Faculty Bibliography

BACKGROUND/UNASSIGNED:Sleep difficulties are common in pregnancy, yet poor prenatal sleep may be related to negative long-term outcomes for the offspring, including risk for attention-deficit/hyperactivity disorder (ADHD). Existing studies are few and have not examined timing of exposure effects or offspring sex moderation. We thus aimed to test the hypotheses that poor sleep health in pregnancy is associated with increased risk for ADHD symptoms and offspring sleep problems at approximately 4 years of age. METHODS/UNASSIGNED:Participants were 794 mother-child dyads enrolled in the NIH Environmental Influences on Child Health Outcomes Study (ECHO). Participants self-reported on sleep duration, quality, and disturbances during pregnancy and on children's ADHD symptoms and sleep problems on the Child Behaviour Checklist. FINDINGS/UNASSIGNED: = 0.026). We did not document substantial offspring sex moderation. INTERPRETATION/UNASSIGNED:Poor prenatal sleep health, particularly quality and duration in the second trimester, may be associated with offspring risk of neurodevelopmental disorders and sleep problems in early childhood. Further research is needed to understand mechanisms, yet our study suggests that prenatal maternal sleep may be a modifiable target for interventions aimed at optimizing early neurodevelopment. FUNDING/UNASSIGNED:NIH grants U2COD023375, U24OD023382, U24OD023319, UH3OD023320, UH3OD023305, UH3OD023349, UH3OD023313, UH3OD023272, UH3OD023328, UH3OD023290, K08MH117452 and NARSAD Young Investigator Award 28545.

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.

Endocrine-disrupting chemicals (EDCs) are substances generated by human industrial activities that are detrimental to human health through their effects on the endocrine system. The global societal and economic burden posed by EDCs is substantial. Poorly defined or unenforced policies can increase human exposure to EDCs, thereby contributing to human disease, disability and economic damage. Researchers have shown that policies and interventions implemented at both individual and government levels have the potential to reduce exposure to EDCs. This Review describes a set of evidence-based policy actions to manage, minimize or even eliminate the widespread use of these chemicals and better protect human health and society. A number of specific challenges exist: defining, identifying and prioritizing EDCs; considering the non-linear or non-monotonic properties of EDCs; accounting for EDC exposure effects that are latent and do not appear until later in life; and updating testing paradigms to reflect 'real-world' mixtures of chemicals and cumulative exposure. A sound strategy also requires partnering with health-care providers to integrate strategies to prevent EDC exposure in clinical care. Critical next steps include addressing EDCs within global policy frameworks by integrating EDC exposure prevention into emerging climate policy.

Silicone wristbands were utilized as personal passive samplers in a sub-cohort of 92 women, who participated in New York University Children's Health and Environment Study, to assess exposure to semi-volatile organic compounds (SVOCs). Wristbands were analyzed for 77 SVOCs, including halogenated and non-halogenated organophosphate esters (OPEs), polychlorinated biphenyls (PCBs), pesticides, phthalates, and brominated flame retardants (BFRs) (e.g. polybrominated diphenyl ethers (PBDEs)). This study aimed to look for patterns in chemical exposure utilizing participant demographics gathered from a questionnaire, and chemical exposure data across multiple timepoints during pregnancy. Analysis focused on 27 compounds detected in at least 80% of the wristbands examined. The chemicals detected most frequently included two pesticides, eight phthalates, one phthalate alternative, seven BFRs, and nine OPEs, including isopropylated and tert-butylated triarylphosphate esters (ITPs and TBPPs). Co-exposure to different SVOCs was most prominent in compounds that were within the same chemical class or were used in similar consumer applications such as phthalates and OPEs, which are often used as plasticizers. Pre-pregnancy BMI was positively associated with multiple compounds, and there were both positive and negative associations between women's parity and SVOC exposure. Outdoor temperature was not correlated with the wristband concentrations over a five-day sampling period. Lastly, significant and moderately high Intraclass Correlation Coefficient (ICC) (0.66-0.84) values for phthalate measurementsacross pregnancy indicate chronic exposure and suggest that using wristbands during one sampling period may reliably predict exposure. However, multiple sampling periods may be necessary to accurately determine indoor exposure to other SVOCs including OPEs and BFRs.

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.

BACKGROUND:Epigenetic clocks are promising tools for assessing biological age. We assessed the accuracy of pediatric epigenetic clocks in gestational and chronological age determination. RESULTS:Our study used data from seven tissue types on three DNA methylation profiling microarrays and found that the Knight and Bohlin clocks performed similarly for blood cells, while the Lee clock was superior for placental samples. The pediatric-buccal-epigenetic clock performed the best for pediatric buccal samples, while the Horvath clock is recommended for children's blood cell samples. The NeoAge clock stands out for its unique ability to predict post-menstrual age with high correlation with the observed age in infant buccal cell samples. CONCLUSIONS:Our findings provide valuable guidance for future research and development of epigenetic clocks in pediatric samples, enabling more accurate assessments of biological age.

