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Prenatal indoor air pollution and maternal psychosocial factors have been associated with adverse psychopathology. We used environmental-exposure mixture methodology to investigate joint effects of both exposure classes on child behavior trajectories. For 360 children from the South African Drakenstein Child Health Study, we created trajectories of Child Behavior Checklist scores (at 24, 42, and 60 months) using latent-class linear mixed effects models. Indoor air pollutants and psychosocial factors were measured during pregnancy (second trimester). After adjusting for confounding, single-exposure effects (per natural log-1 unit increase) were assessed using polytomous logistic regression models, joint effects using self-organizing maps, and principal component analysis. Three trajectories were chosen for both internalizing and externalizing problems, with "high" (externalizing) or "increasing" (internalizing) being the most adverse trajectories. High externalizing trajectory was associated with increased exposure to particulate matter of ≤ 10 microns in diameter (PM10) (odds ratio [OR] = 1.25; 95% CI, 1.01-1.55) and self-organizing maps exposure profile most associated with smoking (OR = 2.67; 95% CI, 1.14-6.27). Medium internalizing trajectory was associated with increased emotional intimate partner violence (OR = 2.66; 95% CI, 1.17-5.57), increasing trajectory with increased benzene (OR = 1.24; 95% CI, 1.02-1.51) and toluene (1.21; 95% CI, 1.02-1.44) and the principal component most correlated with benzene and toluene (OR = 1.25; 95% CI, 1.02-1.54). Prenatal exposure to environmental pollutants and psychosocial factors was associated with internalizing and externalizing child behavior trajectories. Understanding joint effects of adverse exposure mixtures will facilitate targeted interventions to prevent childhood psychopathology. This article is part of a Special Collection on Mental Health. [ABSTRACT FROM AUTHOR]

Prenatal exposures are associated with childhood asthma, and risk may increase with simultaneous exposures. Pregnant women living in lower-income communities tend to have elevated exposures to a range of potential asthma risk factors, which may interact in complex ways. We examined the association between prenatal exposures and the risk of childhood acute-care clinical encounters for asthma (hospitalizations, emergency department visits, observational stays) using conditional logistic regression with a multivariable smoothing term to model the interaction between continuous variables, adjusted for maternal characteristics and stratified by sex. All births near the New Bedford Harbor (NBH) Superfund site (2000-2006) in New Bedford, Massachusetts, were followed through 2011 using the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System to identify children aged 5-11 years with acute-care clinical asthma encounters (265 cases among 7787 children with follow-up). Hazard ratios (HRs) were higher for children living closer to the NBH site with higher umbilical cord blood lead levels than in children living further away from the NBH site with lower lead levels (P  <.001). HRs were higher for girls (HR = 4.17; 95% CI, 3.60-4.82) than for boys (HR = 1.72; 95% CI, 1.46-2.02). Our results suggest that prenatal lead exposure in combination with residential proximity to the NBH Superfund site is associated with childhood asthma acute-care clinical encounters. This article is part of a Special Collection on Environmental Epidemiology. [ABSTRACT FROM AUTHOR]

Epidemiologists face a unique challenge in measuring risk relationships involving time-varying exposures in early pregnancy. Each week in early pregnancy is distinct in its contribution to fetal development, and this period is commonly characterized by shifts in maternal behavior and, consequently, exposures. In this simulation study, we used alcohol as an example of an exposure that often changes during early pregnancy and miscarriage as an outcome affected by early exposures. Data on alcohol consumption patterns from more than 5,000 women in the Right From the Start cohort study (United States, 2000–2012) informed measures of the prevalence of alcohol exposure, the distribution of gestational age at cessation of alcohol use, and the likelihood of miscarriage by week of gestation. We then compared the bias and precision of effect estimates and statistical power from 5 different modeling approaches in distinct simulated relationships. We demonstrate how the accuracy and precision of effect estimates depended on alignment between model assumptions and the underlying simulated relationship. Approaches that incorporated data about patterns of exposure were more powerful and less biased than simpler models when risk depended on timing or duration of exposure. To uncover risk relationships in early pregnancy, it is critical to carefully define the role of exposure timing in the underlying causal hypothesis. [ABSTRACT FROM AUTHOR]

Although effective in controlling malaria, indoor residual spraying results in elevated exposure to insecticides such as dichlorodiphenyltrichloroethane (DDT) and pyrethroids. These chemicals cross the placenta, but no studies have examined their associations with birth outcomes in populations residing in indoor residual spraying areas. We investigated this question in the Venda Health Examination of Mothers, Babies and Their Environment (VHEMBE), a birth cohort study of 751 South African children born between 2012 and 2013. We measured maternal peripartum serum DDT and urine pyrethroid metabolite concentrations and collected data on birth weight, length, head circumference, and duration of gestation. We analyzed the data using marginal structural models with inverse-probability-of-treatment weights, generalized propensity scores, and standard conditional linear regression. Using all 3 analytical methods, p,p'-DDT, o,p'-DDT, and to a lesser extent p,p'-dichlorodiphenyldichloroethylene were related to elevated birth weight, birth length, and head circumference among girls. Changes in gestational duration did not mediate this relationship, suggesting that these exposures accelerate fetal growth, which is consistent with the known estrogenic properties of o,p'-DDT and p,p'-DDT. No associations with pyrethroid metabolites were found. Results suggest that prenatal exposure to DDT is related to elevated birth size. Further studies are needed to elucidate the implications of these findings.

Arsenic in drinking water is known to cause cancer and noncancer diseases, but little is known about its association with age at exposure. Here, we investigated age at arsenic exposure and mortality in Antofagasta, Chile, 30-40 years after a distinct period of very high water arsenic concentrations (1958-1970). We calculated standardized mortality ratios (SMRs) comparing Antofagasta with the rest of Chile for 2001-2010 by sex and age at potential first exposure. A remarkable relationship with age at first exposure was found for bronchiectasis, with increased risk in adults 30-40 years after exposure being confined to those who were in utero (SMR = 11.7, 95% confidence interval (CI): 4.3, 25.4) or aged 1-10 years (SMR = 5.4, 95% CI: 1.1, 15.8) during the high-exposure period. Increased SMRs for lung, bladder, and laryngeal cancer were evident for exposures starting at all ages, but the highest SMRs were for exposures beginning at birth (for bladder cancer, SMR = 16.0 (95% CI: 10.3, 23.8); for laryngeal cancer, SMR = 6.8 (95% CI: 2.2, 15.8); for lung cancer, SMR = 3.8 (95% CI: 2.9, 4.9)). These findings suggest that interventions targeting early-life arsenic exposure could have major impacts in reducing long-term mortality due to arsenic 30-40 years after exposure ends.

