A Trial of Trimethoprim-Sulfamethoxazole in Pregnancy to Improve Birth Outcomes

Chasekwa, Bernard M.Sc.
Munhanzi, Fortunate B.Sc.
Madhuyu, Lenin N.D.
Mbewe, Gabriel B.Sc.
Mabika, Vincent M.B., Ch.B.
Chidhanguro, Dzivaidzo S.C.M.
Kofi, Tendai S.C.M.
Munengiwa, Jonthan S.C.M.
Mapfumo, Hilda S.C.M.
Musapa, Mercy S.C.M.
Shumba, Sipho S.C.M.
Hungwe, Elizabeth S.C.M.
Nhokwara, Mary S.C.M.
Bushe, Nester S.C.M.
Kufa, Rudo P.C.N.
Mazula, Phatisiwe P.C.N.
Chikombingo, Muchaneta P.C.N.
Tengende, Alice B.Sc.
Zanga, Admire M.B., Ch.B.
Ziruma, Asaph M.B., Ch.B.
Bere, Tsitsi B.Sc.
Munyengwa, Success B.Pharm.
Mudimbu, Charity B.Pharm.
Murwira, Zvikomborero B.Pharm.
Mudzingwa, Shepherd B.Pharm.
Mpofu, Eddington M.Com.
Mutasa, Batsirai M.B.A.
Sauramba, Virginia M.S.P.L.
Masakadze, Elisha S.C.M.L.T.
Runodamoto, Thompson S.C.M.L.T.
Chiorera, Courage S.C.M.L.T.
Mushininga, Alfred B.D.S.
Bourke, Claire D. Ph.D.
Robertson, Ruairi C. Ph.D.
Perussolo, Jeniffer Ph.D.
Donos, Nikos Ph.D.
Nyachowe, Chandiwana M.B., Ch.B.
Muchekeza, Mary M.B., Ch.B.
Chikunya, Jefrey C.H.N.
Smuk, Melanie Ph.D.
Mutasa, Kuda M.P.H.
Tavengwa, Naume V. M.S.W.
Langhaug, Lisa L. Ph.D.
Ntozini, Robert Dr.P.H.
Munjanja, Stephen P. Ph.D.
Prendergast, Andrew J. D.Phil.

¹Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
²Blizard Institute, Queen Mary University of London, London
³Ministry of Health and Child Care, Harare, Zimbabwe
⁴University of Zimbabwe, Harare
⁵University of Zimbabwe Clinical Research Centre, Harare
⁶University of Glasgow, Glasgow, United Kingdom
⁷Centre for Oral Clinical Research, Institute of Dentistry, Faculty of Medicine and Dentistry, Queen Mary University of London, London

Mr. Chasekwa can be contacted at [email protected] or at Zvitambo Institute for Maternal and Child Health Research, 16 Lauchlan Ave., Meyrick Park, Harare, Zimbabwe.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Supported by a grant (108065/Z/15/Z, to Dr. Prendergast) from Wellcome, a grant (MR/T039337/1) from the Medical Research Council, United Kingdom, and an award (206225/Z/17/Z, to Dr. Bourke) from Wellcome and the Royal Society.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

New England Journal of Medicine 392(21):p 2125-2134, June 5, 2025. | DOI: 10.1056/NEJMoa2408114

Abstract

Background

Maternal infections underlie several adverse birth outcomes. Whether trimethoprim-sulfamethoxazole prophylaxis during pregnancy will improve birth outcomes is unknown.

Methods

In a double-blind, randomized, placebo-controlled trial in Zimbabwe, we assigned pregnant women to receive trimethoprim-sulfamethoxazole, at a dose of 960 mg daily, or placebo from at least 14 weeks’ gestation until delivery. The primary outcome was birth weight.

Results

Among 993 participants (131 with human immunodeficiency virus infection), 498 were randomly assigned to receive placebo and 495 to receive trimethoprim-sulfamethoxazole, with the first dose received at a median of 21.7 weeks’ gestation (interquartile range, 17.3 to 26.4). In intention-to-treat analyses, the mean (±SD) birth weight was 3040±460 g in the trimethoprim-sulfamethoxazole group and 3019±526 g in the placebo group (mean difference, 20 g, 95% confidence interval, −43 to 83; P=0.53). The number of adverse events was similar in the two groups.

Conclusions

In Zimbabwe, trimethoprim-sulfamethoxazole prophylaxis during pregnancy did not significantly increase infant birth weight. (Funded by Wellcome and others; Pan African Clinical Trials Registry number, PACTR202107707978619.)

Trimethoprim-Sulfamethoxazole to Improve Birth Outcomes

In a double-blind, randomized, placebo-controlled trial in Zimbabwe, treatment of mothers with trimethoprim-sulfamethoxazole daily beginning as early as 14 weeks’ gestation did not significantly increase infant birth weight.