BACKGROUND:Fetal exposure to bisphenols and phthalates may lead to alterations in the respiratory and immune system development in children, and to adverse respiratory health. AIM/OBJECTIVE:To study the associations of fetal bisphenols and phthalates exposure with lung function and asthma at age 13 years. STUDY DESIGN AND METHODS/METHODS:This study among 1020 children was embedded in a population-based prospective cohort study. We measured maternal urine bisphenol and phthalate concentrations in the first, second and third trimester of pregnancy, and lung function by spirometry and asthma by questionnaires at age 13 years. Multivariable linear and logistic regression models were applied. RESULTS:in boys and girls, and of higher first trimester bisphenol S with a decreased risk of asthma in boys and an increased risk of asthma in girls, these results did not remain significant after correction for multiple testing. Results were not modified by maternal history of asthma or atopy. CONCLUSIONS:Maternal urine bisphenol and phthalate concentrations averaged or in specific trimesters during pregnancy were not strongly associated with childhood lung function and asthma at age 13 years. BPS, as a BPA substitute, tended to be associated with impaired lung function and altered risk of asthma, partly sex-dependent, but its strength was limited by a relatively low detection rate and should be queried in contemporary cohorts.

Studying time-dependent exposure mixtures has gained increasing attentions in environmental health research. When a scalar outcome is of interest, distributed lag (DL) models have been employed to characterize the exposures effects distributed over time on the mean of final outcome. However, there is a methodological gap on investigating time-dependent exposure mixtures with different quantiles of outcome. In this article, we introduce semiparametric partial-linear single-index (PLSI) DL quantile regression, which can describe the DL effects of time-dependent exposure mixtures on different quantiles of outcome and identify susceptible periods of exposures. We consider two time-dependent exposure settings: discrete and functional, when exposures are measured in a small number of time points and at dense time grids, respectively. Spline techniques are used to approximate the nonparametric DL function and single-index link function, and a profile estimation algorithm is proposed. Through extensive simulations, we demonstrate the performance and value of our proposed models and inference procedures. We further apply the proposed methods to study the effects of maternal exposures to ambient air pollutants of fine particulate and nitrogen dioxide on birth weight in New York University Children's Health and Environment Study (NYU CHES). This article is protected by copyright. All rights reserved.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

IMPORTANCE:Few population-based studies in the US collected individual-level data from families during the COVID-19 pandemic. OBJECTIVE:To examine differences in COVID-19 pandemic-related experiences in a large sociodemographically diverse sample of children and caregivers. DESIGN, SETTING, AND PARTICIPANTS:The Environmental influences on Child Health Outcomes (ECHO) multi-cohort consortium is an ongoing study that brings together 64 individual cohorts with participants (24 757 children and 31 700 caregivers in this study) in all 50 US states and Puerto Rico. Participants who completed the ECHO COVID-19 survey between April 2020 and March 2022 were included in this cross-sectional analysis. Data were analyzed from July 2021 to September 2022. MAIN OUTCOMES AND MEASURES:Exposures of interest were caregiver education level, child life stage (infant, preschool, middle childhood, and adolescent), and urban or rural (population <50 000) residence. Dependent variables included COVID-19 infection status and testing; disruptions to school, child care, and health care; financial hardships; and remote work. Outcomes were examined separately in logistic regression models mutually adjusted for exposures of interest and race, ethnicity, US Census division, sex, and survey administration date. RESULTS:Analyses included 14 646 children (mean [SD] age, 7.1 [4.4] years; 7120 [49%] female) and 13 644 caregivers (mean [SD] age, 37.6 [7.2] years; 13 381 [98%] female). Caregivers were racially (3% Asian; 16% Black; 12% multiple race; 63% White) and ethnically (19% Hispanic) diverse and comparable with the US population. Less than high school education (vs master's degree or more) was associated with more challenges accessing COVID-19 tests (adjusted odds ratio [aOR], 1.88; 95% CI, 1.06-1.58), lower odds of working remotely (aOR, 0.04; 95% CI, 0.03-0.07), and more food access concerns (aOR, 4.14; 95% CI, 3.20-5.36). Compared with other age groups, young children (age 1 to 5 years) were least likely to receive support from schools during school closures, and their caregivers were most likely to have challenges arranging childcare and concerns about work impacts. Rural caregivers were less likely to rank health concerns (aOR, 0.77; 95% CI, 0.69-0.86) and social distancing (aOR, 0.82; 95% CI, 0.73-0.91) as top stressors compared with urban caregivers. CONCLUSIONS:Findings in this cohort study of US families highlighted pandemic-related burdens faced by families with lower socioeconomic status and young children. Populations more vulnerable to public health crises should be prioritized in recovery efforts and future planning.