Faculty Bibliography

The prenatal period is a critical window for neurodevelopment, during which maternal metabolic processes are increasingly recognized to shape later behavioral and autism-related traits. We examined associations between targeted maternal urinary metabolomic profiles across pregnancy and preschool emotional, behavioral, and autism-related outcomes in the New York University Children's Health and Environment Study (NYU CHES), a large prospective birth cohort. Targeted metabolomics was conducted on maternal urine samples collected in early, mid, and late pregnancy. Child outcomes were assessed at a mean age of 2.3 years using the Child Behavior Checklist (CBCL) total and DSM-5-oriented autism spectrum disorder (ASD) subscale scores. We applied two-stage mixed-effects models to assess overall pregnancy metabolite levels and timepoint-specific negative binomial models to evaluate trimester-specific associations, with covariate adjustment, sex-stratification, and false discovery rate (FDR) correction. Few associations were observed two-stage models. In timepoint-specific analyses, a robust sex- and timing-specific association emerged: among males, higher third-trimester urinary lysoPC a C26:1 was associated with lower CBCL total and ASD subscale scores, surviving stringent FDR correction and remaining robust after adjustment for maternal diet quality. Additional associations involving taurine, inflammatory markers, and acylcarnitines were observed primarily in sex-stratified or diet-adjusted models but were less robust to multiple testing correction. These findings suggest that prenatal metabolic profiles, particularly lipid- and mitochondrial energy-related pathways in late gestation, may contribute to early behavioral and autism-related traits in a sex-specific manner, underscoring the importance of exposure timing and maternal metabolism in the etiology of neurodevelopmental outcomes.

PURPOSE/OBJECTIVE:This study aimed to examine associations of bisphenol and phthalate exposure with arterial stiffness among women of reproductive age. METHODS:Participants include 637 adult women enrolled in the New York University Children's Health and Environment Study (NYU CHES), a prospective pregnancy cohort. The concentrations of eight bisphenols and 22 phthalate metabolites were quantified in up to three spot urine samples. Primary outcomes included brachial artery distensibility (BrachD) and carotid-femoral pulse wave velocity (cfPWV) as measures of peripheral and central arterial stiffness, respectively, along with blood pressure assessed at repeated study visits up to seven years from exposure measures. Associations between averaged, log2-transformed, creatinine-standardized chemical concentrations and subclinical vascular outcomes of interest were examined using linear mixed-effects models. RESULTS:In covariate-adjusted models, a doubling of bisphenol A was positively associated with BrachD (0.09%/mmHg, 95% confidence interval [CI] = 0.02, 0.16), a doubling of bisphenol S was negatively associated with mean arterial pressure (MAP) (-0.52 mmHg, 95% CI = -0.98, -0.05), a doubling of di(2-ethylhexyl) phthalate (DEHP) metabolites was negatively associated with diastolic blood pressure (DBP) (-0.81 mmHg, 95% CI = -1.38, -0.23) and MAP (-0.83 mmHg, 95% CI = -1.45, -0.21), and a doubling of antiandrogenic phthalate metabolites was associated with 0.62 mmHg lower DBP (95% CI = -1.22, -0.03) and 0.66 mmHg lower MAP (95% CI = -1.30, -0.02). CONCLUSION/CONCLUSIONS:These findings suggest that routine exposure to bisphenols and DEHP may be associated with vasorelaxation, potentially related to these chemicals' estrogenic and/or antiandrogenic effects.

BACKGROUND:Emerging data suggests that glyphosate, a non-selective herbicide, can influence reproductive health. We investigated associations of prenatal exposure to glyphosate and aminomethylphosphonic acid (AMPA), with preterm birth and its subtypes. METHODS:We used data from the NYU Children's Health and Environmental Study, a prospective birth cohort in New York City (2016-2019). Participants (n=1450) provided urine samples at 4 to <18 weeks and 18 to 25 weeks gestation. Exposure was adjusted for creatinine and natural log transformed. Preterm birth was defined as a birth occurring before 37 weeks of gestation. We also explored preterm birth subtypes, spontaneous preterm births and medically indicated preterm births as secondary outcomes. To examine associations between glyphosate and AMPA at both timepoints with preterm birth, we used generalized estimating equations with a logit link function. RESULTS:Overall, 7% (n=103) of births were preterm. Glyphosate concentrations at 18-25 weeks was associated with preterm birth (OR: 1.35, 95% CI: 1.04, 1.76) and spontaneous preterm birth (OR: 2.01, 95% CI: 1.40, 2.90). AMPA was not associated with preterm birth in any model. CONCLUSIONS:These results support evidence that glyphosate may act upon pathways leading to preterm birth and spontaneous preterm birth. Our study highlights pregnancy as a vulnerable period to glyphosate exposure.

Relatively few epidemiologic studies in the US have measured the short-chain replacement per- or polyfluoroalkyl substance (PFAS) perfluorobutanesulfonic acid (PFBS), and little is known about its health impacts. We measured prenatal serum concentrations of 13 PFAS, including PFBS, among 500 participants in the New York University Children's Health and Environment Study (NYU CHES) between 2016 and 2019. We investigated associations of PFAS exposures with demographic characteristics, including location of residence, and conducted an exploratory factor analysis to investigate common sources of exposure. PFBS concentrations were quantified in 95.6% of samples (median 0.40 ng/mL), which was unexpectedly higher than serum PFBS concentrations reported in other US-based cohorts. PFBS concentrations were not correlated with other PFAS, though they were positively correlated with each other. Unlike other PFAS, PFBS concentrations were not associated with participant characteristics, and there was no evidence for spatial autocorrelation. The changing PFAS exposure landscape warrants further investigation into the health effects of short-chain replacements, particularly in vulnerable populations.

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.

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.

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.

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.

OBJECTIVES/OBJECTIVE:To assess the effects of World Trade Center (WTC) exposures, obesity, and smoking on post-bronchodilator (post-BD) lung function in WTC Survivors. METHODS:Data included 5,243 participants enrolled in WTC Environmental Health Center (WTC EHC) program between 2005 and 2022. WTC-related exposures included dust-cloud exposure and occupational/residential roles. Lung function included post-BD spirometry (FEV1, FVC) and impulse oscillometry (R5, R20, AX). Multivariable linear and quantile regressions assessed associations with WTC exposures, BMI, and smoking, adjusting for demographics. RESULTS:Dust-cloud exposure and Worker status were associated with elevated AX, R5, and R20, indicating small airway dysfunction. Spirometry showed minimal impact from dust exposure, though Workers had lower FEV₁ and FVC than Residents. Obesity and smoking were consistently linked to poorer lung function, with effect sizes surpassing WTC exposure. No significant interactions were found between BMI and WTC exposures. CONCLUSIONS:WTC exposures are associated with small airway dysfunction, especially in Workers. Obesity and smoking independently worsen lung function, underscoring the importance of both environmental and physiological risk factors in disaster-exposed populations. Post-BD oscillometry adds critical sensitivity in detecting injury to small airways.