Associations of prenatal exposure to perfluoroalkyl substances (PFAS), ubiquitous chemicals used in stain- and water-resistant products, with adverse birth outcomes may be confounded by pregnancy hemodynamics. We measured plasma concentrations of 4 PFAS in early pregnancy (median length of gestation, 9 weeks) among 1,645 women in Project Viva, a study of a birth cohort recruited during 1999-2002 in eastern Massachusetts. We fitted multivariable models to estimate associations of PFAS with birth weight-for-gestational age z score and length of gestation, adjusting for sociodemographic confounders and 2 hemodynamic markers: 1) plasma albumin concentration, a measure of plasma volume expansion, and 2) plasma creatinine concentration, used to estimate glomerular filtration rate. Perfluorooctane sulfonate (PFOS) and perfluorononanoate (PFNA) were weakly inversely associated with birth weight-for-gestational age z scores (adjusted β = -0.04 (95% confidence interval (CI): -0.08, 0.01) and adjusted β = -0.06 (95% CI: -0.11, -0.01) per interquartile-range increase, respectively). PFOS and PFNA were also associated with higher odds of preterm birth (e.g., for highest PFOS quartile vs. lowest, adjusted odds ratio = 2.4, 95% CI: 1.3, 4.4). Adjusting for markers of pregnancy hemodynamics (glomerular filtration rate and plasma albumin), to the extent that they accurately reflect underlying pregnancy physiology, did not materially affect associations. These results suggest that pregnancy hemodynamics may not confound associations with birth outcomes when PFAS are measured early in pregnancy.

Attention-deficit/hyperactivity disorder (ADHD) has an uncertain etiology, with potential contributions from different risk factors such as prenatal environmental exposure to organochlorines and metals, social risk factors, and genetics. The degree to which geographic variability in ADHD is independent of, or explained by, risk factors may provide etiological insight. We investigated determinants of geographic variation in ADHD-related behaviors among children living near the polychlorinated biphenyl-contaminated New Bedford Harbor (NBH) Superfund site in Massachusetts. Participants were 573 children recruited at birth (1993-1998) who were born to mothers residing near the NBH site. We assessed ADHD-related behaviors at age 8 years using Conners' Teacher Rating Scale-Revised: Long Version. Adjusted generalized additive models were used to smooth the association of pregnancy residence with ADHD-related behaviors and assess whether prenatal organochlorine or metal exposures, sociodemographic factors, or other factors explained spatial patterns. Models that adjusted for child's age and sex displayed significantly increased ADHD-related behavior among children whose mothers resided west of the NBH site during pregnancy. These spatial patterns persisted after adjusting for prenatal exposure to organochlorines and metals but were no longer significant after controlling for sociodemographic factors. The findings underscore the value of spatial analysis in identifying high-risk subpopulations and evaluating candidate risk factors.

Discomfort and, to a lesser extent, pain are common complaints during pregnancy, and some patients may turn to opioids for pain relief. Esposito et al. (Am J Epidemiol. 2022;191(5):759–768) report associations between intermittent exposure to opioids during pregnancy and the risk of ischemic placental disease—a syndrome that includes preeclampsia, placental abruption, births that are small for gestational age, and preterm delivery. They found that early opioid exposure in pregnancy was associated with a modestly increased risk for abruption, births that are small for gestational age, and preterm delivery, and both early and late exposures were associated with the greatest risk for these outcomes. Surprisingly, preeclampsia was not associated with opioid use. Through quantitative bias analysis, the authors cleverly tackle a number of biases to assess their roles in explaining the associations, including unmeasured confounding, outcome misclassification, and residual confounding; none exerted strong influences on the associations. Although the findings appear fairly robust on the surface, the lack of association between intermittent opioid use and preeclampsia, and important differences in characteristics of patients in the opioid-exposed group compared with the unexposed group, suggest that further study is needed to clarify the relationship between intermittent opioid use, lifestyle factors, and ischemic placental disease risk. [ABSTRACT FROM AUTHOR]

Current methods for identifying temporal windows of effect for time-varying exposures in omics settings can control false discovery rates at the biomarker-level but cannot efficiently screen for timing-specific effects in high dimensions. Current approaches leverage separate models for site screening and identification of susceptible time windows, which miss associations that vary over time. We introduce the epigenome-wide distributed lag model (EWDLM), a novel approach that combines traditional false discovery rate methods with the distributed lag model (DLM) to screen for timing-specific effects in high dimensional settings. This is accomplished by marginalizing DLM effect estimates over time and correcting for multiple comparisons. In a simulation investigating timing-specific effects of ambient air pollution during pregnancy on DNA methylation across the epigenome at age 12 years, EWDLM achieved an increased sensitivity for associations limited to specific periods of time compared to traditional two-stage approaches. In a real-world EWDLM analysis, 353 CpG sites at which DNAm measured at age 12 was significantly associated with PM2.5 exposure during pregnancy were identified. EWDLM is a novel method that provides an efficient and sensitive way to screen epigenomic datasets for associations with exposures localized to specific time periods., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Adequate thyroid hormone availability is required for normal brain development. Studies have found associations between prenatal exposure to air pollutants and thyroid hormones in pregnant women and newborns. We aimed to examine associations of trimester-specific residential exposure to common air pollutants with congenital hypothyroidism (CHT). All term infants born in Israel during 2009–2015 were eligible for inclusion. We used data on CHT from the national neonatal screening lab of Israel, and exposure data from spatiotemporal air pollution models. We used multivariable logistic regression models to estimate associations of exposures with CHT, adjusting for ethnicity, socioeconomic status, geographical area, conception season, conception year, gestational age, birth weight, and child sex. To assess residual confounding, we used postnatal exposures to the same pollutants as negative controls. The study population included 696,461 neonates. We found a positive association between third-trimester nitrogen oxide exposure and CHT (per interquartile-range change, odds ratio = 1.23, 95% confidence interval: 1.08, 1.41) and a similar association for nitrogen dioxide. There was no evidence of residual confounding or bias by correlation among exposure periods for these associations. [ABSTRACT FROM AUTHOR]

