Faculty Bibliography

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.

OBJECTIVE:Phthalates are recognized endocrine disruptors and emerging neurotoxicants. Prenatal exposure to di-2-ethylhexyl phthalate (DEHP) has been linked to adverse neurodevelopmental and neuropsychiatric outcomes, and maternal oxidative stress may play a mechanistic role in prenatal DEHP's neurotoxicity. MATERIALS AND METHODS/METHODS:Participants were drawn from the New York University Children's Health and Environment Study. Prenatal DEHP exposure and maternal lipid peroxidation were assessed using repeated creatinine-adjusted maternal urinary measurements across pregnancy, collected from January 2016-April 2020. Neonatal brain-derived neurotrophic factor (BDNF) was measured in cord serum (N = 337), and internalizing and externalizing problems were assessed at an average age of 2 years using the Child Behavior Checklist for Ages 1.5-5 (CBCL 1½-5) (N = 824). DEHP metabolites (mEHHP; mEOHP; mECPP) were averaged across pregnancy, and cumulative lipid peroxidation biomarkers (8-iso-PGF2α; 15-PGF2α; 8,15-PGF2α; MDA) were estimated using area-under-the-curve values from linear mixed-effects spline models. Partial least squares path modeling evaluated direct and indirect associations using latent constructs for DEHP exposure, lipid peroxidation, CBCL 1½-5, and socioeconomic status; other covariates were modeled as single variables. Sex differences were assessed using bootstrapping and sex-stratified models, adjusting for maternal and child age, parity, pre-pregnancy body mass index, cotinine exposure, and socioeconomic status. RESULTS:Prenatal DEHP exposure was positively associated with maternal lipid peroxidation in all models (β's = 0.11-0.27). Sex-stratified analyses showed that prenatal DEHP exposure was positively associated with CBCL 1½-5 in male children only (β = 0.11), but not with BDNF in either sex. Maternal lipid peroxidation was not associated with BDNF or CBCL 1½-5 in either sex. CONCLUSION/CONCLUSIONS:Prenatal DEHP exposure is associated with maternal oxidative stress and total behavioral problems in male children only, but maternal oxidative stress does not mediate these relationships. Alternative upstream mechanisms may underlie both maternal oxidative stress and neurobehavioral outcomes. Future studies should investigate endocrine, metabolic, and epigenetic pathways to clarify DEHP neurotoxicity.

BACKGROUND:Individuals are ubiquitously exposed to bisphenols and phthalates, common plasticizers that may affect neurodevelopment. We examined associations of prenatal and childhood bisphenol and phthalate exposure with internalizing and externalizing problems from early childhood through adolescence. METHODS:Within the Generation R study, prenatal urinary concentrations of bisphenol A (BPA) and phthalate metabolites were assessed in early, mid- and late pregnancy and in childhood at age 6 years. Pregnancy levels were averaged and used in analyses. Internalizing and externalizing problems were reported by parents at child age 3, 6, 10 and 14 years and by children at ages 10 and 14 years. Mother-child dyads with at least one prenatal exposure measure and one internalizing or externalizing problem score during follow-up were included (n = 1361). Among children with childhood exposure measures, n = 651 had at least one internalizing or externalizing problem score. Associations were examined using linear mixed models. Mixture analysis was performed for self-reported scores at age 14 with G-computation. FINDINGS/RESULTS: = 0.12, 95%CI: 0.04, 0.20). No associations with BPA were found. G-computation showed positive, but non-significant, associations for the same metabolites as in single chemical analyses. CONCLUSIONS:Associations of BPA and phthalate exposure with internalizing and externalizing problem scores in adolescents were largely null, associations with childhood phthalate exposure were less consistent and harder to interpret.

Growing evidence links prenatal air pollution with early behavioral outcomes, yet U.S. studies remain sparse. We analyzed data from 8370 mother-child dyads from 28 Environmental influences on Child Health Outcomes (ECHO) Cohort sites. Prenatal nitrogen dioxide (NO₂), fine particulate (PM_2.5), and ozone (O₃) levels were estimated using residential addresses. Caregiver-reported Child Behavior Checklist for ages 1.5-5 (CBCL/1.5-5) assessed internalizing and externalizing problems. Covariate-adjusted linear mixed-effects models estimated associations between pollutants and CBCL/1.5-5 T-scores. Child sex, socioeconomic neighborhood conditions, and prenatal depressive symptoms were evaluated as potential modifiers. Each interquartile range increase in pregnancy-average PM_2.5 was associated with higher externalizing (β_{externalizing} = 0.52, 95% confidence intervals: 0.15-0.90) and internalizing (β_{internalizing} = 0.45, 0.07-0.83) T-scores. Trimester-specific associations were observed: first-trimester PM_2.5 was associated with externalizing (β_{externalizing} = 0.39, 0.08-0.70) and second-trimester PM_2.5 with internalizing (β_{internalizing} = 0.32, 0.01-0.64) T-scores. Third-trimester NO₂ was linked to higher behavioral T-scores (β_{externalizing} = 0.52, 0.03-1.01; β_{internalizing} = 0.51, 0.00-1.01). Associations for O₃ were nonsignificant. Children from the lowest-opportunity neighborhoods exhibited stronger positive associations for NO₂. Males and children whose mothers reported lower prenatal depressive symptoms showed stronger inverse associations for O₃. Overall, prenatal PM_2.5 and NO₂ exposures may be associated with modest increases in early behavioral problems, potentially affecting many children given widespread exposure.

