Epigenetic Mechanisms Mediating the Developmental Origins of Non-Communicable Diseases in Nigerian Children Born with Intrauterine Growth Restriction: A Longitudinal Epigenomic Study

The developmental origins of health and disease (DOHaD) hypothesis posits that adverse intrauterine environments programme offspring susceptibility to non-communicable diseases through epigenetic mechanisms. In Nigeria, where intrauterine growth restriction (IUGR) is prevalent due to maternal malnutrition, infection, and anaemia, the epigenomic consequences for affected children remain entirely uncharacterised. This longitudinal epigenomic study investigates DNA methylation patterns at birth and their prospective association with cardiometabolic risk markers at ages two and five years in a birth cohort of IUGR and appropriately grown neonates at University College Hospital Ibadan, Oyo State, South West Nigeria. A total of 280 IUGR cases and 280 gestational-age-matched controls were recruited at birth, with biological specimens including dried blood spots and cord blood collected. Genome-wide DNA methylation was profiled at birth using Illumina EPIC array technology. Cardiometabolic phenotyping at follow-up included blood pressure, fasting insulin, lipid profiles, and body composition by bioelectrical impedance. IUGR neonates demonstrated differential methylation at 1,247 CpG sites compared to controls at false discovery rate less than 0.05. Differentially methylated regions were enriched for genes in insulin signalling, adipogenesis, and inflammatory pathways. Methylation at the IGF2 imprinting control region was significantly inversely correlated with insulin resistance at age five (r negative 0.41, p less than 0.001). This study generates the first Nigerian DOHaD epigenomic dataset, contributing an original theoretical framework for early life epigenetic programming as a mechanism underlying NCD risk. Keywords: epigenetics, IUGR, DOHaD, cardiometabolic risk, South West Nigeria.