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Author Notes:

Correspondence: Susan Andrade, Meyers Primary Care Institute, University of Massachusetts Medical School Worcester, Massachusetts, [sandrade@meyersprimary.org], Tel: (508) 791 7392, Fax: (508) 595 2200

We would like to thank De-Kun Li, George Tiller, William Cooper, and Todd Callahan for their expertise and contribution in adjudicating the medical records for congenital anomalies, and Ariel Porcalla, for his assistance with protocol development; and the project managers, data programmers and abstractors at each study site.

Disclosures: There are none for all authors.


Research Funding:

Funding for this project was contract number HHSF223201000009I. Funding for Dr Dublin was from grant number K23AG028954.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Public, Environmental & Occupational Health
  • Pharmacology & Pharmacy
  • medications
  • pregnancy
  • birth defects
  • sulfonamides
  • antibacterial agents
  • pharmacoepidemiology
  • Folic-acid antagonists
  • Urinary tract infections
  • Birth defects prevention
  • Diseases society
  • Malformations
  • Associations
  • Guidelines
  • Exposure
  • America
  • Clefts

Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies

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Journal Title:

Pharmacoepidemiology and Drug Safety


Volume 25, Number 2


, Pages 170-178

Type of Work:

Article | Post-print: After Peer Review


Background: Sulfonamide antibacterials are widely used in pregnancy, but evidence about their safety is mixed. The objective of this study was to assess the association between first-trimester sulfonamide exposure and risk of specific congenital malformations. Methods: Mother-infant pairs were selected from a cohort of 1.2 million live-born deliveries (2001-2008) at 11 US health plans comprising the Medication Exposure in Pregnancy Risk Evaluation Program. Mothers with first-trimester trimethoprim-sulfonamide (TMP-SUL) exposures were randomly matched 1:1 to (i) a primary comparison group (mothers exposed to penicillins and/or cephalosporins) and (ii) a secondary comparison group (mothers with no dispensing of an antibacterial, antiprotozoal, or antimalarial medication during the same time period). The outcomes were cardiovascular abnormalities, cleft palate/lip, clubfoot, and urinary tract abnormalities. Results: We first identified 7615 infants in the TMP-SUL exposure group, of which 7595 (99%) were exposed to a combination of TMP-SUL and the remaining 1% to sulfonamides alone. After matching (1:1) to the comparator groups and only including those with complete data on covariates, there were 20064 (n=6688 per group) in the primary analyses. Overall, cardiovascular defects (1.52%) were the most common and cleft lip/palate (0.10%) the least common that were evaluated. Compared with penicillin/cephalosporin exposure, and no antibacterial exposure, TMP-SUL exposure was not associated with statistically significant elevated risks for cardiovascular, cleft lip/palate, clubfoot, or urinary system defects. Conclusions: First-trimester TMP-SUL exposure was not associated with a higher risk of the congenital anomalies studied, compared with exposure to penicillins and/or cephalosporins, or no exposure to antibacterials.

Copyright information:

© 2016 John Wiley & Sons, Ltd.

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