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BACKGROUND: The prenatal environment influences lifetime health; epigenetic mechanisms likely predominate. In 2016, the first international consortium paper on cigarette smoking during pregnancy and offspring DNA methylation identified extensive, reproducible exposure signals. This finding raised expectations for epigenome-wide association studies (EWAS) of other exposures. OBJECTIVE: We review the current state-of-the-science for DNA methylation associations across prenatal exposures in humans and provide future recommendations. METHODS: We reviewed 134 prenatal environmental EWAS of DNA methylation in newborns, focusing on 51 epidemiological studies with meta-analysis or replication testing. Exposures spanned cigarette smoking, alcohol consumption, air pollution, dietary factors, psychosocial stress, metals, other chemicals, and other exogenous factors. Of the reproducible DNA methylation signatures, we examined implementation as exposure biomarkers. RESULTS: Only 19 (14%) of these prenatal EWAS were conducted in cohorts of 1,000 or more individuals, reflecting the still early stage of the field. To date, the largest perinatal EWAS sample size was 6,685 participants. For comparison, the most recent genome-wide association study for birth weight included more than 300,000 individuals. Replication, at some level, was successful with exposures to cigarette smoking, folate, dietary glycemic index, particulate matter with aerodynamic diameter <10 μm and <2.5 μm, nitrogen dioxide, mercury, cadmium, arsenic, electronic waste, PFAS, and DDT. Reproducible effects of a more limited set of prenatal exposures (smoking, folate) enabled robust methylation biomarker creation. DISCUSSION: Current evidence demonstrates the scientific premise for reproducible DNA methylation exposure signatures. Better powered EWAS could identify signatures across many exposures and enable comprehensive biomarker development. Whether methylation biomarkers of exposures themselves cause health effects remains unclear. We expect that larger EWAS with enhanced coverage of epigenome and exposome, along with improved single-cell technologies and evolving methods for integrative multi-omics analyses and causal inference, will expand mechanistic understanding of causal links between environmental exposures, the epigenome, and health outcomes throughout the life course. [ABSTRACT FROM AUTHOR]

Background: Childcare settings are important environments for influencing child eating and physical activity (PA). Family childcare homes (FCCH) care for many children of low-income and diverse racial/ethnic backgrounds who are at greater risk for poor diet quality, low PA, and obesity, but few interventions have targeted this setting. The aim of this study was to assess the efficacy of a multicomponent intervention conducted in FCCH on the diet quality and PA of 2–5 year old children in their care. Trial design: Cluster randomized trial. Methods: The cluster-randomized trial, Healthy Start/Comienzos Sanos (2015–2019) evaluated an 8-month nutrition and PA intervention that included four components: (1) monthly telephone calls from a support coach using brief motivational interviewing, (2) tailored reports, newsletters and videos, (3) group support meetings, and (4) active play toys. After completing baseline measurement, FCCH were randomized into intervention or comparison groups in matched pairs. Both groups received the same intervention components but on different topics (intervention: nutrition/PA vs. comparison: reading readiness/literacy). Evaluation staff were blinded to group assignment. Child primary outcome measures collected at baseline and 8-months included: 1) Healthy Eating Index (HEI-2015) scores calculated from diet observation, and 2) accelerometer measurement of PA. Process measures were collected from field data and provider surveys. Generalized Estimating Equation Models assessed changes in HEI-2015 scores and PA over time by experimental condition. Results: Ethnically diverse FCCH providers (n = 119) and 2-to-5-year-old children in their care (n = 377) were included in the final analysis. Process evaluation showed high participation in all intervention components except for group meetings. Compared to children in comparison group FCCH, children in intervention FCCH increased total HEI-2015 scores by 7.2 points (p <.001) including improvement in component scores for vegetables (0.84 points, p =.025) and added sugar (0.94 points, p =.025). For PA, compared to children in the comparison group, children in intervention FCCH decreased sedentary time by 5.7% (p =.021). Conclusions: The multicomponent Healthy Start intervention was effective in improving diet quality and sedentary behavior of children in FCCH, which demonstrates the promise of obesity prevention interventions in this setting. Future research could include enhancing the Healthy Start intervention to strengthen the PA component, considering virtual peer support, and determining how to best translate and disseminate the intervention into FCCH nationally. Trial registration: National Institutes of Health, NCT02452645. Registered 5 May 2015. [ABSTRACT FROM AUTHOR]