Exposure to heavy metals in utero and autism spectrum disorder at age 3: a meta-analysis of two longitudinal cohorts of siblings of children with autism.

BACKGROUND: Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized. METHODS: In Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts. RESULTS: In EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD. A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD. CONCLUSION: Exposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.

Magnitude and determinants of psychological morbidities among pregnant women: Results from a pregnancy cohort in rural Central India.

Background: Psychological morbidities are one of the emerging global health problems. It affects a considerable number of ante-natal women leading to consequences during the postnatal period as well. We conducted this research to study the magnitude and determinants of psychological morbidities during pregnancy. Methods: In this study, we included 650 pregnant women from an established cohort of 2500 pregnant women and assessed the psychological morbidities among them using the GMHAT/PC tool. Results: The overall prevalence of psychological morbidities during pregnancy was 14.6%, with anxiety and depression being the leading ones. Low education levels, lower socio-economic status, unintended pregnancy, complicated previous pregnancy, lack of family and social support, and domestic violence increased the odds of psychological morbidity. On Multivariate logistic regression, Low education levels increased the odds to more than twice [illiterate/primary schooling OR: 4.00, p = 0.026; secondary schooling OR: 2.64, p = 0.034; high school OR: 2.60, p = 0.033] unintended pregnancy [OR: 1.91, p = 0.043] and lack of family support [OR: 7.19, p < 0.001] increased the odds of psychological morbidity among pregnant women. Conclusion: Bringing these issues to the mainstream and addressing them by developing interventions to address them during the lifecycle of a female will help to prevent episodes of psychological stress and morbidity among pregnant females.

Maternal major depression during early pregnancy is associated with impaired child executive functioning at 4.5 years of age.

BACKGROUND: Maternal depression is a serious condition that affects up to 1 in 7 pregnancies. Despite evidence linking maternal depression to pregnancy complications and adverse fetal outcomes, there remain large gaps in its identification and treatment. More work is needed to define the specific timing and severity of depression that most urgently requires intervention, where feasible, to protect maternal health and the developing fetus. OBJECTIVE: This study aimed to examine whether the timing and severity of maternal depression and/or anxiety during pregnancy affect child executive functioning at age 4.5 years. Executive functioning in the preschool years is a strong predictor of both school readiness and long-term quality of life. STUDY DESIGN: This longitudinal observational pregnancy cohort study included a sample of 323 mother-child dyads taking part in the Ontario Birth Study, an open pregnancy cohort in Toronto, Ontario, Canada. Maternal symptoms of depression and anxiety were assessed at 12 to 16 and 28 to 32 weeks of gestation and at the time of child testing at age 4.5 years using the 4-item Patient Health Questionnaire. Child executive functioning was measured during a home visit using standardized computerized administration of the Flanker test (a measure of attention) and the Dimensional Change Card Sort (a measure of cognitive flexibility). Stepwise linear regressions, controlling for possible confounding variables, were used to assess the predictive value of continuous measures of maternal depression and/or anxiety symptoms at each assessment time on the Flanker test and Dimensional Change Card Sort. Posthoc general linear models were used to assess whether maternal depression severity categories (no symptom, mild symptoms, or probable major depressive disorder) were helpful in identifying children at risk. RESULTS: Across all children, after controlling for potential confounds, greater maternal depressive symptoms at weeks 12 to 16 weeks of gestation predicted worse performance on both the Flanker test (ΔR2=0.058; P<.001) and the Dimensional Change Card Sort (ΔR2=0.017; P=.018). Posthoc general linear modeling further demonstrated that the children of mothers meeting the screening criteria for major depression in early pregnancy scored 11.3% lower on the Flanker test and 9.8% lower on the Dimensional Change Card Sort than the children of mothers without maternal depressive symptoms in early pregnancy. Mild depressive symptoms had no significant effect on executive function scores. There was no significant effect of anxiety symptoms or maternal antidepressant use in early pregnancy or pandemic conditions or maternal symptoms in later pregnancy or at the time of child testing on either the Flanker or Dimensional Change Card Sort results. CONCLUSION: This study demonstrated that fetal exposure to maternal major depression, but not milder forms of depression, at 12 to 16 weeks of gestation is associated with impaired executive functioning in the preschool years. Child executive functioning is crucial for school readiness and predicts long-term quality of life. This emphasizes an urgent need to improve the recognition and treatment of maternal major depression, particularly in early pregnancy, to limit its negative effects on the patient and on child cognitive development.

Maternal stress during pregnancy and gestational duration: A cohort study from the Danish National Birth Cohort.

BACKGROUND: Preterm birth is one of the most important contributors to neonatal mortality and morbidity. Experiencing stress during pregnancy may increase the risk of adverse birth outcomes, including preterm birth. This association has been observed in previous studies, but differences in measures used limit comparability. OBJECTIVE: The objective of the study was to investigate the association between two measures of maternal stress during pregnancy, life stress and emotional distress, and gestation duration. METHODS: Women recruited in the Danish National Birth Cohort from 1996 to 2002, who provided information on their stress level during pregnancy and expecting a singleton baby, were included in the study. We assessed the associations between the level of life stress and emotional distress in quartiles, both collected at 31 weeks of pregnancy on average, and the rate of giving birth using Cox regression within intervals of the gestational period. RESULTS: A total of 80,991 pregnancies were included. Women reporting moderate or high levels of life stress vs no stress had a higher rate of giving birth earlier within all intervals of gestational age (e.g. high level: 27-33 weeks: hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.04, 1.84; 34-36 weeks: 1.10, 95% CI 0.97, 1.25; 37-38 weeks: 1.21, 95% CI 1.15, 1.28). These associations between life stress and preterm birth were mainly driven by pregnancy worries. For emotional distress, a high level of distress was associated with shorter length of gestation in the preterm (27-33 weeks: 1.38, 95% CI 1.02, 1.86; 34-36 weeks: 1.05, 95% CI 0.91, 1.19) and early term (1.11, 95% CI 1.04, 1.17) intervals. CONCLUSIONS: Emotional distress and life stress were shown to be associated with gestational age at birth, with pregnancy-related stress being the single stressor driving the association. This suggests that reverse causality may, at least in parts, explain the earlier findings of stress as a risk factor for preterm birth.

How costly is the first prenatal clinic visit? Analysis of out-of-pocket expenditure in rural Sri Lanka - a country with free maternal health care.

BACKGROUND: This study aimed to determine the magnitude of and factors associated with out-of-pocket expenditure (OOPE) during the first prenatal clinic visit among pregnant women in Anuradhapura district, Sri Lanka, which provides free maternal healthcare. METHODS: The study design was a cross-sectional study, and the study setting was 22 Medical Officers of Health (MOOH) areas in Anuradhapura District, Sri Lanka. Data of 1389 pregnant women were analyzed using descriptive statistics and non-parametric tests. RESULTS: The mean OOPE of the first prenatal clinic visit was USD 8.12, which accounted for 2.9 and 4.5% of the household income and expenditure, respectively. Pregnant women who used only government-free health services (which are free of charge at the point of service delivery) had an OOPE of USD 3.49. A significant correlation was recorded between household expenditure (rs = 0.095, p = 0.002) and the number of pregnancies (rs = - 0.155, p < 0.001) with OOPE. Education level less than primary education is positively contributed to OOPE (p < 0.05), and utilizing government-free maternal health services lead to a decrease in the OOPE for the first prenatal clinic visit (p < 0.05). CONCLUSION: Despite having free maternal services, the OOPE of the first prenatal clinic visit is high in rural Sri Lanka. One-fifth of pregnant women utilize private health services, and pregnant women who used only government-free maternal health services also spend a direct medical cost for medicines/micronutrient supplements.

Insufficient maternal iodine intake is associated with subfecundity, reduced foetal growth, and adverse pregnancy outcomes in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Severe iodine deficiency impacts fertility and reproductive outcomes. The potential effects of mild-to-moderate iodine deficiency are not well known. The aim of this study was to examine whether iodine intake was associated with subfecundity (i.e. > 12 months trying to get pregnant), foetal growth, and adverse pregnancy outcomes in a mild-to-moderately iodine-deficient population. METHODS: We used the Norwegian Mother, Father and Child Cohort Study (MoBa) and included 78,318 pregnancies with data on iodine intake and pregnancy outcomes. Iodine intake was calculated using an extensive food frequency questionnaire in mid-pregnancy. In addition, urinary iodine concentration was available in a subsample of 2795 pregnancies. Associations were modelled continuously by multivariable regression controlling for a range of confounding factors. RESULTS: The median iodine intake from food was 121 µg/day and the median urinary iodine was 69 µg/L, confirming mild-to-moderate iodine deficiency. In non-users of iodine supplements (n = 49,187), low iodine intake (< 100-150 µg/day) was associated with increased risk of preeclampsia (aOR = 1.14 (95% CI 1.08, 1.22) at 75 vs. 100 µg/day, p overall < 0.001), preterm delivery before gestational week 37 (aOR = 1.10 (1.04, 1.16) at 75 vs. 100 µg/day, p overall = 0.003), and reduced foetal growth (- 0.08 SD (- 0.10, - 0.06) difference in birth weight z-score at 75 vs. 150 µg/day, p overall < 0.001), but not with early preterm delivery or intrauterine death. In planned pregnancies (n = 56,416), having an iodine intake lower than ~ 100 µg/day was associated with increased prevalence of subfecundity (aOR = 1.05 (1.01, 1.09) at 75 µg/day vs. 100 µg/day, p overall = 0.005). Long-term iodine supplement use (initiated before pregnancy) was associated with increased foetal growth (+ 0.05 SD (0.03, 0.07) on birth weight z-score, p < 0.001) and reduced risk of preeclampsia (aOR 0.85 (0.74, 0.98), p = 0.022), but not with the other adverse pregnancy outcomes. Urinary iodine concentration was not associated with any of the dichotomous outcomes, but positively associated with foetal growth (n = 2795, p overall = 0.017). CONCLUSIONS: This study shows that a low iodine intake was associated with restricted foetal growth and a higher prevalence of preeclampsia in these mild-to-moderately iodine-deficient women. Results also indicated increased risk of subfecundity and preterm delivery. Initiating iodine supplement use in pregnancy may be too late.

Organophosphate pesticides exposure during fetal development and IQ scores in 3 and 4-year old Canadian children.

BACKGROUND: Organophosphate pesticides are widely used in agriculture and for other purposes, leading to ubiquitous exposure in human populations. Some studies reported cognitive deficits in children exposed prenatally to organophosphate pesticides, but findings from recent studies were inconsistent. Furthermore, recent biomonitoring studies suggest exposure levels have decreased. Hence, the risks from current prenatal exposure to organophosphate pesticides for child neurodevelopment are uncertain. Furthermore, sex-differences also remain to be better documented in relation to potential neurodevelopmental effects. OBJECTIVE: To examine the association between prenatal exposure to organophosphate pesticides and IQ scores among boys and girls living in several major Canadian cities. METHODS: We used data from the MIREC cohort (Maternal-Infant Research on Environmental Chemicals). Women were recruited in 2008-2011 from 10 Canadian cities during their first trimester of pregnancy, and urine spot samples were collected for measurement of three dimethyl alkyl phosphate (DMAP) and three diethyl alkyl phosphate (DEAP) metabolites. When children were 3-4 years of age, we used the Wechsler Preschool and Primary Scales of Intelligence-III (WPPSI-III) to assess cognitive ability of children from 6 out of the 10 cities (Halifax, Hamilton, Kingston, Montreal, Toronto, and Vancouver). We analysed the association between maternal exposure to organophosphate pesticides (DMAP and DEAP urinary metabolites) and children's IQ scores with generalized estimating equations (GEEs) to take into account the clustered-data resulting from the six study sites. All analyses were sex-stratified (n = 296 boys and 311 girls). RESULTS: The participants were predominantly well-educated, white women, with a relatively high household income. Children had a mean age of 3.4 years at the moment of IQ assessment (range, 3.0-4.1 years). In girls, there was no association between IQ scores and DEAPs or DMAPs. Higher concentrations of DEAPs were significantly associated with poorer Verbal IQ scores (for a 10-fold increase in concentrations, -6.28; 95% CIs, -12.13, -0.43) in boys. The association for Performance IQ in boys also indicated poorer scores with higher DEAP concentrations, but the confidence intervals included the null value (-4.05; 95% CIs, -10.19, 2.10). The relation between DMAPs and IQ scores in boys was also negative, but association estimates were small and not significant. CONCLUSION: Urinary metabolites of organophosphate pesticides were not associated with IQ in girls, but we observed that higher maternal urinary DEAPs were associated with poorer Verbal IQ in boys. However, exposure misclassification may be an issue as only one urine sample per woman was analysed. The present study contributes to the accumulating evidence linking exposure to organophosphate pesticides during fetal development with poorer cognitive function in children, bringing data on the risks in a context of low exposure levels encountered in primarily urban populations from Canada.

