Faculty Bibliography

IMPORTANCE/UNASSIGNED:Chronic exposure to arsenic in drinking water has been associated with increased chronic disease mortality. However, there is limited evidence on associations between reduced exposure and mortality risk. OBJECTIVE/UNASSIGNED:To examine whether reductions in arsenic exposure, measured using urinary arsenic levels, are associated with lower mortality from chronic diseases, including cancer and cardiovascular disease (CVD). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A prospective cohort of 11 746 adults was enrolled between 2000 and 2002 in Araihazar, Bangladesh, with levels of well-water arsenic ranging from less than 1 µg/L to 864 µg/L (mean, 102 µg/L), exceeding the Bangladesh standard of 50 µg/L. Arsenic levels declined over time as a result of community mitigation. Mortality was tracked through 2022. Analyses included 10 977 participants with calculable changes in urinary arsenic levels. EXPOSURES/UNASSIGNED:Urinary arsenic levels were measured up to 5 times per participant through 2018. Participants were categorized based on changes in urinary arsenic levels. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Adjusted hazard ratios (aHRs) and 95% CIs for mortality from chronic diseases, including cancer and CVD. RESULTS/UNASSIGNED:Among 10 977 participants (57% female; mean age, 37.0 [SD, 10.1] years), mean urinary arsenic levels declined from 283 (SD, 314) to 132 (SD, 161) µg/g creatinine from 2000 to 2018. Each IQR decrease in urinary arsenic (197 µg/g creatinine) was associated with 22% lower chronic disease mortality (aHR, 0.78 [95% CI, 0.75-0.82]), 20% lower cancer mortality (aHR, 0.80 [95% CI, 0.73-0.87]), and 23% lower CVD mortality (aHR, 0.77 [95% CI, 0.73-0.81]). Time-varying Cox and restricted cubic spline analyses showed larger reductions were associated with lower mortality, while increases were linked to higher risk. Compared with participants with consistently high urinary arsenic levels (above the baseline median of 199 µg/g creatinine [n = 1757]), those whose levels declined below the median (n = 3757) had lower mortality from chronic diseases (aHR, 0.46 [95% CI, 0.39-0.53]), including cancer (aHR, 0.51 [95% CI, 0.35-0.73]) and CVD (aHR, 0.43 [95% CI, 0.34-0.53]), similar to those consistently below the median (n = 4959) (aHR, 0.43-0.49). Findings were similar in propensity score-matched analyses. CONCLUSIONS AND RELEVANCE/UNASSIGNED:These findings support an association between reduced arsenic exposure and improved health outcomes in populations exposed to contaminated drinking water.

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.

Phenolic compounds may be harmful to the developing fetus, but many have not been studied in-depth for adverse childhood allergic and respiratory health effects. We hypothesized that higher levels of phenolic compounds in prenatal spot urine would be associated with greater odds of childhood atopic dermatitis, allergic rhinitis, and asthma, and that child sex may modify these associations. 3198 mother-child paired cases were enrolled from 16 cohorts in the U.S. ECHO consortium. Fifteen phenols (e.g. benzophenones, parabens, bisphenols, triclosans) were measured from mother's urine during pregnancy using a multi-class chemical panel. Childhood outcomes included parent-reported atopic dermatitis (1466 mother-child pairs) between ages 0-3 years, and allergic rhinitis (901 mother-child pairs) and asthma (1662 mother-child pairs) between ages 5-9 years. Prenatal parabens were associated with increased odds of atopic dermatitis (odds ratio (OR) 1.13, 95 % confidence intervals (CI) 1.02, 1.26). Benzophenones were associated with lower odds of asthma (OR 0.77, CI 0.66, 0.90). Compared to boys, girls demonstrated higher odds of parabens (1.21, CI 1.04, 1.42), benzophenones (1.18, CI 1.00, 1.38) and bisphenol S (1.21, CI 1.03, 1.43) being associated with atopic dermatitis, and of the benzophenones (1.46, CI 1.11, 1.93) being associated with allergic rhinitis. An association of benzophenones (0.66, CI 0.53, 0.83) with lower odds of asthma was stronger among boys. These findings suggest that prenatal paraben and other phenol exposures may adversely affect early-life allergic and respiratory outcomes, with sex-specific vulnerability. Novel, multi-modality approaches to reduce maternal phenol exposure during pregnancy are urgently needed to protect children's health.

