Longitudinal Dynamics of the Vaginal Microbiome and Preterm Birth Risk in Pregnant Women Across Three Nigerian Geopolitical Zones

Vaginal microbiome dysbiosis, particularly the loss of Lactobacillus dominance and overgrowth of anaerobic organisms, is associated with preterm birth risk, yet longitudinal characterisation of vaginal microbiome dynamics in Nigerian pregnant women spanning multiple geopolitical zones has not been conducted. This dissertation investigates the longitudinal dynamics of the vaginal microbiome from the first to third trimester and its relationship with preterm birth outcomes in pregnant women across South East (Enugu), North Central (FCT Abuja), and South South (Cross River) Nigeria. A prospective cohort of 180 pregnant women (60 per zone) contributed vaginal swab samples at 12, 20, and 32 weeks of gestation. 16S rRNA V1-V3 amplicon sequencing was performed on extracted DNA, with community state type (CST) classification using k-medoids clustering. Cytokine measurements and vaginal pH were assessed at each time point. Preterm birth (<37 weeks) occurred in 18.3 percent of the cohort. CST IV (low Lactobacillus, high anaerobic diversity) at 20 weeks was the strongest independent predictor of preterm birth (OR 4.7, 95% CI 2.1-10.5). Transition from Lactobacillus crispatus-dominated CST I to CST IV between 12 and 20 weeks was associated with elevated IL-8 and IL-1beta. Geographic variation in CST distribution across zones was significant, with higher CST IV prevalence in the South South cohort. The dissertation introduces original longitudinal microbiome-immune pathway models for preterm birth prediction in sub-Saharan African populations. Keywords: vaginal microbiome, preterm birth, community state type, Lactobacillus, Nigeria