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Background Data on the relationship between bariatric surgery and risk of birth defects are conflicting. Objectives We studied the association of bariatric surgery with birth defects in future pregnancies in a large cohort of women. Methods We carried out a retrospective cohort study of 2,194,348 pregnancies that occurred between 1989 and 2016 in Quebec, Canada. We identified women who had bariatric surgery before pregnancy, and included nonobese women with no surgery as a comparison group. We estimated risk ratios (RRs) and 95% CIs for the associations between bariatric surgery and the risk of birth defects, using log-binomial regression models adjusted for maternal age, comorbidities, parity, whether there was a multiple birth, socioeconomic deprivation, and the presence of folic acid food fortification. Results In this study, 1845 deliveries were among women who had bariatric surgery before pregnancy (0.08%). Having bariatric surgery was associated with 1.20 times the risk of birth defects in later pregnancies (95% CI: 1.01, 1.43), compared with having no surgery or obesity. Obesity without having bariatric surgery was, in contrast, more weakly associated with birth defects (RR: 1.09; 95% CI: 1.07, 1.12). The association with bariatric surgery was greater for heart (RR: 1.47; 95% CI: 1.02, 2.12) and musculoskeletal defects (RR: 1.32; 95% CI: 1.02, 1.71). Associations were primarily present before folic acid food fortification was implemented (RR: 2.03; 95% CI: 1.41, 2.92), but not after (RR: 1.05; 95% CI: 0.86, 1.28). Conclusions Having bariatric surgery was a risk factor for birth defects, and particularly heart and musculoskeletal defects. After fortification, however, an association was no longer present. Future studies are needed to determine whether micronutrient supplementation underpins the difference in the changing results pre- and postfortification. [ABSTRACT FROM AUTHOR]

Although the cesarean section (C-section) is known as a lifesaving procedure, it can also increase the risk of maternal mortality and morbidity. This study was conducted to achieve two objectives: (1) determination of maternal near miss (MNM) indicators and pregnancy outcomes among women with a history of C-section and (2) investigation of the women's experience of near miss events during childbirth to provide a deeper understanding of the weaknesses of care delivery process. The present study was conducted using a prospective cross-sectional study using the World Health Organization (organ system dysfunction–based) criteria. All subjects were women at more than 22 weeks of gestation who gave birth in Ali ibn Abi Talib Hospital, Zahedan, Iran, and were referred to this hospital for childbirth or those within 42 days of pregnancy termination. Logistic regression was used to predict the risk factors for severe maternal outcomes (SMOs). Nearly 58% of all MNM cases were related to women with a history of C-section. The MNM ratio was estimated at 8.04 per 1000 live births. Moreover, the frequent causes of SMOs were reported as severe hemorrhage (58.3%), severe pre-eclampsia/eclampsia (27.8%), medical condition (8.3%), and sepsis or severe systemic infection (5.6%). Abnormally invasive placenta (61%) was the most common cause of severe hemorrhage. After adjustment for potential confounder variables, the hemoglobin level of <11 g/dl (odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.09–0.36) and place of residence (OR = 0.41, 95% CI = 0.19–0.90) remained as independent risk factors for SMOs in the final model of multivariate analysis. A risk assessment system is needed to diagnose and manage the risk factors for SMOs during prenatal care. In addition, there should be a continuous audit of the indication and number of C-sections performed across health facilities. • Fifty-eight percent of all maternal near miss (MNM) cases were related to women with a history of cesarean section. • Abnormally invasive placenta was the most common cause of sever hemorrhage. • Anemia and living in rural areas were the determinants of severe maternal outcomes. • Delay in providing care and harmful practices were contributed to MNM incidence. [ABSTRACT FROM AUTHOR]

Infertility, may be a harbinger for future health risk in women, including early mortality. Fertility status itself could serve as an early biomarker, (present in a woman's reproductive years) for risk stratification later in life. The relationship between infertility and early mortality involves the impact of nulliparity on future adverse health events, potential sequelae from the underlying cause(s) of infertility, the risks of fertility treatments, as well as the potential for risk reduction from a healthy pregnancy. This complex interplay coupled with difficulties ascertaining infertility on a population level has presented unique challenges to assessing infertility and early mortality risk. With further study, a better understanding the role of fertility status in health at various stages of life may provide unique opportunities for surveillance and risk reduction. [ABSTRACT FROM AUTHOR]

Highlights • E-cigarette use is increasing rapidly yet there is limited data available regarding its effects during pregnancy. • E-cigarette conditioned-media impaired placental trophoblast function. • The impaired trophoblast function does not appear to be dependent on the presence of nicotine. • E-cigarette exposure may cause placental dysfunction which is consistent with adverse pregnancy outcomes. Abstract Despite evidence that maternal smoking is associated with numerous adverse outcomes, 10–35% of women still smoke during pregnancy. Recently, many smokers have turned to electronic cigarettes (e-cigarettes) as a smoking cessation tool. However, there is considerable uncertainty regarding their safety for use during pregnancy. The goal of this study was to examine the effects of e-cigarette vapour on placental trophoblast function. HTR-8/SVneo cells were exposed to unflavored e-cigarette vapour-conditioned media with and without nicotine to assess cell viability, proliferation, migration (wound healing assay), invasion (transwell extracellular matrix invasion assay), and tube formation, a surrogate for angiogenesis. While there was no effect on cell viability, proliferation or migration (all p > 0.05), e-cigarette conditioned media significantly reduced trophoblast invasion and tube formation; these effects could not be solely attributed to the presence of nicotine. These results suggest that an evaluation of the safety of e-cigarette use during pregnancy is urgently required. [ABSTRACT FROM AUTHOR]

Highlights • largest monocentric cohort study on metformin safety during the first trimester. • 336 pregnancies with metformin exposure and 1011 matched controls. • no increase in major birth defects and spontaneous abortions. • no distinct pattern of major birth defects. Abstract The aim of this study was to evaluate the risk of major birth defects and spontaneous abortion after metformin use during the first trimester of pregnancy. We conducted an observational cohort study comparing pregnancies with metformin treatment during the first trimester with non-exposed women matched for BMI and year of enrolment. Pregnancies were prospectively ascertained in the German Embryotox pharmacovigilance database between 2004 and 2014. The study sample included 336 pregnancies with metformin exposure for PCOS and fertility disorders (56.8%), diabetes (25.9%) and insulin resistance (14.9%) and 1011 matched controls. Independent of the treatment indication, neither the rate of major birth defects (OR adjusted 0.58, 95% CI 0.3–1.3) nor of spontaneous abortions (HR adjusted 0.95, 95% CI 0.6–1.5) was significantly increased among metformin exposed. Our study supports the evidence that metformin does not carry a developmental risk for the fetus when used during the first trimester. [ABSTRACT FROM AUTHOR]

Background: Aripiprazole is a second generation antipsychotic medication that has been a useful addition to the treatment of severe mental illness due to its low metabolic and sedation risk profile. Pregnancy is a time of high risk of metabolic complications such as gestational diabetes and the postpartum period is often a time when sedation can compromise infant care. To date there is limited data in pregnancy on the safety of aripiprazole use. While available data do not suggest an elevated malformation risk in pregnancy, there is less information available on pregnancy and neonatal complications.Methods: This study presents preliminary data on pregnancy and neonatal complications on 26 women who took aripiprazole in pregnancy. These women attended at antenatal clinics for women with severe mental illness at two hospitals in Australia.Results: Overall aripiprazole was not associated with an increased risk of gestational diabetes. However, use of aripiprazole in pregnancy was associated with an increased risk of pregnancy hypertension, lower birth weight, shorter gestation at birth and higher rates of admission of the neonate than the expected population rates.Limitations: These findings need to be replicated in a larger, well-designed study to ensure they do not reflect confounding factors.Conclusions: Findings demonstrate that aripiprazole is unlikely to pose a metabolic risk in pregnancy but other pregnancy complications including hypertension, need to be examined in further studies. [ABSTRACT FROM AUTHOR]

