Faculty Bibliography

The exponential rise in plastic production has driven widespread contamination by micro- and nanoplastics (MNPs) in the environment. These plastic particles and their chemical additives have been detected in water sources, human bodily fluids, and reproductive tissues. With global fertility rates declining, their role as potential contributors is under investigation. This scoping review compares findings from in vitro experiments, in vivo studies across animal models, and epidemiological data to assess potential reproductive hazards associated with MNP exposure. Forty original studies published within the last decade were identified. MNPs have been detected in human breast milk, placenta, endometrium, ovaries, testis, semen, follicular fluid, blood, and urine samples. Humans are estimated to absorb 74,000-121,000 particles annually through inhalation, ingestion, skin contact, and use of plastic materials, including medical devices. Experimental evidence demonstrates that MNPs can cross biological barriers, interact with cells, and disrupt cellular pathways, including steroidogenesis, energy metabolism, inflammatory pathways, and oxidative stress. Thirty in vivo animal studies have associated MNPs with altered reproductive endpoints in both males (i.e., altered semen quality and spermatogenesis) and females (i.e., altered folliculogenesis, depleted ovarian reserve, and reduced litter sizes), with possible transgenerational effects. In conclusion, current evidence suggests MNPs may represent a reproductive health hazard to humans and animals. The relative contributions of particle toxicity and their chemical additives remain difficult to disentangle. Overall, plastics and their associated chemicals represent a serious health and environmental concern, which continues to grow in the absence of restrictions and international agreements.

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.

Children face an urgent threat in the form of hazards posed by plastics in the environment. Despite robust and rapidly accumulating evidence on the effects of plastic on children's health, plastic presents a paradox for child health providers: while plastic is a vehicle for so many interventions, robust evidence from laboratory and human studies show that chemicals used to produce plastics contribute to chronic conditions in multiple organ systems and disrupt hormone function, and exposure to plastic-derived toxins is associated with adverse birth outcomes, metabolic conditions, neurodevelopmental disease and disability, and reproductive conditions. Evidence-based, safe, simple, and low-cost steps exist for child health providers in primary care to help families limit children's exposure to plastic-derived toxins. Health-care providers also have a crucial opportunity to protect the health and wellbeing of future generations of children by supporting local and global campaigns for governments, industries, and the general public to reduce the accumulation of plastics in the environment and minimise the use of plastics within health-care systems.

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

BACKGROUND/UNASSIGNED:While there is wide evidence on concentrations of cytokines in patients attending health care facilities, evidence is scant on physiological, basal concentrations of cytokines in the general population and across sociodemographic groups, as well as on their potential stability over time. Furthermore, from a public health perspective it is remarkable that no studies have analyzed intraindividual changes in such concentrations from before the COVID-19 pandemic until its outbreak. OBJECTIVES/UNASSIGNED:To investigate: (a) prepandemic concentrations of cytokines and immunoglobulins to viral exposures in a general, non-institutionalized population, and their associated sociodemographic variables; (b) the intraindividual change in such concentrations between a prepandemic period (2016-17) and the initial pandemic period (2020-21); and (c) whether such change was similar in participants who in 2020-21 were SARS-CoV-2 seronegative and seropositive, and between participants who did and did not develop COVID-19. METHODS/UNASSIGNED:We conducted a prospective cohort study in 240 individuals from the general population of Barcelona, Spain. Thirty cytokines and 31 immunoglobulins were measured in paired serum samples collected in 2016-17 and 2020-21 in the same individuals. RESULTS/UNASSIGNED:The median value of the relative intraindividual change in cytokine concentrations between 2016 and 2020 was <15% for 29 of the 30 cytokines. A substantial number of participants had an intraindividual increase or decrease ≥15% in some cytokines. No major differences in intraindividual changes of cytokine and immunoglobulin levels between 2016 and 2020 were observed between participants who did and did not develop COVID-19. CONCLUSION/UNASSIGNED:We provide novel information on physiological, basal ex-vivo concentrations of cytokines and immunoglobulins in a general population, which should be relevant for clinical practice and public health. Intraindividual changes in cytokines and immunoglobulins during the 4 years from 2016-17 to 2020-21 were moderate, and they did not differ between participants who in 2020-21 were SARS-CoV-2 seropositive and seronegative, nor between participants who did and did not develop COVID-19 disease. These findings are also novel and relevant for medicine and public health. In particular, the stability in the biomarkers is relevant to assess the role of the immunological and inflammatory state (measured through baseline levels of cytokines and immunoglobulins) in the development of SARS-CoV-2 seropositivity and COVID-19 disease, as well as in the susceptibility to other infections and pathologies.

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.

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.

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.