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Background: Although a number of studies have investigated correlations of maternal age with birth outcomes, an extensive assessment using age as a continuous variable is lacking. In the current study, we estimated age-specific risks of adverse birth outcomes in childbearing women. Method: National population-based data containing maternal and neonatal information were derived from the Health Promotion Administration, Taiwan. A composite adverse birth outcome was defined as at least anyone of stillbirth, preterm birth, low birth weight, macrosomia, neonatal death, congenital anomaly, and small for gestational age (SGA). Singletons were further analyzed for outcomes of live birth in relation to each year of maternal age. A log-binomial model was used to adjust for possible confounders of maternal and neonatal factors. Results: In total, 2,123,751 births between 2001 and 2010 were utilized in the analysis. The risk of a composite adverse birth outcome was significantly higher at extreme maternal ages. In specific, risks of stillbirth, neonatal death, preterm birth, congenital anomaly, and low birth weight were higher at the extremes of maternal age. Furthermore, risk of macrosomia rose proportionally with an increasing maternal age. In contrast, risk of SGA declined proportionally with an increasing maternal age. The log-binomial model showed greater risks at the maternal ages of <26 and > 30 years for a composite adverse birth outcome. Conclusions: Infants born to teenagers and women at advanced age possess greater risks for stillbirth, preterm birth, neonatal death, congenital anomaly, and low birth weight. Pregnancies at advanced age carry an additional risk for macrosomia, while teenage pregnancies carry an additional risk for SGA. The data suggest that the optimal maternal ages to minimize adverse birth outcomes are 26∼30 years. [ABSTRACT FROM AUTHOR]

Background: Established causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations and abnormal embryonic karyotype. A systematic review concluded that coagulation factor XII (FXII) deficiency was associated with RPL. However, it could not be established whether the 46 C/T SNP of FXII or low activity of FXII was a risk factor for RPL because of the small sample size. Methods and Findings: We conducted a cross-sectional and cohort study in 279 patients with two or more unexplained consecutive pregnancy losses and 100 fertile women. The association between the lupus anticoagulant (LA) activity and FXII activity was examined. The frequency of the CC, CT and TT genotypes and the FXII activity were also compared between the patients and controls. Subsequent miscarriage rates among the CC, CT, TT genotypes and according to the FXII activity was examined. LA was associated with reduced FXII activity. The CT, but not the TT, genotype was confirmed to be a risk factor for RPL in the cross-sectional study using multivariate logistic regression analysis (OR, 2.8; 95% CI, 1.37–5.85). The plasma FXII activity in the patients was similar to that in the controls. Neither low FXII activity nor the CT genotype predicted the subsequent pregnancy outcome in the cohort study. On the other hand, and intermediate FXII activity level of 85–101% was predictive of subsequent miscarriage. Conclusions: Low FXII activity was not associated with RPL. The FXII gene was found to be one of the significant susceptibility genes for RPL, similar to the FV Leiden mutation. However, the clinical influence of the CT genotype might be relatively small, because the presence/absence of this genotype did not have any predictive value for the subsequent pregnancy outcome. This was the first study indicating the influence of FXII 46C/T on further pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of published reports on pregnancy outcome following scrub and murine typhus despite these infections being leading causes of undifferentiated fever in Asia. This study aimed to relate pregnancy outcome with treatment of typhus. Methodology/Principal Findings: Data were analyzed from: i) pregnant women with a diagnosis of scrub and/or murine typhus from a fever cohort studies; ii) case series of published studies in PubMed using the search terms “scrub typhus” (ST), “murine typhus” (MT), “Orientia tsutsugamushi”, “Rickettsia tsutsugamushi”, “Rickettsia typhi”, “rickettsiae”, “typhus”, or “rickettsiosis”; and “pregnancy”, until February 2014 and iii) an unpublished case series. Fever clearance time (FCT) and pregnancy outcome (miscarriage and delivery) were compared to treatment. Poor neonatal outcome was a composite measure for pregnancies sustained to 28 weeks or more of gestation ending in stillbirth, preterm birth, or delivery of a growth restricted or low birth weight newborn. Results: There were 26 women in the fever cohort. MT and ST were clinically indistinguishable apart from two ST patients with eschars. FCTs (median [range] hours) were 25 [16–42] for azithromycin (n = 5), 34 [20–53] for antimalarials (n = 5) and 92 [6–260] for other antibiotics/supportive therapy (n = 16). There were 36.4% (8/22) with a poor neonatal outcome. In 18 years, 97 pregnancies were collated, 82 with known outcomes, including two maternal deaths. Proportions of miscarriage 17.3% (14/81) and poor neonatal outcomes 41.8% (28/67) were high, increasing with longer FCTs (p = 0.050, linear trend). Use of azithromycin was not significantly associated with improved neonatal outcomes (p = 0.610) Conclusion: The published ST and MT world literature amounts to less than 100 pregnancies due to under recognition and under diagnosis. Evidence supporting the most commonly used treatment, azithromycin, is weak. Collaborative, prospective clinical trials in pregnant women are urgently required to reduce the burden of adverse maternal and newborn outcomes and to determine the safety and efficacy of antimicrobial treatment. [ABSTRACT FROM AUTHOR]

Objective: Maternal recreational drug use may be associated with the development of fetal malformations such as gastroschisis, brain and limb defects, the aetiology due to vascular disruption during organogenesis. Using forensic hair analysis we reported evidence of recreational drug use in 18% of women with a fetal gastroschisis. Here we investigate this association in a variety of fetal malformations using the same method. Methods: In a multi-centre study, women with normal pregnancies (controls) and those with fetal abnormalities (cases) gave informed consent for hair analysis for recreational drug metabolites using mass spectrometry. Hair samples cut at the root were tested in sections corresponding to 3 month time periods (pre and periconceptual period). Results: Women whose fetus had gastroschisis, compared to women with a normal control fetus, were younger (mean age 23.78±SD4.79 years, 18–37 vs 29.79±SD6 years, 18–42, p = 0.00001), were more likely to have evidence of recreational drug use (15, 25.4% vs 21, 13%, OR2.27, 95thCI 1.08–4.78, p = 0.028), and were less likely to report periconceptual folic acid use (31, 53.4% vs 124, 77.5%, OR0.33, 95thCI 0.18–0.63, p = 0.001). Age-matched normal control women were no less likely to test positive for recreational drugs than women whose fetus had gastroschisis. After accounting for all significant factors, only young maternal age remained significantly associated with gastroschisis. Women with a fetus affected by a non-neural tube central nervous system (CNS) anomaly were more likely to test positive for recreational drugs when compared to women whose fetus was normal (7, 35% vs 21, 13%, OR3.59, 95th CI1.20–10.02, p = 0.01). Conclusions: We demonstrate a significant association between non neural tube CNS anomalies and recreational drug use in the periconceptual period, first or second trimesters, but we cannot confirm this association with gastroschisis. We confirm the association of gastroschisis with young maternal age. [ABSTRACT FROM AUTHOR]

