The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis

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Abstract
Premature birth is the major cause of perinatal mortality and morbidity in both high- and low-income countries. The causes of preterm labour are multiple but infection is important. We have previously described an unusually high incidence of preterm birth (20%) in an ultrasound-dated, rural, pregnant population in Southern Malawi with high burdens of infective morbidity. We have now studied the impact of routine prophylaxis with azithromycin as directly observed, single-dose therapy at two gestational windows to try to decrease the incidence of preterm birth. We randomized 2,297 pregnant women attending three rural and one peri-urban health centres in Southern Malawi to a placebo-controlled trial of oral azithromycin (1 g) given at 16–24 and 28–32 wk gestation. Gestational age was determined by ultrasound before 24 wk. Women and their infants were followed up until 6 wk post delivery. The primary outcome was incidence of preterm delivery, defined as 6,200 pregnancies) shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86–1.22). This study provides no support for the use of antibiotics as routine prophylaxis to prevent preterm birth in high risk populations; prevention of preterm birth requires alternative strategies. Current Controlled Trials ISRCTN84023116 Please see later in the article for the Editors' Summary