The Effect of Second-Trimester Antibiotic Therapy on the Rate of Preterm Birth

Objective: As many as 50% of spontaneous preterm births are infection-related, with Mycoplasma species being the most common microbial isolates from the amniotic cavity. The goal of our study was to evaluate the effect of macrolides, a specific group of antibiotics known to be effective against Mycoplasma species, on the rate of preterm births. Methods: We performed a systematic review of the literature and a meta-analysis. We searched PubMed, Medline (1965-March 2006), Embase, and the Cochrane Library, using the key words "pregnancy," "macrolides," "erythromycin," "azithromycin," and "clarithromycin." The research was limited to randomized controlled trials and to human females. Studies included for analysis were of women in the second trimester of pregnancy who received either macrolides or placebo (or no treatment) in order to prevent preterm delivery with at least 95% of patient follow-up. We excluded studies involving women with preterm premature rupture of membranes or regular uterine contractions. Meta-analysis of the retrieved data was performed using RevMan 4.2.8 (Cochrane Collaboration) with dichotomous analyses and delivery prior to 37 weeks' gestation as the primary outcome. The analysis was subsequently repeated using the same methodology for clindamycin and metronidazole administered during the second trimester. Results: Of the 61 articles yielded by our search, three original papers, investigating a total of 1807 women, examined macrolide utilization and met our criteria. Women included in our analysis were all considered to be at higher risk for preterm delivery (vaginal fetal fibronectin positivity, urogenital Mycoplasma infection, prior preterm delivery, and/or pregestational maternal weight < 50 kg). Compared with placebo, macrolides were associated with a lower rate of preterm births (odds ratio [OR] 0.72; 95% confidence intervals [CI] 0.56-0.93), as was clindamycin (OR 0.68; 95% CI 0.49-0.95). On the other hand, metronidazole (OR 1.10; 95% CI 0.95-1.29) was not linked with significant changes in the rate of preterm births. A higher rate of preterm delivery was found when mid-trimester metronidazole was the only antibiotic administered (OR 1.31; 95% CI 1.08-1.58). Conclusion: Macrolides and clindamycin, given during the second trimester of pregnancy, are associated with a lower rate of preterm delivery, whereas second-trimester metronidazole used alone is linked with a greater risk of preterm delivery in a high-risk population. Use of metronidazole, a common treatment for bacterial vaginosis and Trichomonas vaginalis, should be avoided during the second trimester of pregnancy in this population.