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Showing papers on "Pregnancy published in 2012"


Journal ArticleDOI
03 Aug 2012-Cell
TL;DR: It is indicated that host-microbial interactions that impact host metabolism can occur and may be beneficial in pregnancy and when transferred to germ-free mice, T3 microbiota induced greater adiposity and insulin insensitivity compared to T1.

1,466 citations



Journal ArticleDOI
TL;DR: This body of evidence, and the developing consensus regarding biological and behavioral mechanisms, sets the stage for a next era of psychiatric and collaborative interdisciplinary research on pregnancy to reduce the burden of maternal stress, depression, and anxiety in the perinatal period.
Abstract: Purpose of reviewTo briefly review results of the latest research on the contributions of depression, anxiety, and stress exposures in pregnancy to adverse maternal and child outcomes, and to direct attention to new findings on pregnancy anxiety, a potent maternal risk factor.Recent findingsAnxiety,

982 citations


Journal ArticleDOI
TL;DR: Understanding molecular signaling networks that coordinate strategies for successful implantation and decidualization may lead to approaches to improve the outcome of natural pregnancy and pregnancy conceived from in vitro fertilization.
Abstract: Physiological and molecular processes initiated during implantation for pregnancy success are complex but highly organized. This review primarily highlights adverse ripple effects arising from defects during the peri-implantation period that perpetuate throughout pregnancy. These defects are reflected in aberrations in embryo spacing, decidualization, placentation and intrauterine embryonic growth, manifesting in preeclampsia, miscarriages and/or preterm birth. Understanding molecular signaling networks that coordinate strategies for successful implantation and decidualization may lead to approaches to improve the outcome of natural pregnancy and pregnancy conceived from in vitro fertilization.

949 citations


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

750 citations


Journal ArticleDOI
TL;DR: Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes and their combination has a greater impact than either one alone.
Abstract: OBJECTIVE To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS Participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes. RESULTS Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m 2 ), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93, 2.47), for obesity alone 1.73 (1.50, 2.00), and for both GDM and obesity 3.62 (3.04, 4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women). CONCLUSIONS Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.

710 citations


Journal ArticleDOI
04 Dec 2012-BMJ
TL;DR: Survival of babies born between 22 and 25 weeks’ gestation has increased since 1995 but the pattern of major neonatal morbidity and the proportion of survivors affected are unchanged, reflecting an important increase in the number of preterm survivors at risk of later health problems.
Abstract: Objective To determine survival and neonatal morbidity for babies born between 22 and 26 weeks’ gestation in England during 2006, and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks’ gestation. Design Prospective national cohort studies. Setting Maternity and neonatal units in England. Participants 3133 births between 22 and 26 weeks’ gestation in 2006; 666 admissions to neonatal units in 1995 and 1115 in 2006 of babies born between 22 and 25 weeks’ gestation. Main outcome measures Survival to discharge from hospital, pregnancy and delivery outcomes, infant morbidity until discharge. Results In 2006, survival of live born babies was 2% (n=3) for those born at 22 weeks’ gestation, 19% (n=66) at 23 weeks, 40% (n=178) at 24 weeks, 66% (n=346) at 25 weeks, and 77% (n=448) at 26 weeks (P Conclusion Survival of babies born between 22 and 25 weeks’ gestation has increased since 1995 but the pattern of major neonatal morbidity and the proportion of survivors affected are unchanged. These observations reflect an important increase in the number of preterm survivors at risk of later health problems.

688 citations


Journal ArticleDOI
TL;DR: The findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.
Abstract: Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear. Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy. Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K). Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10–7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke. Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.

676 citations


Journal ArticleDOI
TL;DR: Clear protocols for early detection and management of hypertension in pregnancy at all levels of health care are required for better maternal as well as perinatal outcome, especially important in the developing countries.

669 citations


Journal ArticleDOI
TL;DR: Singletons pregnancies after IVF/ICSI are associated with higher risks of obstetric and perinatal complications when compared with spontaneous conception, and further research is needed to determine which aspect of assisted reproduction technology poses most risk and how this risk can be minimized.
Abstract: 1.33-2.09), hypertensive disorders of pregnancy (1.49, 1.39-1.59), preterm rupture of membranes (1.16, 1.07-1.26), Caesarean section (1.56, 1.51-1.60), low birthweight (1.65, 1.56-1.75), perinatal mortality (1.87, 1.48-2.37), preterm delivery (1.54, 1.47-1.62), ges- tational diabetes (1.48, 1.33- 1.66), induction of labour (1.18, 1.10-1.28) and small for gestational age (1.39, 1.27-1.53).