Background: Recent studies have indicated the use of gonadotropin-releasing hormone antagonists (GnRH-ant) as an adjuvant treatment to prevent premature luteinization (PL) and improve the clinical outcomes in patients undergoing controlled ovarian stimulation (COS) with intrauterine insemination (IUI). However, the results of these studies are conflicting. Methods: We conducted a systematic review and meta-analysis of randomized trials aiming to compare the clinical efficacy of GnRH-ant in COS/IUI cycles. Twelve studies were identified that met inclusion criteria and comprised 2,577 cycles assigned to COS/IUI combined GnRH-ant or COS/IUI alone. Results: Meta-analysis results suggested that GnRH-ant can significantly increase the clinical pregnancy rate (CPR) (OR = 1.42; 95% CI, 1.13–1.78) and decrease the PL rate (OR = 0.22, 95% CI, 0.16–0.30) in COS/IUI cycles. Subgroup analysis results suggested statistically significant improvement in the CPR in non-PCOS patients (OR = 1.54; 95% CI, 1.03–2.31) but not in the PCOS population (OR = 1.65; 95% CI, 0.93–2.94) and multiple mature follicle cycles (OR = 1.87; 95% CI, 0.27–12.66). There were no difference in the miscarriage and multiple pregnancy rates between the groups. Conclusion: This meta-analysis suggested that GnRH-ant can reduce the incidence of PL and increase the CPR when used in COS/IUI cycles, and it was especially useful for non-PCOS patients. However, evidence to support its use in PCOS patients is still insufficient [ABSTRACT FROM AUTHOR]

: Louise Kenny and colleagues conduct a population-based cohort study in Denmark to assess the likelihood of stillbirth, miscarriage, and ectopic pregnancy following cesarean section compared to women who gave birth by vaginal delivery. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation between maternal magnetic field (MF) exposure in daily life and embryonic development. Methods: A cross-sectional study was conducted among 149 pregnant women who were seeking induced abortion of unwanted pregnancies. Participating women were asked to wear an EMDEX Lite magnetic field meter for a 24-h period to obtain MF exposure level within 4 weeks following the abortion. Embryonic bud and sac lengths were measured through B-mode ultrasound before the surgical abortion. Embryo sections were prepared and examined for histological changes, and the apoptosis status of the deciduas was examined using the TUNEL apoptosis assay. Results: Embryonic bud length was inversely associated with maternal daily MF exposure level; the association was statistically significant at the time-weighted-average and 75th percentile of MF exposure levels, with coefficients of −3.09 (P = 0.0479) and −3.07(P = 0.0228), respectively. Logistic regression for examining the risk of higher MF exposure indicated that women with her 75th percentile of daily MF measurements ≥0.82 mG had a 3.95-fold risk of having a fetus with a shorter embryonic bud length than those whose daily MF exposure were <0.82 mG. MF exposure was associated with a higher degree of apoptosis, but the association was not statistically significant. We failed to find a statistical correlation between MF exposure and embryonic sac length and histological changes in the first trimester. Conclusion: Prenatal MF exposure may have an adverse effect on embryonic development. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the use of manual vacuum aspiration in postabortion care in Malawi between 2008–2012. Methods: A retrospective cross-sectional study was done at the referral hospital Queen Elisabeth Central Hospital, and the two district hospitals of Chiradzulu and Mangochi. The data were collected simultaneously at the three sites from Feb-March 2013. All records available for women admitted to the gynaecological ward from 2008-2012 were reviewed. Women who had undergone surgical uterine evacuation after incomplete abortion were included and the use of manual vacuum aspiration versus sharp curettage was analysed. Results: Altogether, 5121 women were included. One third (34.2%) of first trimester abortions were treated with manual vacuum aspiration, while all others were treated with sharp curettage. There were significant differences between the hospitals and between years. Overall there was an increase in the use of manual vacuum aspiration from 2008 (19.7%) to 2009 (31.0%), with a rapid decline after 2010 (28.5%) ending at only 4.9% in 2012. Conversely there was an increase in use of sharp curettage in all hospitals from 2010 to 2012. Conclusion: Use of manual vacuum aspiration as part of the postabortion care in Malawi is rather low, and decreased from 2010 to 2012, while the use of sharp curettage became more frequent. This is in contrast with current international guidelines. [ABSTRACT FROM AUTHOR]

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

Aneuploidy in fetal chromosomes is one of the causes of pregnancy loss and of congenital birth defects. It is known that the frequency of oocyte aneuploidy increases with the human maternal age. Recent data have highlighted the contribution of cohesin complexes in the correct segregation of meiotic chromosomes. In mammalian oocytes, cohesion is established during the fetal stages and meiosis-specific cohesin subunits are not replenished after birth, raising the possibility that the long meiotic arrest of oocytes facilitates a deterioration of cohesion that leads to age-related increases in aneuploidy. We here examined the cohesin levels in dictyate oocytes from different age groups of humans and mice by immunofluorescence analyses of ovarian sections. The meiosis-specific cohesin subunits, REC8 and SMC1B, were found to be decreased in women aged 40 and over compared with those aged around 20 years (P<0.01). Age-related decreases in meiotic cohesins were also evident in mice. Interestingly, SMC1A, the mitotic counterpart of SMC1B, was substantially detectable in human oocytes, but little expressed in mice. Further, the amount of mitotic cohesins of mice slightly increased with age. These results suggest that, mitotic and meiotic cohesins may operate in a coordinated way to maintain cohesions over a sustained period in humans and that age-related decreases in meiotic cohesin subunits impair sister chromatid cohesion leading to increased segregation errors. [ABSTRACT FROM AUTHOR]

