From the Journals

First trimester antibiotics may increase birth defect risk



Exposure to clindamycin and doxycycline during the first trimester may be associated with an increased risk of organ-specific malformations such as ventricular/atrial septal defect, new research suggests.

In a population-based cohort study in 139,938 liveborn singletons, there was an 81% increased risk of ventricular/septal defect (adjusted odds ratio, 1.81) associated with clindamycin exposure during the first trimester, compared with no exposure. Similarly, there was a 67% greater risk of musculoskeletal system malformations (aOR, 1.67) associated with clindamycin exposure (Br J Clin Pharmacol. 2017 Jul 19. doi: 10.1111/bcp.13364).

clindamycin Kathy Scarbeck/Frontline Medical News
Clindamycin has been classified as a nitrosatable drug (tertiary amine) given its chemical structure, according to Flory T. Muanda, MD, of the University of Montreal, and his colleagues. “Studies reported that nitrosatable drugs were associated with an increased risk of many congenital malformations, including heart and musculoskeletal system malformations,” they wrote.

Doxycycline exposure was associated with a greater than threefold increased risk of ventricular/atrial septal defect (aOR, 3.19), and greater than twofold increase in the risk of circulatory system malformation (aOR, 2.38) and cardiac malformations (aOR, 2.46).

The study also found a 46% higher risk of digestive system malformations associated with macrolide exposure (aOR, 1.46), while quinolone exposure was associated with an 89% higher risk of urinary system malformations (aOR, 1.89).

“There is currently a debate on a possible association between macrolide use and infantile pyloric stenosis,” the researchers wrote. “Though evidence suggested that late pregnancy and early infancy were the time windows of interest for this malformation, little attention has been paid to the first trimester of pregnancy.”

Phenoxymethylpenicillin exposure was associated with a 85% increased risk of nervous system malformations (aOR, 1.85), and erythromycin exposure doubled the risk of urinary system malformations (aOR, 2.12). Moxifloxacin exposure was associated with a fivefold increased risk of respiratory system malformations (aOR, 5.48), but the authors noted that there were just two exposed cases.

However, there was no increased risk for major congenital malformation seen with amoxicillin, cephalosporins, and nitrofurantoin.

Overall, 11% of pregnancies in the study recorded exposure to antibiotics during the first trimester, and 9.9% of the study population were diagnosed with a major congenital malformation in the first year of life.

“Though the absolute risks for specific birth defects was small, physicians should consider prescribing safer antibiotics for the treatment of maternal infections when possible until more data are available,” the researchers wrote.

The study was supported by the Réseau Québécois. One author reported being a consultant on litigation involving antidepressants and birth defects. No other conflicts of interest were declared.

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