Giving macrolides or clindamycin during the second trimester of pregnancy to women at risk of preterm births can lower the risk, a new systematic review and meta-analysis by Canadian researchers indicates. But the study also found that giving metronidazole alone in the second trimester is linked with a greater risk of preterm birth in the high risk population.
The study's authors, from the University of Montreal and Laval University, Quebec, say that delivery before 37 weeks' gestation complicates between 7% and 11% of all pregnancies, is the leading cause of perinatal morbidity and mortality, and is responsible for high healthcare costs (Journal of Obstetrics and Gynaecology of Canada 2007;29:35-44).
Anne-Maude Morency and Emmanuel Bujold undertook a systematic review and meta-analysis of randomised controlled trials that evaluated the effects of antibiotics administered during the second trimester on the rate of preterm delivery. Of the 61 articles yielded by their search, three original papers, investigating a total of 1807 women, examined the use of macrolides.
Women whose data were included in the analysis were all considered to be at an increased risk of preterm delivery (for example, they tested positive for vaginal fetal fibronectin, had a urogenital mycoplasmal infection, had had a preterm delivery before, or had a pregestational weight of less than 50 kg).
Dr Morency and Dr Bujold found that, in comparison with placebo, macrolides were associated with a lower rate of preterm births (odds ratio 0.72 (95% confidence interval (0.56 to 0.93), as was clindamycin (odds ratio 0.68 (0.49 to 0.95)).
However, metronidazole was not linked with significant changes in the rate of preterm births (odds ratio 1.1 (0.95 to 1.29)). In fact, women who were given only mid-trimester metronidazole showed a higher rate of preterm delivery (odds ratio 1.31 (1.08 to 1.58)).
“There have been a lot of conflicting results about the role of antibiotics in preventing preterm birth,” said Dr Bujold, an assistant professor in the department of obstetrics and gynaecology at Laval University.
“These findings will go a long way towards dispelling some of the confusion around the use of antibiotics during pregnancy and help open up new thinking about how certain antibiotics can be used to help prevent preterm birth,” she said.
As many as 50% of spontaneous preterm births are related to infections, with Mycoplasma species being the most common microbial isolates from the amniotic cavity, said Dr Bujold.
Dr Bujold and Dr Morency say that more research is needed regarding their finding—they point out that uncertainty remains about how erythromycin and clindamycin should be administered, because of the different dosing regimens, different drug preparations, and different timing of administration in their analysis. They stressed that the target population needs to be defined and the optimal treatment determined.
In light of their findings the authors conclude that metronidazole should be avoided during the second trimester of pregnancy in women at a high risk of preterm birth.