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.

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: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.

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.

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: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.

BACKGROUND/UNASSIGNED:Pregnancy requires finely tuned immune changes that support implantation, placental development, maternal-fetal tolerance, and preparation for labor, yet the normative trajectories of circulating inflammatory proteins across gestation remain poorly defined. This cross-sectional study investigates how circulating inflammatory proteins vary with gestational age in pregnancy and examines the impacts of fundamental biological characteristics, such as gravidity and fetal sex. METHODS/UNASSIGNED:Data were drawn from 1154 pregnant individuals from six study sites of the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Cohort. We used Olink high-throughput proteomic profiling to map cross-sectional associations between protein expression levels and gestational age at blood draw using linear, spline-based, and generalized additive modeling approaches. RESULTS/UNASSIGNED:Generalized additive models provided the best fit, revealing that immune changes across pregnancy were predominantly nonlinear. Sixty-one proteins showed significant associations with gestational age, with many exhibiting shared inflection points that aligned with major physiological transitions. A small subset of proteins also showed evidence of modification by fetal and maternal characteristics. CD244 displayed different gestational patterns by fetal sex, while CST5 and SIRT2 showed varied gestational associations by maternal gravidity. CONCLUSION/UNASSIGNED:The findings highlight pregnancy as a sequence of coordinated immune transitions rather than a simple linear shift and provide one of the most detailed characterizations to date of circulating inflammatory protein dynamics across human gestation. Establishing these normative trajectories offers a crucial reference for detecting early deviations that may signal risk for pregnancy complications and for identifying biomarkers in maternal and fetal health research.

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.