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)(2002)(2003)(2004)(2005)(2006)(2007)(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.

Maternal genitourinary infections and risk of birth defects in the National Birth Defects Prevention Study

“…The treatments for GUIs vary widely, so it seems unlikely that one medication is responsible for the range of significant associations observed. Studies exploring risk of medications used to treat GUIs, including antibiotics and antiherpetic medications, have been inconsistent (Ahrens et al, 2013;Ailes et al, 2016;Andersen et al, 2013;Hansen et al, 2016;Pasternak & Hviid, 2010;Reiff-Eldridge et al, 2000). We did not explore medications in this analysis.…”

An assessment of pregnant women's knowledge and use of the Internet for medication safety information and purchase

“…The lack of evidence to inform specific recommendations for medication use by pregnant women has been identified as a critical issue for women's health care (de Jonge et al, ; Thorpe et al., ; Thomas & Yates, ; Sundseth & Semancik, ) and this is challenging for healthcare staff and pregnant women who need robust evidence to make informed treatment decisions (Hansen et al., ). Due to the risk of potential harm to the foetus in a vulnerable state of development, pregnant women are usually excluded from premarketing trials and scientific evidence depends on postmarketing observational studies (Thomas & Yates, ).…”

Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011

“…More recent epidemiologic studies have found trimethoprim to be associated with both miscarriage and birth defects, but trimethoprim-sulfonamides not to be associated with birth defects (Andersen et al, 2013a(Andersen et al, , 2013bHansen et al, 2016). Subsequent studies of nitrofurantoin use in pregnancy have not found it to be associated with birth defects, although these studies may have been underpowered to detect associations with specific birth defect types (Goldberg et al, 2013;Nordeng et al, 2013).…”