BACKGROUND/UNASSIGNED:Phthalates, widely used as plasticizers, have been associated with adverse pregnancy outcomes, including preterm birth (PTB). This analysis quantifies the global burden of PTB associated with exposure to di (2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DINP). METHODS/UNASSIGNED:A disease burden model was constructed using 2018 exposure estimates from available population-level biomonitoring surveys and meta-analyses in regions lacking such surveys. Hazard ratios (HRs) for PTB associated with phthalate exposure were derived from a previous cohort study and applied to regional exposure distributions, and a search from 2016 to 2026 was completed to identify uncertainty intervals for effect estimates. PTB-attributable outcome estimates were obtained from the Institute for Health Metrics and Evaluation's. Phthalate-associated PTB outcomes were calculated using a population attributable fraction approach. FINDINGS/UNASSIGNED:In 2018, 1.97 million DEHP-attributable PTBs (8.74% of global PTBs) were estimated, alongside 74,000 deaths, 6.69 million years of life lost (YLLs) and 1.22 million years of life lived with disability (YLDs). 1.93 million of these incident PTBs, 72,500 deaths, 6.56 million YLLs, and 1.20 million YLDs could be linked to plastics. The highest absolute burden was estimated in the Middle East and South Asia, representing over 54% of estimated attributable PTBs, followed by Africa at 26%. Attributable morbidity and mortality trends differed in accordance with underlying regional patterns of burden. Estimates were similar for DiNP (64,000 deaths, 1.88 million PTB cases, 5.77 YLLs, 1.35 YLDs, and PAF of 8.32%). To account for uncertainties in extrapolating effect estimates from the US, effect estimates from four previous global meta-analyses were also used to calculate uncertainty intervals. Uncertainty intervals revealed as low as 4 times lower estimates for DEHP, and 10 times lower DiNP estimates, highlighting the need for further investigation to refine DiNP associated morbidity and mortality. INTERPRETATION/UNASSIGNED:This model presents the first global estimate of the PTB burden linked to exposure to certain phthalates. Burden was estimated to be disproportionate in South Asia, the Middle East, and Africa. Implementing regulatory measures to limit exposure to phthalates as a class could help reduce the global PTB burden, particularly in and areas with high PTB risk, limited regulations, and growing plastics industries. FUNDING/UNASSIGNED:Funding was provided by Beyond Petrochemicals and National Institutes of Health grant number: P2CES033423.

BACKGROUND:The role of maternal and fetal characteristics in determining kidney size in early childhood remains largely unexplored. This study aims to evaluate the association between birth weight and kidney size in children aged one to six years and explore other children and maternal determinants in a United States cohort. METHODS:We analyzed data from 892 mother-child pairs enrolled in the New York University Children's Health and Environment Study (CHES). Renal sonographic measurements were taken from one to six years of age. Kidney size outcomes included average kidney length, width, depth, total kidney volume (TKV), adjusted kidney length (kidney length/body length), and adjusted TKV (TKV/body surface area). Maternal determinants include age, demographic characteristics, pre-pregnancy BMI, lifestyle, pregnancy complications, and diet during pregnancy. Fetal determinants included sex, birth weight for gestational age z-score, and gestational age at delivery. Anthropometric z change and breastfeeding duration were also considered. Associations were examined using crude and covariate-adjusted linear mixed models. RESULTS:Birth weight z-score and anthropometric z change were observed positively associated with all measures except adjusted kidney length. Female children had smaller average kidney length and TKV, and breastfeeding duration was negatively associated with average kidney depth and TKV. Children of non-Hispanic Black mothers and parous mothers had smaller kidney measures. CONCLUSION/CONCLUSIONS:In NYU CHES, we found that early childhood kidney size measures were consistently influenced by birth weight z-scores and changes in postnatal weight gain z-scores. Additionally, we observed racial differences and the influence of breastfeeding duration on kidney size. TRIAL REGISTRATION/BACKGROUND:Not applicable.