: Radek Bukowski and colleagues conducted a case control study in 59 US hospitals to determine the relationship between fetal growth and stillbirth, and find that both restrictive and excessive growth could play a role. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Cigarette smoking can harm fertility, but the existing research has targeted primarily on ovarian follicles, embryos or sex hormone. In this study, we tested cigarette smoke extract on ovulation, oocyte morphology and ovarian gene expression associated with inhibition of oxidative stress using C57BL/6 mice. Mice in the experimental group were administered a cigarette smoke extract (CSE) solution (2 mg/ml) orally daily, while the blank control group was given dimethylsulfoxide (DMSO). A positive control group (menadione) was used that received an intraperitoneal injection of 15 mg/kg menadione in oil solution daily. We found that the CSE group manifested a reduced diameter of zona pellucida-free oocyte (ZP-free OD) and a morphologically misshapen first polar body (PB). Our results suggest that CSE exposure is associated with a shrink size and poor quality of oocytes. Quitting smoking is a wise choice to ensure good fertility. [ABSTRACT FROM AUTHOR]

While grief, emotional distress and other mental health conditions have been associated with pregnancy loss, less is known about the mental health impact of these events during subsequent pregnancies and births. This paper examined the impact of any type of pregnancy loss on mental health in a subsequent pregnancy and postpartum. Data were obtained from a sub-sample (N = 584) of the 1973-78 cohort of the Australian Longitudinal Study on Women's Health, a prospective cohort study that has been collecting data since 1996. Pregnancy loss was defined as miscarriage, termination due to medical reasons, ectopic pregnancy and stillbirth. Mental health outcomes included depression, anxiety, stress or distress, sadness or low mood, excessive worry, lack of enjoyment, and feelings of guilt. Demographic factors and mental health history were controlled for in the analysis. Women with a previous pregnancy loss were more likely to experience sadness or low mood (AOR = 1.75, 95% CI: 1.11 to 2.76, p = 0.0162), and excessive worry (AOR = 2.01, 95% CI: 1.24 to 3.24, p = 0.0043) during a subsequent pregnancy, but not during the postpartum phase following a subsequent birth. These results indicate that while women who have experienced a pregnancy loss are a more vulnerable population during a subsequent pregnancy, these deficits are not evident in the postpartum. [ABSTRACT FROM AUTHOR]

Objective: To elucidate the mechanism by which embryo-resorption and preterm birth were enhanced by pathogenic CpG motif and to develop a counter strategy for normal pregnancy outcome. Methods: This is an animal model-based study. In pregnant nonobese diabetic (NOD) mice and wild-type (WT) mice in the same strain background, an infection was mimicked by toll-like receptor 9 (TLR9) activation through CpG1826-injection. In vivo inactivation of IL-10 was performed to enhance pregnancy loss. Regulatory T cells induced by FTY720 in vitro from splenic CD4+CD25−Foxp3− cells (iTreg cells) were transferred to improve pregnancy outcomes in NOD mice. Results: Embryo-resorption and preterm birth were readily induced by CpG1826 in NOD mice, but not in WT mice. However, inactivation of IL-10 using neutralizing antibody injections enhanced pregnancy loss in WT mice exposed to CpG, while adoptive transfer of iTreg cells increased decidual Foxp3+ Treg cells and IL-10+ cell number and rescued pregnancy. Conclusions: NOD mice are prone to abortion and preterm birth. This can be attributed to lacking Treg cells and insufficient IL-10 expression. Adoptive transfer of iTreg cells can rescue CpG-mediated pregnancy failure. [ABSTRACT FROM AUTHOR]

Background: We have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 (MIC-1) levels are lower in women in early pregnancy who are destined to miscarriage. While promising, the diagnostic performance of measuring MIC-1 alone was not sufficient for it to be a useful predictive test for miscarriage. Besides MIC-1, there are other cytokines, as well as chemokines, involved in facilitating early pregnancy. We reasoned that screening these factors in maternal plasma could uncover other predictive markers of miscarriage. Methods: This was a nested case control study, of 78 women from a prospective study of 462 attending the Early Pregnancy Assessment Unit in the first trimester (EPAU) with a threatened miscarriage; 34 of these subsequently miscarried (cases) and 44 went on to have a normal delivery (controls) Cytokines IL-1β, IL-6 and IL-10, and the chemokines, CXCL8, CCL2, CCL5, CCL7 and CX3CL1 were measured in plasma from our cohort. Results: The cytokines IL-1β, IL-6, IL-10 and the chemokine CXCL8 were not detectable in first trimester plasma. The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in all samples but levels did not vary across 5–12 weeks of gestation among controls. Plasma levels of these chemokines were no different in the miscarriage cohort compared to controls. Conclusion: The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in plasma during the first trimester while IL-1β, IL-6, IL-10 and CXCL8 were not. However, none of the cytokines and chemokines screened were different in maternal plasma in cases or controls. These therefore do not appear to have potential for application as predictive biomarkers of miscarriage. [ABSTRACT FROM AUTHOR]

Objective: We examined the association between occupational lifting during pregnancy and risk of fetal death and preterm birth using a job exposure matrix (JEM). Methods: For 68,086 occupationally active women in the Danish National Birth Cohort, interview information on occupational lifting was collected around gestational week 16. We established a JEM based on information from women, who were still pregnant when interviewed. The JEM provided mean total loads lifted per day within homogeneous exposure groups as informed by job and industry codes. All women were assigned an exposure estimate from the JEM. We used Cox regression models with gestational age as underlying time variable and adjustment for covariates. Results: We observed 2,717 fetal deaths and 3,128 preterm births within the study cohort. No exposure-response relation was observed for fetal death, but for women with a prior fetal death, we found a hazard ratio (HR) of 2.87 (95% CI 1.37, 6.01) for stillbirth (fetal death ≥22 completed gestational weeks) among those who lifted >200 kg/day. For preterm birth, we found an exposure-response relation for primigravid women, reaching a HR of 1.43 (95% CI 1.13, 1.80) for total loads >200 kg per day. These findings correspond to an excess fraction of 11% for stillbirth and 10% for preterm birth. Conclusion: We found an increased risk of stillbirth among women with a prior fetal death, who lifted >200 kg/day, and an exposure-response relationship between occupational lifting and preterm birth among primigravid women. The study adds to a large body of prospective studies on occupational lifting and adverse pregnancy outcomes by refined exposure assessment. [ABSTRACT FROM AUTHOR]

