Interconceptional antibiotics to prevent spontaneous preterm birth: A randomized clinical trial

doi:10.1016/j.ajog.2005.11.049

American Journal of Obstetrics and Gynecology

Volume 194, Issue 3, March 2006, Pages 617-623

https://doi.org/10.1016/j.ajog.2005.11.049 Get rights and content

Objective

We hypothesized that upper genital tract microbial infection associated with spontaneous preterm birth may precede conception. Our objective was to estimate if antibiotic administration during the interpregnancy interval in nonpregnant women with a previous preterm birth before 34 weeks' gestational age would reduce the rate of spontaneous preterm birth in the subsequent pregnancy.

Study design

Women with a spontaneous preterm birth <34 weeks' gestational age were randomized at 4 months' postpartum to receive oral azithromycin 1 g twice (4 days apart) plus sustained-release metronidazole 750 mg daily for 7 days, or identical-appearing placebos. This regimen was repeated every 4 months until the subsequent pregnancy.

Results

A total of 241 women were randomized; 124 conceived a subsequent pregnancy and were available for study, including 59 in the antibiotic group and 65 in the placebo group. In the antibiotic versus placebo group, neither subsequent spontaneous preterm birth (<37 weeks: 52% vs 46%, P = .568; <35 weeks: 40% vs 30%, P = .276; <32 weeks: 31% vs 23%, P = .376) nor miscarriage (<15 weeks: 12% vs 14%, P = .742) was significantly different. Although not statistically significant, mean delivery gestational age in the subsequent pregnancy was 2.4 weeks earlier in the antibiotic versus placebo group (32.0 ± 7.9 vs 34.4 ± 6.3 weeks, P = .082), and mean birth weight was lower in the antibiotic group (2046 ± 1209 vs 2464 ± 1067 g, P =.060).

Conclusion

Intermittent treatment with metronidazole plus azithromycin of nonpregnant women with a recent early spontaneous preterm birth does not significantly reduce subsequent preterm birth, and may be associated with a lower delivery gestational age and lower birth weight.

Section snippets

Material and methods

This was a double-masked randomized clinical trial conducted at the Center for Research in Women's Health, University of Alabama at Birmingham that enrolled women between January 1998 and August 2001. Follow-up was continued through March 2003. Women with singleton pregnancies who presented with spontaneous labor or preterm premature rupture of membranes that ultimately resulted in a preterm birth or pregnancy loss between 16 weeks, 0 days and 33 weeks, 6 days' gestation were prospectively

Results

A total of 241 women were randomized, and 124 women ultimately conceived a subsequent pregnancy and were available for study. Among these 124 women, there were 59 in the antibiotic-treated group and 65 in the placebo group (Figure). There were no significant differences between the groups regarding maternal age, ethnicity, marital status, tobacco use, education, history of spontaneous preterm birth, or history of spontaneous abortion (Table I). There were no significant differences between the

Comment

Considerable evidence supports the notion that ascension of bacteria from the lower to the upper tract results in a chronic and clinically silent intrauterine infection/inflammation that ultimately results in a spontaneous preterm birth in some women.3, 4, 5, 6, 7, 8 This is thought to be the mechanism leading to a majority of the spontaneous preterm births that occur early in gestation, and that give rise to most of the morbidity and mortality resulting from prematurity.1, 2, 3, 4, 5, 6 The

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Funded by a grant from the National Institute of Child Health and Human Development (HD33883). Searle Pharmaceuticals provided the metronidazole and placebos. Pfizer Pharmaceuticals provided the azithromycin and placebos.

Presented at the 24th Annual Meeting of the Society for Maternal-Fetal Medicine, 2004 and received the March of Dimes Award for Excellence for Research in Prematurity.

Reprints not available from the authors.

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Editors' ChoiceInterconceptional antibiotics to prevent spontaneous preterm birth: A randomized clinical trial

Objective

Study design

Results

Conclusion

Section snippets

Material and methods

Results

Comment

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Intrauterine infection and preterm delivery

N Engl J Med

Infection and preterm birth

Am J Perinatol

Editors' Choice
Interconceptional antibiotics to prevent spontaneous preterm birth: A randomized clinical trial