Faculty Bibliography

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used to replace bisphenol A (BPA), an endocrine-disrupting chemical with putative obesogenic properties; whether and how BPS and BPF affect adiposity in humans remains to be determined. Therefore, we examined the association of BPA, BPS， and BPF with body composition among US adults. We included 1787 participants aged 20-59 years old in the National Health and Nutrition Examination Survey 2013-2016 who had information on urinary BPA, BPS, and BPF concentrations, and body composition measured using dual-energy x-ray absorptiometry. After full adjustment for potential confounders in linear regression models, BPA was significantly associated with the % body fat of the whole body, arm, and leg, with the β (95% CI) for the highest quartile vs. the lowest quartile of 1.34 (95%CI [0.11, 2.58], P = 0.03), 1.60 (95%CI [0.20, 3.00], P = 0.03), and 1.63 (95%CI [0.24, 3.02], P = 0.02), respectively. No association between BPA and lean mass was found. For BPS, significant associations were found for % body fat of the whole body (β [95% CI] = 1.42 [0.49, 2.36], P = 0.004), trunk (β[95% CI] = 1.92 [0.86, 2.97], P = 0.001), and arm (β [95% CI] = 1.60 [0.49, 2.70], P = 0.01), as well as lean mass of the whole body (β [95% CI] = 2610.6 [1324.3, 3896.8], P < 0.001), trunk (β [95% CI] = 1467.0 [745.3, 2188.7], P < 0.001), arm (β [95% CI] = 113.4 [10.3, 216.5], P = 0.03), and leg (β [95% CI] = 431.5 [219.6, 643.4], P < 0.001), comparing the third quartile vs. the lowest quartile. No significant association was observed between BPF and % body fat and lean mass. Results suggest that higher BPA levels were significantly associated with greater % body fat of the whole body and limbs, and there was suggestive evidence that BPS levels were associated with both % body fat and lean mass of the whole body and body parts in a nonmonotonic relationship.

BACKGROUND:Synthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1-2 spot samples during pregnancy and limited diversity of populations. OBJECTIVE:To study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program. RESULTS:pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: -67%, -2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: -53%, 8%). DISCUSSION/CONCLUSIONS:In a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life.

Prenatal exposures to chemical and psychosocial stressors can impact the developing brain, but few studies have examined their joint effects. We examined associations between prenatal phthalate exposures and child behavior, hypothesizing that prenatal stressful life events (PSLEs) may exacerbate risks. To do so, we harmonized data from three U.S. pregnancy cohorts comprising the ECHO-PATHWAYS consortium. Phthalate metabolites were measured in single mid-pregnancy urine samples. When children were ages 4-6 years, mothers completed the Child Behavior Checklist (CBCL), from which a Total Problems score was calculated. Mothers additionally provided recall on their exposure to 14 PSLEs during pregnancy. Primary models examined problem behaviors in relation to: (1) phthalate mixtures calculated through weighted quantile sums regression with permutation test-derived p-values; and (2) joint exposure to phthalate mixtures and PSLEs (counts) using interaction terms. We subsequently refitted models stratified by child sex. Secondarily, we fit linear and logistic regression models examining individual phthalate metabolites. In our main, fully adjusted models (n = 1536 mother-child dyads), we observed some evidence of weak main effects of phthalate mixtures on problem behaviors in the full cohort and stratified by child sex. Interaction models revealed unexpected relationships whereby greater gestational exposure to PSLEs predicted reduced associations between some phthalates (e.g., the metabolites of di-2-ethylhexyl phthalate, di-n-octyl phthalate, di-iso-nonyl phthalate) and problem behaviors, particularly in males. Few associations were observed in females. Additional research is needed to replicate results and examine potential mechanisms.