Background: The placenta plays a crucial role during pregnancy for growth and development of the fetus. Less than optimal placental performance may result in morbidity or even mortality of both mother and fetus. Awareness among pediatricians, however, of the benefit of placental findings for neonatal care, is limited. Objectives: To provide a systematic overview of the relation between placental lesions and neonatal outcome. Data sources: Pubmed database, reference lists of selected publications and important research groups in the field. Study appraisal and synthesis methods: We systematically searched the Pubmed database for literature on the relation between placental lesions and fetal and neonatal mortality, neonatal morbidity and neurological outcome. We conducted three separate searches starting with a search for placental pathology and fetal and neonatal mortality, followed by placental pathology and neonatal morbidity, and finally placental pathology and neurological development. We limited our search to full-text articles published in English from January 1995 to October 2013. We refined our search results by selecting the appropriate articles from the ones found during the initial searches. The first selection was based on the title, the second on the abstract, and the third on the full article. The quality of the selected articles was determined by using the Newcastle-Ottawa Quality Assessment Scale. Results: Placental lesions are one of the main causes of fetal death, where placental lesions consistent with maternal vascular underperfusion are most important. Several neonatal problems are also associated with placental lesions, whereby ascending intrauterine infection (with a fetal component) and fetal thrombotic vasculopathy constitute the greatest problem. Conclusions: The placenta plays a key role in fetal and neonatal mortality, morbidity, and outcome. Pediatricians should make an effort to obtain the results of placental examinations. [ABSTRACT FROM AUTHOR]

Introduction: There are an increasing number of reports of pregnancy in transplant recipients but many questions remain regarding the effect of the transplant on pregnancy outcome, the pregnancy on the graft and the medication on the fetus. The majority of studies reporting outcomes in transplant recipients have focused on women with kidney transplants, and have included retrospective, voluntary registries or single centre studies. Methods: The UK Obstetric Surveillance System (UKOSS) was used to prospectively identify all pregnant women with a liver or cardiothoracic transplant in the United Kingdom, between January 2007 and January 2012. Data were collected on demographics, transplant characteristics, immunosuppression regimens, antenatal care, maternal, graft and neonatal outcomes. In an exploratory analysis, we tested for associations between “poor fetal outcome” and medications used before or during pregnancy. Results and conclusions: We report 62 pregnancies in 56 liver transplant recipients and 14 pregnancies in 14 cardiothoracic transplant recipients (including 10 heart, three lung and one heart-lung recipient). Liver transplant recipients, in comparison to cardiothoracic, had similar livebirth rates (92% vs. 87%) but better fetal outcomes (median gestational age 38 weeks vs. 35 weeks; median birthweight 2698 g vs. 2365 g), fewer caesarean deliveries (47% vs. 62%), fewer maternal intensive care (ICU) admissions (19% vs. 29%) and fewer neonatal ICU admissions (25% vs. 54%). Nine women (12%) were taking mycophenolate mofetil at conception, which was associated with adverse fetal outcomes. Pregnancy in transplant recipients may have successful outcomes, but complication rates are high, emphasising the role of pre-conception counselling and further research into the long-term effect on maternal and graft survival rates. [ABSTRACT FROM AUTHOR]

Exposure to fine particulate air pollution (PM2.5) is strongly associated with cardiovascular morbidity and mortality. Exposure to PM2.5 during pregnancy promotes reduced birthweight, and the associated adverse intrauterine conditions may also promote adult risk of cardiovascular disease. Here, we investigated the potential for in utero exposure to diesel exhaust (DE) air pollution, a major source of urban PM2.5, to promote adverse intrauterine conditions and influence adult susceptibility to disease. We exposed pregnant female C57Bl/6J mice to DE (≈300 µg/m3 PM2.5, 6 hrs/day, 5 days/week) from embryonic day (E) 0.5 to 17.5. At E17.5 embryos were collected for gravimetric analysis and assessed for evidence of resorption. Placental tissues underwent pathological examination to assess the extent of injury, inflammatory cell infiltration, and oxidative stress. In addition, some dams that were exposed to DE were allowed to give birth to pups and raise offspring in filtered air (FA) conditions. At 10-weeks of age, body weight and blood pressure were measured. At 12-weeks of age, cardiac function was assessed by echocardiography. Susceptibility to pressure overload-induced heart failure was then determined after transverse aortic constriction surgery. We found that in utero exposure to DE increases embryo resorption, and promotes placental hemorrhage, focal necrosis, compaction of labyrinth vascular spaces, inflammatory cell infiltration and oxidative stress. In addition, we observed that in utero DE exposure increased body weight, but counterintuitively reduced blood pressure without any changes in baseline cardiac function in adult male mice. Importantly, we observed these mice to have increased susceptibility to pressure-overload induced heart failure, suggesting this in utero exposure to DE ‘reprograms’ the heart to a heightened susceptibility to failure. These observations provide important data to suggest that developmental exposure to air pollution may strongly influence adult susceptibility to cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: The association between cholera in pregnancy and negative fetal outcome has been described since the 19th century. However, there is limited published literature on the subject. We describe pregnancy outcomes from a specialized multidisciplinary hospital unit at the onset of a large cholera outbreak in Haiti in 2010 and 2011. Methods: Pregnant women with cholera were hospitalized in a specialized unit within the MSF hospital compound in Léogâne and treated using standard cholera treatment guidelines but with earlier, more intense fluid replacement. All women had intravenous access established at admission regardless of their hydration status, and all received antibiotic treatment. Data were collected on patient demographics, pregnancy and cholera status, and pregnancy outcome. In this analysis we calculated risk ratios for fetal death and performed logistic regression analysis to control for confounding factors. Results: 263 pregnant women with cholera were hospitalized between December 2010 and July 2011. None died during hospitalization, 226 (86%) were discharged with a preserved pregnancy and 16 (6%) had live fullterm singleton births, of whom 2 died within the first 5 days postpartum. The remaining 21 pregnancies (8%) resulted in intrauterine fetal death. The risk of fetal death was associated with factors reflecting severity of the cholera episode: after adjusting for confounding factors, the strongest risk factor for fetal death was severe maternal dehydration (adjusted risk ratio for severe vs. mild dehydration was 9.4, 95% CI 2.5–35.3, p = 0.005), followed by severe vomiting (adjusted risk ratio 5.1, 95% 1.1–23.8, p = 0.041). Conclusion: This is the largest cohort of pregnant women with cholera described to date. The main risk factor identified for fetal death was severity of dehydration. Our experience suggests that establishing specialized multidisciplinary units which facilitate close follow-up of both pregnancy and dehydration status due to cholera could be beneficial for patients, especially in large epidemics. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the risk of spontaneous abortion after use of antidepressant medication during pregnancy. Methods: From the Danish Medical Birth Registry and the Danish National Hospital Registry, we identified all pregnancies leading to in- or outpatient contacts in Denmark from February 1997 to December 2008. The Danish Registry of Medicinal Product Statistics provided information on the women's prescriptions for antidepressants during pregnancy. We obtained information on women who were diagnosed with depression from the Danish Psychiatric Central Registry. Adjusted relative risks (aRR) of spontaneous abortion were estimated according to exposure to antidepressants or maternal depression using binomial regression. Results: Of the 1,005,319 pregnancies (547,300 women) identified, 114,721 (11.4%) ended in a spontaneous abortion. We identified 22,061 pregnancies exposed to antidepressants and 1,843 with a diagnosis of depression with no antidepressant use, of which 2,637 (12.0%) and 205 (11.1%) ended in a spontaneous abortion, respectively. Antidepressant exposure was associated with an aRR of 1.14 (95% confidence interval (CI) 1.10–1.18) for spontaneous abortion compared with no exposure to antidepressants. Among women with a diagnosis of depression, the aRR for spontaneous abortion after any antidepressant exposure was 1.00 (95% CI 0.80–1.24). No individual selective serotonin reuptake inhibitor (SSRI) was associated with spontaneous abortions. In unadjusted analyses, we found that mirtazapine, venlafaxine, and duloxetine were associated with spontaneous abortions among women with depression but we had no information on potential differences in disease severity and only few pregnancies were exposed in the population. Conclusion: We identified a slightly increased risk of spontaneous abortion associated with the use of antidepressants during pregnancy. However, among women with a diagnosis of depression, antidepressants in general or individual SSRI in particular were not associated with spontaneous abortions. Further studies are warranted on the newer non-SSRI antidepressants, as we had insufficient data to adjust for important confounding factors. [ABSTRACT FROM AUTHOR]