Resumption of sex after a second birth: An Australian prospective cohort.

BACKGROUND: Few longitudinal studies have examined women's experiences of sex after childbirth. Much of the advice given to couples about what to expect in relation to sex after childbirth is based on cross-sectional studies. OBJECTIVE: To investigate timing of resumption of sex after a second birth and assess associations with obstetric factors (method of birth and perineal trauma) and time interval between first and second births. METHOD: Prospective cohort of 1507 nulliparous women recruited before 25 weeks' gestation in Melbourne, Australia followed up at 3, 6, 9, and 12 months after first births, and 6 and 12 months after second births. Measures include: obstetric factors and resumption of vaginal sex after first and second births. RESULTS: By 8 weeks after their second birth, 56% of women had resumed vaginal sex, compared with 65% after their first birth. Women were more likely to resume sex later than 8 weeks postpartum if they had a spontaneous vaginal birth with episiotomy or sutured perineal tear (aOR: 2.21, 95% CI: 1.5-3.2), operative vaginal birth (aOR: 2.60, 95% CI: 1.3-5.3) or cesarean delivery (aOR: 2.15, 95% CI: 1.4-3.3) compared with a vaginal birth with minimal or no perineal trauma. There was no association between timing of resumption of sex and the time interval between births. CONCLUSION: For almost half of the cohort, sex was not resumed until at least 8 weeks after the second birth. Timing of resumption of sex was influenced by obstetric factors, but not the time interval between births.

Environmental exposures and fetal growth: the Haifa pregnancy cohort study.

BACKGROUND: The developing fetus is susceptible to environmental insults. Studying the effects of environmental exposures on fetal growth is essential for understanding the causal pathway between prenatal exposures and pregnancy outcomes. Here we describe the Haifa Pregnancy Cohort Study (HPCS) and discuss challenges and opportunities in applying "big data" paradigm. METHODS: Maccabi Healthcare Services (MHS), is the second largest Israeli health maintenance organization (HMO) providing care services to two million beneficiaries. The HPCS cohort potentially includes ~750,000 newborns born between 1998 and 2017. We will estimate daily exposures to air pollutants, temperature and greenness, using satellite-based data and models. We hypothesize that residents of Haifa have higher exposures to environmental pollutants and that in pregnant women this higher exposure is associated with poorer fetal growth. We will evaluate outcomes such as birth-weight, head-circumference and gestational age at birth. We will adjust for pregnancy complications such as pre-eclampsia and gestational diabetes and parental variables, such as maternal weight, age and smoking habits as potential confounders. In addition, we will conduct a multi-tiered field study, nested within this population, among 150 pregnant women residing in two geographical regions-one in the polluted Haifa area, and one in a relatively unpolluted area in central Israel. Blood and urinary samples will be collected, as well as personal and indoor exposure to air pollution. DISCUSSION: Evaluating environmental exposures of pregnant women and assessing in utero growth over the course of the pregnancy during different exposure windows, is of great scientific and public health interest. Recent advances in data collection and analysis pose great promise to provide insights into contribution of environment to the health of the developing fetus, but also pose major challenges and pitfalls, such as data management, proper statistical framework and integration of data in the population-based study and selectiveness in the nested field study. Yet the continuing follow-up of the study cohort, integrating data from different services, health-promotion, and eventually, application later in real life of our main promises. Our study aims to meet these challenges and to provide evidence of the environmental exposures associated with fetal growth.

SSRI and SNRI use during pregnancy and the risk of persistent pulmonary hypertension of the newborn.

AIM: The use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy may be associated with an increased risk of persistent pulmonary hypertension of the newborn (PPHN). Limited data are available on the risk of PPHN associated with serotonin norepinephrine reuptake inhibitors (SNRIs). We aimed to quantify both associations. METHODS: Using data from the Quebec Pregnancy Cohort between 1998 and 2009, we included women covered by the provincial drug plan who had a singleton live birth. Exposure categories were SSRI, SNRI and other antidepressant use; non-users were considered as the reference category. Generalized estimating equation models were used to obtain risk estimates and 95% confidence intervals (CIs). Confounding by indication was minimized by adjusting for history of maternal depression/anxiety before pregnancy. RESULTS: Overall, 143 281 pregnancies were included; PPHN was identified in 0.2% of newborns. Adjusting for maternal depression, and other potential confounders, SSRI use during the second half of pregnancy was associated with an increased risk of PPHN [adjusted odds ratio (aOR) 4.29, 95% CI 1.34, 13.77] compared with non-use of antidepressants; SNRI use during the same time window was not statistically associated with the risk of PPHN (aOR 0.59, 95% CI 0.06, 5.62). Use of SSRIs and SNRIs before the 20th week of gestation was not associated with the risk of PPHN. CONCLUSIONS: Use of SSRIs in the second half of pregnancy was associated with the risk of PPHN. Given our results on SNRIs and the lack of statistical power for these analyses, it is unclear whether SNRI use during pregnancy also increases the risk of PPHN.

Antidepressant Use in Pregnancy and the Risk of Attention Deficit with or without Hyperactivity Disorder in Children.

BACKGROUND: The association between antidepressant (AD) use during pregnancy and the risk of attention deficit with or without hyperactivity disorder (ADHD) in children is debated. We investigated the risk of ADHD associated with overall and class-specific antidepressant exposure in utero. METHODS: We designed a register-based cohort study using the Quebec Pregnancy/Children Cohort (QPC). A total of 144 406 singleton full-term live-born from 1998 to 2009 were included. Cox proportional hazards regression models were used to estimate unadjusted and adjusted hazard ratio with 95% confidence interval (CI). RESULTS: During 542 897 person-years of follow-up, 4564 (3.2%) infants were identified with ADHD. The mean age at first ADHD diagnosis was 6.3 ± 2.3 years (range 0-11 years), and the mean age at first ADHD medication use was 7.0 ± 1.5 years. Adjusting for potential confounders, including maternal history of depression/anxiety and ADHD, AD use during the 2nd or 3rd trimester of pregnancy was associated with an increased risk of (HR 1.3, 95% CI 1.0, 1.6; 134 exposed cases). More specifically, tricyclic use was associated with an increased risk of ADHD (HR 1.8, 95% CI 1.0, 3.1; 16 exposed cases); SSRI and SNRI use were not associated with increased ADHD risk. CONCLUSION: This study suggests that AD use during the 2nd and 3rd trimester of pregnancy, specifically tricyclics, is an independent risk factor for ADHD in children above and beyond the risk associated with maternal depression/anxiety or ADHD. However, residual confounding by indication severity could not be completely ruled out.

Maternal and infant inflammatory markers in relation to prenatal arsenic exposure in a U.S. pregnancy cohort.

INTRODUCTION: Accumulating evidence indicates that arsenic (As), a potent environmental toxicant, may increase cardiovascular disease risk and adversely affect endothelial function at high levels of exposure. Pregnancy is a vulnerable time for both mother and child; however, studies examining the association between prenatal As exposure and plasma biomarkers of inflammation and endothelial function in mothers and newborns are lacking. METHODS: We examined maternal urinary As levels at gestational weeks 24-28 and levels of inflammatory biomarkers in plasma from 563 pregnant women and 500 infants' cord blood. We assessed a multiplexed panel of circulating inflammatory and endothelial function markers, including tumor necrosis factor alpha (TNFα), monocyte chemoattractant protein 1 (MCP1), intercellular adhesion molecule (ICAM1) and vascular cell adhesion molecule (VCAM1). RESULTS: Compared with the bottom tertile, the highest tertile of maternal urinary As during pregnancy was associated with a 145.2ng/ml (95% CI 4.1, 286.3; p=0.04) increase in cord blood ICAM1 and 557.3ng/ml (95% CI -56.4, 1171.1; p=0.09) increase in cord blood VCAM1. Among mothers, the highest tertile of maternal urinary As during pregnancy was related to a 141.8ng/ml (95% CI 26.1, 257.5; p=0.02) increase maternal plasma VCAM1 levels. Urinary As was unrelated to MCP1 or TNFα in maternal plasma and cord blood. In structural equation models, the association between maternal urinary As and infant VCAM was mediated by maternal levels of VCAM (ßmediation: 0.024, 95% CI: 0.002, 0.050). CONCLUSION: Our observations indicate that As exposure during pregnancy may affect markers of vascular health and endothelial function in both pregnant women and children, and suggest further investigation of the potential impacts on cardiovascular health in these susceptible populations.

