Preconception Maternal Nutrition, Offspring DNA Methylation, and InfantGrowth in Low Resource Settings

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ABSTRACT High ambient temperature and heat stress, closely linked to climate change are an imminent threat to the health of mothers and children globally. Chronic nutritional impoverishments already contribute to inadequate fetal and postnatal growth in many developing countries. The goal of this administrative supplement is to examine the double-burden of poor maternal nutrition and heat exposure by linking state-of-the-art thermal stress indicators, anthropometry, and epigenetics. Data from a multi-country randomized controlled trial (Women First, NCT01883193) revealed detrimental impact of excessive heat in the first trimester on birth length and head circumference of the infant in Pakistan, one of the four trial sites. This trial, which compared the effects of a comprehensive nutritional supplement (CNS) uncovered that impacts of heat on birth length were mitigated in women randomized to CNS suggesting potential interactions between heat and maternal nutritional status. This administrative supplement will conduct analysis of thermal stress indices among all sites of the WF trial (4 countries on 3 continents) integrating universal thermal climate index (UTCI) with existing longitudinal anthropometric data (from birth to 24 mo) and newly generated epigenetic data from the WF trial. Studies in Specific Aim 1 will examine associations between UTCI in mother-child dyads and neonatal/child outcomes from birth through 2 y of age and effect-modification by CNS supplementation. Using newly developed high-resolution spatiotemporal maps of UTCI derived from the ERA5-Land reanalysis (HiTiSEA), the studies will examine 1) associations between maternal heat stress and fetal growth in all sites (DRC, Guatemala, India and Pakistan, n= 2,442) from the WF trial; 2) associations between heat exposure and child growth in the first two years of life; and 3) examine interactions between heat and maternal CNS supplementation. In Specific Aim 2, we will examine the interaction between UTCI and nutritional status on placental (N = 463) and neonatal DNA methylation (buccal, 3 months, N = 391). Leveraging DNAme data generated in the parent R01, we will investigate associations between maternal heat exposure (UTCImax) in each trimester and targeted DNAme (metastable epialleles & epigenetic age acceleration) and an epigenome-wide association analysis. Collectively the proposed work will bridge critical gaps in our current understanding of how climate and environmental change adversely impact pregnant women and children, and the potential for nutrition to mitigate this burden.