Objective: Small for gestational age (SGA) infants comprise up to 50% of all stillbirths and a minority are detected before birth. We aimed to develop and validate early pregnancy predictive models for SGA infants. Methods: 5628 participants from SCOPE, a prospective study of nulliparous pregnant women, were interviewed at 15±1 weeks’ gestation. Fetal anthropometry, uterine and umbilical Doppler studies were performed at 20±1 weeks’. The cohort was divided into training (n = 3735) and validation datasets (n = 1871). All-SGA (birthweight <10th customised centile), Normotensive-SGA (SGA with normotensive mother) and Hypertensive-SGA (SGA with mother who developed hypertension) were the primary outcomes. Multivariable analysis was performed using stepwise logistic regression firstly using clinical variables and then with clinical and ultrasound variables. Receiver operator curves were constructed and areas under the curve (AUC) calculated. Results: 633 infants (11.3%) in the whole cohort were SGA; 465 (8.3%) Normotensive-SGA and 165 (3.0%) Hypertensive-SGA. In the training dataset risk factors for All-SGA at 15±1 weeks’ included: family history of coronary heart disease, maternal birthweight <3000 g and 3000 g to 3499 g compared with ≥3500 g, >12 months to conceive, university student, cigarette smoking, proteinuria, daily vigorous exercise and diastolic blood pressure ≥80. Recreational walking ≥4 times weekly, rhesus negative blood group and increasing random glucose were protective. AUC for clinical risk factors was 0.63. Fetal abdominal or head circumference z scores <10th centile and increasing uterine artery Doppler resistance at 20±1 weeks’ were associated with increased risk. Addition of these parameters increased the AUC to 0.69. Clinical predictors of Normotensive and Hypertensive-SGA were sub-groups of All-SGA predictors and were quite different. The combined clinical and ultrasound AUC for Normotensive and Hypertensive-SGA were 0.69 and 0.82 respectively. Conclusion: Predictors for SGA of relevance to clinical practice were identified. The identity and predictive potential differed in normotensive women and those who developed hypertension. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-related (PR) deaths are often a result of direct obstetric complications occurring at childbirth. Methods and Findings: To estimate the burden of and characterize risk factors for PR mortality, we evaluated deaths that occurred between 2003 and 2008 among women of childbearing age (15 to 49 years) using Health and Demographic Surveillance System data in rural western Kenya. WHO ICD definition of PR mortality was used: “the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death”. In addition, symptoms and events at the time of death were examined using the WHO verbal autopsy methodology. Deaths were categorized as either (i) directly PR: main cause of death was ascribed as obstetric, or (ii) indirectly PR: main cause of death was non-obstetric. Of 3,223 deaths in women 15 to 49 years, 249 (7.7%) were PR. One-third (34%) of these were due to direct obstetric causes, predominantly postpartum hemorrhage, abortion complications and puerperal sepsis. Two-thirds were indirect; three-quarters were attributable to human immunodeficiency virus (HIV/AIDS), malaria and tuberculosis. Significantly more women who died in lower socio-economic groups sought care from traditional birth attendants (p = 0.034), while less impoverished women were more likely to seek hospital care (p = 0.001). The PR mortality ratio over the six years was 740 (95% CI 651–838) per 100,000 live births, with no evidence of reduction over time (χ2 linear trend = 1.07; p = 0.3). Conclusions: These data supplement current scanty information on the relationship between infectious diseases and poor maternal outcomes in Africa. They indicate low uptake of maternal health interventions in women dying during pregnancy and postpartum, suggesting improved access to and increased uptake of skilled obstetric care, as well as preventive measures against HIV/AIDS, malaria and tuberculosis among all women of childbearing age may help to reduce pregnancy-related mortality. [ABSTRACT FROM AUTHOR]

