Faculty Bibliography

OBJECTIVE:Anogenital distance (AGD) is a postnatal marker of in utero exposure to androgens and anti-androgens, and a predictor of reproductive health. We examined the association between gestational exposure to phthalates and AGD in male and female infants. METHODS:In 506 mother-infant pairs (276 males, 230 females), we measured urinary concentrations of phthalate metabolites at < 18 and 18-25 weeks of gestation and AGD at child age 12.9 months (95 % range 11.4-21.1). Phthalate metabolite concentrations were adjusted for urinary dilution, averaged, and natural log-transformed. We measured anus-clitoris distance (AGDac) and anus-fourchette distance (AGDaf) in females, and anus-scrotum distance, anus-penis distance, and penile width in males. We used linear regression and partial-linear single-index (PLSI) models to examine associations between phthalates and AGD as single pollutants and in mixture. RESULTS:Fifty-eight percent of mothers were Hispanic, followed by 27 % non-Hispanic White. Higher exposures to ∑di-isononyl(phthalate) (∑DiNP) was associated with longer AGDaf [1.28 mm (95 % confidence interval [CI]: 0.52, 2.03) and 0.97 mm (95 %CI: 0.25, 1.69), respectively]. Higher exposures to ∑di(2-ethylhexyl)phthalate (∑DEHP) was associated with longer AGDac [2.80 mm (95 %CI: 1.17, 4.44), and 1.90 mm (95 %CI: 0.76, 3.04), respectively]. No association was observed between phthalate metabolites and AGD in males after multiple testing correction. In mixture analyses, ∑DiNP and ∑DEHP were the main contributors to longer AGD in females. We also detected an interaction between ∑DiNP and ∑DEHP in association with AGD in females. CONCLUSION/CONCLUSIONS:Early pregnancy phthalate exposure was associated with longer AGD in female infants. Biological mechanisms underlying these associations should be further investigated.

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at three time points. Fetal biometrics were obtained from ultrasounds in the second (n=773) and third (n=535) trimesters. Associations between pregnancy-averaged ΣDAP and fetal biometry z-scores were determined through multiple linear regression. Modification by sex was investigated through stratification and interaction. In the second trimester, one ln-unit increase in ΣDAP was associated with lower estimated fetal weight (-0.15 SD; 95% CI: -0.29, -0.01), head circumference (-0.11 SD; CI: -0.22, 0.01), biparietal diameter (-0.14 SD; CI: -0.27, -0.01), and abdominal circumference (-0.12 SD; CI: -0.26, 0.01) in females. In the third trimester, one ln-unit increase in ΣDAP was associated with lower head circumference (-0.14 SD; CI: -0.28, 0.00) and biparietal diameter (-0.12 SD; CI: -0.26, 0.03) in males. Our results suggest that prenatal OP pesticide exposure is negatively associated with fetal growth in a sex-specific manner, with associations present for females in mid-gestation and males in late gestation.

OBJECTIVE:Poverty and systemic racism within rare intertwined. Children of marginalized racial and ethnic identities experience higher levels of poverty and adverse psychiatric outcomes. Thus, in models of poverty and neurodevelopment, race and ethnicity-as proxies for exposure to systemic disadvantage-are regularly considered confounders. Recently, however, some researchers claimed that using race and ethnicity as confounders is statistically dubious, and potentially socially damaging. Instead, they argue for the use of variables measuring other social determinants of health (SDoH). We explore this approach. METHOD/METHODS:Data are from 7,836 10-year-olds in the Adolescent Brain and Cognitive Development study. We fit mixed regression models for the association of household poverty measures with psychiatric symptoms, magnetic resonance imaging-derived (MRI) cortical measures, and cognition with and without (1) race and ethnicity adjustment; (2); poverty-by-race and ethnicity interaction terms and (3) alternative SDoH variables. Propensity-based weights were used to calibrate the sample to key US demographics. RESULTS:For psychiatric and cognitive outcomes, poverty-outcome relationships differed across racial and ethnic groups (poverty-by-race-and-ethnicity interaction p<0.05). For MRI outcomes, adjusting for race and ethnicity changed the estimate of poverty's impact. Alternative SDoH adjustment could not fully account for the impact of race and ethnicity on the associations explored. CONCLUSION/CONCLUSIONS:Poverty and race and ethnicity combine to influence neurodevelopment. Results suggest effects of poverty are generally inconsistent across race and ethnicity, which supports prior research demonstrating the non-equivalence of SDoH indicators by race and ethnicity. Studies exploring these relationships should assess interaction between poverty and race and ethnicity and/or stratify when appropriate. Replacing race and ethnicity with alternative SDoH may induce bias.