605 citations



Journal ArticleDOI
TL;DR: The role of metformin in improving reproductive outcomes in women with PCOS appears to be limited, and there was no evidence that met formin improves live birth rates whether it is used alone or in combination with clomiphene, or when compared with clmiphene.
Abstract: Background Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation, and high levels of androgens and insulin (hyperinsulinaemia). Hyperinsulinaemia occurs secondary to insulin resistance and is associated with increased risk of cardiovascular disease and diabetes mellitus. Insulin-sensitising agents such as metformin may be effective in treating PCOS-related anovulation. Objectives To evaluate the effectiveness and safety of insulin-sensitising drugs in improving reproductive and metabolic outcomes for women with PCOS undergoing ovulation induction. Search methods We searched the following databases from inception to January 2017: Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. We searched registers of ongoing trials and reference lists from relevant studies. Selection criteria We included randomised controlled trials of insulin-sensitising drugs compared with placebo, no treatment, or an ovulation-induction agent for women with oligo and anovulatory PCOS. Data collection and analysis Two review authors independently assessed studies for eligibility and bias. Primary outcomes were live birth rate and gastrointestinal adverse effects. Secondary outcomes included other pregnancy outcomes, menstrual frequency and metabolic effects. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I2 statistic and reported quality of the evidence for primary outcomes using GRADE methodology. Main results We assessed the interventions metformin, clomiphene citrate, metformin plus clomiphene citrate, D-chiro-inositol, rosiglitazone and pioglitazone. We compared these with each other, placebo or no treatment. We included 48 studies (4451 women), 42 of which investigated metformin (4024 women). Evidence quality ranged from very low to moderate. Limitations were risk of bias (poor reporting of methodology and incomplete outcome data), imprecision and inconsistency. Metformin versus placebo or no treatment The evidence suggests that metformin may improve live birth rates compared with placebo (OR 1.59, 95% CI 1.00 to 2.51, 4 studies, 435 women, I2 = 0%, low-quality evidence). The metformin group experienced more gastrointestinal side effects (OR 4.76, 95% CI 3.06 to 7.41, 7 studies, 670 women, I2 = 61%, moderate-quality evidence) but had higher rates of clinical pregnancy (OR 1.93, 95% CI 1.42 to 2.64, 9 studies, 1027 women, I2 = 43%, moderate-quality evidence), ovulation (OR 2.55, 95% CI 1.81 to 3.59, 14 studies, 701 women, I2 = 58%, moderate-quality evidence) and menstrual frequency (OR 1.72, 95% CI 1.14 to 2.61, 7 studies, 427 women, I2 = 54%, low-quality evidence). There was no clear evidence of a difference in miscarriage rates (OR 1.08, 95% CI 0.50 to 2.35, 4 studies, 748 women, I2 = 0%, low-quality evidence). Metformin plus clomiphene citrate versus clomiphene citrate alone There was no conclusive evidence of a difference between the groups in live birth rates (OR 1.21, 95% CI 0.92 to 1.59, 9 studies, 1079 women, I2 = 20%, low-quality evidence), but gastrointestinal side effects were more common with combined therapy (OR 3.97, 95% CI 2.59 to 6.08, 3 studies, 591 women, I2 = 47%, moderate-quality evidence). However, the combined therapy group had higher rates of clinical pregnancy (OR 1.59, 95% CI 1.27 to 1.99, 16 studies, 1529 women, I2 = 33%, moderate-quality evidence) and ovulation (OR 1.57, 95% CI 1.28 to 1.92, 21 studies, 1624 women, I2 = 64%, moderate-quality evidence). There was a statistically significant difference in miscarriage rate per woman, with higher rates in the combined therapy group (OR 1.59, 95% CI 1.03 to 2.46, 9 studies, 1096 women, I2 = 0%, low-quality evidence) but this is of uncertain clinical significance due to low-quality evidence, and no clear difference between groups when we analysed miscarriage per pregnancy (OR 1.30, 95% CI 0.80 to 2.12, 8 studies; 400 pregnancies, I2 = 0%, low-quality evidence). Metformin versus clomiphene citrate When all studies were combined, findings for live birth were inconclusive and inconsistent (OR 0.71, 95% CI 0.49 to 1.01, 5 studies, 741 women, I2 = 86%, very low-quality evidence). In subgroup analysis by obesity status, obese women had a lower birth rate in the metformin group (OR 0.30, 95% CI 0.17 to 0.52, 2 studies, 500 women, I2 = 0%, very low-quality evidence), while data from the non-obese group showed a possible benefit from metformin, with high heterogeneity (OR 1.71, 95% CI 1.00 to 2.94, 3 studies, 241 women, I2 = 78%, very low-quality evidence). Similarly, among obese women taking metformin there were lower rates of clinical pregnancy (OR 0.34, 95% CI 0.21 to 0.55, 2 studies, 500 women, I2 = 0%, very low-quality evidence) and ovulation (OR 0.29, 95% CI 0.20 to 0.43 2 studies, 500 women, I2 = 0%, low-quality evidence) while among non-obese women, the metformin group had more pregnancies (OR 1.56, 95% CI 1.05 to 2.33, 5 studies, 490 women, I2 = 41%, very low-quality evidence) and no clear difference in ovulation rates (OR 0.81, 95% CI 0.51 to 1.28, 4 studies, 312 women, low-quality evidence, I2=0%). There was no clear evidence of a difference in miscarriage rates (overall: OR 0.92, 95% CI 0.50 to 1.67, 5 studies, 741 women, I2 = 52%, very low-quality evidence). D-chiro-inositol (2 studies), rosiglitazone (1 study) or pioglitazone (1 study) versus placebo or no treatment We were unable to draw conclusions regarding other insulin-sensitising drugs as no studies reported primary outcomes. Authors' conclusions Our updated review suggests that metformin alone may be beneficial over placebo for live birth, although the evidence quality was low. When metformin was compared with clomiphene citrate, data for live birth were inconclusive, and our findings were limited by lack of evidence. Results differed by body mass index (BMI), emphasising the importance of stratifying results by BMI. An improvement in clinical pregnancy and ovulation suggests that clomiphene citrate remains preferable to metformin for ovulation induction in obese women with PCOS. An improved clinical pregnancy and ovulation rate with metformin and clomiphene citrate versus clomiphene citrate alone suggests that combined therapy may be useful although we do not know whether this translates into increased live births. Women taking metformin alone or with combined therapy should be advised that there is no evidence of increased miscarriages, but gastrointestinal side effects are more likely.