Twins account for 2–3% of all births. They carry significant risks to both mothers and babies. These risks include preterm delivery, intrauterine growth restriction, and pre-eclampsia. In addition, monochorionic gestations confer an even higher rate of perinatal morbidity and mortality arising from a shared placenta due to placental anastomoses, which may lead to twin-to-twin transfusion syndrome (TTTS) or twin anaemia-polycythaemia sequence (TAPS). It is essential that chorionicity is established in the first trimester in order to initiate the appropriate antenatal management and surveillance. In view of the high risk of both maternal and fetal complications, twin pregnancies are ideally managed in a dedicated clinic according to agreed protocols with both obstetric and midwifery input. [ABSTRACT FROM AUTHOR]

During pregnancy, exposure to environmental contaminants can lead to adverse effects on fetal growth and development, especially by targeting the placenta. Di(2-ethylhexyl)phthalate (DEHP), the most abundant chemical used in plastic materials, is known to induce toxicity on animals reproductive system and is suspected to give rise to similar effect in humans. Toxicity of DEHP is due to its main metabolite, MEHP, which is also known to disturb lipid synthesis in several organs. Moreover, mono-(2-ethylhexyl)phtalate (MEHP) is a high affinity ligand of the peroxisome proliferator-activated receptor PPARγ which is essential for placental development and lipid metabolism. In order to investigate possible lipid disruptions induced by MEHP, in the JEG-3 human trophoblast cell line, a differential lipidomic analysis was carried out by UPLC-MS on both exposed and control cells. Our results showed that MEHP induced an important change of JEG-3 cells lipidome, especially in glycerolipids and glycerophospholipids, with a marked accumulation of triacylglycerols. For the first time, our results highlighted adverse effects of MEHP on human placental cells lipidome and thus, its potential effect on placental physiology. [ABSTRACT FROM AUTHOR]

Background Exposure to perfluoroalkyl substances (PFASs) may impact children's neurodevelopment. Objective To examine the association of prenatal and early childhood serum PFAS concentrations with children's reading skills at ages 5 and 8 years. Methods We used data from 167 mother-child pairs recruited during pregnancy (2003–2006) in Cincinnati, OH, quantified prenatal serum PFAS concentrations at 16 ± 3 weeks of gestation and childhood sera at ages 3 and 8 years. We assessed children's reading skills using Woodcock-Johnson Tests of Achievement III at age 5 years and Wide Range Achievement Test-4 at age 8 years. We used general linear regression to quantify the covariate-adjusted associations between natural log-transformed PFAS concentrations and reading skills, and used multiple informant model to identify the potential windows of susceptibility. Results Median serum PFASs concentrations were PFOS > PFOA > PFHxS > PFNA in prenatal, 3-year, and 8-year children. The covariate-adjusted general linear regression identified positive associations between serum PFOA, PFOS and PFNA concentrations and children's reading scores at ages 5 and 8 years, but no association between any PFHxS concentration and reading skills. The multiple informant model showed: a) Prenatal PFOA was positively associated with higher children's scores in Reading Composite (β: 4.0, 95% CI: 0.6, 7.4 per a natural log unit increase in exposure) and Sentence Comprehension (β: 4.2, 95% CI: 0.5, 8.0) at age 8 years; b) 3-year PFOA was positively associated with higher children's scores in Brief Reading (β: 7.3, 95% CI: 0.9, 13.8), Letter Word Identification (β: 6.6, 95% CI: 1.1, 12.0), and Passage Comprehension (β: 5.9, 95% CI: 1.5, 10.2) at age 5 years; c) 8-year PFOA was positively associated with higher children's Word Reading scores (β: 5.8, 95% CI: 0.8, 10.7) at age 8 years. Prenatal PFOS and PFNA were positively associated with children's reading abilities at age 5 years, but not at age 8 years; 3-year PFOS and PFNA were positively associated with reading scores at age 5 years. But PFHxS concentrations, at any exposure windows, were not associated with reading skills. Conclusion Prenatal and childhood serum PFOA, PFOS and PFNA concentrations were positively associated with better children's reading skills at ages 5 and 8 years, but no association was found between serum PFHxS and reading skills. [ABSTRACT FROM AUTHOR]

The prevalence of obesity has reached alarming proportions globally, and continues to rise in both developed and developing countries. Maternal obesity has become one of the most commonly occurring risk factors in obstetric practice. For the mother, obesity increases the risk of obstetric complications during the antenatal, intrapartum and postnatal period, as well as contributing to technical difficulties with fetal assessment. The offspring of obese mothers also have a higher rate of perinatal morbidity and an increased risk of long-term health problems. [ABSTRACT FROM AUTHOR]

Background It has been suggested that prenatal maternal stress may increase the risk of childhood externalizing disorders, yet no large cohort study has investigated this association across a large range of acute stressors. Our objective was to estimate the association between prenatal stressful events and risk of offspring conduct disorder and hyperactivity. Methods We used data from 10,184 mother–offspring pairs from the United Kingdom–based Avon Longitudinal Study of Parents and Children. Mothers self - reported 42 prenatal stressful life events at 18 weeks’ gestation. Symptoms of conduct disorder and hyperactivity in their offspring were measured at 6, 9, 11, 13, and 16 years of age using the Strengths and Difficulties Questionnaire. The primary outcome was membership in high-symptom trajectories of 1) conduct disorder and 2) hyperactivity throughout childhood, identified using latent class growth modeling. Multinomial logistic regression models estimated the association between prenatal stress and both conduct disorder and hyperactivity, after adjusting for sex, parental education, low birth weight, preterm birth, parental social class, maternal smoking and drinking, maternal mental health, offspring stressful life events, and offspring depressive and anxious symptoms. Results Those exposed to the highest quartile of prenatal stress were more likely to belong to the high symptom trajectory for hyperactivity ( B = 0.46, p < .05) and conduct disorder ( B = 0.88, p < .01), respectively. Prenatal stress further demonstrated a positive, dose–response relationship with symptoms of externalizing disorders at independent time points. Conclusions The findings suggest that prenatal stressful events may be an independent risk factor for offspring externalizing symptoms, regardless of maternal mental health and offspring internalizing. [ABSTRACT FROM AUTHOR]

Objective: To estimate the association of pregnancy loss with common air pollutant exposure. Ambient air pollution exposure has been linked to adverse pregnancy outcomes, but few studies have investigated its relationship with pregnancy loss.Design: Prospective cohort study.Setting: Not applicable.Patient(s): A total of 343 singleton pregnancies in a multisite prospective cohort study with detailed protocols for ovulation and pregnancy testing.Intervention(s): None.Main Outcome Measure(s): Timing of incident pregnancy loss (from ovulation).Result(s): The incidence of pregnancy loss was 28% (n = 98). Pollutant levels at women's residences were estimated using modified Community Multiscale Air Quality models and averaged during the past 2 weeks (acute) and the whole pregnancy (chronic). Adjusted Cox proportional hazards models showed that an interquartile range increase in average whole pregnancy ozone (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.07-1.17) and particulate matter <2.5 μm (HR 1.13, 95% CI 1.03-1.24) concentrations were associated with faster time to pregnancy loss. Sulfate compounds also appeared to increase risk (HR 1.58, 95% CI 1.07-2.34). Last 2 weeks of exposures were not associated with loss.Conclusion(s): In a prospective cohort of couples trying to conceive, we found evidence that exposure to air pollution throughout pregnancy was associated with loss, but delineating specific periods of heightened vulnerability await larger preconception cohort studies with daily measured air quality. [ABSTRACT FROM AUTHOR]

