Faculty Bibliography

While maternal histories of adverse childhood experiences (ACEs) have been linked to altered immune signaling during pregnancy, the specific inflammatory pathways underlying these associations remain poorly characterized. We leveraged high-dimensional proteomics to examine associations between maternal ACEs and pregnancy-associated inflammatory signaling pathways defined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and tested whether these associations were moderated by neighborhood-level social vulnerability during pregnancy. Participants included pregnant individuals enrolled in the Environmental influences on Child Health Outcomes (ECHO) Cohort (N = 770). Circulating inflammatory proteins were assayed from maternal plasma using the Olink Target 96 Inflammation panel. Protein markers were mapped to Human Genome Organisation (HUGO) Gene Nomenclature Committee gene symbols and aggregated into KEGG pathway scores using curated definitions. Linear regression models evaluated associations between continuous maternal ACE scores and each pathway score. Following correction for multiple comparisons, higher maternal ACE exposure was associated with higher activity across 12 KEGG-annotated protein pathways, including AGE-RAGE, non-alcoholic fatty liver disease, chemokine, Th17 differentiation, HIF-1, cellular senescence, Rap1, NOD-like receptor signaling, transcriptional misregulation in cancer, and infection-related pathway signaling. Domain-specific analyses identified the most consistent associations for childhood household dysfunction. Neighborhood-level social vulnerability during pregnancy did not moderate ACE-inflammation associations but was independently associated with higher KSHV infection and NOD-like receptor signaling pathway scores. Together, these findings indicate that maternal ACEs and prenatal social vulnerability are independently associated with small, but directionally consistent, differences in overlapping inflammatory and growth-related protein signals during pregnancy.

Limited studies have explored the modifying role of neighborhood factors in the association between prenatal air pollution exposure and child neurodevelopment. We investigated whether the relationship between prenatal ambient air pollution and autism-related traits differed by neighborhood-level opportunity and vulnerability. This study drew data from 8598 mother-child pairs from 35 sites participating in the Environmental influences on Child Health Outcomes (ECHO) Cohort. Ambient air pollutants, including fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and ozone (O₃), were estimated at residential addresses during pregnancy. The Social Vulnerability Index (SVI) and Child Opportunity Index (COI) at the census tract level were linked to residential addresses at birth. The associations of pregnancy average and trimester-specific air pollution with autism-related traits, as measured by the Social Responsiveness Scale (SRS), stratified by SVI and COI quintiles were evaluated using generalized estimating equation models with a p-value <0.10 for the interaction term as suggestive evidence of signficance. There was evidence of interaction between prenatal exposure to O₃ with SRS by SVI (interaction p = 0.07) and by COI (interaction p = 0.01). Prenatal exposure to O₃ during pregnancy was associated with higher SRS score in the lowest SVI (β = 0.05, 95% CI: -0.005, 0.10) and highest COI (β = 0.04, 95% CI:0.00, 0.08). Differential associations of trimester-specific O₃ and PM_2.5 by SVI and COI were also observed (interaction p < 0.10), although stratified associations within each SVI and COI category were not statistically significant. Our findings suggest that neighborhood level social factors may modify the associaitons between prenatal air pollution and autism-related traits and warrant further consideration of neighborhood factors in environmental epidemiological studies.

BACKGROUND/UNASSIGNED:Pregnancy requires finely tuned immune changes that support implantation, placental development, maternal-fetal tolerance, and preparation for labor, yet the normative trajectories of circulating inflammatory proteins across gestation remain poorly defined. This cross-sectional study investigates how circulating inflammatory proteins vary with gestational age in pregnancy and examines the impacts of fundamental biological characteristics, such as gravidity and fetal sex. METHODS/UNASSIGNED:Data were drawn from 1154 pregnant individuals from six study sites of the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Cohort. We used Olink high-throughput proteomic profiling to map cross-sectional associations between protein expression levels and gestational age at blood draw using linear, spline-based, and generalized additive modeling approaches. RESULTS/UNASSIGNED:Generalized additive models provided the best fit, revealing that immune changes across pregnancy were predominantly nonlinear. Sixty-one proteins showed significant associations with gestational age, with many exhibiting shared inflection points that aligned with major physiological transitions. A small subset of proteins also showed evidence of modification by fetal and maternal characteristics. CD244 displayed different gestational patterns by fetal sex, while CST5 and SIRT2 showed varied gestational associations by maternal gravidity. CONCLUSION/UNASSIGNED:The findings highlight pregnancy as a sequence of coordinated immune transitions rather than a simple linear shift and provide one of the most detailed characterizations to date of circulating inflammatory protein dynamics across human gestation. Establishing these normative trajectories offers a crucial reference for detecting early deviations that may signal risk for pregnancy complications and for identifying biomarkers in maternal and fetal health research.

