Faculty Bibliography

BACKGROUND:Emerging evidence suggests endocrine disrupting chemicals, including bisphenols and phthalates, may affect behavioral development in children and adolescents. Risk behavior constitutes a potentially sex hormone sensitive behavioral construct. Here, we examined longitudinal associations of phthalate and bisphenol exposure with performance-based tasks and self-reported risk-taking behaviors. METHODS:Within a population-based birth cohort in the Netherlands, urinary bisphenols and phthalate metabolite concentrations were measured in women during pregnancy (three times, n = 1379) and in children (once at 6 years, n = 775). At 10 years, child risk-taking behavior was assessed with the computerized experimental Columbia Card Task (CCT). At 14 years, adolescents completed a computerized self-assessment of real-life risk-taking behaviors. Linear regression and hurdle models adjusted for confounders were applied in the whole sample and stratified by sex at birth. RESULTS:After multiple testing correction, no associations in all children or in boys were found for prenatal or childhood phthalate exposure with the average CCT-score. In girls, prenatal mono-isobutyl phthalate was associated with a higher average CCT-score, indicting more risk-taking (B per 10-fold increase in creatinine-adjusted average prenatal levels = 2.10, 95% CI: 0.69,3.52). No associations were observed for bisphenol exposure nor for self-reported risk-taking. CONCLUSIONS:Prenatal phthalate exposure was associated with more risk-taking in an experimental task at 10 years-of-age in girls only. The task reflects risky decision-making, which may be a hormonally sensitive construct. Risky decision making potentially precedes real-life risk-taking, which was captured by the self-reported measure and was limited in this young sample.

Growing evidence suggests that exposure to air pollution during early life is associated with autism spectrum disorder (ASD). However, results have been inconsistent for autism-like traits and in low exposure settings. Here, we assessed sensitive windows of exposure to fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃) and joint effects of exposure to sources and constituents of PM_2.5 on autism-like traits among 798 children in the Upstate KIDS cohort. Residential air pollution exposures were assessed with machine learning and land use regression models. Autism-like traits at age 10 were assessed via the ASD subscale on the Child Behavior Checklist. Treed distributed lag mixture model was used to identify critical windows of exposure to PM_2.5, NO₂, and O₃ and partial linear single index model was applied to estimate contributions of sources and constituents of PM_2.5 on autism-like traits. The median PM_2.5 exposures were 8.36 and 8.00 μg/m³ for pregnancy and the first year of life. We did not observe critical windows of exposure to PM_2.5, NO₂, or O₃ for autism-like traits. Exposures to elemental carbon (EC) PM_2.5 during gestation and to EC and traffic PM_2.5 during the first year of life were associated with higher odds of autism-like traits (prenatal EC adjusted odds ratio (aOR): 1.72, 95% CI: 1.04-2.83; first year EC aOR: 1.72, 95% CI: 1.21-2.46; traffic aOR: 1.31, 95% CI: 1.01-1.71). Our results suggest that exposure to motor vehicle traffic sources of PM_2.5 may drive previously reported associations between total PM_2.5 and autism-like traits.

BACKGROUND/UNASSIGNED:Prior work has suggested poorer performance on Fluid, but not Crystallized, NIH Toolbox Cognition Battery (NTCB) subtests in autistic youth relative to neurotypical individuals. This study sought to extend previous findings using a larger sample from a nationwide multi-cohort study and to examine the effect of attention-deficit/hyperactivity disorder (ADHD) status on cognitive functioning. METHODS/UNASSIGNED: = 737) were included in the analyses. We used a general linear model framework to examine group differences in task performance, and we used latent profile analysis (LPA) to identify subgroups of individuals with similar cognitive profiles. RESULTS/UNASSIGNED:The AUT and AUT + ADHD groups had lower NTCB Fluid Cognition Index Scores compared to the noAUTADHD group, whereas no group differences in the Crystallized Cognition Index Score were observed. No significant differences in the NTCB subtest or index scores were found between the AUT and AUT + ADHD groups. Sex-stratified analyses revealed no sex differences. LPA identified four distinct NTCB groups, with a substantial proportion of the AUT group (19%) assigned to the class with higher Crystallized versus Fluid Cognition Index Scores; however, there was considerable overlap between the diagnostic groups within the LPA classes. CONCLUSIONS/UNASSIGNED:Autistic individuals experience difficulties with fluid NTCB tasks and those with co-occurring ADHD do not appear to face greater difficulties than those with autism alone. However, there was a notable proportion of autistic individuals with average or superior cognitive performance, highlighting the importance of strength-based and transdiagnostic research approaches.