The brain's prefrontal cortex directs higher-order cognitive and behavioral processes that are important for attention, working memory, and inhibitory control. We investigated whether gestational exposure to organophosphate (OP) pesticides was associated with these abilities in childhood and early adolescence. Between 1999 and 2000, we enrolled pregnant women in a birth cohort drawn from an agricultural region of California. We measured dialkyl phosphate (DAP) metabolites of OP pesticides in maternal pregnancy urine samples (13 and 26 weeks) and estimated associations with behaviors related to attention-deficit/hyperactivity disorder and executive function, assessed longitudinally; 351 families provided neurodevelopmental outcome data at any point when the child was aged 7–12 years. We assessed function across multiple dimensions (e.g. working memory, attention), methods (e.g. behavior reports, child assessment), and reporters (e.g. mothers, teachers, child self-reports). Higher gestational DAP concentrations were consistently associated with behaviors related to attention-deficit/hyperactivity disorder and executive function. For example, a 10-fold increase in gestational DAP concentration was associated with poorer longitudinally assessed Behavior Rating Inventory of Executive Function scores, as reported by mothers (β = 4.0 (95% confidence interval: 2.1, 5.8); a higher score indicates more problems), and Weschler Intelligence Scale for Children—Fourth Edition Working Memory scores (a 3.8-point reduction; β = −3.8 (95% confidence interval: −6.2, −1.3)). Reducing gestational exposure to OP pesticides through public health policy is an important goal. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder, which is characterized by impaired social communication and stereotypic behaviors, affects 1%–2% of children. Although prenatal exposure to toxicants has been associated with autistic behaviors, most studies have been focused on shifts in mean behavior scores. We used Bayesian quantile regression to assess the associations between log2-transformed toxicant concentrations and autistic behaviors across the distribution of behaviors. We used data from the Maternal–Infant Research on Environmental Chemicals study, a pan-Canadian cohort (2008–2011). We measured metal, pesticide, polychlorinated biphenyl, phthalate, bisphenol-A, and triclosan concentrations in blood or urine samples collected during the first trimester of pregnancy. Using the Social Responsiveness Scale (SRS), in which higher scores denote more autistic-like behaviors, autistic behaviors were assessed in 478 children aged 3–4 years old. Lead, cadmium, and most phthalate metabolites were associated with mild increases in SRS scores at the 90th percentile of the SRS distribution. Manganese and some pesticides were associated with mild decreases in SRS scores at the 90th percentile of the SRS distribution. We identified several monotonic trends in which associations increased in magnitude from the bottom to the top of the SRS distribution. These results suggest that quantile regression can reveal nuanced relationships and, thus, should be more widely used by epidemiologists. [ABSTRACT FROM AUTHOR]

In-utero exposure to endocrine-disrupting compounds, including dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenylethylene (DDE), has been hypothesized to increase the risk of obesity later in life. We examined the associations of maternal serum concentrations of DDT and DDE during pregnancy with body mass index, obesity, waist circumference, and percentage of body fat in 9-year-old children (n = 261) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal birth cohort study in the Salinas Valley, California (2000-2010). We found associations between prenatal exposure to DDT and DDE and several measures of obesity at 9 years of age in boys but not in girls. For example, among boys, 10-fold increases in prenatal DDT and DDE concentrations were associated with increased odds of becoming overweight or obese (for o,p'-DDT, adjusted odds ratio (OR) = 2.5, 95% confidence interval (CI): 1.0, 6.3; for p,p'-DDT, adjusted OR = 2.1, 95% CI: 1.0, 4.5; and for p,p'-DDE, adjusted OR = 1.97, 95% CI: 0.94, 4.13). The odds ratios for girls were nonsignificant. Results were similar for body mass index z score, waist circumference z score, and odds of increased waist circumference but were less consistent for percentage of body fat. The difference by sex persisted after considering pubertal status. These results provide support for the chemical obesogen hypothesis.

We examined whether early gestational exposures to pesticides were associated with an increased risk of anencephaly, spina bifida, cleft lip with or without cleft palate (CLP), or cleft palate only. We used population-based data along with detailed information from maternal interviews. Exposure estimates were based on residential proximity to agricultural pesticide applications during early pregnancy. The study population derived from the San Joaquin Valley, California (1997-2006). Analyses included 73 cases with anencephaly, 123 with spina bifida, 277 with CLP, and 117 with cleft palate only in addition to 785 controls. A total of 38% of the subjects were exposed to 52 chemical groups and 257 specific chemicals. There were relatively few elevated odds ratios with 95% confidence intervals that excluded 1 after adjustment for relevant covariates. Those chemical groups included petroleum derivatives for anencephaly, hydroxybenzonitrile herbicides for spina bifida, and 2,6-dinitroaniline herbicides and dithiocarbamates-methyl isothiocyanate for CLP. The specific chemicals included 2,4-D dimethylamine salt, methomyl, imidacloprid, and α-(para-nonylphenyl)-ω-hydroxypoly(oxyethylene) phosphate ester for anencephaly; the herbicide bromoxynil octanoate for spina bifida; and trifluralin and maneb for CLP. Adjusted odds ratios ranged from 1.6 to 5.1. Given that such odds ratios might have arisen by chance because of the number of comparisons, our study showed a general lack of association between a range of agricultural pesticide exposures and risks of selected birth defects.

Laboratory-based animal research has revealed a number of exposures with multigenerational effects—ones that affect the children and grandchildren of those directly exposed. An important task for epidemiology is to investigate these relationships in human populations. Without the relative control achieved in laboratory settings, however, population-based studies of multigenerational associations have had to use a broader range of study designs. Current strategies to obtain multigenerational data include exploiting birth registries and existing cohort studies, ascertaining exposures within them, and measuring outcomes across multiple generations. In this paper, we describe the methodological challenges inherent to multigenerational studies in human populations. After outlining standard taxonomy to facilitate discussion of study designs and target exposure associations, we highlight the methodological issues, focusing on the interplay between study design, analysis strategy, and the fact that outcomes may be related to family size. In a simulation study, we show that different multigenerational designs lead to estimates of different exposure associations with distinct scientific interpretations. Nevertheless, target associations can be recovered by incorporating (possibly) auxiliary information, and we provide insights into choosing an appropriate target association. Finally, we identify areas requiring further methodological development. [ABSTRACT FROM AUTHOR]

