Do preconception antibiotics thwart preterm births?

Theorizing that women at risk for preterm delivery might benefit from antibiotics between pregnancies, researchers gave 124 women with a history of spontaneous preterm birth either placebo or oral azithromycin 1 g BID (4 days apart) plus sustained release metronidazole, 750 mg a day, for 7 days. The regimen was started at 3 months postpartum and repeated every 4 months until the women conceived again.

Unfortunately this "preemptive strike" did not significantly reduce preterm births. In the antibiotic group, delivery at less than 37 weeks occurred in 62% of the patients, compared to 55% in the placebo group (P=0.515). There was also no difference in miscarriages between the two groups. Of more concern was the fact that mean birthweight was significantly lower among women on the antibiotics (1,989 vs. 2,464 g, P=0.032).

Andrews W, Goldenberg R, Hauth J, et al. Interconceptional antibiotics to prevent spontaneous preterm birth (SPTB): a randomized trial. Am J Obstet Gynecol. 2003;189(6 suppl):S56-S57. (Abstract 5).

Commentary by Charles J. Lockwood, MD:This report adds to the growing body of research suggesting that while inflammation may account for 40% to 60% of preterm births, antibiotics alone don't prevent prematurity. The explanation for this paradox may lie in the immune system of affected patients. Mounting evidence suggests that a genetic predisposition to an exaggerated cytokine response to potentially innocuous bacteria or an exaggerated protease response to a given cytokine may underlie many inflammation-induced preterm births. Indeed, at the same meeting, Gravett and associates (Abstract 3) reported that in rhesus monkeys, antibiotics alone had only a modest effect in prolonging pregnancy and little effect on amniotic cytokine or protease expression after intra-amniotic injection of group B streptococcus. In contrast, combining antibiotics with the anti-inflammatory drugs dexamethasone and indomethacin suppressed preterm birth for far longer and reduced amniotic fluid cytokine, but not protease production. We need to increase our focus on modulating maternal cytokine and protease responses to see improvements in the prevention of inflammation-induced prematurity.