit that is commonly traceable using vessel duplex ultra sound in pre-eclampsia. PMID:19433886

  1. 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 programme for Research and Technological development of the EU. http://www.fp7-improved.eu/ PMID:24314209

  2. Inflammatory Bowel Disease and Risk of Adverse Pregnancy Outcomes

    PubMed Central

    Boyd, Heather A.; Basit, Saima; Harpsøe, Maria C.; Wohlfahrt, Jan; Jess, Tine

    2015-01-01

    Background and Objectives Existing data on pregnancy complications in inflammatory bowel disease (IBD) are inconsistent. To address these inconsistencies, we investigated potential associations between IBD, IBD-related medication use during pregnancy, and pregnancy loss, pre-eclampsia, preterm delivery, Apgar score, and congenital abnormalities. Methods We conducted a cohort study in >85,000 Danish National Birth Cohort women who were pregnant in the period 1996-2002 and had information on IBD, IBD-related medication use (systemic or local corticosteroids, 5-aminosalicylates), pregnancy outcomes and potential confounders. We evaluated associations between IBD and adverse pregnancy/birth outcomes using Cox regression and log-linear binomial regression. Results IBD was strongly and significantly associated with severe pre-eclampsia, preterm premature rupture of membranes and medically indicated preterm delivery in women using systemic corticosteroids during pregnancy (hazard ratios [HRs] >7). IBD was also associated with premature preterm rupture of membranes in women using local corticosteroid medications (HR 3.30, 95% confidence interval [CI] 1.33-8.20) and with medically indicated preterm delivery (HR 1.91, 95% CI 0.99-3.68) in non-medicated women. Furthermore, IBD was associated with low 5-minute Apgar score in term infants (risk ratio [RR] 2.19, 95% CI 1.03-4.66). Finally, Crohn’s disease (but not ulcerative colitis) was associated with major congenital abnormalities in the offspring (RR 1.85, 95% CI 1.06-3.21). No child with a congenital abnormality born to a woman with IBD was exposed to systemic corticosteroids in utero. Conclusion Women with IBD are at increased risk of severe pre-eclampsia, medically indicated preterm delivery, preterm premature rupture of membranes, and delivering infants with low Apgar score and major congenital malformations. These associations are only partly explained by severe disease as reflected by systemic corticosteroid use. PMID:26083614

  3. Effect of lycopene in prevention of preeclampsia in high risk pregnant women

    PubMed Central

    Antartani, Ramalingappa; Ashok, Kiran

    2011-01-01

    Objective To evaluate the effect of pre-natal supplementation of antioxidant Lycopene in prevention of pre-eclampsia in the high risk pregnant women. We also assessed the effect of lycopene supplementation on intra-uterine growth restriction and the perinatal outcome in women at high risk of developing pre-eclampsia. Materials and Methods A total of 54 women between 14–28 weeks of pregnancy who were at high risk of developing pre-eclampsia were considered for the study. Inclusion criteria were women with a previous history of preeclampsia, a growth-retarded fetus, perinatal death, multifetal gestation and chronic hypertension. Of the total of 54 women, 30 women were randomized to receive Lycopene in a dose of 2 mg twice daily starting from the date of entry and were instructed to continue the drug regularly until delivery. The other 24 women were randomized to the control group and they did not take lycopene. The controls were matched to cases with respect to the risk factors for the development of preeclampsia. Both groups were followed at monthly intervals. In addition, a Doppler assessment for evidence of intrauterine growth retardation was done at around 28 wks of gestation. Data regarding development of preeclampsia, period of gestation during delivery, mode of delivery, fetal weight and perinatal outcome were recorded and subjected to statistical analysis. Results Of the 30 women randomized to receive the drug, ten women were lost to follow-up. Thus only 20 women in the treatment group completed the study. All the 24 women in the control group completed the study. Lycopene was not found to decrease the incidence of pre-eclampsia in high risk women. Women in the lycopene supplementation group had significantly lesser incidence of growth restricted babies and had a significantly better perinatal outcome compared to women in the placebo group. Conclusion Lycopene supplementation does not decrease the incidence of preeclampsia in high risk women. However lycopene supplementation does seem to help in reducing the incidence of intra-uterine growth restriction. PMID:24591955

  4. Partial HELLP syndrome with unilateral exudative retinal detachment treated conservatively

    PubMed Central

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

    2014-01-01

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

  5. 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

  6. Postpartum hemolytic uremic syndrome in a 17-year-old Filipina primigravid.

    PubMed

    Anacleto, Francisco E; Cifra, Christina L; Elises, Joel S

    2003-12-01

    A 17-year-old Filipina primigravid developed acute renal failure secondary to hemolytic uremic syndrome (HUS) after undergoing emergency cesarean section for severe pre-eclampsia and abruptio placenta. She underwent hemodialysis with concurrent infusions of fresh-frozen plasma and packed red cells for 5 weeks. Renal biopsy revealed findings consistent with HUS with glomerular crescents. She received three doses of pulse methylprednisolone followed by oral prednisone. Renal function improved 5 weeks after the onset of HUS. The pathogenesis, differential diagnosis, and treatment options of postpartum HUS are discussed. PMID:14564496

  7. 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

  8. Successful angioplasty during pregnancy for renal artery stenosis.

    PubMed

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

    2016-03-01

    Renal artery stenosis can be diagnosed during pregnancy and treated at the same time. A 30-year-old woman had a sudden, severe but asymptomatic hypertensive crisis at 21 weeks of gestation. The diagnosis of renal artery stenosis suspected on Doppler ultrasonography was confirmed and treated by renal angioplasty, which reduced her blood pressure. At 27 weeks of gestation, her blood pressure increased again, associated with significant proteinuria, suggesting pre-eclampsia. A cesarean section was performed giving birth to a healthy 940-g child. Renal artery stenosis should be considered when sudden and early-onset hypertension appears during pregnancy. PMID:26818942

  9. 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

  10. Pregnancy outcome after illegal induced abortion in Nigeria: a retrospective controlled historical study.

    PubMed

    Okonofua, F E; Onwudiegwu, U; Odutayo, R

    1994-06-01

    The effect of illegal abortion on subsequent reproduction was studied in 46 Nigerian women who gave a history of illegal termination of pregnancy. There was a statistically significant increase in the incidences of premature rupture of membranes, premature labour and low birth weight when compared to 53 primigravida who gave no such history of abortion. The perinatal mortality was also significantly higher in the abortion group. In contrast, pre-eclampsia was less common in the abortion group. These findings indicate that illegal abortion has adverse effects on pregnancy outcome in Nigerian women. PMID:7625306

  11. 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

  12. Successful management of discordant alobar holoprosencephaly in monochorionic diamniotic twins with normal karyotype: a case report.

    PubMed

    Zhang, J; Yang, T; Wang, X; Yu, H

    2015-01-01

    Holoprosencephaly (HPE), a complex brain malformation resulting from incomplete cleavage of the prosencephalon into distinct cerebral hemispheres, is rare in newborns. Two preterm male neonates were born at 34 weeks' and five days' gestation in the monochorionic diamniotic twin pregnancy complicated with pre-eclampsia and intrahepatic cholestasis of pregnancy, and one of them was prenatally diagnosed with alobar HPE by ultrasonography with frontal bossing, hydrocephaly, hypotelorism of eyes, flat nasal bridge, macroglossia, and cheilo/palatoschisis at birth. Karyotyping by G-banding of amniocentesis specimens in normal twin and fetal umbilical blood in both fetuses showed 46, XY. This report expands discordant alobar holoprosencephaly in monochorionic diamniotic twins. PMID:25864296

  13. 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

  14. Complete hydatidiform mole coexisting with a live fetus.

    PubMed

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

    2014-01-01

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

  15. 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

  16. 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

  17. [Risk of maternal and fetal disease among women older than 40 years].

    PubMed

    Vanya, Melinda; Szili, Károly; Devosa, Iván; Bártfai, György

    2015-12-01

    A rising trend in advanced maternal age has been observed over the last few decades. Several studies have assessed the association between advanced maternal age and adverse pregnancy outcome, including miscarriage, stillbirth, pre-eclampsia, gestational hypertension, gestational diabetes mellitus, preterm birth, delivery of a small- or large-for-gestational-age neonates and elective or emergency Cesarean section. These studies reported contradictory findings. The aim of the present paper is to summarize the evidence-based information regarding advanced maternal age and pregnancy outcomes. PMID:26614540

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

    PubMed

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

    2016-05-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome. PMID:26921648

  19. Glucose-6-phosphate dehydrogenase is present in normal and pre-eclamptic placental trophoblasts: ultrastructural enzyme-histochemical evidence.

    PubMed

    Matsubara, S; Takizawa, T; Suzuki, T; Minakami, H; Sato, I

    2001-01-01

    The present study investigated the localization of glucose-6-phosphate dehydrogenase (G6PD) activity in the human placenta at various gestational ages. Placentae from patients with severe pre-eclampsia were also studied. Ultrastructural enzyme-histochemical analysis was performed by newly developed G6PD histochemistry using copper ferrocyanide as a capturing agent. Precipitates indicative of G6PD activity were markedly visible in the cytotrophoblastic cytoplasm and faintly in the syncytiotrophoblastic cytoplasm of placentae at various gestational ages, as well as those from pre-eclampsia. Frequently, precipitations were localized on the cytosolic side of the endoplasmic reticular membranes of the cytotrophoblasts. Stringent cytochemical control experiments performed also ensured the specific detection of G6PD activity. The results indicated that cytochemically detectable G6PD was localized in cytotrophoblastic cytoplasm. This enzyme may play significant roles in the carbohydrate metabolism of the human placenta, and further maintenance of villous tree architecture. Combining the previous data, the human placenta has many carbohydrate metabolizing-enzymes, similar to the adult liver. PMID:11162357

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

    PubMed

    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

  1. 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

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

    PubMed

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

    2015-03-01

    As the age of pregnant women and prevalence of obesity and diabetes are increasing, so is the prevalence of medical disorders during pregnancy, particularly hypertension and the associated CKD. Pregnancy can worsen kidney function in women with severe disease, and hypertension puts them at risk for pre-eclampsia and the associated complications. There are no specific guidelines for hypertension management in this population, and tight control will not prevent pre-eclampsia. Women with end-stage kidney disease should be placed on intense dialysis regimens to improve obstetric outcomes, and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are best avoided. This article will review the rationale for a management plan that includes a multidisciplinary team to discuss risks and develop a plan before conception, antepartum monitoring for maternal and fetal morbidity, individualization of medical management using medications with established records during pregnancy, and balancing the level of blood pressure control proved to protect kidney function against the potential effects that aggressive blood pressure control could have on the fetal-placental unit. PMID:25704354

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

    PubMed

    Pourrat, O; Coudroy, R; Pierre, F

    2015-06-01

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

  4. Treatment of poor placentation and the prevention of associated adverse outcomes--what does the future hold?

    PubMed

    Spencer, R N; Carr, D J; David, A L

    2014-07-01

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

  5. 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

  6. 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

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

    PubMed

    Lie, Rolv T

    2007-07-01

    Population-based data that cover reproductive health outcomes across two complete generations have recently become available in the Nordic countries. Such data enable estimation of recurrence risks from one generation to the next of different conditions such as birth defects or pre-eclampsia. Risks related to a singleton pregnancy involve the contribution of three individuals: the mother, the father and the fetus. A paternal contribution is mainly through the father's contribution of half of the alleles of the fetus. A maternal contribution may occur in three fundamentally different ways. First, the mother provides half of the genomic alleles to the fetus, with contribution of paternal alleles completing the whole genome. Second, the mother provides the fetal environment and possible susceptibility to complications during pregnancy which she may have inherited from her mother. Finally, she provides the fetal mitochondria. Because of these different contributions, recurrence from mother to offspring is fundamentally different from recurrence from father to offspring. How recurrence risks reflect and shape the underlying contributions to overall perinatal risk is illustrated through a review of published data from Norway on gestational age, pre-eclampsia and birth defects. PMID:17593192

  8. 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

  9. 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 [RR 0.70; 95 % CI 0.56-0.88] and risk of pre-term birth [RR 0.88, 95 % CI 0.78-0.99]. Recommendations for LiST for reduction in maternal mortality were based on risk reduction in gestational hypertensive related severe morbidity/mortality [RR 0.80; 95% CI 0.70-0.91] and that for neonatal mortality were based on risk reduction in all-cause neonatal mortality [RR 0.70; 95% CI 0.56-0.88]. Conclusion Calcium supplementation during pregnancy is associated with a reduction in risk of gestational hypertension, pre-eclampsia neonatal mortality and pre-term birth in developing countries. PMID:21501435

  10. 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 factors for hypertension were relatively more likely to be selected for early delivery. PMID:26438140

  11. 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 NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes. Trial registration Italian trial: ClinicalTrials.gov Identifier: NCT01244347. Dutch trial: Dutch Trial Register ID: NTR3161. PMID:24884885

  12. Previous miscarriage and the subsequent risk of preterm birth in Scotland, 1980–2008: a historical cohort study

    PubMed Central

    Oliver-Williams, C; Fleming, M; Wood, AM; Smith, GCS

    2015-01-01

    Objective To determine whether the relationship between previous miscarriage and risk of preterm birth changed over the period 1980–2008, and to determine whether the pattern varied according to the cause of the preterm birth. Design Linked birth databases. Setting All Scottish NHS hospitals. Population A total of 732 719 nulliparous women with a first live birth between 1980 and 2008. Methods Risk was estimated using logistic regression. Main outcome measures Preterm birth, subdivided by cause (spontaneous, induced with a diagnosis of pre-eclampsia, or induced without a diagnosis of pre-eclampsia) and severity [extreme (24–28 weeks of gestation), moderate (29–32 weeks of gestation), and mild (33–36 weeks of gestation)]. Results Consistent with previous studies, previous miscarriage was associated with an increased risk of all-cause preterm birth (adjusted odds ratio, aOR 1.26; 95% confidence interval, 95% CI 1.22–1.29). This arose from associations with all subtypes. The strongest association was found with extreme preterm birth (aOR 1.73; 95% CI 1.57–1.90). Risk increased with the number of miscarriages. Women with three or more miscarriages had the greatest risk of all-cause preterm birth (aOR 2.14; 95% CI 1.93–2.38), and the strongest association was with extreme preterm birth (aOR 3.87; 95% CI 2.85–5.26). The strength of the association between miscarriage and preterm birth decreased from 1980 to 2008. This was because of weakening associations with spontaneous preterm birth and induced preterm birth without a diagnosis of pre-eclampsia. Conclusions The association between a prior history of miscarriage and the risk of preterm birth declined in Scotland over the period 1980–2008. We speculate that changes in the methods of managing incomplete termination of pregnancy might explain the trend, through reduced cervical damage. PMID:25626593

  13. Iontophoresis of vasoactive drugs. Effect on peripheral blood flow during pregnancy.

    PubMed

    Eneroth-Grimfors, E; Lindblad, L E; Westgren, M; Etzell, B M; Bevegård, S

    1991-01-01

    The aim of this study was to evaluate whether iontophoretic administration of the vasoactive agents noradrenaline (NA) and angiotensin (AII) combined with measurement of skin blood flow with a laser Doppler technique could serve as a predictive method for pre-eclampsia. Nine healthy non-pregnant women, 9 healthy pregnant women and 9 pre-eclamptic patients were investigated. A significant reduction of skin blood flow was induced by NA in all three groups and by AII in the non-pregnant group. There was no significant difference between healthy pregnant and pre-eclamptic patients in the degree of reduction of blood flow with respect to NA and AII administration. PMID:1858491

  14. Endogenous digitalis

    PubMed Central

    Bagrov, Alexei Y; Shapiro, Joseph I

    2008-01-01

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

  15. Posterior reversible encephalopathy syndrome following an inadvertent dural puncture during an emergency laparotomy for ischemic colitis – a case report

    PubMed Central

    Shah, Reena; Kubisz-Pudelko, Agnieszka; Reid, Jeremy

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome characterized by various symptoms of neurological disease. It has commonly been reported in association with acute hypertension, pre-eclampsia, eclampsia, sepsis, and exposure to immunosuppressants. Here, we report on a normotensive woman who developed a severe frontal headache, visual disturbances, and hypertension 3 days after undergoing an emergency laparotomy for ischemic colitis during which she suffered an inadvertent dural puncture. Neuro-imaging revealed features consistent with PRES. The patient went on to make a good recovery, being discharged 21 days postoperatively, with only minor visual disturbances and memory problems. This case highlights the importance of awareness of PRES to all specialties. On reviewing the literature, we feel that PRES may be a potential differential diagnosis to post-procedural neurological symptoms in those patients undergoing routine procedures such as spinal anesthetics or lumbar punctures. PMID:24600245

  16. Posterior reversible encephalopathy syndrome following an inadvertent dural puncture during an emergency laparotomy for ischemic colitis - a case report.

    PubMed

    Shah, Reena; Kubisz-Pudelko, Agnieszka; Reid, Jeremy

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome characterized by various symptoms of neurological disease. It has commonly been reported in association with acute hypertension, pre-eclampsia, eclampsia, sepsis, and exposure to immunosuppressants. Here, we report on a normotensive woman who developed a severe frontal headache, visual disturbances, and hypertension 3 days after undergoing an emergency laparotomy for ischemic colitis during which she suffered an inadvertent dural puncture. Neuro-imaging revealed features consistent with PRES. The patient went on to make a good recovery, being discharged 21 days postoperatively, with only minor visual disturbances and memory problems. This case highlights the importance of awareness of PRES to all specialties. On reviewing the literature, we feel that PRES may be a potential differential diagnosis to post-procedural neurological symptoms in those patients undergoing routine procedures such as spinal anesthetics or lumbar punctures. PMID:24600245

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

    PubMed Central

    Samra, Khawla Abu

    2013-01-01

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

  18. Determinants of birthweight of twins.

    PubMed

    MacGillivray, I

    1983-01-01

    The low birthweight of twins compared with singletons is only slightly influenced by the higher congenital abnormality rate in twins, or the increased incidence of proteinuric pre-eclampsia in the mothers. Reduced intakes of energy food or of zinc, copper, and iron do not account for the lower birthweight. The main cause of low birthweight is preterm delivery, and this is more common in monozygotic than dizygotic twin pregnancies, due particularly to premature rupture of the membranes. The type of placentation did not influence the preterm onset of labor. Preterm labor in monozygotic twin pregnancies is associated with a very high boy:girl ratio, but this did not apply in dizygotic twin pregnancies. PMID:6650100

  19. 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

  20. 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

  1. 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

  2. Recruiting American Indian women for a genetic epidemiology study.

    PubMed

    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

  3. 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

  4. [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

  5. 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

  6. Villitis of unknown aetiology: Clinical implications in preterm population.

    PubMed

    Iskender, C; Zergeroglu, S; Kaymak, O; Çelen, S; Danisman, N

    2016-02-01

    Villitis of unknown aetiology (VUE) is a chronic inflammatory process of chorionic villi which is reported to occur in up to 15% of term placentas. The present study aimed to investigate the association between VUE and perinatal complications in a population who delivered before term. Patients with VUE had a significantly higher rate of intrauterine growth restriction than the control group (47.1% vs. 20.6%, p < 0.01). In addition patients with VUE had a higher rate of deliveries due to absent diastolic flow on umbilical artery doppler than the control group (17.6% vs. 4.4%, p: 0.03). The rate of spontaneous preterm birth or pre-eclampsia was similar in patients with VUE and control groups. The present study provides some evidence that VUE is associated with abnormal perinatal outcomes in pregnant women who give birth before term. PMID:26431437

  7. Obstetric performance following an induced abortion.

    PubMed

    Lowit, Alison; Bhattacharya, Sohinee; Bhattacharya, Siladitya

    2010-10-01

    Abortion has been legalised in most of the Western world for the past four decades. In areas where abortion practices are legal and easy to access, the risk of short-term complications is very low. As most women requesting induced abortion (IA) are young, potential adverse effects on subsequent reproductive function are important to them. This review investigates obstetric performance following IA and highlights methodological problems associated with research in this area. Some data suggest that IA may be linked with an increased risk of low birth weight, miscarriage and placenta previa but could be protective for pre-eclampsia. Current evidence also suggests an association between IA and pre-term birth. Large prospective cohort studies, which permit meaningful subgroup analyses, are needed to provide definitive answers on outcomes following alternative methods of IA and the impact of gestational age at abortion on future obstetric outcomes. PMID:20362515

