Faculty Bibliography

OBJECTIVES/OBJECTIVE:Rural residents face unique challenges that contribute to poor diet quality and health. The objective of this study was to assess diet quality using the Alternative Healthy Eating Index (aHEI) among residents of a rural New York county with poor health outcomes, and identify geographic and individual-level factors associated with lower diet quality. DESIGN/METHODS:We performed a cross-sectional study using survey data and multivariable linear regression analyses, supplemented by geographic distribution assessment of aHEI scores. SETTING/METHODS:Sullivan County, New York, a rural county with poor health outcomes. PARTICIPANTS/METHODS:Households in Sullivan County who responded to a dietary and sociodemographic health survey in 2021-2022. OUTCOME MEASURES/METHODS:The primary outcome was the aHEI score and its dietary subscores. Secondary measures included sociodemographic characteristics, receipt of income assistance, financial hardship, food and housing insecurity, primary food store type, distance to food store and frequency of canned or plastic-wrapped food consumption. RESULTS:The overall survey response rate was 42.5%. The mean aHEI score was 56.5 (SD: 11.9), normally distributed across respondents. Lower aHEI scores were associated with not completing high school (10.0 points lower vs college graduates, p<0.01), reporting a disability (3.5 points lower, p<0.01), experiencing food insecurity (3.0 points lower, p<0.01) and frequent consumption of canned foods (6.2 points lower compared with those who never consumed canned foods, p<0.01). Geographic analysis revealed clustering of predictors but no substantial geographic clustering of aHEI scores. CONCLUSIONS:Poor diet quality in rural areas is associated with education level, disability, food insecurity and canned food consumption. These findings highlight potentially modifiable risk factors and support the need for targeted interventions to improve diet quality and reduce health disparities in rural populations.

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.

IMPORTANCE/UNASSIGNED:Identifying atypical body mass index (BMI) trajectories in children and understanding associated, modifiable early-life factors may help prevent childhood obesity. OBJECTIVE/UNASSIGNED:To characterize multiphase BMI trajectories in children and identify associated modifiable early-life factors. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study included longitudinal data obtained from January 1997 to June 2024, from the Environmental influences on Child Health Outcomes (ECHO) cohort, which included children aged 1 to 9 years with 4 or more weight and height assessments. Analyses were conducted from January to June 2024. EXPOSURES/UNASSIGNED:Prenatal exposure to substances and stress (smoking, alcohol, depression, anxiety), maternal characteristics (prepregnancy BMI, gestational weight gain), child characteristics (preterm birth, birth weight, breastfeeding), and demographic covariates. MAIN OUTCOMES AND MEASURES/UNASSIGNED:BMI (calculated as weight in kilograms divided by length in meters squared for children aged 1 and 2 years and as weight in kilograms divided by height in meters squared for children older than 2 years) obtained using medical records, staff measurements, caregiver reports, or remote study measures. The analysis was conducted using a multiphase latent growth mixture model. RESULTS/UNASSIGNED:This study included 9483 children (4925 boys [51.9%]). Two distinct 2-phase BMI patterns were identified: typical and atypical. The typical group (n = 8477 [89.4%]) showed linear decreases in BMI (b2, -0.23 [95% CI, -0.24 to -0.22]), with the lowest BMI at age 6 years (95% CI, 5.94-6.11), followed by linear increases from 6 to 9 years (slope difference [b4 - b2], 0.81 [95% CI, 0.76-0.86]; mean BMI at 9 years: 17.33). The atypical group (n = 1006 [10.6%]) showed a stable BMI from ages 1 to 3.5 years (b6, 0.06 [95% CI, -0.04 to 0.15]), followed by rapid linear increases from ages 3.5 to 9 years (slope difference [b8 - b6], 1.44 [95% CI, 1.34-1.55]). At age 9 years, this group reached a mean BMI (26.2) that exceeded the 99th percentile. Prenatal smoking, high prepregnancy BMI, high gestational weight gain, and high birth weight were key risk factors for the atypical trajectory. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of children in the ECHO cohort, analyses identified children on the path to obesity as early as age 3.5 years. Modifiable factors could be targeted for early prevention and intervention programs aimed at reducing childhood obesity.

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.

Humans are widely exposed to synthetic chemicals, especially via food. The types of chemical contaminants in food (including food contact chemicals) are diverse, and many of these are known to be hazardous, with mounting evidence that some contribute to noncommunicable diseases. The increasing consumption of ultra-processed foods, which contain synthetic chemicals, also contributes to adverse health. If the chemical contamination of foods were better characterized, then this issue would likely receive more attention as an important opportunity for disease prevention. In this Review, we discuss types and sources of synthetic food contaminants, focusing on food contact chemicals and their presence in ultra-processed foods. We outline future research needs and highlight possible responses at different food system levels. A sustainable transition of the food system must address the health impacts of synthetic chemicals in food; we discuss existing solutions that do justice to the complexity of the issue while avoiding regrettable substitutions and rebound effects.

