Faculty Bibliography

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.

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.

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: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.