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

Craig Anthony Hansen, Susan E. Andrade, Heather Freiman, Sascha Dublin, Katie Haffenreffer, William O. Cooper, T. Craig Cheetham, Sengwee Toh, De Kun Li, Marsha A. Raebel, Jennifer L. Kuntz, Nancy Perrin, A. Gabriela Rosales, Shelley Carter, Pamala A. Pawloski, Elizabeth M. Maloney, David J. Graham, Leyla Sahin, Pamela E. Scott, John Yap & 1 others Robert Davis

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 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.

LanguageEnglish
Pages170-178
Number of pages9
JournalPharmacoepidemiology and Drug Safety
Volume25
Issue number2
DOIs
Publication statusPublished - 1 Feb 2016

Keywords

  • Antibacterial agents
  • Birth defects
  • Medications
  • Pharmacoepidemiology
  • Pregnancy
  • Sulfonamides

ASJC Scopus subject areas

  • Epidemiology
  • Pharmacology (medical)

Cite this

Hansen, C. A., Andrade, S. E., Freiman, H., Dublin, S., Haffenreffer, K., Cooper, W. O., ... Davis, R. (2016). Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies. Pharmacoepidemiology and Drug Safety, 25(2), 170-178. https://doi.org/10.1002/pds.3919
Hansen, Craig Anthony ; Andrade, Susan E. ; Freiman, Heather ; Dublin, Sascha ; Haffenreffer, Katie ; 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 ; Davis, Robert. / Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies. In: Pharmacoepidemiology and Drug Safety. 2016 ; Vol. 25, No. 2. pp. 170-178.
@article{142493a0160f4f8f90cd86bbf15e9269,
title = "Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies",
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 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.",
keywords = "Antibacterial agents, Birth defects, Medications, Pharmacoepidemiology, Pregnancy, Sulfonamides",
author = "Hansen, {Craig Anthony} and Andrade, {Susan E.} and Heather Freiman and Sascha Dublin and Katie Haffenreffer and Cooper, {William O.} and Cheetham, {T. Craig} and Sengwee Toh and Li, {De Kun} and Raebel, {Marsha A.} and Kuntz, {Jennifer L.} and Nancy Perrin and Rosales, {A. Gabriela} and Shelley Carter and Pawloski, {Pamala A.} and Maloney, {Elizabeth M.} and Graham, {David J.} and Leyla Sahin and Scott, {Pamela E.} and John Yap and Robert Davis",
year = "2016",
month = "2",
day = "1",
doi = "10.1002/pds.3919",
language = "English",
volume = "25",
pages = "170--178",
journal = "Pharmacoepidemiology and Drug Safety",
issn = "1053-8569",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

Hansen, CA, Andrade, SE, Freiman, H, Dublin, S, Haffenreffer, K, Cooper, WO, Cheetham, TC, Toh, S, Li, DK, Raebel, MA, Kuntz, JL, Perrin, N, Rosales, AG, Carter, S, Pawloski, PA, Maloney, EM, Graham, DJ, Sahin, L, Scott, PE, Yap, J & Davis, R 2016, 'Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies', Pharmacoepidemiology and Drug Safety, vol. 25, no. 2, pp. 170-178. https://doi.org/10.1002/pds.3919

Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies. / Hansen, Craig Anthony; Andrade, Susan E.; Freiman, Heather; Dublin, Sascha; Haffenreffer, Katie; 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; Davis, Robert.

In: Pharmacoepidemiology and Drug Safety, Vol. 25, No. 2, 01.02.2016, p. 170-178.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Trimethoprim-sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies

AU - Hansen, Craig Anthony

AU - Andrade, Susan E.

AU - Freiman, Heather

AU - Dublin, Sascha

AU - Haffenreffer, Katie

AU - Cooper, William O.

AU - Cheetham, T. Craig

AU - Toh, Sengwee

AU - Li, De Kun

AU - Raebel, Marsha A.

AU - Kuntz, Jennifer L.

AU - Perrin, Nancy

AU - Rosales, A. Gabriela

AU - Carter, Shelley

AU - Pawloski, Pamala A.

AU - Maloney, Elizabeth M.

AU - Graham, David J.

AU - Sahin, Leyla

AU - Scott, Pamela E.

AU - Yap, John

AU - Davis, Robert

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 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.

AB - 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.

KW - Antibacterial agents

KW - Birth defects

KW - Medications

KW - Pharmacoepidemiology

KW - Pregnancy

KW - Sulfonamides

UR - http://www.scopus.com/inward/record.url?scp=84955605448&partnerID=8YFLogxK

U2 - 10.1002/pds.3919

DO - 10.1002/pds.3919

M3 - Article

VL - 25

SP - 170

EP - 178

JO - Pharmacoepidemiology and Drug Safety

T2 - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

SN - 1053-8569

IS - 2

ER -