Faculty Bibliography

BACKGROUND:There is growing interest in understanding the link between early life exposures to ambient air pollution and childhood blood pressure; however, existing findings, largely from single site/cohort studies, are inconclusive. METHODS:(per 10-ppb) exposures with blood pressure outcomes were estimated using linear and Poisson regressions adjusted for sociodemographic, lifestyle, temporal, and spatial confounders. RESULTS:with both SBP (β: -2.42, 95 %CI: -4.70, -0.14) and DBP (β: -1.94, 95 %CI: -3.81, -0.08) percentiles were suggested. CONCLUSION/CONCLUSIONS:and blood pressure was counterintuitive and warrants further investigation.

Evidence is inconsistent regarding which windows of PM_2.5 exposure are critical for adverse perinatal outcomes. We investigated associations between timing of gestational PM_2.5 exposure and perinatal outcomes. Participants included 19,108 mother-infant dyads from 51 sites of the Environmental influences on Child Health Outcomes (ECHO) cohort. Repeated measures of PM_2.5 exposure were included based on high-resolution spatiotemporal models for trimesters 1-3, early first trimester (≤14 days), and late first trimester (70-92 days). We estimated associations of PM_2.5 exposure (per 5 μg/m³ increase) and continuous outcomes (gestational age at birth [GA] and birthweight for gestational age z-scores [BWZs]) using generalized estimating equation (GEE) models for linear regression. Poisson regression via GEE was used to estimate risk ratios (RRs) of PM_2.5 exposure (per 5 μg/m³ increase) with binary outcomes (preterm birth [PTB], <37 completed weeks of gestation), and term small for gestational age [SGA], <10th percentile). We explored effect modification by participants' characteristics. In fully adjusted models, early 1st trimester PM_2.5 exposure was associated with lower BWZ (β = -0.03, 95 % CI -0.06, -0.001); association with term SGA was RR = 1.06, 95 % CI 0.99, 1.13. Results were mostly null for other windows of gestational exposure. When stratified by sex, early pregnancy PM_2.5 exposure and lower BWZ associations were observed among females, but not males. Suggestive evidence indicates that associations of PM_2.5 exposure with GA, PTB risk, and term SGA risk may vary by maternal race and ethnicity. Our results suggest that policies and practices that reduce the risks of PM_2.5 exposure, particularly in pre-conception and early pregnancy, may improve perinatal outcomes.

CONTEXT/UNASSIGNED:Plasticizers such as bisphenols and phthalates are endocrine-disrupting chemicals and lead to development of metabolic diseases. OBJECTIVE/UNASSIGNED:To examine associations of prenatal exposure to bisphenols and phthalates with metabolic dysfunction. DESIGN/UNASSIGNED:This study was nested in the New York University (NYU) Children's Health and Environment Study, a prospective birth cohort. SETTING/UNASSIGNED:Participants were recruited at three NYU-affiliated hospitals. PATIENTS OR OTHER PARTICIPANTS/UNASSIGNED:Eligible participants were ≥18 years old, <18 weeks pregnant, and had a medically stable pregnancy. EXPOSURES/UNASSIGNED:Twelve phthalate metabolites and two bisphenols were measured in early and mid-pregnancy (<18 and 18-25 weeks) urine samples. Bisphenols were summed, and phthalate metabolites were grouped based by molecular weights and relevant parent compounds. MAIN OUTCOME MEASURES/UNASSIGNED:Logistic and linear regression models assessed chemicals groups' associations with gestational diabetes mellitus (GDM), glucose disturbance (including impaired glucose tolerance (IGT)), and blood glucose response to glucose challenge test (GCT), adjusting for sociodemographic and pregnancy-related factors. RESULTS/UNASSIGNED:Seventy-nine (6.8%) had GDM, 303 (26.1%) had IGT, and blood glucose response to GCT ranged from 22-386 mg/dL. Bisphenol A (BPA) was negatively associated with blood glucose response to GCT (-1.47 [-2.84, -0.10]), while diethylhexyl phthalate (DEHP; 2.67 [0.98, 4.36]) and high molecular weight phthalates (1.94, [0.17, 3.71]) were positively associated with blood glucose response to GCT. DEHP was also linked to glucose disturbance (1.16 [1.02, 1.31]). CONCLUSION/UNASSIGNED:Our findings suggest that phthalate exposure is associated with GDM. Further mechanistic studies are warranted, particularly given the inverse associations with BPA exposure.

