Association Between First-Trimester UTI Antibiotics and Birth Defects

A study conducted by researchers from Vanderbilt University and Washington University examined the link between first-trimester antibiotic use for urinary tract infections (UTIs) and the risk of congenital malformations. The findings suggest that treatment with trimethoprim-sulfamethoxazole (TMP-SMX) during this period may increase the likelihood of birth defects compared to β-lactam antibiotics, while no significant heightened risk was observed with nitrofurantoin or fluoroquinolones.

Untreated UTIs can lead to adverse pregnancy outcomes such as preterm delivery, low birth weight, pyelonephritis, and maternal sepsis. Screening for asymptomatic UTIs is commonly recommended during the initial prenatal visit, often resulting in antibiotic treatment within the first trimester.

Many antibiotics have the ability to cross the placenta, including TMP and SMX, which can inhibit folic acid metabolism and potentially disrupt fetal development.

The American College of Obstetricians and Gynecologists (ACOG) recommends avoiding nitrofurantoin and TMP-SMX during the first trimester when possible. Despite this guidance, these antibiotics still account for more than half of UTI prescriptions in early pregnancy.

Published in JAMA Network Open, the study "First-Trimester Antibiotic Use for Urinary Tract Infection and Risk of Congenital Malformations" compared the risk of malformations following exposure to various antibiotics: nitrofurantoin, TMP-SMX, fluoroquinolones, and β-lactams.

The study utilized data from 71,604 pregnancies among women aged 15 to 49 who had received first-trimester antibiotic therapy for UTI, and who resulted in live births. This information was gathered from the Merative MarketScan Commercial Database. The analysis identified specific prescription fills through outpatient pharmacy dispensing records and used validated diagnosis-code algorithms to detect congenital malformations in infants up to a year post-birth.

Propensity score weighting accounted for various factors, including demographic characteristics, comorbidities, concomitant medications, healthcare utilization, and calendar year. Log-binomial regression was used to estimate weighted risk ratios (RRs) and risk differences per 1,000 infants.

Out of the studied pregnancies, 59.2% were exposed to nitrofurantoin, 4.9% to TMP-SMX, 5.1% to fluoroquinolones, and 30.8% to β-lactams.

Unadjusted absolute risk of any congenital malformation per 1,000 infants was 19.8 for β-lactams, 21.2 for nitrofurantoin, 23.5 for fluoroquinolones, and 26.9 for TMP-SMX.

After adjusting for confounding variables, TMP-SMX was associated with a higher risk of any malformation compared to β-lactams (risk ratio, 1.35; 95% CI, 1.04–1.75). Both nitrofurantoin and fluoroquinolones showed similar adjusted risk compared to β-lactams.

Exposure to TMP-SMX was linked with an increased risk of severe cardiac malformations (risk ratio, 2.09; 95% CI, 1.09–3.99), other cardiac issues (risk ratio, 1.52; 95% CI, 1.02-2.25), and cleft lip/palate (risk ratio, 3.23; 95% CI, 1.44–7.22).

Analyses of other malformation types did not reveal consistent differences across antibiotic groups, and some estimates were imprecise. Sensitivity analyses confirmed the main findings.

The authors concluded that their results "...support the current ACOG recommendation for caution in using TMP-SMX during the first trimester but do not support current recommendations to limit nitrofurantoin use."

This article was authored by Justin Jackson, edited by Sadie Harley, and fact-checked and reviewed by Andrew Zinin. We appreciate your support to keep independent science journalism alive through donations, including monthly contributions.