BACKGROUND:Exposure to endocrine-disrupting chemicals such as bisphenols and phthalates might lead to adverse fertility and early pregnancy outcomes. METHODS:This study was embedded in the Generation R Next Study, a population-based cohort study from preconception onwards. Urinary phthalate and bisphenol concentrations were assessed in the preconception period (938 women), defined as the period in which couples were actively trying to conceive, and early pregnancy (1,366 women and 1,202 men, mean gestational age at sampling 8·6 weeks). Time to pregnancy and miscarriage were assessed using questionnaires and ultrasounds. Subfertility was defined as the inability to conceive within 12 months or need for assisted reproductive technologies. FINDINGS/RESULTS:Higher preconception urinary bisphenol S (BPS) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (mCOCH) concentrations in women were associated with longer time to pregnancy. Higher preconception mono-[(2-carboxymethyl)hexyl] phthalate, mono-2-ethyl-5-oxohexyl phthalate (mEOHP), mono-(7-carboxy-n-heptyl)phthalate (mCHpP), and mono benzyl phthalate (mBzBP) were associated with shorter time to pregnancy, and higher mono-2-ethyl-5-hydroxyhexyl phthalate (mEHHP), mEOHP, and mBzBP with lower odds of subfertility. In men, higher early pregnancy BPS, mCHpP, mono-4-methyl-7-hydroxyoctyl phthalate, mono-4-methyl-7-oxooctyl phthalate, and mono-ethyl phthalate were associated with shorter time to pregnancy or lower odds of subfertility. Higher preconception or early pregnancy BPS, phthalic acid, and mCHpP in women were associated with lower odds of miscarriage, whereas higher mono-carboxy-isoctyl phthalate, mCOCH, and mono-2-(propyl-6-carboxy-hexyl)-phthalate (cxmPHxP) with higher odds of miscarriage (all p-values <0·05). INTERPRETATION/CONCLUSIONS:Preconception and early pregnancy exposure to bisphenols and phthalates may affect couple fertility. Our results should be considered as hypothesis generating and replicated in future studies, possibly including repeated chemical measurements and mixture analysis.

BACKGROUND:New evidence has emerged that plastic polymers and their chemical additives, particularly di-2-ethylhexylphthalate (DEHP), contribute to cardiovascular disease (CVD). Phthalates are commonly used in the production of plastic materials and have been linked to increased oxidative stress, metabolic dysfunction, and cardiovascular disease. Estimates of phthalate-attributable cardiovascular mortality have been made for the US, but global estimates are needed to inform ongoing negotiations of a Global Plastics Treaty. METHODS:Cardiovascular mortality data from the Institute for Health Metrics and Evaluation (IHME) and regional DEHP exposure estimates from several sources were used to estimate burden. Hazard ratios of CV mortality were calculated using published exposure estimates, and country-level cardiovascular mortality rates were used to calculate excess deaths and years of life lost (YLL) due to DEHP exposure. FINDINGS/RESULTS:In 2018, an estimated 356,238 deaths globally were attributed to DEHP exposure, representing 13.497% of all cardiovascular deaths among individuals aged 55-64. Of these, 349,113 were attributed to the use of plastics. Geographic disparities were evident, with South Asia and the Middle East suffering the greatest percentage of cardiovascular deaths attributable to DEHP exposure (16.807%). The Middle East, South Asia, East Asia, and the Pacific accounted for the largest shares of DEHP-attributable CVD deaths (73.163%). Globally, DEHP resulted in 10.473 million YLL. INTERPRETATION/CONCLUSIONS:Plastics pose a significant risk to increased cardiovascular mortality, disproportionately impacting regions which have developing plastic production sectors. The findings underscore the need for urgent global and local regulatory interventions to kerb mortality from DEHP exposure. FUNDING/BACKGROUND:Bloomberg Philanthropies and the National Institutes of Health.

OBJECTIVE:Anogenital distance (AGD) is a postnatal marker of in utero exposure to androgens and anti-androgens, and a predictor of reproductive health. We examined the association between gestational exposure to phthalates and AGD in male and female infants. METHODS:In 506 mother-infant pairs (276 males, 230 females), we measured urinary concentrations of phthalate metabolites at < 18 and 18-25 weeks of gestation and AGD at child age 12.9 months (95 % range 11.4-21.1). Phthalate metabolite concentrations were adjusted for urinary dilution, averaged, and natural log-transformed. We measured anus-clitoris distance (AGDac) and anus-fourchette distance (AGDaf) in females, and anus-scrotum distance, anus-penis distance, and penile width in males. We used linear regression and partial-linear single-index (PLSI) models to examine associations between phthalates and AGD as single pollutants and in mixture. RESULTS:Fifty-eight percent of mothers were Hispanic, followed by 27 % non-Hispanic White. Higher exposures to ∑di-isononyl(phthalate) (∑DiNP) was associated with longer AGDaf [1.28 mm (95 % confidence interval [CI]: 0.52, 2.03) and 0.97 mm (95 %CI: 0.25, 1.69), respectively]. Higher exposures to ∑di(2-ethylhexyl)phthalate (∑DEHP) was associated with longer AGDac [2.80 mm (95 %CI: 1.17, 4.44), and 1.90 mm (95 %CI: 0.76, 3.04), respectively]. No association was observed between phthalate metabolites and AGD in males after multiple testing correction. In mixture analyses, ∑DiNP and ∑DEHP were the main contributors to longer AGD in females. We also detected an interaction between ∑DiNP and ∑DEHP in association with AGD in females. CONCLUSION/CONCLUSIONS:Early pregnancy phthalate exposure was associated with longer AGD in female infants. Biological mechanisms underlying these associations should be further investigated.

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.