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Interconceptional antibiotics to prevent spontaneous preterm birth (SPTB): a randomized trial

      Objective

      We hypothesized that upper genital tract microbial infection associated with SPTB may precede conception. Our objective was to determine if antibiotic administration during the interpregnancy interval in non-pregnant women with a prior early (<34 wks') SPTB would reduce the rate of SPTB in the subsequent pregnancy.

      Study design

      Women with an SPTB <34 wks' gestational age (GA) were randomized at 3 months post partum to receive oral azithromycin 1 gram×2 (4 days apart) plus sustained-release metronidazole 750mg QD×7 days or identical placebos. This regimen was repeated every 4 months until conception of another pregnancy. Outcomes of the subsequent pregnancy were assessed.

      Results

      A total of 241 women were randomized and 134 conceived a subsequent pregnancy. Of these, 3 were lost to follow-up and 7 had elective terminations. Thus, 124 women were available for study: 59 in the active drug and 65 in the placebo group. There was no significant difference between the groups for maternal age, ethnicity, education, tobacco use, marital status, delivery GA of prior pregnancy, days between delivery and randomization, days between last treatment to subsequent conception, or interpregnancy interval duration (520±409 vs 540±373 days, P = .790). In the active drug vs placebo group, neither subsequent SPTB (<37 wks: 62% vs 55%, P = .515; <35 wks: 46% vs 32%, P = .136; <32 wks: 35% vs 25%, P = .274) nor miscarriage (<15 wks: 12% vs 14%, P = .742) were significantly different. Although not statistically significant, mean delivery GA in the subsequent pregnancy was 2.4 wks earlier in the active drug vs placebo group (32.0±7.9 vs 34.4±6.3 wks, P = .082) and mean birthweight was significantly lower in the active drug group (1989±1199 vs 2464±1067 g, P = .032).

      Conclusion

      Intermittent treatment with metronidazole and azithromycin of non-pregnant women with a recent early SPTB does not significantly reduce subsequent SPTB but rather may be associated with a lower delivery GA and lower birthweight.