Vaginal microbial dysbiosis increases risk of preterm pre-labor rupture of the fetal membranes, funisitis and neonatal sepsis and is adversely effected by oral administration of erythromycin.

Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for chorioamnionitis, and early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection and adverse maternal and neonatal sequela, there is widespread use of prophylactic antibiotics following PPROM. However, the evolution of vaginal microbiota composition associated with PPROM and the impact of antibiotic treatment on bacterial composition is unknown. We prospectively assessed vaginal microbiota profiles prior to and following PPROM and 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% versus 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 species. Lactobacillus depletion and increased relative abundance of Sneathia spp. was associated with the development of funisitis and early onset neonatal sepsis. Sub-analysis showed that in women with Lactobacillus spp. dominance, erythromycin associated with a potentially detrimental shift towards dysbiotic community structures, but in women with Lactobacillus spp. depleted vaginal microbiota with a potentially beneficial reduction in both richness and diversity. Our data highlight vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that erythromycin therapy may have a deleterious effect upon vaginal microbial community composition. Therefore we propose that routine use of erythromycin in women with PPROM requires re-examination.