Selenium (Se) has been positively associated with neurodevelopment in early life. However, its margin of safety is rather narrow, and few prospective studies have evaluated its potential neurotoxic effects at intermediate levels. We aimed to explore the association between maternal Se concentrations and child neuropsychological development, including the genetic effect modification of the Se metabolizing gene INMT . Study subjects were 650 mother-child pairs from the Spanish Childhood and Environment Project (INMA, 2003–2005). Infant neuropsychological development was assessed around 12 months of age by the Bayley Scales of Infant Development. Sociodemographic and dietary characteristics were collected by questionnaire at the first and third trimester of gestation. Se was measured in serum samples at the first trimester. The mean serum Se concentration was 79.7 (standard deviation = 7.9) μg/L. In multivariate analysis, nonsignificant inverse linear associations were found between Se concentrations and standardized mental and psychomotor development scores (β (95% CI) = − 0.13 (− 0.29, 0.03) and β (95% CI) = − 0.08 (− 0.24, 0.07), respectively). Generalized additive models indicated inverted U-shaped relationships between Se concentrations and both scales. Using segmented regression, the turning point for the associations was estimated at 86 μg/L for both scales. The association between Se and neuropsychological development was inverted U-shaped for children with the AG + AA genotype for rs6970396 INMT but a descending curve was suggested for the GG genotype. Further studies would be necessary in order to disentangle the complex equilibrium between the toxicity and benefits of Se exposure during the prenatal period. [ABSTRACT FROM AUTHOR]

Pregnant women are particularly vulnerable to iron deficiency and related adverse pregnancy outcomes and, as such, are routinely recommended for iron supplementation. Emerging evidence from both animal and population-based studies, however, has raised potential concerns because significant associations have been observed between greater iron stores and disturbances in glucose metabolism, including increased risk of type 2 diabetes among nonpregnant individuals. Yet, the evidence is uncertain regarding the role of iron in the development of gestational diabetes mellitus (GDM), a common pregnancy complication which has short-term and long-term adverse health ramifications for both women and their children. In this review, we critically and systematically evaluate available data examining the risk of GDM associated with dietary iron, iron supplementation, and iron status as measured by blood concentrations of several indicators. We also discuss major methodologic concerns regarding the available epidemiologic studies on iron and GDM. [ABSTRACT FROM AUTHOR]

Pregnant nulliparous adolescents are at increased risk, inversely proportional to their age, of major obstetric syndromes, including preeclampsia, fetal growth restriction, and preterm birth. Emerging evidence indicates that biological immaturity of the uterus accounts for the increased incidence of obstetrical disorders in very young mothers, possibly compounded by sociodemographic factors associated with teenage pregnancy. The endometrium in most newborns is intrinsically resistant to progesterone signaling, and the rate of transition to a fully responsive tissue likely determines pregnancy outcome during adolescence. In addition to ontogenetic progesterone resistance, other factors appear important for the transition of the immature uterus to a functional organ, including estrogen-dependent growth and tissue-specific conditioning of uterine natural killer cells, which plays a critical role in vascular adaptation during pregnancy. The perivascular space around the spiral arteries is rich in endometrial mesenchymal stem-like cells, and dynamic changes in this niche are essential to accommodate endovascular trophoblast invasion and deep placentation. Here we evaluate the intrinsic (uterine-specific) mechanisms that predispose adolescent mothers to the great obstetrical syndromes and discuss the convergence of extrinsic risk factors that may be amenable to intervention. [ABSTRACT FROM AUTHOR]

Objectives: The contraceptive prevalence rate (CPR) is generally reported among in-union women ages 15-49. Here, union status and age serve as proxies for exposure to the risk of pregnancy. As a result of changing dynamics, age and union status proxies may be insufficient for determining the rate of contraceptive use among women at risk of pregnancy. Our objectives are to define a measure of contraceptive use among women at risk, to measure contraceptive use among such women and to compare this rate with conventional CPR.Study Design: Using data from the United States 2011-2013 National Survey of Family Growth (NSFG), we explore self-reported data on contraceptive use, sexual recency, pregnancy status and fecundity to develop an alternative CPR (ACPR) measure, contraceptive prevalence among women at risk of pregnancy. After defining and measuring ACPR, we compare ACPR and conventional CPR estimates using NSFG and Demographic and Health Survey data from 48 surveys completed from 2000 to 2015 in low- and middle-income countries.Results: For measuring ACPR, it is best to limit sexual activity recency component to "four weeks" to minimize underreport of coital-specific methods. It is best to limit the contraceptive use component to "current use" rather than "use at last sex" to minimize underreport of permanent methods. In the United States, 86% of women at risk of pregnancy are currently using contraception.Conclusion: Women at risk of pregnancy report higher levels of contraceptive use than the conventional CPR indicates.Implications Statement: Development of ACPR exposed some potential family planning measurement weaknesses. Specifically, because CPR is based on report of "current use," our analyses show that CPR may underreport coital-specific methods. As a result, CPR estimates may be somewhat deflated, and unmet need estimates may be somewhat inflated. [ABSTRACT FROM AUTHOR]

This article examines the causal effect of women's education on maternal health in Peru, a country where maternal mortality has declined by more than 70% in the last two and a half decades. To isolate the effects of education, the author employs an instrumented regression discontinuity that takes advantage of an exogenous source of variation—an amendment to compulsory schooling laws in 1993. The results indicate that extending women's years of schooling reduced the probability of several maternal health complications at last pregnancy/birth, sometimes by as much as 29%. Underlying these effects, increasing women's education is found to decrease the probability of short birth intervals and unwanted pregnancies (which may result in unsafe abortions) and to increase antenatal healthcare use, potentially owing to changes in women's cognitive skills, economic resources, and autonomy. These findings underscore the influential role of education in reducing maternal morbidity and highlight the contributions of women's education to population health and health transitions. [ABSTRACT FROM AUTHOR]

The aim was to evaluate the relationship between maternal corticosteroid use during first trimester of pregnancy and risk of orofacial clefts (OC). The overall findings showed a certain association between maternal corticosteroid use and occurrence of OC, compared with non-users (OR = 1.16 [95% CI: 1.01–1.33]). When study type was considered this association was significant only for case-control studies (OR = 1.22 [95% CI: 1.02–1.47]), and not for cohort studies (OR = 1.09 [95% CI: 0.88–1.34]) when there are many confounders (dose, route of application, disease etc.) and biases (re-call, loss-to follow-up etc.) that still need to be considered. A subgroup analysis based on the type of OC gave an overall OR of 1.41 (95% CI: 1.14–1.74) in the case-control studies for cleft lip with or without palate (CL/P) and 1.09 (95% CI: 0.80–1.48) for cleft palate only (CPO), when comparing maternal corticosteroid users with non-users. However, for cohort studies, the overall OR for CL/P is 1.06 (95% CI: 0.82–1.37) and 1.20 (95% CI: 0.83–1.75) for CPO. The absolute risk of facial cleft after prenatal exposure to corticosteroids, if any, is small. [ABSTRACT FROM AUTHOR]

