The Promise of a Common antibiotic

A recent study conducted in Zimbabwe suggests that a common, safe, and inexpensive antibiotic could substantially
reduce the number of preterm births. The research, which involved nearly 1,000 pregnant women, found that a daily
dose of trimethoprim-sulfamethoxazole may lead to improved birth outcomes, particularly for women living with HIV.
Among this group, the antibiotic was associated with larger babies and a decreased likelihood of premature birth.

The findings were published in the New England Journal of Medicine.

Global Impact of Preterm Births

Preterm birth, defined as birth before 37 weeks of gestation, remains a notable global health challenge.
Worldwide, one in four live-born infants is either preterm, small for gestational age, or has a low birth weight.
This vulnerability leads to high mortality rates,with prematurity now recognized as the leading cause of death among
children under the age of five.

Maternal infections and inflammation during pregnancy are known risk factors for adverse birth outcomes,especially
for mothers living with HIV. These infants face a heightened risk of being born too small or too soon.

The COMBI Trial: Investigating Trimethoprim-Sulfamethoxazole

To explore potential interventions,an international team of researchers conducted the Cotrimoxazole for Mothers to
Improve Birthweight in Infants (COMBI) trial. This randomized controlled trial aimed to determine whether prescribing
pregnant women a daily dose of trimethoprim-sulfamethoxazole,a broad-spectrum antimicrobial agent with
anti-inflammatory properties commonly used in sub-Saharan Africa,woudl result in:

• Heavier birth weights
• Decreased premature births
• Improved health outcomes for their babies

The research team was led by Professor Andrew Prendergast from Queen Mary University of london,and Bernard
Chasekwa from the Zvitambo Institute for Maternal and Child Health Research in Zimbabwe.

Study Design and results

The study enrolled 993 pregnant women from three antenatal clinics in Shurugwi, a district in central Zimbabwe.
Participants were randomly assigned to receive either 960 mg of trimethoprim-sulfamethoxazole or a placebo daily.
All women received regular antenatal care, and data on birth outcomes were meticulously recorded.

While the study did not find a significant difference in birth weight between the two groups, it revealed a notable
40% reduction in the proportion of preterm births in the trimethoprim-sulfamethoxazole group compared to the placebo
group.

Specifically, 6.9% of mothers receiving the antibiotic had babies born preterm, compared to 11.5% of mothers
receiving the placebo. Notably, no women in the antibiotic group had babies born before 28 weeks of gestation.

Significant Impact on HIV-Positive mothers

The reduction in premature births was particularly pronounced among the 131 women living with HIV. In this subgroup,
only 2% of births in the trimethoprim-sulfamethoxazole group were preterm, compared to 14% in the placebo group.
Moreover, babies exposed to antibiotics during pregnancy showed a 177-gram increase in their birth weight.

Expert Perspectives

Bernard Chasekwa, the study’s first author, noted:

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. However, there was an
intriguing suggestion that it may have improved the length of pregnancy and reduced the proportion of preterm
births.

Bernard Chasekwa, Zvitambo Institute for Maternal and Child Health Research

Chasekwa emphasized the need for further research:

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.

Bernard Chasekwa, Zvitambo Institute for Maternal and Child Health Research

Professor Prendergast added:

Our findings suggest that a low-cost, daily antibiotic, in a setting were infections like HIV are common, might
reduce the risk of preterm births. We desperately need new strategies to prevent preterm births, which are the
leading cause of under-5 child mortality.

Professor Andrew Prendergast,Queen Mary University of London

He also expressed optimism about the potential impact of the findings:

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.

Professor Andrew prendergast, Queen Mary University of London

Sophie Hawksworth, Senior Manager of Clinical Revelation Research at Wellcome, commented on the global implications:

If we are to reduce child mortality globally, it is indeed critical to reduce the risk of preterm births, especially in
areas with limited access to neonatal intensive care units and resources. This is a promising study and while the
primary outcome of birthweight was unaffected in the trial, the prospect that this treatment prevents preterm births
warrants further study.

Sophie Hawksworth, Senior Manager of Clinical Discovery Research at Wellcome

Further details

For more detailed information, refer to the original research article:

Chasekwa, B., et al. (2025). A Trial of Trimethoprim-Sulfamethoxazole in Pregnancy to Improve Birth Outcomes.
New England Journal of Medicine. DOI: 10.1056/NEJMoa2408114