Introduction: Epidemiological studies commonly use residential addresses at birth to estimate exposures throughout pregnancy, ignoring residential mobility. Lack of consideration for residential mobility during pregnancy might lead to exposure misclassification that should be addressed in environmental epidemiology. Methods: We investigated potential exposure misclassification from estimating exposure during pregnancy by residence at delivery utilizing a prospective cohort of pregnant women in New York, United States (n = 1899; 2016-2019). We calculated exposure during pregnancy corresponding to each address for fine particles (PM2.5), temperature, and greenness (Enhanced Vegetation Index [EVI]). Results: Twenty-two percent of participants moved at least once during pregnancy; 82.3% of movers changed residences during the second or third trimesters. Participants with better health, lower parity, and higher socioeconomic status were more likely to move. Exposures based on address at delivery rather than residential history overestimated exposure for PM2.5(exposure error: range -5.7 to 4.6 µg/m³, average -0.6 µg/m³) and EVI (range -0.305 to 0.307, average -0.013), but not temperature. Overestimations were significantly larger for mothers with higher socioeconomic status. Our findings indicate that the error for prenatal exposure can occur when residential mobility is not considered and is disproportional by maternal characteristics. Conclusions: Epidemiological studies should consider residential mobility in exposure assessments based on geolocation when possible, and results based on mother's residence at birth should be interpreted with understanding of potential differential exposure misclassification.

BACKGROUND:Phthalates are endocrine-disrupting chemicals with anti-androgenic qualities and studies reported associations between prenatal phthalate exposure and infant genitalia. This study investigated whether increased prenatal phthalate exposure is associated with decreased fetal penile measures. METHODS:Data was from the New York University Children's Health and Environment Study (2016-2019). Maternal urinary concentrations of 16 phthalate metabolites were quantified at <18 weeks gestation as a proxy for fetal exposure (n = 334 male pregnancies). We retrospectively measured penile length and width using ultrasounds conducted 18-24 weeks gestation (n = 173 fetuses). Associations of maternal urinary levels of phthalates with fetal penile length and width were determined using linear regression models. RESULTS:57.2% of women were Hispanic, 31.8% Non-Hispanic White, 6.4% Asian, 2.3% Non-Hispanic Black, and 2.3% multiple races. Mean maternal age was 32 years (standard deviation [SD] = 5.7). Mean penile length was 7.13 mm (SD = 1.47) and width was 6.16 mm (SD = 0.87). An inverse relationship was observed between maternal levels of mono-ethyl phthalate and fetal penile length, and mono-(7-carboxy-n-heptyl) phthalate and penile width, though estimates were small and not significant when considering correction for multiple comparisons. CONCLUSIONS:In our cohort we found no clinically meaningful associations between early pregnancy phthalate exposure and fetal penile length or width. IMPACT/CONCLUSIONS:First-trimester phthalate metabolites were assessed in pregnant women in New York City. Penile length and width were retrospectively measured on clinically assessed ultrasounds conducted ≥18 weeks and <24 weeks of gestation. In this cohort, no clinically meaningful associations were observed between first-trimester prenatal phthalate exposure and fetal penile length. This study contributes to the limited but growing research on the impact of prenatal phthalate exposure on male fetal genital development. The results emphasize that there may not be a clear association between prenatal phthalate exposure and fetal penile length and width, and further research on this topic may be required.

Plastics are everywhere. They are in many goods that we use every day. However, they are also a source of pollution. In 2022, at the resumed fifth session of the United Nations Environment Assembly, a historic resolution was adopted with the aim of convening an Intergovernmental Negotiating Committee to develop an international legally binding instrument on plastic pollution, including in the marine environment, with the intention to focus on the entire life cycle of plastics. Plastics, in essence, are composed of chemicals. According to a recent report from the secretariat of the Basel, Rotterdam, and Stockholm conventions, around 13 000 chemicals are associated with plastics and plastic pollution. Many of these chemicals are endocrine-disrupting chemicals and, according to reports by members of the Endocrine Society and others, exposure to some of these chemicals causes enormous costs due to the development of preventable diseases. The global plastics treaty brings the opportunity for harmonized, international regulation of chemicals with endocrine disrupting properties present in plastic products.

