Faculty Bibliography

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.

Cardio-obstetrics is a growing subspecialty focused on the prevention, diagnosis, and management of high-risk pregnancies in women with cardiac disease, a condition affecting 1-4 % of pregnancies and a leading cause of indirect maternal mortality in developed countries. The prevalence of maternal cardiac disease is rising as a result of increasing maternal age, obesity, comorbidities, and improved survival of individuals with congenital heart disease. Artificial intelligence (AI) is increasingly used in cardiology to enhance early diagnosis, risk stratification, and treatment planning, offering promising tools to support the diagnostic and therapeutic complexities of maternal cardiac disease. This review explores current applications of AI in cardio-obstetrics and highlights potential opportunities and barriers to its future integration in clinical care.

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.

INTRODUCTION/BACKGROUND:Placental development, involving rapid vascularization, is regulated by concentration gradients of numerous growth factors and hormones. Placental growth factor (PlGF) promotes vasculogenesis and angiogenesis in the placenta, while soluble fms-like tyrosine kinase-1 (sFlt-1) inhibits these processes. An elevated ratio of sFlt-1/PlGF in maternal serum is predictive of preeclampsia. Exposure to two classes of ubiquitous endocrine-disrupting chemicals, bisphenols and phthalates, has also been previously linked to preeclampsia development. METHODS:We investigated the relation of urinary concentrations of bisphenols and phthalate metabolites, measured up to three times during pregnancy, with serum concentrations of sFlt-1, PlGF, and their ratio in the New York University Children's Health and Environment Study. Linear mixed models were used to analyze up to three measurements of PlGF and sFlt-1 adjusted for gestational age at the time of serum collection. RESULTS:We found that higher molar sum concentration of bisphenol A and bisphenol S was associated with lower sFlt-1 (-0.12, 95 % CI: -0.22, -0.03), higher PlGF (0.08, 95 % CI: -0.01, 0.18), and lower sFlt-1/PlGF ratio (-0.12, 95 % CI: -0.21, -0.02). Phthalic acid and metabolites of anti-androgenic and low molecular weight phthalates were similarly associated with higher PlGF and lower sFlt-1/PlGF, but only after 20 weeks of gestation. DISCUSSION/CONCLUSIONS:The unexpected relationship between prenatal bisphenol and phthalate exposure and lower sFlt-1/PlGF warrants further investigation. Our results suggest that the effect of these endocrine-disrupting chemicals on placental health may be more complicated than what is currently understood through these angiogenic biomarkers.

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.

Our objective was to examine the role of structural racism and economic disadvantage in perinatal health inequities using the Environmental influences on Child Health Outcomes Cohort. Participants' addresses were linked to area-level measures of life expectancy, education, unemployment, health insurance, jail rate, segregation, and housing cost burden. We created absolute measures to represent economic disadvantage and relative measures comparing values for Black or Latinx people to White people in the same area to represent structural racism. We used quantile G-computation to estimate the effects of a one-quartile increase in all exposures simultaneously on fetal growth and gestational age measures. A one-quartile increase in economic disadvantage was associated with a reduction in birthweight [(-25.65 grams, 95% CI (-45.83, -5.48)], but not gestational age [-0.02 weeks, 95% CI (-0.13, 0.09)]. With a one-quartile increase in Latinx-White structural racism, we observed reductions in birthweight [-80.83, 95% CI (-143.42, -18.23)) among Latinx participants. A one-quartile increase in Black-White structural racism was weakly associated with lower birthweight among Black participants [-15.70, 95% CI (-82.89, 51.48)] but was associated with higher birthweight among White participants [57.47, 95% CI (13.26, 101.67)]. Our findings suggest co-occurring forms of structural inequity likely influence racialized disparities in fetal growth outcomes.

