Faculty Bibliography

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.

In the original publication [...].

BACKGROUND:Evidence suggests prenatal phthalate exposure adversely affects children's behavior. However, epidemiological studies on alternative plasticizers remain scarce. This study investigated associations of gestational exposure to phthalates and alternative plasticizers with internalizing and externalizing behaviors in children aged 1.5-5 years. METHODS:The study included 2617 mother-child dyads from 13 Environmental influences on Child Health Outcomes (ECHO) cohorts. Maternal urine samples, primarily collected mid- to late-pregnancy, were analyzed for 27 phthalate metabolites and 6 alternative plasticizer metabolites. Based on detection frequency, metabolite concentrations were modeled either continuously or categorically (Group 1: non-detectable, 2: lower detectable, 3: higher detectable). Covariate-adjusted associations between individual metabolite concentrations and internalizing and externalizing T-scores on the Child Behavior Checklist for Ages 1½-5 were estimated using linear mixed-effects models. Effect modification by child sex was also examined. RESULTS:for MHxP Group 3 = 1.23, 95% CI: 0.35, 2.12). We observed no robust associations between phthalate metabolites and internalizing T-scores, nor between cyclohexane-1,2-dicarboxylic acid mono carboxyisooctyl ester (DINCH) metabolites and any behavioral outcomes. Child sex modified associations between several metabolites and externalizing T-scores, although the direction of effect varied by metabolite. CONCLUSION/CONCLUSIONS:This large-scale study suggests that prenatal exposure to several phthalates, but not to the alternative plasticizer DINCH, may be associated with a small-to-modest increase in externalizing behaviors in young children.

BACKGROUND:Prenatal exposure to organophosphate esters (OPEs) has been linked to neurotoxic effects in children; however, epidemiological evidence remains inconclusive. We investigated associations of prenatal OPE exposure with child behaviors. METHODS:We analyzed data of 2948 mother-child dyads from 12 prospective cohorts of the Environmental influences on Child Health Outcomes (ECHO) Cohort. Nine OPE biomarkers quantified in prenatal maternal urine were modeled based on detection frequency. Child behaviors were assessed using the Child Behavior Checklist for Ages 1½-5. We used linear mixed effects models to examine associations between each OPE biomarker and composite T-scores. We evaluated child sex and social vulnerability as potential effect modifiers. RESULTS: = -0.89, 95% CI: -1.74, -0.04). Associations between high BCPP exposure and higher externalizing and total problem T-scores were stronger among children from highly vulnerable neighborhoods compared to those from less vulnerable neighborhoods (p-interaction < 0.1). Child sex modified associations for bis(1,3-dichloro-2-propyl) phosphate and high BCPP exposure, with males exhibiting greater adverse behaviors for all associations. DISCUSSION/CONCLUSIONS:Gestational exposure to several OPEs may be adversely associated with early behavioral development.

BACKGROUND/UNASSIGNED:Organophosphate ester flame retardants and plasticizers (OPEs) have myriad uses in industry and consumer products. Increasing human exposure to OPEs has raised concerns about their potential effects on child neurodevelopment during pregnancy. OBJECTIVE/UNASSIGNED:We investigated whether OPE urinary concentrations during pregnancy were associated with child autism-related outcomes. METHODS/UNASSIGNED:We included 4159 mother-child pairs from 15 cohorts in the NIH Environmental influences on Child Health Outcomes (ECHO) Consortium, with children born from 2006-2020 (median age [interquartile range]: 6 [4,10] years). Nine OPE biomarkers were measured in urine samples collected mid- to late pregnancy. Dilution-adjusted biomarkers were modeled continuously, categorically (high [> median], moderate [≤ median], non-detect), or as detect/non-detect depending on their detection frequency. We assessed child autism-related traits via a) parent report on the Social Responsiveness Scale (SRS) and b) clinical autism diagnosis. We examined associations of OPEs with child outcomes, including modification by child sex, using generalized estimating equations to account for clustering by ECHO cohort. RESULTS/UNASSIGNED:Compared with non-detectable concentrations, high exposure to bis(butoxyethyl) phosphate (BBOEP) was associated with higher autistic trait scores (adj-β 0.97, 95% confidence interval [CI]: 0.42, 1.52) and greater odds of autism diagnosis (adjusted odds ratio [adj-OR]: 1.27, 95% CI: 1.07, 1.50). Bis(1-chloro-2-propyl) phosphate (BCPP) showed associations with autistic trait scores (BCPP adj-β for high exposure vs. non-detect: 0.34, 95% CI: -0.46, 1.13; BCPP adj-β for moderate exposure vs. non-detect: 0.72, 95% CI: 0.24, 1.20). High exposure to bis(2-chloroethyl) phosphate (BCETP) was associated with lower odds of autism diagnosis (adj-OR: 0.76, 95% CI: 0.60, 0.95). Other OPEs showed no associations in adjusted models. Associations between BBOEP and higher autistic trait scores were stronger in males than females. DISCUSSION/UNASSIGNED:Prenatal exposure to OPEs, specifically BCPP and BBOEP, may be associated with higher risk of autism diagnosis and related traits in childhood. https://doi.org/10.1289/EHP16177.

