Epigenetic Mechanisms Linking Early Life Nutritional Exposures to Non-Communicable Disease Risk in Nigerian Children: A Prospective Birth Cohort Study

The developmental origins of health and disease hypothesis proposes that nutritional exposures during critical early life windows, including conception, gestation, and infancy, programme metabolic phenotypes through epigenetic mechanisms with consequences for non-communicable disease risk in later life. While the evidence base for this hypothesis is robust in high-income settings, longitudinal prospective data linking early nutritional exposures to epigenetic signatures and metabolic outcomes in Nigerian children are virtually non-existent. This thesis reports findings from a prospective birth cohort study establishing the epigenetic links between early life nutritional exposures and non-communicable disease risk indicators in Nigerian children. A cohort of 480 mother-child pairs was recruited at first antenatal care contact in Ibadan, South West Nigeria, and followed from conception through the child's fifth birthday. Detailed nutritional assessments of mothers during pregnancy and children through infancy were conducted. Genome-wide DNA methylation profiling using the Illumina EPIC array was performed on cord blood and child blood samples at 24 and 60 months. Metabolic phenotyping of children at age five including body composition, fasting glucose, insulin, lipid panels, and blood pressure was completed. Differentially methylated regions associated with maternal protein-energy malnutrition during pregnancy were identified and linked to adiposity-related methylation signatures. Exposure to traditional plant-based complementary foods was associated with protective methylation patterns in immune and metabolic regulatory gene regions. The study provides original mechanistic data linking Nigerian-specific nutritional exposures to epigenetic and metabolic programming. Keywords: epigenetics, DNA methylation, early life nutrition, non-communicable diseases, birth cohort.