IMPORTANCE/UNASSIGNED:Gestational environmental chemical exposures are widespread. Some chemicals are known to adversely affect birth outcomes, but many remain understudied. OBJECTIVE/UNASSIGNED:To evaluate associations of gestational exposure to a priori identified chemicals in 10 classes with birth outcomes in a large, diverse US cohort. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:In the prospective Environmental influences on Child Health Outcomes Cohort study, 5318 mother-child pairs were enrolled from January 1, 2000, to December 31, 2021, with data on gestational urinary chemical concentrations, gestational age at birth, and birth weight. Statistical analysis was performed from January 2024 to February 2026. EXPOSURES/UNASSIGNED:In single, midgestation (median, 25 weeks [IQR, 21-30 weeks]) urine samples, concentrations of 113 analytes (chemicals or their metabolites) from 10 chemical classes were simultaneously measured: fungicides and herbicides (n = 11), insecticides (n = 20), halogenated phenols (n = 5), organophosphate esters (n = 10), benzophenones (n = 6), bisphenols (n = 14), parabens (n = 6), antimicrobials (n = 2), phthalates or alternative plasticizers (n = 32), and polycyclic aromatic hydrocarbons (PAHs) (n = 7). MAIN OUTCOMES AND MEASURES/UNASSIGNED:Linear mixed-effects regression models with a random effect for site were used to estimate covariate-adjusted differences in gestational age at birth (days) and birth weight-for-gestational age (BW-GA) z scores per IQR increase in urinary analyte concentrations. In secondary analyses, odds ratios (ORs) for preterm birth and small for gestational age (SGA) were estimated. RESULTS/UNASSIGNED:In the sample of 5318 mother-child pairs, most infants (2667 female [50%]; median gestational age at birth, 39.0 weeks [IQR, 38.0-40.0 weeks]) were born to college-educated (67% [3218 of 4785]), parous (56% [2815 of 5007]) mothers (median age at delivery, 30.7 years [IQR, 26.1-34.3 years]). A total of 43 of 113 analytes (38%) were detected in 50% or more of samples. Multiple phthalates or alternative plasticizers were associated with younger gestational age at birth or lower BW-GA z scores; for example, summed diisononyl phthalate metabolites were associated with a 0.6-day (95% CI, -1.0 to -0.1 days) younger gestational age (preterm birth OR, 1.16 [95% CI, 1.01-1.34]), and summed phthalate or alternative plasticizers were associated with a 0.06 (95% CI, -0.11 to -0.02) lower BW-GA z score (SGA OR, 1.09 [95% CI, 0.93-1.27]). Two halogenated phenols, benzophenone 8, bisphenol F, and several PAHs were associated with lower BW-GA z scores; for example, 1- and 9-hydroxphenanthrene were associated with a 0.04 (95% CI, -0.08 to -0.01) lower BW-GA z score (SGA OR, 1.13 [95% CI, 1.01-1.27]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This large cohort study of diverse US pregnancies found widespread exposure to 10 classes of environmental chemicals, many of which were associated with differences in gestational age at birth or lower BW-GA z scores. These findings indicate that reducing gestational exposure to chemicals, particularly phthalates or alternative plasticizers and PAHs, could promote healthy deliveries and better child outcomes.

IMPORTANCE/UNASSIGNED:Increasing numbers of children are conceived using infertility treatment; concerns remain about potential effects on child neurodevelopment. OBJECTIVE/UNASSIGNED:To evaluate whether infertility treatment is associated with child neurodevelopment and whether such an association may be attributable to underlying subfecundity. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study was conducted among mother-child dyads in the National Institutes of Health Environmental Influences on Child Health Outcomes Cohort, with infants conceived between 1998 and 2022. Associations of subfecundity and infertility treatment with neurodevelopmental outcomes were assessed among children ages 2 to 10 years. Data were analyzed from May 14, 2025, to March 31, 2026. EXPOSURE/UNASSIGNED:Subfecundity was defined as prior consultation for, treatment of, or diagnosis of infertility for either partner; at least 2 prior miscarriages; or ever having had unprotected heterosexual intercourse for 12 months without conceiving. Infertility treatment was categorized as in vitro fertilization (IVF) or non-IVF treatment. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Harmonized caregiver responses to the Strengths and Difficulties Questionnaire and the Child Behavior Checklist yielded continuous raw scores for externalizing and internalizing problems. The total raw Social Responsiveness Scale (SRS) score quantified autism-like symptoms. Caregivers reported physician diagnosis of autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). RESULTS/UNASSIGNED:Among 15 382 mother-infant dyads, there were 14 191 unique maternal participants (mean [SD] age at delivery, 30.9 [5.33] years; 8780 parous participants [57.1%]). ASD and ADHD were diagnosed in 876 offspring (7.6%) and 819 offspring (7.1%), respectively. In generalized linear models, subfecundity was associated with higher externalizing problem and SRS scores among all pregnancies (externalizing problems: b = 0.47 [95% CI, 0.14-0.81]; SRS score: b = 1.08 [95% CI, 0.01-2.14]) and when restricted to natural conceptions (externalizing problems: b = 0.45 [95% CI, 0.07-0.83]; SRS score: b = 1.12 [95% CI, -0.09 to 2.34]). Offspring of parents with subfecundity had higher odds of ASD (overall: odds ratio [OR], 1.27 [95% CI, 1.03-1.57]; natural conceptions: OR, 1.31 [95% CI, 1.04-1.64]). Children conceived via non-IVF treatment had higher odds of ADHD compared with those conceived via natural conception with subfecundity (OR, 1.77 [95% CI, 1.16-2.68]) or without subfecundity (OR, 1.54 [95% CI, 1.05-2.25]). There were no significant associations for IVF treatment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this large US cohort study, subfecundity was associated with elevated scores for caregiver-reported symptoms of behavioral problems and higher odds of ASD diagnosis, independent of infertility treatment. Non-IVF treatment was associated with ADHD, warranting further research into specific indications for treatment that may increase risk of offspring neurodevelopmental problems.