Journal ArticleDOI
TL;DR: Several risk factors for both overweight and obesity in childhood are identifiable during infancy and future research needs to focus on whether it is clinically feasible for healthcare professionals to identify infants at greatest risk.
Abstract: Objective To determine risk factors for childhood overweight that can be identified during the first year of life to facilitate early identification and targeted intervention. Design Systematic review and meta-analysis. Search strategy Electronic database search of MEDLINE, EMBASE, PubMed and CAB Abstracts. Eligibility criteria Prospective observational studies following up children from birth for at least 2 years. Results Thirty prospective studies were identified. Significant and strong independent associations with childhood overweight were identified for maternal prepregnancy overweight, high infant birth weight and rapid weight gain during the first year of life. Meta-analysis comparing breastfed with non-breastfed infants found a 15% decrease (95% CI 0.74 to 0.99; I2=73.3%; n=10) in the odds of childhood overweight. For children of mothers smoking during pregnancy there was a 47% increase (95% CI 1.26 to 1.73; I2=47.5%; n=7) in the odds of childhood overweight. There was some evidence associating early introduction of solid foods and childhood overweight. There was conflicting evidence for duration of breastfeeding, socioeconomic status at birth, parity and maternal marital status at birth. No association with childhood overweight was found for maternal age or education at birth, maternal depression or infant ethnicity. There was inconclusive evidence for delivery type, gestational weight gain, maternal postpartum weight loss and ‘fussy’ infant temperament due to the limited number of studies. Conclusions Several risk factors for both overweight and obesity in childhood are identifiable during infancy. Future research needs to focus on whether it is clinically feasible for healthcare professionals to identify infants at greatest risk.

Journal ArticleDOI
TL;DR: The bidirectional interactions between hormones and the immune system contribute to both the outcome of pregnancy and female susceptibility to disease.

