N Engl J Med 2020 12 23;383(26):2514-2525. Epub 2020 Oct 23.
The affiliations of the members of the writing committee are as follows: World Health Organization, Geneva (O.T.O., J.P.V., G.P., M.-H.N., F.A., A.M.G., R.B., S.P.N.R., A.D.C., S.G.); Johns Hopkins Bloomberg School of Public Health, Baltimore (A.H.B., R.K.); Bangabandhu Sheikh Mujib Medical University (M.S., S.B. Chowdhury), Projahnmo Research Foundation (S. Ahmed, N.B., A.D.R., M.A. Shahed, I.A.J.), Institute of Child and Mother Health (F.Y., M.M.R.), Center for Woman and Child Health (A.A., S.K.), and Enam Medical College and Hospital (G.A., S. Akter), Dhaka, and Sylhet Muhammad Ataul Gani Osmani Medical College Hospital (N. Akhter, P.R.D.), Jalalabad Ragib-Rabeya Medical College Hospital (M.A. Sabur, M.T.A.), and Sylhet Women's Medical College Hospital (S.F.C., M.A.M.), Sylhet - both in Bangladesh; KLE Academy of Higher Education and Research, Jawaharlal Nehru Medical College, Belagavi (S.S.G., S.M.D., M.C.M., Y.V.P., M.S.S., S.S.V., V.R.H.), Shri B.M. Patil Medical College, Vijayapura (S.R.B., S.S. Mathapati, P.G.P., M.M.P., M.R.G., H.R.B.), S. Nijalingappa Medical College, Bagalkot (A.A.M., G.M.K., S.B. Chikkamath, B.C.Y., R.R.P.), Srirama Chandra Bhanja Medical College, Cuttack (S.S. Misra, L.D., S.N., R.B.N., B.S.), and Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi (H.K.C.) - all in India; University of Nairobi (Z.Q., F.W., A. Osoti, G.G., A.L.) and Kenyatta National Hospital (J.K.), Nairobi, Coast Provincial General Hospital, Mombasa (H.M., N. Aliyan), Nakuru Level 5 Hospital, Nakuru (A.B., E.K.), Kiambu Level 5 Hospital, Kiambu (M.M., L.T.), and Thika Level 5 Hospital, Thika (N.J.G., B.L.) - all in Kenya; the College of Medicine, University of Ibadan, and University College Hospital, Ibadan (A.I.A., A.G.F., O.A.A., A.M.A., O.O.I.), Kubwa General Hospital, Kubwa (W.S., I.K.E.), Nyanya General Hospital, Nyanya (H.A.I., C.V.O.), State Specialist Hospital (T.A.I., O.A. Olubosede, O.B.) and Mother and Child Hospital (A.L.A., O.O.O., R.O.O., I.P.E.), Akure, Lagos Island Maternity Hospital (O.M.O., O.A. Olutekunbi), and Lagos State University Teaching Hospital (A.O. Fabamwo, E.A.D., J.O.A.), Lagos, Obafemi Awolowo University, Ile-Ife (E.A.A., O.K., H.C.A., I.O.A., A.O. Fehintola, B.P.K.), University of Abuja, Abuja (A.D.I., E.K.O.), Sacred Heart Hospital, Abeokuta (O. Abiodun, O.F.D.), Mother and Child Hospital, Ondo (F.B.A., L.O.), University of Ilorin, Ilorin (O. Adesiyun, H.O.R.), and University of Benin, Benin City (A.B.A.A., I.O.) - all in Nigeria; Aga Khan University, Karachi (S. Ariff, S.B.S., L.S.), Sheikh Zayed Medical College and Hospital, Rahim Yar Khan (S.Z., S.O.), and Liaquat University Hospital, Hyderabad (R.S., S.S.) - all in Pakistan; Centro Rosarino de Estudios Perinatales, Rosario, Argentina (D.G., H.G., G.C.); Statistika Consultoria, Campinas, Brazil (J.C.); University of Liverpool, Liverpool, United Kingdom (J.N.); College of Medicine, University of Malawi, Blantyre (E.M.); American University of Beirut, Beirut, Lebanon (K.Y.); and the Makerere University College of Health Sciences, Kampala, Uganda (K.M.).
Background: The safety and efficacy of antenatal glucocorticoids in women in low-resource countries who are at risk for preterm birth are uncertain.
Methods: We conducted a multicountry, randomized trial involving pregnant women between 26 weeks 0 days and 33 weeks 6 days of gestation who were at risk for preterm birth. The participants were assigned to intramuscular dexamethasone or identical placebo. The primary outcomes were neonatal death alone, stillbirth or neonatal death, and possible maternal bacterial infection; neonatal death alone and stillbirth or neonatal death were evaluated with superiority analyses, and possible maternal bacterial infection was evaluated with a noninferiority analysis with the use of a prespecified margin of 1.25 on the relative scale.
Results: A total of 2852 women (and their 3070 fetuses) from 29 secondary- and tertiary-level hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan underwent randomization. The trial was stopped for benefit at the second interim analysis. Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and in 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% confidence interval [CI], 0.72 to 0.97; P = 0.03). Stillbirth or neonatal death occurred in 393 of 1532 fetuses and infants (25.7%) and in 444 of 1519 fetuses and infants (29.2%), respectively (relative risk, 0.88; 95% CI, 0.78 to 0.99; P = 0.04); the incidence of possible maternal bacterial infection was 4.8% and 6.3%, respectively (relative risk, 0.76; 95% CI, 0.56 to 1.03). There was no significant between-group difference in the incidence of adverse events.
Conclusions: Among women in low-resource countries who were at risk for early preterm birth, the use of dexamethasone resulted in significantly lower risks of neonatal death alone and stillbirth or neonatal death than the use of placebo, without an increase in the incidence of possible maternal bacterial infection. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization; Australian and New Zealand Clinical Trials Registry number, ACTRN12617000476336; Clinical Trials Registry-India number, CTRI/2017/04/008326.).