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

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

Abstract

© 2018 The Author(s). Background: 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. Methods: 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. Results: 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. Conclusions: 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.

• Journal Article Type: Article
• Acceptance Date: Dec 20, 2017
• Online Publication Date: Jan 24, 2018
• Publication Date: Jan 24, 2018
• Deposit Date: Oct 2, 2019
• Publicly Available Date: Oct 4, 2019
• Journal: BMC Medicine
• Electronic ISSN: 1741-7015
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Issue: 1
• Article Number: 9
• DOI: https://doi.org/10.1186/s12916-017-0999-x
• Public URL: https://uwe-repository.worktribe.com/output/3453020
• Additional Information: Received: 18 July 2017; Accepted: 20 December 2017; First Online: 24 January 2018; : Ethics approval for this studied was granted by the National Research Ethics Service Committee London–Stanmore of the National Health Service (REC 14/LO/0328), and all participants provided written informed consent.; : PRB serves as a consultant for ObsEva, a company that works in the field of preterm birth. All other authors declare that they have no competing interests.; : Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.