  8. 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

  9. Coagulation and Placenta-Mediated Complications

    PubMed Central

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

    2014-01-01

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

  10. 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

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

    PubMed Central

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

    2013-01-01

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

  12. 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

  13. 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

  14. 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

  15. A second delivery after heart transplantation - a case study.

    PubMed

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

    2014-09-01

    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

  16. 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

  17. 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

  18. Extracellular vesicles and reproduction–promotion of successful pregnancy

    PubMed Central

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

    2014-01-01

    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

  19. 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

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

    PubMed Central

    Lalitha, Rejani; Opio, Christopher Kenneth

    2013-01-01

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

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

    PubMed

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

    2015-11-01

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

  2. A short history of sonography in obstetrics and gynaecology.

    PubMed

    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

  3. 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

  4. 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

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

    PubMed

    Nash, P; Eriksson, U J

    2007-01-01

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

  6. 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

  7. 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 with pre-eclampsia. PMID:27088357

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

    PubMed

    Hyvönen-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). PMID:6323054

  9. Intensive care unit admission of obstetric cases: a single centre experience with contemporary update.

    PubMed

    Ng, Vivian K S; Lo, T K; Tsang, H H; Lau, W L; Leung, W C

    2014-02-01

    OBJECTIVES. To review the characteristics of a series of obstetric patients admitted to the intensive care unit in a regional hospital in 2006-2010, to compare them with those of a similar series reported from the same hospital in 1989-1995 and a series reported from another regional hospital in 1998-2007. DESIGN. Retrospective case series. SETTING. A regional hospital in Hong Kong. PATIENTS. Obstetric patients admitted to the Intensive Care Unit of Kwong Wah Hospital from 1 January 2006 to 31 December 2010. RESULTS. From 2006 to 2010, there were 67 such patients admitted to the intensive care unit (0.23% of total maternities and 2.34% of total intensive care unit admission), which was a higher incidence than reported in two other local studies. As in the latter studies, the majority were admitted postpartum (n=65, 97%), with postpartum haemorrhage (n=39, 58%) being the commonest cause followed by pre-eclampsia/eclampsia (n=17, 25%). In the current study, significantly more patients had had elective caesarean sections for placenta praevia but fewer had had a hysterectomy. The duration of intensive care unit stay was shorter (mean, 1.8 days) with fewer invasive procedures performed than in the two previous studies, but maternal and neonatal mortality was similar (3% and 6%, respectively). CONCLUSION. Postpartum haemorrhage and pregnancy-induced hypertension were still the most common reasons for intensive care unit admission. There was an increasing trend of intensive care unit admissions following elective caesarean section for placenta praevia and for early aggressive intervention of pre-eclampsia. Maternal mortality remained low but had not decreased. The intensive care unit admission rate by itself might not be a helpful indicator of obstetric performance. PMID:23784532

  10. The use of oral hypoglycaemic agents in pregnancy.

    PubMed

    Holt, R I G; Lambert, K D

    2014-03-01

    While insulin has been the treatment of choice when lifestyle measures do not maintain glycaemic control during pregnancy, recent studies have suggested that certain oral hypoglycaemic agents may be safe and acceptable alternatives. With the exception of metformin and glibenclamide (glyburide), there are insufficient data to recommend treatment with any other oral hypoglycaemic agent during pregnancy. There are no serious safety concerns with metformin, despite it crossing the placenta. When used in the first trimester, there is no increase in congenital abnormalities and there appears to be a reduction in miscarriage, pre-eclampsia and subsequent gestational diabetes. Studies of the use of metformin in gestational diabetes show at least equivalent neonatal outcomes, while reporting reductions in neonatal hypoglycaemia, maternal hypoglycaemia and weight gain and improved treatment satisfaction. Glibenclamide effectively lowers blood glucose in women with gestational diabetes, possibly 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 a paucity of long-term follow-up data on children exposed to oral agents in utero. The American College of Obstetrics and Gynecology and the UK National Institute of Health and Care Excellence (NICE) have recommended that either metformin or glibenclamide can be used to treat gestational diabetes. Metformin is also recommended for use in the pre-conception period by NICE. By contrast, the American Diabetes Association recommends that both drugs should only be used during pregnancy in the context of clinical trials. PMID:24528229

  11. 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

  12. Placental weight and efficiency in relation to maternal body mass index and the risk of pregnancy complications in women delivering singleton babies.

    PubMed

    Wallace, J M; Horgan, G W; Bhattacharya, S

    2012-08-01

    Herein we report placental weight and efficiency in relation to maternal BMI and the risk of pregnancy complications in 55,105 pregnancies. Adjusted placental weight increased with increasing BMI through underweight, normal, overweight, obese and morbidly obese categories and accordingly underweight women were more likely to experience placental growth restriction [OR 1.69 (95% CI 1.46-1.95)], while placental hypertrophy was more common in overweight, obese and morbidly obese groups [OR 1.59 (95% CI 1.50-1.69), OR 1.97 (95% CI 1.81-2.15) and OR 2.34 (95% CI 2.08-2.63), respectively]. In contrast the ratio of fetal to placental weight (a proxy for placental efficiency) was lower (P < 0.001) in overweight, obese and morbidly obese than in both normal and underweight women which were equivalent. Relative to the middle tertile reference group (mean 622 g), placental weight in the lower tertile (mean 484 g) was associated with a higher risk of pre-eclampsia, induced labour, spontaneous preterm delivery, stillbirth and low birth weight (P < 0.001). Conversely placental weight in the upper tertile (mean 788 g) was associated with a higher risk of caesarean section, post-term delivery and high birth weight (P < 0.001). With respect to assumed placental efficiency a ratio in the lower tertile was associated with an increased risk of pre-eclampsia, induced labour, caesarean section and spontaneous preterm delivery (P < 0.001) and a ratio in both the lower and higher tertiles was associated with an increased risk of low birth weight (P < 0.001). Placental efficiency was not related to the risk of stillbirth or high birth weight. No interactions between maternal BMI and placental weight tertile were detected suggesting that both abnormal BMI and placental growth are independent risk factors for a range of pregnancy complications. PMID:22695104

  13. 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

  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. 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).

  16. 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.

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

    PubMed Central

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

    2009-01-01

    Objectives Previously published data from the Cleveland Childrens Sleep and Health Study (CCSHS) demonstrated that preterm infants are especially vulnerable both to sleep disordered breathing (SDB) and its neurocognitive sequelae at age 811 years. In this analysis, we aimed to identify the components of the neonatal medical history associated with childhood SDB among children born prematurely. Study design This analysis focuses on the 383 children in the population-based CCSHS cohort who were born <37 weeks gestational age and who had technically acceptable sleep studies performed at ages 811 years (92% of all preterm children). Logistic regression was used to evaluate the associations between candidate perinatal and neonatal risk factors and the presence of childhood SDB by sleep study. Results Twenty-eight preterm children (7.3%) met the definition for SDB at age 811 years. Having a single mother and mild maternal pre-eclampsia were strongly associated with SDB in unadjusted and race-adjusted models. Unadjusted analyses also identified xanthine use and CPR and/or intubation in the delivery room as potential risk-factors for SDB. We did not find a significant link between traditional markers of severity of neonatal illness -- such as gestational age, birth weight, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), or duration of ventilation -- and childhood SDB at school age. Conclusions These results represent a first step in identifying prenatal and neonatal characteristics which place preterm infants at higher risk for childhood SDB. The strong association between mild pre-eclampsia and childhood SDB underscores the importance of research aimed at understanding in utero risk factors for neurorespiratory development. PMID:18534222

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

    PubMed Central

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

    2012-01-01

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

  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 widely discussed. Furthermore, the current literature is systematically reviewed by Scopus analysis. PMID:25194281

  20. [Spontaneous liver haemorrhage during pregnancy: a rare and life-threatening situation].

    PubMed

    Boormans, E M A; Bekedam, D J; Lenters, E; Schoonderbeek, F J; Tilanus, H W

    2007-05-26

    Three pregnant women, of whom 2 were 33 and 1 was 35 years of age, were seen; 2 of them had upper abdominal pain and 1had oedema. All had proteinuria and liver enzyme abnormalities, and pre-eclampsia or the HELLP syndrome was suspected. They were consequently admitted and at first treated with antihypertensive agents. One patient underwent a Caesarean section and the baby had a good start. Afterwards, however, the patient developed shock. A CT-scan revealed a hepatic rupture, for which repeated surgical packing of the liver was carried out. The postoperative course was complicated. A second patient developed shock and the foetus died. Here the CT-scan revealed a liver haematoma. At surgery the next day, removal of the foetus was followed by heavy uterine bleeding. The patient again developed shock and the uterus was resected. A haematoma that was seen in the liver was treated expectatively. The postoperative course was not complicated. In a third patient, abdominal echography revealed bleeding from the liver. Simultaneous Caesarean section and surgical exploration of the liver took place, with packing of the liver. The child had Apgar scores of 4, 7 and 9. After re-laparotomy because of persistent bleeding from the liver the patient recovered. Spontaneous liver haemorrhage and hepatic rupture during pregnancy is a rare condition associated with significant maternal and perinatal mortality. The majority of cases occur during pregnancies complicated by pre-eclampsia or the HELLP syndrome. The presenting symptoms are non-specific. A high index of suspicion is important and early evaluation with imaging is necessary to improve the prognosis of both mother and child. PMID:17557753

  1. 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

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

    PubMed Central

    2014-01-01

    Objective To provide an accurate assessment of complications of pregnancy in women with chronic hypertension, including comparison with population pregnancy data (US) to inform pre-pregnancy and antenatal management strategies. Design Systematic review and meta-analysis. Data sources Embase, Medline, and Web of Science were searched without language restrictions, from first publication until June 2013; the bibliographies of relevant articles and reviews were hand searched for additional reports. Study selection Studies involving pregnant women with chronic hypertension, including retrospective and prospective cohorts, population studies, and appropriate arms of randomised controlled trials, were included. Data extraction Pooled incidence for each pregnancy outcome was reported and, for US studies, compared with US general population incidence from the National Vital Statistics Report (2006). Results 55 eligible studies were identified, encompassing 795 221 pregnancies. Women with chronic hypertension had high pooled incidences of superimposed pre-eclampsia (25.9%, 95% confidence interval 21.0% to 31.5 %), caesarean section (41.4%, 35.5% to 47.7%), preterm delivery <37 weeks’ gestation (28.1% (22.6 to 34.4%), birth weight <2500 g (16.9%, 13.1% to 21.5%), neonatal unit admission (20.5%, 15.7% to 26.4%), and perinatal death (4.0%, 2.9% to 5.4%). However, considerable heterogeneity existed in the reported incidence of all outcomes (τ2=0.286-0.766), with a substantial range of incidences in individual studies around these averages; additional meta-regression did not identify any influential demographic factors. The incidences (the meta-analysis average from US studies) of adverse outcomes in women with chronic hypertension were compared with women from the US national population dataset and showed higher risks in those with chronic hypertension: relative risks were 7.7 (95% confidence interval 5.7 to 10.1) for superimposed pre-eclampsia compared with pre-eclampsia, 1.3 (1.1 to 1.5) for caesarean section, 2.7 (1.9 to 3.6) for preterm delivery <37 weeks’ gestation, 2.7 (1.9 to 3.8) for birth weight <2500 g, 3.2 (2.2 to 4.4) for neonatal unit admission, and 4.2 (2.7 to 6.5) for perinatal death. Conclusions This systematic review, reporting meta-analysed data from studies of pregnant women with chronic hypertension, shows that adverse outcomes of pregnancy are common and emphasises a need for heightened antenatal surveillance. A consistent strategy to study women with chronic hypertension is needed, as previous study designs have been diverse. These findings should inform counselling and contribute to optimisation of maternal health, drug treatment, and pre-pregnancy management in women affected by chronic hypertension. PMID:24735917

  3. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence

    PubMed Central

    Rogozińska, E; Jolly, K; Glinkowski, S; Roseboom, T; Tomlinson, J W; Kunz, R; Mol, B W; Coomarasamy, A; Khan, K S

    2012-01-01

    Objective To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. Design Systematic review and meta-analysis. Data sources Major databases from inception to January 2012 without language restrictions. Study selection Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. Data synthesis Results summarised as relative risks for dichotomous data and mean differences for continuous data. Results We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference −50 g, −100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference −60 g, −120 to −10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. Conclusions Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes. PMID:22596383

  4. 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 may not be as serious as perceived to be. PMID:27099539

  5. 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

  6. Biological functions of thyroid hormone in placenta.

    PubMed

    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

  7. 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

  8. 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

  9. 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

  10. The effects of transplacental cell (antigen) traffic.

    TOXLINE Toxicology Bibliographic Information

    Anderson JM

    1982-11-01

    The feto-placental unit is a successful natural graft without the direct vascularization from the host seen in contrived surgical grafts. Our concept of the mechanisms whereby immunological rejection between mother and fetus is avoided, has changed from emphasizing single features such as the suppression of immunological properties or the vascular separation of the two participants. It is now clear that the interposed tissues of the placenta are vital filters with species differences and temporal morphological changes of probable relevance within each species, and that a number of adaptations of what is regarded as normal immunity occur in the mother and in the developing fetus. Much remains to be learned about transplacental traffic and about the adaptations of immunity found in normal pregnancy as well as those peculiar to abnormalities such as haemolytic disease, spontaneous abortion and pre-eclampsia. The development of a reproducible in-vitro system which reliably reflects the status of the graft rejection response is likely to lead to enlightening findings.

  11. The effects of transplacental cell (antigen) traffic.

    PubMed

    Anderson, J M

    1982-11-01

    The feto-placental unit is a successful natural graft without the direct vascularization from the host seen in contrived surgical grafts. Our concept of the mechanisms whereby immunological rejection between mother and fetus is avoided, has changed from emphasizing single features such as the suppression of immunological properties or the vascular separation of the two participants. It is now clear that the interposed tissues of the placenta are vital filters with species differences and temporal morphological changes of probable relevance within each species, and that a number of adaptations of what is regarded as normal immunity occur in the mother and in the developing fetus. Much remains to be learned about transplacental traffic and about the adaptations of immunity found in normal pregnancy as well as those peculiar to abnormalities such as haemolytic disease, spontaneous abortion and pre-eclampsia. The development of a reproducible in-vitro system which reliably reflects the status of the graft rejection response is likely to lead to enlightening findings. PMID:6762429

  12. New frontiers in heart hypertrophy during pregnancy

    PubMed Central

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

    2012-01-01

    During Pregnancy, heart develops physiological left ventricular hypertrophy as a result of the natural volume overload. Previously we have characterized the molecular and functional signature of heart hypertrophy during pregnancy. Cardiac hypertrophy during pregnancy is a complex process that involves many changes including in the signalling pathways, composition of extracellular matrix as well as the levels of sex hormones. This review summarises the recent advances and the new frontiers in the context of heart hypertrophy during pregnancy. In particular we focus on structural and extracellular matrix remodelling as well as signalling pathways in pregnancy-induced physiological heart hypertrophy. Emerging evidence shows that various microRNAs modulate key components of hypertrophy, therefore the role of microRNAs in the regulation of gene expression in pregnancy induced hypertrophy is also discussed. We also review the role of ubiquitin proteasome system, the major machinery for the degradation of damaged and misfolded proteins, in heart hypertrophy. The role of sex hormones in particular estrogen in cardiac remodeling during pregnancy is also discussed. We also review pregnancy-induced cardiovascular complications such as peripartum cardiomyopathy and pre-eclampsia and how the knowledge from the animal studies may help us to develop new therapeutic strategies for better treatment of cardiovascular diseases during pregnancy. Special emphasis has to be given to the guidelines on disease management in pregnancy. PMID:22937489

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

    PubMed

    Weinert, Letcia Schwerz; Silveiro, Sandra Pinho

    2015-01-01

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

  14. The distribution of angiopoietin-1, angiopoietin-2 and their receptors tie-1 and tie-2 in the very early human placenta.

    PubMed

    Seval, Y; Sati, L; Celik-Ozenci, C; Taskin, O; Demir, R

    2008-09-01

    Angiopoietins are integral to vasculogenesis and angiogenesis, which play crucial roles in the growth and development of the placenta. The current study assessed expression of angiopoietins (Ang-1 and Ang-2) and their receptors (Tie-1 and Tie-2) during development of the early human placenta. First-trimester placental tissues were obtained from women undergoing curettage during normal pregnancies. The use of immunohistochemistry (IHC) showed that Ang-1 was primarily localized to syncytiotrophoblasts where it displayed moderate immunoreactivity, whereas weak immunoreactivity for Ang-1 was observed in endothelial cells and angiogenic cell cords (ACC). Strong immunoreactivity for Ang-2 was also found predominantly in syncytiotrophoblasts with lower immunostaining levels evident in cytotrophoblasts. Moderate immunoreactivity for Ang-2 was observed in endothelial cells, ACC and Hofbauer cells. By contrast, the trophoblastic shell, as well as endothelial cells and ACC exhibited strong staining intensity for Tie-1 with the strongest immunoreactivity for Tie-2 observed in cytotrophoblasts, ACC and endothelial cells. Western blotting of tissue extracts confirmed the IHC results. Previous studies focused on VEGF and its receptors in controlling vasculogenesis and angiogenesis in human placenta. However, the specific localization patterns of angiopoietins and their receptors revealed by the current study emphasize the importance of these molecules in placental vascular development. Functional studies aimed at identifying the molecular mechanisms of actions of these factors and receptors may prove essential in elucidating the pathophysiology of placental disorders such as intrauterine growth restriction and pre-eclampsia. PMID:18675456

  15. Clinical profile and predisposing factors of cerebral palsy.

    PubMed

    Anwar, S; Chowdhury, J; Khatun, M; Mollah, A H; Begum, H A; Rahman, Z; Nahar, N

    2006-07-01

    This was an analysis of one hundred ten children with cerebral palsy (CP) attending at the Child Development & Neurology Care Center of Dhaka Medical College Hospital during January 2002 to December 2003. These children were observed to study their clinical profile, etiological factors and associated problems. The mean age of these children was 2.9 +/- 2.9 years, mostly being males (n=79, 71.8%). Most of the families of these children belonged to poorer socioeconomic strata. Spastic diplegia constituted the predominant group (34.5 per cent), followed by spastic quadriplegia (25.5 per cent). Dyskinetic CP was present in 15.5 percent of the cases. Hypotonic CP constituted a significant proportion of cases. Delayed Motor Function was observed in all 110 cases, delayed speech was complained in 67.3% cases and impaired hearing was identified in 26.8% CP children. Mothers of 43.6% CP cases reported that they had prolonged labour during delivery and almost one third (29.1%) had suffered from pre-eclampsia or eclampsia. Majority (53.6%) of the CP cases were reported to have had perinatal asphyxia. Comprehensive assessment and early management of these problems are emphasized, which can minimize the extent of disabilities. By proper perinatal care, CP can be prevented. PMID:16878093

  16. Pregnancy and autoimmune diseases.

    PubMed

    Gordon, Caroline

    2004-06-01

    Until about 15 years ago, the general advice to women with autoimmune rheumatic diseases, especially systemic lupus erythematosus, systemic sclerosis and vasculitic syndromes, was to avoid pregnancy as there was a high risk of maternal and fetal morbidity and mortality. However, it is now clear that these risks can be reduced in general by avoiding pregnancy when the diseases are active and continuing appropriate medication to reduce the chances of disease flare during pregnancy. This article will review the evidence for this advice and will also consider other issues that should be discussed with women before they attempt to become pregnant. This will include the influence of pregnancy on the individual autoimmune diseases, as well as the potential impact of the diseases and drug therapy on fertility and pregnancy outcomes. Anti-phospholipid antibody syndrome has emerged as a major cause of fetal loss, pre-eclampsia and premature birth. The clinical and laboratory diagnosis of this condition will not be covered, but the reader is referred to an excellent recent review. Much of the data on pregnancy and autoimmune rheumatic diseases come from retrospective analyses, but some prospective studies have been reported over the past 10 years. There have been very few meta-analyses or randomized clinical trials. PMID:15158746

  17. 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

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

    PubMed

    Yang, Zhenyu; Huffman, Sandra L

    2011-10-01

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

  19. Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure.