There is growing concern that exposure to per/polyfluoroalkyl substances (PFAS), persistent chemicals used widely to make consumer products water- or grease-proof, may alter immune function, leading to reduced vaccine response or greater susceptibility to infections. We investigated associations between two legacy PFAS (PFOA and PFOS) and infant cytokine levels measured in newborn dried bloodspots (NDBS) from a large population-based birth cohort in Upstate New York, to determine whether exposure to legacy PFAS is associated with variability in cytokine profiles in newborns. We performed adjusted mixed effects regressions for each cytokine against PFOS and PFOA followed by exploratory factor analysis (EFA) on specific cytokine subsets selected via the prior regressions. Among 3448 neonates (2280 singletons and 1168 twins), significant cytokines were dominated by cytokines negatively associated with the given PFAS. Adjusted single-pollutant models with continuous log-transformed PFOA showed significant negative associations with IL-16 (-0.07, 95% CI: -0.3, -0.1), IL-5 (-0.05, 95%CI: -0.09, -0.02), IL-6 (-0.06, 95%CI: -0.1, -0.02), 6-Ckine (0.06, 95% CI: -0.10, -0.02) and significant positive associations with IL-1α (0.066, 95%CI: 0.03, 0.11), MCP-1 (0.06, 95%CI: 0.03, 0.10). Estimates for PFOS were slightly larger than estimates for PFOA but only significant for 6-Ckine (-0.21, 95%CI: -0.09, -0.33) after correction for multiplicity. Our data consistently suggest that legacy PFAS exposures are associated with disrupted, typically reduced, cytokine levels in neonates, with PFOA exposure resulting in more significant differences in individual cytokines and cytokine groupings than PFOS. Regression by PFAS quartile shows evidence of nonlinear dose-response relationships for most cytokines and cytokine groupings.

This is an invitation letter for the principal investigators and cohort studies to join the Consortium on Thyroid and Pregnancy. The inclusion criteria are population-based cohorts with data on maternal thyroid function during pregnancy and any measurement of known groups of endocrine disrupting chemicals.

PURPOSE/OBJECTIVE:Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems. METHODS: Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.5-18 years by surveys. We examined mean differences in CBCL Total Problems and DSM-oriented subscale scores by autism diagnosis and by child sex. Analyses using logistic regression were conducted to examine whether autism was associated with higher CBCL scores. We further examined if these relationships differed by child age category (< 6 years, 6-11 years, 12 + years). The relationships between SRS score and CBCL total and subscale scores were examined using quantile regression models, with analyses adjusted for child sex and age. RESULTS: In ECHO, 553 youth were reported by a parent to have a clinician diagnosis of autism spectrum disorder (ASD) (432 [78%] boys and 121 [22%] girls). Youth on the spectrum had higher mean CBCL raw scores on Total Problems and all DSM-oriented subscales compared to those not on the spectrum (all p < 0.0001). Analyses adjusted for sex and stratified by age group indicated that higher odds of autism diagnosis were associated with total, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scales in the top 30% of the CBCL score distribution. Autistic girls were more likely to have parent-reported depression and anxiety compared to autistic boys. In quantile regression analyses, we observed evidence of stronger associations between SRS and CBCL for those in higher quantiles of CBCL total problems scale score (beta representing 1-unit change in SRS associated with 1-unit increase in CBCL total problems scale score), among children in the 70-90th percentile (β = 1.60, p < 0.01), or top 10th percentile (β = 2.43, p < 0.01) of the CBCL total problems scale score distribution. Similar findings were seen for the DSM-oriented depression, anxiety, and ADHD subscales. CONCLUSION/CONCLUSIONS: Results from this large national sample suggest increased behavioral and emotional problems among autistic children compared to non-autistic children throughout early life. Among children on the spectrum this may warrant increased monitoring for co-occurring behavioral and emotional problems.

