Faculty Bibliography

OBJECTIVE:Poverty and systemic racism within rare intertwined. Children of marginalized racial and ethnic identities experience higher levels of poverty and adverse psychiatric outcomes. Thus, in models of poverty and neurodevelopment, race and ethnicity-as proxies for exposure to systemic disadvantage-are regularly considered confounders. Recently, however, some researchers claimed that using race and ethnicity as confounders is statistically dubious, and potentially socially damaging. Instead, they argue for the use of variables measuring other social determinants of health (SDoH). We explore this approach. METHOD/METHODS:Data are from 7,836 10-year-olds in the Adolescent Brain and Cognitive Development study. We fit mixed regression models for the association of household poverty measures with psychiatric symptoms, magnetic resonance imaging-derived (MRI) cortical measures, and cognition with and without (1) race and ethnicity adjustment; (2); poverty-by-race and ethnicity interaction terms and (3) alternative SDoH variables. Propensity-based weights were used to calibrate the sample to key US demographics. RESULTS:For psychiatric and cognitive outcomes, poverty-outcome relationships differed across racial and ethnic groups (poverty-by-race-and-ethnicity interaction p<0.05). For MRI outcomes, adjusting for race and ethnicity changed the estimate of poverty's impact. Alternative SDoH adjustment could not fully account for the impact of race and ethnicity on the associations explored. CONCLUSION/CONCLUSIONS:Poverty and race and ethnicity combine to influence neurodevelopment. Results suggest effects of poverty are generally inconsistent across race and ethnicity, which supports prior research demonstrating the non-equivalence of SDoH indicators by race and ethnicity. Studies exploring these relationships should assess interaction between poverty and race and ethnicity and/or stratify when appropriate. Replacing race and ethnicity with alternative SDoH may induce bias.

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.

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.

IMPORTANCE/UNASSIGNED:Prior studies report negative associations between prenatal exposure to fine particulate matter (ie, aerodynamic diameter <2.5 µg; PM2.5) and birth weight, but have typically averaged exposure across pregnancy, which may not reveal windows of susceptibility. OBJECTIVE/UNASSIGNED:To identify windows of prenatal susceptibility to PM2.5. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This was a retrospective analysis of a prospectively enrolled cohort study. Participants were enrolled at 1 of 50 sites participating in the US Environmental Influences on Child Health Outcomes Cohort. The study included full-term, singleton births occurring between September 2003 and December 2021. Statistical analyses were conducted from March 2024 to February 2025. EXPOSURES/UNASSIGNED:Daily residential PM2.5 exposure was estimated using a machine-learning model covering the contiguous US and mean exposure estimates were calculated for each week of pregnancy. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Bayesian distributed lag interaction models were used to examine cumulative and week-specific associations between PM2.5 exposure and birth weight for gestational age (BWGA) z scores. Interactions with sex, race and ethnicity, and region were also examined. RESULTS/UNASSIGNED:The sample of 16 868 mother-newborn pairs (maternal mean [SD] age, 30.4 [5.5] years; 605 [3.6%] Asian, 2197 [13.0%] Black or Black-Hispanic, 3407 [20.2%] Hispanic, 9251 [54.8%] non-Hispanic White, and 1408 [8.4%] other) included 15 806 unique mothers and 1062 mothers with 2 or more children in the study. Mean (SD) weekly PM2.5 exposure during pregnancy was relatively low, at 8.03 (2.3) µg/m3, and overall mean (SD) birth weight was 3410.7 (464.5) g. In the sample overall, there was a negative association between PM2.5 exposure and BWGA z score (β = -0.06; 95% credible interval [CrI], -0.10 to -0.03), with a critical window in early gestation (weeks 1-5) that persisted only among males (β = -0.06; 95% CrI, -0.10 to -0.02). When examining differences by region, there were negative associations in the Northeast (β = -0.09; 95% CrI, -0.15 to -0.03), Midwest (β = -0.11; 95% CrI, -0.17 to -0.05; critical window, 12-18 weeks), and South (β = -0.18; 95% CrI, -0.17 to -0.05; critical window, 3-9 weeks). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, higher PM2.5 exposure was associated with lower BWGA z score, with critical windows identified during early pregnancy to midpregnancy; however, findings varied by sex and region. Understanding windows of susceptibility to environmental exposures can help guide research on underlying biological processes and can inform strategies for limiting exposure during certain periods of pregnancy.

The exponential rise in plastic production has driven widespread contamination by micro- and nanoplastics (MNPs) in the environment. These plastic particles and their chemical additives have been detected in water sources, human bodily fluids, and reproductive tissues. With global fertility rates declining, their role as potential contributors is under investigation. This scoping review compares findings from in vitro experiments, in vivo studies across animal models, and epidemiological data to assess potential reproductive hazards associated with MNP exposure. Forty original studies published within the last decade were identified. MNPs have been detected in human breast milk, placenta, endometrium, ovaries, testis, semen, follicular fluid, blood, and urine samples. Humans are estimated to absorb 74,000-121,000 particles annually through inhalation, ingestion, skin contact, and use of plastic materials, including medical devices. Experimental evidence demonstrates that MNPs can cross biological barriers, interact with cells, and disrupt cellular pathways, including steroidogenesis, energy metabolism, inflammatory pathways, and oxidative stress. Thirty in vivo animal studies have associated MNPs with altered reproductive endpoints in both males (i.e., altered semen quality and spermatogenesis) and females (i.e., altered folliculogenesis, depleted ovarian reserve, and reduced litter sizes), with possible transgenerational effects. In conclusion, current evidence suggests MNPs may represent a reproductive health hazard to humans and animals. The relative contributions of particle toxicity and their chemical additives remain difficult to disentangle. Overall, plastics and their associated chemicals represent a serious health and environmental concern, which continues to grow in the absence of restrictions and international agreements.

