Faculty Bibliography

Oxidative stress, an imbalance between reactive oxygen species and antioxidants, has been linked to impaired placental function and suboptimal fetal growth, yet trimester-specific associations remain poorly understood. We examined 561 mother-infant pairs from The Infant Development and Environmental Study (TIDES), measuring maternal urinary biomarkers of DNA oxidation (8- hydroxydeoxyguanosine (8-OHdG)), lipid peroxidation (malondialdehyde (MDA), and F2-isoprostanes), and protein oxidation (dityrosine (diY)) at first and second trimesters. Using generalized linear models, we examined prospective associations between oxidative stress and ultrasound-derived growth velocities. Early pregnancy oxidative stress biomarkers were persistently associated with reduced second and third trimester growth velocities. First trimester lipid peroxidation markers (8-PGF2α, 15-PGF2α, and 8,15-PGF2α) were associated with slower estimated fetal weight growth velocity in both second trimester (-0.81, -0.93, and -1.72 g/week per log-unit increase, respectively) and third trimester (-4.25, -5.60, and -6.74 g/week). Similarly, first trimester 8-OHdG and diY were associated with both second trimester (-1.31 and -1.17 g/week, respectively) and third trimester estimated fetal weight velocity (-8.01 and -6.75 g/week, respectively). Second trimester 8-OHdG and MDA were associated with slower third trimester estimated fetal weight velocity (-8.57 and -9.25 g/week, respectively). These results provide novel insights into trimester-specific associations between oxidative stress and fetal growth.

Environmental exposures can have adverse associations with perinatal health and birth outcomes. This study aimed to identify the overlap and association between urban areas of environmental risk and adverse perinatal health indicator hotspots in New York City. We examined 2101 census tracts representing 575,257 births from 2016 to 2020 recorded by the New York City Bureau of Vital Statistics looking at preterm birth, adolescent pregnancy, and pre-pregnancy obesity rates. The Getis-Ord Gi* statistic was used to identify geospatial hotspots of adverse indicators. We used multivariable logistic regression to assess associations between areas of environmental risk and odds of indicator hotspot status and Poisson regression to assess associations of hotspot overlap. Overall, 54.6% of environmental risk areas were hotspots for at least one adverse perinatal indicator, accounting for 63.7% of preterm birth hotspots, 93.7% of adolescent pregnancy hotspots, and 67.3% of pre-pregnancy obesity hotspots. Compared with non-risk areas, risk areas had greater odds of being a hotspot of preterm birth (aOR = 2.11; 95% CI 1.60-2.78), adolescent pregnancy (aOR = 32.8; 21.8-49.4), and pre-pregnancy obesity (aOR = 3.15; 2.56-3.87). Environmental risk areas were expected to have 3.36 times the number of overlapping hotspots after adjusting for parental birthplace and parity. The overlap between environmental risk areas and hotspots of adverse perinatal health indicators and the associations with individual indicators and overlapping hotspots suggest that environmental risk area designation may be a useful measure of perinatal health vulnerability for targeted community interventions.

BACKGROUND:Pregnant women are widely exposed to organophosphate esters (OPEs). Few studies have examined how gestational OPE exposures may influence child growth rates, which are important predictors of subsequent cardiometabolic health. METHODS:Among 4566 mother-child dyads from 14 sites within the Environmental influences on Child Health Outcomes (ECHO) Cohort, we evaluated associations of gestational urinary concentrations of nine OPE metabolites with early and mid-childhood rates of change in age- and sex-standardized weight (WAZ), height (HAZ), and body mass index (BMIZ). Using linear mixed models, we estimated associations between each OPE metabolite and each growth measure separately in early childhood (2-5 years; n = 4321) and mid-childhood (6-10 years; n = 2504). We evaluated effect modification by child sex and maternal pre-pregnancy BMI. RESULTS:. DISCUSSION/CONCLUSIONS:In this large, diverse sample of U.S. children, gestational exposure to OPEs was associated with child growth rates, but the direction and magnitude differed by OPE biomarker and developmental period (early- or mid-childhood).

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.

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.

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.

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.

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.