Background Obesity and being overweight are becoming epidemic, and indeed, the proportion of such women of reproductive age has increased in recent times. Being overweight or obese prior to pregnancy is a risk factor for gestational diabetes mellitus, and increases the risk of adverse pregnancy outcome for both mothers and their offspring. Furthermore, the combination of gestational diabetes mellitus with obesity/overweight status may increase the risk of adverse pregnancy outcome attributable to either factor alone. Regular exercise has the potential to reduce the risk of developing gestational diabetes mellitus and can be used during pregnancy; however, its efficacy remain controversial. At present, most exercise training interventions are implemented on Caucasian women and in the second trimester, and there is a paucity of studies focusing on overweight/obese pregnant women. Objective We sought to test the efficacy of regular exercise in early pregnancy to prevent gestational diabetes mellitus in Chinese overweight/obese pregnant women. Study Design This was a prospective randomized clinical trial in which nonsmoking women age >18 years with a singleton pregnancy who met the criteria for overweight/obese status (body mass index 24≤28 kg/m 2 ) and had an uncomplicated pregnancy at <12 +6 weeks of gestation were randomly allocated to either exercise or a control group. Patients did not have contraindications to physical activity. Patients allocated to the exercise group were assigned to exercise 3 times per week (at least 30 min/session with a rating of perceived exertion between 12-14) via a cycling program begun within 3 days of randomization until 37 weeks of gestation. Those in the control group continued their usual daily activities. Both groups received standard prenatal care, albeit without special dietary recommendations. The primary outcome was incidence of gestational diabetes mellitus. Results From December 2014 through July 2016, 300 singleton women at 10 weeks’ gestational age and with a mean prepregnancy body mass index of 26.78 ± 2.75 kg/m 2 were recruited. They were randomized into an exercise group (n = 150) or a control group (n = 150). In all, 39 (26.0%) and 38 (25.3%) participants were obese in each group, respectively. Women randomized to the exercise group had a significantly lower incidence of gestational diabetes mellitus (22.0% vs 40.6%; P < .001). These women also had significantly less gestational weight gain by 25 gestational weeks (4.08 ± 3.02 vs 5.92 ± 2.58 kg; P < .001) and at the end of pregnancy (8.38 ± 3.65 vs 10.47 ± 3.33 kg; P < .001), and reduced insulin resistance levels (2.92 ± 1.27 vs 3.38 ± 2.00; P = .033) at 25 gestational weeks. Other secondary outcomes, including gestational weight gain between 25-36 gestational weeks (4.55 ± 2.06 vs 4.59 ± 2.31 kg; P = .9), insulin resistance levels at 36 gestational weeks (3.56 ± 1.89 vs 4.07 ± 2.33; P = .1), hypertensive disorders of pregnancy (17.0% vs 19.3%; odds ratio, 0.854; 95% confidence interval, 0.434–2.683; P = .6), cesarean delivery (except for scar uterus) (29.5% vs 32.5%; odds ratio, 0.869; 95% confidence interval, 0.494–1.529; P = .6), mean gestational age at birth (39.02 ± 1.29 vs 38.89 ± 1.37 weeks’ gestation; P = .5); preterm birth (2.7% vs 4.4%, odds ratio, 0.600; 95% confidence interval, 0.140–2.573; P = .5), macrosomia (defined as birthweight >4000 g) (6.3% vs 9.6%; odds ratio, 0.624; 95% confidence interval, 0.233–1.673; P = .3), and large-for-gestational-age infants (14.3% vs 22.8%; odds ratio, 0.564; 95% confidence interval, 0.284–1.121; P = .1) were also lower in the exercise group compared to the control group, but without significant difference. However, infants born to women following the exercise intervention had a significantly lower birthweight compared with those born to women allocated to the control group (3345.27 ± 397.07 vs 3457.46 ± 446.00 g; P = .049). Conclusion Cycling exercise initiated early in pregnancy and performed at least 30 minutes, 3 times per week, is associated with a significant reduction in the frequency of gestational diabetes mellitus in overweight/obese pregnant women. And this effect is very relevant to that exercise at the beginning of pregnancy decreases the gestational weight gain before the mid-second trimester. Furthermore, there was no evidence that the exercise prescribed in this study increased the risk of preterm birth or reduced the mean gestational age at birth. [ABSTRACT FROM AUTHOR]

Pregnancy is an immune challenge to the maternal immune system. The effects of pregnancy on maternal immunity and particularly on memory T cells during and after pregnancy are not fully known. This observational study aims to show the short term and the long term effects of pregnancy on the constitution, size and activation status of peripheral human memory T-lymphocyte populations. Effector memory (EM) and central memory (CM) T-lymphocytes were analyzed using flow cytometry of peripheral blood from 14 nulligravid, 12 primigravid and 15 parous women that were on average 18 months postpartum. The short term effects were shown by the significantly higher CD4+ EM cell and activated CD4+ memory cell proportions in primigravid women compared to nulligravid women. The persistent effects found in this study were the significantly higher proportions of CD4+ EM, CD4+ CM and activated memory T cells in parous women compared to nulligravid women. In contrast to CD4+ cells, activation status of CD8+ memory cells did not differ between the groups. This study shows that pregnancy persistently affects the pre-pregnancy CD4+ memory cell pool in human peripheral blood. During pregnancy, CD4+ T-lymphocytes might differentiate into EM cells followed by persistent higher proportions of CD4+ CM and EM cells postpartum. The persistent effects of pregnancy on memory T cells found in this study support the hypothesis that memory T cells are generated during pregnancy and that these cells could be involved in the lower complication risks in multiparous pregnancies in humans. [ABSTRACT FROM AUTHOR]

Both the under 18 conception and birth rates are falling. However, despite this the United Kingdom has a high rate of teenage pregnancy compared to similar countries in Western Europe. Young mothers and their babies have poorer access to maternity care and experience worse obstetric outcomes than older mothers. It is likely that the risks associated with teenage pregnancy reflect a significant interplay between the socio-demographic status of many of these teenagers, their nutritional status and their uptake of antenatal care. This review looks at the complications associated with teenage pregnancy and how the implementation of specialized antenatal care aims to improve outcomes. [ABSTRACT FROM AUTHOR]

Placental insufficiency leads to intrauterine growth restriction (IUGR) and a lifelong risk of developing type 2 diabetes. Impaired islet development in the growth restricted fetus, including decreased β-cell replication, mass, and insulin secretion, is strongly implicated in the pathogenesis of later life type 2 diabetes. Currently, standard medical management of a woman with a pregnancy complicated by placental insufficiency and fetal IUGR is increased fetal surveillance and indicated preterm delivery. This leads to the dual complications of IUGR and preterm birth – both of which may increase the lifelong risk for type 2 diabetes. In order to develop therapeutic interventions in IUGR pregnancies complicated by placental insufficiency and decrease the risk of later development of type 2 diabetes in the offspring, the mechanisms responsible for impaired islet development in these cases must be determined. This review focuses on current investigations testing the hypothesis that decreased nutrient supply to the IUGR fetus inhibits an intra-islet hepatocyte growth factor – vascular endothelial growth factor A (HGF – VEGFA) feed forward signaling pathway and that this is responsible for developmental islet defects. [ABSTRACT FROM AUTHOR]

This opinion addresses the ethics of providing fertility treatment to women at elevated risk from fertility treatment or pregnancy. Providers ethically may treat women at elevated risk provided that they are carefully assessed; that specialists in their medical condition are consulted as appropriate; and that patients are fully informed about risks, benefits, and alternatives, including oocyte and embryo donation, use of a gestational surrogate, not undergoing fertility care, and adoption. Providers also may conclude that the risks are too high for them to treat particular patients ethically; such determinations must be made in a medically objective and unbiased manner and patients must be fully informed of the decision. Counseling of women who wish to initiate fertility treatment with underlying medical conditions that confer increased risk during treatment or pregnancy should incorporate the most current knowledge available, being cognizant of the woman's personal determinants in relation to her reproductive desires. In such a way, both physician and patient will optimize decision making in an ethically sound, patient-supportive context. [ABSTRACT FROM AUTHOR]

Background Exposure to road traffic noise has been associated with adiposity and diabetes in adults. The suggested pathways have been through sleep disturbance and stress. Children may be particularly susceptible to noise induced sleep disturbance and stress and the effects hereof. Objectives To examine the association between traffic noise exposure during pregnancy and early childhood and adiposity in children. Methods We identified 40,974 singletons from the Danish National Birth Cohort with parentally given questionnaire information on weight and height at 7-years of age. Road and railway traffic noise were modeled at all historical addresses and expressed as time-weighted means for two exposure periods (pregnancy and childhood). Adiposity was assessed using BMI z-scores and a dichotomous measure of childhood overweight based on age and sex specific cut-offs. Associations were analyzed using linear regression for BMI z-scores and logistic regression for risk of childhood overweight, adjusting for socioeconomic position, maternal BMI, maternal smoking, maternal age, parity and degree of urbanization. Results We found both pregnancy and childhood exposure to road traffic noise to be associated with a higher risk for childhood overweight (odds ratio (OR) = 1.06 per 10 dB, 95% confidence interval (CI): 1.00–1.12 for exposure during pregnancy and OR = 1.06 per 10 dB, 95% CI: 0.99–1.12 for childhood exposure). There were no associations between road traffic noise and BMI z-scores. We found no associations between railway noise and adiposity. Conclusions We found suggestions of a positive association between road traffic noise and risk of overweight in 7-years old children. [ABSTRACT FROM AUTHOR]

