Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies
Meyers Primary Care Institute
Clinical Epidemiology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Female Urogenital Diseases and Pregnancy Complications | Maternal and Child Health | Pharmacy and Pharmaceutical Sciences
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 20 064 (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.
antibacterial agents, birth defects, medications, pharmacoepidemiology, pregnancy, sulfonamides
DOI of Published Version
Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):170-8. doi: 10.1002/pds.3919. Epub 2015 Nov 24. Link to article on publisher's site
Pharmacoepidemiology and drug safety
Hansen, Craig; Andrade, Susan; Freiman, Heather; Dublin, Sascha; Haffenreffer, Katherine; Cooper, William O.; Cheetham, T. Craig; Toh, Sengwee; Li, De-Kun; Raebel, Marsha A.; Kuntz, Jennifer L.; Perrin, Nancy; Rosales, A. Gabriela; Carter, Shelley; Pawloski, Pamala A.; Maloney, Elizabeth M.; Graham, David J.; Sahin, Leyla; Scott, Pamela E.; Yap, John; and Davis, Robert, "Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies" (2016). University of Massachusetts Medical School Faculty Publications. 852.