Ectopic pregnancy (EP) is difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a ‘pregnancy of unknown location’ (PUL), and diagnosis and exclusion of EP is challenging due to a lack of reliable biomarkers. The objective of this study was to identify novel diagnostic biomarkers for EP. Shotgun proteomics, incorporating combinatorial-ligand library pre-fractionation, was used to interrogate pooled sera (n = 40) from women undergoing surgery for EP, termination of viable intrauterine pregnancy and management of non-viable intrauterine pregnancy. Western blot was used to validate results in individual sera. ELISAs were developed to interrogate sera from women with PUL (n = 120). Sera were collected at time of first symptomatic presentation and categorized according to pregnancy outcome. The main outcome measures were differences between groups and area under the receiver operating curve (ROC). Proteomics identified six biomarker candidates. Western blot detected significant differences in levels of two of these candidates. ELISA of sera from second cohort revealed that these differences were only significant for one of these candidates, fibronectin. ROC analysis of ability of fibronectin to discriminate EP from other pregnancy outcomes suggested that fibronectin has diagnostic potential (ROC 0.6439; 95% CI 0.5090 to 0.7788; P>0.05), becoming significant when ‘ambiguous’ medically managed PUL excluded from analysis (ROC 0.6538; 95% CI 0.5158 to 0.7918; P<0.05). Fibronectin may make a useful adjunct to future multiplex EP diagnostic tests. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) in high doses inhibits placental multidrug resistance P-glycoprotein (P-gp - Abcb1a/b) and breast cancer resistance protein (BCRP - Abcg2). This potentially impairs fetal protection against harmful factors in the maternal circulation. However, it is unknown whether LPS exposure, at doses that mimic sub-lethal clinical infection, alters placental multidrug resistance. We hypothesized that sub-lethal (fetal) LPS exposure reduces placental P-gp activity. Acute LPS (n = 19;150 µg/kg; ip) or vehicle (n = 19) were given to C57BL/6 mice at E15.5 and E17.5. Placentas and fetal-units were collected 4 and 24 h following injection. Chronic LPS (n = 6; 5 µg/kg/day; ip) or vehicle (n = 5) were administered from E11.5–15.5 and tissues were collected 4 h after final treatment. P-gp activity was assessed by [3H]digoxin accumulation. Placental Abcb1a/b, Abcg2, interleukin-6 (Il-6), Tnf-α, Il-10 and toll-like receptor-4 (Tlr-4) mRNA were measured by qPCR. Maternal plasma IL-6 was determined. At E15.5, maternal IL-6 was elevated 4 h after single (p<0.001) and chronic (p<0.05) LPS, but levels had returned to baseline by 24 h. Placental Il-6 mRNA was also increased after acute and chronic LPS treatments (p<0.05), whereas Abcb1a/b and Abcg2 mRNA were unaffected. However, fetal [3H]digoxin accumulation was increased (p<0.05) 4 h after acute LPS, and maternal [3H]digoxin myocardial accumulation was increased (p<0.05) in mice exposed to chronic LPS treatments. There was a negative correlation between fetal [3H]digoxin accumulation and placental size (p<0.0001). Acute and chronic sub-lethal LPS exposure resulted in a robust inflammatory response in the maternal systemic circulation and placenta. Acute infection decreased placental P-gp activity in a time- and gestational age-dependent manner. Chronic LPS decreased P-gp activity in the maternal myocardium and there was a trend for fetuses with smaller placentas to accumulate more P-gp substrate than their larger counterparts. Collectively, we demonstrate that acute sub-lethal LPS exposure during pregnancy impairs fetal protection against potentially harmful xenobiotics in the maternal circulation. [ABSTRACT FROM AUTHOR]

Background: Labour induction should be performed where benefit outweighs potential harm, however epidemiology of induction in lower-income countries is not well described. We used the WHO Global Survey dataset to describe the epidemiology and outcomes of labour induction in 192,538 deliveries in 253 facilities across 16 countries in Africa and Asia. Methods: Data was analyzed separately for Africa and Asia. Prevalence of indications, methods, success and characteristics associated with labour induction were determined. Multilevel logistic regression was used to determine the relationship between induction (with medical indication and elective) and maternal/perinatal outcomes. Results: Induction accounted for 4.4% (Africa) and 12.1% (Asia) of deliveries. Oxytocin alone was the most common method (45.9% and 37.5%) and success rates were generally over 80%. Medically indicated inductions were associated with increased adjusted odds of Apgar <7 at 5 minutes, low birthweight, NICU admission and fresh stillbirth in both regions. The odds of caesarean section in Africa were reduced (Adj OR 0.61, 95%CI 0.42–0.88). Elective induction was associated with increased adjusted odds of NICU (Africa) and ICU (Asia) admissions. Discussion: Induction was generally less common than in higher-income countries. Prostaglandin use was uncommon despite evidence supporting use. Induction for medical indications may be associated with poorer outcomes due to maternal baseline risks. Despite one-third of elective inductions occurring at <39 weeks, the risk of maternal, fetal and neonatal mortality was not elevated following elective inductions. [ABSTRACT FROM AUTHOR]

Background: Fetal and neonatal mortality rates are essential indicators of population health, but variations in recording of births and deaths at the limits of viability compromises international comparisons. The World Health Organization recommends comparing rates after exclusion of births with a birth weight less than 1000 grams, but many analyses of perinatal outcomes are based on gestational age. We compared the effects of using a 1000-gram birth weight or a 28-week gestational age threshold on reported rates of fetal and neonatal mortality in Europe. Methods: Aggregated data from 2004 on births and deaths tabulated by birth weight and gestational age from 29 European countries/regions participating in the Euro-Peristat project were used to compute fetal and neonatal mortality rates using cut-offs of 1000-grams and 28-weeks (2.8 million total births). We measured differences in rates between and within countries using the Wilcoxon signed rank test and 95% confidence intervals, respectively. Principal Findings: For fetal mortality, rates based on gestational age were significantly higher than those based on birth weight (p<0.001), although these differences varied between countries. The use of a 1000-gram threshold included 8823 fetal deaths compared with 9535 using a 28-week threshold (difference of 712). In contrast, the choice of a cut-off made little difference for comparisons of neonatal deaths (difference of 16). Neonatal mortality rates differed minimally, by under 0.1 per 1000 in most countries (p = 0.370). Country rankings were comparable with both thresholds. Conclusions: Neonatal mortality rates were not affected by the choice of a threshold. However, the use of a 1000-gram threshold underestimated the health burden of fetal deaths. This may in part reflect the exclusion of growth restricted fetuses. In high-income countries with a good measure of gestational age, using a 28-week threshold may provide additional valuable information about fetal deaths occurring in the third trimester. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss (RPL) in polycystic ovary syndrome (PCOS), which occurs in ∼50% of total pregnancies is a frequent obstetric complication. Among the several hypotheses, insulin resistance (IR), obesity and hyperhomocysteinemia (HHcy) play significant role/s in RPL. This study was conducted to assess the link between elevated levels of homocysteine and IR in PCOS-associated women with RPL in Kolkata, India. A retrospective study was conducted of one hundred and twenty six PCOS women (<30 years) who experienced two or more spontaneous abortions during the first trimester presenting to Institute of Reproductive Medicine (IRM) in Kolkata during the period of March 2008 through February 2011. One hundred and seventeen non-PCOS subjects with matching age range were randomly chosen as controls. Incidence of HHcy and IR was 70.63% (n = 89) and 56.34% (n = 71), respectively, in RPL-affected PCOS population which was significantly higher (p<0.04; p<0.0001) when compared to the non-PCOS set (HHcy: 57.26%; IR: 6.83%). Rates of miscarriage were significantly higher (p<0.008; p<0.03) in hyperhomocysteinemia-induced miscarriage when compared to the normohomocysteinemic segment (PCOS: 70.63% vs.29.36% & non-PCOS: 57.26% vs. 42.73%) along with the insulin resistant (p<0.04; p<0.0001) population (PCOS: 70.63% vs. 56.34% & non-PCOS: 57.26% vs. 6.83%) in both groups. A probabilistic causal model evaluated HHcy as the strongest plausible factor for diagnosis of RPL. A probability percentage of 43.32% in the cases of HHcy- mediated RPL suggests its increased tendency when compared to IR mediated miscarriage (37.29%), further supported by ROC-AUC (HHcy: 0.778vs. IR: 0.601) values. Greater susceptibility towards HHcy may increase the incidence for miscarriage in women in India and highlights the need to combat the condition in RPL control programs in the subcontinent. [ABSTRACT FROM AUTHOR]

Background: There is evidence that induction of labour (IOL) around term reduces perinatal mortality and caesarean delivery rates when compared to expectant management of pregnancy (allowing the pregnancy to continue to await spontaneous labour or definitive indication for delivery). However, it is not clear whether IOL in women with a previous caesarean section confers the same benefits. The aim of this study was to describe outcomes of IOL at 39–41 weeks in women with one previous caesarean delivery and to compare outcomes of IOL or planned caesarean delivery to those of expectant management. Methods and Findings: We performed a population-based retrospective cohort study of singleton births greater than 39 weeks gestation, in women with one previous caesarean delivery, in Scotland, UK 1981–2007 (n = 46,176). Outcomes included mode of delivery, perinatal mortality, neonatal unit admission, postpartum hemorrhage and uterine rupture. 40.1% (2,969/7,401) of women who underwent IOL 39–41 weeks were ultimately delivered by caesarean. When compared to expectant management IOL was associated with lower odds of caesarean delivery (adjusted odds ratio [AOR] after IOL at 39 weeks of 0.81 [95% CI 0.71–0.91]). There was no significant effect on the odds of perinatal mortality but greater odds of neonatal unit admission (AOR after IOL at 39 weeks of 1.29 [95% CI 1.08–1.55]). In contrast, when compared with expectant management, elective repeat caesarean delivery was associated with lower perinatal mortality (AOR after planned caesarean at 39 weeks of 0.23 [95% CI 0.07–0.75]) and, depending on gestation, the same or lower neonatal unit admission (AOR after planned caesarean at 39 weeks of 0.98 [0.90–1.07] at 40 weeks of 1.08 [0.94–1.23] and at 41 weeks of 0.77 [0.60–1.00]). Conclusions: A more liberal policy of IOL in women with previous caesarean delivery may reduce repeat caesarean delivery, but increases the risks of neonatal complications. [ABSTRACT FROM AUTHOR]

Background: The incidence of several adverse pregnancy outcomes including fetal growth restriction are higher in pregnancies where the fetus is male, leading to suggestions that placental insufficiency is more common in these fetuses. Placental insufficiency associated with fetal growth restriction may be identified by multi-vessel Doppler assessment, but little evidence exists regarding sex specific differences in these Doppler indices or placental function. This study aims to investigate sex specific differences in fetal and placental perfusion and to correlate these changes with intra-partum outcome. Methods and Findings: This is a prospective cohort study. We measured Doppler indices of 388 term pregnancies immediately prior to the onset of active labour (≤3 cm dilatation). Fetal sex was unknown at the time of the ultrasound assessment. Information from the ultrasound scan was not made available to clinical staff. Case notes and electronic records were reviewed following delivery. We report significantly lower Middle Cerebral artery pulsatility index (1.34 vs. 1.43, p = 0.004), Middle Cerebral artery peak velocity (53.47 cm/s vs. 58.10 cm/s, p = <0.001), and Umbilical venous flow/kg (56 ml/min/kg vs. 61 ml/min/kg, p = 0.02) in male fetuses. These differences however, were not associated with significant differences in intra-partum outcome. Conclusion: Sex specific differences in feto-placental perfusion indices exist. Whilst the physiological relevance of these is currently unknown, the identification of these differences adds to our knowledge of the physiology of male and female fetuses in utero. A number of disease processes have now been shown to have an association with changes in fetal haemodynamics in-utero, as well as having a sex bias, making further investigation of the sex specific differences present during fetal life important. Whilst the clinical application of these findings is currently limited, the results from this study do provide further insight into the gender specific circulatory differences present in the fetal period. [ABSTRACT FROM AUTHOR]

Background: Cell-free fetal DNA and cell-free total DNA in maternal circulation have been proposed as potential markers for noninvasive monitoring of the placental condition during the pregnancy. However, the correlation of and change in cell-free fetal DNA and cell-free total DNA in spontaneous abortion (SA) with fetal chromosomal aneuploidy have not yet been reported. Therefore, we investigated cell-free fetal DNA and cell-free total DNA levels in SA women with fetal chromosomal aneuploidy. Methodology/Principal Findings: A nested case-control study was conducted with maternal plasma collected from 268 women in their first trimester of pregnancy. Subjects included 41 SA with normal fetal karyotype, 26 SA with fetal chromosomal aneuploidy, and 201 normal controls. The unmethylated PDE9A gene was used to measure the maternal plasma levels of cell-free fetal DNA. The GAPDH gene was used to measure the maternal plasma levels of cell-free total DNA. The diagnostic accuracy was measured using receiver-operating characteristic (ROC) curves. Levels of cell-free fetal DNA and cell-free total DNA were significantly higher in both SA women with normal fetal karyotype and SA women with fetal chromosomal aneuploidy in comparison with the normal controls (P<0.001 in both). The correlation between cell-free fetal DNA and cell-free total DNA levels was stronger in the normal controls (r = 0.843, P<0.001) than in SA women with normal karyotype (r = 0.465, P = 0.002) and SA women with fetal chromosomal aneuploidy (r = 0.412, P = 0.037). The area under the ROC curve for cell-free fetal DNA and cell-free total DNA was 0.898 (95% CI, 0.852–0.945) and 0.939 (95% CI, 0.903–0.975), respectively. Conclusions: Significantly high levels of cell-free fetal DNA and cell-free total DNA were found in SA women with fetal chromosomal aneuploidy. Our findings suggest that cell-free fetal DNA and cell-free total DNA may be useful biomarkers for the prediction of SA with fetal chromosomal aneuploidy, regardless of fetal gender. [ABSTRACT FROM AUTHOR]