Concerns over adverse effects of air pollution on children's health have been rapidly rising. However, the effects of air pollution on childhood growth remain to be poorly studied. We investigated the association between prenatal and postnatal exposure to PM10 and children's weight from birth to 60 months of age. This birth cohort study evaluated 1129 mother-child pairs in South Korea. Children's weight was measured at birth and at six, 12, 24, 36, and 60 months. The average levels of children's exposure to particulate matter up to 10 μm in diameter (PM10) were estimated during pregnancy and during the period between each visit until 60 months of age. Exposure to PM10 during pregnancy lowered children's weight at 12 months. PM10 exposure from seven to 12 months negatively affected weight at 12, 36, and 60 months. Repeated measures of PM10 and weight from 12 to 60 months revealed a negative association between postnatal exposure to PM10 and children's weight. Children continuously exposed to a high level of PM10 (> 50 μg/m 3 ) from pregnancy to 24 months of age had weight z -scores of 60 that were 0.44 times lower than in children constantly exposed to a lower level of PM10 (≤ 50 μg/m 3 ) for the same period. Furthermore, growth was more vulnerable to PM10 exposure in children with birth weight < 3.3 kg than in children with birth weight > 3.3 kg. Air pollution may delay growth in early childhood and exposure to air pollution may be more harmful to children when their birth weight is low. [ABSTRACT FROM AUTHOR]

Abstract Folate (vitamin B9) is one of thirteen vital vitamins and is found in dietary products, while folic acid is the synthetic supplement used to fortify foods with. Both are metabolically inactive and through an enzymatic process mediated by MTHFR become active. Active metabolites have a key role in the DNA methylation process. Due to genetic polymorphisms of the MTHFR gene, impairment of folate activation is common as 60% of the population are heterozygous and 25% homozygous for this. Pregnancy complications that are related to folic acid deficiency includes primarily neural tube defects, as studies suggest a 72% protective effect of folic acid supplementation. An inadequate supply of nucleotides to neuroepithelial cells and/or neural fold retardation and disturbed methylation are possible pathogenetic mechanisms. A possible link between folic acid deficiency and other pregnancy complications such as congenital heart disease, preeclampsia, intrauterine growth restriction, recurrent pregnancy loss, placental abruption, preterm labour and multiple pregnancy has been reported. Folic acid daily intake in pregnant women is 400 μg received from fortified food and vitamin supplementation to decrease risk of neural tube defects by 50%. In high risk pregnancies (previously affected) this dose is recommended for 1–3 months prior to conception. [ABSTRACT FROM AUTHOR]

Background Women who are overweight or have obesity at pregnancy onset, and those who gain excessive weight during pregnancy, are at increased risk of pregnancy-related complications and large for gestational age infants. Objective This report describes methodology for the Prepare study, a randomized, controlled clinical trial testing a preconception and pregnancy weight management program for women who are overweight or have obesity (BMI ≥ 27 kg/m 2 ). Outcomes This trial examines multiple pregnancy and neonatal outcomes, with the primary outcome being gestational weight gain (GWG). Secondary outcomes include change in weight before conception, offspring birth weight adjusted for gestational age, offspring weight for length, and pregnancy diet quality and physical activity level. Methods Nonpregnant women who anticipate becoming pregnant in the next 2 years are randomly assigned to an intervention program or a usual care control condition. Intervention participants receive weight management counseling by telephone before and during pregnancy, with weekly contacts during the first 6 months and monthly contacts for the next 18 months. Intervention participants also have unlimited access to a study website that provides self-management tools. All participants who become pregnant are contacted at 20 weeks' gestation to assess physical activity levels and dietary habits. All other outcome data are obtained from medical records. Intervention satisfaction is assessed via questionnaire. Summary This clinical trial tests the efficacy of an intervention program designed to help overweight and obese women achieve healthy lifestyle changes that will result in a healthy weight prior to pregnancy and appropriate weight gain during pregnancy. [ABSTRACT FROM AUTHOR]

Intrahepatic cholestasis of pregnancy, also known as obstetric cholestasis, is a pruritic condition of pregnancy characterized by an underlying elevation in circulating bile acids and liver derangement, and associated with adverse fetal outcomes, such as preterm labor and stillbirth. Limited understanding of the underlying pathophysiology and mechanisms involved in adverse outcomes has previously restricted treatment options and pregnancy management. Recent advances in these research fields provide tantalizing targets to improve the care of pregnant women affected by this condition. [ABSTRACT FROM AUTHOR]

Findings from studies investigating associations of residential environment with poor birth outcomes have been inconsistent. In a systematic review and meta-analysis, we examined associations of neighborhood disadvantage with preterm birth (PTB) and low birthweight (LBW), and explored differences in relationships among racial groups. Two reviewers searched English language articles in electronic databases of published literature. We used random effects logistic regression to calculate odds ratios (and 95% confidence intervals) relating neighborhood disadvantage with PTB and LBW. Neighborhood disadvantage, most disadvantaged versus least disadvantaged neighborhoods, was defined by researchers of included studies, and comprised of poverty, deprivation, racial residential segregation or racial composition, and crime. We identified 1314 citations in the systematic review. The meta-analyses included 7 PTB and 14 LBW cross-sectional studies conducted in the United States (U.S.). Overall, we found 27% [95%CI: 1.16, 1.39] and 11% [95%CI: 1.07, 1.14] higher risk for PTB and LBW among the most disadvantaged compared with least disadvantaged neighborhoods. No statistically significant association was found in meta-analyses of studies that adjusted for race. In race-stratified meta-analyses models, we found 48% [95%CI: 1.25, 1.75] and 61% [95%CI: 1.30, 2.00] higher odds of PTB and LBW among non-Hispanic white mothers living in most disadvantaged neighborhoods compared with those living in least disadvantaged neighborhoods. Similar, but less strong, associations were observed for PTB (15% [95%CI: 1.09, 1.21]) and LBW (17% [95%CI: 1.10, 1.25]) among non-Hispanic black mothers. Neighborhood disadvantage is associated with PTB and LBW, however, associations may differ by race. Future studies evaluating causal mechanisms underlying the associations, and racial/ethnic differences in associations, are warranted. [ABSTRACT FROM AUTHOR]

Background Borderline personality disorder (BPD) is a serious mental disorder commonly associated with functional impairments and adverse health outcomes. Very little is known about BPD in pregnant women; hence, our study objective was to evaluate the effect of BPD on obstetrical and neonatal outcomes. Methods We carried out a retrospective cohort study using the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample from 2003 to 2012. We identified births using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic and procedure codes and classified women by BPD status. Multivariate logistic regression was used to evaluate the effect of BPD on obstetrical and neonatal outcomes, adjusted for subject baseline characteristics. Findings During the study period, there were 989 births to women with BPD with an overall incidence of 11.65 in 100,000 births. Women with BPD were more likely younger, of lower socioeconomic status, smoked or used drugs, and had an underlying mental disorder. Unadjusted models revealed that BPD was associated with an increased risk of almost all adverse maternal and fetal outcomes we examined, the exception being post partum hemorrhage and instrumental delivery, which both had a null association with BPD, and induction of labor, which was negatively associated with BPD. Upon full adjustment, BPD was found to be associated with the following obstetrical and neonatal outcomes: gestational diabetes (odds ratio [OR], 1.45; 95% CI, 1.13–1.85), premature rupture of the membranes (OR, 1.40; 95% CI, 1.07–1.83), chorioamnionitis (OR, 1.65; 95% CI, 1.14–2.39), venous thromboembolism (OR, 2.11; 95% CI, 1.12–3.96), caesarian delivery (OR, 1.44; 95% CI, 1.26–1.64), and preterm birth (OR, 1.54; 95% CI, 1.29–1.83). Conclusion BPD is associated with several adverse obstetrical and neonatal outcomes. Hence, pregnant women who suffer from BPD should be monitored closely by a multidisciplinary health care team both before and during their pregnancies. This oversight would allow for the receipt of treatment for BPD and also interventions to help them to cease tobacco and drug use, which may ultimately decrease the incidence of poor obstetrical and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Summary Objective To compare pregnancy outcomes of overweight and obese pregnant women aged 35 years or older to women aged less than 35 years old. Methods A registry-based study covering years 2004–2008 including data on women ≥35 years ( N = 45,718) compared to those <35 years ( N = 203,930) and their pre-pregnancy body mass index (BMI) (<25, 25–29 and ≥30). In multivariable modelling, the main outcome measures were preterm delivery (<28 weeks, 28–31weeks and 32–36 weeks), low Apgar scores at 5 min, small-for-gestational age (SGA), foetal death, asphyxia, Caesarean section, induction, preeclampsia, blood transfusion, admission to a neonatal intensive care unit (NICU), shoulder dystocia, and large for gestational age (LGA). Results Maternal overweight and obesity along with advanced maternal age (AMA) significantly increased the risks of preterm delivery, preeclampsia, foetal death, LGA and Caesarean as compared to women of average weight aged <35 years. When comparing overweight and obese women aged ≥35 years to normal weight women of the same age, the rates of preeclampsia, preterm delivery <28 weeks, LGA and low Apgar score were significantly increased. When observing overweight and obese women <35 years as a reference group, the risks of preterm delivery and foetal death were significantly increased. Conclusions The risks were increased by maternal age ≥ 35 years and both obesity and overweight. The combined effect of AMA and either overweight or obesity appeared to be a high risk state particularly for stillbirth and preterm delivery. [ABSTRACT FROM AUTHOR]

