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.

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.

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: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.

Findings for greenspace's impacts on birth outcomes are largely dependent on vegetation indexes. Examinations are needed for various greenspace indicators given varying pathways for fetal development. This prospective cohort study assessed the impacts of prenatal greenspace exposure on preterm birth (PTB), term low birthweight (TLBW), birthweight, and estimated fetal weight (EFW) for pregnant women in the New York City area, 2016-2023 (n=2765). Longitudinal greenspace exposure was measured for residential histories during pregnancy using the Enhanced Vegetation Index (EVI) for 1000m buffers and four park metrics, namely, the total number, sum of area, and the accessibility of parks within residential buffers (500 m) and the distance to the closest park. Multivariable regression models were used to estimate the associations for quartiles of exposure (with the first quartile [Q1] as reference). Greenspace exposure was not associated with TLBW, birthweight, or EFW. Odds ratios of PTB for the Q2, Q3, and Q4 EVI exposure groups compared to the Q1 group were 0.65 (95% CI: 0.43-0.98), 0.51 (0.32-0.80), and 0.56 (0.35-0.90), respectively. PTB risks decreased in higher exposure groups (Q2-Q4) of the total park number. Results indicate the benefits of prenatal greenspace exposure for fetal maturity and neonatal outcomes.

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:Maternal vitamin D level is an important determinant of pregnancy and child health outcomes. Exposure to air pollution is suspected to increase the risk of vitamin D deficiency, but the evidence is scarce. We investigated the association between air pollution during pregnancy and maternal vitamin D levels. METHODS:A total of 15,935 pregnant women from 5 birth cohorts in Europe and U.S were included. Averaged concentrations of nitrogen oxides, fine and coarse particles, and composition of fine particles from conception until vitamin D measurement were estimated at participants' residential addresses using land-use regression or other spatiotemporal models. Cohorts measured vitamin D as 25(OH)D or 25(OH)D3 levels in serum or plasma at early or mid-pregnancy. We defined suboptimal vitamin D levels as levels below 20 ng/mL. We performed logistic regression models for each cohort to estimate the association between air pollution exposure and suboptimal vitamin D levels and pooled cohort-specific estimates in a random-effect meta-analysis. Models were adjusted for sociodemographic and lifestyle characteristics and month of conception. RESULTS:We found an association between PM2.5 and higher odds of suboptimal vitamin D levels (i.e., below 20 ng/mL) (odds ratio per 5 μg/m3 increase in PM2.5, 1.43 95%CI: 1.02, 1.99). There was no association between other air pollutant exposure and vitamin D levels. CONCLUSIONS:PM2.5 exposure might contribute to suboptimal levels of vitamin D in pregnancy. Reducing air pollution exposure should be a priority because vitamin D deficiency may adversely influence offspring development.

Environmental racism poses a significant threat to child health. It is a major contributor to disproportionate exposure to environmental hazards that are linked to adverse health outcomes. This narrative review shows the profound impact that environmental racism poses to healthy child development through 3 examples. Historical redlining provides compelling evidence of how historical policies continue to influence neighborhoods' physical and social conditions. Exploring chemicals in beauty products reveals how anti-Black perceptions of beauty work to expose children of color to endocrine-disrupting chemicals. Finally, by exploring childhood lead exposure, we see how decades of inequitable implementation of lead exposure prevention policies contribute to persistent disparities in the United States today. Fixing these structural issues is complex and will require political will and investment. Yet, individual clinicians play an important role in their local communities in protecting children from the harms of environmental racism, through education, genuine collaboration with the community, and advocacy.