Journal ArticleDOI
TL;DR: Higher maternal cortisol levels in early gestation was associated with more affective problems in girls, and this association was mediated, in part, by amygdala volume, while no association between maternal cortisol in pregnancy and child hippocampus volume was observed in either sex.
Abstract: Stress-related variation in the intrauterine milieu may impact brain development and emergent function, with long-term implications in terms of susceptibility for affective disorders. Studies in animals suggest limbic regions in the developing brain are particularly sensitive to exposure to the stress hormone cortisol. However, the nature, magnitude, and time course of these effects have not yet been adequately characterized in humans. A prospective, longitudinal study was conducted in 65 normal, healthy mother–child dyads to examine the association of maternal cortisol in early, mid-, and late gestation with subsequent measures at approximately 7 y age of child amygdala and hippocampus volume and affective problems. After accounting for the effects of potential confounding pre- and postnatal factors, higher maternal cortisol levels in earlier but not later gestation was associated with a larger right amygdala volume in girls (a 1 SD increase in cortisol was associated with a 6.4% increase in right amygdala volume), but not in boys. Moreover, higher maternal cortisol levels in early gestation was associated with more affective problems in girls, and this association was mediated, in part, by amygdala volume. No association between maternal cortisol in pregnancy and child hippocampus volume was observed in either sex. The current findings represent, to the best of our knowledge, the first report linking maternal stress hormone levels in human pregnancy with subsequent child amygdala volume and affect. The results underscore the importance of the intrauterine environment and suggest the origins of neuropsychiatric disorders may have their foundations early in life.

Journal ArticleDOI
TL;DR: Providing additional placental blood to the preterm baby by either delaying cord clamping for 30 to 120 seconds, rather than early clamping, seems to be associated with less need for transfusion, better circulatory stability, less intraventricular haemorrhage (all grades) and lower risk for necrotising enterocolitis.
Abstract: Background Optimal timing for clamping the umbilical cord at preterm birth is unclear. Early clamping allows for immediate transfer of the infant to the neonatologist. Delaying clamping allows blood flow between the placenta, the umbilical cord and the baby to continue. The blood which transfers to the baby between birth and cord clamping is called placental transfusion. Placental transfusion may improve circulating volume at birth, which may in turn improve outcome for preterm infants. Objectives To assess the short- and long-term effects of early rather than delaying clamping or milking of the umbilical cord for infants born at less than 37 completed weeks' gestation, and their mothers. Search methods We searched the Cochrane Pregnancy and Childbirth Group Trials Register (31 May 2011). We updated this search on 26 June 2012 and added the results to the awaiting classification section. Selection criteria Randomised controlled trials comparing early with delayed clamping of the umbilical cord and other strategies to influence placental transfusion for births before 37 completed weeks' gestation. Data collection and analysis Three review authors assessed eligibility and trial quality. Main results Fifteen studies (738 infants) were eligible for inclusion. Participants were between 24 and 36 weeks' gestation at birth. The maximum delay in cord clamping was 180 seconds. Delaying cord clamping was associated with fewer infants requiring transfusions for anaemia (seven trials, 392 infants; risk ratio (RR) 0.61, 95% confidence interval (CI) 0.46 to 0.81), less intraventricular haemorrhage (ultrasound diagnosis all grades) 10 trials, 539 infants (RR 0.59, 95% CI 0.41 to 0.85) and lower risk for necrotising enterocolitis (five trials, 241 infants, RR 0.62, 95% CI 0.43 to 0.90) compared with immediate clamping. However, the peak bilirubin concentration was higher for infants allocated to delayed cord clamping compared with immediate clamping (seven trials, 320 infants, mean difference 15.01 mmol/L, 95% CI 5.62 to 24.40). For most other outcomes (including the primary outcomes infant death, severe (grade three to four) intraventricular haemorrhage and periventricular leukomalacia) there were no clear differences identified between groups; but for many there was incomplete reporting and wide CIs. Outcome after discharge from hospital was reported for one small study; there were no significant differences between the groups in mean Bayley II scores at age seven months (corrected for gestation at birth (58 children)). No studies reported outcomes for the women. Authors' conclusions Providing additional placental blood to the preterm baby by either delaying cord clamping for 30 to 120 seconds, rather than early clamping, seems to be associated with less need for transfusion, better circulatory stability, less intraventricular haemorrhage (all grades) and lower risk for necrotising enterocolitis. However, there were insufficient data for reliable conclusions about the comparative effects on any of the primary outcomes for this review.

Journal ArticleDOI
TL;DR: The review resulted in several conclusions: the diagnosis of placenta accreta and cesarean scar pregnancy is difficult; transvaginal ultrasound seems to be the best diagnostic tool to establish the diagnosis and local methotrexate- and hysteroscopic-directed procedures had the lowest complication rates.

