The online version of this article https://doi.org/10.1186/s12916-017-0999-x) contains supplementary material, which is available to authorized users.
Preterm 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.
We 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.
In 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.
Our 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.
Additional file 1: Figure S1. Characteristics of vaginal microbiota groups (VMGs) defined using Ward clustering. Figure S2. Bacterial taxonomic groups discriminate between normal-term delivery and samples taken following membrane rupture. Figure S3. Bacterial taxonomic groups associated with early onset neonatal sepsis (EONS) following PPROM, for neonates delivered at or before 28 weeks gestation (n = 27). Table S1. Bacterial diversity, richness and relative abundance of Lactobacillus spp. for VMGs 1–8. Table S2. Linear regression analysis comparing proportion of Lactobacillus spp. dominance across all patient groups corrected for potential confounders. Table S3. Linear regression analysis comparing proportion of Lactobacillus spp. dominance in paired samples before and after 48 hours erythromycin treatment. Table S4. Maternal and neonatal factors in the presence and absence of chorioamnionitis +/- funisitis. Table S5. Linear regression analysis comparing proportion of Lactobacillus spp. dominance in cases with and without chorioamnionitis +/- funisitis. Table S6. Maternal and neonatal factors associated with EONS. (DOCX 1632 kb)12916_2017_999_MOESM1_ESM.docx
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- Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin
Richard G. Brown
Julian R. Marchesi
Yun S. Lee
Lindsay M. Kindinger
Jeremy K. Nicholson
Phillip R. Bennett
David A. MacIntyre
- BioMed Central
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