Organophosphates (OPs) are the most heavily used pesticides in China. The Chinese population, including preconceptional women, is highly exposed, yet little is known regarding the associations between OP exposure and menstruation in humans. We conducted a cross-sectional analysis in women preparing for pregnancy to investigate the relationship between biomarkers of OP exposure and menstrual cycle characteristics. From 2013 to 2015, 627 women visiting free preconception-care clinics at 2 maternity hospitals in Shanghai, China, were included. Information on menstrual cycle characteristics was obtained through questionnaires. OP exposure was assessed by measuring urine concentrations of 6 dialkylphosphate metabolites (dimethylphosphate, dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate, and diethyldithiophosphate). The relationship between concentrations of dialkylphosphate metabolites and menstrual cycle characteristics was analyzed using multiple linear regression models and logistic regression models. Log-transformed levels of diethyl phosphate metabolites (the sum of diethylphosphate and diethylthiophosphate levels) were related to a higher risk of irregularity of menstrual cycles (adjusted odds ratio = 2.36, 95% confidence interval: 1.28, 4.34). Subjects with a higher concentration of diethyl phosphate metabolites (log-transformed) had a shorter duration of menstrual bleeding (adjusted β = −0.33, 95% confidence interval: −0.64, −0.02). The findings suggest that OP exposure may be associated with alterations in menstrual function in preconceptional women. [ABSTRACT FROM AUTHOR]

Traffic-related air pollution has been linked to higher risks of infertility and miscarriage. We evaluated whether folate intake modified the relationship between air pollution and livebirth among women using assisted reproductive technology (ART). Our study included 304 women (513 cycles) presenting to a fertility center in Boston, Massachusetts (2005–2015). Diet and supplements were assessed by food frequency questionnaire. Spatiotemporal models estimated residence-based daily nitrogen dioxide (NO2), ozone, fine particulate, and black carbon concentrations in the 3 months before ART. We used generalized linear mixed models with interaction terms to evaluate whether the associations between air pollutants and livebirth were modified by folate intake, adjusting for age, body mass index, race, smoking, education, infertility diagnosis, and ART cycle year. Supplemental folate intake significantly modified the association of NO2 exposure and livebirth (P = 0.01). Among women with supplemental folate intakes of <800 μg/day, the odds of livebirth were 24% (95% confidence interval: 2, 42) lower for every 20-parts-per-billion increase in NO2 exposure. There was no association among women with intakes of ≥800 μg/day. There was no effect modification of folate on the associations between other air pollutants and livebirth. High supplemental folate intake might protect against the adverse reproductive consequences of traffic-related air pollution. [ABSTRACT FROM AUTHOR]

Exposure to ambient fine particulate matter (particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5)) during pregnancy is associated with preterm birth (PTB), a leading cause of infant morbidity and mortality. Results from studies attempting to identify etiologically relevant exposure periods of vulnerability have been inconsistent, possibly because of failure to consider the time-to-event nature of the outcome and lagged exposure effects of PM2.5. In this study, we aimed to identify critical exposure windows for weekly PM2.5 exposure and PTB in California using California birth cohort data from 2005–2010. Associations were assessed using distributed-lag Cox proportional hazards models. We assessed effect-measure modification by race/ethnicity by calculating the weekly relative excess risk due to interaction. For a 10-μg/m3 increase in PM2.5 exposure over the entire period of gestation, PTB risk increased by 11% (hazard ratio = 1.11, 95% confidence interval: 1.09, 1.14). Gestational weeks 17–24 and 36 were associated with increased vulnerability to PM2.5 exposure. We find that non-Hispanic black mothers may be more susceptible to effects of PM2.5 exposure than non-Hispanic white mothers, particularly at the end of pregnancy. These findings extend our knowledge about the existence of specific exposure periods during pregnancy that have the greatest impact on preterm birth. [ABSTRACT FROM AUTHOR]

Infants and children are particularly vulnerable to in utero and early-life exposures. Thus, a mother's exposures before and during pregnancy could have important consequences for her child's health, including cancer development. We examined whether birth certificate–derived maternal anthropometric characteristics were associated with increased risk of subsequent childhood cancer development, accounting for established maternal and infant risk factors. Pennsylvania birth and cancer registry files were linked by the state Department of Health, yielding a virtual cohort of births and childhood cancers from 2003 through 2016. The analysis included 1,827,875 infants (13,785,309 person-years at risk), with 2,352 children diagnosed with any cancer and 747 with leukemia before age 14 years. Children born to mothers with a body mass index (weight (kg)/height (m)2) of ≥40 had a 57% (95% confidence interval: 12, 120) higher leukemia risk. Newborn size of ≥30% higher than expected was associated with 2.2-fold and 1.8-fold hazard ratios for total childhood cancer and leukemia, respectively, relative to those with expected size. Being <30% below expected size also increased the overall cancer risk (P for curvilinearity < 0.0001). Newborn size did not mediate the association between maternal obesity and childhood cancer. The results suggest a significant role of early-life exposure to maternal obesity- and fetal growth–related factors in childhood cancer development. [ABSTRACT FROM AUTHOR]

Arsenic crosses the placenta, possibly increasing the risk of adverse reproductive outcomes. We aimed to examine the association between maternal arsenic exposure and fetal/neonatal survival using data from a prospective cohort study of 1,616 maternal-infant pairs recruited at a gestational age of ≤16 weeks in Bangladesh (2008–2011). Arsenic concentration in maternal drinking water was measured at enrollment. Extended Cox regression (both time-dependent coefficients and step functions) was used to estimate the time-varying association between maternal arsenic exposure and fetal/neonatal death (all mortality between enrollment and 1 month after birth). In a sensitivity analysis, we assessed gestational arsenic exposure using maternal urine samples taken at enrollment. We observed 203 fetal losses and 20 neonatal deaths. Higher arsenic exposure was associated with a slightly decreased mortality rate up to the middle of the second trimester, and then the mortality rate switched directions around 20 weeks' gestation. In the step function model, the hazard ratios for combined mortality (fetal loss and neonatal death) per unit increase in the natural log of drinking water arsenic concentration (μg/L) ranged from 1.35 (95% CI: 1.08, 1.69) in weeks 25–28 to 0.81 (95% CI: 0.65, 1.02) in weeks 9–12. This nonlinear association suggests that arsenic may exert survival pressure on developing fetuses, potentially contributing to survival bias, and may also indicate that arsenic toxicity differs by fetal developmental stage. [ABSTRACT FROM AUTHOR]

