Faculty Bibliography

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.

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.

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.

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.

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: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: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.

PURPOSE/OBJECTIVE:Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems. METHODS: Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.5-18 years by surveys. We examined mean differences in CBCL Total Problems and DSM-oriented subscale scores by autism diagnosis and by child sex. Analyses using logistic regression were conducted to examine whether autism was associated with higher CBCL scores. We further examined if these relationships differed by child age category (< 6 years, 6-11 years, 12 + years). The relationships between SRS score and CBCL total and subscale scores were examined using quantile regression models, with analyses adjusted for child sex and age. RESULTS: In ECHO, 553 youth were reported by a parent to have a clinician diagnosis of autism spectrum disorder (ASD) (432 [78%] boys and 121 [22%] girls). Youth on the spectrum had higher mean CBCL raw scores on Total Problems and all DSM-oriented subscales compared to those not on the spectrum (all p < 0.0001). Analyses adjusted for sex and stratified by age group indicated that higher odds of autism diagnosis were associated with total, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scales in the top 30% of the CBCL score distribution. Autistic girls were more likely to have parent-reported depression and anxiety compared to autistic boys. In quantile regression analyses, we observed evidence of stronger associations between SRS and CBCL for those in higher quantiles of CBCL total problems scale score (beta representing 1-unit change in SRS associated with 1-unit increase in CBCL total problems scale score), among children in the 70-90th percentile (β = 1.60, p < 0.01), or top 10th percentile (β = 2.43, p < 0.01) of the CBCL total problems scale score distribution. Similar findings were seen for the DSM-oriented depression, anxiety, and ADHD subscales. CONCLUSION/CONCLUSIONS: Results from this large national sample suggest increased behavioral and emotional problems among autistic children compared to non-autistic children throughout early life. Among children on the spectrum this may warrant increased monitoring for co-occurring behavioral and emotional problems.

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.