A new clinical trial, published in The New England Journal of Medicine conducted in Zimbabwe, has revealed that trimethoprim–sulfamethoxazole (TMP-SMX) prophylaxis during pregnancy does not lead to a significant improvement in infant birth weight.
The study, recently published and funded by Wellcome and other collaborators, aimed to determine whether daily administration of TMP-SMX could enhance birth outcomes by reducing maternal infections, an established cause of low birth weight and other complications. TMP-SMX, also known as cotrimoxazole, is a combination antibiotic commonly used for prophylaxis against opportunistic infections, particularly in HIV-infected individuals. Its use during pregnancy, however, has been a subject of extensive research due to potential risks to the fetus. TMP-SMX has been reported to be effective in preventing infections such as Pneumocystis jirovecii pneumonia and toxoplasmosis, which can be life-threatening in immunocompromised individuals. Use of TMP-SMX during pregnancy has been associated with reduced preterm delivery and neonatal mortality rates among HIV-exposed infants.
Sulfamethoxazole inhibits dihydropteroate synthase, blocking dihydrofolate synthesis, while trimethoprim inhibits dihydrofolate reductase, preventing tetrahydrofolate formation. Together, they disrupt sequential steps in bacterial folate metabolism, essential for DNA and protein synthesis. This synergistic combination exerts a bactericidal effect, especially useful in treating infections.
In this randomized, double-blind, placebo-controlled trial, 993 pregnant women, including 131 with HIV infection, were enrolled. Participants were assigned to receive either TMP-SMX (960 mg daily) or a placebo from at least 14 weeks of gestation until delivery. The median gestational age at first dose was 21.7 weeks.
At birth, the mean birth weight was 3040 grams in the TMP-SMX group versus 3019 grams in the placebo group, a marginal difference of 20 grams that was not statistically significant (95% CI: −43 to 83 grams; P=0.53). Adverse event rates were similar across both groups, indicating no additional safety concerns associated with the prophylaxis.
Another related study from 2006 observed that after the introduction of cotrimoxazole (TMP-SMX) prophylaxis in pregnant women with low CD4 counts, there was a significant reduction in preterm births and neonatal mortality, along with a trend toward increased birth weight, although the birth weight increase was not statistically significant. This supports the idea that TMP-SMX may reduce preterm delivery without a strong effect on birth weight.
The findings suggest that while TMP-SMX is a widely used prophylactic agent, its use in pregnancy for the purpose of improving birth weight may offer limited benefit. Researchers emphasize the importance of exploring alternative strategies to address infection-related birth complications in low-resource settings.
Reference
- Chasekwa B, Munhanzi F, Madhuyu L, Mbewe G, Mabika V, Chidhanguro D, et al. A Trial of Trimethoprim–Sulfamethoxazole in Pregnancy to Improve Birth Outcomes. New England Journal of Medicine. 2025 Jun 4;392(21):2125–34.
- Kemnic TR, Coleman M. Trimethoprim Sulfamethoxazole. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Jun 5]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK513232/
- Walter J, Mwiya M, Scott N, Kasonde P, Sinkala M, Kankasa C, Kauchali S, Aldrovandi GM, Thea DM, Kuhn L. Reduction in preterm delivery and neonatal mortality after the introduction of antenatal cotrimoxazole prophylaxis among HIV-infected women with low CD4 cell counts. J Infect Dis. 2006 Dec 1;194(11):1510-8.