Early clindamycin for bacterial vaginosis in pregnancy (PREMEVA): a multicentre, double-blind, randomised controlled trial

Abstract

BackgroundTreatment for bacterial vaginosis in pregnant women to reduce risk of spontaneous very preterm birth and late miscarriage remains controversial. We conducted a randomized control trial to determine whether bacterial vaginosis treatment could decrease spontaneous very preterm births and late miscarriages. MethodsThe PREMEVA trial was a multicenter randomized control double-blinded trial performed in 40 French centers. A total of 84,530 pregnant women were screened for bacterial vaginosis before 14 weeks of gestation. Women with bacterial vaginosis in the first trimester of pregnancy were randomly assigned to three similarly sized parallel arms: one four-day course of 600 mg oral clindamycin daily, three four-day courses of 600 mg daily a month apart or placebo. The primary outcome was a composite of late miscarriage (16-21 weeks) or spontaneous very preterm delivery (22-32 weeks) according to clindamycin treatment or placebo. Secondary outcomes included spontaneous preterm delivery before 37 weeks (22-36 weeks). FindingsBetween 04/01/2006 and 06/30/2011, 84,530 pregnant women were screened before 14 weeks of gestation, 5630 (6•7%) had bacterial vaginosis and 2869 were randomized. The primary outcome did not differ significantly between the groups (1•2% in the clindamycin group and 1.0% in the placebo group, relative risk, 1.10; 95% confidence interval [CI], 0•53 to 2•32), nor in the rate of spontaneous preterm delivery before 37 weeks (4•8% and 4•1%, respectively; relative risk, 1•17; 95% CI, 0•81 to 1•69). Side effects were more common in the clindamycin group (3•0% vs 1•3%, p=0•003) but not severe. InterpretationSystematic screening and subsequent treatment for bacterial vaginosis in low-risk pregnant women does not decrease late miscarriage, spontaneous very preterm birth, or spontaneous preterm birth.

Screening for Bacterial Vaginosis in Pregnant Adolescents and Women to Prevent Preterm Delivery

“…Among the 8 studies reporting spontaneous preterm deliveries, the pooled ARD comparing active treatment with control was −1.44% (95% CI, −3.31% to 0.43%; 7571 participants; I 2 = 61.9%), and the pooled RR was 0.78 (95% CI, 0.56 to 1.07). 45, [48][49][50][51][52]55,56 Two of the 8 studies reported statistically significant reductions in spontaneous preterm delivery for active treatment compared with control, 50,56 while the other 6 reported no significant differences between active treatment and control. One of the studies that reported a significant reduction in spontaneous preterm delivery enrolled participants (n = 409) with either bacterial vaginosis or intermediate flora 50 ; other population or intervention characteristics that might explain this inconsistency could not be identified.…”

“…Three RCTs reported the incidence of preterm delivery prior to 32 weeks' completed gestation among a general obstetric population (eFigures 4 and 5 in the Supplement). 45,51,55 The pooled ARD was −0.30% (95% CI, −0.97% to 0.38%; 5564 participants; I 2 = 15.4%), and the pooled RR was 0.87 (95% CI, 0.54 to 1.42). All 3 studies observed no significant differences between active treatment and control.…”

Re‐assessing microbiomes in the low‐biomass reproductive niche

“…Adverse outcomes associated with pregnancy and the early postpartum period in mothers and neonates have previously been diagnosed and treated based on traditional microbiological culture. However, there exists a vast body of literature highlighting failure of such techniques to identify specific aetiological agents, or for treatment to result in resolution of the condition or to prevent adverse outcomes . This suggests that the presence of the microorganisms alone is not causative, rather interactions between the host, the microbe, microbial components, and the environment represent a complex interplay with multiple potential outcomes.…”

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, February 2019) – Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth

“…The results of the PREMEVA trial were recently published [58]. More than 84 000 pregnant women were screened for bacterial vaginosis before the end of their 14th week of gestation.…”