Journal ArticleDOI
TL;DR: AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDssuch as lamotrigine and levetiracetam, and topiramate was associated with an increased risk of cleft lip compared with that of a reference population.
Abstract: Objective: To assess the safety of the newer antiepileptic drugs (AEDs) during pregnancy. Methods: The study population was pregnant women who enrolled in the North American AED Pregnancy Registry between 1997 and 2011. Data on AED use and maternal characteristics were collected through phone interviews at enrollment, at 7 months9 gestation, and postpartum. Malformations were confirmed by medical records. The risk of major malformations was calculated among infants exposed to specific AEDs in monotherapy during the first trimester of pregnancy and among an unexposed group. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with logistic regression. Results: The risk of major malformations was 9.3% (30 of 323) for valproate, 5.5% (11 of 199) for phenobarbital, 4.2% (15 of 359) for topiramate, 3.0% (31 of 1.033) for carbamazepine, 2.9% (12 of 416) for phenytoin, 2.4% (11 of 450) for levetiracetam, and 2.0% (31 of 1,562) for lamotrigine. Compared with lamotrigine, the RR was 5.1 (95% CI 3.0–8.5) for valproate, 2.9 (1.4–5.8) for phenobarbital, and 2.2 (1.2–4.0) for topiramate. The proportion of women with epilepsy who had seizures during pregnancy ranged from 23% for valproate to 31% for lamotrigine. Valproate was associated with a higher risk of neural tube defects, hypospadias, cardiac defects, and oral clefts and phenobarbital with a higher risk of cardiac defects and oral clefts; 5 infants exposed to topiramate (1.4%) had a cleft lip. Conclusions: AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDs such as lamotrigine and levetiracetam. Topiramate was associated with an increased risk of cleft lip compared with that of a reference population.

Journal ArticleDOI
TL;DR: Lifestyle modification is the primary approach; use of medications for diabetes prevention after GDM remains controversial and family planning enables optimization of health in subsequent pregnancies.
Abstract: Gestational diabetes mellitus (GDM) carries a small but potentially important risk of adverse perinatal outcomes and a long-term risk of obesity and glucose intolerance in offspring. Mothers with GDM have an excess of hypertensive disorders during pregnancy and a high risk of developing diabetes mellitus thereafter. Diagnosing and treating GDM can reduce perinatal complications, but only a small fraction of pregnancies benefit. Nutritional management is the cornerstone of treatment; insulin, glyburide and metformin can be used to intensify treatment. Fetal measurements complement maternal glucose monitoring in the identification of pregnancies that require such intensification. Glucose testing shortly after delivery can stratify the short-term diabetes risk in mothers. Thereafter, annual glucose and HbA(1c) testing can detect deteriorating glycaemic control, a harbinger of future diabetes mellitus, usually type 2 diabetes mellitus. Interventions that mitigate obesity or its metabolic effects are most potent in preventing or delaying diabetes mellitus. Lifestyle modification is the primary approach; use of medications for diabetes prevention after GDM remains controversial. Family planning enables optimization of health in subsequent pregnancies. Breastfeeding may reduce obesity in children and is recommended. Families should be encouraged to help children adopt lifestyles that reduce the risk of obesity.

Journal ArticleDOI
TL;DR: In general, women have partners who are several years older than themselves and it is important to focus more on the combined effect of higher female and male age on infertility and reproductive outcome.
Abstract: BACKGROUND Across the developed world couples are postponing parenthood. This review assesses the consequences of delayed family formation from a demographic and medical perspective. One main focus is on the quantitative importance of pregnancy postponement. METHODS Medical and social science databases were searched for publications on relevant subjects such as delayed parenthood, female and male age, fertility, infertility, time to pregnancy (TTP), fetal death, outcome of medically assisted reproduction (MAR) and mental well-being. RESULTS Postponement of parenthood is linked to a higher rate of involuntary childlessness and smaller families than desired due to increased infertility and fetal death with higher female and male age. For women, the increased risk of prolonged TTP, infertility, spontaneous abortions, ectopic pregnancies and trisomy 21 starts at around 30 years of age with a more pronounced effects >35 years, whereas the increasing risk of preterm births and stillbirths starts at around 35 years with a more pronounced effect >40 years. Advanced male age has an important but less pronounced effect on infertility and adverse outcomes. MAR treatment cannot overcome the age-related decline in fecundity. CONCLUSIONS In general, women have partners who are several years older than themselves and it is important to focus more on the combined effect of higher female and male age on infertility and reproductive outcome. Increasing public awareness of the impact of advanced female and male age on the reproductive outcome is essential for people to make well-informed decisions on when to start family formation.

