Faculty Bibliography

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.

BACKGROUND:Neighborhood quality may contribute to child mental health, but families with young children often move, and residential instability has also been tied to adverse mental health. This study's primary goal was to disentangle the effects of neighborhood quality from those of residential instability on mental health in middle childhood. METHODS:1,946 children from 1,652 families in the Upstate KIDS cohort from New York state, US, were followed prospectively from birth to age 10. Residential addresses were linked at the census tract level to the Child Opportunity Index 2.0, a multidimensional indicator of neighborhood quality. The number of different addresses reported from birth to age 10 was counted to indicate residential instability, and the change in COI quintile indicated social mobility. Parents completed three assessments of attention-deficit/hyperactivity disorder, problematic behavior, and internalizing psychopathology symptoms at ages 7, 8, and 10. Child and family covariates were selected a priori to adjust sample characteristics, increase estimate precision, and account for potential confounding. RESULTS:In unadjusted models, higher neighborhood quality at birth was associated with fewer psychopathology symptoms in middle childhood, but associations were largely mediated by residential instability. In adjusted models, residential instability was associated with more psychopathology symptoms, even accounting for social mobility. Neighborhood quality at birth had indirect effects on child mental health symptoms through residential instability. CONCLUSIONS:Children born into lower-quality neighborhoods moved more, and moving more was associated with higher psychopathology symptoms. Findings were similar across different timings of residential moves, for girls and boys, and for children who did not experience a major life event. Additional research is needed to better understand which aspects of moving are most disruptive to young children.

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.

Melamine, its analogues, and aromatic amines (AAs) were commonly detected in a previous study of pregnant women in the Environmental influences on Child Health Outcomes (ECHO) Cohort. While these chemicals have identified toxicities, little is known about their influences on fetal development. We measured these chemicals in gestational urine samples in 3 ECHO cohort sites to assess associations with birth outcomes (n = 1,231). We estimated beta coefficients and 95% confidence intervals (CIs) using adjusted linear mixed models with continuous dilution-standardized concentrations (log₂ transformed and scaled by interquartile range, IQR) or binary indicators for detection. As secondary analyses, we repeated analyses using categorical outcomes. Forty-one of 45 analytes were detected in at least one sample, with > 95 % detection of melamine, cyanuric acid, ammelide, and aniline. Higher melamine concentration was associated with longer gestational age (β^ per IQR increase of log₂-transformed: 0.082 [95 % CI: -0.012, 0.177]; 2nd vs 1st tertile: 0.173 [-0.048, 0.394]; 3rd vs 1st tertile: 0.186 [-0.035, 0.407]). Similarly in secondary analyses using categorical outcomes, an IQR increase in log₂(melamine) was associated with 1.22 [0.99, 1.50] higher odds of post-term (>40 & ≤42 weeks) as compared to full-term (≥38 & ≤40 weeks). Several AAs were associated with birthweight and gestational length, with the direction of associations varying by AA. Some stronger associations were observed in females. Our findings suggest melamine and its analogs and AAs may influence gestational length and birthweight.

The effects of plastics on human health include allergy, atopy, asthma, and immune disruption, but the consequences of chemicals used in plastic materials span nearly every organ system and age group as well. Behavioral interventions to reduce plastic chemical exposures have reduced exposure in low- and high-income populations, yet health care providers know little about plastic chemical effects and seldom offer steps to patients to limit exposure. Health care facilities also use many products that increase the risk of chemical exposures, particularly for at-risk populations such as children in neonatal intensive care units. Given that disparities in plastic chemical exposure are well documented, collaborative efforts are needed between scientists and health care organizations, to develop products that improve provider knowledge about chemicals used in plastic materials and support the use of safer alternatives in medical devices and other equipment.

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.

BACKGROUND:Evidence suggests historical redlining shaped the built environment and health outcomes in urban areas. Only a handful of studies have examined redlining's association with air pollution and adverse birth outcomes in New York City (NYC). Additionally, no NYC-specific studies have examined the impact of redlining on birth weight. METHODS:) exposure during pregnancy using multivariable regression models. Additionally, we examined how maternal residence in a historically redlined neighbourhood during pregnancy influenced birth weight z-score, preterm birth and low birth weight. RESULTS:in our models assessing the relationship between redlining grade and birth outcome, our results did not change. DISCUSSION/CONCLUSIONS:levels today.