OBJECTIVE:Research on the link between antenatal depression and alterations in offspring DNA methylation is sparse and inconsistent. This study aimed to provide a robust and rigorous test of the association between maternal antenatal depression and offspring DNA methylation in neonatal and middle childhood (8-10 years) periods. METHODS:Moderate to severe maternal antenatal depression was identified via a combination of diagnosis codes from outpatient and inpatient encounters during pregnancy and self-reported symptom severity on birth certificates. Offspring DNA methylation was quantified from dried blood spot and venous blood samples in the neonatal and middle childhood periods, respectively. RESULTS:Of 733 mothers with available data in the neonatal period, 53 (7%) experienced moderate to severe antenatal depression. In middle childhood, 15 (9%) of the 161 mothers with available data experienced moderate to severe antenatal depression. In the neonatal period, no probes passed false discovery rate (FDR) correction. In middle childhood, antenatal depression was associated with hypomethylation at two probes after adjustment and FDR correction: cg06112204 (in MAD1L1; β = -1.68, SE = 0.29) and cg17830140 (in POLRMT, β = -1.94, SE = 0.36). Both probes had a similar direction and magnitude when controlling for postnatal depression (β = -1.71, SE = 0.34 and β = -1.78, SE = 0.42, respectively). cg06112204 was also hypomethylated in the neonatal sample (β = -0.49, SE = 0.21), but cg17830140 was not (β = 0.07, SE = 0.22). CONCLUSIONS:Methylation of other probes in the MAD1L1 gene have previously been associated with depression phenotypes in adolescents and adults, lending credibility to the finding that antenatal depression is associated with hypomethylation of cg06112204 in offspring.

OBJECTIVE:It is critical to understand the characteristics of people who use cannabis during pregnancy. We examined the prevalence and sociodemographic and clinical correlates of current, recent, former, and never cannabis use among pregnant individuals in the U.S. METHODS:We analyzed pooled data from 1,992 pregnant participants in the National Survey on Drug Use and Health (NSDUH) from 2021 to 2023. We used multinomial regression to identify correlates of cannabis use status (i.e., never use vs. current [past 30-day], recent [past 2-12-month], and former [nonuse in the past year], respectively). RESULTS:Overall, nearly 7% of pregnant participants reported current cannabis use. Among current users, 31% reported any doctor-recommended cannabis use in the past year and 52% bought their cannabis from a dispensary. Compared to never users, current cannabis use was more likely among those aged 18-25 (vs. 26+; Relative Risk Ratio [RRR] = 2.08, 95% CI: 1.04-4.18), unmarried (vs. married; RRR = 2.54, 95% CI: 1.05-6.14), with greater education (vs. < high school; RRR = 2.97, 95% CI: 1.42-6.23), past 30-day cigarette use (RRR = 2.57, 95% CI: 1.11-5.94), alcohol use (RRR = 7.24, 95% CI: 1.52-34.49), e-cigarette use (RRR = 4.92, 95% CI: 1.71-14.10), or serious psychological distress (RRR = 6.25, 95% CI: 2.46-15.85); current use was less likely among those perceiving some risk of weekly cannabis use (vs. no risk; RRR = 0.07, 95% CI: 0.03-0.14). Recent use (vs. never use) was less likely in states where cannabis was illegal (RRR = 0.45, 95% CI: 0.22-0.95). CONCLUSION/CONCLUSIONS:Cannabis use during pregnancy remains high among certain subgroups. Future research should develop tailored interventions targeting motivations of cannabis use during pregnancy, such as risk perceptions and polysubstance use, which negatively impact maternal and fetal health.

Pediatric hypertension is increasing in prevalence and is associated with cardiovascular and kidney outcomes in adulthood. Beyond traditional contributors such as obesity and kidney disease, a growing body of evidence implicates environmental exposures in the early disruption of blood pressure regulation. This review aims to evaluate and synthesize current evidence on key exposure routes, including airborne pollutants, heavy metals, and endocrine-disrupting chemicals, and their impact on pediatric blood pressure regulation through biological pathways involving vascular integrity, kidney sodium handling, neurohormonal signaling, and epigenetic programming. Mechanistic studies support roles for oxidative stress, endothelial dysfunction, hormonal dysregulation, and persistent transcriptional changes in mediating exposure-related blood pressure elevations. Although pediatric data remain limited and often are derived from observational studies, the plausibility of these pathways and the developmental sensitivity of the cardiovascular system underscore the urgency for longitudinal research. Clinical and public health strategies should incorporate environmental risk assessment to better identify modifiable exposures contributing to hypertension in children.

