Vaginal Microbiome Topic Modelling of Laboring Ugandan Women With and Without Fever

Author:

Movassagh Mercedeh,Bebell Lisa M.,Burgoine Kathy,Hehnly Christine,Zhang Lijun,Moran Kim,Sheldon Kathryn,Sinnar Shamim A.,Mbabazi Edith,Kumbakumba Elias,Bazira Joel,Ochoa Moses,Mulondo Ronnie,Nsubuga Brian K.,Weeks Andrew,Gladstone MelissaORCID,Olupot-Olupot Peter,Ngonzi Joseph,Roberts Drucilla J.,Meier Frederick A.,Irizarry RafaelORCID,Broach James,Schiff Steven J.,Paulson Joseph N.ORCID

Abstract

AbstractThe composition of the maternal vaginal microbiome may influence 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. We examined the vaginal microbiome composition of 99 laboring Ugandan women using routine microbiology and 16S ribosomal DNA sequencing from two hypervariable regions (V1-V2 and V3-V4), using standard hierarchical methods. We then introduce Grades of Membership (GoM) modeling for the vaginal microbiome, a method often used in the text mining machine learning literature. Leveraging GoM models, we create a basis composed of a small number of microbial ‘topic’s whose linear combination optimally represents each patient yielding more accurate associations. We identified relationships between defined communities and the presentation or absence of intrapartum fever. Using a random forest model we showed that by including novel microbial topic models we improved upon clinical variables to predict maternal fever. We also show by integrating clinical variables with a microbial topic model into this model found young maternal age, fever report earlier in the current pregnancy, and longer labors, as well as a more diverse, lessLactobacillusdominated microbiome were features of labor associated with intrapartum fever. These results better define relationships between presentation or absence of intrapartum fever, demographics, peripartum course, and vaginal microbial communities, and improve our understanding of the impact of the microbiome on maternal and neonatal infection risk.

Publisher

Cold Spring Harbor Laboratory

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