Vaginal Dysbiosis Increases Risk for Preterm Fetal Membrane Rupture
Routine use of erythromycin for preterm prelabor rupture of the fetal membranes may need to be re-examined.
According to the results of a recent study published in BMC Medicine, vaginal dysbiosis characterized by reduced Lactobacillus bacteria was associated with an increased incidence of rupture of fetal membranes. Erythromycin prophylaxis for membrane ruptures was associated with Lactobacillus depletion of vaginal microbiota.
In this prospective analysis of 250 pregnant women, researchers evaluated cervicovaginal fluid samples throughout the pregnancy. Women who had preterm ruptured fetal membranes (n=15) were gestational age-matched with women who delivered at term after uncomplicated pregnancy (n=20). In a second cohort of 87 women enrolled on presentation with ruptured membranes, cervicovaginal swabs were collected on presentation but before erythromycin treatment, 48 hours after erythromycin treatment, and 1 week and 2 weeks postdiagnosis. Vaginal microbiota were characterized with MiSeq-based sequencing of 16S ribosomal RNA. The association of vaginal microbiota composition and erythromycin treatment with ruptured fetal membranes was analyzed.
Among control women, vaginal microbiota were characterized by low diversity and dominated by Lactobacillus species. In contrast, cervicovaginal samples from women who experienced preterm fetal membranes rupture had a high proportion of samples with intermediate or low Lactobacillus species dominance and high diversity (P =.011).
After membrane rupture but before erythromycin prophylaxis, bacterial load was reduced compared with control samples (P <.001) and compared with samples collected before membranes rupture (P =.001). Samples collected after membrane rupture had increased richness and diversity.
Up to 1 week after erythromycin prophylaxis, Lactobacillus species were depleted in vaginal microbiota, and intermediate communities were increased (P =.001).
Lactobacillus depletion and enrichment for Prevotella, Sneathia, Peptostreptococcus, and Catonella in samples obtained immediately before delivery was associated with an increased risk for chorioamnionitis with funisitis. Similarly, an enrichment for Catonella and Sneathia was associated with early-onset neonatal sepsis.
"Our data show that the composition of the vaginal microbiome is a risk factor for subsequent [preterm prelabor rupture of the fetal membranes] and is associated with adverse short-term maternal and neonatal outcomes," the study authors concluded. They added that "there is an urgent need to review the continued use of prophylactic erythromycin in the context of [preterm prelabor rupture of the fetal membranes] and to develop alternative treatment strategies, such as patient-specific therapy, selective antibiotics or different routes of administration."
Brown RG, Marchesi JR, Lee YS, et al. Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin. BMC Med. 2018;16:9.