Journal ArticleDOI
04 Oct 2012-Nature
TL;DR: Pregnancy selectively stimulates the accumulation of maternal FOXP3+ CD4 cells with fetal specificity using tetramer-based enrichment that allows the identification of rare endogenous T cells, and pregnancy imprints FoxP3-CD4 cells that sustain protective regulatory memory to fetal antigen.
Abstract: Pregnancy is an intricately orchestrated process where immune effector cells with fetal specificity are selectively silenced. This requires the sustained expansion of immune-suppressive maternal FOXP3(+) regulatory T cells (T(reg) cells), because even transient partial ablation triggers fetal-specific effector T-cell activation and pregnancy loss. In turn, many idiopathic pregnancy complications proposed to originate from disrupted fetal tolerance are associated with blunted maternal T(reg) expansion. Importantly, however, the antigen specificity and cellular origin of maternal T(reg) cells that accumulate during gestation remain incompletely defined. Here we show that pregnancy selectively stimulates the accumulation of maternal FOXP3(+) CD4 cells with fetal specificity using tetramer-based enrichment that allows the identification of rare endogenous T cells. Interestingly, after delivery, fetal-specific T(reg) cells persist at elevated levels, maintain tolerance to pre-existing fetal antigen, and rapidly re-accumulate during subsequent pregnancy. The accelerated expansion of T(reg) cells during secondary pregnancy was driven almost exclusively by proliferation of fetal-specific FOXP3(+) cells retained from prior pregnancy, whereas induced FOXP3 expression and proliferation of pre-existing FOXP3(+) cells each contribute to T(reg) expansion during primary pregnancy. Furthermore, fetal resorption in secondary compared with primary pregnancy becomes more resilient to partial maternal FOXP3(+) cell ablation. Thus, pregnancy imprints FOXP3(+) CD4 cells that sustain protective regulatory memory to fetal antigen. We anticipate that these findings will spark further investigation on maternal regulatory T-cell specificity that unlocks new strategies for improving pregnancy outcomes and novel approaches for therapeutically exploiting T(reg) cell memory.

Journal ArticleDOI
TL;DR: There is a need for well-designed prospective studies and controlled trials in developing country settings that examine relationships with low birthweight, SGA, PTD, stillbirth and maternal and neonatal mortality.
Abstract: Current understanding of biologic processes indicates that women's nutritional status before and during early pregnancy may play an important role in determining early developmental processes and ensuring successful pregnancy outcomes. We conducted a systematic review of the evidence for the impact of maternal nutrition before and during early pregnancy (<12 weeks gestation) on maternal, neonatal and child health outcomes and included 45 articles (nine intervention trials and 32 observational studies) that were identified through PubMed and EMBASE database searches and examining review articles. Intervention trials and observational studies show that periconceptional (<12 weeks gestation) folic acid supplementation significantly reduced the risk of neural tube defects. Observational studies suggest that preconceptional and periconceptional intake of vitamin and mineral supplements is associated with a reduced risk of delivering offspring who are low birthweight and/or small-for-gestational age (SGA) and preterm deliveries (PTD). Some studies report that indicators of maternal prepregnancy size, low stature, underweight and overweight are associated with increased risks of PTD and SGA. The available data indicate the importance of women's nutrition prior to and during the first trimester of pregnancy, but there is a need for well-designed prospective studies and controlled trials in developing country settings that examine relationships with low birthweight, SGA, PTD, stillbirth and maternal and neonatal mortality. The knowledge gaps that need to be addressed include the evaluation of periconceptional interventions such as food supplements, multivitamin-mineral supplements and/or specific micronutrients (iron, zinc, iodine, vitamin B-6 and B-12) as well as the relationship between measures of prepregnancy body size and composition and maternal, neonatal and child health outcomes.

