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Antibiotic use linked to increased miscarriage risk

The use of certain antibiotics, including macrolides, metronidazole, sulfonamides, tetracyclines and quinolones, during early pregnancy was associated with an increased risk of spontaneous abortion, according research recently published in Canadian Medical Association Journal.

The only exception researchers found among the macrolides was erythromycin.

“Although antibiotics are widely used during pregnancy, the fetal safety of macrolides, quinolones, tetracyclines, metronidazole and nitrofurantoin remains a concern,” Flory T. Muanda, MD, Faculty of Pharmacy, Université de Montréal, and colleagues wrote. “Existing literature on the association between gestational antibiotic use and the risk of spontaneous abortion provides conflicting results ... Studies of the risk of spontaneous abortion associated with tetracyclines and nitrofurantoin are lacking.”

Researchers used the Quebec Pregnancy Cohort to perform a nested case-control study involving 8,702 pregnancies that ended in spontaneous abortion. The mean gestational age of the participants was 14.1 weeks. Antibiotics use was defined by filled prescriptions between the first day of gestation and the index date and was compared with both exposure and nonexposure to cephalosporins or penicillins. The antibiotic type was studied separately using the same comparator groups.

The researchers found that quinolones (adjusted OR = 2.72; 95% CI, 2.27–3.27), clarithromycin (aOR = 2.35; 95% CI, 1.9–2.91), azithromycin (aOR = 1.65; 95% CI, 1.34–2.02), tetracyclines (aOR = 2.59; 95% CI, 1.97–3.41), metronidazole (aOR = 1.7; 95% CI, 1.27–2.26), and sulfonamides (aOR = 2.01; 95% CI, 1.36–2.97) were associated with an increased risk for spontaneous abortion after adjustment for potential confounders. Researchers also found similar results when penicillins or cephalosporins were used as the comparator group.

“The presence of unmeasured confounders could be a possible explanation for these results. Some potential confounders are not available in the Quebec Pregnancy Cohort, including smoking status, folic acid use, alcohol intake, [BMI] and other dietary factors,” Muanda and colleagues wrote. “However, we used [two] active comparator groups to attenuate potential differences related to these variables between treatment groups. Therefore, unmeasured confounding, if present, would not fully explain this finding.”

Researchers concluded by expressing hope their findings would be used by policy makers to update treatment guidelines for infections during pregnancy.

A presenter at this year’s ACP Internal Medicine Annual Meeting said that though rare, another possible adverse effect from quinolones includes peripheral neuropathy. This, coupled with other potential side effects from quinolones such as insomnia, confusion and arrhythmia, has put quinolones under greater scrutiny. – by Janel Miller

Disclosure: Muanda reports no relevant financial disclosures. Please see the study for a full list of the researchers’ relevant financial disclosures.