Studies of the effects on pregnancy outcomes of in utero exposure to phthalates, contaminants that are widely present in the environment, have yielded conflicting results. In addition, the mode of assessment of exposure varies between studies. The aim of this review was therefore to establish a current state of knowledge of the phthalates and metabolites involved in unfavorable pregnancy outcomes. Extant data were analyzed to determine which biomarker is the best suited to assess the relation between in utero exposure to phthalates and pregnancy outcomes. This review of the literature was conducted using the database of PubMed. A search was made of studies investigating exposure to phthalates and the following birth outcomes: preterm birth (gestational age < 37 weeks), change in gestational age, change in body size at birth (birth weight, length, head circumference), anti-androgenic function, decreased anogenital distance, cryptorchidism, hypospadias and congenital malformation. The methodological approach adopted in each study was examined, in particular the methods used for exposure assessment (biomarkers and/or questionnaire). Thirty-five studies were included. Premature birth and decreased anogenital distance were the most commonly reported outcomes resulting from a moderate level of exposure to phthalates. The principal metabolites detected and involved were primary metabolites of di-2(ethylhexyl)-phthalate (DEHP) and di- n -butyl-phthalate (DnBP). No clear conclusion could be drawn with regard to gestational age at birth, body size at birth and congenital malformations. In epidemiological studies, maternal urine is the most suitable matrix to assess the association between in utero exposure to phthalates and pregnancy outcomes: in contrast to other matrices (cord blood, amniotic fluid, meconium and milk), sampling is easy, non-invasive and, can be repeated to assess exposure throughout pregnancy. Oxidative metabolites are the most relevant biomarkers since they are not prone to external contamination. Further epidemiological studies are required during pregnancy to i) determine the role of phthalates other than DEHP [currently replaced by various substitution products, in particular diisononyl-phthalate (DiNP)]; ii) establish the effect of phthalates on other outcomes (body size adjusted for gestational age, and congenital malformations); iii) determine the pathophysiological pathways; and iv) identify the most suitable time for biomarker determination of in utero exposure to phthalates. [ABSTRACT FROM AUTHOR]

Background Studies from several countries report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Exposure to environmental chemicals could contribute to this trend. Objectives To determine the associations between plasticisers and metals measured in early pregnancy with impaired glucose tolerance (IGT) and GDM in a Canadian pregnancy cohort. Methods Women enrolled in the Maternal–Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Eleven phthalate metabolites and total bisphenol A (BPA) were measured in first-trimester urine samples, and four metals (lead, cadmium, mercury and arsenic) were measured in first-trimester blood samples. IGT and GDM were assessed in accordance with standard guidelines by chart review. Chemical concentrations were grouped by quartiles, and associations with outcomes were examined using logistic regression with adjustment for maternal age, race, pre-pregnancy BMI, and education. Restricted cubic spline analysis was performed to help assess linearity and nature of any dose–response relationships. Results Of 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome data and biomonitoring data measured for at least one of the chemicals we examined. Elevated odds of GDM were observed in the highest quartile of arsenic exposure (OR = 3.7, 95% CI = 1.4–9.6) in the adjusted analyses. A significant dose–response relationship was observed in a cubic spline model between arsenic and odds of GDM (p < 0.01). No statistically significant associations were observed between phthalates or BPA or other metals with IGT or GDM. Conclusions Our findings add to the growing body of evidence supporting the role of maternal arsenic exposure as a risk factor for gestational diabetes. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and pre-eclampsia, are common obstetric complications associated with adverse health outcomes for the mother and child. It remains unclear how dietary intake can influence HDP risk. Objective: We investigated associations between prepregnancy dietary patterns and risk of HDPs. Design: We selected 3582 women participating in the Australian Longitudinal Study on Women's Health, which is an observational population-based study. Women were not pregnant at baseline in 2003 and reported at least one live birth between 2003 and 2012. Diet was assessed by using a validated 101-item food-frequency questionnaire in 2003, and factor analysis was used to identify dietary patterns. HDPs were assessed by using the question, "Were you diagnosed or treated for hypertension during pregnancy?" Generalized estimating equation models were used to estimate RRs (95% CIs) adjusted for dietary, reproductive, sociodemographic, and lifestyle factors. Results: During 9 y of follow-up of 3582 women, 305 women (8.5%) reported a first diagnosis of HDPs in 6149 pregnancies. We identified 4 dietary patterns labeled as meat, high-fat, and sugar; Mediterranean-style; fruit and low-fat dairy; and cooked vegetables. In the adjusted model, the meat, high-fat, and sugar, fruit and low-fat dairy, and cooked vegetable dietary patterns were not associated with HDP risk. The Mediterranean-style dietary pattern (characterized by vegetables, legumes, nuts, tofu, rice, pasta, rye bread, red wine, and fish) was inversely associated with risk of developing HDPs (quartile 4 compared with quartile 1: RR, 0.58; 95% CI, 0.42, 0.81). Conclusions: In this population-based study of Australian women, we observed an independent protective dose-response association between prepregnancy consumption of a Mediterranean-style dietary pattern and HDP risk. Additional studies are recommended to confirm our findings by prospectively examining whether the implementation of the Mediterranean-style dietary pattern before pregnancy has a role in the prevention of HDPs. [ABSTRACT FROM AUTHOR]

Objective To determine whether 1,5-anhydroglucitol is predictive of neonatal birth weight. Study design A retrospective cohort study including 85 pregnancies complicated by diabetes (Type 1 = 37, Type 2 = 24, gestational = 24). Women had simultaneous hemoglobin A1c and 1,5-anhydroglucitol measurements every 4–8 weeks throughout pregnancy until delivery. Neonatal birth weight was evaluated by standardized z-scores. Linear regression analysis was performed to determine an association of 1,5-anhydroglucitol with neonatal birth weight z -score. Results Type 1 diabetic patients had the lowest mean 1,5-anhydroglucitol of 3.5 mcg/mL (SD = 1.6 mcg/mL) and highest mean hemoglobin A1c of 6.5% (SD = 0.74%) compared to gestational diabetic patients who had the highest mean 1,5-anhydroglucitol of 6.7 mcg/mL (SD = 3.8 mcg/mL) and lowest mean hemoglobin A1c of 6.0% (SD = 0.94%). Mean 1,5-anhydroglucitol values were significantly different between diabetes types ( p < 0.01). Mean neonatal birth weight was above population averages for all diabetes classifications, although mean birth weight z -scores did not differ significantly between diabetic types ( p = 0.38). Multivariate linear regression showed a negative association between log-transformed 1,5-anhydroglucitol and birth weight (coefficient −0.82, 95% CI −1.19, −0.46). Conclusion In pregnancies complicated by diabetes, low 1,5-anhydroglucitol was associated with increased neonatal birth weight. 1,5-Anhydroglucitol may be useful in the assessment of glycemic control in pregnancy in addition to A1c. [ABSTRACT FROM AUTHOR]