Experimental evidence shows that organophosphate esters (OPEs), common flame retardants and plasticizers, can cause developmental neurotoxicity. We investigated the extent to which prenatal OPE exposure was associated with child cognition. Participants were 831 mother-child pairs from 3 sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort with data on urinary levels of 9 OPE analytes during gestation (2009-2019) and child cognition. Based on detection frequencies, analytes were modeled continuously (adjusted for urinary dilution and log2-transformed), categorically (high/low/non-detect), or dichotomously (detect/non-detect). Children's cognition was measured using the Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children at mean age 5.7 years (SD=0.7). We examined associations of OPE analyte with age- and sex-standardized cognition scores using linear regression with generalized estimating equations to account for clustering within sites. We also tested for effect measure modification by sex. The analyte with the highest detection frequency (96.4%) was diphenyl phosphate (DPHP), a primary metabolite of triphenyl phosphate (TPHP). Higher concentrations of DPHP were associated with lower cognition scores ( per doubling of concentrations=-0.46, 95%CI: -0.90, -0.02). Bis(butoxyethyl) phosphate (BBOEP), bis(1-chloro-2-propyl) phosphate (BCPP), and bis(2-methylphenyl) phosphate (BMPP) above the detection limit (vs. below) were associated with higher cognition scores mainly in boys; but, sex interaction with BMPP was not significant. Prenatal exposure to DPHP, a widely detected OPE, was associated with lower cognitive functioning, though the effect size was small. Given widespread exposure, findings related to this and other OPEs should be further examined in mechanistic studies.

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.

Children face an urgent threat in the form of hazards posed by plastics in the environment. Despite robust and rapidly accumulating evidence on the effects of plastic on children's health, plastic presents a paradox for child health providers: while plastic is a vehicle for so many interventions, robust evidence from laboratory and human studies show that chemicals used to produce plastics contribute to chronic conditions in multiple organ systems and disrupt hormone function, and exposure to plastic-derived toxins is associated with adverse birth outcomes, metabolic conditions, neurodevelopmental disease and disability, and reproductive conditions. Evidence-based, safe, simple, and low-cost steps exist for child health providers in primary care to help families limit children's exposure to plastic-derived toxins. Health-care providers also have a crucial opportunity to protect the health and wellbeing of future generations of children by supporting local and global campaigns for governments, industries, and the general public to reduce the accumulation of plastics in the environment and minimise the use of plastics within health-care systems.

Phenolic compounds may be harmful to the developing fetus, but many have not been studied in-depth for adverse childhood allergic and respiratory health effects. We hypothesized that higher levels of phenolic compounds in prenatal spot urine would be associated with greater odds of childhood atopic dermatitis, allergic rhinitis, and asthma, and that child sex may modify these associations. 3198 mother-child paired cases were enrolled from 16 cohorts in the U.S. ECHO consortium. Fifteen phenols (e.g. benzophenones, parabens, bisphenols, triclosans) were measured from mother's urine during pregnancy using a multi-class chemical panel. Childhood outcomes included parent-reported atopic dermatitis (1466 mother-child pairs) between ages 0-3 years, and allergic rhinitis (901 mother-child pairs) and asthma (1662 mother-child pairs) between ages 5-9 years. Prenatal parabens were associated with increased odds of atopic dermatitis (odds ratio (OR) 1.13, 95 % confidence intervals (CI) 1.02, 1.26). Benzophenones were associated with lower odds of asthma (OR 0.77, CI 0.66, 0.90). Compared to boys, girls demonstrated higher odds of parabens (1.21, CI 1.04, 1.42), benzophenones (1.18, CI 1.00, 1.38) and bisphenol S (1.21, CI 1.03, 1.43) being associated with atopic dermatitis, and of the benzophenones (1.46, CI 1.11, 1.93) being associated with allergic rhinitis. An association of benzophenones (0.66, CI 0.53, 0.83) with lower odds of asthma was stronger among boys. These findings suggest that prenatal paraben and other phenol exposures may adversely affect early-life allergic and respiratory outcomes, with sex-specific vulnerability. Novel, multi-modality approaches to reduce maternal phenol exposure during pregnancy are urgently needed to protect children's health.

Prior research links prenatal exposure to organophosphate (OP) pesticides to adverse health outcomes via molecular mechanisms, such as oxidative stress, neurotransmitter disruption, and mitochondrial dysfunction. This study investigates such mechanisms by assessing the relationships between prenatal OP pesticide exposure and targeted urinary maternal metabolomic profiles using data from the New York University Children's Health and Environment Study (NYU CHES) cohort (n = 890). Urine samples were collected at three time points during pregnancy (T