    PubMed

    Jauniaux, E; Watson, A L; Hempstock, J; Bao, Y P; Skepper, J N; Burton, G J

    2000-12-01

    The aim was to measure changes in the oxygen tension within the human placenta associated with onset of the maternal arterial circulation at the end of the first trimester of pregnancy, and the impact on placental tissues. Using a multiparameter probe we established that the oxygen tension rises steeply from <20 mmHg at 8 weeks of gestation to >50 mmHg at 12 weeks. This rise coincides with morphological changes in the uterine arteries that allow free flow of maternal blood into the placenta, and is associated with increases in the mRNA concentrations and activities of the antioxidant enzymes catalase, glutathione peroxidase, and manganese and copper/zinc superoxide dismutase within placental tissues. Between 8 to 9 weeks there is a sharp peak of expression of the inducible form of heat shock protein 70, formation of nitrotyrosine residues, and derangement of the mitochondrial cristae within the syncytiotrophoblast. We conclude that a burst of oxidative stress occurs in the normal placenta as the maternal circulation is established. We speculate that this may serve a physiological role in stimulating normal placental differentiation, but may also be a factor in the pathogenesis of pre-eclampsia and early pregnancy failure if antioxidant defenses are depleted. PMID:11106583

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

    PubMed Central

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

    2009-01-01

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

  1. 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

  2. Maternal and neonatal outcomes of hospital vaginal deliveries in Tibet

    PubMed Central

    Miller, S; Tudor, C; Nyima; Thorsten, VR; Sonam; Droyoung; Craig, S; Le, P; Wright, LL; Varner, MW

    2007-01-01

    Introduction To determine the outcomes of vaginal deliveries in three study hospitals in Lhasa, Tibet Autonomous Region (TAR), People's Republic of China (PRC), at high altitude (3,650 m). Methods Prospective observational study of 1,121 vaginal deliveries. Results Pre-eclampsia/gestational hypertension (PE/GH) was the most common maternal complication 18.9% (n=212), followed by postpartum hemorrhage (blood loss ≥ 500 ml) 13.4%. There were no maternal deaths. Neonatal complications included: low birth weight (10.2%), small for gestational age (13.7%), preterm delivery (4.1%) and low Apgar (3.7%). There were 11 stillbirths (9.8/1,000 live births) and 19 early neonatal deaths (17/1,000 live births). Conclusion This is the largest study of maternal and newborn outcomes in Tibet. It provides information on the outcomes of institutional vaginal births among women delivering infants at high altitude. There was a higher incidence of PE/GH and low birth weight; rates of PPH were not increased compared to those at lower altitudes. PMID:17481630

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

    PubMed Central

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

    2009-01-01

    Aim To compare maternal and neonatal outcomes of Tibetan and Han Chinese women delivering vaginally at high altitude (3650 meters) in Lhasa, Tibet Autonomous Region, People’s Republic of China. Method Comparative analysis of data from a prospective observational study of Tibetan (n = 938) and Han Chinese (n = 146) women delivering at three hospitals between January 2004 and May 2005. Results Han Chinese women had higher rates of pre-eclampsia/gestational hypertension than Tibetan women, (10.3% vs 5.9%, P = 0.04). There was no difference in rates of postpartum hemorrhage between Tibetan and Han women (12.8% vs 17.1%, P = 0.15). Han newborns weighed significantly less than Tibetan newborns (P < 0.01), and were twice as likely to be small for gestational age, (24.5% vs 11.6%, P < 0.01). Tibetan newborns were less likely to have poor neonatal outcomes than Han newborns (P < 0.01). Conclusion In high altitude deliveries in Tibet, adverse outcomes were significantly more common among Han Chinese. PMID:19012697

  4. Overweight and Obesity before, during and after Pregnancy

    PubMed Central

    Stupin, J. H.; Arabin, B.

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

    The treatment of degenerative hip joint disease involves modern operative techniques and the use of prosthetic devices individualized on each patient. Being a surgery of considerable importance, great attention is always given by the anaesthesiologist to postoperative analgesia. In general, our goal is to limit the doses of NSAIDs, known to be associated with haemostasis interference and alteration of gastrointestinal apparatus; component of our baseline analgesic protocols after arthroplasty is morphine given parenterally. In order to steadily improve analgesic techniques, which directly impact on patient outcome, we experimented the use of a continuous infusion of magnesium sulphate during subarachnoid anaesthesia. Magnesium sulphate is the drug of choice in case of eclampsia, and pre-eclampsia (for the risk of evolution in eclampsia). According to the most recent findings, this drug has also analgesic properties: its use as an adjunct to analgesia is based on a non-competitive antagonism towards the NMDA receptor and on the blocking of calcium channels: these properties prevent the mechanisms of central sensitization due to nociceptive stimulation of peripheral nerves. PMID:23905078

  6. 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.

  7. 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

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

    PubMed

    Milas, Vesna; Puseljić, Silvija; Stimac, Maja; Dobrić, Hana; Lukić, Gordana

    2013-09-01

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

  9. 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

  10. The Centre for Trophoblast Research: improving health through placental research.

    PubMed

    Burton, Graham J

    2012-07-01

    The placenta is an essential but widely neglected organ. As the interface between the mother and her fetus, the placenta represents the platform for a healthy life. The majority of the major complications of pregnancy, including miscarriage, pre-eclampsia, intrauterine growth restriction and stillbirth, have their pathophysiological roots in poor placentation. In addition, there is now irrefutable evidence that low birthweight predisposes to a higher risk of cardiovascular and other disorders in later life. The Centre for Trophoblast Research was established in the University of Cambridge with the aim of generating new impetus and a fresh approach to address these problems. Placentation involves many different cell biological processes, some of which are unique to the trophoblast, as well as complex interactions with the maternal immune system. The Centre brings together academic clinicians and basic scientists working in diverse disciplines and provides a rich intellectual environment that facilitates novel collaborative links. The Centre also encourages new investigators into the field and fosters their careers through a number of initiatives, including support for studentships and fellowships, developing research resources, hosting an annual scientific meeting and running a training course in placental biology. Full details can be found at www.trophoblast.cam.ac.uk. PMID:22560116

  11. Autoantibodies as predictors of pregnancy complications.

    PubMed

    Carp, H J A; Meroni, P L; Shoenfeld, Y

    2008-06-01

    Certain autoantibodies which are found in autoimmune diseases including CTDs can impair fertility. Reproductive failure may present as pregnancy loss, either as miscarriage, intrauterine fetal death or stillbirth. There are also late obstetric complications such as intrauterine growth restriction, pre-eclampsia and pre-term birth. This review summarizes the possible influences of autoantibodies in reproductive failure, and particularly their predictive value (if available). The aPLs detectable by lupus anticoagulant, anti-cardiolipin or anti-beta2 glycoprotein I assays are associated with pregnancy loss and have a positive predictive value (PPV) of 75%. In spite of the general consensus on the management of pregnant aPL-positive women, few well-designed clinical trials have been reported and there is also insufficient data about the PPV of treatment. Anti-thyroid antibodies have been associated with pregnancy loss, and indeed have a PPV of 40%. However, no antibody is pathognomic for pregnancy loss. It may be more appropriate to assess a combination of antibodies rather than one antibody. However, a large meta-analysis of published trials is required in order to determine the prevalence of each particular autoantibody and different combinations of antibodies in different forms of reproductive failure. PMID:18504286

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

    PubMed

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

    2011-05-01

    Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications. PMID:21646675

  13. The role of macrophages in utero-placental interactions during normal and pathological pregnancy.

    PubMed

    Renaud, Stephen J; Graham, Charles H

    2008-01-01

    The intimate association between maternal and placental tissues elicits an interesting immunological paradox. Placental tissue contains paternal antigens, but under normal circumstances the semi-allogeneic fetus and placenta are not attacked by the maternal immune system. Interestingly, this tolerance to fetal antigens occurs in the presence of a large number of maternal leukocytes, almost all of which are members of the innate immune system. Macrophages are one of the most abundant leukocytes in the decidua and their numbers remain constant throughout gestation. They are recruited to the decidua by both stromal cells and trophoblast cells, where they adopt a specialized phenotype that may assist in various aspects of decidual homeostasis, placental development, and tolerance to the semi-allogeneic trophoblast. Aberrant behavior of these macrophages can affect trophoblast function and placental development, potentially leading to a spectrum of adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth restriction or demise. This review will focus on the phenotype and putative functions of decidual macrophages in normal pregnancy, and how abnormal activation of these cells can affect various aspects of placental development. PMID:18716937

  14. 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

  15. 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

  16. 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

  17. Diffuse multifocal chorangiomatosis of the placenta with multiple intestinal stenosis of the fetus: combination of rare causes for nonimmune hydrops fetalis.

    PubMed

    Chopra, Anita; Iyer, Venkateswaran K; Thapar, Rajeev; Singh, Neeta

    2006-10-01

    Non-immune causes of hydrops fetalis are rare but frequently fatal. Identification of the cause for hydrops fetalis is essential to institute therapy. Chorangiomatosis and intestinal stenosis have not been previously reported as aetiological factors for the development of hydrops. We report a fetus born with hydrops associated with both of these conditions. A 1575 gms preterm neonate was born to a multigravida at 31 weeks of gestation. Emergency caesarean section was performed after detection of hydrops by prenatal ultrasonography. Baby had generalized edema at birth and died after 3 days due to progressive heart failure. At autopsy there was generalized edema and effusions. There were multiple stenotic segments in the intestine. Placenta showed numerous chorangiomas varying from 0.2 to 3 cm in diameter, hence diagnosed as diffuse multifocal chorangiomatosis. Examination of the placenta at neonatal autopsy is an essential part of assessment for hydrops fetalis. Chorangiomatosis is a rare and under reported condition which can cause prematurity, intrauterine growth retardation, pre-eclampsia and rarely hydrops fetalis. PMID:17183871

  18. Three-dimensional ultrasound evaluation of the placenta.

    PubMed

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

    2011-02-01

    Conventional two-dimensional (2D) ultrasound has been widely used for the evaluation of the placenta during pregnancy. This 2D ultrasound evaluation includes the morphology, anatomy, location, implantation, anomaly, size, and color/power and pulsed Doppler sonographic assessment of the placenta. The introduction of three-dimensional (3D) ultrasound would facilitate the novel assessment of the placenta, such as surface-rendered imaging and volume measurement. With the recent advances in 3D power Doppler (3DPD) ultrasound as well as quantitative 3DPD histogram analysis, quantitative and qualitative assessments of the vascularization and blood flow of the placenta have become feasible. These novel techniques may assist in the evaluation of the feto-placental function, and offer potential advantages relative to conventional 2D sonographic assessments. 3D ultrasound may be an important modality in future placental research, in the evaluation of feto-placental insufficiency in clinical practice, and in the prediction of fetal growth restriction and pre-eclampsia, although some limitations regarding the assessment of the placenta employing 3D ultrasound still remain unresolved. PMID:21115197

  19. Blood Pressure in Third Trimester of Pregnancy.

    PubMed

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

    2016-01-01

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

  20. 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. 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. Antiphospohlipid syndrome in obstetrics.

    PubMed

    Danza, Alvaro; Ruiz-Irastorza, Guillermo; Khamashta, Munther

    2012-02-01

    Antiphospholipid syndrome is characterised by a variety of clinical and immunological manifestations. The clinical hallmarks of this syndrome are thrombosis and poor obstetric outcomes, including miscarriages, fetal loss and severe pre-eclampsia. The main antiphospholipid antibodies include lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I. The combination of aspirin and heparin is considered the standard of care for women with antiphospholipid syndrome and embryo-fetal losses; however, aspirin in monotherapy may have a place in women with recurrent early miscarriage. A good benefit-risk ratio of low-molecular-weight heparin in pregnancy thrombosis treatment has been reported. Warfarin must be avoided if possible throughout the first trimester of pregnancy. Adequate pregnancy management of women with antiphospholipid syndrome should include co-ordinated medical-obstetrical care, a close follow-up protocol and a good neonatal unit. Close blood pressure control and early detection of proteinuria, together with Doppler studies of the utero-placental circulation should be included in the management protocol. PMID:22079775

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

    PubMed

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

    2013-01-01

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

  4. Amniotic fluid phospholipid profile determined by two-dimensional thin-layer chromatography as index of fetal lung maturation.

    PubMed Central

    Whittle, M J; Wilson, A I; Whitfield, C R; Paton, R D; Logan, R W

    1981-01-01

    A phospholipid profile, the main features of which were the lecithin/sphingomyelin (L/S) ratio and the presence or absence of phosphatidylglycerol (PG), was determined in amniotic fluid from 188 patients. There was a mature profile (L/S ratio of at least 2 . 0 and detectable PG) in 145 patients, including seven insulin-dependent diabetics, and noe of their babies developed respiratory distress syndrome (RDS). The L/S ratio was less than 2 . 0 and PG absent in 12 patients, nine of whose babies developed RDS, whereas only three small babies (delivered between 28 and 35 weeks because of fulminant pre-eclampsia or severe abruptio placentae) out of 31 developed RDS when the L/S ratio was less than 2 . 0 but PG was present. When amniotic fluid was collected from the vagina only one out of 69 babies developed RDS when PG was present (regardless of the L/S ratio), while all of seven babies developed RDS when PG was absent. It is concluded that the amniotic fluid phospholipid profile, particularly the presence or absence of PG, gives an accurate assessment of fetal lung maturation. The profile may prove a useful adjunct to the management of high-risk pregnancies, especially after premature membrane rupture and perhaps also when the mother is diabetic. PMID:6780058

  5. Low birth weight incidence in Lundu, Sarawak.

    PubMed

    Yadav, H

    1994-06-01

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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review).

    PubMed

    Zhou, Qun; Cao, Jiangang; Chen, Linxi

    2016-05-01

    Apelin, the endogenous ligand of APJ which is a member of G protein-coupled receptors, has been shown to be expressed in a variety of tissues in vivo and to exert significant biological effects. Studies have indicated that the apelin/APJ system is involved in the regulation of a variety of physiological functions and pathological processes, and that it is associated with cardiovascular diseases (such as atherosclerosis, hypertension, heart failure and myocardial injury), diabetes with microvascular complications, ischemia reperfusion injury, tumors, pre-eclampsia, as well as others. The occurrence of these diseases is closely related to endothelial dysfunction and the local inflammatory response; however, the occurrence of oxidative stress is related to vascular injury, due to the excessive generation of reactive oxygen species (ROS) and can lead to vascular damage and a series of inflammatory reactions. Therefore, this review summarizes the association between apelin/APJ, oxidative stress and inflammation-related diseases. In addition, drugs targeting the apelin/APJ system are recommended, thus providing a novel therapeutic strategy for oxidative stress-related inflammatory diseases. PMID:27035220

  11. 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

  12. 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

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

    PubMed Central

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

    2011-01-01

    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

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

    PubMed

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

    2012-01-01

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

  16. Pregnancy in an achondroplastic dwarf: a case report.

    PubMed

    Ghumman, S; Goel, N; Rajaram, S; Singh, K C; Kansal, B; Dewan, P

    2005-10-01

    Achondroplasia is a rare disorder occurring 1 in 1 5,000 to 1 in 40,000 live births. It is, however, the commonest cause of short-limbed dwarfism. It is a genetic disorder and inherited as an autosomal dominant trait but most cases (80%) are due to mutations of fibroblast growth factor receptor 3 (FGFR3). These individuals have normal mental and sexual development, and life span may be normal. Certain gynaecological problems like infertility, menorrhagia, dysmenorrhoea, leiomyomata and early menopause are more common in these patients. Information regarding obstetric behaviour in achondroplastic females is scarce in literature. However, problems such as pre-eclampsia, polyhydramnios, respiratory compromise, contracted pelvis necessitating lower section caesarean section, prematurity and foetal wastage, etc, have been reported. General anaesthesia is preferred to regional anaesthesia because of the spinal abnormalities. There is increased neonatal mortality due to hydrocephalus and thoracic cage abnormality. Such a patient is considered high risk in terms of anaesthesia and obstetric outcome and there is enough room for prenatal counselling and diagnosis. Here a case of achondroplasia with pregnancy is reported. The patient, an achondroplastic dwarf presented with 30 weeks pregnancy. She was prenatally screened with ultrasonography to rule out affection in baby. She had a caesarean section for contracted pelvis. PMID:16498757

  17. 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

  18. 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

  19. 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

  20. 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

  1. Selective prophylactic transfusion in sickle cell disease.

    PubMed

    Grossetti, Elizabeth; Carles, Gabriel; El Guindi, Wael; Seve, Beatrice; Montoya, Yohni; Creveuil, Christian; Dreyfus, Michel

    2009-01-01

    OBJECTIVE. To record feto-maternal complications following the use of selective prophylactic transfusions in women with major sickle cell disease (SCD) and determine whether selective prophylactic transfusion reduces these complications, through a comparison with a population of women who received transfusions for complications only. DESIGN. A retrospective cohort study. SETTING. Public regional referral hospital in western French Guyana. POPULATION. Between 1992 and 2004, in all 29 women, 55 pregnancies, and 56 neonates. METHODS. Close obstetric follow-up and selective prophylactic transfusions after 26 weeks. Main outcome measures. Adverse obstetric outcome (pre-eclampsia, preterm delivery, intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), cesarean delivery, neonatal and maternal mortality) and end-points for SCD outcome (vaso-occlusive crisis (VOC), acute chest syndrome, and infections). RESULTS. Complications involved the different major SCD types to an equal extent. Comparison with the control group showed that women who had received prophylactic transfusions had lower rates of VOC (p=0.002) and preterm deliveries (p=0.036), but a significant increase in IUGR cases (p=0.048). CONCLUSION. Selective prophylactic transfusion seems to reduce certain maternal and fetal complications in women with severe forms of SCD. These results can only be confirmed through a randomized prospective study. PMID:19639465

  2. [Pregnancy, labour, and puerperium in heroin addicted women, with reference to experience and the present state of knowledge (author's transl)].

    PubMed

    Stauber, M; Schwerdt, M; Hollenbach, B

    1982-05-01

    The mounting problems of drug addiction now also confront the obstetrician and pediatrician. 1/3 of the 60,000 addicts to opiates in the Federal Republic of Germany are women. Of these 80% are in the reproductive age group. Despite endocrine problems pregnancies do occur and are high risk pregnancies because of hepatitis, venereal disease, malnutrition, phlebitis, abscesses, premature deliveries, premature rupture of the membranes, malpresentations, dysmaturity, pre-eclampsia, and numerous other social and psychological problems. Because of the varying content of heroin on the black market the fetus runs the risk of acute overdose or withdrawal. Withdrawal results in extremely marked fetal movements, with increased oxygen consumption and a danger of intra-uterine asphyxia sometimes resulting in intra-uterine fetal death. Most newborns develop a withdrawal syndrome with irritability, high pitched cries, shivering, tachycardia, perspirations, fever and generalized seizures. The experience of the Department for Women for the Free University in Berlin-Charlottenburg are presented and compared to a review of the literature. The medical, social, and psychological aspects of the problem are discussed. PMID:6921111

  3. Identifying implementation bottlenecks for maternal and newborn health interventions in rural districts of the United Republic of Tanzania

    PubMed Central

    Peterson, Stefan; Marchant, Tanya; Mbaruku, Godfrey; Temu, Silas; Manzi, Fatuma; Hanson, Claudia

    2015-01-01

    Abstract Objective To estimate effective coverage of maternal and newborn health interventions and to identify bottlenecks in their implementation in rural districts of the United Republic of Tanzania. Methods Cross-sectional data from households and health facilities in Tandahimba and Newala districts were used in the analysis. We adapted Tanahashi’s model to estimate intervention coverage in conditional stages and to identify implementation bottlenecks in access, health facility readiness and clinical practice. The interventions studied were syphilis and pre-eclampsia screening, partograph use, active management of the third stage of labour and postpartum care. Findings Effective coverage was low in both districts, ranging from only 3% for postpartum care in Tandahimba to 49% for active management of the third stage of labour in Newala. In Tandahimba, health facility readiness was the largest bottleneck for most interventions, whereas in Newala, it was access. Clinical practice was another large bottleneck for syphilis screening in both districts. Conclusion The poor effective coverage of maternal and newborn health interventions in rural districts of the United Republic of Tanzania reinforces the need to prioritize health service quality. Access to high-quality local data by decision-makers would assist planning and prioritization. The approach of estimating effective coverage and identifying bottlenecks described here could facilitate progress towards universal health coverage for any area of care and in any context. PMID:26240459

  4. Lipotoxicity in obese pregnancy and its potential role in adverse pregnancy outcome and obesity in the offspring

    PubMed Central

    Jarvie, Eleanor; Hauguel-de-Mouzon, Sylvie; Nelson, Scott M.; Sattar, Naveed; Catalano, Patrick M.; Freeman, Dilys J.

