Anne Mobley Butler, PhD, MS, Associate Professor of Medicine in the Division of Infectious Diseases at WashU Medicine, was senior author of a study published in JAMA Network Open about the incidence of serious perinatal outcomes when treated for a urinary tract infection (UTI) during pregnancy . Co-authors include Michael Durkin, MD, MPH, Associate Professor of Medicine in the Division of Infectious Diseases at WashU Medicine.
Urinary tract infections (UTIs) are among the most common infections during pregnancy. Because UTIs during pregnancy are associated with serious perinatal outcomes such as preterm birth, pyelonephritis, and maternal sepsis, screening for asymptomatic bacteriuria is recommended during the first trimester. Despite universal screening recommendations, there is limited guidance on antibiotic selection for UTI treatment in the first trimester due to the potential risk of congenital malformations associated with some antibiotics commonly used to treat UTIs. The study sought to evaluate whether nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), or fluoroquinolones were associated with congenital malformations compared to β-lactam antibiotics using a large database of commercially-insured individuals in the U.S.
In a cohort of over 70,000 pregnant individuals who filled an antibiotic to treat UTI, the risk of congenital malformations was higher for TMP-SMX compared to β-lactams, but similar for nitrofurantoin and fluoroquinolones compared to β-lactams. Outside of the first trimester of pregnancy, nitrofurantoin and TMP-SMX are considered first-line agents for UTI treatment. Results suggest that TMP-SMX may be associated with increased risk of congenital malformations; other antibiotics used to treat UTI may be preferable in the first trimester. Nitrofurantoin and TMP-SMX have higher efficacy in treating UTI than β-lactams. However, every antibiotic has risk-benefit tradeoffs that need to be balanced when considering UTI treatment. TMP-SMX resistance can be high in some geographical areas such that it shouldn’t be used in the absence of culture results. Nitrofurantoin works well for lower urinary tract infections (acute cystitis and asymptomatic bacteriuria) but is not recommended for suspected upper urinary tract infections (pyelonephritis).
Existing evidence has been mixed regarding the association between nitrofurantoin and TMP-SMX and the risk of congenital malformations. This study—the largest to date—suggests that TMP-SMX may be associated with increased risk of malformations and that no elevated risk of congenital malformations was seen for nitrofurantoin, compared to β-lactam antibiotics. The study design addressed some major limitations of prior studies by using an active comparator design and restricting the cohort to individuals treated for UTI rather than for any indication, and we explored numerous potential biases and could not identify a likely alternative explanation for our findings. However, despite using a national database, analyses included a small number of some specific malformation types and some results were imprecise, which could be improved with a future larger study. Also, the individuals in the cohort were commercially-insured, thus results may not be generalizable to Medicaid or uninsured populations.
Publication Details:
First-Trimester Antibiotic Use for Urinary Tract Infection and Risk of Congenital Malformations. Osmundson SS, Nickel KB, Shortreed SM, Dublin S, Stwalley D, Durkin MJ, Wartko PD, Sahrmann JM, Colvin R, Butler AM.JAMA Netw Open. 2025 Jul 1;8(7):e2519544. doi: 10.1001/jamanetworkopen.2025.19544.
Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD107083), Washington University Institute of Clinical and Translational Sciences grant from the National Center for Advancing Translational Sciences of the NIH (UL1TR002345).
ts of mothers treated in the first trimester of pregnancy with trimethoprim/sulfamethoxazole (TMP-SMX) antibiotics for urinary tract infection (UTI) appeared to have a higher risk for any malformation, severe cardiac malformation, and cleft lip and palate than those exposed to beta-lactam antibiotics, a large cohort study of commercially insured pregnant individuals found.
Recommended routine screening for asymptomatic bacteriuria at the initial prenatal visit often leads to antibiotics being given in the first trimester when the fetus is most susceptible to teratogenic medications and adverse effects from infections.
The study, published in JAMA Network Open found no elevated malformation risk for nitrofurantoin, however, although current American College of Obstetricians and Gynecologists (ACOG) guidance recommends that it be avoided in the first trimester unless there is no other appropriate alternative.