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Published on: June 24, 2020
Neonatal azithromycin administration for prevention of infant mortality
Catherine E Oldenburg1,2,3, Ali Sié4, Mamadou Bountogo4
1Francis I Proctor Foundation, University of California, San Francisco, USA.
Insights
This study investigated azithromycin for neonates in Burkina Faso, finding no significant reduction in mortality. The trial did not support routine use of azithromycin for preventing infant mortality in similar settings.
Area of Science:
- Global Health
- Pediatric Infectious Diseases
- Clinical Trials
Background:
- Biannual mass azithromycin administration is known to reduce childhood mortality in Sub-Saharan Africa, particularly in children aged 1-5 months.
- Concerns regarding infantile hypertrophic pyloric stenosis (IHPS) have previously limited azithromycin distribution to neonates (infants under 1 month old).
Purpose of the Study:
- To evaluate the safety and efficacy of a single oral dose of azithromycin in reducing all-cause mortality among neonates (8-27 days old) in Burkina Faso.
- To assess the risk of infantile hypertrophic pyloric stenosis (IHPS) associated with neonatal azithromycin administration.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 21,832 neonates in Burkina Faso.
- Participants received either a single oral dose of azithromycin (20 mg/kg) or a placebo.
- Primary outcome was all-cause mortality at 6 months of age, with ongoing surveillance for IHPS.
Main Results:
- All-cause mortality at 6 months was 0.44% in the azithromycin group (42 deaths) and 0.52% in the placebo group (50 deaths), a non-significant difference (HR, 0.85; 95% CI, 0.56 to 1.28).
- One case of IHPS was detected, occurring in the azithromycin arm.
- Serious adverse events within 28 days were slightly higher in the azithromycin group (0.27%) compared to placebo (0.14%).
Conclusions:
- The study's power to detect a mortality reduction was limited by lower-than-anticipated overall mortality rates.
- Current evidence does not support the routine use of azithromycin for mortality prevention in neonates in similar Sub-Saharan African settings.
- Further research may be needed to clarify the risk-benefit profile of azithromycin in this age group.
Abstract:
BACKGROUND: Biannual mass azithromycin administration reduces all-cause childhood mortality in some sub-Saharan African settings, with the largest effects in children 1 to 5 months of age. Azithromycin has not been distributed to children younger than 1 month of age because of the risk of infantile hypertrophic pyloric stenosis (IHPS). METHODS: In this 1:1 placebo-controlled trial, neonates 8 to 27 days of age were randomly assigned to a single oral dose of azithromycin (20 mg/kg) or an equivalent volume of placebo in five regions of Burkina Faso during 2019 and 2020. The primary outcome was all-cause mortality at 6 months of age. Infants were evaluated at 21 days after treatment and at 3 and 6 months of age for vital status; family and provider surveillance for IHPS continued throughout. RESULTS: Of 21,832 enrolled neonates, 10,898 were allocated to azithromycin and 10,934 to placebo. At 6 months of age, 92 infants had died: 42 (0.44%) in the azithromycin group and 50 (0.52%) in the placebo group (hazard ratio, 0.85; 95% confidence interval [CI], 0.56 to 1.28; P=0.46). A single IHPS case was detected, which was in the azithromycin arm. Serious adverse events, including death and hospitalization within 28 days of treatment, occurred in 0.27% of infants in the azithromycin group and 0.14% in the placebo group, for an absolute risk difference of 0.14 percentage points (95% CI, 0.01 to 0.26). CONCLUSIONS: Overall mortality was lower than anticipated when the trial was designed, thus limiting its power. The available data do not support the routine use of azithromycin for the prevention of mortality in neonates in sub-Saharan African settings similar to the one in which this trial was conducted. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT03682653.)
