Craig Hansen1,2, Susan E Andrade3, Heather Freiman1,4, Sascha Dublin5, Katie Haffenreffer6, William O Cooper7,8, T Craig Cheetham9, Sengwee Toh6, De-Kun Li10, Marsha A Raebel11, Jennifer L Kuntz12, Nancy Perrin12, A Gabriela Rosales12, Shelley Carter13, Pamala A Pawloski14, Elizabeth M Maloney15, David J Graham15, Leyla Sahin16, Pamela E Scott17, John Yap18, Robert Davis1,19,20. 1. Center for Clinical and Outcomes Research, Kaiser Permanente Georgia, Atlanta, GA, USA. 2. South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia. 3. Meyers Primary Care Institute, University of Massachusetts Medical School Worcester, Worcester, MA, USA. 4. Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. 5. Group Health Research Institute, Seattle, WA, USA. 6. Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. 7. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA. 8. Department of Health Policy, Vanderbilt University School of Medicine, Nashville, TN, USA. 9. Pharmacy Analytical Services, Kaiser Permanente Southern California, Downey, CA, USA. 10. Division of Research, Kaiser Foundation Research Institute, Kaiser Permanente, Oakland, CA, USA. 11. Kaiser Permanente Colorado Institute for Health Research, Denver, CO, USA. 12. Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA. 13. LCF Research, Albuquerque, NM, USA. 14. Health Partners Institute for Education and Research, Minneapolis, MN, USA. 15. Office of Surveillance and Epidemiology, Food and Drug Administration, Silver Spring, MD, USA. 16. Office of New Drugs, Food and Drug Administration, Silver Spring, MD, USA. 17. Office of Women's Health, Food and Drug Administration, Silver Spring, MD, USA. 18. Office of Biostatistics, Food and Drug Administration, Silver Spring, MD, USA. 19. Center in Biomedical Informatics, University of Tennessee, Memphis, TN, USA. 20. Department of Pediatrics, University of Tennessee, Memphis, TN, USA.
Abstract
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.
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.
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