Objective: Despite an increase in the proportion of women who access antenatal care, mother-to-child transmission of syphilis continues to be a consequence of undiagnosed, untreated, or inadequately treated maternal syphilis. We reviewed evidence on the optimal timing of antenatal interventions to prevent mother-to-child transmission of syphilis and its associated adverse outcomes. Design: Systematic review and meta-analysis of published literature. English-language articles were included if they (1) reported the gestational age at which the mother was screened or tested for syphilis; (2) reported on pregnancy outcome. No publication date limits were set. Results: We identified a total of 1,199 publications, of which 84 were selected for further review and five were included. All showed a lower prevalence of any adverse outcome among women who received an intervention (to include screening and treatment) in the first and second trimesters of pregnancy compared to the third trimester. The overall odds ratio for any adverse outcome was 2.24 (95% CI 1.28, 3.93). All sub-analyses by type of outcome presented important heterogeneity between studies, except for those studies reporting an infected infant (odds ratio 2.92, 95% CI 0.66, 12.87; I2 = 48.2%, p = 0.165). Conclusions: Our review has shown that the timing of antenatal care interventions makes a significant difference in the risk of having an adverse outcome due to syphilis. Women who sought care in the first two trimesters of their pregnancy, and received the appropriate intervention, were more likely to have a healthy infant, compared to women screened and treated in the third trimester. Encouraging ALL pregnant women to seek care in the first two trimesters of their pregnancy should be a priority for health programmes. For interventions to be effective within these health programmes, health systems and community engagement programmes need to be strengthened to enable pregnant women to seek antenatal care early. [ABSTRACT FROM AUTHOR]

Background: Recent decades have witnessed an increase in mean maternal age at childbirth in most high-resourced countries. Advanced maternal age has been associated with several adverse maternal and perinatal outcomes. Although there are many studies on this topic, data from large contemporary population-based cohorts that controls for demographic variables known to influence perinatal outcomes is limited. Methods: We performed a population-based cohort study using data on all singleton births in 2004–2008 from the North Western Perinatal Survey based at The University of Manchester, UK. We compared pregnancy outcomes in women aged 30–34, 35–39 and ≥40 years with women aged 20–29 years using log-linear binomial regression. Models were adjusted for parity, ethnicity, social deprivation score and body mass index. Results: The final study cohort consisted of 215,344 births; 122,307 mothers (54.19%) were aged 20–29 years, 62,371(27.63%) were aged 30–34 years, 33,966(15.05%) were aged 35–39 years and 7,066(3.13%) were aged ≥40 years. Women aged 40+ at delivery were at increased risk of stillbirth (RR = 1.83, [95% CI 1.37–2.43]), pre-term (RR = 1.25, [95% CI: 1.14–1.36]) and very pre-term birth (RR = 1.29, [95% CI:1.08–1.55]), Macrosomia (RR = 1.31, [95% CI: 1.12–1.54]), extremely large for gestational age (RR = 1.40, [95% CI: 1.25–1.58]) and Caesarean delivery (RR = 1.83, [95% CI: 1.77–1.90]). Conclusions: Advanced maternal age is associated with a range of adverse pregnancy outcomes. These risks are independent of parity and remain after adjusting for the ameliorating effects of higher socioeconomic status. The data from this large contemporary cohort will be of interest to healthcare providers and women and will facilitate evidence based counselling of older expectant mothers. [ABSTRACT FROM AUTHOR]

Background: To analyze the effects of IL-10 on the HLA-G expression and the apoptosis of trophoblasts infected with Toxoplasma gondii. Methods: T. gondii-infected or uninfected human trophoblasts and immortalized human placental BeWo cells were cultured with or without human IL-10. Uninfected and infected cells without IL-10 cells served as controls. HLA-G expression was measured by real-time PCR and flow cytometry, respectively. Cells apoptosis were analyzed by flow cytometry. Apoptosis associated moleculars were measured by real-time PCR and Western bolt. Results: HLA-G expression was increased in the infected trophoblasts and BeWo cells compared to uninfected cells. Treatment of infected cells with IL-10 decreased HLA-G expression compared to infected cells while no change in treatment of uninfected cells compared with uninfected cells. Levels of apoptosis and apoptosis associated caspase-3 and caspase-8 decreased and c-FLIP levels increased in treated infected cells with IL-10 compared to infected cells and no difference in IL-10 treated uninfected cells compared to uninfected cells. Conclusions: IL-10 regulates HLA-G expression in T. gondii-infected trophoblasts. IL-10 treatment of infected trophoblasts reduced levels of apoptosis. This may contribute to the improvement in pregnancy outcomes when women infected with T. gondii treated with IL-10. [ABSTRACT FROM AUTHOR]

Objectives: To explore the “how” and “why” of care decision making by frontline providers of maternal and newborn services in the Greater Accra region of Ghana and determine appropriate interventions needed to support its quality and related maternal and neonatal outcomes. Methods: A cross sectional and descriptive mixed method study involving a desk review of maternal and newborn care protocols and guidelines availability, focus group discussions and administration of a structured questionnaire and observational checklist to frontline providers of maternal and newborn care. Results: Tacit knowledge or ‘mind lines’ was an important primary approach to care decision making. When available, protocols and guidelines were used as decision making aids, especially when they were simple handy tools and in situations where providers were not sure what their next step in management had to be. Expert opinion and peer consultation were also used through face to face discussions, phone calls, text messages, and occasional emails depending on the urgency and communication medium access. Health system constraints such as availability of staff, essential medicines, supplies and equipment; management issues (including leadership and interpersonal relations among staff), and barriers to referral were important influences in decision making. Frontline health providers welcomed the idea of interventions to support clinical decision making and made several proposals towards the development of such an intervention. They felt such an intervention ought to be multi-faceted to impact the multiple influences simultaneously. Effective interventions would also need to address immediate challenges as well as more long-term challenges influencing decision-making. Conclusion: Supporting frontline worker clinical decision making for maternal and newborn services is an important but neglected aspect of improved quality of care towards attainment of MDG 4 & 5. A multi-faceted intervention is probably the best way to make a difference given the multiple inter-related issues. [ABSTRACT FROM AUTHOR]