Prior research links prenatal exposure to organophosphate (OP) pesticides to adverse health outcomes via molecular mechanisms, such as oxidative stress, neurotransmitter disruption, and mitochondrial dysfunction. This study investigates such mechanisms by assessing the relationships between prenatal OP pesticide exposure and targeted urinary maternal metabolomic profiles using data from the New York University Children's Health and Environment Study (NYU CHES) cohort (n = 890). Urine samples were collected at three time points during pregnancy (T

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.

Environmental exposure-associated diseases, particularly in the context of rising air pollution and inhalant use, are an active area of research. Our group is dedicated to the study of exposure-related inflammation and its downstream adverse health effects. While many studies have focused on the impact of environmental exposures on respiratory sequelae, there is growing evidence of the involvement of other systems including gastrointestinal. This systematic review provides updates on the associations between inhalation exposures and the risk of upper gastrointestinal disease. Primary search identified N = 764 PubMed and N = 1,036 Web of Science studies, of which N = 111 met eligibility criteria. Our systematic review and meta-analysis showed significant associations between inhalational exposures (cigarette smoking, waterpipe smoking, and particulate matter) and upper gastrointestinal diseases. The pooled estimate of esophagitis was 1.32 (95% confidence interval [CI], 1.06-1.65; I²:86%), gastroesophageal reflux disease was 1.71 (1.14-2.55; I²:94%), peptic ulcer disease was 1.21 (1.03-1.43; I²:93%), esophageal cancer was 1.83 (1.54-2.18; I²:73%), and gastric cancer was 1.71 (1.39-2.10; I²:73%). However, the pooled estimate for Barrett's esophagus was 0.93 (0.65-1.34; I²:76%), indicating no significant association. Sensitivity analyses confirmed these findings. Risk of bias assessment showed most studies were of good quality. Our findings emphasize the impact of inhalational exposures on gastrointestinal disease risk, highlighting the need for further research to better understand this interaction and targeted public health interventions.

INTRODUCTION/BACKGROUND:Secondhand exposure to e-cigarettes represents a potential population health risk given e-cigarette's prevalence and their unknown health effects, particularly among vulnerable populations such as pregnant people. OBJECTIVES/OBJECTIVE:To explore metabolomic differences between pregnant people exposed vs. not exposed to secondhand e-cigarette aeresols, to identify possible biomarkers of exposure and metabolic pathways perturbed by e-cigarettes. METHODS:Exposed participants (n = 19) from the NYU Children's Health and Environment Study were matched to unexposed participants (n = 57) at a 1:3 ratio on age, hospital of recruitment, and race/ethnicity. Early-pregnancy urine samples were analyzed via an untargeted metabolomics platform using reverse-phase liquid chromatography mass-spectrometry. Feature-exposure associations were estimated using conditional logistic regression to adjust for matching factors. A sensitivity analysis was conducted adjusting for secondhand tobacco exposure. RESULTS:Among features enriched in the exposed group were flavonoids and flavor-related compounds including homoeriodictyol and naringenin-7-O-beta-D-glucuronide, 3-acetomidocoumarin, and guaiacol pentosylglucoside; synthetic drugs such as the endocannabinoid AM1172 and the stimulant alpha-PVP; and metabolites associated with lipid metabolism, including 2,4-undecadiene-8,10-diynoic acid isobutylamide, palmitamide, glycerol trihexanoate, and tetradecyl phosphonate. Among features negatively associated with exposure were xanthines. CONCLUSION/CONCLUSIONS:This study is the first untargeted metabolomics study investigating metabolomic markers of e-cigarette exposure, including secondhand exposure, in a pregnant cohort. Despite this study's small size and exploratory nature, the results of this work suggest that flavoring components could be biomarkers for e-cigarette exposure, and that co-exposure to e-cigarettes and other drugs may be prevalent.

Environmental exposures often exhibit temporal variability, prompting extensive research to understand their dynamic impacts on human health. There has been a growing interest in studying time-dependent exposure mixtures beyond a single exposure. However, current analytic methods typically assess each exposure individually or assume an additive relationship. This paper aims to fill the gap in method development for evaluating the joint effects of multiple time-dependent exposures on a scalar outcome. We introduce a dynamic single-index scalar-on-function model to characterize the exposure mixture's time-varying effect through a non-parametric bivariate exposure-time-outcome surface function. Utilizing B-spline tensor product bases to approximate the surface function, we propose a profiling algorithm for model estimation and establish large-sample properties for the resulting single-index estimators. In addition, we introduce a non-parametric hypothesis testing procedure to determine whether the surface function varies over time at each fixed mixture level and a model averaging solution to circumvent the issue of knot selection for spline approximations. The performance of our proposed methods is examined through extensive simulations and further illustrated using real-world applications.