Journal ArticleDOI
TL;DR: The effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS and the high heterogeneity in this subgroup could not be explained by population differences or differences in quality of the trials.
Abstract: Background Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned both due to the risk of postsurgical adhesions and the introduction of medical ovulation induction. However, women with PCOS who are treated with medical ovulation induction, with drugs such as gonadotrophins, often have an over-production of follicles which may result in ovarian hyperstimulation syndrome and multiple pregnancies. Moreover, gonadotrophins, though effective, are costly and time-consuming and their use requires intensive monitoring. Surgical therapy with laparoscopic ovarian 'drilling' (LOD) may avoid or reduce the need for medical ovulation induction, or may facilitate its usefulness. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception, or that subsequent medical ovulation induction becomes easier. Objectives To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. Search methods We used the search strategy of the Menstrual Disorders and Subfertility Group (MDSG) to search the MDSG Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO. The keywords included polycystic ovary syndrome, laparoscopic ovarian drilling, electrocautery and diathermy. Searches were conducted in September 2011, and a further search of the MDSG Trials Register was made on 14 May 2012. Selection criteria We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS who undertook laparoscopic ovarian drilling in order to induce ovulation. Data collection and analysis This is an update of a previously updated review. There were nine RCTs in the previous version; an additional 16 trials were added in the current (2012) update. All trials were assessed for quality. The primary outcomes were live birth and multiple pregnancy. The secondary outcomes were rate of miscarriage, ovulation and pregnancy rates, ovarian hyperstimulation syndrome (OHSS), quality of life and cost. Main results Nine trials, including 1210 women, reported on the primary outcome of live birth rate per couple. Live births were reported in 34% of women in the LOD groups and 38% in other medical treatment groups. There were five different comparisons with LOD and there was no evidence of a difference in live births when compared with clomiphene citrate + tamoxifen (OR 0.81; 95% CI 0.42 to 1.53; P = 0.51, 1 trial, n = 150), gonadotrophins (OR 0.97; 95% CI 0.59 to 1.59; P = 0.89, I(2) = 0%, 2 trials, n = 318), aromatase inhibitors (OR 0.84; 95% CI 0.54 to 1.31; P = 0.44, I(2) = 0%, 2 trials, n = 407) or clomiphene citrate (OR 1.21; 95%CI 0.64 to 2.32; 1 trial, n=176, P= 0.05). There was evidence of significantly fewer live births following LOD compared with clomiphene citrate + metformin (OR 0.44; 95% CI 0.24 to 0.82; P = 0.01, I(2) = 78%, 2 trials, n = 159); the high heterogeneity in this subgroup could not be explained by population differences or differences in quality of the trials.Thirteen trials reported on multiple pregnancies (n= 1305 women). There were no cases of multiple pregnancies in either group for clomiphene citrate or aromatase inhibitors compared with LOD. The rate of multiple pregnancies was significantly lower in the LOD group compared with trials using gonadotrophins (OR 0.13; 95% CI 0.03 to 0.52; P=0.004, I(2) = 0%, 5 trials, n = 166). Authors' conclusions There was no evidence of a significant difference in rates of clinical pregnancy, live birth or miscarriage in women with clomiphene-resistant PCOS undergoing LOD compared to other medical treatments. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about the long-term effects of LOD on ovarian function.

Journal ArticleDOI
01 Mar 2012
TL;DR: Results suggest that health outcomes of moderate/late preterm and early term babies are worse than those of full term babies, and large numbers of these babies present a greater burden on public health services than very preterm babies.
Abstract: Objective To investigate the burden of later disease associated with moderate/late preterm (32-36 weeks) and early term (37-38 weeks) birth.

Journal ArticleDOI
TL;DR: The results do not suggest that mild infections, febrile episodes, or use of antibiotics during pregnancy are strong risk factors for ASD/infantile autism, but suggest that prolonged episodes of fever caused a threefold increased risk of infantile autism.
Abstract: WHAT'S KNOWN ON THIS SUBJECT: It has been suggested that maternal immune activation during pregnancy is associated with cardinal behaviors of autism in the offspring. Epidemiologic studies have yielded conflicting results concerning the association between any infection during pregnancy and the development of autism. WHAT THIS STUDY ADDS: This population-based cohort study investigated the association between specific common infectious diseases, febrile episodes, or use of antibiotics during pregnancy by using maternal population-based self-reported data. abstract Results of animal studies suggest that maternal immune activation during pregnancy causes deficiencies in fetal neurodevelop- ment. Infectious disease is the most common path to maternal immune activation during pregnancy. The goal of this study was to determine the occurrence of common infections, febrile episodes, and use of anti- biotics reported by the mother during pregnancy and the risk for au- tism spectrum disorder (ASD) and infantile autism in the offspring. METHODS: We used a population-based cohort consisting of 96 736 children aged 8 to 14 years and born from 1997 to 2003 in Denmark. Information on infection, febrile episodes, and use of antibiotics was self-reported through telephone interviews during pregnancy and early postpartum. Diagnoses of ASD and infantile autism were retrieved from the Danish Psychiatric Central Register; 976 children (1%) from the cohort were diagnosed with ASD. RESULTS: Overall, we found little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism. However, our data suggest that maternal influenza infection was associated with a twofold increased risk of infantile autism, prolonged episodes of fever caused a threefold increased risk of infantile autism, and use of various antibiotics during pregnancy were potential risk factors for ASD/infantile autism.

Journal ArticleDOI
TL;DR: The major adaptations of the maternal cardiovascular system that progress throughout gestation may unmask previously unrecognized heart disease and result in significant morbidity and mortality.