    2010-01-01

    Increasing maternal obesity is a challenge that has an impact on all aspects of female reproduction. Lean and obese pregnant women gain similar fat mass, but lean women store fat in the lower-body compartment and obese women in central compartments. In the non-pregnant, central storage of fat is associated with adipocyte hypertrophy and represents a failure to adequately store excess fatty acids, resulting in metabolic dysregulation and ectopic fat accumulation (lipotoxicity). Obese pregnancy is associated with exaggerated metabolic adaptation, endothelial dysfunction and increased risk of adverse pregnancy outcome. We hypothesize that the preferential storage of fat in central rather than ‘safer’ lower-body depots in obese pregnancy leads to lipotoxicity. The combination of excess fatty acids and oxidative stress leads to the production of oxidized lipids, which can be cytotoxic and influence gene expression by acting as ligands for nuclear receptors. Lipid excess and oxidative stress provoke endothelial dysfunction. Oxidized lipids can inhibit trophoblast invasion and influence placental development, lipid metabolism and transport and can also affect fetal developmental pathways. As lipotoxicity has the capability of influencing both maternal endothelial function and placental function, it may link maternal obesity and placentally related adverse pregnancy outcomes such as miscarriage and pre-eclampsia. The combination of excess/altered lipid nutrient supply, suboptimal in utero metabolic environment and alterations in placental gene expression, inflammation and metabolism may also induce obesity in the offspring. PMID:20443782

  5. Purification and characterization of a complex from placental syncytiotrophoblast microvillous membranes which inhibits the proliferation of human umbilical vein endothelial cells.

    PubMed

    Kertesz, Z; Hurst, G; Ward, M; Willis, A C; Caro, H; Linton, E A; Sargent, I L; Redman, C W

    1999-01-01

    The signs of pre-eclampsia are thought to arise from maternal endothelial dysfunction caused by circulating factors of placental origin. Syncytiotrophoblast microvillous membranes (STBM) cause endothelial disruption and inhibit proliferation in vitro. Significantly increased amounts of STBM can be detected in blood from pre-eclamptic women and could contribute to endothelial dysfunction in vivo. This study purified a complex from STBM which inhibits the proliferation of cultured human endothelial cells. Integral membrane proteins were solubilized with sucrose monolaurate. Anion exchange chromatography yielded two peaks of anti-proliferative activity. Only the second peak was specific to STBM and was subjected to further separation by Sephacryl S-200 gel filtration chromatography (GFC). A single peak of specific activity eluted close to the void volume, at a position unaltered by added denaturing agents, guanidium chloride or urea. On Sephacryl S-300 GFC, two peaks were obtained of 410 and 820 kDa, with similar anti-proliferative activity and protein components (by SDS-polyacrylamide gel electrophoresis). The major protein bands were as integrins alpha5 and alpha v, dipeptidyl peptidase IV, alpha-actinin, transferrin, transferrin receptor, placental alkaline phosphatase and monoamine oxidase A. PMID:9950147

  6. The role of visfatin (PBEF/Nampt) in pregnancy complications.

    PubMed

    Pavlová, Tereza; Novák, Jan; Bienertová-Vašků, Julie

    2015-11-01

    Visfatin (PBEF/Nampt) is an adipocytokine that exerts pleiotropic effects within the human body, particularly affecting its metabolism and immunity. Visfatin was originally identified as being secreted by peripheral blood lymphocytes acting as a pre-B-cell colony-enhancing factor (PBEF). However, it was subsequently reported to be expressed in almost every tissue of the human body, with visceral fat deposits being the main source of visfatin. In addition to its secreted form, visfatin may also be found intracellularly where it functions as a nicotinamide phosphoribosyltransferase (Nampt). Visfatin maternal plasma concentrations increase during pregnancy, suggesting its important role in this complicated process. Alterations in visfatin level also take place in patients during pregnancy complications. This review focuses on the ones that most commonly occur in connection with visfatin: preterm labor, pre-eclampsia and gestational diabetes mellitus. The review aims to provide a better understanding of the role of visfatin during pregnancy and the causes of its alteration in maternal plasma, highlighting the potential use of visfatin as a diagnostic marker of pregnancy complications in the future. PMID:26451650

  7. The effect of genetic diversity on angiogenesis.

    PubMed

    Rogers, Michael S; D'Amato, Robert J

    2006-03-10

    Angiogenesis is the process by which new blood vessels are formed from existing vessels. Mammalian populations harbor genetic variations that alter angiogenesis. Some of these changes result in Mendelian traits of variable penetrance, with telangiectasia being a common symptom. Other more subtle variations exist, with promoter variations in the VEGF gene being of particular interest. Genetic diversity in angiogenesis-regulating genes has been linked to increased susceptibility to multiple angiogenesis-dependent diseases in humans. These diseases include cancer, arthritis, atherosclerosis, and cardiovascular disease, endometriosis, diabetic retinopathy, retinopathy of prematurity, psoriasis, and sarcoidosis. Also, multiple disturbances in pregnancy including miscarriage, spontaneous preterm delivery, and severe pre-eclampsia have been linked to alterations in angiogenesis-regulating genes. Present efforts to dissect the complexity of the genetic diversity that regulates angiogenesis have used laboratory animals due to the availability of genome sequence for many species and the ability to perform high volume controlled breeding. Ongoing mapping studies have identified multiple loci that control angiogenic responsiveness in several mouse models. Genetic alterations responsible for discrete angiogenic alterations will then be studied in appropriate mouse disease models. PMID:16321383

  8. Outcomes of Spontaneous and Assisted Pregnancies in Turner Syndrome: The NIH Experience

    PubMed Central

    Hadnott, Tracy N; Gould, Harley N; Gharib, Ahmed M; Bondy, Carolyn A

    2011-01-01

    Objective To assess fetal and maternal outcomes of pregnancies in women with Turner syndrome (TS). Design Retrospective case series. Setting Clinical research center. Patients 276 adults with cytogenetically-proven TS participating in an intramural natural history protocol Interventions None. Main Outcome Measures Menstrual and obstetric histories, 50-cell karyotypes, and cardiovascular evaluation including aortic diameter measurements. Results Our cohort included five women with spontaneous pregnancies and five with pregnancies using assisted reproduction (ART). All five women with spontaneous pregnancies had spontaneous puberty, despite 45,X in ≥90% of their 50-cell karyotype. Participants had a total of 13 pregnancies and 14 live births. One child had cerebral palsy; the others were chromosomally and developmentally normal. Delivery was by Cesarean section in 4/7 spontaneous and 6/6 ART-related pregnancies. One mother experienced pre-eclampsia in an ART-related twin pregnancy requiring preterm delivery; she has marked but stable aortic dilation years later. Conclusions Approximately 2% of our study cohort experienced spontaneous pregnancies despite high grade X monosomy, and a similar number achieved pregnancy via oocyte donation and ART. The potential for life-threatening cardiovascular complications warrants comprehensive screening prior to conception, single embryo transfer, and caution regarding unintentional pregnancies for TS women. PMID:21496813

  9. 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

  10. 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

  11. 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

  12. 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

  13. Gestational Diabetes Mellitus.

    PubMed

    Spaight, Caroline; Gross, Justine; Horsch, Antje; Puder, Jardena Jacqueline

    2016-01-01

    Based on the Hyperglycemia and Adverse Pregnancy Outcome study, new universal screening recommendations and cut-offs for gestational diabetes mellitus (GDM) have been proposed. In addition to the immediate perinatal risk, GDM carries an increased risk of metabolic disease in the mother and child. Maternal obesity has even been shown to be associated with increased all-cause mortality in offspring. In addition to known risk factors, excessive gestational weight gain, increased fat consumption, a low vitamin D level, psychological stress and negative mood are risk factors for GDM. Regarding therapy, the US Preventive Task Force concluded in 2013 that GDM treatment significantly reduces the risks of pre-eclampsia, macrosomia and shoulder dystocia (relative risks of 0.62, 0.5 and 0.42, respectively). Although nutrition therapy represents a cornerstone in GDM management, the results of studies are not clear regarding which types of dietary advice are the most suitable. Most physical activity interventions improve glucose control and/or reduce insulin use. Recent studies have evaluated and provided more information about treatment with metformin or glyburide. Postpartum management is essential and should focus on long-term screening and diabetes prevention strategies. PMID:26824237

  14. 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

  15. 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

  16. Regulation of MT1-MMP/MMP-2/TIMP-2 axis in human placenta

    PubMed Central

    Vincent, Zoë L; Mitchell, Murray D; Ponnampalam, Anna P

    2015-01-01

    Matrix metalloproteinases (MMPs) and specific endogenous tissue inhibitors of metalloproteinases (TIMPs) mediate rupture of the fetal membranes in both physiological and pathological conditions. MMPs and TIMPs are subject to regulation by DNA methylation in human malignancies and pre-eclampsia. To determine if membrane type 1 MMP (MT1-MMP), MMP2, and TIMP2 are regulated by DNA methylation in human placentas, we employed an in vitro model where human placental tissues were collected at term gestation and cultured with methylation inhibiting agent 5-AZA-2′-deoxycytidine (AZA) and lipopolysaccharide. The results suggest that DNA methylation is not directly involved in the regulation of MT1-MMP in placental tissue; however, remodeling of chromatin by a pharmacologic agent such as AZA potentiates an infection-related increase in MT1-MMP. MT1-MMP is a powerful activator of MMP2 and this action, coupled with either no change or a decrease in TIMP2 concentrations, favors a gelatinolytic state leading to extracellular matrix degradation, which could predispose fetal membranes to rupture prematurely during inflammation. PMID:26491367

  17. 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

  18. Magnesium sulphate given topically by iontophoresis for viability of random skin flaps in rats.

    PubMed

    André Yu, Renato; Brumini, Christine; Esteves Junior, Ivaldo; Masako Ferreira, Lydia; Eloin Liebano, Richard

    2009-01-01

    Our aim was to assess the effects of magnesium sulphate given by iontophoresis on the viability of random skin flaps in rats. Endovenous magnesium sulphate is used to treat pre-eclampsia and diseases of blood vessels. Iontophoresis is an electrotherapeutic method which has shown satisfactory results in controlling ischaemia within the boundaries of the area in which it was given. Forty-five adult male Wistar rats, weighing 300 to 440 g were randomly divided into three groups of 15 animals each: random skin flap (control); random skin flap treated with magnesium sulphate without electrical stimulation; and random skin flap treated with magnesium sulphate with electrical stimulation of 4 mA for 20 minutes. The treatments were applied immediately after the operation and repeated on the following two days. The percentage of necrotic area was measured on the seventh postoperative day using a paper template. For each group, the mean percentage of flap necrosis was as follows: control, 46%; magnesium sulphate without electrical stimulation, 34%; and magnesium sulphate with electrical stimulation, 42%. There was no significant difference among the groups (p = 0.18). Magnesium sulphate given by iontophoresis does not increase the viability of random skin flaps in rats. PMID:19688642

  19. 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

  20. 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

  1. Outcomes of pregnancy following liver transplantation: The King's College Hospital experience.

    PubMed

    Westbrook, Rachel H; Yeoman, Andrew D; Agarwal, Kosh; Aluvihare, Varuna; O'Grady, John; Heaton, Nigel; Penna, Leonie; Heneghan, Michael A

    2015-09-01

    Reports of pregnancy in liver transplantation (LT) patients have largely favorable outcomes. Concerns remain with regards to maternal and graft risk, optimal immunosuppression (IS), and fetal outcomes. We review all post-LT pregnancies at our center with regard to the outcomes and safety for the patient, graft, and fetus. A total of 117 conceptions occurred in 79 patients. Median age at conception was 29 years. Maternal complications included graft loss (2%), acute cellular rejection (ACR; 15%), pre-eclampsia/eclampsia (15%), gestational diabetes (7%), and bacterial sepsis (5%). ACR was significantly more common in those women who conceived within 12 months of LT (P = 0.001). The live birth rate was 73%. Prematurity occurred in 26 (31%) neonates, and 24 (29%) neonates were of low or very low birth weight. IS choice (cyclosporine versus tacrolimus) had no significant effect on pregnancy outcomes and complications. No congenital abnormalities occurred, and only 1 child born at 24 weeks had delayed developmental milestones. In conclusion, pregnancy following LT has a favorable outcome in the majority, but severe maternal risks remain. Patients should be counseled with regard to the above information so informed decisions can be made, and pregnancy must be considered high risk with regular monitoring by transplant clinicians and specialist obstetricians. PMID:26013178

  2. 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

  3. 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

  4. Autonomic denervation: A new aetiological framework for clinical obstetrics and gynaecology.

    PubMed

    Quinn, M J

    2016-04-01

    The hypothesis is that many clinical conditions in obstetrics and gynaecology result from the diverse and varying consequences of injuries to pelvic autonomic nerves. These injuries result from difficult first labours, persistent physical efforts during defaecation, and, medical and surgical techniques for evacuation of the uterus. The neuro-immunohistochemical "signatures" of these injuries are variations of the Dixon-Robertson-Brosens (DRB) lesion in preeclampsia, where there is hyperplasia of the tunica intima and media of arterioles with narrowing of the lumen of the vessel. In stage IV, nulliparous "endometriosis" (and other gynaecological conditions) there are circumferential layers of abnormal nerves around a narrowed arteriole, whereas in early-onset preeclampsia (and other obstetric conditions) there are similar histological findings in uterine arterioles but there is no sign of injured nerves. During pregnancy there is elongation of blood vessels but no elongation of injured nerves leading to relative denervation of the myometrium. These lesions are detectable in most of the "great" obstetric syndromes, and, across the spectrum of gynaecological syndromes. They provide a coherent explanation of the natural history and clinical presentations of many of these syndromes. Clinical features vary with the site, nature and extent of the injury; a minor injury may enable pregnancy though it is complicated by late-onset pre-eclampsia whereas a more extensive injury may prevent pregnancy and present with chronic pelvic pain with, or without, endometriosis. PMID:26968908

  5. 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

  6. Vitamin D supplementation for women during pregnancy

    PubMed Central

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

    2013-01-01

    Background Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse gestational outcomes. Objectives To examine whether supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011), the International Clinical Trials Registry Platform (ICTRP) (31 October 2011), the Networked Digital Library of Theses and Dissertations (28 October 2011) and also contacted relevant organisations (8 April 2011). Selection criteria Randomised and quasi-randomised trials with randomisation at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy. Data collection and analysis Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy. Main results The search strategy identified 34 potentially eligible references. We included six trials assessing a total of 1023 women, excluded eight studies, and 10 studies are still ongoing. Five trials involving 623 women compared the effects of vitamin D alone versus no supplementation/placebo and one trial with 400 women compared the effects of vitamin D and calcium versus no supplementation. Only one trial with 400 women reported on pre-eclampsia: women who received 1200 IU vitamin D along with 375 mg of elemental calcium per day were as likely to develop pre-eclampsia as women who received no supplementation (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.33 to 1.35). Data from four trials involving 414 women consistently show that women who received vitamin D supplements had higher concentrations of vitamin D in serum at term than those women who received no intervention or a placebo; however the magnitude of the response was highly heterogenous. Data from three trials involving 463 women suggest that women who receive vitamin D supplements during pregnancy less frequently had a baby with a birthweight below 2500 grams than those women receiving no treatment or placebo; statistical significance was borderline (RR 0.48; 95% CI 0.23 to 1.01). In terms of other conditions, there were no significant differences in adverse side effects including nephritic syndrome (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women); stillbirths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) or neonatal deaths (RR 0.17; 95% CI 0.01 to 4.06; one trial, 135 women) between women who received vitamin D supplements in comparison with women who received no treatment or placebo. No studies reported on preterm birth, maternal death, admission to neonatal intensive care unit/special nursery or Apgar scores. Authors' conclusions Vitamin D supplementation in a single or continued dose during pregnancy increases serum vitamin D concentrations as measured by 25-hydroxyvitamin D at term. The clinical significance of this finding and the potential use of this intervention as a part of routine antenatal care are yet to be determined as the number of high quality trials and outcomes reported is too limited to draw conclusions on its usefulness and safety. Further rigorous randomised trials are required to evaluate the role of vitamin D supplementation in pregnancy. PMID:22336854

  7. 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 commenced antenatally (MD 8.10, 95% CI 6.23 to 9.97) and postnatally (MD 3.70, 95% CI 0.96 to 6.44). Authors’ conclusions There was no clear evidence of any effect of corticosteroids on substantive clinical outcomes. Those receiving steroids showed significantly greater improvement in platelet counts which was greater for those receiving dexamethasone than those receiving betamethasone. There is to date insufficient evidence of benefits in terms of substantive clinical outcomes to support the routine use of steroids for the management of HELLP. The use of corticosteroids may be justified in clinical situations in which increased rate of recovery in platelet count is considered clinically worthwhile. PMID:20824872

  8. 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

  9. Heme oxygenase induction attenuates TNF-α-induced hypertension in pregnant rodents

    PubMed Central

    George, Eric M.; Stout, Jacob M.; Stec, David E.; Granger, Joey P.

    2015-01-01

    Pre-eclampsia is a hypertensive disorder of pregnancy initiated by placental insufficiency and chronic ischemia. In response, several pathways activated in the placenta are responsible for the maternal syndrome, including increased production of the anti-angiogenic protein, sFlt-1, and inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α). Previous studies have demonstrated that heme oxygenase (HO) induction can block TNF-α pathways in vitro and attenuate placental ischemia-induced sFlt-1 in vivo. Here, we investigated whether HO-1 induction could attenuate TNF-α-induced hypertension in pregnant rats. In response to TNF-α infusion (100 ng/day i.p.), maternal mean arterial pressure (MAP) increased vs. control animals (104 ± 3 vs. 119 ± 3 mmHg). HO-1 induction had no effect in control animals, but significantly decreased MAP in TNF-α-infused animals (108 ± 2 mmHg). Placental vascular endothelial growth factor (VEGF) was decreased in response to TNF-α infusion (92 ± 4 vs. 76 ± 2 pg/mg). Placental sFlt-1 was increased by TNF-α infusion (758 ± 45 vs. 936 ± 46 pg/mg, p < 0.05), which trended to normalization by HO-1 induction (779 ± 98 pg/mg). In contrast, HO-1 induction had no significant effect on placental VEGF in TNF-α-infused animals. Taken together, these data suggest that one of the key mechanisms by which HO exerts cytoprotective actions in the placenta during inflammation due to chronic ischemia is through suppression of sFlt-1. Further work elucidating the bioactive metabolites of HO-1 in innate inflammatory responses to placental ischemia is warranted. PMID:26347650

  10. Psychosocial deprivation in women with gestational diabetes mellitus is associated with poor fetomaternal prognoses: an observational study

    PubMed Central

    Cosson, Emmanuel; Bihan, Hélène; Reach, Gérard; Vittaz, Laurence; Carbillon, Lionel; Valensi, Paul

    2015-01-01

    Objective To evaluate the prognoses associated with psychosocial deprivation in women with gestational diabetes mellitus (GDM). Design Observational study considering the 1498 multiethnic women with GDM who gave birth between January 2009 and February 2012. Setting Four largest maternity units in the northeastern suburban area of Paris. Participants The 994 women who completed the Evaluation of Precarity and Inequalities in Health Examination Centers (EPICES) questionnaire. Main outcome measure Main complications of GDM (large infant for gestational age (LGA), shoulder dystocia, caesarean section, pre-eclampsia). Results Psychosocial deprivation (EPICES score ≥30.17) affected 577 women (56%) and was positively associated with overweight/obesity, parity and non-European origin, and negatively associated with family history of diabetes, fruit and vegetable consumption and working status. The psychosocially deprived women were diagnosed with GDM earlier, received insulin treatment during pregnancy more often and were more likely to have LGA infants (15.1% vs 10.6%, OR=1.5 (95% CI 1.02 to 2.2), p<0.05) and shoulder dystocia (3.1% vs 1.2%, OR=2.7 (0.97 to 7.2), p<0.05). In addition to psychosocial deprivation, LGA was associated with greater parity, obesity, history of GDM, ethnicity, excessive gestational weight gain and insulin therapy. A multivariate analysis using these covariates revealed that the EPICES score was independently associated with LGA infants (per 10 units, OR=1.12 (1.03 to 1.20), p<0.01). Conclusions In our area, psychosocial deprivation is common in women with GDM and is associated with earlier GDM diagnoses and greater insulin treatment, an increased likelihood of shoulder dystocia and, independently of obesity, gestational weight gain and other confounders with LGA infants. PMID:25748416

  11. Tissue-Specific Education of Decidual NK Cells.

    PubMed

    Sharkey, Andrew M; Xiong, Shiqiu; Kennedy, Philippa R; Gardner, Lucy; Farrell, Lydia E; Chazara, Olympe; Ivarsson, Martin A; Hiby, Susan E; Colucci, Francesco; Moffett, Ashley

