Original Contributions to Understanding the Biochemical Pathogenesis of Preterm Birth Through Placental Metabolomics and Proteomics in a Nigerian Cohort

Preterm birth contributes disproportionately to neonatal mortality in Nigeria, yet the biochemical pathogenic mechanisms operating at the placental level in Nigerian preterm births, which occur in a distinct infectious and nutritional context compared to Western populations, are incompletely characterised. This dissertation investigates the biochemical pathogenesis of preterm birth through integrated placental metabolomics and proteomics in a Nigerian cohort, making original contributions to understanding the molecular mechanisms of spontaneous preterm birth in high-burden sub-Saharan African settings. Placental tissue samples were collected at delivery from one hundred and twenty spontaneous preterm births (gestational age twenty-eight to thirty-six weeks) and one hundred and twenty matched term deliveries at Lagos Island General Hospital and Federal Medical Centre Owerri. Placental proteomics was performed by data-independent acquisition mass spectrometry with tandem mass tag labelling. Metabolomics employed targeted and untargeted approaches combining GC-MS and LC-MS/MS platforms. Pathway analysis, network biochemistry, and multi-omics integration was performed using MetaboAnalyst, STRING, and MOFA2 platforms. Proteomic analysis identified three hundred and fourteen differentially abundant proteins in preterm placentas, with significant enrichment of proteins in complement activation, coagulation cascade, and oxidative phosphorylation pathways. Metabolomic analysis revealed significantly elevated prostaglandins, lysophospholipids, and arachidonic acid pathway metabolites in preterm placental tissue, alongside depleted nicotinamide and carnitine levels suggesting mitochondrial metabolic stress. Multi-omics integration identified a lipid-inflammatory biochemical axis as the primary preterm birth molecular signature in this Nigerian cohort, distinct from the infection-dominant model proposed by earlier single-marker studies. An original placental biochemical pathogenesis model specific to Nigerian preterm birth is constructed. Keywords: preterm birth, placental metabolomics, proteomics, biochemical pathogenesis, Nigeria.