Journal ArticleDOI
TL;DR: The evidence suggests antenatal dietary and lifestyle intervention in obese pregnant women reduces maternal pregnancy weight gain and a trend towards a reduction in the prevalence of gestational diabetes in the overweight and obese population.
Abstract: Overweight and obesity pose a big challenge to pregnancy as they are associated with adverse maternal and perinatal outcome. Evidence of lifestyle intervention resulting in improved pregnancy outcome is conflicting. Hence the objective of this study is to determine the efficacy of antenatal dietary, activity, behaviour or lifestyle interventions in overweight and obese pregnant women to improve maternal and perinatal outcomes. A systematic review and meta-analyses of randomised and non-randomised clinical trials following prior registration (CRD420111122 http://www.crd.york.ac.uk/PROSPERO ) and PRISMA guidelines was employed. A search of the Cochrane Library, EMBASE, MEDLINE, CINAHL, Maternity and Infant care and eight other databases for studies published prior to January 2012 was undertaken. Electronic literature searches, study selection, methodology and quality appraisal were performed independently by two authors. Methodological quality of the studies was assessed according to Cochrane risk of bias tool. All appropriate randomised and non-randomised clinical trials were included while exclusions consisted of interventions in pregnant women who were not overweight or obese, had pre-existing diabetes or polycystic ovarian syndrome, and systematic reviews. Maternal outcome measures, including maternal gestational weight gain, gestational diabetes and Caesarean section, were documented. Fetal outcomes, including large for gestational age and macrosomia (birth weight > 4 kg), were also documented. Thirteen randomised and six non-randomised clinical trials were identified and included in the meta-analysis. The evidence suggests antenatal dietary and lifestyle intervention in obese pregnant women reduces maternal pregnancy weight gain (10 randomised clinical trials; n = 1228; -2.21 kg (95% confidence interval -2.86 kg to -1.59 kg)) and a trend towards a reduction in the prevalence of gestational diabetes (six randomised clinical trials; n = 1,011; odds ratio 0.80 (95% confidence interval 0.58 to 1.10)). There were no clear differences reported for other outcomes such as Caesarean delivery, large for gestational age, birth weight or macrosomia. All available studies were assessed to be of low to medium quality. Antenatal lifestyle intervention is associated with restricted gestational weight gain and a trend towards a reduced prevalence of gestational diabetes in the overweight and obese population. These findings need to be interpreted with caution as the available studies were of poor to medium quality.

Journal ArticleDOI
TL;DR: The risks for influenza-associated complications among pregnant women and infants <6 months old are reviewed and influenza vaccination during pregnancy is shown to decrease the risk of influenza and its complications.

20 Jun 2012
TL;DR: Pregnancy rates for women in their early 20s declined to the lowest level in more than three decades, although the declines have been more modest than for teenagers.
Abstract: Objectives This report presents detailed pregnancy rates for 1990-2008, updating a national series of rates extending since 1976. Methods Tabular and graphical data on pregnancy rates by age, race, and Hispanic origin, and by marital status are presented and described. Results In 2008, an estimated 6,578,000 pregnancies resulted in 4,248,000 live births, 1,212,000 induced abortions, and 1,118,000 fetal losses. The 2008 pregnancy rate of 105.5 pregnancies per 1000 women aged 15-44 is 9 percent below the 1990 peak of 115.8. The teen pregnancy rate dropped 40 percent from 1990 to 2008, reaching a historic low of 69.8 per 1000 women aged 15-19. Pregnancy rates have declined significantly for non-Hispanic white, non-Hispanic black, and Hispanic teenagers. Rates in 2008 for non-Hispanic black and Hispanic teenagers were two to three times higher than the rates for non-Hispanic white teenagers. Pregnancy rates for women in their early 20s declined to the lowest level in more than three decades, although the declines have been more modest than for teenagers. Pregnancy rates for women aged 25-29 have changed relatively little since 1990, while rates for women in their 30s and early 40s increased.

Journal ArticleDOI
TL;DR: In this article, the authors estimate the risk of women dying from pregnancy complications in the United States and examine the risk factors for and changes in the medical causes of these deaths, using de-identified copies of death certificates for women who died during or within 1 year of pregnancy.
Abstract: OBJECTIVE:To estimate the risk of women dying from pregnancy complications in the United States and to examine the risk factors for and changes in the medical causes of these deaths.METHODS:De-identified copies of death certificates for women who died during or within 1 year of pregnancy and matchin