Article Title

Sulfonamide Use During the First Trimester of Pregnancy and Risk of Selected Congenital Anomalies Among Live Births

Publication Date



pregnancy, medication safety


Background/Aims: Sulfonamide antibacterials are widely used in pregnancy, but evidence about their safety is mixed. Our aim was to assess the association between first-trimester sulfonamide exposure and risk of specific congenital malformations.

Methods: This retrospective cohort study included 1.2 million live born deliveries between 2001 and 2008 at 11 U.S. health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program, which has linked health plan with birth certificate data. Deliveries to mothers with first-trimester sulfonamide exposure were randomly matched 1:1 to those exposed to penicillins or cephalosporins (primary comparator) or no antibacterials (secondary comparator). We examined anomalies that in prior studies were associated with sulfonamide use: cardiovascular abnormalities, cleft lip/palate, clubfoot, neural tube defects (NTDs), and urinary tract abnormalities. Outcomes were validated by medical record review. Analyses used conditional logistic regression.

Results: There were 6,688 deliveries in each exposure group included in primary analyses. Cardiovascular defects occurred in 1.6%, urinary system defects in 0.7%, clubfoot in 0.2% and cleft lip/palate in 0.1%. NTDs were too rare for further evaluation (n = 5). Sulfonamide exposure was not associated with significantly elevated risks for these anomalies. The adjusted odds ratio (OR) for cardiovascular defects was 0.94 (95% confidence interval: 0.71–1.23) for sulfonamide exposure compared to penicillin/cephalosporin exposure. The comparable odds ratios were 0.83 (0.18–3.88) for cleft lip/palate and 1.08 (0.70–1.65) for urinary defects. For clubfoot, the odds ratio was elevated but not statistically significant (1.58 [0.71–3.50]). In comparison, analyses comparing sulfonamide exposure to no antibiotic use yielded estimates that were further from the null though still statistically nonsignificant.

Conclusion: First-trimester sulfonamide exposure was not associated with a higher risk of the congenital anomalies studied compared to exposure to penicillins or cephalosporins. Our results highlight the need to use active comparator groups exposed to medications with the same indication to minimize confounding.




June 30th, 2016


August 12th, 2016