BACKGROUND/UNASSIGNED:The relationship between prenatal exposure to low-level air pollution and child autism spectrum disorder (ASD) is unclear. OBJECTIVE/UNASSIGNED:To examine associations of prenatal air pollution exposure with autism. METHODS/UNASSIGNED:quantiles) using quantile regression and with ASD diagnosis using logistic regression. Models were run within census divisions, and coefficients were pooled in a meta-analysis. RESULTS/UNASSIGNED:also was associated with ASD. DISCUSSION/UNASSIGNED:Associations with ASD outcomes were present even at low levels of air pollutants. https://doi.org/10.1289/EHP16675.

BACKGROUND/UNASSIGNED:Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear. OBJECTIVE/UNASSIGNED:To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e., maternal exposure to secondhand smoke [SHS] exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, paternal quitting before pregnancy). METHODS/UNASSIGNED:We conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements, available in a few studies, provided objective data on maternal SHS and smoking during pregnancy. Primary analyses used Illumina450K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array. RESULTS/UNASSIGNED:) was associated with paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (n=3,415), differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs). Smoking-associated CpGs in blood were strongly enriched for functional elements across multiple tissues. CONCLUSIONS/UNASSIGNED:Maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. We observed minimal impacts for less studied exposures including SHS, maternal former smoking and paternal smoking. https://doi.org/10.1289/EHP16303.

UNLABELLED:Exposures to phthalates and synthetic phenols are common among expectant mothers in the US. Previous studies on the neurotoxicity of these compounds have primarily assessed the effects of individual compounds on child behavior, but have not assessed potential combined effects of these substances. We assessed associations between prenatal exposure to a mixture of phthalates and phenols with behavioral problems among preschool-age children participating in the Environmental influences on Child Health Outcome (ECHO) Program. The study sample included 878 mother-child pairs from three cohorts with data on urinary concentrations of 10 phenols and 11 phthalate metabolites during pregnancy, along with caregiver reported Child Behavioral Checklist Ages 1½ to 5 (CBCL) data. Using covariate-adjusted weighted quantile sum (WQS) regression, we estimated associations between the phenol - phthalate mixture and CBCL behavioral scales T-scores. We fitted additional models stratified by sex due to previous reports of sex-specific associations. No statistically significant associations were observed in the overall sample when both male and female children were combined. However, in males, a quintile increase in the WQS index was associated with a 0.04 (95% CI: 0.00; 0.08) higher T-score of externalizing problems. The major contributors to this mixture effect were butylparaben (with a weight of 21%), benzophenone-3 (15%) and MCNP (11%). Conversely, in females, significant negative associations were observed between the WQS index with the total behavioral problems scale (beta = −0.05, 95% CI: −0.09; −0.01), externalizing problems (beta = −0.06, 95% CI = −0.10; −0.02) and internalizing problems (beta = −0.04, 95% CI: −0.08; −0.00). CONCLUSION::Our findings suggest that exposure to synthetic phenols and phthalate metabolite mixtures during pregnancy may impact childhood externalizing behavior with distinct associations in males and females. These findings contribute to the existing evidence on the combined effects of these compounds during development, emphasizing the need for further research on the combined effects of these mixtures.

Environmental exposures often exhibit temporal variability, prompting extensive research to understand their dynamic impacts on human health. There has been a growing interest in studying time-dependent exposure mixtures beyond a single exposure. However, current analytic methods typically assess each exposure individually or assume an additive relationship. This paper aims to fill the gap in method development for evaluating the joint effects of multiple time-dependent exposures on a scalar outcome. We introduce a dynamic single-index scalar-on-function model to characterize the exposure mixture's time-varying effect through a non-parametric bivariate exposure-time-outcome surface function. Utilizing B-spline tensor product bases to approximate the surface function, we propose a profiling algorithm for model estimation and establish large-sample properties for the resulting single-index estimators. In addition, we introduce a non-parametric hypothesis testing procedure to determine whether the surface function varies over time at each fixed mixture level and a model averaging solution to circumvent the issue of knot selection for spline approximations. The performance of our proposed methods is examined through extensive simulations and further illustrated using real-world applications.

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.