Placental and cord blood DNA methylation in preterm birth: exploring the epigenetic role of maternal dietary protein

Emerging evidence suggests that maternal nutrition plays a critical role in fetal development and pregnancy outcomes. This study explores the epigenetic link between maternal nutrition and preterm birth (PTB) by analyzing DNA methylation (DNAm) in placental and cord blood samples from PTB and full-term pregnancies among Karen and Burmese populations in Myanmar and Thailand. Mothers who experienced PTB exhibited significantly lower intake of several nutrients, especially protein. DNAm profiling revealed hypomethylation of the LIPF promoter in placenta and hypermethylation of the SSB promoter in cord blood, with corresponding downregulation of SSB gene expression. Gene ontology analysis highlighted PTB-specific enrichment in inflammatory, developmental, and metabolic pathways, with cord blood notably enriched in genes involved in "embryo development ending in birth." Low protein intake correlated with SSB hypermethylation and differential methylation of IGKV1D-39. These findings provide novel insight into how protein deficiency may epigenetically predispose to PTB and suggest potential biomarkers for early detection and intervention. The clinical trial was registered on ClinicalTrials.gov registry, under NCT02797327, on 13-06-2016.