    2015-10-01

    During human pregnancy, fetal trophoblast cells invade the decidua and remodel maternal spiral arteries to establish adequate nutrition during gestation. Tissue NK cells in the decidua (dNK) express inhibitory NK receptors (iNKR) that recognize allogeneic HLA-C molecules on trophoblast. Where this results in excessive dNK inhibition, the risk of pre-eclampsia or growth restriction is increased. However, the role of maternal, self-HLA-C in regulating dNK responsiveness is unknown. We investigated how the expression and function of five iNKR in dNK is influenced by maternal HLA-C. In dNK isolated from women who have HLA-C alleles that carry a C2 epitope, there is decreased expression frequency of the cognate receptor, KIR2DL1. In contrast, women with HLA-C alleles bearing a C1 epitope have increased frequency of the corresponding receptor, KIR2DL3. Maternal HLA-C had no significant effect on KIR2DL1 or KIR2DL3 in peripheral blood NK cells (pbNK). This resulted in a very different KIR repertoire for dNK capable of binding C1 or C2 epitopes compared with pbNK. We also show that, although maternal KIR2DL1 binding to C2 epitope educates dNK cells to acquire functional competence, the effects of other iNKR on dNK responsiveness are quite different from those in pbNK. This provides a basis for understanding how dNK responses to allogeneic trophoblast affect the outcome of pregnancy. Our findings suggest that the mechanisms that determine the repertoire of iNKR and the effect of self-MHC on NK education may differ in tissue NK cells compared with pbNK. PMID:26320253

  12. Zinc, copper and selenium in reproduction.

    PubMed

    Bedwal, R S; Bahuguna, A

    1994-07-15

    Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body. Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis. Defects in spermatozoa are frequently observed in the zinc-deficient rat. Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa. Zinc deficiency in the female can lead to such problems as impaired synthesis/secretion of (FSH) and (LH), abnormal ovarian development, disruption of the estrous cycle, frequent abortion, a prolonged gestation period, teratogenicity, stillbirths, difficulty in parturition, pre-eclampsia, toxemia and low birth weights of infants. The level of testosterone in the male has been suggested to play a role in the severity of copper deficiency. Copper-deficient female rats are protected against mortality due to copper deficiency, and the protection has been suggested to be provided by estrogens, since estrogens alter the subcellular distribution of copper in the liver and increase plasma copper levels by inducing ceruloplasmin synthesis. The selenium content of male gonads increases during pubertal maturation. Selenium is localized in the mitochondrial capsule protein (MCP) of the midpiece. Maximal incorporation in MCP occurs at steps 7 and 12 of spermatogenesis and uptake decreases by step 15. Selenium deficiency in females results in infertility, abortions and retention of the placenta. The newborns from a selenium-deficient mother suffer from muscular weakness, but the concentration of selenium during pregnancy does not have any effect on the weight of the baby or length of pregnancy. The selenium requirements of a pregnant and lactating mother are increased as a result of selenium transport to the fetus via the placenta and to the infant via breast milk. PMID:8033970

  13. Heme oxygenase induction attenuates TNF-α-induced hypertension in pregnant rodents.

    PubMed

    George, Eric M; Stout, Jacob M; Stec, David E; Granger, Joey P

    2015-01-01

    Pre-eclampsia is a hypertensive disorder of pregnancy initiated by placental insufficiency and chronic ischemia. In response, several pathways activated in the placenta are responsible for the maternal syndrome, including increased production of the anti-angiogenic protein, sFlt-1, and inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α). Previous studies have demonstrated that heme oxygenase (HO) induction can block TNF-α pathways in vitro and attenuate placental ischemia-induced sFlt-1 in vivo. Here, we investigated whether HO-1 induction could attenuate TNF-α-induced hypertension in pregnant rats. In response to TNF-α infusion (100 ng/day i.p.), maternal mean arterial pressure (MAP) increased vs. control animals (104 ± 3 vs. 119 ± 3 mmHg). HO-1 induction had no effect in control animals, but significantly decreased MAP in TNF-α-infused animals (108 ± 2 mmHg). Placental vascular endothelial growth factor (VEGF) was decreased in response to TNF-α infusion (92 ± 4 vs. 76 ± 2 pg/mg). Placental sFlt-1 was increased by TNF-α infusion (758 ± 45 vs. 936 ± 46 pg/mg, p < 0.05), which trended to normalization by HO-1 induction (779 ± 98 pg/mg). In contrast, HO-1 induction had no significant effect on placental VEGF in TNF-α-infused animals. Taken together, these data suggest that one of the key mechanisms by which HO exerts cytoprotective actions in the placenta during inflammation due to chronic ischemia is through suppression of sFlt-1. Further work elucidating the bioactive metabolites of HO-1 in innate inflammatory responses to placental ischemia is warranted. PMID:26347650

  14. Intensive care management and outcome of women with hypertensive diseases of pregnancy

    PubMed Central

    Imarengiaye, Charles Osalumese; Isesele, Theodore Ojeide

    2015-01-01

    Introduction: The burden of hypertensive diseases on the health care is enormous given to the high population in Sub-Saharan Africa and related disproportionate representation in global maternal mortality. Materials and Methods: All women with hypertensive diseases of pregnancy who got admitted into the general ICU of the University of Benin Teaching Hospital between January 2006 and December 2010 were studied. Only the records of women who completed 28 weeks of gestation and were admitted during labour and delivery or puerperium to the ICU were examined. Results: There were 13061 deliveries within the 5-year study period; 9301 by vaginal delivery and 3860 through Caesarean section. 52 (51.5%) of the obstetric patients had hypertensive diseases of pregnancy. Of 52 women with pre-eclampsia and eclampsia, 45/52 had caesarean section and 7/52 had SVD. Admission was mainly postpartum 48/52 (92.3%). 35/52 (67.3%) were transferred to the ward and 17 died (32.7%), giving the ICU maternal mortality rate of 307/1000 deliveries. 30 women developed pulmonary oedema alone or with renal impairment; 14 women were transferred and 16 died while 21 other patients who had renal impairment alone, HELLP, sepsis, etc were transferred out. There was about a 12-fold risk of death in the unit if the patient developed pulmonary oedema when compared to the other factors combined (p = 0.0002, RR = 11.7, 95%CI = 1.7 – 82.). Conclusion: Primiparity, unbooked status and caesarean delivery were leading factors for ICU admission in women with preeclampsia/eclampsia. The women who developed pulmonary oedema in the course of treatment had poor outcome and avoidance of pulmonary oedema may improve ICU outcome in women with preeclampsia/eclampsia. PMID:26778884

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

    PubMed

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

    2014-03-01

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

  16. 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

  17. Pattern of severe maternal morbidity in a tertiary hospital of Delhi, India: a pilot study.

    PubMed

    Chhabra, Pragti; Guleria, Kiran; Saini, Narinder Kumar; Anjur, Kannan Tupil; Vaid, Neelam Bala

    2008-10-01

    Severe maternal morbidity also known as 'near miss' may be a good indicator of the quality and effectiveness of obstetric care, as it may identify priorities in maternal care more rapidly than mortality alone. The objective of the study was to observe the pattern of severe maternal morbidity and its associated factors in a tertiary care hospital in Delhi. All patients admitted to the obstetrics and gynaecology department who fulfilled the definition of severe maternal morbidity conditions were included. A proforma was used to record sociodemographic, obstetric, antenatal care treatment and outcome details. A total of 63 women were included for analysis. The incidence of severe maternal morbidity was 3.3/100 deliveries. The mean age of the patients was 26.3 +/- 5 years. More than half (55.5%) were uneducated: almost one-third (32%) were from outside Delhi - the median distance travelled was 10 km. The majority were antenatal admissions (68.3%). The proportion of postdelivery or abortion cases were greater among women who came from outside Delhi. Only 38.1% were registered during the antenatal period. The diagnoses were: eclampsia/pre-eclampsia (35%); haemorrhage (35%); sepsis (13%); obstructed labour (9.5%) and other medical conditions (11%). Severe anaemia was observed in 22% of cases. Only 43.5% were normal vaginal deliveries and 54.5% were delivered by caesarean section or with the use of instruments; 61.3% were live births. Hysterectomy was performed in 14.8%: the proportion of hysterectomy was higher in obstructed labour. Severe maternal morbidity cases constitute a significant burden on health resources. PMID:18820181

  18. Management of pregnancy in women with type 1 diabetes.

    PubMed

    Azar, M; Lyons, T J

    2013-12-01

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

  19. 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

  20. Lack of beneficial effects on the NO-donor, molsidomine, in the L-NAME-induced pre-eclamptic syndrome in pregnant rats.

    PubMed Central

    Richer, C.; Boulanger, H.; Es-Slami, S.; Giudicelli, J. F.

    1996-01-01

    1. In pregnant rats, chronic NO-synthase inhibition induces the development of a pre-eclamptic syndrome, characterized by an increase in maternal blood pressure, a loss of vascular refractoriness to pressor stimuli, a reduction in litter size and a decrease in pups (and maternal) weight. We investigated whether a NO-donor, molsidomine, administered during NO synthase inhibition, could restore a normal pregnancy. 2. Pregnant rats were given daily, starting from day 14 of gestation, saline (controls), or L-NAME (50 mg kg-1 d-1), or molsidomine (15 or 30 mg kg-1 d-1), or the L-NAME + molsidomine combinations. Maternal blood pressure and body weight, litter size, pups weight and vascular reactivity to pressor stimuli (angiotensin II, noradrenaline, electrical stimulation of the spinal cord) were investigated. 3. L-NAME alone, as compared to controls, increased maternal blood pressure, reduced litter size (-59%), increased foetal reabsorptions (+ 625%) and decreased foetal weight (-10%). Vascular reactivity to pressor stimuli was enhanced. 4. Molsidomine alone, as compared to controls, dose-dependently decreased maternal blood pressure but had no effect vascular reactivity and, whatever the dose, on foetal outcome. 5. The L-NAME-molsidomine combinations dose (of molsidomine)-dependently limited the rise in maternal blood pressure induced by L-NAME alone but unexpectedly, dose-dependently and significantly worsened pregnancy evolution, e.g., at 30 mg kg-1 d-1: litter size (-80%), foetal reabsorptions (+ 1025%), foetal weight (-24%). Vascular reactivity to pressor stimuli was paradoxically further enhanced. 6. Thus, in a chronic NO deprivation-induced model of pre-eclampsia in rats, molsidomine, possibly because of its hypotensive action, worsens the foetal outcome, which questions the usefulness of NO-donors in pre-eclamptic women. PMID:8982513

  1. [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

  2. 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 severity of SDB, the epidemiology and the risk factors of SDB in pregnancy, the association of SDB with adverse pregnancy outcomes, and screening and management options specific for this population. PMID:27064321

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

    PubMed Central

    2011-01-01

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

  4. Comparison of obstetric outcome in pregnant women with and without microalbuminuria

    PubMed Central

    Singh, Harneet; Samal, Sunita; Mahapatro, Akshaya; Ghose, Seetesh

    2015-01-01

    Background: Maternal and neonatal outcome is an index of quality of health and life in human society. To predict serious outcomes in pregnancy various parameters are being researched so that pregnant women who are at risk are identified early and measures taken to ensure a good outcome of pregnancy. Studies have shown an association between microalbuminuria and adverse pregnancy outcome. This study was undertaken to compare obstetric outcome in pregnant women with and without microalbuminuria. Materials and Methods: A prospective cohort study was performed on 69 pregnant women between 20 and 28 weeks of gestation. Urine tests for albuminuria and creatinine measurements were performed in all women and the albumin to creatinine ratio was calculated. The women with microalbuminuria and those without microalbuminuria were monitored until the end of their pregnancy and compared for pregnancy outcome. Results: The age distribution in the two groups was found to be similar and comparable. Preterm labor was strongly associated with microalbuminuria group (P = 0.001**)strongly significant. Incidence of maternal complications were more with microalbuminuria group (P < 0.001**). Fetal complications were significantly more in terms of intrauterine growth restriction, prematurity, low birth weight, low Apgar score and more incidence of neonatal intensive care unit admission with microalbuminuria group (P = 0.010*)moderately significant. Conclusion: It was found that fetal complications were more associated with babies of pregnant women with microalbuminuria. Though maternal complications were more associated with microalbuminuria group, individual events like premature rupture of membrane, preterm premature rupture of membrane had no statistically significant association with microalbuminuria except preterm labor. However, occurrence of pre-eclampsia was more with microalbuminuria, though it didn’t carry any statistical significance. PMID:25810648

  5. 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:25964759

  6. The lost children.

    PubMed

    Smith, S

    1999-03-01

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

  7. A systems biology perspective on sVEGFR1: its biological function, pathogenic role and therapeutic use

    PubMed Central

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

    2010-01-01

    Abstract Angiogenesis is the growth of new capillaries from pre-existent microvasculature. A wide range of pathological conditions, from atherosclerosis to cancer, can be attributed to either excessive or deficient angiogenesis. Central to the physiological regulation of angiogenesis is the vascular endothelial growth factor (VEGF) system – its ligands and receptors (VEGFRs) are thus prime molecular targets of pro-angiogenic and anti-angiogenic therapies. Of growing interest as a prognostic marker and therapeutic target in angiogenesis-dependent diseases is soluble VEGF receptor-1 (sVEGFR1, also known as sFlt-1) – a truncated version of the cell membrane-spanning VEGFR1. For instance, it is known that sVEGFR1 is involved in the endothelial dysfunction characterizing the pregnancy disorder of pre-eclampsia, and sVEGFR1’s therapeutic potential as an anti-angiogenic agent is being evaluated in pre-clinical models of cancer. This mini review begins with an examination of the protein domain structure and biomolecular interactions of sVEGFR1 in relation to the full-length VEGFR1. A synopsis of known and inferred physiological and pathological roles of sVEGFR1 is then given, with emphasis on the utility of computational systems biology models in deciphering the molecular mechanisms by which sVEGFR1’s purported biological functions occur. Finally, we present the need for a systems biology perspective in interpreting circulating VEGF and sVEGFR1 concentrations as surrogate markers of angiogenic status in angiogenesis-dependent diseases. PMID:19840194

  8. 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

  9. 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

  10. A New Mouse Model to Explore Therapies for Preeclampsia

    PubMed Central

    Khan, Ysodra; Seshan, Surya V.; Girardi, Guillermina

    2010-01-01

    Background Pre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. This syndrome has been known to medical science since ancient times. However, despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment. Methodology/Principal Findings Here we show that the CBA/J x DBA/2 mouse model of recurrent miscarriage is also a model of immunologically-mediated preeclampsia (PE). DBA/J mated CBA/J females spontaneously develop many features of human PE (primigravidity, albuminuria, endotheliosis, increased sensitivity to angiotensin II and increased plasma leptin levels) that correlates with bad pregnancy outcomes. We previously reported that antagonism of vascular endothelial growth factor (VEGF) signaling by soluble VEGF receptor 1 (sFlt-1) is involved in placental and fetal injury in CBA/J x DBA/2 mice. Using this animal model that recapitulates many of the features of preeclampsia in women, we found that pravastatin restores angiogenic balance, ameliorates glomerular injury, diminishes hypersensitivity to angiotensin II and protects pregnancies. Conclusions/Significance We described a new mouse model of PE, were the relevant key features of human preeclampsia develop spontaneously. The CBA/J x DBA/2 model, that recapitulates this complex disorder, helped us identify pravastatin as a candidate therapy to prevent preeclampsia and its related complications. We recognize that these studies were conducted in mice and that clinical trials are needed to confirm its application to humans. PMID:21048973

  11. Nationwide maternal mortality in Surinam.

    PubMed

    Mungra, A; van Kanten, R W; Kanhai, H H; van Roosmalen, J

    1999-01-01

    This study assessed the extent, causes, and factors associated with maternal mortality (MM) during 1991-93 in Surinam. Data were obtained from a national mortality survey and verified with the doctors who signed death certificates. A single underlying cause was assigned to each death. Findings indicate that the national MM ratio was 226/100,000 live births (64 maternal deaths), which was 6 times higher than the official figures for the same period. 76.6% were due to direct maternal causes; 23.4% to indirect maternal causes. The main causes of death were hemorrhage (29.7%), pre-eclampsia (20.3%), complications from cesarean section (7.8%), sepsis from genital tract infections (6.3%), and other (7.8%). 87.5% died in the densely populated coastal area, 12.5% died inland, 82.8% died in a hospital, 3.1% died in health centers, and 14.1% at home. 71.7% had vaginal deliveries; 28.3% were delivered by cesarean section. Among 59 maternal deaths, 22% had no prenatal care, 45.8% had their first prenatal visit in the second half of the pregnancy, and 32.2% began prenatal care before the 20th week of gestation. 61.9% had uneventful obstetric histories. 12.7% had health risk factors. 95.2% of cases involved substandard care practices by the woman and her family, obstetricians, hospital care, and/or the organization of health care. Deaths from hemorrhage were mostly due to late blood transfusion. Deaths from eclampsia were due to late transport to the hospital. PMID:10426260

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

    PubMed Central

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

    2013-01-01

    Purpose Physical activity (PA) typically declines throughout pregnancy. Low levels of PA are associated with excessive weight gain and subsequently increase risk of pre-eclampsia, gestational diabetes mellitus, hypertension disorders, delivery by caesarean section and stillbirth. Systematic reviews on PA during pregnancy have not explored the efficacy of behaviour change techniques or related theory in altering PA behaviour. This systematic review evaluated the content of PA interventions to reduce the decline of PA in pregnant women with a specific emphasis on the behaviour change techniques employed to elicit this change. Search and Review Methodology Literature searches were conducted in eight databases. Strict inclusion and exclusion criteria were employed. Two reviewers independently evaluated each intervention using the behaviour change techniques (BCT) taxonomy to identify the specific behaviour change techniques employed. Two reviewers independently assessed the risk of bias using the guidelines from the Cochrane Collaboration. Overall quality was determined using the GRADE approach. Findings A total of 1140 potentially eligible papers were identified from which 14 studies were selected for inclusion. Interventions included counselling (n?=?6), structured exercise (n?=?6) and education (n?=?2). Common behaviour change techniques employed in these studies were goal setting and planning, feedback, repetition and substitution, shaping knowledge and comparison of behaviours. Regular face-to-face meetings were also commonly employed. PA change over time in intervention groups ranged from increases of 28% to decreases of 25%. In 8 out of 10 studies, which provided adequate data, participants in the intervention group were more physically active post intervention than controls. Conclusions and Implications Physical activity interventions incorporating behaviour change techniques help reduce the decline in PA throughout pregnancy. Range of behaviour change techniques can be implemented to reduce this decline including goals and planning, shaping knowledge and comparison of outcomes. A lack of high quality interventions hampers conclusions of intervention effectiveness. PMID:23799096

  13. Severe maternal morbidity associated with maternal birthplace in three high-immigration settings

    PubMed Central

    Glazier, Richard H.; Mortensen, Laust; Nybo-Andersen, Anne-Marie; Small, Rhonda; Davey, Mary-Ann; Rööst, Mattias; Essén, Birgitta

    2015-01-01

    Background: Maternal mortality and morbidity vary substantially worldwide. It is unknown if these geographic differences translate into disparities in severe maternal morbidity among immigrants from various world regions. We assessed disparities in severe maternal morbidity between immigrant women from various world regions giving birth in three high-immigration countries. Methods: We used population-based delivery data from Victoria; Australia and Ontario, Canada and national data from Denmark, in the most recent 10-year period ending in 2010 available to each participating centre. Each centre provided aggregate data according to standardized definitions of the outcome, maternal regions of birth and covariates for pooled analyses. We used random effects and stratified logistic regression to obtain odds ratios (ORs) with 95% confidence intervals (95% CIs), adjusted for maternal age, parity and comparability scores. Results: We retrieved 2,322,907 deliveries in all three receiving countries, of which 479,986 (21%) were to immigrant women. Compared with non-immigrants, only Sub-Saharan African women were consistently at higher risk of severe maternal morbidity in all three receiving countries (pooled adjusted OR: 1.67; 95% CI: 1.43, 1.95). In contrast, both Western and Eastern European immigrants had lower odds (OR: 0.82; 95% CI: 0.70, 0.96 and OR: 0.64; 95% CI: 0.49, 0.83, respectively). The most common diagnosis was severe pre-eclampsia followed by uterine rupture, which was more common among Sub-Saharan Africans in all three settings. Conclusions: Immigrant women from Sub-Saharan Africa have higher rates of severe maternal morbidity. Other immigrant groups had similar or lower rates than the majority locally born populations. PMID:25587005

  14. Three-Dimensional Segmented Poincar 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 68% 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 Poincar 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