Letrozole is an aromatase inhibitor that has an unapproved use for ovulation induction with infertility. Because of the proximity of this use to conception, we selected letrozole to study the effect of 3 different methods for identifying the pregnancy start date and their impact on exposure misclassification. Using electronic health data from the US Sentinel database (2001–2015), we identified live-birth pregnancies conceived through in-vitro fertilization or intrauterine insemination. The pregnancy start was calculated using 1) a validated algorithm to estimate the last menstrual period (LMP), 2) LMP + 14 days (i.e. conception estimate), and 3) the fertility-procedure date. We identified 47,628 live-births after intrauterine insemination (n = 24,962) and in-vitro fertilization (n = 22,666), in which 2,458 (5.3%) mothers received letrozole. The algorithm-based conception estimate occurred within 14 days of the fertility procedure for 78.3% of pregnancies. Defining pregnancy start as LMP (45.7/1,000 pregnancies) or LMP + 14 days (12.7/1,000 pregnancies) overestimated letrozole exposure during pregnancy by 8.4-fold and 2.3-fold, respectively, compared with defining it at the date of the fertility procedure (5.5/1,000 pregnancies). While most studies of drug utilization in pregnancy use LMP as the conventional pregnancy start, this introduced substantial exposure misclassification in the example of letrozole. LMP + 14 days was less biased. Researchers should carefully consider the impact of the method for identifying the pregnancy start date on the potential for exposure misclassification. [ABSTRACT FROM AUTHOR]

Because early puberty has been linked to diseases later in life, identification of modifiable causes of early puberty is of interest. We explored the possible associations between maternal smoking during pregnancy and pubertal development in sons and daughters. Between 2012 and 2017, 15,819 children from the Danish National Birth Cohort, born during 2000–2003, provided half-yearly information on puberty from the age of 11 years. We estimated adjusted age differences (in months) at attaining various pubertal milestones, including Tanner stages, per 10 daily cigarettes smoked in the first trimester of gestation. In sons, exposure to smoking in utero was associated with earlier genital development (Tanner 2, −1.3 months, 95% confidence interval (CI): −2.5, 0.0; Tanner 5, −3.7 months, 95% CI: −5.3, −2.0), pubic hair development (Tanner 2, −1.8 months, 95% CI: −2.9, −0.6; Tanner 5, −2.9 months, 95% CI: −4.2, −1.7), and voice break (−2.4 months, 95% CI: −3.6, −1.3). In daughters, maternal smoking was associated with earlier breast development (Tanner 2, −3.4 months, 95% CI: −5.3, −1.5; Tanner 5, −4.7 months, 95% CI: −6.5, −2.9), pubic hair development stages 3–5 (Tanner 5, −2.5 months, 95% CI: −4.1, −1.0), and menarche (−3.1 months, 95% CI: −4.0, −2.3). Fetal exposure to tobacco smoke might advance timing of puberty in boys and girls. [ABSTRACT FROM AUTHOR]

This study explored the association between exposure to acetaminophen during pregnancy and pubertal development using data from 15,822 boys and girls in the longitudinal Puberty Cohort, nested within the Danish National Birth Cohort. Use of acetaminophen was reported 3 times during pregnancy and 6 months postpartum. In total, 54% of mothers indicated use at least once during pregnancy. Between 2012 and 2017, sons and daughters provided information on a wide range of pubertal milestones—including Tanner stages, axillary hair growth, and age at menarche or voice break and first ejaculation—every 6 months from 11 years of age until full sexual maturation. Data were analyzed using a regression model for interval-censored data, providing adjusted mean monthly differences in age at attaining the pubertal milestones according to intrauterine cumulative (weeks) and trimester-specific acetaminophen exposure. Our results suggested a tendency towards slightly earlier attainment of almost all studied markers of female pubertal development with increasing number of weeks of exposure (i.e. about 1.5–3 months earlier age at pubic hair, axillary hair, and acne development comparing unexposed with those prenatally exposed for more than 12 weeks). Male pubertal development had no strong association with acetaminophen exposure. [ABSTRACT FROM AUTHOR]

Few investigations have explored temperature and birth outcomes. In a retrospective cohort study, we examined apparent temperature, a combination of temperature and relative humidity, and term low birth weight (LBW) among 43,629 full-term LBW infants and 2,032,601 normal-weight infants in California (1999–2013). The California Department of Public Health provided birth certificate data, while meteorological data came from the California Irrigation Management Information System, US Environmental Protection Agency, and National Centers for Environmental Information. After considering several temperature metrics, we observed the best model fit for term LBW over the full gestation (per 10-degrees-Fahrenheit (°F) increase in apparent temperature, 13.0% change, 95% confidence interval: 4.1, 22.7) above 55°F, and the greatest association was for third-trimester exposure above 60°F (15.8%, 95% confidence interval: 5.0, 27.6). Apparent temperature during the first month of pregnancy exhibited no significant risk, while the first trimester had a significantly negative association, and second trimester, last month, and last 2 weeks had slightly increased risks. Mothers who were black or older, delivered male infants, or gave birth during the warm season had infants at the highest risks. This study provides further evidence for adverse birth outcomes from heat exposure for vulnerable subgroups of pregnant women. [ABSTRACT FROM AUTHOR]

Children whose mothers experienced childhood abuse are more likely to suffer various neurodevelopmental deficits. Whether an association exists specifically for attention deficit hyperactivity disorder (ADHD) is unknown. We examined the association of maternal experience of childhood abuse with ADHD in offspring, assessed by maternal report of diagnosis and validated with the ADHD Rating Scale-IV in a subsample, in the Nurses’ Health Study II (n = 49,497 mothers; n = 7,607 case offspring; n = 102,151 control offspring). We examined whether 10 adverse perinatal circumstances (e.g. prematurity, smoking) or socioeconomic factors accounted for a possible association. Exposure to abuse was associated with greater prevalence of ADHD in offspring (8.7% of offspring of women exposed to severe abuse vs. 5.5% of offspring of women not abused, P = 0.0001) and with greater risk for ADHD when the model was adjusted for demographic factors (male offspring, risk ratio (RR) = 1.6, 95% confidence interval (CI): 1.3, 1.9; female offspring, RR = 2.3, 95% CI: 1.7, 3.0). After adjustment for perinatal factors, the association of maternal childhood abuse with ADHD in offspring was slightly attenuated (male offspring, RR = 1.5, 95% CI: 1.2, 1.8; female offspring, RR = 2.1, 95% CI: 1.6, 2.8). We identified an association between maternal experience of childhood abuse and risk for ADHD in offspring, which was not explained by several important perinatal risk factors or socioeconomic status. [ABSTRACT FROM AUTHOR]

