Faculty Bibliography

BACKGROUND:The role of maternal and fetal characteristics in determining kidney size in early childhood remains largely unexplored. This study aims to evaluate the association between birth weight and kidney size in children aged one to six years and explore other children and maternal determinants in a United States cohort. METHODS:We analyzed data from 892 mother-child pairs enrolled in the New York University Children's Health and Environment Study (CHES). Renal sonographic measurements were taken from one to six years of age. Kidney size outcomes included average kidney length, width, depth, total kidney volume (TKV), adjusted kidney length (kidney length/body length), and adjusted TKV (TKV/body surface area). Maternal determinants include age, demographic characteristics, pre-pregnancy BMI, lifestyle, pregnancy complications, and diet during pregnancy. Fetal determinants included sex, birth weight for gestational age z-score, and gestational age at delivery. Anthropometric z change and breastfeeding duration were also considered. Associations were examined using crude and covariate-adjusted linear mixed models. RESULTS:Birth weight z-score and anthropometric z change were observed positively associated with all measures except adjusted kidney length. Female children had smaller average kidney length and TKV, and breastfeeding duration was negatively associated with average kidney depth and TKV. Children of non-Hispanic Black mothers and parous mothers had smaller kidney measures. CONCLUSION/CONCLUSIONS:In NYU CHES, we found that early childhood kidney size measures were consistently influenced by birth weight z-scores and changes in postnatal weight gain z-scores. Additionally, we observed racial differences and the influence of breastfeeding duration on kidney size. TRIAL REGISTRATION/BACKGROUND:Not applicable.

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.

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.

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).

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.

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.