3D Cohort Study: The Integrated Research Network in Perinatology of Quebec and Eastern Ontario.

BACKGROUND: The 3D Cohort Study (Design, Develop, Discover) was established to help bridge knowledge gaps about the links between various adverse exposures during pregnancy with birth outcomes and later health outcomes in children. METHODS: Pregnant women and their partners were recruited during the first trimester from nine sites in Quebec and followed along with their children through to 2 years of age. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, mental health and life style, medical history, psychosocial measures, diet, infant growth, and neurodevelopment. Information on the delivery and newborn outcomes were abstracted from medical charts. Biological specimens were collected from mothers during each trimester, fathers (once during the pregnancy), and infants (at delivery and 2 years of age) for storage in a biological specimen bank. RESULTS: Of the 9864 women screened, 6348 met the eligibility criteria and 2366 women participated in the study (37% of eligible women). Among women in the 3D cohort, 1721 of their partners (1704 biological fathers) agreed to participate (73%). Two thousand two hundred and nineteen participants had a live singleton birth (94%). Prenatal blood and urine samples as well as vaginal secretions were collected for ≥98% of participants, cord blood for 81% of livebirths, and placental tissue for 89% of livebirths. CONCLUSIONS: The 3D Cohort Study combines a rich bank of multiple biological specimens with extensive clinical, life style, and psychosocial data. This data set is a valuable resource for studying the developmental etiology of birth and early childhood neurodevelopmental outcomes.

Frequency, severity and risk factors for urinary and faecal incontinence at 4 years postpartum: a prospective cohort.

OBJECTIVES: To investigate frequency, severity and risk factors for urinary incontinence and faecal incontinence 4 years after a first birth. DESIGN: Prospective pregnancy cohort study. SETTING: Melbourne, Australia. SAMPLE: A total of 1011 nulliparous women recruited in early pregnancy. METHODS: Participants were followed up at 32 weeks of gestation; then at 3, 6, 9 and 12 months and 4 years postpartum. MAIN OUTCOME MEASURES: Frequency and severity of urinary and faecal incontinence. RESULTS: At 4 years, 29.6% of women reported urinary incontinence and 7.1% reported faecal incontinence. Compared with women having only spontaneous vaginal births, women who delivered exclusively by caesarean section were less likely to have urinary incontinence at 4 years postpartum (adjusted odds ratio 0.4, 95% confidence interval 0.3-0.6). Women who reported urinary incontinence before or during the index pregnancy, and those experiencing symptoms in the first year postpartum had increased odds of incontinence at 4 years, with the highest odds (6-12 times higher) among women who had previously reported moderate or severe symptoms. The odds of reporting faecal incontinence at 4 years were two to six times higher for women experiencing symptoms in pregnancy, and around four to eight times higher for those with symptoms in the first year postpartum. CONCLUSION: Urinary and faecal incontinence are prevalent conditions 4 years after a first birth. Women reporting urinary or faecal incontinence during pregnancy had markedly higher odds of reporting symptoms at 4 years postpartum, suggesting a need for further investigation and elucidation of aetiological pathways involving nonbirth-related risk factors. TWEETABLE ABSTRACT: Moderate/severe incontinence prevalent 4 years after first birth in population cohort. Prior symptoms are biggest predictor.

