Antibiotics and Pregnancy: Risks of TMP-SMX in Infant Birth Defects

Antibiotics are a cornerstone of modern medicine, critical for treating bacterial infections. However, their use during pregnancy requires careful consideration due to potential risks to the developing fetus. A recent study published in JAMA Network Open highlights the risks associated with using trimethoprim-sulfamethoxazole (TMP-SMX) during pregnancy, particularly its link to a higher incidence of infant birth defects compared to other commonly used antibiotics. This study underscores the importance of selecting appropriate treatments for urinary tract infections (UTIs) in pregnant patients.

Understanding UTIs in Pregnancy

Urinary tract infections are among the most common infections during pregnancy, affecting up to 10% of pregnant individuals. These infections are associated with adverse outcomes like preterm birth, low birth weight, and maternal complications such as pyelonephritis and sepsis. Antibiotics, including TMP-SMX, are often prescribed to manage UTIs, especially during the first trimester. However, concerns about congenital malformations linked to certain antibiotics necessitate a closer examination of their safety profiles.

The Study and Its Objectives

Researchers aimed to evaluate the risk of congenital malformations associated with antibiotics prescribed for UTIs during pregnancy. They compared TMP-SMX, nitrofurantoin, fluoroquinolones, and β-lactam antibiotics, focusing on malformations affecting various organ systems. The study analyzed data from 71,604 pregnancies, with infants monitored for malformations up to one year after birth.

Key Findings

The study revealed significant differences in malformation rates among infants exposed to different antibiotics during the first trimester:

Antibiotic	Malformation Rate (per 1000 infants)
β-lactams (reference group)	19.8
Nitrofurantoin	21.2
Fluoroquinolones	23.5
TMP-SMX	26.9

Infants exposed to TMP-SMX exhibited a 35% higher risk of any malformation compared to those exposed to β-lactams. Specific malformations, such as cardiac defects and cleft lip or palate, were notably more prevalent among TMP-SMX-exposed pregnancies.

Clinical Implications

These findings align with current American College of Obstetricians and Gynecologists (ACOG) guidelines, which recommend caution when prescribing TMP-SMX during the first trimester. The study supports nitrofurantoin’s safety profile, suggesting its suitability as an alternative treatment for UTIs during pregnancy.

A Case Scenario

Consider Emily, a 29-year-old pregnant patient presenting with symptoms of a UTI during her first trimester. After consulting her healthcare provider, she is prescribed nitrofurantoin instead of TMP-SMX, minimizing potential risks to her developing baby. Emily’s case illustrates the importance of informed antibiotic selection.

Conclusion

The choice of antibiotics during pregnancy has significant implications for maternal and fetal health. This study emphasizes the need for careful consideration of TMP-SMX use due to its association with increased birth defect risks. Healthcare providers should weigh the benefits and risks of antibiotic treatments, prioritizing safer options like nitrofurantoin to manage UTIs effectively while safeguarding fetal development. Ongoing research and adherence to updated guidelines are essential to optimizing care for pregnant patients.

References

1. Osmundson SS, Nickel KB, Shortreed SM, et al. First-trimester antibiotic use for urinary tract infection and risk of congenital malformations. JAMA Netw Open. 2025;8(7):e2519544. doi:10.1001/jamanetworkopen.2025.19544IF: 9.7 Q1
2. Kazemier BM, Koningstein FN, Schneeberger C, et al. Maternal and neonatal consequences of treated and untreated asymptomatic bacteriuria in pregnancy: a prospective cohort study with an embedded randomised controlled trial. Lancet Infect Dis. 2015;15(11):1324-1333. doi:10.1016/S1473-3099(15)00070-5