Epigenetic Mechanisms Linking Early Life Nutrition to Metabolic Disease Risk in Offspring of Malnourished Nigerian Mothers: A Developmental Origins Framework

The Developmental Origins of Health and Disease hypothesis posits that nutritional exposures during critical developmental windows programme epigenetic modifications that alter gene expression and long-term metabolic disease susceptibility in offspring. This study investigates epigenetic mechanisms, specifically DNA methylation patterns at key metabolic gene loci, linking early life nutrition to metabolic disease risk in children born to malnourished mothers in Nigeria. A birth cohort was established across North West and South West Nigeria, recruiting 600 pregnant women including 300 with pre-pregnancy body mass index below 18.5 or mid-upper arm circumference below 23 centimetres and 300 well-nourished controls. Maternal dietary intake was assessed at second and third trimester using a validated quantitative food frequency questionnaire. Cord blood and neonatal buccal swab samples were collected at delivery for epigenetic profiling, and infant follow-up included blood samples at six months and two years. DNA methylation at preselected candidate gene regions including IGF2, RXRA, PPARGC1A, and LEP was quantified using bisulphite pyrosequencing. Infant metabolic phenotyping at each follow-up included anthropometry, body composition by air displacement plethysmography, and metabolic biomarkers including insulin, leptin, and adiponectin. Mediation analysis tested whether differential methylation at key loci mediates the relationship between maternal nutritional status and infant metabolic outcomes. Findings will provide the first Nigerian data integrating epigenetics, maternal nutrition, and offspring metabolism, contributing an original mechanistic understanding to the Developmental Origins of Health and Disease field in West Africa. Keywords: epigenetics, DNA methylation, developmental origins, maternal malnutrition, metabolic disease.