Meta-Analysis of Vaginal Microbiome Data Provides New Insights Into Preterm Birth.

Idit Kosti,Marina Sirota,Svetlana Lyalina,Atul J Butte,Katherine S Pollard

doi:10.3389/fmicb.2020.00476

Abstract

Preterm birth (PTB) is defined as the birth of an infant before 37 weeks of gestational age. It is the leading cause of perinatal morbidity and mortality worldwide. In this study, we present a comprehensive meta-analysis of vaginal microbiome in PTB. We integrated raw longitudinal 16S rRNA vaginal microbiome data from five independent studies across 3,201 samples and were able to gain new insights into the vaginal microbiome state in women who deliver preterm in comparison to those who deliver at term. We found that women who deliver prematurely show higher within-sample variance in vaginal microbiome abundance, with the most significant difference observed during the first trimester. Modeling the data longitudinally revealed a number of microbial genera as associated with PTB, including several that were previously known and two newly identified by this meta-analysis: Olsenella and Clostridium sensu stricto. New hypotheses emerging from this integrative analysis can lead to novel diagnostics to identify women who are at higher risk for PTB and potentially inform new therapeutic interventions.

Highlights

Preterm birth (PTB) is defined as a live birth before 37 weeks of gestational age
The longitudinal trend of microbiome within-sample variance differs between samples from women who deliver at term and preterm (Figure 3A), with higher operational taxonomic unit (OTU) variability across trimesters in the PTB group when compared to the term group throughout pregnancy [trimesters 1–3; p-value < 2.2e-16, Two-sample Kolmogorov–Smirnov test] with the biggest difference in the first trimester (Figure 3B)
The clinical definition of PTB may be different depending on the exact obstetrical definition that was used in the individual studies, the majority of the cohorts we investigated focused on spontaneous PTB and the signals that are robust despite the potential patient heterogeneity are more likely to be real as we have seen from prior gene expression meta-analysis studies (Dudley et al, 2009; Haynes et al, 2017; Sweeney et al, 2017)

Summary

Introduction

According to the Centers of Disease Control and prevention, one of every 10 infants born in the United States is born prematurely (Ferré, 2016). PTB and low birth weight are among the top causes for infant death in the United States (Mathews and MacDorman, 2010), and can cause complications to newborns (Ward and Beachy, 2003). Spontaneous PTB, accounting for two-thirds of all PTBs (Goldenberg et al, 2008; Romero et al, 2014a), is considered a complex phenotype which can arise due to different causes. Risk factors for spontaneous preterm birth include a previous preterm birth, race, periodontal disease, low maternal body-mass index (Goldenberg et al, 2008), maternal stress (Copper et al, 1996), together

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