Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin

Richard G Brown,Ann Smith,Elaine Holmes,Vasso Terzidou,Benjamin Lehne,Jeremy K Nicholson,Julian R Marchesi,Yun S Lee,David A Macintyre,Phillip R Bennett,Lindsay M Kindinger

doi:10.1186/s12916-017-0999-x

Abstract

BackgroundPreterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown.MethodsWe prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures.ResultsIn contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis.ConclusionsOur data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.

Highlights

Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis
We examined vaginal microbiota compositions prior to and following PPROM, both before and following erythromycin prophylaxis, and correlated these findings with evidence of funisitis and neonatal sepsis
Our results indicate that around one third of patients have vaginal dysbiosis prior to membrane rupture, providing further evidence for ascending vaginal infection in the pathophysiology of PPROM and preterm birth

Summary

Introduction

Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. Rupture of the fetal membranes prior to 37 weeks of gestation and before the onset of labour, Brown et al BMC Medicine (2018) 16:9 exposed to ascending infection and increased risk of chorioamnionitis and funisitis, which are associated with poor maternal and neonatal outcomes [13,14,15,16,17,18,19]. Recent studies have found that the dominance of vaginal bacterial communities by L. iners is a risk factor for preterm birth [25, 26]. Despite a well-described infectious aetiology and high prevalence of chorioamnionitis in PPROM patients, the few studies to have examined vaginal bacterial composition in women with PPROM are limited to small sample sizes collected only after membrane rupture [35,36,37]

Results

Discussion

Conclusion