Findings for greenspace's impacts on birth outcomes are largely dependent on vegetation indexes. Examinations are needed for various greenspace indicators given varying pathways for fetal development. This prospective cohort study assessed the impacts of prenatal greenspace exposure on preterm birth (PTB), term low birthweight (TLBW), birthweight, and estimated fetal weight (EFW) for pregnant women in the New York City area, 2016-2023 (n=2765). Longitudinal greenspace exposure was measured for residential histories during pregnancy using the Enhanced Vegetation Index (EVI) for 1000m buffers and four park metrics, namely, the total number, sum of area, and the accessibility of parks within residential buffers (500 m) and the distance to the closest park. Multivariable regression models were used to estimate the associations for quartiles of exposure (with the first quartile [Q1] as reference). Greenspace exposure was not associated with TLBW, birthweight, or EFW. Odds ratios of PTB for the Q2, Q3, and Q4 EVI exposure groups compared to the Q1 group were 0.65 (95% CI: 0.43-0.98), 0.51 (0.32-0.80), and 0.56 (0.35-0.90), respectively. PTB risks decreased in higher exposure groups (Q2-Q4) of the total park number. Results indicate the benefits of prenatal greenspace exposure for fetal maturity and neonatal outcomes.

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at three time points. Fetal biometrics were obtained from ultrasounds in the second (n=773) and third (n=535) trimesters. Associations between pregnancy-averaged ΣDAP and fetal biometry z-scores were determined through multiple linear regression. Modification by sex was investigated through stratification and interaction. In the second trimester, one ln-unit increase in ΣDAP was associated with lower estimated fetal weight (-0.15 SD; 95% CI: -0.29, -0.01), head circumference (-0.11 SD; CI: -0.22, 0.01), biparietal diameter (-0.14 SD; CI: -0.27, -0.01), and abdominal circumference (-0.12 SD; CI: -0.26, 0.01) in females. In the third trimester, one ln-unit increase in ΣDAP was associated with lower head circumference (-0.14 SD; CI: -0.28, 0.00) and biparietal diameter (-0.12 SD; CI: -0.26, 0.03) in males. Our results suggest that prenatal OP pesticide exposure is negatively associated with fetal growth in a sex-specific manner, with associations present for females in mid-gestation and males in late gestation.

BACKGROUND:Fetal growth is shaped by a complex interplay of parental traits, environmental exposures, nutritional intake, and genetic predispositions. In epidemiological research, birth weight is widely used as a proxy of impaired or favorable fetal growth; but it fails to provide a comprehensive measure, particularly if used alone. METHODS:In a cohort of 538 mother-fetal pairs from the New York University Children's Health and Environment Study (NYU CHES), we utilized multiple linear regression and structural equation modeling (SEM) to assess the influence of various determinants-maternal characteristics, chemical exposures, and dietary factors-on fetal growth. To comprehensively evaluate fetal growth, we employed the concept of latent variable Favorable Fetal Growth Conditions (FFGC), together with three observed outcomes: birth weight, birth length, and gestational age. RESULTS:Maternal characteristics such as height, BMI, race/ethnicity, and maternal alcohol intake were significantly associated with birth weight, birth length, and gestational age in both the linear regression and with FFGC in the SEM. However, SEM additionally revealed significant relationships that were not detected by linear regression. Specifically, di(2-ethylhexyl) phthalate (DEHP) latent factor showed a negative association with the FFGC (β=-0.16, 95% confidence interval (CI)=-0.27, -0.04). The diet latent variable positively impacted FFGC (β=0.15, 95% CI=0.04, 0.25), whereas total calorie intake exhibited a negative effect (β=-0.13, 95% CI=-0.22, -0.05). CONCLUSION/CONCLUSIONS:The SEM provided a thorough understanding of the multifaceted pathways through which multiple factors of chemical mixtures, diet intakes, and maternal characteristics affected fetal development, uncovering nuanced associations that were not apparent in direct effects models. Our findings highlight the intricate interplay of maternal characteristics, chemical exposures, and dietary factors in shaping fetal growth.