OBJECTIVE:To examine the association between prenatal exposure to a mixture of EDCs and attention-deficit/hyperactivity disorder (ADHD) symptoms in children. METHODS:Participating were mother-child pairs from the Environmental influences on Child Health Outcomes (ECHO) Cohort (n = 3,962, 18 Sites, 2001-2021). Maternal spot urine samples collected during pregnancy were sent to the Wadsworth Center Human Health Exposure Analysis Resource laboratory and analyzed using a single assay workflow. From those samples, 24 urinary metabolites of EDCs with detection frequency > 70%, were grouped as molar sum of high- and low-molecular-weight phthalates, polycyclic aromatic hydrocarbons, bisphenol S, organophosphate esters, and organophosphate and pyrethroid pesticides. Child ADHD symptoms were assessed using raw scores from the Child Behavior Checklist for preschool-aged (CBCL/1½-5) and school-aged (CBCL/6-18) Attention-Deficit/Hyperactivity Problems subscale. Scores ≥ the 85th and 95th percentiles were respectively classified as borderline and clinical thresholds. Quantile g-computation estimated the expected change in ADHD outcome associated with a one-quartile increase in all prenatal EDC mixture concentrations, using negative binomial models for raw scores and binomial models for percentile thresholds. RESULTS:Prenatal exposure to the EDC mixture was not associated with child ADHD symptoms in preschool-aged or school-aged children in adjusted models for either continuous raw scores or percentile thresholds. CONCLUSION/CONCLUSIONS:Overall our findings on prenatal EDC mixture exposure and ADHD symptoms were not robust to full adjustment. Future research that can delineate factors such as windows of vulnerability and trajectories of ADHD-related symptoms may help clarify mixed findings in the literature.

IMPORTANCE/UNASSIGNED:Organophosphate pesticides (OPs) are established neurotoxicants; prenatal OP exposure is widespread in the US population, primarily through diet. Evidence linking prenatal OP exposure to autism spectrum disorder (ASD) and autism-related traits remains inconsistent. OBJECTIVE/UNASSIGNED:To examine the association between prenatal OP exposure and autism-related traits in childhood and to assess potential differences in the association by child sex and maternal diet. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This pooled prospective cohort study used harmonized data from mother-child pairs from 20 study sites in the Environmental influences on Child Health Outcomes (ECHO) cohort. Participants were recruited from January 1997 through December 2019, and autism-related outcomes were assessed in children ages 2 to 19 years. Data analysis was performed from April 2024 and November 2025. EXPOSURE/UNASSIGNED:Prenatal OP exposure using urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCPy) and the sum of 6 dialkyl phosphate (ΣDAP) metabolites. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Parents reported autism-related traits in children using the Social Responsiveness Scale (SRS). Multivariable linear, quantile, and logistic regression models were used to estimate associations between biomarkers and SRS T scores overall and by child sex, adjusting for maternal sociodemographic and behavioral factors. We further adjusted for dietary factors in additional models and tested effect modification by maternal diet quality in exploratory analyses. RESULTS/UNASSIGNED:Among 3339 mother-child pairs examined, mean (SD) maternal age was 31 (6) years, 1665 children (49.9%) were female, and the SRS was administered at a mean (SD) age of 6.4 (3.87) years. Crude or minimally adjusted models suggested inverse associations between prenatal TCPy or ΣDAP levels and SRS scores, but these associations attenuated and lost statistical significance after full adjustment (β per doubling of TCPy concentration [ng/mL] = -0.13; 95% CI, -0.57 to 0.31; β per doubling of ΣDAP [nmol/L] = -0.42; 95% CI, -1.03 to 0.19). Results were consistent across sex-stratified models, secondary analyses using quantile and logistic regressions, various sensitivity analyses, and after adjustments for dietary confounders. There was no evidence of effect modification by diet quality. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this large, prospective cohort study among the ECHO cohort, prenatal OP exposure was not associated with autism-related traits in childhood. Given the known adverse impacts of pesticides in other contexts, further research should consider interactions with other factors, genetic susceptibility, higher exposures, or combined chemical mixtures.