Acetaminophen is the analgesic and antipyretic most commonly used during pregnancy. Evidence of neurodisruptive properties is accumulating. Therefore, we sought to evaluate the risk for attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) in the offspring of women exposed to acetaminophen during pregnancy. We searched MEDLINE, Embase, and Cochrane databases for relevant studies up to January 2017. Data were independently extracted and assessed by 2 researchers. Seven eligible retrospective cohorts included 132,738 mother-child pairs, with follow-up periods ranging from 3 to 11 years. The pooled risk ratio for ADHD was 1.34 (95% confidence interval (CI): 1.21, 1.47; I 2 = 72%); for ASD, the risk ratio was 1.19 (95% CI: 1.14, 1.25; I 2 = 14%), and for hyperactivity symptoms, it was 1.24 (95% CI: 1.04, 1.43; I 2 = 93%). In meta-regression analysis, the association between exposure and ADHD increased with the child’s age upon follow-up (β = 0.03, 95% CI: 0.00, 0.07) and with the mean duration of exposure (β = 0.00, 95% CI: 0.00, 0.01). The available data is of observational nature only. Studies differed widely in exposure and outcome assessment. Acetaminophen use during pregnancy is associated with an increased risk for ADHD, ASD, and hyperactivity symptoms. These findings are concerning; however, results should be interpreted with caution given that the available evidence consists of observational studies and is susceptible to several potential sources of bias. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that perinatal air pollutant exposures are associated with increased risk of autism spectrum disorder (ASD), but evidence for traffic pollutants outside the United States is inconclusive. We assessed the association between nitrogen dioxide, a traffic pollution tracer, and risk of ASD. We conducted a nested casecontrol study among the entire population of children born during 2005-2009 in the central coastal area of Israel. Cases were identified through the National Insurance Institute of Israel (n = 2,098). Controls were a 20% random sample of the remaining children (n = 54,191). Exposure was based on an optimized dispersion model. We estimated adjusted odds ratios and 95% confidence intervals using logistic regression and a distributed-lag model. In models mutually adjusted for the 2 periods, the odds ratio per 5.85-parts per billion (ppb) increment of nitrogen dioxide exposure during pregnancy (median, 16.8 ppb; range, 7.5-31.2 ppb) was 0.77 (95%confidence interval: 0.59, 1.00), and the odds ratio for exposure during the 9 months after birth was 1.40 (95% confidence interval: 1.09, 1.80). A distributed-lag model revealed reduced risk around week 13 of pregnancy and elevated risk around week 26 after birth. These findings suggest that postnatal exposure to nitrogen dioxide in Israel is associated with increased odds of ASD, and prenatal exposure with lower odds. The latter may relate to selection effects. [ABSTRACT FROM AUTHOR]

Prenatal exposure to fever and infections has been linked to various neurodevelopmental disorders, but it is not yet known whether more subtle effects on neurodevelopment may exist as well. Therefore, we aimed to investigate whether these early-life exposures were associated with academic performance in childhood and early adolescence. Children and mothers who were enrolled in the Danish National Birth Cohort during 1996-2002 were included in this study. Information on fever and infections common in pregnancy was prospectively collected in 2 pregnancy interviews and linked with assessments of academic performance from the 2010-2013 Danish National Tests. Hierarchical multilevel linear regression of 216,350 assessments made in 71,850 children born to 67,528 mothers revealed no differences in academic performance among the children according to prenatal exposure to fever (odds ratio (OR) = 1.01, 95% confidence interval (CI): 1.00,1.03), any infection (OR = 1.00, 95% CI: 0.99, 1.01), genitourinary infection (OR = 1.01, 95% CI: 0.99, 1.02), prolonged cough (OR = 1.00, 95% CI: 0.99, 1.02), or diarrhea (OR = 0.99, 95% CI: 0.97, 1.00). The findings were supported in different types of academic as-sessments, with different timings of exposure, and in sibling comparisons. This large population-based study suggested that prenatal exposure to fever and common infections does not affect the child's basic school performance. [ABSTRACT FROM AUTHOR]

Atmospheric pollutants and meteorological conditions are suspected to be causes of preterm birth. We aimed to characterize their possible association with the risk of preterm birth (defined as birth occurring before 37 completed gestational weeks). We pooled individual data from 13 birth cohorts in 11 European countries (71,493 births from the period 1994-2011, European Study of Cohorts for Air Pollution Effects (ESCAPE)). City-specific meteorological data from routine monitors were averaged over time windows spanning from 1 week to the whole pregnancy. Atmospheric pollution measurements (nitrogen oxides and particulate matter) were combined with data from permanent monitors and land-use data into seasonally adjusted land-use regression models. Preterm birth risks associated with air pollution and meteorological factors were estimated using adjusted discrete-time Cox models. The frequency of preterm birth was 5.0%. Preterm birth risk tended to increase with first-trimester average atmospheric pressure (odds ratio per 5-mbar increase = 1.06, 95% confidence interval: 1.01, 1.11), which could not be distinguished from altitude. There was also some evidence of an increase in preterm birth risk with first-trimester average temperature in the -5°C to 15°C range, with a plateau afterwards (spline coding, P = 0.08). No evidence of adverse association with atmospheric pollutants was observed. Our study lends support for an increase in preterm birth risk with atmospheric pressure. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl substances (PFAS) are ubiquitous, persistent chemicals that have been widely used in the production of common household and consumer goods for their nonflammable, lipophobic, and hydrophobic properties. Inverse associations between maternal or umbilical cord blood concentrations of perfluorooctanoic acid and perfluorooctanesulfonate and birth weight have been identified. This literature has primarily examined each PFAS individually without consideration of the potential influence of correlated exposures. Further, the association between PFAS exposures and indicators of metabolic function (i.e., leptin and adiponectin) has received limited attention. We examined associations between first-trimester maternal plasma PFAS concentrations and birth weight and cord blood concentrations of leptin and adiponectin using data on 1,705 mother-infant pairs from the Maternal Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada birth cohort study that recruited women between 2008 and 2011. Bayesian hierarchical models were used to quantify associations and calculate credible intervals. Maternal perfluorooctanoic acid concentrations were inversely associated with birth weight z score, though the null value was included in all credible intervals (log10 β = -0.10, 95% credible interval: -0.34, 0.13). All associations between maternal PFAS concentrations and cord blood adipocy-tokine concentrations were of small magnitude and centered around the null value. Follow-up in a cohort of children is required to determine how the observed associations manifest in childhood. [ABSTRACT FROM AUTHOR]