Exposure to phthalates, used as plasticizers and solvents in consumer products, is ubiquitous. Despite growing concerns regarding their neurotoxicity, brain differences associated with gestational exposure to phthalates are understudied. We included 775 mother-child pairs from Generation R, a population-based pediatric neuroimaging study with prenatal recruitment, who had data on maternal gestational phthalate levels and T₁-weighted magnetic resonance imaging in children at age 10 years. Maternal urinary concentrations of phthalate metabolites were measured at early, mid-, and late pregnancy. Child IQ was assessed at age 14 years. We investigated the extent to which prenatal exposure to phthalates is associated with brain volumetric measures and whether brain structural measures mediate the association of prenatal phthalate exposure with IQ. We found that higher maternal concentrations of monoethyl phthalate (mEP, averaged across pregnancy) were associated with smaller total gray matter volumes in offspring at age 10 years (β per log10 increase in creatinine adjusted mEP = -10.7, 95%CI: -18.12, -3.28). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (β for mediated path =-0.31, 95%CI: -0.62, 0.01, p = 0.05, proportion mediated = 18%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development.

To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13-21 years) and adult self-report and caregiver-report on 3-12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3-12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

BACKGROUND/UNASSIGNED:The extent to which physical and social attributes of neighborhoods play a role in childhood asthma remains understudied. OBJECTIVE/UNASSIGNED:To examine associations of neighborhood-level opportunity and social vulnerability measures with childhood asthma incidence. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used data from children in 46 cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) Program between January 1, 1995, and August 31, 2022. Participant inclusion required at least 1 geocoded residential address from birth and parent or caregiver report of a physician's diagnosis of asthma. Participants were followed up to the date of asthma diagnosis, date of last visit or loss to follow-up, or age 20 years. EXPOSURES/UNASSIGNED:Census tract-level Child Opportunity Index (COI) and Social Vulnerability Index (SVI) at birth, infancy, or early childhood, grouped into very low (<20th percentile), low (20th to <40th percentile), moderate (40th to <60th percentile), high (60th to <80th percentile), or very high (≥80th percentile) COI or SVI. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The main outcome was parent or caregiver report of a physician's diagnosis of childhood asthma (yes or no). Poisson regression models estimated asthma incidence rate ratios (IRRs) associated with COI and SVI scores at each life stage. RESULTS/UNASSIGNED:The study included 10 516 children (median age at follow-up, 9.1 years [IQR, 7.0-11.6 years]; 52.2% male), of whom 20.6% lived in neighborhoods with very high COI and very low SVI. The overall asthma incidence rate was 23.3 cases per 1000 child-years (median age at asthma diagnosis, 6.6 years [IQR, 4.1-9.9 years]). High and very high (vs very low) COI at birth, infancy, or early childhood were associated with lower subsequent asthma incidence independent of sociodemographic characteristics, parental asthma history, and parity. For example, compared with very low COI, the adjusted IRR for asthma was 0.87 (95% CI, 0.75-1.00) for high COI at birth and 0.83 (95% CI, 0.71-0.98) for very high COI at birth. These associations appeared to be attributable to the health and environmental and the social and economic domains of the COI. The SVI during early life was not significantly associated with asthma incidence. For example, compared with a very high SVI, the adjusted IRR for asthma was 0.88 (95% CI, 0.75-1.02) for low SVI at birth and 0.89 (95% CI, 0.76-1.03) for very low SVI at birth. CONCLUSIONS/UNASSIGNED:In this cohort study, high and very high neighborhood opportunity during early life compared with very low neighborhood opportunity were associated with lower childhood asthma incidence. These findings suggest the need for future studies examining whether investing in health and environmental or social and economic resources in early life would promote health equity in pediatric asthma.

Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. To identify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs.