Daily antibiotic use during pregnancy may reduce risk of preterm birth

Daily antibiotic use during pregnancy may reduce risk of preterm birth | Image Credit: © ondrooo - stock.adobe.com.

A randomized controlled trial conducted in Zimbabwe has found that a daily dose of trimethoprim–sulfamethoxazole during pregnancy may reduce the risk of preterm birth, particularly among women living with HIV.¹

The COMBI trial, which enrolled 993 pregnant women, tested whether this inexpensive, broad-spectrum antibiotic could improve birth outcomes by reducing infection-driven inflammation.¹

Globally, 1 in 4 live-born infants is born preterm, small for gestational age, or has low birth weight. Prematurity remains the leading cause of death among children younger than 5 years. Maternal infections and inflammation are known contributors to these outcomes, especially among women with HIV.²

Participants in the COMBI trial were randomly assigned to receive either 960 mg of trimethoprim–sulfamethoxazole or a placebo daily from at least 14 weeks’ gestation until delivery. Most of the women were from rural areas and received routine antenatal care. Primary outcome data were collected for 950 participants (95.7%), with over 90% initiating treatment at a median gestational age of 21.7 weeks.¹

According to trial findings published in The New England Journal of Medicine, the antibiotic did not significantly increase mean birth weight compared with placebo (3040 g vs 3019 g; mean difference, 20 g; 95% CI, –43 to 83; P = 0.53). However, secondary outcomes indicated a potential benefit for pregnancy duration and risk of preterm birth. The preterm birth rate (<37 weeks’ gestation) was 6.9% in the antibiotic group, compared to 11.5% in the placebo group (relative risk, 0.60; 95% CI, 0.39 to 0.91). No births before 28 weeks occurred in the antibiotic group, whereas five were recorded in the placebo group.¹

For the subgroup of 131 women living with HIV, the reduction in preterm births was even more pronounced. Only 2% of births were preterm in the antibiotic group, compared to 14% in the placebo group. These infants also had a 177-gram higher mean birth weight.¹

“Our trial, conducted within routine antenatal care and enrolling women predominantly from rural areas, showed that trimethoprim-sulfamethoxazole did not improve birthweight, which was our main outcome,” said Bernard Chasekwa, first author of the study. “However, there was an intriguing suggestion that it may have improved the length of pregnancy and reduced the proportion of preterm births. We now need to repeat this trial in different settings around the world to see whether antibiotics during pregnancy can help reduce the risk of prematurity.”²

Although secondary outcomes such as small-for-gestational-age status and neonatal hospitalization showed no significant differences between groups, the observed reduction in preterm births suggests that trimethoprim–sulfamethoxazole may have an important role in select maternal populations. Future trials are needed to confirm these findings and explore potential implications for antenatal care in high-risk regions.¹

“Our findings suggest that a low-cost, daily antibiotic, in a setting where infections like HIV are common, might reduce the risk of preterm births," noted Andrew Prendergast, senior author and professor of paediatric infection and immunology at Queen Mary University of London. "We desperately need new strategies to prevent preterm births, which are the leading cause of under-5 child mortality. If we can confirm in other trials that trimethoprim-sulfamethoxazole reduces the risk of babies being born too soon, it would be a promising new approach to help newborns survive and thrive.”²

References:

1. Chasekwa B, Munhanzi F, Madhuyu L, et al. A Trial of Trimethoprim-Sulfamethoxazole in Pregnancy to Improve Birth Outcomes. N Engl J Med. 2025;392(21):2125-2134. doi:10.1056/NEJMoa2408114

2. Queen Mary University of London. Antibiotics taken during pregnancy may reduce preterm births. Eurekalert. June 4, 2025. Accessed June 10, 2025. https://www.eurekalert.org/news-releases/1085923