Objective To compare the efficacy of intrauterine insemination (IUI) cycles undergoing ovarian hyperstimulation with recombinant FSH (rFSH) or clomiphene citrate (CC) in couples with unexplained and male subfertility. Study design Two hundred and nineteen subfertile couples were enrolled in this randomized prospective study. Patients were randomly assigned to receive 75 IU rFSH or 100 mg CC for two cycles. Cycles with more than four dominant follicles and/or serum E 2 levels higher than 1500 pg/ml were cancelled. Primary outcomes were live birth rates per patient and per cycle, secondary outcomes were clinical and multiple pregnancy rates. Results One hundred and nine women received rFSH and 110 received CC. Both cumulative clinical pregnancy and live birth rates per patient were significantly higher in gonadotropin group (43.1% and 37.6%) as compared to CC group (28.2% and 20%) ( p < 0.05 and p < 0.01, respectively). Live birth rate per cycle were significantly higher in gonadotropin group (24.3%) in comparison with CC group (13.8%) ( p < 0.05). However, clinical pregnancy rate per cycle was not different between groups (28.4% vs 20%) ( p > 0.05). There was no significant difference between gonadotropin and CC group groups in terms of multiple pregnancy rates (10.4% vs 12.5%, p > 0.05). Continuous variables were compared with Student's t test. Categorical variables were compared with Chi square test. Conclusion rFSH has significantly higher cumulative clinical pregnancy and live birth rates when compared to CC with similar multiple pregnancy rates in subfertile patients undergoing IUI. [ABSTRACT FROM AUTHOR]

Extensive research defines the impact of advanced maternal age on couples' fecundity and reproductive outcomes, but significantly less research has been focused on understanding the impact of advanced paternal age. Yet it is increasingly common for couples at advanced ages to conceive children. Limited research suggests that the importance of paternal age is significantly less than that of maternal age, but advanced age of the father is implicated in a variety of conditions affecting the offspring. This review examines three aspects of advanced paternal age: the potential problems with conception and pregnancy that couples with advanced paternal age may encounter, the concept of discussing a limit to paternal age in a clinical setting, and the risks of diseases associated with advanced paternal age. As paternal age increases, it presents no absolute barrier to conception, but it does present greater risks and complications. The current body of knowledge does not justify dissuading older men from trying to initiate a pregnancy, but the medical community must do a better job of communicating to couples the current understanding of the risks of conception with advanced paternal age. [ABSTRACT FROM AUTHOR]

Objective The rate of placenta accreta, a life threatening condition, is constantly increasing, mainly due to the rise in the rates of cesarean sections. This study is aimed to determine the effect of a history of placenta accreta on subsequent pregnancies. Study design A population based retrospective cohort study was designed, including all women who delivered at our medical center during the study period. The study population was divided into two groups including pregnancies with: (1) a history of placenta accreta ( n = 514); and (2) control group without placenta accreta ( n = 239,126). Results (1) A history of placenta accreta is an independent risk factor for postpartum hemorrhage (adjusted OR 4.1, 95% CI 1.5–11.5) as were placenta accreta (adjusted OR 22.0, 95% CI 14.0–36.0) and placenta previa (adjusted OR 7.6, 95% CI 4.4–13.2) in the current pregnancy, and a prior cesarean section (adjusted OR 1.7, 95% CI 1.3–2.2); (2) in addition, placenta accreta in a previous pregnancy is associated with a reduced rate of mild preeclampsia in future pregnancies (1.8% vs. 3.4%, RR 0.51, 95% CI 0.26–0.98); (3) however, in spite of the higher rate of neonatal deaths in the study group, a history of placenta accreta was not an independent risk factor for total perinatal mortality (adjusted OR 1.0, 95% CI 0.5–1.9) after adjusting for confounders. Conclusion A history of placenta accreta is an independent risk factor for postpartum hemorrhage. This should be taken into account in order to ensure a safety pregnancy and delivery of these patients. [ABSTRACT FROM AUTHOR]

Phenylketonuria remains one of the most common inborn errors in the United Kingdom. It is detected on the newborn heel-prick screening sample allowing early treatment with a strict low phenylalanine diet supplemented with artificial amino acids, and appropriate vitamin and minerals. Although the long-term prognosis is good, there is an increasing body of evidence highlighting subtle problems in neuropsychological function with slower reaction times and poorer executive function than peers. White matter changes clearly seen on brain magnetic resonance imaging may have some relationship to these neuropsychological difficulties but their significance is not clearly understood. The diet, although successful, is difficult to follow lifelong and with its attendant risks of nutritional deficiencies needs careful specialist management. In view of these challenges new treatments such as sapropterin (a tetrahydrobiopterin analogue) and large neutral amino acids are currently being used in phenylketonuria and a human trial has started using ammonia lyase as enzyme replacement therapy. Maternal phenylketonuria syndrome remains a risk for those who conceive whilst blood phenylalanine is elevated and females must be counselled early in childhood to avoid this risk. [ABSTRACT FROM AUTHOR]

After kidney transplantation (KT), pregnancy is possible, although the risk of maternal and fetal complications is much higher than in the general population. Outcome of 22 pregnancies in 17 patients transplanted in the Gdańsk center in the period 1980–2012 was studied. Mean maternal age at pregnancy was 30 ± 5 (range, 23–39) years, interval between transplantation and conception 3.4 ± 2.5 (range, 0.6–11) years. Mean creatinine concentration before conception was 1.29 ± 0.36 (range, 0.8–2.45) mg/dL and was stable during 1 year preceding pregnancy (mean increase, 0.01 mg/dL). Nine of the 17 patients received 1 and 4 received ≥2 antihypertensive drugs, and 1 had proteinuria. Twelve of the 17 patients were primagravidas, 1 was pregnant 3 times, and 14 times. At the time of conception, 20 patients received CNI (14 cyclosporine, 6 tacrolimus), 15 antimetabolites (3 mycophenolate mofetil [MMF], 12 azathioprine), 1 mammalian target of rapamycin inhibitor (mTORi; sirolimus), and all prednisone. MMF and mTORi were discontinued before or during the 1st weeks of pregnancy. Maternal outcome: all survived the pregnancy. None experienced rejection or graft loss as a direct result of pregnancy. Maternal complications included edema (5/17), worsening of blood pressure control (5/17), and worsening (1/17) or new onset of proteinuria (2/17). Mean creatinine decrease during pregnancy was 0.06 mg/dL. Mean creatinine 1 year after pregnancy was 1.49 ± 0.53 mg/dL. There were 12 cesarean sections. Fetal outcomes: 17 live births (2 with serious congenital defects), 2 spontaneous and 1 induced abortion, 2 stillbirths. Mean pregnancy age and neonate birth weights were 35 ± 4 (range, 23–39) weeks and 2,552 ± 629 (range, 1,480–3,420) g, respectively. During mean 8.5 (range, 1–25) years of follow-up after pregnancy, 4/17 patients lost grafts. Grafts were lost in the 3rd to 7th years after pregnancy. We conclude that pregnancy does not exert a direct negative influence on patient and graft survivals; 68% of all pregnancies resulted in delivering healthy neonates. [ABSTRACT FROM AUTHOR]

