Vaginal microbiome topic modeling of laboring Ugandan women with and without fever

Mercedeh Movassagh,Rafael A Irizarry,Lijun Zhang,Kathryn Sheldon,Peter Olupot‐Olupot ,Andrew Weeks ,James R Broach,Shamim A Sinnar,Frederick A Meier,Elias Kumbakumba,Steven J Schiff,Melissa Gladstone,Brian Nsubuga Kaaya ,Kim Moran,Ronnie Mulondo,Kathy Burgoine,Joseph Ngonzi,Christine Hehnly,Joel Bazira,Edith Mbabazi-Kabachelor,Lisa M Bebell,Drucilla J Roberts,Moses Ochora,Joseph N Paulson

doi:10.1038/s41522-021-00244-1

Abstract

The composition of the maternal vaginal microbiome influences the duration of pregnancy, onset of labor, and even neonatal outcomes. Maternal microbiome research in sub-Saharan Africa has focused on non-pregnant and postpartum composition of the vaginal microbiome. Here we aimed to illustrate the relationship between the vaginal microbiome of 99 laboring Ugandan women and intrapartum fever using routine microbiology and 16S ribosomal RNA gene sequencing from two hypervariable regions (V1–V2 and V3–V4). To describe the vaginal microbes associated with vaginal microbial communities, we pursued two approaches: hierarchical clustering methods and a novel Grades of Membership (GoM) modeling approach for vaginal microbiome characterization. Leveraging GoM models, we created a basis composed of a preassigned number of microbial topics whose linear combination optimally represents each patient yielding more comprehensive associations and characterization between maternal clinical features and the microbial communities. Using a random forest model, we showed that by including microbial topic models we improved upon clinical variables to predict maternal fever. Overall, we found a higher prevalence of Granulicatella, Streptococcus, Fusobacterium, Anaerococcus, Sneathia, Clostridium, Gemella, Mobiluncus, and Veillonella genera in febrile mothers, and higher prevalence of Lactobacillus genera (in particular L. crispatus and L. jensenii), Acinobacter, Aerococcus, and Prevotella species in afebrile mothers. By including clinical variables with microbial topics in this model, we observed young maternal age, fever reported earlier in the pregnancy, longer labor duration, and microbial communities with reduced Lactobacillus diversity were associated with intrapartum fever. These results better defined relationships between the presence or absence of intrapartum fever, demographics, peripartum course, and vaginal microbial topics, and expanded our understanding of the impact of the microbiome on maternal and potentially neonatal outcome risk.

Highlights

The vaginal microbiome consists of an ecological community (CMT) of microorganisms that are important in both maternal and neonatal health[1]
In sub-Saharan Africa, group B Streptococcal infections are relatively uncommon in early-onset neonatal sepsis and there is a lack of understanding of how the peripartum vaginal microbiome contributes to maternal and neonatal disease[5,6]
Changes in the vaginal microbial CMT could lead to increased risk of early-onset neonatal sepsis due to the presence of pathogenic bacteria or dysbiotic CMTs42,44

Summary

Introduction

The vaginal microbiome consists of an ecological community (CMT) of microorganisms that are important in both maternal and neonatal health[1]. The vaginal microbiome composition is known to change, which has a role in ascending infection in puerperal sepsis[2]. Exposure to the vaginal microbiome during birth or through premature rupture of membranes is an important route to early-onset neonatal sepsis[3]. In sub-Saharan Africa (sSA), group B Streptococcal infections are relatively uncommon in early-onset neonatal sepsis and there is a lack of understanding of how the peripartum vaginal microbiome contributes to maternal and neonatal disease[5,6]. Most maternal microbiome research in sSA has focused mainly on non-pregnant or postpartum composition of the vaginal microbiome[7,8]

Objectives

Methods

Findings

Conclusion