  15. 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

  16. Multiple assessment techniques evaluate antepartum fetal risks.

    PubMed

    Bobby, Paul

    2003-09-01

    As technology has advanced, the field of antepartum fetal evaluation has grown. As reviewed here, a variety of options are available for use in the complicated pregnancy, including application of fetal heart rate monitoring techniques, noninvasive assessment of amniotic fluid volume, sonographic evaluation of fetal behavior, and Doppler assessment of fetal blood flow. It remains unclear which test is the best for any particular situation. The NST is the simplest test to perform but has a higher false-positive rate than the biophysical profile or the CST. These two tests also appear to demonstrate superior sensitivity, at the expense of increased testing time and cost. The application of vibroacoustic stimulation improves the specificity of the NST, while the addition of a sonographic assessment of amniotic fluid volume increases sensitivity and creates an acceptable alternative as a primary test. The limited biophysical profile, with the NST component initially omitted, provides some savings in time and cost without apparent loss of sensitivity or specificity when compared with the full profile. Ultimately, while one particular technique of fetal assessment may never prove to be the best, certain techniques may have advantages over others in particular clinical situations. Umbilical artery Doppler velocimetry appears to be a useful adjunct to other forms of testing, especially in the pregnancy at risk for intrauterine growth restriction and pre-eclampsia. Recent data have shown the biophysical profile predicts the onset of amnionitis in the setting of preterm premature rupture of membranes (PROM). The sonographic assessment of amniotic fluid volume is particularly important in the serial evaluation of the pregnancy complicated by fetal growth restriction. As new technology leads to innovative forms of testing, it is expected that these new tests of fetal status will similarly add to, rather than replace, the existing items in our armamentarium. PMID:14508894

  17. 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

  18. Therapeutics and anaesthesia.

    PubMed

    Magee, Laura A; Lowe, S; Douglas, M J; Kathirgamanathan, A

    2011-08-01

    Many aspects of hypertension care outside pregnancy may be applied in pregnancy, but little information is available on which to base decision-making. It would seem reasonable to continue previous dietary salt restriction and physical activity in women with pre-existing (and controlled) hypertension, encourage a heart-healthy diet in all women with a hypertension disorder of pregnancy, and take patient preference into account when deciding on place of care. Although bed rest has become a key part of obstetric practice and for care of women with a hypertension disorder of pregnancy, in particular, the evidence is lacking to support this practice. This may also increase thromboembolic risk. Antihypertensive treatment is strongly advised for women with severe hypertension. The most common agents are parenteral labetalol, hydralazine, or oral nifedipine capsules. Clinicians should familiarise themselves with multiple agents. Until the role of antihypertensive treatment for non-severe hypertension in pregnancy is clarified by ongoing research, clinicians should explicitly state an individual patient's blood pressure goal, which could reasonably be anywhere between 130/80 and 155/105 mmHg. Labetalol and methyldopa are used most commonly. Breastfeeding should be encouraged. Many risk factors for hypertension (e.g. obesity), as well as hospitalisation and pre-eclampsia, all increase the thromboembolic risk for pregnant women, and care providers should consider thromboprophylaxis in the appropriate setting. Finally, anaesthetists play a critical role in the management of women with a hypertension disorder of pregnancy, and should be involved earlier rather than later in the course of their care. PMID:21478058

  19. 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

  20. 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

  1. Physical activity, sedentary behavior and risk of hypertensive disorders of pregnancy in Hispanic women

    PubMed Central

    Chasan-Taber, Lisa; Silveira, Marushka; Pekow, Penelope; Braun, Barry; Manson, JoAnn E.; Solomon, Caren G.; Markenson, Glenn

    2016-01-01

    Objective Prior studies of the association between physical activity and hypertensive disorders of pregnancy have been conflicting; the majority focused on leisure-time activity only, did not use physical activity questionnaires validated for pregnancy, and were conducted in primarily non-Hispanic white populations. Methods We prospectively evaluated this association among 1240 Hispanic women in Proyecto Buena Salud. The Pregnancy Physical Activity Questionnaire, validated for use in pregnancy, was used to assess pre- and early pregnancy sports/exercise, household/caregiving, occupational and transportation activity. Diagnoses of hypertensive disorders of pregnancy were based on medical record abstraction and confirmed by the study obstetrician. Results A total of 49 women (4.0%) were diagnosed with a hypertensive disorder of pregnancy, including 32 women (2.6%) with pre-eclampsia. In age-adjusted analyses, high levels of early pregnancy household/caregiving activity were associated with reduced risk of total hypertensive disorders (OR = 0.4, 95% CI 0.1–0.9) and preeclampsia (OR = 0.3, 95% CI 0.1–0.9) relative to low levels; however, these findings were no longer statistically significant in multivariable models. Pre-pregnancy activity and pattern of activity from pre- to early-pregnancy were not significantly associated with risk. Finally, sedentary behavior was not significantly associated with hypertensive disorders. Conclusion Findings from this prospective study of Hispanic women were consistent with those of prior prospective cohorts indicating that physical activity prior to and during early pregnancy does not significantly reduce risk of hypertensive disorders of pregnancy. PMID:25121645

  2. 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

  3. 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

  4. 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

  5. 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

  6. Immune aspects of pathology of the placental bed contributing to pregnancy pathology.

    PubMed

    Bulmer, J N

    1992-09-01

    Interest has recently focused on the role of the placental bed in the pathogenesis of a variety of pregnancy disorders. Considerable advances have been made in the understanding of the complex relationships between maternal and fetal trophoblast in the placental bed in normal pregnancy. Invasion of uterine spiral arteries by extravillous trophoblast effects the physiological changes required to accommodate increased blood flow to the fetoplacental unit. Control of trophoblast invasion may depend on intrinsic properties, such as production of proteolytic enzymes and expression of a non-classical class I MHC antigen, but maternal cells within decidua may also play a role. Leukocytes form a major component of human decidualized endometrium and in the first trimester consist of granulated lymphocytes, macrophages and T lymphocytes. Suggested roles for decidualized leukocytes include natural killer cell activity, cytokine secretion, antigen presentation and immunosuppression. Several pregnancy disorders, including pre-eclampsia and intrauterine growth retardation, may be due to abnormal maternofetal cellular relationships within the placental bed causing inadequate invasion of spiral arteries and acute atherosis. However, the role of immunological factors in the pathogenesis of these disorders is uncertain since deposition of immunoglobulins and complement has also been detected in spiral arteries in normal pregnancy. Placenta accreta may reflect undue invasiveness of trophoblast and immunohistochemical studies of subinvolution of uteroplacental arteries also suggest an abnormal maternofetal relationship in the placental bed. Although the in vivo role of decidual leukocytes is not known, studies of infertile endometrium have reported a deficiency of granulated lymphocytes, suggesting a possible role in early implantation and placentation. Granulated lymphocytes may also play a role in pregnancy loss. There have been considerable advances in understanding of the abnormal maternofetal relationships in the placental bed which can lead to pregnancy disorders. However, the aetiology and pathogenesis of the various clinical conditions is unlikely to be fully established until regulatory mechanisms in normal pregnancy are elucidated. PMID:1332834

  7. 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

  8. 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

  9. 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

  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 young children to help advance the global MNCH agenda. PMID:26166560

  11. Transcriptional regulation of human thromboxane synthase gene expression

    SciTech Connect

    Lee, K.D.; Baek, S.J.; Fleischer, T

    1994-09-01

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

  12. 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 will contribute to streamlining MNH program evaluations in LMICs. PMID:25875252

  13. 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

  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 environmental factors for high-risk groups, and should consider this capacity in their usual practice. PMID:22224116

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

    PubMed Central

    2012-01-01

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

  16. 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

  17. 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

  18. A simple-potentiometric method for determination of acid and alkaline phosphatase enzymes in biological fluids and dairy products using a nitrophenylphosphate plastic membrane sensor.

    PubMed

    Hassan, Saad S M; Sayour, Hossam E M; Kamel, Ayman H

    2009-04-27

    A novel poly(vinyl chloride) matrix membrane sensor responsive to 4-nitrophenylphosphate (4-NPP) substrate is described, characterized and used for the potentiometric assay of acid (ACP) and alkaline (ALP) phosphatase enzymes. The sensor is based on the use of the ion-association complex of 4-NPP anion with nickel(II)-bathophenanthroline cation as an electroactive material and nitrophenyloctyl ether (NPOE) as a solvent mediator. The sensor displays good selectivity and stability and demonstrates a near-Nernstian response for 4-NPP over the concentration range 9.6x10(-6) to 1.0x10(-2) M with an anionic slope of 28.6+/-0.3 mV decade(-1) and a detection limit of 6.3x10(-6) M over the pH range 4.5-10. The sensor is used to measure the decrease of a fixed concentration of 4-NPP substrate as a function of acid and alkaline phosphatase enzyme activities at optimized conditions of pH and temperature. A linear relationship between the initial rate of 4-NPP substrate hydrolysis and enzyme activity holds over 0.05-3.0 and 0.03-3.4 IU L(-1) of ACP and ALP enzymes, respectively. Validation of the method by measuring the lower detection limit, range, accuracy, precision, within-day repeatability and between-day-variability reveals good performance characteristics of the proposed sensor. The sensor is used for the determination of acid and alkaline phosphatase enzyme activities in biological fluids of some patients suffering from alcoholic cirrhosis, acute myelocytic leukemia, pre-eclampsia and prostatic cancer. The sensor is also utilized for assessment of alkaline phosphatase enzyme in milk and dairy products. The results obtained agree fairly well with data obtained by the standard spectrophotometric methods. PMID:19362623

  19. 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

  20. Mean platelet volume: association with adverse neonatal outcome.

    PubMed

    Gioia, S; Piazze, J; Anceschi, M M; Cerekja, A; Alberini, A; Giancotti, A; Larciprete, G; Cosmi, E V

    2007-06-01

    The aim of the study was to investigate on a possible association between maternal mean platelet volume (MPV) and oxygen-metabolic changes in pregnancies affected by altered maternal-fetal Doppler velocimetry. We considered the altered maternal-fetal Doppler velocimetry group (n = 57) pregnant women admitted to our Institution for a pregnancy complication associated to the event Pre-eclampsia (PE) and intrauterine growth retardation (IUGR), with altered Doppler velocimetry in the umbilical artery ( UA) (high pulsatility index, absence or reverse end diastolic flow (ARED), blood flow cephalisation) and/or bilateral increased resistance in uterine arteries. Out of these cases, 25 pregnancies were complicated by PE and 32 pregnancies were complicated by IUGR. We included 145 normotensive third trimester pregnant women as a normal maternal-fetal Doppler velocimetry control group. From all women, 20 ml of whole venous blood was obtained from the antecubital vein soon after Doppler velocimetry evaluation. MPV was significantly higher in women with abnormal Doppler velocimetry compared to those with normal Doppler velocimetry (8.0 fl [7.0-8.7] vs. 9.1 fl [8.0-10.6], <0.001. Values are median [interquartiles]). We performed a ROC curve in order to find an MPV cut-off able to predict an uneventful event in Doppler velocimetry compromised fetuses (neonatal O(2) support > 48 hrs or intubation and/or pH < 7.2 at umbilical blood gas analysis (UBGA)). An MPV > or = 10 fl was significantly related to the former diagnostic endpoints compared to that of non-compromised fetuses (sensitivity: 45%, specificity: 89.7%, 95 CI: 18.8-66, p < 0.01). Our study suggests that pregnancies affected by Doppler velocimetry alterations, an MPV value > or = 10 fl may be associated with severe oxygen support and/or low UA ph at birth. PMID:17538849

  1. Doppler velocimetry alterations related to platelet changes in third trimester pregnancies.

    PubMed

    Piazze, J; Gioia, S; Cerekja, A; Larciprete, G; Argento, T; Pizzulo, S; Cosmi, E V

    2007-02-01

    The aim of this study was to evaluate the correlations between the haematological parameter mean platelet volume and Doppler velocimetry parameters in order to improve clinical management in third trimester complicated pregnancies (pre-eclampsia, PE, and IUGR) affected by altered uterine resistances. Fifty-one patients were included in the abnormal uterine arteries Doppler velocimetry group (25 pregnancies were complicated by PE, 26 pregnancies were complicated by IUGR). Ninety-nine normotensive pregnant women taking no drugs for at least 2 weeks prior to testing and with no difference in gestational age at evaluation, with normal Doppler velocimetry profiles at routine screen, were used as controls. From all pregnant women, 20 mL of whole blood were obtained into citrate tubes after Doppler velocimetry evaluation and analysed for red blood cell counts (RBC), mean corpuscular volume (MCV), haemoglobin (HGB), haematocrit level (HCT), white blood cells count (WBC), platelet counts (PLT), mean platelets volume (MPV) and other biochemical parameters. From all blood parameters studied, MPV was significantly higher in women with altered uterine artery Doppler velocimetry compared with those with normal Doppler profiles (9.4 +/- 1.0 vs. 8.05 +/- 1.2 fL, P<0.001). In the group with altered uterine artery Doppler velocimetry, pregnancies complicated by PE showed a MPV value higher than pregnancies affected by IUGR (9.5 +/- 1.6 vs. 8.9 +/- 1.1, P<0.001). Finally, mean uterine arteries RI values were significantly related to MPV (fL) in both PE and IUGR groups (P<0.01, r=0.37 and P<0.01, r=0.38, respectively). Our study shows that a periodical monitoring of haematological parameters such as MPV can be associated to Doppler velocimetry in order to improve the management of pregnancies with uterine arteries Doppler velocimetry alterations. PMID:17365848

  2. 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

  3. [Maternal mortality. A necessary revision for its acknowledgement, its medical and social causes and a proposal of actions to be undertaken for its reduction].

    PubMed

    Rizzi, Ricardo G

    2005-01-01

    Maternal mortality is a portrait not only related to maternal health and to the characteristic of the medical services, but also to the social, cultural and political conditions of a given society. It occurs 120 billons pregnancy every year and almost 600.000 women die because of causes related to pregnancy, delivery or puerperal diseases, 95% of those deaths occur in underdeveloped countries. In Swiss, Finland, Canada and Holland, 4 deaths are registered, while in Somalia and Nigeria 1000 death are reported for each 100.000 alive new baby (NV), Meanwhile, in Latin America and the Caribe, 190 death are reported, almost 23.000 women death every year, which clearly shows a great difference between countries. These differences also occur within a given country, as in Argentina, where the prevalence is 44 for each 100.000 NV, Buenos Aires has 9 while Formosa as 177. We pointed out that nonqualified medical services is a very important fact on the above mentioned maternal death, because of the lack of attention of the sepsis, the hemorrahages, the prolonged delivery work and the eclampsia. But abortion is the most important cause of maternal death. We mentioned the social, educational and sanitary facts of illegal abortion. In developed countries pre eclampsia is the main factor. It is mentioned the strategies of the International Conference "Maternity without Risk" carried out in Nairobi in 1987 and the Task Force Inter Regional Agency for the Reduction of Maternal Mortality. 2004 as a good recommendation to be taken into account in order to diminish maternal mortality. We propose to highlight the use of the Maternal Mortality Committee and the application of the Epidemiological Survey System, in order to diminish maternal mortality and some particular ones for the prevalent pathologies and it is concluded that maternal mortality could diminish not only with better sanitary conditions, but also with equal social conditions, specially in underdeveloped, countries where this situation is a real problem. PMID:16281419

  4. 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

  5. [Hypothyroidism: from the desire for pregnancy to delivery].

    PubMed

    Ouzounian, S; Bringer-Deutsch, S; Jablonski, C; Théron-Gérard, L; Snaifer, E; Cédrin-Durnerin, I; Hugues, J-N

    2007-03-01

    The link between hypothyroidism and infertility is still a matter of debate. Hypothyroidism can result in cycle disturbances, such as oligomennorhea and functional bleeding. Additionally, several studies have shown that thyroid autoimmunity (detection of anti peroxydase antibodies) may account for the occurrence of repetitive miscarriages. In infertility work-up, screening thyroid function should be specifically recommended for women with clinical hypothyroidism, with a personal, familial history of thyroid or other auto immune diseases (such as type I diabetes) as well as for women with unexplained anovulation or functional bleeding. Moreover, detection of thyroid antibody seems to be worthwhile for the assessment of recurrent miscarriages, due to the potential benefit of thyroid supplementation. In pregnant women, assessment of thyroid function seems specifically crucial to ensure adequate foetal development. Indeed, it has been well established that untreated maternal hypothyroidism may be associated with disturbances of brain development and low intellectual quotient. Additionally, other foetal (growth deficiency, premature birth, low birth weight) as well as maternal (gestational hypertension, pre-eclampsia...) complications have been also reported in pregnant women with untreated hypothyroidism. Consequently, screening of thyroid function should be performed in every woman at risk of thyroid disease. Recent studies even advocate that thyroid screening should be extended to the overall pregnant population. The objective is to adjust L-thyroxin supplementation to maintain serum TSH concentrations below the threshold of 2.5 mUI/l. Finally, iodine deficiency, currently observed in pregnant women, should be prevented by iodine supply prior to conception, during pregnancy and during breast feeding as well. PMID:17321188

  6. 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

  7. 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:25964759

  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. PMID:23798298

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

    PubMed

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

    2014-08-01

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

  10. Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor.

    PubMed

    Evans, Jemma

    2016-03-01

    Human chorionic gonadotropin (hCG), as one of the first embryonic products, has been extensively investigated for its role in implantation and placental development. Discovery of an over-glycosylated form of this hormone, hyperglycosylated hCG (hCG-H), has provided an additional level of complexity in our understanding of the implantation and placentation process; the structure, activity and functional implications of alterations in hCG isoforms throughout pregnancy are still being characterized. HCG-H comprises up to 90% of total hCG measurable in serum and urine during the first 2-3 weeks of pregnancy when invasive trophoblast activity is high, dropping to negligible proportions, less than 5%, of total hCG at the end of the first trimester. Functionally, hCG-H promotes trophoblast invasion during early pregnancy and has potential roles in immune cell modulation and endothelial function within the uterus at the time of pregnancy initiation. Altered levels of hCG-H are characteristics of pregnancy complications of altered trophoblast function and inadequate placentation, such as pre-eclampsia, and also over-abundance of invasive cytotrophoblasts, such as Down's syndrome. Improving our basic knowledge of the functional role-specific hCG isoforms plays in the complex cascade of events involved in implantation and placental development, and determining dynamic changes in the structure and activity of hCG isoforms throughout gestation will facilitate evidence-based decisions in assisted reproduction/in vitro fertilization based on the potential of embryos to implant, provide biomarkers for diagnosis of pregnancy complications associated with altered placental development and enhance understanding of how hCG isoforms may influence receptivity of the endometrium. PMID:26676718

  11. 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

  12. Interventions to reduce or prevent obesity in pregnant women: a systematic review.

    PubMed Central

    Thangaratinam, S; Rogozińska, E; Jolly, K; Glinkowski, S; Duda, W; Borowiack, E; Roseboom, T; Tomlinson, J; Walczak, J; Kunz, R; Mol, B W; Coomarasamy, A; Khan, K S

    2012-01-01

    BACKGROUND Around 50% of women of childbearing age are either overweight [body mass index (BMI) 25-29.9 kg/m(2)] or obese (BMI ≥ 30 kg/m(2)). The antenatal period provides an opportunity to manage weight in pregnancy. This has the potential to reduce maternal and fetal complications associated with excess weight gain and obesity. OBJECTIVES To evaluate the effectiveness of dietary and lifestyle interventions in reducing or preventing obesity in pregnancy and to assess the beneficial and adverse effects of the interventions on obstetric, fetal and neonatal outcomes. DATA SOURCES Major electronic databases including MEDLINE, EMBASE, BIOSIS and Science Citation Index were searched (1950 until March 2011) to identify relevant citations. Language restrictions were not applied. REVIEW METHODS Systematic reviews of the effectiveness and harm of the interventions were carried out using a methodology in line with current recommendations. Studies that evaluated any dietary, physical activity or mixed approach intervention with the potential to influence weight change in pregnancy were included. The quality of the studies was assessed using accepted contemporary standards. Results were summarised as pooled relative risks (RRs) with 95% confidence intervals (CIs) for dichotomous data. Continuous data were summarised as mean difference (MD) with standard deviation. The quality of the overall evidence synthesised for each outcome was summarised using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology and reported graphically as a two-dimensional chart. RESULTS A total of 88 studies (40 randomised and 48 non-randomised and observational studies, involving 182,139 women) evaluated the effect of weight management interventions in pregnancy on maternal and fetal outcomes. Twenty-six studies involving 468,858 women reported the adverse effect of the interventions. Meta-analysis of 30 RCTs (4503 women) showed a reduction in weight gain in the intervention group of 0.97 kg compared with the control group (95% CI -1.60 kg to -0.34 kg; p = 0.003). Weight management interventions overall in pregnancy resulted in a significant reduction in the incidence of pre-eclampsia (RR 0.74, 95% CI 0.59 to 0.92; p = 0.008) and shoulder dystocia (RR 0.39, 95% CI 0.22 to 0.70; p = 0.02). Dietary interventions in pregnancy resulted in a significant decrease in the risk of pre-eclampsia (RR 0.67, 95% CI 0.53 to 0.85; p = 0.0009), gestational hypertension (RR 0.30, 95% CI 0.10 to 0.88; p = 0.03) and preterm birth (RR 0.68, 95% CI 0.48 to 0.96; p = 0.03) and showed a trend in reducing the incidence of gestational diabetes (RR 0.52, 95% CI 0.27 to 1.03). There were no differences in the incidence of small-for-gestational-age infants between the groups (RR 0.99, 95% CI 0.76 to 1.29). There were no significant maternal or fetal adverse effects observed for the interventions in the included trials. The overall strength of evidence for weight gain in pregnancy and birthweight was moderate for all interventions considered together. There was high-quality evidence for small-for-gestational-age infants as an outcome. The quality of evidence for all interventions on pregnancy outcomes was very low to moderate. The quality of evidence for all adverse outcomes was very low. LIMITATIONS The included studies varied in the reporting of population, intensity, type and frequency of intervention and patient complience, limiting the interpretation of the findings. There was significant heterogeneity for the beneficial effect of diet on gestational weight gain. CONCLUSIONS Interventions in pregnancy to manage weight result in a significant reduction in weight gain in pregnancy (evidence quality was moderate). Dietary interventions are the most effective type of intervention in pregnancy in reducing gestational weight gain and the risks of pre-eclampsia, gestational hypertension and shoulder dystocia. There is no evidence of harm as a result of the dietary and physical activity-based interventions in pregnancy. Individual patient data meta-analysis is needed to provide robust evidence on the differential effect of intervention in various groups based on BMI, age, parity, socioeconomic status and medical conditions in pregnancy. PMID:22814301

  13. 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 lower than those from uncomplicated pregnancies, although only when the babies were born prematurely. Children born at term to normotensive mothers or mothers suffering from PE had comparable birth weights. PMID:26637176

  14. Differential Effects of Complement Activation Products C3a and C5a on Cardiovascular Function in Hypertensive Pregnant Rats

    PubMed Central

    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.

