Major congenital malformations not linked to first trimester tetracycline use

Major congenital malformations not linked to first trimester tetracycline use | Image Credit: © Bostan Natalia - © Bostan Natalia - stock.adobe.com.

The risks of major congenital malformations (MCMs) are not increased by first trimester tetracycline exposure, according to a recent study published in JAMA Network Open.¹

Bacterial infections are often managed using tetracycline antibiotics, with use during pregnancy most common during the first trimester. However, tetracyclines are not recommended during pregnancy because of evidence indicating inhibition of skeletal development, dental hypoplasia, and irreversible discoloration.²

The current evidence against tetracyclines is from an older generation and based on use later in pregnancy. Therefore, updated data is needed about the safety of tetracycline use during pregnancy.¹

To determine the association between first trimester tetracycline exposure and MCMs risk, investigators conducted a population-based cohort study. Singleton births from July 1, 2006, to December 31, 2018, in Sweden were selected from the Medical Birth Register.

Exclusion criteria included missing gestational age at birth, known teratogens exposure during the first trimester, mothers not residing in Sweden during the 1-year period before pregnancy and until birth, or not residing in Sweden in the first year of life. Data about drug prescription fills was obtained from the Prescribed Drug Register.

Investigators defined first trimester exposure as “having had at least 1 prescription filled by the mother between the first day of the last menstrual period and 97 days of gestation.” Gestational age was measured through ultrasonography at approximately 18 weeks’ gestation.

Unexposed infants were those born to mothers without any tetracycline prescription fills during the first trimester. The presence of any MCM within the first year of life was reported as the primary outcome, determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision Swedish diagnostic codes.

All infants were observed during a 1-year follow-up period. Secondary outcomes included all European Surveillance of Congenital Anomalies MCM organ system subgroups.

There were 1,245,889 infants included in the source cohort, with first trimester tetracycline exposure reported in 0.5%. These infants were more often born in earlier calendar years and had mothers who were in the youngest and oldest age strata, Swedish-born, with a lower education level, smoked during pregnancy, and used prescription drugs.

The analytical cohort included 69,656 infants, 6340 of whom were exposed to tetracyclines and 63,316 were unexposed. Of tetracycline-exposed infants, 39.75 per 1000 presented with any MCMs, vs 38.76 per 1000 infants in the unexposed cohort. This indicated no increased risk of any MCM between groups, with a relative risk (RR) of 1.03.

Of 12 MCM subgroups, 10 had no increased risk from tetracycline exposure. However, increased risks were reported for nervous system anomalies and eye anomalies, with RRs of 1.92 and 1.76, respectively. In the sensitivity analyses, these RRs were 2.64 and 1.35, respectively.

During the 3-year follow-up period, infants exposed to tetracyclines had a 1.6-fold increased risk of nervous system anomalies vs unexposed infants. Similarly, a 1.5-fold increased risk of eye anomalies was reported in these individuals.

When analyzing risk based on tetracycline type, the RRs for any MCM compared with unexposed infants were 1.07 for doxycycline only, 0.83 for lymecycline only, and 0.78 for tetracycline or oxytetracycline only. Increased rates of comorbidities, health care use, and drug use were reported in patients with short-term tetracycline use vs long-term use.

These results indicated no increased risks of MCMs from first trimester tetracycline exposure. Investigators recommended additional research to rule out potential risks.

References

1. Nakitanda AO, Odsbu I, Cesta CE, Pazzagli L, Pasternak B. First trimester tetracycline exposure and risk of major congenital malformations. JAMA Netw Open. 2024;7(11):e2445055. doi:10.1001/jamanetworkopen.2024.45055
2. Demers P, Fraser D, Goldbloom RB, et al. Effects of tetracyclines on skeletal growth and dentition: a report by the Nutrition Committee of the Canadian Paediatric Society.CMAJ. 1968;99(17):849-854.