Maternal arsenic exposure and gestational diabetes and glucose intolerance in the New Hampshire birth cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major pregnancy complication with detrimental effects for both mothers and their children. Accumulating evidence has suggested a potential role for arsenic (As) exposure in the development of GDM, but current studies have not assessed As exposure from water, urine or toenail samples. METHODS: We investigated the association between As exposure and risk of glucose intolerance and GDM among 1151 women enrolled in the New Hampshire Birth Cohort Study. Arsenic was measured in home well water and via biomarkers (i.e., maternal urine collected ~24-28 weeks gestation and toenail clippings collected 2 weeks postpartum). RESULTS: A total of 105 (9.1 %) of women were diagnosed with glucose intolerance and 14 (1.2 %) of women were diagnosed with GDM. A total of 10.3 % of women had water As levels above 10 µg/L, with a mean As level of 4.2. Each 5 µg/L increase in As concentration in home well water was associated with a ~10 % increased odds of GDM (OR: 1.1, 95 % CI 1.0, 1.2). A positive and statistically significant association also was observed between toenail As and GDM (OR: 4.5, 95 % CI 1.2, 16.6), but not urinary arsenic (OR: 0.8, 95 % CI 0.3, 2.4). In a stratified analysis, the association between water As and GDM and glucose intolerance was largely limited to obese women (OR: 1.7, 95 % CI 1.0, 2.8). CONCLUSIONS: Our findings support the role of As exposure via water from private wells in the incidence of GDM and that this association may be modified by body composition.

Association of trimester-specific gestational weight gain with fetal growth, offspring obesity, and cardiometabolic traits in early childhood.

OBJECTIVE: The purpose of this study was to investigate the association of trimester-specific gestational weight gain with offspring fetal growth, obesity risk, and cardiometabolic health outcomes from birth to 4 years of age. STUDY DESIGN: We conducted the present study with 977 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. We measured birthweight, body mass index from 6 months to 4 years of age, waist circumference, skinfold thickness, blood pressure, and blood levels of lipids, C-reactive protein, and adipose tissue hormones at 4 years of age. We used multiple linear and log Poisson regression models to examine the association of exposure with continuous or binary outcomes, respectively. RESULTS: Greater rate of gestational weight gain in the first trimester of pregnancy (per 200 g/wk) was associated with increased risk of overweight/obesity from 2 years (relative risk [RR], 1.25; 95% confidence interval [CI], 1.09-1.42) to 4 years of age (RR, 1.15; 95% CI, 1.05-1.25), but not with birth size. Each 200 g/wk of weight gain in the first trimester of pregnancy was also associated with greater risk of high waist circumference (RR, 1.13; 95% CI, 1.04-1.23), high sum of skinfold thickness (RR, 1.15; 95% CI, 1.02-1.29), and higher diastolic blood pressure at 4 years of age (ß, 0.43 mm Hg; 95% CI, 0.00-0.86). Greater rate of gestational weight gain during the second and third trimesters of pregnancy (per 200 g/wk) was associated with greater risk of large-for-gestational-age neonates (RR, 1.22; 95% CI, 1.02, 1.45) and higher levels of cord blood leptin (ratio of geometric means, 1.08; 95% CI, 1.00-1.17), but not with child anthropometry at later ages. CONCLUSION: Timing of gestational weight gain may influence childhood cardiometabolic outcomes differentially.

Consultation about urinary and faecal incontinence in the year after childbirth: a cohort study.

OBJECTIVE: To investigate the extent to which primary-care practitioners routinely inquire about postpartum urinary and faecal incontinence, and assess the proportion of women who disclose symptoms. DESIGN: Prospective pregnancy cohort study of nulliparous women. SETTING: Melbourne, Australia. SAMPLE: A total of 1507 nulliparous women recruited in early pregnancy. METHOD: Women were recruited from six public maternity hospitals, with follow up at 3, 6, 9 and 12 months postpartum. MAIN OUTCOME MEASURES: Standardised measures of urinary and bowel symptoms, and measures of health service use. RESULTS: In the first 12 months postpartum, the period prevalence of urinary incontinence was 47%, and of faecal incontinence was 17%. In all, 86% of women visited a primary health-care practitioner at least once to discuss their own health in the first year after childbirth. However, only around a quarter were asked about urinary incontinence, and fewer than one in five women were asked about faecal incontinence. Discussion of symptoms with health professionals was most likely to occur in the first 3 months postpartum, and happened only rarely during the remainder of the first postnatal year. Over 70% of women reporting severe urinary incontinence and/or faecal incontinence had not discussed symptoms with a health professional. CONCLUSION: The findings provide robust evidence that many women experiencing postpartum urinary and faecal incontinence­including women with moderate and severe symptoms­do not receive adequate primary-care follow up in the first 12 months postpartum. Systems of maternal health surveillance need to include routine inquiry about urinary and faecal incontinence to overcome women's reluctance to seek help.