Individuals are exposed to chemicals in daily life. Yet, few studies have examined the long-lasting joint effect of prenatal and childhood exposure to endocrine-disrupting chemical (EDC) on cognitive performance. We analyzed data from mother-child pairs from the Generation R birth cohort (The Netherlands, 2002-2006) with urinary levels of ten phthalate metabolites, bisphenol A, and five nonspecific organophosphate pesticides metabolites three times during pregnancy (n = 565) and at 5 years of age (n = 539). Child cognitive performance was assessed using the vocabulary, matrix reasoning, digit span, and coding subtests of the Wechsler Intelligence Scale at 13 years. Using hierarchical Bayesian kernel machine regression, we found that prenatal EDC mixture level at 75th percentile versus the median was associated with 0.33 decrease (95% credible interval: -0.60, -0.06) in verbal comprehension and with 0.26 decrease (-0.51, -0.02) in matrix reasoning scores, with di(2-ethyhexyl) phthalate and dibutyl phthalates as primary contributing chemicals to the mixture effect for matrix reasoning. Higher childhood levels of EDC mixture were associated with higher verbal scores, in contrast to the inverse associations observed for prenatal exposure, although this finding should be interpreted with caution due to potential exposure misclassification, selection bias, and residual confounding. Overall, our findings suggest that prenatal exposure to a mixture of plasticizers and pesticides may have a long-lasting adverse effect on offspring's cognition.

Introduction Cordon-based congestion policies have demonstrated air quality and health benefits in cities outside the United States (U.S.), yet selecting comparison areas to evaluate these policies remains a methodological challenge. Using two pre-policy administrative health datasets, we examined the feasibility of constructing local, state, and regional counterfactual populations to inform an evaluation of child health impacts of the recently implemented New York City (NYC) congestion pricing policy, focusing on pediatric asthma emergency department visits. Methods Our study population included children aged 0-17 years. Using a difference-in-differences approach for repeated measures, we evaluated crude pre-policy pediatric asthma trends between the congestion relief zone (CRZ) and three comparison areas: (1) NYC neighborhoods outside the CRZ, (2) nine major New York State cities, and (3) dense, heavily trafficked Northeast regional U.S. cities. We compared this approach with a generalized synthetic control method (G-SCM). Results Crude pre-policy pediatric asthma trends were most parallel between the CRZ and the local NYC comparison zone. Socioeconomic, built environment, and environmental exposure covariates varied across comparison areas at baseline. G-SCM improved visual pre-policy trend alignment across all three comparison areas; however, placebo tests revealed statistically significant parallel trend violations persisted for non-local comparison areas. Conclusions Local comparison populations may offer the most representative counterfactual for evaluating NYC congestion pricing child health impacts. Residual parallel trend violations in non-local areas underscore the methodological challenges of counterfactual selection for geographically concentrated urban policies, highlighting the value of triangulating findings across comparison areas and analytic approaches in future post-implementation evaluations.

Acetaminophen is among the most common over-the-counter medications used during pregnancy. Given inconsistent findings from both experimental and epidemiological studies on associations between use and adverse health outcomes, further research is warranted. To address this, our objective was to assess the relationship between prenatal acetaminophen use and birth outcomes. We studied 8957 mother-infant pairs from 36 pediatric study sites participating in the Environmental influences on Child Health Outcomes (ECHO) program. After imputation and inverse probability weighting, we used regression models to examine the relationship between acetaminophen during pregnancy and the following outcomes: (1) preterm birth, (2) birthweight, (3) small-for-gestational age (SGA), and (4) large-for-gestational-age (LGA). Approximately 59% of mothers reported using acetaminophen at any point during their pregnancy (n = 5257). After adjustment for relevant covariates, prenatal acetaminophen use was associated with lower odds of LGA (adjusted odds ratio (aOR): 0.87; 95% CI: 0.79, 0.96). Prenatal acetaminophen use was not associated with preterm birth (aOR: 0.99; 95% CI: 0.86, 1.14), birthweight (aβ: -7.52 g; 95% CI: -27.80, 12.77) or SGA (aOR: 1.02; 95% CI: 0.88, 1.18). Based on these findings, future research should test for dose-response, trimester-specific exposures, and factors affecting individual responses.