No increased risk of major congenital malformations associated with tetracycline use was found during the first trimester of pregnancy, according to a recent study.

In the Swedish population-based cohort study, published in JAMA Network Open, the investigators examined the association between first-trimester tetracycline antibiotic exposure and the risk of major congenital malformations (MCMs). Using nationwide registry data, 6,340 infants exposed to tetracyclines were matched with 63,316 unexposed controls based on propensity scores.

The prevalence of MCMs was similar between groups, with 39.75 cases per 1,000 infants in the exposed cohort (95% confidence interval [CI] = 35.14–44.93) compared with 38.76 cases per 1,000 in the unexposed cohort (95% CI = 37.27–40.30). The relative risk (RR) of any MCM associated with tetracycline exposure was 1.03 (95% CI = 0.90–1.16). Subgroup analysis by specific tetracycline agents also demonstrated no significant association for doxycycline (RR = 1.07, 95% CI = 0.93–1.23), lymecycline (RR = 0.83, 95% CI = 0.60–1.15), and tetracycline-oxytetracycline (RR = 0.78, 95% CI = 0.32–1.92).

No increased risks were observed for 10 of 12 MCM subgroups or for 16 individual malformations. Initial analyses suggested elevated risks for nervous system anomalies (RR = 1.92, 95% CI = 0.98–3.78) and eye anomalies (RR = 1.76, 95% CI = 1.07–2.91). However, these associations attenuated in sensitivity analyses with extended follow-up for up to 3 years (nervous system anomalies: RR = 1.08, 95% CI = 0.52–2.24; eye anomalies: RR = 1.42, 95% CI = 0.88–2.29).

The findings indicated that first-trimester tetracycline exposure is not associated with increased risks of MCMs. Further research may help clarify potential risks for specific malformation subgroups. 

Full disclosures can be found in the published study.