We conducted a systematic review and 3-part meta-analysis to characterize the relationship between smoking and perinatal death, defined as the combination of stillbirth and neonatal death. The PubMed database was searched (1956-August 31, 2011) with keywords, and manual reference searches of included articles and Surgeon Generals' reports were conducted. The full texts of 1,713 articles were reviewed, and 142 articles that examined the associations between active or passive smoking and perinatal death were included in themeta-analyses. Datawere abstracted by 2 reviewers. Any active maternal smoking was associated with increased risks of stillbirth (summary relative risk (sRR) = 1.46, 95% confidence interval (CI): 1.38, 1.54 (n = 57 studies)), neonatal death (sRR = 1.22, 95% CI: 1.14, 1.30 (n = 28)), and perinatal death (sRR = 1.33, 95% CI: 1.25, 1.41 (n = 46)). The risks of stillbirth, neonatal death, and perinatal death increased with the amount smoked by the mother. Biases in study publication, design, and analysis were present but did not significantly affect the results. These findings strengthen the evidence that women should not smoke while pregnant, and all women of reproductive age should be warned that smoking increases the risks of stillbirth, neonatal death, and perinatal death. [ABSTRACT FROM AUTHOR]

Previous evidence suggests that exposure to outdoor air pollution during pregnancy could alter fetal metabolic function, which could increase the risk of obesity in childhood. However, to our knowledge, no epidemiologic study has investigated the association between prenatal exposure to air pollution and indicators of fetal metabolic function. We investigated the association between maternal exposure to nitrogen dioxide and fine particulate matter (aerodynamic diameter ≤2.5 urn) and umbilical cord blood leptin and adiponectin levels with mixed-effects linear regression models among 1,257 mother-infant pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, conducted in Canada (2008-2011). We observed that an interquartile-range increase in average exposure to fine particulate matter (3.2 µg/m³) during pregnancy was associated with an 11% (95% confidence interval: 4, 17) increase in adiponectin levels. We also observed 13% (95% confidence interval: 6, 20) higher adiponectin levels per interquartile-range increase in average exposure to nitrogen dioxide (13.6 parts per billion) during pregnancy. Significant associations were seen between air pollution markers and cord blood leptin levels in models that adjusted for birth weight z score but not in models that did not adjust for birth weight z score. The roles of prenatal exposure to air pollution and fetal metabolic function in the potential development of childhood obesity should be further explored. [ABSTRACT FROM AUTHOR]

Nitrosatable drugs (NSDs) can, in the presence of nitrosating agents and highly acidic conditions, form N-nitroso compounds that have been found to be teratogenic in animal models. Using data from the Slone Epidemiology Center Birth Defects Study collected from1998 to 2012, we compared maternal periconceptional NSD use between 334 neural tube defect cases and 7,619 nonmal formed controls. We categorized NSDs according to their functional group (secondary amine, tertiary amine, and amide). With logistic regression models, we estimated adjusted odds ratios and 95% confidence intervals. Neural tube defect risk was associated with maternal periconceptional use of secondary (adjusted odds ratio (aOR) = 1.7, 95% confidence interval (CI): 1.1, 2.4) and tertiary (aOR = 1.7, 95%CI: 1.2, 2.5) amines; an association was observed for amides, but the 95%confidence interval included the null (aOR = 1.4, 95% CI: 0.7, 2.5). Within the secondary amine group, elevated adjusted odds ratios were observed for 3 drugs but were null for the remaining medications. Increases in risk were observed for both strata of folic acid intake (<400 µg/day, ≥400 µg/day), with a slightly higher risk in the ≥400-µg/day stratum. Our findings support previously reported positive associations between neural tube defects and periconceptional exposure to NSDs containing a secondary or tertiary amine or amide. [ABSTRACT FROM AUTHOR]

Recent studies have suggested an association between air pollution and stillbirth. In this California study, we examined the records of 13,999 stillbirths and 3,012,270 livebirths occurring between 1999 and 2009. Using a retrospective cohort design and logistic regression models, we calculated the odds of stillbirth associated with each pollutant exposure by trimester and throughout the entire pregnancy. Covariates considered in the model included infant sex, maternal demographic characteristics, season of lastmenstrual period, apparent temperature, air basin of mother's residence, and year of conception. In single-pollutant models, we found that a 10-μg/m3 increase in particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (odds ratio (OR) = 1.06, 95% confidence interval (CI): 0.99, 1.13) and a 10-ppb increase in nitrogen dioxide (OR = 1.08, 95% CI: 1.03, 1.13) during the entire pregnancy were associated with stillbirth. A 10-ppb increase in ozone exposure during the third trimester was also associated with a slightly elevated risk (OR = 1.03, 95% CI: 1.01, 1.05). These ozone and nitrogen dioxide findings were fairly stable after adjustment in 2-pollutantmodels. However, adjustment for nitrogen dioxide attenuated the fullpregnancy-particulate matter relationship. No significant associations were found for sulfur dioxide or carbon monoxide. These findings support growing evidence of an association between air pollution and adverse birth outcomes. [ABSTRACT FROM AUTHOR]

Nutritional conditions in early life may affect adult health, but prior studies of mortality have been limited to small samples. We evaluated the relationship between pre-/perinatal famine exposure during the Dutch Hunger Winter of 1944–1945 and mortality through age 63 years among 41,096 men born in 1944–1947 and examined at age 18 years for universal military service in the Netherlands. Of these men, 22,952 had been born around the time of the Dutch famine in 6 affected cities; the remainder served as unexposed controls. Cox proportional hazards models were used to estimate hazard ratios for death from cancer, heart disease, other natural causes, and external causes. After 1,853,023 person-years of follow-up, we recorded 1,938 deaths from cancer, 1,040 from heart disease, 1,418 from other natural causes, and 523 from external causes. We found no increase in mortality from cancer or cardiovascular disease after prenatal famine exposure. However, there were increases in mortality from other natural causes (hazard ratio = 1.24, 95% confidence interval: 1.03, 1.49) and external causes (hazard ratio = 1.46, 95% confidence interval: 1.09, 1.97) after famine exposure in the first trimester of gestation. Further follow-up of the cohort is needed to provide more accurate risk estimates of mortality from specific causes of death after nutritional disturbances during gestation and very early life. [ABSTRACT FROM PUBLISHER]

Prenatal exposure to ambient air pollutants might cause adverse birth outcomes; however, there have been few studies in which the association between air pollution and preterm birth was examined after stratifying by pregnancy complications. We conducted a population-based case-control study of 1,510,064 singleton births from the Taiwanese birth registry during 2001–2007. Of the total of 1,510,064 births, we designated all 86,224 preterm births as the case group and then randomly selected an additional 344,896 from the remaining births (equivalent to 4 full-term births for every 1 preterm birth) as the control sample. We used an inverse distance weighting approach to calculate an average exposure parameter for air pollutants. The adjusted odds ratio for preterm birth per 10-ppb increase in ozone was 1.12 (95% confidence interval: 1.01, 1.23) for women with gestational diabetes mellitus who were exposed in the third trimester and 1.02 (95% confidence interval: 1.01, 1.03) for women without gestational diabetes (P for interaction <0.001). These findings suggest that exposure to ozone in pregnancy is associated with an increased risk of preterm birth, particularly for women who have gestational diabetes mellitus. [ABSTRACT FROM PUBLISHER]

