Faculty Bibliography

Fetoplacental ratio (FPR), the ratio of birthweight (BW) to placental weight (PW), indicates placental efficiency. Changes in FPR are linked to poor pregnancy outcomes and child health risks. Bisphenols and phthalates are endocrine disruptors found in plastics and personal care products that can cross the placenta and have been linked to pregnancy complications and adverse child health outcomes. We examined prenatal exposure to these chemicals in relation to FPR as a possible explanation for these risks. Our analysis included 393 participants in the New York University Children's Health and Environment Study with data on prenatal chemical exposure, BW, and PW from singleton live births. We calculated molar sums of bisphenols and of metabolites of low and high molecular weight (LMW, HMW) phthalates, diethylhexyl phthalate (DEHP), and antiandrogenic phthalates. Linear regression models were adjusted for maternal age, prepregnancy BMI, parity, gestational age at delivery, and fetal sex. Analyses were stratified by fetal sex. HMW were positively associated with FPR in the combined fetal sex sample (beta=0.26, [0.01, 0.50]) with a similar trend for DEHP and antiandrogenic phthalates (betas=0.21 [-0.04, 0.45] and 0.21 [-0.04, 0.45], respectively). Stratified analyses revealed that these results were driven by females, among whom LMW were also associated with higher FPR (beta=0.23 [0.003, 0.45]). No associations were observed between chemicals and BW in either combined or sex-stratified models. In contrast, HMW, LMW, DEHP, di-n-octylphthalate and bisphenols had negative associations with PW, suggesting placental growth as a target for phthalate-mediated endocrine disruption.

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.

The prevalence and incidence of Crohn's disease (CD) in pediatric populations have been steadily increasing. Growing evidence suggests that gut microbiomal community differences play a critical role in the pathogenesis of CD. Additionally, the clinical course of patients with CD is unpredictable, making treatment decisions challenging. We investigated the fecal microbiome of newly diagnosed, treatment-naïve pediatric CD patients (n = 43) compared to age- and sex-matched controls with other functional gastrointestinal disorders (n = 139). We also correlated microbial changes with CD disease activity, measured by the Pediatric Crohn's Disease Activity Index (PCDAI). Our results showed that microbial richness and diversity were significantly lower in CD patients. Furthermore, taxonomic analysis revealed an enrichment in pro-inflammatory bacteria (Fusobacteria and Proteobacteria) and depletion in favorable bacteria (Firmicutes and Verrucomicrobia). Higher PCDAI scores were linked to the enrichment of genera harboring pro-inflammatory taxa (Hungatella and Veillonella) and decreased abundance of genera harboring protective taxa (Lachnospiraceae). Our study underscores the potential of fecal microbiome profiling as an effective tool for understanding CD pathogenesis, identifying microbial biomarkers, and predicting disease activity for treatment response. This, in turn, can help to improve personalized treatment and management strategies in pediatric CD.

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.

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.

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.

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.

OBJECTIVE:To examine associations between oxidative stress and fetal weight across pregnancy. STUDY DESIGN/METHODS:Cohort study of pregnant participants from 2016-2021 in New York City with urinary lipid, protein, and DNA oxidative stress biomarkers (<18, 18-25, >25 weeks) and estimated fetal weight from ultrasound fetal biometry with the HadlockIII formula (20, 30, 36 weeks). RESULT/RESULTS:percentile. Oxidative stress biomarkers of protein damage were associated with larger estimated fetal weight at 20 (3.4 [95% CI: 1.2, 5.7]) and 36 weeks (16.5 [95% CI: 5.2, 27.8]). CONCLUSION/CONCLUSIONS:These findings advance our understanding of different oxidative stress pathways and their potential role in fetal growth.

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and infant mortality and morbidity worldwide. This prospective cohort study investigated the association of racial and ethnic disparities in HDP and explored the potential mediation effect of environmental chemical exposures on excess HDP risk among non-Hispanic Black pregnant people. A total of 3,279 pregnant people were included from 11 cohorts across the United States in the Environmental influences on Child Health Outcomes (ECHO) Program. We analyzed 20 environmental chemicals detected in over 70 % of biospecimens collected during pregnancy. Among Hispanic, non-Hispanic White, and non-Hispanic Black participants, 11.8 %, 10.8 %, and 16.6 % were diagnosed with HDP, respectively. Compared with non-Hispanic White participants, non-Hispanic Black participants had a higher risk of HDP (aRR = 1.48; 95 % CI 1.13-1.94) and higher levels of traditional phthalate metabolites, but lower levels of phthalate alternative metabolites and perfluorooctanoic acid. Hispanic participants had a lower risk of gestational hypertension (aRR = 0.62; 95 % CI 0.40-0.98) and lower levels of perfluoroalkyl substances than non-Hispanic White participants. Critically, despite these race/ethnicity-specific exposure patterns, individual chemical exposures did not mediate the association between racial/ethnic group and HDP. These findings highlight the need to investigate cumulative chemical mixtures and non-chemical environmental and social determinants as potential drivers of HDP disparities.