Effect of Intrapartum Azithromycin vs Placebo on Neonatal Sepsis and Death
Authors: Roca Anna , Camara Bully , Bognini Joel D. , Nakakana Usman N. , Somé Athasana M. , Beloum Nathalie , Rouamba Toussaint , Sillah Fatoumata , Danso Madikoi , Jones Joquina C. , Graves Shashu , Jagne Isatou , Getanda Pauline , Darboe Saffiatou , Tahita Marc C. , Ndure Ebrahim , Franck Hien S. , Edmond Sawadogo Y. , Dondeh Bai L. , Nassa Wilfried G. J. , Garba Zakaria , Bojang Abdoulie , Njie Yusupha , Bottomley Christian , Tinto Halidou , D’Alessandro Umberto ,   PregnAnZI-2 Working Group, Secka Ousman , Sabally Edrissa , Badjie Siaka , Jarra Omar B. , Bah Sulayman , Suso Abdoulie , Fatty Bakary , Lush Alyson , Mahmoud Asheme , Barry Momodou , Sambou Ellen , Kassibo Kady , Haffner Maxine , Bojang Lamin , Manneh Kebba , Waggeh Momodou Lamin , Diagniagou Lankoandé , Ibrahima Karama , Rodrigue Yonli Lan-Boado , Nadège Millogo Ouédalo , Sourabié Aboubakary , Chandramohan Daniel , Greenwood Brian , Blencowe Hannah K. , Ashorn Per , Quigley Maria , Schrag Stephanie , Solomon Anthony , Vila Jordi , Oluwalana Claire , Kaboré William 
Published: March 2023

Importance

Neonatal sepsis is a leading cause of neonatal mortality. New interventions are needed to decrease neonatal sepsis and mortality in regions with highest burden.

Objective

To evaluate the efficacy of intrapartum azithromycin to reduce neonatal sepsis or mortality, as well as neonatal and maternal infections.

Design, Setting, and Participants

This double-blind, placebo-controlled, randomized clinical trial enrolled and followed up birthing parents and their infants at 10 health facilities in The Gambia and Burkina Faso, West Africa, between October 2017 and May 2021.

Interventions

Participants were assigned at random to receive oral azithromycin (2 g) or placebo (ratio 1:1) during labor.

Main Outcomes and Measures

The primary outcome was a composite of neonatal sepsis or mortality, with the former defined based on microbiologic or clinical criteria. Secondary outcomes were neonatal infections (skin, umbilical, eye and ear infections), malaria, and fever; postpartum infections (puerperal sepsis, mastitis), fever, and malaria; and use of antibiotics during 4-week follow-up.

Results

The trial randomized 11 983 persons in labor (median age, 29.9 years). Overall, 225 newborns (1.9% of 11 783 live births) met the primary end point. The incidence of neonatal mortality or sepsis was similar in the azithromycin and placebo groups (2.0% [115/5889] vs 1.9% [110/5894]; risk difference [RD], 0.09 [95% CI, −0.39 to 0.57]), as was the incidence of neonatal mortality (0.8% vs 0.8%; RD, 0.04 [95% CI, −0.27 to 0.35]) and neonatal sepsis (1.3% vs 1.3%; RD, 0.02 [95% CI, −0.38 to 0.43]). Newborns in the azithromycin group compared with the placebo group had lower incidence of skin infections (0.8% vs 1.7%; RD, −0.90 [95% CI, −1.30 to −0.49]) and need for antibiotics (6.2% vs 7.8%; RD, −1.58 [95% CI, −2.49 to −0.67]). Postpartum parents in the azithromycin group had lower incidence of mastitis (0.3% vs 0.5%; RD, −0.24 [95% CI, −0.47 to −0.01]) and puerperal fever (0.1% vs 0.3%; RD, −0.19 [95% CI, −0.36 to −0.01]).

Conclusions and Relevance

Azithromycin administered orally during labor did not reduce neonatal sepsis or mortality. These results do not support routine introduction of oral intrapartum azithromycin for this purpose.

Trial Registration

ClinicalTrials.gov Identifier: NCT03199547