Preterm birth is a common adverse birth outcome known to be associated with increased infant mortality, and it often results in a higher burden of offspring morbidity in both the short and long terms. The potential for environmental factors, particularly air pollution and meteorological parameters, to increase preterm birth risk has received significant attention worldwide, but the findings are generally inconsistent, with variations in study designs and methods across populations and geographic locations. In the current issue of the Journal, Giorgis-Allemand et al. (Am J Epidemiol. 2017;185(4):247-258) take the field a step further than most prior investigations of the ambient environment. They examined the associations of ambient air pollution and meteorological factors with preterm risk among 13 cohorts across 11 European countries. No association with air pollution was observed, but associations with increased preterm birth risk were found for both increased atmospheric pressure and ambient temperature exposures during the first trimester. The study is notable in attempting to address several important issues that challenge the field, including exposure misclassification and defining critical windows of exposure. Their comprehensive evaluation of ambient exposures is to be commended. [ABSTRACT FROM AUTHOR]

Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio = 0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (−7.23 days, 95% CI: −10.64, −3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (−8.46 days, 95% CI: −14.48, −2.44) and morphine dose lower (−3.60 mg, 95% CI: −7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio = 0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices. [ABSTRACT FROM PUBLISHER]

Preterm premature rupture of membranes (PROM) is the leading identifiable predisposing factor for preterm birth. Although maternal exposure to air pollution can potentially have an impact on preterm PROM, there is no available evidence on such an impact. In this study, based on 5,555 singleton births occurring in Barcelona, Spain (2002–2005), we investigated the associations of maternal exposure to nitrogen dioxide, nitrogen oxides, and particulate matter with aerodynamic diameters of ≤2.5 µm (PM2.5), 2.5 µm–10 µm, and ≤10 µm and PM2.5 light absorption with preterm PROM and gestational age at the rupture of membranes (ROM). We utilized temporally adjusted land-use regression models to predict pollutant levels at each subject's home address during each week of her pregnancy. We conducted matched (according to the length of exposure) case-control analyses to estimate the preterm PROM risk associated with 1 interquartile-range increase in exposure levels during the entire pregnancy and during the last 3 months prior to ROM. We found an increase in preterm PROM risk of up to 50% (95% confidence interval: 4, 116) and a 1.3-day (95% confidence interval: −1.9, −0.6) reduction in gestational age at ROM associated with PM2.5 absorbance, nitrogen dioxide exposure, and nitrogen oxide exposure during the entire pregnancy and the last 3 months prior to ROM. [ABSTRACT FROM AUTHOR]

Previous studies suggested that early pregnancy exposure to specific oral decongestants increases the risks of several birth defects. Using January 1993–January 2010 data from the Slone Epidemiology Center Birth Defects Study, we tested those hypotheses among 12,734 infants with malformations (cases) and 7,606 nonmalformed control infants in the United States and Canada. Adjusted odds ratios and 95% confidence intervals were estimated for specific birth defects, with controlling for potential confounders. Findings did not replicate several hypotheses but did support 3 previously reported associations: phenylephrine and endocardial cushion defect (odds ratio = 8.0; 95% confidence interval: 2.5, 25.3; 4 exposed cases), phenylpropanolamine and ear defects (odds ratio = 7.8; 95% confidence interval: 2.2, 27.2; 4 exposed cases), and phenylpropanolamine and pyloric stenosis (odds ratio = 3.2; 95% confidence interval: 1.1, 8.8; 6 exposed cases). Hypothesis-generating analyses involving multiple comparisons identified a small number of associations with oral and intranasal decongestants. Accumulating evidence supports associations between first-trimester use of specific oral and possibly intranasal decongestants and the risk of some infrequent specific birth defects. [ABSTRACT FROM PUBLISHER]

Maternal smoking during pregnancy is associated with attention deficit hyperactivity disorder (ADHD) in offspring. It is assumed by many that this association is causal. Others suggest that observed associations are due to unmeasured genetic factors or other confounding factors. The authors compared risks of maternal smoking during pregnancy with those of paternal smoking during pregnancy. With a causal intrauterine effect, no independent association should be observed between paternal smoking and offspring ADHD. If the association is due to confounding factors, risks of offspring ADHD should be of similar magnitudes regardless of which parent smokes. This hypothesis was tested in 8,324 children from a well-characterized United Kingdom prospective cohort study, the Avon Longitudinal Study of Parents and Children (data from 1991–2000). Associations between offspring ADHD and maternal and paternal smoking during pregnancy were compared using regression analyses. Offspring ADHD symptoms were associated with exposure to both maternal and paternal smoking during pregnancy (mothers: β = 0.25, 95% confidence interval: 0.18, 0.32; fathers: β = 0.21, 95% confidence interval: 0.15, 0.27). When paternal smoking was examined in the absence of maternal smoking, associations remained and did not appear to be due to passive smoking exposure in utero. These findings suggest that associations between maternal smoking during pregnancy and child ADHD may be due to genetic or household-level confounding rather than to causal intrauterine effects. [ABSTRACT FROM PUBLISHER]

Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation, its impact on fetal growth remains an open question. The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction (FGR) and preterm birth in the PELAGIE cohort, a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006. Exposure was assessed by estimating levels of trihalomethanes (THMs) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid (TCAA) during early pregnancy in a nested case-control design that compared 174 FGR cases, 114 preterm births, and 399 controls. Higher uptake of THMs (especially brominated THMs) was associated with a higher risk of FGR. Women with TCAA detected in their urine (>0.01 mg/L) had a higher risk of FGR than those with TCAA levels below the detection limit (adjusted odds ratio = 1.8, 95% confidence interval: 0.9, 3.7) and had an odds ratio for preterm birth below 1 (adjusted odds ratio = 0.8, 95% confidence interval: 0.3, 2.6). Results from this prospective study, the first to use a biomarker of disinfection by-product exposure, suggest that prenatal exposure affects fetal growth, but the causal agent or agents remain to be identified. [ABSTRACT FROM PUBLISHER]