Pregnant women and neonates represent high-risk groups for influenza infection, and in general have suppressed responses to standard influenza vaccines due to pregnancy-associated immune suppression and immune system immaturity, respectively. We therefore wished to test whether addition of Advax™, a polysaccharide adjuvant based on delta inulin, to an inactivated influenza vaccine (A/H1N1/PR8) administered during pregnancy would safely enhance vaccine immunogenicity and thereby provide improved protection of pregnant mothers and their newborns. Pregnant mice received a single intramuscular injection of β-propiolactone-inactivated H1N1 antigen alone or with Advax adjuvant. Pregnant dams receiving Advax-adjuvanted vaccine exhibited significantly increased serum and breast milk anti-influenza IgG titers. This translated into higher serum anti-influenza IgG titers in the pups of these dams. Complete protection was seen in pups of dams that received Advax-adjuvanted vaccine whereas no survival was seen in pups of control mothers or mothers immunized with unadjuvanted influenza vaccine. Cross-fostering studies confirmed that enhanced protection of pups of dams that received Advax-adjuvanted vaccine was mediated by enhanced transfer of maternal IgG to the pups via breast-feeding. The delta inulin adjuvant was not associated with any reproductive or developmental adverse effects. This study shows that Advax adjuvant was safe when administered with influenza vaccine during pregnancy and provided protection of pups via enhanced breast milk transfer of anti-influenza antibodies, not seen with administration of unadjuvanted vaccine. [ABSTRACT FROM AUTHOR]

Objective: To evaluate factors associated with monozygosity (MZ) (number of fetal heartbeats on early ultrasound greater than the number of embryos transferred) and the risk of recurrence in subsequent pregnancies using a national assisted reproduction database. Design: Historical cohort study. Setting: Clinic-based data. Patient(s): 197,327 pregnancies (including 2,824 with evidence of MZ) from cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) between 2004 and 2010. Intervention(s): None. Main Outcome Measure(s): Evidence of MZ, adjusted odds ratios and their 95% confidence intervals computed from logistic regression models. Result(s): In the univariate analysis, the risk of MZ was increased with ovulation disorders, donor oocytes, gonadotropin-releasing hormone agonist (GnRH-a) suppression, assisted hatching (AZH), and day 5–6 transfer, and was decreased with higher follicle-stimulating hormone (FSH) doses (≥3,000 IU). In the multivariate analysis, the risk of MZ was increased with GnRH-a suppression, AZH, and decreased with intracytoplasmic sperm injection (ICSI) and higher FSH dose. The interaction showed that although MZ was more likely with day 5–6 embryos, AZH had a minimal nonsignificant effect, whereas in day 2–3 embryos, AZH had a substantial statistically significant effect. Only one woman had a recurrence of MZ in a subsequent assisted reproduction pregnancy, which is consistent with randomness. Conclusion(s): The risk of MZ was higher with fresh day 5–6 embryos, donor oocytes, GnRH-a suppression, lower FSH doses, and AZH (particularly with day 2–3 embryos). [ABSTRACT FROM AUTHOR]

Over the past 20 years, a substantial body of research has accumulated about ectopic pregnancy, especially about its epidemiology, risk factors, and diagnosis. Nonetheless, the care of women with these pregnancies remains a topic of debate, and no consensus or guidelines exist to clarify the optimal treatment choices. This review revisits the four primary treatments for ectopic pregnancy and defines and details the concept of “activity,” which guides the indications for each treatment. Recent findings of no difference in fertility during the 2 years after an ectopic pregnancy have answered some old questions and raised new ones for determining the optimal management of ectopic pregnancies. Most especially, they allow the consideration and weighing of a wider range of factors, including the woman's own preferences as well as efficacy and the monitoring time until recovery. [ABSTRACT FROM AUTHOR]

Abstract: Each year, a small number of expectant mothers with high-risk pregnancies in British Columbia (BC) are sent to the United States (US) because of a lack of neonatal intensive care unit (NICU) beds. We developed a discrete-event simulation model to determine the impact of changing the number of NICU beds in BC on the probability of transfer to the US and on overall system costs. The model includes births in 25 different zones at five different levels of care; transitions between levels of care over time; and transfers of patients between zones and to the US when there is insufficient capacity. We parameterized the model using data from the BC Health System, the Canadian Institute for Health Information, published reports, internal hospital data and expert opinion. Our analysis suggests that the province should consider a modest increase in NICU capacity. In particular, the use of a bottleneck approach to identify the type and location of 4 new beds at select hospitals throughout the system resulted in a reduction in the probability of transfer to the US and an increase in annual system costs. A model like the one described in this paper may be useful to evaluate the tradeoffs associated with capacity expansion for a number of different services where Canadians seek care in the US. [Copyright &y& Elsevier]

Maternal obesity is defined as a body mass index of 30 or above. It is a common clinical problem and its incidence is increasing. It is associated with an increase in both maternal and perinatal mortality and morbidity. Super-obesity in particular poses unique challenges during the antenatal, intrapartum and postnatal periods and may require the involvement of specialists from a number of fields. Women who are obese are a high-risk group and must be carefully risk assessed in order to optimize their care. [Copyright &y& Elsevier]

Abstract: Deficiencies in calcium (Ca) and magnesium (Mg) are associated with various complications during pregnancy. To test the hypothesis that the status of these minerals is inadequate in pregnancy, a cross-sectional study was conducted of the dietary intake and status of Ca and Mg in pregnant women (n = 50) attending a general public university hospital in Brazil. Dietary intake was assessed from 4-day food records; levels of plasma Mg, erythrocyte Mg, and urinary Ca and Mg excretion were determined by flame atomic absorption spectroscopy; and type I collagen C-telopeptides were evaluated by enzyme-linked immunosorbent assay. Probabilities of inadequate Ca and Mg intake were exhibited by 58 and 98% of the study population, respectively. The mean levels of urinary Ca and Mg excretion were 8.55 and 3.77 mmol/L, respectively. Plasma C-telopeptides, plasma Mg, and erythrocyte Mg were within normal levels. Multiple linear regression analysis revealed positive relationships among urinary Ca excretion, Ca intake (P = .002) and urinary Mg excretion (P < .001) and between erythrocyte Mg and Mg intake (P = .023). It is concluded that the Ca and Mg status of participants was adequate even though the intake of Ca and Mg was lower than the recommended level. [Copyright &y& Elsevier]

The purpose of this committee opinion, which replaces the 2006 ASRM Practice Committee document titled Multiple Pregnancy Associated with Infertility Therapy, is to provide physicians with pertinent information that may help to avoid multiple gestations and to aid in patient counseling regarding the associated risks. [Copyright &y& Elsevier]

Abstract: Background: The study was conducted to compare 6-month usage of the levonorgestrel-releasing intrauterine device (LNG-IUD) when placed immediately or 3 to 6 weeks after dilation and evacuation (D&E) procedure. Study Design: We enrolled women undergoing D&E at 15 to 23 weeks of gestation. After completion of the D&E, subjects without contraindications to immediate IUD insertion were randomized to immediate or delayed (3 to 6 weeks later) LNG-IUD insertion. Subjects in the immediate group had the LNG-IUD placed using ultrasound guidance. All subjects returned at 3 to 6 weeks and 8 to 10 weeks after D&E and were contacted by phone at 6 months. Results: Of the 93 subjects enrolled, 88 were randomized. All 44 subjects (100%) randomized to immediate insertion had successful IUD placement, while only 20 (45.5%) of the 44 subjects randomized to delayed insertion returned for IUD placement, all of which were successful [difference 54.5%, 95% confidence interval (CI) 39.8%–69.3%]. Seventeen (38.6%) participants in each group were lost to follow-up. Of subjects contacted at the 6-month follow-up phone call, 23 of 27 women (85.2%) and 17 of 27 women (62.9%) were utilizing the LNG-IUD in the immediate and delayed groups, respectively (difference 22.2%, 95% CI −0.4% to 44.8%). Intrauterine device expulsion occurred in three subjects (6.8%) and one subject (5.0%) in whom the IUD was placed in the immediate and delayed groups, respectively (p=1.0). No significant adverse events occurred. Conclusion: Significantly more participants had the LNG-IUD placed in the immediate insertion group compared with the delayed insertion group. Given the low risk of complications, immediate post-D&E insertion of the LNG-IUD should be offered, especially for populations that may have difficulty returning for follow-up. [Copyright &y& Elsevier]