Faculty Bibliography

INTRODUCTION/BACKGROUND:Identifying strategies to mitigate the effects of secondhand smoke exposure is crucial for public health. Thus, we estimated the effect of a 2018 federal smoke-free housing (SFH) policy on adverse birth outcomes among New York City (NYC) public-housing residents. METHODS:We obtained data on all live births to NYC residents in NYC from 2013 to 2022, using the borough-block-lot of the birthing person's address to identify births to public-housing residents. We then estimated the effect of the SFH policy on risk of preterm birth or low birth weight among births to NYC public-housing residents using a linear-probability difference-in-differences estimator, weighted by inverse probability weights to increase the plausibility of the parallel-trends assumption. RESULTS:Our sample included 44 455 births to public-housing residents and 803 648 births to non-public-housing residents. Difference-in-difference analyses suggested the SFH policy did not affect risk of preterm birth (risk difference (RD) per 100: 0.1; 95% CI -0.6 to 0.9) or low birth weight (RD per 100: 0.3, 95% CI -0.4 to 1.0). Event-study analyses supported these findings and lent credibility to the parallel-trends assumption. CONCLUSIONS:We estimated no initial effects of a federal SFH policy on risk of preterm birth or low birth weight among births to NYC public-housing residents.

OBJECTIVES/OBJECTIVE:To evaluate whether parents who assess their infants as more developmentally advanced are more likely to begin feeding their infants complementary foods before 6 months, and whether developmental readiness explains racial and ethnic differences in complementary food introduction. STUDY DESIGN/METHODS:In a cohort of mothers of 5475 infants from New York state, 9 markers of infant development and timing of initiating complementary feeding were assessed. Mixed effect models assessed associations between developmental markers and initiation of complementary feeding before 6 months term-corrected age. Direct and indirect effects of racial and ethnic differences in complementary feeding through a total development score were computed. RESULTS:In a fully adjusted model, infant sitting (adjusted odds ratio [aOR]:1.60, 95% CI:1.32, 1.93), head control (aOR:1.51, 95% CI:1.26, 1.81), reaching (aOR:1.19, 95% CI:1.04, 1.37), mouthing (aOR:1.26, 95%CI:1.08, 1.46), and having a good appetite (aOR:1.61, 95%CI:1.15, 2.24) were uniquely associated with complementary feeding before age 6 months. A 1-point increase in a total development score was also associated with higher odds of complementary feeding (aOR:1.26, 95% CI:1.19, 1.33). The development score explained some racial and ethnic differences in the odds of complementary feeding before 6 months. CONCLUSIONS:Results suggest that parents are using their children's developmental markers to decide when to begin complementary feeding. Furthermore, observations of racial and ethnic differences in the timing of complementary feeding may be explained by perceptions of developmental readiness, in line with recommendations. Future research on complementary feeding should incorporate assessments of infant developmental readiness.

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.

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/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.

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.

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.