Faculty Bibliography

BACKGROUND:Maternal thyroid dysfunction and maternal depression during pregnancy may increase the risk of child behavioral and emotional problems. We sought to investigate the independent and interactive associations of these two risk factors with child behavior problems. METHODS:We combined data from four cohorts in the Environmental influences on Child Health Outcomes (ECHO) program (N = 949). Maternal thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [fT4], thyroid peroxidase autoantibodies [TPO-Ab], fT4/TSH ratio) was measured predominantly during the first half of pregnancy. We harmonized maternal depression into a continuous measure of antepartum depressive symptomatology and a dichotomous measure reflecting (history of) clinical depression. Child internalizing and externalizing problems were harmonized to the T-score metric of the Child Behavior Checklist. We used multiple linear regression and random effects meta-analysis to assess the average relationship between each predictor and outcome, and the variability in these relationships across cohorts. RESULTS:Across cohorts, antepartum depressive symptomatology was positively associated with both internalizing (meta B = 2.879, 95 % CI 1.87-3.89, p < .001) and externalizing problems (meta B = 1.683, 95 % CI 0.67-2.69, p = .001). None of the indicators of maternal thyroid function was associated with child behavior problems across cohorts. TPO-Ab concentrations were positively associated with child externalizing problems only in offspring of depressed mothers (meta B = 3.063, 95 % CI 0.73-5.40, p = .010). CONCLUSIONS:This study supports the importance of maternal antepartum mental health for child behavior across diverse populations. However, we found little empirical evidence for an association between maternal thyroid function within the normal range during pregnancy and child behavioral problems.

Prenatal exposure to phthalates might influence the development of childhood obesity. Most previous studies used body mass index (BMI) at a specific age instead of BMI development, which might be a better indicator of later health. We aimed to assess the association of prenatal phthalate exposure with longitudinal BMI development from infancy to adolescence. Among 1,379 mother-child pairs from a population-based cohort study, phthalate concentrations were measured in maternal spot urine samples, collected during first, second and third trimester. We estimated age- and sex-adjusted BMI standard deviation scores (SDS) at 6 months and 1, 2, 3, 4, 6, 10 and 13 years. We examined the associations of maternal phthalate urine concentrations during pregnancy with repeated measures of BMI using linear mixed effects models. An interquartile range higher natural log-transformed maternal first trimester high-molecular weight phthalate and di-2-ethylhexylphthalate (DEHP) urine concentrations were associated with a -0.10 (95% confidence interval (CI) -0.15 to -0.04), and -0.09 (95% CI -0.15 to -0.04) lower age- and sex-adjusted BMI at 6 months. An interquartile range higher natural log-transformed maternal first trimester phthalic acid and low-molecular weight phthalate urine concentrations were associated with a 0.11 (95% CI 0.03 to 0.18) and 0.13 (95% CI 0.04 to 0.21) higher age- and sex-adjusted BMI at 13 years old. No significant associations were observed for maternal second and third trimester phthalate urine concentrations with BMI. Thus, higher maternal phthalate metabolites urine concentrations appear to be related to lower BMI at early ages but with higher BMI at later ages.

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.

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.

Many phthalates have been identified as endocrine-disrupting chemicals because they alter hormone functions throughout the lifespan. Nationally representative biomonitoring data are available from the United States, Canada, and Europe, but data elsewhere are sparse, making extrapolations of related disease and disability burdens difficult. We therefore examined trends in urinary phthalate metabolite concentrations in non-occupationally exposed populations in countries other than the United States, Canada, and Europe, where representative data are already available at the country level. We systematically reviewed studies published between 2000 and 2023 and analyzed changes in urinary phthalate metabolite concentrations across time using mixed-effects meta-regression models with and without a quadratic term for time. We controlled for region, age, and pregnancy status, and identified heterogeneity using Cochran's Q-statistic and I² index. Our final analysis consisted of 216 studies. Non-pregnant and youth populations exhibited nearly 2.0-fold or greater difference in concentration compared to pregnant and adult populations. Phthalates with significant regional differences had 10-fold higher concentrations in the Middle East and South Asia than in other regions. Our meta-regressions identified an exponential increase in DBP exposure through MnBP concentration internationally (beta: 0.65 ng/mL/year²) and in Eastern and Pacific Asia (EPA) (beta: 0.78 ng/mL/year²). Most DEHP and DnOP metabolites significantly declined internationally and in EPA, while MEP concentration declined by 10.62 ng/mL in Latin America and 8.98 ng/mL in Africa over time. Our findings fill gaps in phthalate exposure data and set the stage for further analysis of the attributable disease burden and cost at regional and international levels, especially in low- and middle-income countries.

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.

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.