    2014-01-01

    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 (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14–18. Both the C3aRA and C5aRA attenuated placental ischemia–induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia–induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia–induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia–induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti-inflammatory approach. PMID:25150279

  15. Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older.

    PubMed

    Sauer, M V; Paulson, R J; Lobo, R A

    1996-11-01

    We analysed the results of oocyte donation to women of advanced reproductive age (> or = 45 years old) and followed their pregnancies through to delivery in order to assess obstetrical outcomes. Patients (n = 162) aged 45-59 years (mean +/- SD; 47.3 +/- 3.4 years) underwent 218 consecutive attempts to achieve pregnancy. Oocytes (16.2 +/- 7.2 per retrieval) were provided by donors < or = 35 years old. Cleaving embryos (8.2 +/- 4.8 zygotes/couple) were transferred transcervically (4.5 +/- 1.1 per embryo transfer) to recipients prescribed oral micronized oestradiol and intramuscular progesterone. Following oocyte aspiration there were six instances of non-fertilization (2.8%) and 212 embryo transfers. A total of 103 pregnancies was established for an overall pregnancy rate (PR) of 48.6%, which included 17 preclinical pregnancies, 12 spontaneous abortions, and 74 delivered pregnancies (clinical PR 40.6%; delivered PR 34.9%). Multiple gestations were frequent (n = 29; 39.2% of pregnancies) and included 20 twins, seven triplets, and two quadruplets. Two of the triplet and both of the quadruplet pregnancies underwent selective reduction to twins. Antenatal complications occurred in 28 women (37.8% of deliveries) and included preterm labour (n = 9), gestational hypertension (n = 8), gestational diabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia (n = 2), HELLP syndrome (n = 2), and fetal growth retardation (n = 2). 48 (64.8%) deliveries were by Caesarean section. The gestational age at delivery for singletons was 38.3 +/- 1.3 weeks (range 35-41 weeks), with birth weight 3218 +/- 513 g (range 1870-4775 g); twins 35.9 +/- 2.0 weeks (range 32-39 weeks), birth weight 2558 +/- 497 g (range 1700-3450 g); and triplets 33.5 +/- 0.7 weeks (range 32-34 weeks), birth weight 1775 +/- 190 g (range 1550-2100 g). Neonatal complications (4.6% of babies born) included growth retardation (n = 2), trisomy 21 (n = 1), ventricular septal defect (n = 1), and small bowel obstruction (n = 1). There were no maternal or neonatal deaths. We conclude that oocyte donation to women of advanced reproductive age is highly successful in establishing pregnancy. However, despite careful antenatal screening, obstetrical complications are common, often secondary to multiple gestation. PMID:8981151

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

    PubMed Central

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

    2013-01-01

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

  17. THE IMPACT OF MATERNAL OBESITY ON MOTHER AND NEONATAL HEALTH: STUDY IN A TERTIARY HOSPITAL OF ASTANA, KAZAKHSTAN

    PubMed Central

    AIMUKHAMETOVA, GULZHAN; UKYBASOVA, TALSHYN; HAMIDULLINA, ZAITUNA; ZHUBANYSHEVA, KARLYGASH; HARUN-OR-RASHID, MD.; YOSHIDA, YOSHITOKU; KASUYA, HIDEKI; SAKAMOTO, JUNICHI

    2012-01-01

    ABSTRACT This study was aimed to investigate the impact of maternal obesity on mothers and their neonatal health. Our study population consisted of 157 women with completed singleton pregnancies, which included both obese (Body mass index, BMI≥30) and non-obese women (BMI<30). Data were collected from case histories, and ante- and postnatal records at the tertiary hospital in Astana, Kazakhstan between January and February of 2008. Associations between pregnancy and delivery-related complications, outcomes, and maternal obesity were estimated as odds ratios (ORs) and 95% confidence intervals (CIs) using a logistic regression model. Women aged 30 years or more were at higher risk of obesity (OR=3.1, 95% CI=0.8–11.6) than women less than 30 years old. Multiparous women were also at higher risk of obesity (OR=4.1, 95% CI=0.9–19.6) than primiparous ones. Obese women were also more likely to have longer hospital stays of more than 10 days (OR=2.2, 95% CI=0.8–6.2), and were more prone to eclampsia/pre-eclampsia (OR=24.7, 95% CI=2.2–44.8), cesarean sections (OR=2.1, 95% CI=0.7–6.2), and abnormal labor (OR=8.1, 95% CI=1.0–63.8) compared to non-obese women. Neonatal complications such as pneumonia (OR=3.4, 95% CI=0.6–20.2) and fetal macrosomia (OR=2.2, 95% CI=0.6–8.0) were also more common among babies born to obese mothers. Congenital baby birth defects were strongly associated with maternal obesity (P=0.016). We concluded that maternal obesity is associated with increased risks of both maternal and neonatal complications, and that such risks increase with advanced age and parity of the mother. Hence, medical practices must take these complications into account by ensuring an adaptable and early management in order to improve mothers and their neonatal health. PMID:22515114

  18. 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 infant mortality it is necessary to know more about the nature, etiology, and prevention of LBW in developing countries. PMID:3886185

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

    PubMed Central

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

    2014-01-01

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

  20. Selenium status in UK 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

    2015-01-01

    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 UK 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 UK 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. UK pregnant women had whole-blood Se concentration lower than the mid-range of other populations, toenail Se concentration considerably lower than US women, GPx3 activity considerably lower than US 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, UK women have low Se status that increases their risk of developing PE/PIH. Therefore, UK women of childbearing age need to improve their Se status. PMID:25571960

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

    PubMed

    Moslehi, R; Signore, C; Tamura, D; Mills, J L; Digiovanna, J J; Tucker, M A; Troendle, J; Ueda, T; Boyle, J; Khan, S G; Oh, K-S; Goldstein, A M; Kraemer, K H

    2010-04-01

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

  2. 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-Right-Pointing-Pointer Endothelial VEGFR levels are modulated during this response. Black-Right-Pointing-Pointer The cell regulates VEGF-A bioavailability and cell survival. Black-Right-Pointing-Pointer This may partly underlie endothelial dysfunction seen in many pathologies.

  3. 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 symptoms, an association possibly mediated by other factors such as fetal/neonatal condition. Conclusions Despite the absence of robust evidence regarding the relationship between severe maternal morbidity and PTSD/PTSD symptoms, it is crucially important that clinicians and policy makers are aware of a potential higher risk of PTSD among women who experience severe morbidity. Further studies are now needed to confirm this risk as well as to understand underlying mechanisms in order to minimise the longer term psychiatric impact of severe maternal morbidity. PMID:23140343

  4. 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 blood residue area and volume compared to the non-structured controls of the same material. In addition, blood clotting area is reduced >5x using whole blood directly from the patient. In this study, biocompatible SH surfaces are achieved using commodity shrink-wrap film and are scaled up for R2R manufacturing. The purely structural modification negates complex and expensive post processing, and SH features are achieved in commercially-available and FDA-approved plastics.

  5. 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 outcomes after 12 weeks of pregnancy. Trial registration number NCT00198068. PMID:26835148

  6. 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 secondary outcomes are also considered. A comprehensive cost-effectiveness analysis and women's and providers' satisfaction evaluation are performed concurrently with the trial. Health-care programmes should be rigorously evaluated by randomised controlled trials, which are feasible in developing countries and should be conducted before introducing new treatments or health interventions. PMID:9805722

  7. 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 pregnant mothers, were stabilised and transported to hospital by the new emergency ambulance service. 293 resuscitation attempts were documented in personal logbooks. A sustainable system for better managing emergencies has been established and is helping to negate the main obstacle impeding progress: the country's lack of available trained medical and nursing staff. However, insufficient attention was paid to improving staff morale and accommodation representing significant failings of the programme. PMID:20718979

  8. Lupus nephritis is associated with poor pregnancy outcomes in pregnant SLE patients in Cape Town: a retrospective analysis

    PubMed Central

    Mbuli, Lindisa; Mapiye, Darlington; Okpechi, Ikechi

    2015-01-01

    Introduction Systemic lupus erythematosus (SLE) is a multi-system auto-immune disease common in females of child-bearing age. The effect of pregnancy on SLE and vice versa have not been well characterised in Africans. The aim of this study is to describe the pregnancy outcomes of patients with SLE presenting to the maternity department of Groote Schuur Hospital, Cape Town. Methods This study was designed as a retrospective review of records of pregnant women known with SLE and followed-up at the maternity section of Groote Schuur Hospital. The duration of survey was from the 1st January 2003 to 31st December 2013. Results There were 61 pregnancies reviewed in 49 patients; 80.3% of the pregnancies were in patients of mixed ancestry and the rest (19.7%) in black African patients. The mean age at presentation of the current pregnancy was 27.2±5.0 years. Mean gestational age at presentation and delivery was 13.0 ± 6.0 weeks and 28.9 ± 9.8 weeks respectively and 47.5% of the pregnancies were in patients with lupus nephritis (LN). Thirty nine (63.9%) pregnancies reached the third trimester and 11.5% of all pregnancies ended in the first trimester. There was a lower number of live births to mothers of African ancestry than to those of mixed ancestry (p=0.001). In 55.7% of the pregnancies, no flare was reported while a renal flare was reported in 23%. Pregnancies in patients with LN had higher frequencies of flares (58.6% vs 31.3%; p=0.032), pre-eclampsia (34.5% vs 12.5%; p=0.041), longer stay in hospital (12.0 ± 9.1 days vs 6.1 ± 5.1 days; p=0.004) and low birth weight babies (1.94 ± 1.02 kg vs 2.55±0.95 kg; p=0.046) than in patients without LN. Only 36 (59%) of the neonates were discharged home alive and of these 2 (5.6%) were to mothers of black African ancestry (p=0.001). Conclusion Increased lupus activity in pregnant SLE patients may account for the increased deaths of neonates born to SLE mothers. Patients of black African descent and those with LN tend to have a poorer outcome. A multi-disciplinary approach to the management of SLE patients (of child-bearing age or pregnant) needs to be further assessed for better outcomes.

  9. 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 manifestations of the disorder. A role may exist for anti inflammatory agents in the management of women with preeclampsia. PMID:26113950

  10. 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 exploration of which complications are specifically prevented by low-molecular-weight heparin. Systematic review registration PROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249 PMID:24969227

  11. 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 pregnancy and birth outcomes. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426). PMID:24513442

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

    PubMed Central

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

    2013-01-01

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

  13. 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 on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed. Conclusion Although the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs. PMID:19426469

  14. 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 should be sufficient to correct deficiency. PMID:22742603

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

    PubMed Central

    2012-01-01

    Background Criteria-based audits (CBA) have been used to improve clinical management in developed countries, but have only recently been introduced in the developing world. This study discusses the use of a CBA to improve quality of care among eclampsia patients admitted at a University teaching hospital in Dar es Salaam Tanzania. Objective The prevalence of eclampsia in MNH is high (?6%) with the majority of cases arriving after start of convulsions. In 20042005 the case-fatality rate in eclampsia was 5.1% of all pregnant women admitted for delivery (MNH obstetric data base). A criteria-based audit (CBA) was used to evaluate the quality of care for eclamptic mothers admitted at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania after implementation of recommendations of a previous audit. Methods A CBA of eclampsia cases was conducted at MNH. Management practices were evaluated using evidence-based criteria for appropriate care. The Ministry of Health (MOH) guidelines, local management guidelines, the WHO manual supplemented by the WHO Reproductive Health Library, standard textbooks, the Cochrane database and reviews in peer reviewed journals were adopted. At the initial audit in 2006, 389 case notes were assessed and compared with the standards, gaps were identified, recommendations made followed by implementation. A re-audit of 88 cases was conducted in 2009 and compared with the initial audit. Results There was significant improvement in quality of patient management and outcome between the initial and re-audit: Review of management plan by senior staff (76% vs. 99%; P=0.001), urine for albumin test (61% vs. 99%; P=0.001), proper use of partogram to monitor labour (75% vs. 95%; P=0.003), treatment with steroids for lung maturity (2.0% vs. 24%; P=0.001), Caesarean section within 2 hours of decision (33% vs. 61%; P=0.005), full blood count (28% vs. 93%; P=0.001), serum urea and creatinine (44% vs. 86%; P=0.001), liver enzymes (4.0% vs. 86%; P=0.001), and specialist review within 2 hours of admission (25% vs. 39%; P=0.018). However, there was no significant change in terms of delivery within 24 hours of admission (69% vs. 63%; P=0.33). There was significant reduction of maternal deaths (7.7% vs. 0%; P=0.001). Conclusion CBA is applicable in low resource setting and can help to improve quality of care in obstetrics including management of pre-eclampsia and eclampsia. PMID:23170817

  16. Levothyroxine treatment and pregnancy outcome in women with subclinical hypothyroidism undergoing assisted reproduction technologies: systematic review and meta-analysis of RCTs.

    PubMed

    Velkeniers, B; Van Meerhaeghe, A; Poppe, K; Unuane, D; Tournaye, H; Haentjens, P

    2013-01-01

    BACKGROUND Previous meta-analyses of observational data indicate that pregnant women with subclinical hypothyroidism have an increased risk of adverse pregnancy outcome. Potential benefits of levothyroxine (LT4) supplementation remain unclear, and no systematic review or meta-analysis of trial findings is available in a setting of assisted reproduction technologies (ART). METHODS Relevant trials published until August 2012 were identified by searching MEDLINE, EMBASE, Web of Knowledge, the Cochrane Controlled Trials Register databases and bibliographies of retrieved publications without language restrictions. RESULTS From 630 articles retrieved, we included three trials with data on 220 patients. One of these three trials stated 'live delivery' as outcome. LT4 treatment resulted in a significantly higher delivery rate, with a pooled relative risk (RR) of 2.76 (95% confidence limits 1.20-6.44; P = 0.018; I(2) = 70%), a pooled absolute risk difference (ARD) of 36.3% (3.5-69.0%: P = 0.030) and a summary number needed to treat (NNT) of 3 (1-28) in favour of LT4 supplementation. LT4 treatment significantly lowered miscarriage rate with a pooled RR of 0.45 (0.24-0.82; P = 0.010; I(2) = 26%), a pooled ARD of -31.3% (-48.2 to -14.5%: P < 0.001) and a summary NNT of 3 (2-7) in favour of LT4 supplementation. LT4 treatment had no effect on clinical pregnancy (RR 1.75; 0.90-3.38; P = 0.098; I(2) = 82%). In an ART setting, no data are available on the effects of LT4 supplementation on premature delivery, arterial hypertension, placental abruption or pre-eclampsia. CONCLUSIONS Our meta-analyses provide evidence that LT4 supplementation should be recommended to improve clinical pregnancy outcome in women with subclinical hypothyroidism and/or thyroid autoimmunity undergoing ART. Further research is needed to determine pregnancy outcome after close monitoring of thyroid function to maintain thyroid-stimulating hormone and free T4 levels within the trimester-specific reference ranges for pregnancy. PMID:23327883

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

    PubMed Central

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

    2014-01-01

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

  18. 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 could lower syncytiotrophoblast taurine concentration, compromise placental development and function, and reduce the driving force for taurine efflux to the fetus, thereby increasing the risk of poor pregnancy outcome. PMID:25547282

  19. 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-inflammatory approach. PMID:25150279

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

    PubMed Central

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

    2014-01-01

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

  1. Study on the Expressions of PHD and HIF in Placentas from Normal Pregnant Women and Patients with Preeclampsia

    PubMed Central

    Liu, Wei; Wang, Shu-Jun; Lin, Qi-De

    2014-01-01

    Objective: To investigate the relationship between oxygen sensitivity of trophoblast and hypoxia in preeclamptic placenta by the study on the expressions of hypoxia-inducible factor prolyl 4-hydroxylase (PHD) and hypoxia-inducible factor (HIF) in placentas from normal pregnant women and patients with pre-eclampsia. Methods: Subjects were chosen from the in-patients or the out-patients from May 2003 to May 2004. They were divided into 5 groups: early pregnancy group (EP), 13 cases; middle pregnancy group (MP), 9 cases; late pregnancy group (LP, or control group), 12 cases; preeclampsia (PE) group, 20 cases; gestational hypertension group (GH), 10 cases. The mRNA expressions of PHD-1 and -2 and -3 in placentas from all the subjects were assessed by in situ hybridization and Real-time PCR. The expressions of HIF-1α and -2α in placentas from different groups were assessed by immunohistochemistry and western blot. Results: PHD-1,-2 and -3 mRNA were mainly expressed in cytoplasm of trophoblast, especially strongly expressed in extravillous trophoblast. During the progress of pregnancy, the expression of PHD-1 increased significantly (R=0.616, P<0.001). The PHD-1mRNA expression in placentas from PE group decreased significantly compared with that from control group, P<0.05. A significant direct correlation between the PHD-1 mRNA expression in placentas from PE group and their placenta weight was found (R=0.457, P<0.05). The HIF-2α, not the HIF-1α expression, from PE group was significantly higher than that from control group, P<0.01; The HIF-2α expression in trophoblast from PE was inversely correlated to the date of the onset of the disease (R=-0.730, P<0.01). Conclusions: PHD-1 played an important role in hypoxic response pathway of trophoblast through modulating the level of HIF-2α. The overly activated hypoxic response pathway of trophoblast in preeclamptic placenta, which is manifested as the result of HIF-2α over-expression, is the key point to hypoxic dysfunction of trophoblast. PMID:24644426

  2. Risks and benefits of psychotropic medication in pregnancy: cohort studies based on UK electronic primary care health records.