Phthalates are widely used in consumer products and are recognized as endocrine disruptors. Prenatal exposure to phthalates has been associated with various adverse health outcomes, including preterm birth and impaired fetal growth, and growing attention is being paid to their potential impact on child neurodevelopment. However, previous epidemiological studies examining prenatal phthalate exposure and child neurodevelopment have produced inconsistent or inconclusive findings, and evidence on phthalate mixtures remains limited. In this study, we utilized data from the Environmental influences on Child Health Outcomes (ECHO) Cohort to investigate associations between urinary biomarkers of prenatal phthalate exposure, both individually and as a mixture, and likelihood of neurodevelopmental delay (NDD) in offspring at ages 1 to 3 years. This study included 2378 pregnant person-child dyads from 10 ECHO cohorts who had measurements of NDD odds assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3). Our single-pollutant analyses revealed mixed findings. Higher prenatal exposure to certain phthalates was associated with higher odds of NDD across multiple domains, including motor and problem-solving skills, with evidence of effect modification by child sex. Conversely, we observed negative associations between specific prenatal phthalate concentrations and lower odds of NDD, particularly in communication domain. From mixture analyses, however, no significant associations were observed between the overall phthalate mixture and NDD odds in most domains, except for negative association for the personal-social domain. Further investigation into the biological mechanisms underlying these relationships, as well as more detailed evaluations of phthalate mixtures, will help advance our understanding of how prenatal phthalate exposure may influence early childhood neurodevelopment.

PURPOSE/OBJECTIVE:To examine factors associated with moving during pregnancy and impacts of assigning nSES at enrollment, delivery, or a time-weighted average on birth outcomes (birthweight, birthweight-for-gestational-age z-score, low birthweight, gestational age, small-for-gestational age, preterm birth). METHODS:We used data from the Environmental influences on Child Health Outcomes (ECHO) Cohort Study (2010-2019) with nSES data from the American Community Survey (ACS) matched by time and location to monthly residential histories. We used multivariable logistic models with Generalized Estimating Equations to identify factors associated with moving and quantify exposure misclassification in model estimates. RESULTS:Approximately 7% of 15,376 participants moved at least once during pregnancy. Maternal age (OR: 0.97, 95% CI: 0.95, 0.98) and other race vs. White (OR: 0.39, 95% CI: 0.20, 0.80) were associated with lower odds of moving; lower neighborhood-level education (OR: 1.34, 95% CI: 1.11, 1.62) and living in urban neighborhoods (OR: 3.03, 95% CI: 1.39, 6.59) were associated with higher odds. Among movers, estimates between nSES and birth outcomes changed ≥16% by address assignment; birthweight-for-gestational-age z-score was significant only when using nSES at delivery. CONCLUSION/CONCLUSIONS:Sociodemographic and nSES characteristics are associated with moving during pregnancy; movers may experience exposure misclassification and underestimated effects on birth outcomes.

OBJECTIVE:Early-life exposure to phthalates, widely used in consumer products, may induce developmental lung adaptations and predispose to respiratory morbidity throughout childhood. We assessed the associations of fetal phthalate exposure with wheezing, asthma, and lung function from birth to adolescence. METHODS:We performed 1-stage individual participant data meta-analyses with data from six European birth cohorts (3,745 mother-child pairs) to assess associations of pregnancy-averaged maternal urinary concentrations of 7 phthalate metabolites and 3 phthalate groups (high- and low-molecular-weight phthalate metabolites and sum of di-2-ethylhexyl phthalate metabolites) with wheezing in infancy (0-1 years) and at preschool age (1-5 years), and asthma and lung function at school age (5-12 years). RESULTS:z-scores after multiple testing correction. CONCLUSION/CONCLUSIONS:Fetal exposure to higher phthalate concentrations is associated with lung function adaptations, while overall no consistent associations were observed with childhood wheezing or asthma. Future studies are needed to assess the causality of the observed associations, to identify the underlying mechanisms, and to assess potential respiratory consequences in adult life.