The safety of amoxicillin and clavulanic acid use during the first trimester of pregnancy

Aims: The goal of the current study was to assess the risk for major congenital malformations following first-trimester exposure to amoxicillin, or amoxicillin and clavulanic acid (ACA). Methods: A population-based retrospective cohort study was conducted, by linking 4 computerized databases: maternal and infant hospitalization records, drug dispensing database of Clalit Health Services in Israel and data concerning pregnancy terminations. Multivariate negative-binomial regression was used to assess the risk for major malformations following first-trimester exposure, adjusted for mother's age, ethnicity (Bedouin vs Jewish), parity, diabetes mellitus, lack of perinatal care, and the year of birth. Results: The study included 101 615 pregnancies, of which 6919 (6.8%) were exposed to amoxicillin: 1045 (1.0%) to amoxicillin only and 6041 (5.9%) to ACA. No significant association was found, in the univariate and multivariate analyses, between first-trimester exposure to amoxicillin or ACA and major malformations in general (crude relative risk, 1.05 95% confidence interval 0.95–1.16; adjusted relative risk 1.09, 95% confidence interval 0.98–1.20), or for major malformations according to organ systems. No dose–response relationship was found between exposure in terms of the defined daily dose and major malformations. Conclusion: Exposure to amoxicillin and ACA during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations.