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

Abstract

Background: Previous studies noted associations between birth defects and some antibiotics (e.g., nitrofurantoin, sulfonamides) but not others (e.g., penicillins). It is unclear if previous findings were due to antibiotic use, infections, or chance. To control for potential confounding by indication, we examined associations between antibiotic use and birth defects, among women reporting urinary tract infections (UTIs).

Methods: The National Birth Defects Prevention Study is a multi-site, population-based case-control study. Case infants/fetuses have any of over 30 major birth defects and controls are live-born infants without major birth defects. We analyzed pregnancies from 1997 to 2011 to estimate the association between maternally reported periconceptional (month before conception through the third month of pregnancy) use of nitrofurantoin, trimethoprim-sulfamethoxazole, or cephalosporins and specific birth defects, among women with periconceptional UTIs. Women with periconceptional UTIs who reported penicillin use served as the comparator.

Results: Periconceptional UTIs were reported by 7.8% (2029/26,068) of case and 6.7% (686/10,198) of control mothers. Most (68.2% of case, 66.6% of control mothers) also reported antibiotic use. Among 608 case and 231 control mothers reporting at least one periconceptional UTI and certain antibiotic use, compared with penicillin, nitrofurantoin use was associated with oral clefts in the offspring (adjusted odds ratio, 1.97 [95% confidence interval, 1.10-3.53]), trimethoprim-sulfamethoxazole use with esophageal atresia (5.31 [1.39-20.24]) and diaphragmatic hernia (5.09 [1.20-21.69]), and cephalosporin use with anorectal atresia/stenosis (5.01 [1.34-18.76]).

Conclusion: Periconceptional exposure to some antibiotics might increase the risk for certain birth defects. However, because individual birth defects are rare, absolute risks should drive treatment decisions.Birth Defects Research (Part A) 106:940-949, 2016.© 2016 Wiley Periodicals, Inc.

Keywords: antibiotic; birth defects; cephalosporin; nitrofurantoin; penicillin; trimethoprim-sulfamethoxazole; urinary tract infection.

FIGURE 1

Selection of subjects with UTIs and antibiotic use, National Birth Defects Prevention Study, 1997 to 2011. B1, month before conception; B3, 3 months before conception; EDD, estimated date of delivery; P3, third month of pregnancy; P9, ninth month of pregnancy. ^aAfter restricting to defects with 100 total or at least 4 cases exposed to and unexposed to a specific antibiotic group (see the Materials and Methods section). ^bOnly included in descriptive analysis.

FIGURE 2

Proportion of women reporting each type of antibiotic, among women with UTIs and antibiotic use in the month before conception through the third month of pregnancy, by Era, Among Mothers of Cases (A), and Controls (B), National Birth Defects Prevention Study, 1997 to 2011.