BACKGROUND:Exposure to polycyclic aromatic hydrocarbons (PAHs) during childhood has been associated with altered growth and adiposity in children. The effects of prenatal exposure to PAHs on developmental programming of growth and adiposity are still unknown. OBJECTIVE:To study the association of prenatal exposure to PAHs with early childhood growth and adiposity measures. METHODS:In NYU Children's Health and Environment Study (2016-2019), we studied 880 mother-child pairs for maternal urinary PAH metabolites in early, mid, and late pregnancy and measured child weight, length/height, triceps, and subscapular skinfold thicknesses at 1, 2, 3, and 4 years. We used linear mixed models to investigate associations between average pregnancy exposure to PAHs and the z-scores of child repeated measures. The models were adjusted for sociodemographic and health-related factors. RESULTS:Children prenatally exposed to higher levels of PAHs had greater weight and length/height z scores. We found an interaction with time-point of child assessment, showing stronger associations at later ages. For instance, PAH exposure was associated with higher weight z-scores at 3 years: coefficient per Ln-unit increase in 2-NAP=0.25 (95%CI: 0.13, 0.37), 2-PHEN=0.25 (95%CI: 0.11, 0.39), 1-PYR=0.13 (95%CI: 0.02, 0.24), and 4-PHEN=0.09 (95%CI: 0.02, 0.15). Higher concentrations of 2-NAP (coefficient=0.21, 95%CI: 0.11, 0.31), 2-PHEN (coefficient=0.24, 95%CI: 0.12, 0.35), 3-PHEN (coefficient=0.13, 95%CI: 0.02, 0.24]), 4-PHEN (coefficient=0.09, 95%CI: 0.04, 0.15), and 1-PYR (coefficient=0.11, 95%CI: 0.02, 0.21) were associated with higher weight z-score at 4 years. CONCLUSION/CONCLUSIONS:Prenatal PAH exposure may contribute to the developmental programming of growth in childhood.

BACKGROUND:Fetal growth is shaped by a complex interplay of parental traits, environmental exposures, nutritional intake, and genetic predispositions. In epidemiological research, birth weight is widely used as a proxy of impaired or favorable fetal growth; but it fails to provide a comprehensive measure, particularly if used alone. METHODS:In a cohort of 538 mother-fetal pairs from the New York University Children's Health and Environment Study (NYU CHES), we utilized multiple linear regression and structural equation modeling (SEM) to assess the influence of various determinants-maternal characteristics, chemical exposures, and dietary factors-on fetal growth. To comprehensively evaluate fetal growth, we employed the concept of latent variable Favorable Fetal Growth Conditions (FFGC), together with three observed outcomes: birth weight, birth length, and gestational age. RESULTS:Maternal characteristics such as height, BMI, race/ethnicity, and maternal alcohol intake were significantly associated with birth weight, birth length, and gestational age in both the linear regression and with FFGC in the SEM. However, SEM additionally revealed significant relationships that were not detected by linear regression. Specifically, di(2-ethylhexyl) phthalate (DEHP) latent factor showed a negative association with the FFGC (β=-0.16, 95% confidence interval (CI)=-0.27, -0.04). The diet latent variable positively impacted FFGC (β=0.15, 95% CI=0.04, 0.25), whereas total calorie intake exhibited a negative effect (β=-0.13, 95% CI=-0.22, -0.05). CONCLUSION/CONCLUSIONS:The SEM provided a thorough understanding of the multifaceted pathways through which multiple factors of chemical mixtures, diet intakes, and maternal characteristics affected fetal development, uncovering nuanced associations that were not apparent in direct effects models. Our findings highlight the intricate interplay of maternal characteristics, chemical exposures, and dietary factors in shaping fetal growth.