Prior studies suggest fluoride exposure in drinking water above 1500 μg/L is associated with lower child cognition, but evidence is limited at lower exposure levels and in U.S. populations. We evaluated whether prenatal exposure to fluoride in regulated public drinking water was associated with cognition in a pooled U.S. cohort. We analyzed observational data from the Environmental influences on Child Health Outcomes (ECHO) Cohort, including 2514 children born 2006-2019 across 17 sites in 23 states. Individual prenatal time-weighted average public water fluoride concentrations were estimated by linking census tract-level concentrations to residential addresses across pregnancy. Fluid and crystallized cognition were assessed using NIH Toolbox scores. Generalized estimating equation models estimated adjusted mean differences using restricted cubic spline and linear change-point models. Individual prenatal time-weighted average water fluoride concentrations ranged from < 1.0-1940.0 μg/L (mean = 396.9 μg/L). Cubic spline models showed significant inverse associations for fluid cognition above 1107.0 μg/L. Linear change-point models identified 675 μg/L as the best-fitting change-point for fluid cognition; above this value, fluid scores were 0.67 points lower (95% CI, -0.92, -0.42) per 100 μg/L higher fluoride. These findings indicate that prenatal fluoride exposure in regulated public water is nonlinearly associated with lower fluid cognition scores in U.S. children at concentrations below current WHO and U.S. EPA thresholds.

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.

BACKGROUND:We investigated whether OPE urinary concentrations during pregnancy were associated with child's autism-related outcomes. METHODS:We included 4159 mother-child pairs from 15 cohorts in the NIH Environmental influences on Child Health Outcomes (ECHO) Consortium, with children born from 2006-2020 (median age [interquartile range]: 6 [4,10] years). Nine OPE biomarkers were measured in urine samples collected mid- to late pregnancy. Dilution-adjusted biomarkers were modeled continuously, categorically (high [>median], moderate [≤median], nondetect), or as detect/nondetect depending on their detection frequency. We assessed child autism-related traits via a) parent report on the Social Responsiveness Scale (SRS) and b) clinical autism diagnosis. We examined associations of OPEs with child outcomes, including modification by child sex, using generalized estimating equations to account for clustering by ECHO cohort. RESULTS:Compared with nondetectable concentrations, high exposure to bis-(butoxyethyl) phosphate (BBOEP) was associated with higher autistic trait scores (adj-β 0.97, 95% confidence interval [CI]: 0.42, 1.52) and greater odds of autism diagnosis (adjusted odds ratio [adj-OR]: 1.27, 95% CI: 1.07, 1.50). Bis-(1-chloro-2-propyl) phosphate (BCPP) showed associations with autistic trait scores (BCPP adj-β for high exposure vs nondetect: 0.34, 95% CI: -0.46, 1.13; BCPP adj-β for moderate exposure vs nondetect: 0.72, 95% CI: 0.24, 1.20). High exposure to bis-(2-chloroethyl) phosphate (BCETP) was associated with lower odds of autism diagnosis (adj-OR: 0.76, 95% CI: 0.60, 0.95). Other OPEs showed no associations in adjusted models. Associations between BBOEP and higher autistic trait scores were stronger in males than females. DISCUSSION:Prenatal exposure to OPEs, specifically BCPP and BBOEP, may be associated with a higher risk of autism diagnosis and related traits in childhood.

OBJECTIVE/UNASSIGNED:Gender-diverse individuals often face a burden of poor mental health. This study examined whether gender-diverse experiences were associated with higher levels of loneliness in adolescents, over and above depression and anxiety, and how family environmental factors, including maladaptive parenting, being bullied by a sibling at home (victimization), and bullying a sibling at home (perpetration), moderate the associations between gender-diverse and loneliness experiences among 4,424 adolescents in a population-based cohort. METHOD/UNASSIGNED:This cross-sectional study was embedded in Generation R, a multiethnic population-based cohort from fetal life onward. Adolescents with information on self-reported or parent-reported gender diversity and loneliness at ages 13 to 15 years were included. RESULTS/UNASSIGNED:s > .10). CONCLUSION/UNASSIGNED:Gender diversity is associated with higher levels of loneliness in adolescents. Being a target of bullying modified the association of gender diversity with loneliness experiences, suggesting that gender-diverse adolescents who are bullied by siblings experience particularly higher levels of loneliness.

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.