Use of macrolides during pregnancy and the risk of birth defects: a population-based study.

PURPOSE: Macrolides have been linked to the occurrence of congenital heart defects, but findings are inconsistent. We therefore aimed to estimate the risk of major congenital malformations (MCMs) after fetal exposure to macrolides, focusing on cardiac malformations. METHODS: From the Quebec Pregnancy Cohort (1998-2008), women exposed to a macrolide or penicillin in the first trimester and unexposed women were studied. There were 135 859 pregnancies included; 914 were exposed to azithromycin, 734 to erythromycin, 686 to clarithromycin, and 9106 to penicillin during the first trimester. Cases of MCMs were identified within the first year of life. RESULTS: After adjusting for potential confounders, azithromycin (RR = 1.19, 95%CI: 0.98, 1.44; 120 exposed cases), erythromycin (RR = 0.96, 95%CI: 0.74, 1.24; 66 exposed cases) and clarithromycin use (RR = 1.12, 95%CI: 0.99, 1.42; 79 exposed cases) during the first trimester of pregnancy were not statistically significantly associated with the risk of MCMs; no associations were observed for cardiac malformations. CONCLUSIONS: First trimester exposure to any of the macrolides was not associated with an increased risk of overall MCMs or cardiac malformations specifically.

Metals exposure and risk of small-for-gestational age birth in a Canadian birth cohort: The MIREC study.

BACKGROUND: Lead, mercury, cadmium and arsenic are some of the most common toxic metals to which Canadians are exposed. The effect of exposure to current low levels of toxic metals on fetal growth restriction is unknown. OBJECTIVE: The aim of this study was to examine relationships between exposure to lead, mercury, cadmium and arsenic during pregnancy, and risk of small for gestational age (SGA) birth. METHODS: Lead, mercury, cadmium and arsenic levels were measured in blood samples from the first and third trimesters in 1835 pregnant women from across Canada. Arsenic species in first trimester urine were also assessed. Relative risks and 95% confidence intervals were estimated using log binomial multivariate regression. Important covariates including maternal age, parity, pre-pregnancy BMI, and smoking, were considered in the analysis. An exploratory analysis was performed to examine potential effect modification of these relationships by single nucleotide polymorphisms (SNPs) in GSTP1 and GSTO1 genes. RESULTS: No association was found between blood lead, cadmium or arsenic and risk for SGA. We observed an increased risk for SGA for the highest compared to the lowest tertile of exposure for mercury (>1.6 µg/L, RR=1.56.; 95% CI=1.04-2.58) and arsenobetaine (>2.25 µg/L, RR=1.65; 95% CI=1.10-2.47) after adjustment for the effects of parity and smoking. A statistically significant interaction was observed in the relationship between dimethylarsinic acid (DMA) levels in urinary arsenic and SGA between strata of GSTO1 A104A (p for interaction=0.02). A marginally significant interaction was observed in the relationship between blood lead and SGA between strata of GSTP1 A114V (p for interaction=0.06). CONCLUSIONS: These results suggest a small increase in risk for SGA in infants born to women exposed to mercury and arsenic. Given the conflicting evidence in the literature this warrants further investigation in other pregnant populations.

Adolescent peer aggression and its association with mental health and substance use in an Australian cohort.

Prospective longitudinal birth cohort data was used to examine the association between peer aggression at 14 years and mental health and substance use at 17 years. A sample of 1590 participants from the Western Australian Pregnancy Cohort (Raine) study were divided into mutually exclusive categories (victims, perpetrators, victim-perpetrators and uninvolved). Involvement in any type of peer aggression as a victim (10.1%), perpetrator (21.4%), or a victim-perpetrator (8.7%) was reported by 40.2% of participants. After adjusting for confounding factors, those who were a victim of peer aggression had increased odds of later depression and internalising symptoms whilst perpetrators of peer aggression were found to be at increased risk of depression and harmful alcohol use. Victim-perpetrators of peer aggression were more likely to have externalising behaviours at 17 years. These results show an independent temporal relationship between peer aggression and later mental health and substance use problems in adolescence.