    PubMed Central

    Petersen, Irene; McCrea, Rachel L; Sammon, Cormac J; Osborn, David Pj; Evans, Stephen J; Cowen, Phillip J; Freemantle, Nick; Nazareth, Irwin

    2016-01-01

    BACKGROUND Although many women treated with psychotropic medication become pregnant, no psychotropic medication has been licensed for use in pregnancy. This leaves women and their health-care professionals in a treatment dilemma, as they need to balance the health of the woman with that of the unborn child. The aim of this project was to investigate the risks and benefits of psychotropic medication in women treated for psychosis who become pregnant. OBJECTIVE(S) (1) To provide a descriptive account of psychotropic medication prescribed before pregnancy, during pregnancy and up to 15 months after delivery in UK primary care from 1995 to 2012; (2) to identify risk factors predictive of discontinuation and restarting of lithium (multiple manufacturers), anticonvulsant mood stabilisers and antipsychotic medication; (3) to examine the extent to which pregnancy is a determinant for discontinuation of psychotropic medication; (4) to examine prevalence of records suggestive of adverse mental health, deterioration or relapse 18 months before and during pregnancy, and up to 15 months after delivery; and (5) to estimate absolute and relative risks of adverse maternal and child outcomes of psychotropic treatment in pregnancy. DESIGN Retrospective cohort studies. SETTING Primary care. PARTICIPANTS Women treated for psychosis who became pregnant, and their children. INTERVENTIONS Treatment with antipsychotics, lithium or anticonvulsant mood stabilisers. MAIN OUTCOME MEASURES Discontinuation and restarting of treatment; worsening of mental health; acute pre-eclampsia/gestational hypertension; gestational diabetes; caesarean section; perinatal death; major congenital malformations; poor birth outcome (low birthweight, preterm birth, small for gestational age, low Apgar score); transient poor birth outcomes (tremor, agitation, breathing and muscle tone problems); and neurodevelopmental and behavioural disorders. DATA SOURCES Clinical Practice Research Datalink database and The Health Improvement Network primary care database. RESULTS Prescribing of psychotropic medication was relatively constant before pregnancy, decreased sharply in early pregnancy and peaked after delivery. Antipsychotic and anticonvulsant treatment increased over the study period. The recording of markers of worsening mental health peaked after delivery. Pregnancy was a strong determinant for discontinuation of psychotropic medication. However, between 40% and 76% of women who discontinued psychotropic medication before or in early pregnancy restarted treatment by 15 months after delivery. The risk of major congenital malformations, and neurodevelopmental and behavioural outcomes in valproate (multiple manufacturers) users was twice that in users of other anticonvulsants. The risks of adverse maternal and child outcomes in women who continued antipsychotic use in pregnancy were not greater than in those who discontinued treatment before pregnancy. LIMITATIONS A few women would have received parts of their care outside primary care, which may not be captured in this analysis. Likewise, the analyses were based on prescribing data, which may differ from usage. CONCLUSIONS Psychotropic medication is prescribed before, during and after pregnancy. Many women discontinue treatment before or during early pregnancy and then restart again in late pregnancy or after delivery. Our results support previous associations between valproate and adverse child outcomes but we found no evidence of such an association for antipsychotics. FUTURE WORK Future research should focus on (1) curtailing the use of sodium valproate; (2) estimating the benefits of psychotropic drug use in pregnancy; and (3) investigating the risks associated with lifestyle choices that are more prevalent among women using psychotropic drugs. FUNDING DETAILS The National Institute for Health Research Health Technology Assessment programme. PMID:27029490

  3. 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

    STUDY QUESTION How does the placenta protect the fetus from immune rejection by the mother? SUMMARY ANSWER The placenta can produce IgG that is glycosylated at one of its Fab arms (asymmetric IgG; aIgG) which can interact with other antibodies and certain leukocytes to affect local immune reactions at the junction between the two genetically distinct entities. WHAT IS KNOWN ALREADY The placenta can protect the semi-allogenic fetus from immune rejection by the immune potent mother. aIgG in serum is increased during pregnancy and returns to the normal range after giving birth. aIgG can react to antigens to form immune complexes which do not cause a subsequent immune effector reaction, including fixing complements, inducing cytotoxicity and phagocytosis, and therefore has been called ‘blocking antibody’. STUDY DESIGN, SIZE, DURATION Eighty-eight human placentas, four trophoblast cell lines (TEV-1, JAR, JEG and BeWo), primary culture of human placental trophoblasts and a gene knock-out mouse model were investigated in this study. PARTICIPANTS/MATERIALS, SETTING, METHODS The general approach included the techniques of cell culture, immunohistochemistry, in situ hybridization, immuno-electron microscopy, western blot, quantitative PCR, protein isolation, glycosylation analysis, enzyme digestion, gene sequencing, mass spectrophotometry, laser-guided microdissection, enzyme-linked immunosorbent assay, pulse chase assay, double and multiple staining to analyze protein and DNA and RNA analysis at the cellular and molecular levels. MAIN RESULTS AND THE ROLE OF CHANCE Three major discoveries were made: (i) placental trophoblasts and endothelial cells are capable of producing IgG, a significant portion of which is aberrantly glycosylated at one of its Fab arms to form aIgG; (ii) the asymmetrically glycosylated IgG produced by trophoblasts and endothelial cells can react to immunoglobulin molecules of human, rat, mouse, goat and rabbit at the Fc portion; (iii) asymmetrically 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

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

    PubMed

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

    2010-06-01

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

  5. Vitamin D supplementation in pregnancy: a systematic review.

    PubMed Central

    Harvey, Nicholas C; Holroyd, Christopher; Ntani, Georgia; Javaid, Kassim; Cooper, Philip; Moon, Rebecca; Cole, Zoe; Tinati, Tannaze; Godfrey, Keith; Dennison, Elaine; Bishop, Nicholas J; Baird, Janis; Cooper, Cyrus

    2014-01-01

    BACKGROUND: It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved. OBJECTIVES: To answer the following questions: (1) What are the clinical criteria for vitamin D deficiency in pregnant women? (2) What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)D? (3) Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)? (4) What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy? (5) Is supplementation with vitamin D in pregnancy likely to be cost-effective? METHODS: We performed a systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases [including Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR) and the Health Technology Assessment (HTA) database] were searched from inception up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary. Abstracts were reviewed by two reviewers. INCLUSION AND EXCLUSION CRITERIA: SUBJECTS: pregnant women or pregnant women and their offspring. EXPOSURE: either assessment of vitamin D status [dietary intake, sunlight exposure, circulating 25(OH)D concentration] or supplementation of participants with vitamin D or food containing vitamin D (e.g. oily fish). OUTCOMES: offspring - birthweight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes mellitus, low birthweight, serum calcium concentration, blood pressure and rickets; mother - pre-eclampsia, gestational diabetes mellitus, risk of caesarean section and bacterial vaginosis. RESULTS: Seventy-six studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence. The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes. For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)D and (1) offspring birthweight in meta-analysis of three observational studies using log-transformed 25(OH)D concentrations after adjustment for potential confounding factors [pooled regression coefficient 5.63 g/10% change maternal 25(OH)D, 95% confidence interval (CI) 1.11 to 10.16 g], but not in those four studies using natural units, or across intervention studies; (2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of six intervention studies (all found to be at high risk of bias; mean difference 0.05 mmol/l, 95% CI 0.02 to 0.05 mmol/l); and (3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis. The evidence base was insufficient to reliably answer questions 4 and 5. LIMITATIONS: Study methodology varied widely in terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition. CONCLUSIONS: The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birthweight, bone mass) or risk of bias and low quality (calcium concentrations). High-quality randomised trials are now required. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001426. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID:25025896

  6. 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

    Small for gestational age (SGA) is defined by weight (in utero estimated fetal weight or birth weight) below the 10th percentile (professional consensus). Severe SGA is SGA below the third percentile (professional consensus). Fetal growth restriction (FGR) or intra-uterine growth restriction (IUGR) usually correspond with SGA associated with evidence indicating abnormal growth (with or without abnormal uterine and/or umbilical Doppler): arrest of growth or a shift in its rate measured longitudinally (at least two measurements, 3 weeks apart) (professional consensus). More rarely, they may correspond with inadequate growth, with weight near the 10th percentile without being SGA (LE2). Birthweight curves are not appropriate for the identification of SGA at early gestational ages because of the disorders associated with preterm delivery. In utero curves represent physiological growth more reliably (LE2). In diagnostic (or reference) ultrasound, the use of growth curves adjusted for maternal height and weight, parity and fetal sex is recommended (professional consensus). In screening, the use of adjusted curves must be assessed in pilot regions to determine the schedule for their subsequent introduction at national level. This choice is based on evidence of feasibility and the absence of any proven benefits for individualized curves for perinatal health in the general population (professional consensus). Children born with FGR or SGA have a higher risk of minor cognitive deficits, school problems and metabolic syndrome in adulthood. The role of preterm delivery in these complications is linked. The measurement of fundal height remains relevant to screening after 22 weeks of gestation (Grade C). The biometric ultrasound indicators recommended are: head circumference (HC), abdominal circumference (AC) and femur length (FL) (professional consensus). They allow calculation of estimated fetal weight (EFW), which, with AC, is the most relevant indicator for screening. Hadlock's EFW formula with three indicators (HC, AC and FL) should ideally be used (Grade B). The ultrasound report must specify the percentile of the EFW (Grade C). Verification of the date of conception is essential. It is based on the crown-rump length between 11 and 14 weeks of gestation (Grade A). The HC, AC and FL measurements must be related to the appropriate reference curves (professional consensus); those modelled from College Francais d'Echographie Fetale data are recommended because they are multicentere French curves (professional consensus). Whether or not a work-up should be performed and its content depend on the context (gestational age, severity of biometric abnormalities, other ultrasound data, parents' wishes, etc.) (professional consensus). Such a work-up only makes sense if it might modify pregnancy management and, in particular, if it has the potential to reduce perinatal and long-term morbidity and mortality (professional consensus). The use of umbilical artery Doppler velocimetry is associated with better newborn health status in populations at risk, especially in those with FGR (Grade A). This Doppler examination must be the first-line tool for surveillance of fetuses with SGA and FGR (professional consensus). A course of corticosteroids is recommended for women with an FGR fetus, and for whom delivery before 34 weeks of gestation is envisaged (Grade C). Magnesium sulphate should be prescribed for preterm deliveries before 32-33 weeks of gestation (Grade A). The same management should apply for preterm FGR deliveries (Grade C). In cases of FGR, fetal growth must be monitored at intervals of no less than 2 weeks, and ideally 3 weeks (professional consensus). Referral to a Level IIb or III maternity ward must be proposed in cases of EFW <1500g, potential birth before 32-34 weeks of gestation (absent or reversed umbilical end-diastolic flow, abnormal venous Doppler) or a fetal disease associated with any of these (professional consensus). Systematic 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

  7. In Vitro Fertilization and Multiple Pregnancies

    PubMed Central

    2006-01-01

    Executive Summary Objective The objective of this health technology policy assessment was to determine the clinical effectiveness and cost-effectiveness of IVF for infertility treatment, as well as the role of IVF in reducing the rate of multiple pregnancies. Clinical Need: Target Population and Condition Typically defined as a failure to conceive after a year of regular unprotected intercourse, infertility affects 8% to 16% of reproductive age couples. The condition can be caused by disruptions at various steps of the reproductive process. Major causes of infertility include abnormalities of sperm, tubal obstruction, endometriosis, ovulatory disorder, and idiopathic infertility. Depending on the cause and patient characteristics, management options range from pharmacologic treatment to more advanced techniques referred to as assisted reproductive technologies (ART). ART include IVF and IVF-related procedures such as intra-cytoplasmic sperm injection (ICSI) and, according to some definitions, intra-uterine insemination (IUI), also known as artificial insemination. Almost invariably, an initial step in ART is controlled ovarian stimulation (COS), which leads to a significantly higher rate of multiple pregnancies after ART compared with that following natural conception. Multiple pregnancies are associated with a broad range of negative consequences for both mother and fetuses. Maternal complications include increased risk of pregnancy-induced hypertension, pre-eclampsia, polyhydramnios, gestational diabetes, fetal malpresentation requiring Caesarean section, postpartum haemorrhage, and postpartum depression. Babies from multiple pregnancies are at a significantly higher risk of early death, prematurity, and low birth weight, as well as mental and physical disabilities related to prematurity. Increased maternal and fetal morbidity leads to higher perinatal and neonatal costs of multiple pregnancies, as well as subsequent lifelong costs due to disabilities and an increased need for medical and social support. The Technology Being Reviewed IVF was first developed as a method to overcome bilateral Fallopian tube obstruction. The procedure includes several steps: (1) the woman’s egg is retrieved from the ovaries; (2) exposed to sperm outside the body and fertilized; (3) the embryo(s) is cultured for 3 to 5 days; and (4) is transferred back to the uterus. IFV is considered to be one of the most effective treatments for infertility today. According to data from the Canadian Assisted Reproductive Technology Registry, the average live birth rate after IVF in Canada is around 30%, but there is considerable variation in the age of the mother and primary cause of infertility. An important advantage of IVF is that it allows for the control of the number of embryos transferred. An elective single embryo transfer in IVF cycles adopted in many European countries was shown to significantly reduce the risk of multiple pregnancies while maintaining acceptable birth rates. However, when number of embryos transferred is not limited, the rate of IVF-associated multiple pregnancies is similar to that of other treatments involving ovarian stimulation. The practice of multiple embryo transfer in IVF is often the result of pressures to increase success rates due to the high costs of the procedure. The average rate of multiple pregnancies resulting from IVF in Canada is currently around 30%. An alternative to IVF is IUI. In spite of reported lower success rates of IUI (pregnancy rates per cycle range from 8.7% to 17.1%) it is generally attempted before IVF due to its lower invasiveness and cost. Two major drawbacks of IUI are that it cannot be used in cases of bilateral tubal obstruction and it does not allow much control over the risk of multiple pregnancies compared with IVF. The rate of multiple pregnancies after IUI with COS is estimated to be about 21% to 29%. Ontario Health Insurance Plan Coverage Currently, the Ontario Health Insurance Plan covers the cost of IVF for women with bilaterally blocked Fallopian tubes only, in which case it is funded for 3 cycles, excluding the cost of drugs. The cost of IUI is covered except for preparation of the sperm and drugs used for COS. Diffusion of Technology According to Canadian Assisted Reproductive Technology Registry data, in 2004 there were 25 infertility clinics across Canada offering IVF and 7,619 IVF cycles performed. In Ontario, there are 13 infertility clinics with about 4,300 IVF cycles performed annually. Literature Review Royal Commission Report on Reproductive Technologies The 1993 release of the Royal Commission report on reproductive technologies, Proceed With Care, resulted in the withdrawal of most IVF funding in Ontario, where prior to 1994 IVF was fully funded. Recommendations of the Commission to withdraw IVF funding were largely based on findings of the systematic review of randomized controlled trials (RCTs) published before 1990. The review showed IVF effectiveness only in cases of bilateral tubal obstruction. As for nontubal causes of infertility, there was not enough evidence to establish whether IVF was effective or not. Since the field of reproductive technology is constantly evolving, there have been several changes since the publication of the Royal Commission report. These changes include: increased success rates of IVF; introduction of ICSI in the early 1990’s as a treatment for male factor infertility; and improved embryo implantation rates allowing for the transfer of a single embryo to avoid multiple pregnancies after IVF. Studies After the Royal Commission Report: Review Strategy Three separate literature reviews were conducted in the following areas: clinical effectiveness of IVF, cost-effectiveness of IVF, and outcomes of single embryo transfer (SET) in IVF cycles. Clinical effectiveness of IVF: RCTs or meta-analyses of RCTs that compared live birth rates after IVF versus alternative treatments, where the cause of infertility was clearly stated or it was possible to stratify the outcome by the cause of infertility. Cost effectiveness of IVF: All relevant economic studies comparing IVF to alternative methods of treatment were reviewed Outcomes of IVF with SET: RCTs or meta-analyses of RCTs that compared live birth rates and multiple birth rates associated with transfer of single versus double embryos. OVID MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Library, the International Agency for Health Technology Assessment database, and websites of other health technology assessment agencies were searched using specific subject headings and keywords to identify relevant studies. Summary of Findings Comparative Clinical Effectiveness of IVF Overall, there is a lack of well composed RCTs in this area and considerable diversity in both definition and measurement of outcomes exists between trials. Many studies used fertility or pregnancy rates instead of live birth rates. Moreover, the denominator for rate calculation varied from study to study (e.g. rates were calculated per cycle started, per cycle completed, per couple, etc...). Nevertheless, few studies of sufficient quality were identified and categorized by the cause of infertility and existing alternatives to IVF. The following are the key findings: A 2005 meta-analysis demonstrated that, in patients with idiopathic infertility, IVF was clearly superior to expectant management, but there were no statistically significant differences in live birth rates between IVF and IUI, nor between IVF and gamete-intra-Fallopian transfer. A subset of data from a 2000 study showed no significant differences in pregnancy rates between IVF and IUI for moderate male factor infertility. In patients with moderate male factor infertility, standard IVF was also compared with ICSI in a 2002 meta-analysis. All studies included in the meta-analysis showed superior fertilization rates with ICSI, and the pooled risk ratio for oocyte fertilization was 1.9 (95% Confidence Interval 1.4-2.5) in favour of ICSI. Two other RCTs in this area published after the 2002 meta-analysis had similar results and further confirmed these findings. There were no RCTs comparing IVF with ICSI in patients with severe male factor infertility, mainly because based on the expert opinion, ICSI might only be an effective treatment for severe male factor infertility. Cost-Effectiveness of IVF Five economic evaluations of IVF were found, including one comprehensive systematic review of 57 health economic studies. The studies compared cost-effectiveness of IVF with a number of alternatives such as observation, ovarian stimulation, IUI, tubal surgery, varicocelectomy, etc... The cost-effectiveness of IVF was analyzed separately for different types of infertility. Most of the reviewed studies concluded that due to the high cost, IVF has a less favourable cost-effectiveness profile compared with alternative treatment options. Therefore, IVF was not recommended as the first line of treatment in the majority of cases. The only two exceptions were bilateral tubal obstruction and severe male factor infertility, where an immediate offer of IVF/ICSI might the most cost-effective option. Clinical Outcomes After Single Versus Double Embryo Transfer Strategies of IVF Since the SET strategy has been more widely adopted in Europe, all RCT outcomes of SET were conducted in European countries. The major study in this area was a large 2005 meta-analysis, followed by two other published RCTs. All of these studies reached similar conclusions: Although a single SET cycle results in lower birth rates than a single double embryo transfer (DET) cycle, the cumulative birth rate after 2 cycles of SET (fresh + frozen-thawed embryos) was comparable to the birth rate after a single DET cycle (~40%). SET was associated with a significant reduction in multiple births compared with DET (0.8% vs. 33.1% respectively in the largest RCT). Most trials on SET included women younger than 36 years old with a sufficient number of embryos available for transfer that allowed for selection of the top quality embryo(s). A 2006 RCT, however, compared SET and DET strategies in an unselected group of patients without restrictions on the woman’s age or embryo quality. This study demonstrated that SET could be applied to older women. Estimate of the Target Population Based on results of the literature review and consultations with experts, four categories of infertile patients who may benefit from increased access to IVF/ICSI were identified: Patients with severe male factor infertility, where IVF should be offered in conjunction with ICSI; Infertile women with serious medical contraindications to multiple pregnancy, who should be offered IVF-SET; Infertile patients who want to avoid the risk of multiple pregnancy and thus opt for IVF-SET; and Patients who failed treatment with IUI and wish to try IVF. Since, however, the latter indication does not reflect any new advances in IVF technology that would alter existing policy, it was not considered in this analysis. Economic Analysis Economic Review: Cost–Effectiveness of SET Versus DET Conclusions of published studies on cost-effectiveness of SET versus DET were not consistent. While some studies found that SET strategy is more cost-effective due to avoidance of multiple pregnancies, other studies either did not find any significant differences in cost per birth between SET and DET, or favoured DET as a more cost-effective option. Ontario-Based Economic Analysis An Ontario-based economic analysis compared cost per birth using three treatment strategies: IUI, IVF-SET, and IVF-DET. A decision-tree model assumed three cycles for each treatment option. Two separate models were considered; the first included only fresh cycles of IVF, while the second had a combination of fresh and frozen cycles. Even after accounting for cost-savings due to avoidance of multiple pregnancies (only short-term complications), IVF-SET was still associated with a highest cost per birth. The approximate budget impact to cover the first three indications for IVF listed above (severe male factor infertility, women with medical contraindications to multiple pregnancy, and couples who wish to avoid the risk of multiple pregnancy) is estimated at $9.8 to $12.8 million (Cdn). Coverage of only first two indications, namely, ICSI in patients with severe male factor infertility and infertile women with serious medical contraindications to multiple pregnancy, is estimated at $3.8 to $5.5 million Cdn. Other Considerations International data shows that both IVF utilization and the average number of embryos transferred in IVF cycles are influenced by IVF funding policy. The success of the SET strategy in European countries is largely due to the fact that IVF treatment is subsidized by governments. Surveys of patients with infertility demonstrated that a significant proportion (~40%) of patients not only do not mind having multiple babies, but consider twins being an ideal outcome of infertility treatment. A women’s age may impose some restrictions on the implementation of a SET strategy. Conclusions and Recommendations A review of published studies has demonstrated that IVF-SET is an effective treatment for infertility that avoids multiple pregnancies. However, results of an Ontario-based economic analysis shows that cost savings associated with a reduction in multiple pregnancies after IVF-SET does not justify the cost of universal IVF-SET coverage by the province. Moreover, the province currently funds IUI, which has been shown to be as effective as IVF for certain types of infertility and is significantly less expensive. In patients with severe male factor infertility, IVF in conjunction with ICSI may be the only effective treatment. Thus, 2 indications where additional IVF access should be considered include: IVF/ICSI for patients with severe male factor infertility IVF-SET in infertile women with serious medical contraindications to multiple pregnancy PMID:23074488