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.
METHODS AND FINDINGS: 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 <37 wk. Secondary outcomes were mean gestational age at delivery, perinatal mortality,
birthweight, maternal
malaria, and anaemia. Analysis was by intention to treat. There were no significant differences in outcome between the
azithromycin group (n = 1,096) and the placebo group (n = 1,087) in respect of
preterm birth (16.8% versus 17.4%), odds ratio (OR) 0.96, 95% confidence interval (0.76-1.21); mean gestational age at delivery (38.5 versus 38.4 weeks), mean difference 0.16 (-0.08 to 0.40); mean
birthweight (3.03 versus 2.99 kg), mean difference 0.04 (-0.005 to 0.08);
perinatal deaths (4.3% versus 5.0%), OR 0.85 (0.53-1.38); or maternal malarial parasitaemia (11.5% versus 10.1%), OR 1.11 (0.84-1.49) and anaemia (44.1% versus 41.3%) at 28-32 weeks, OR 1.07 (0.88-1.30). Meta-analysis of the primary outcome results with seven other studies of routine
antibiotic prophylaxis in pregnancy (>6,200 pregnancies) shows no effect on
preterm birth (relative risk 1.02, 95% confidence interval 0.86-1.22).
CONCLUSIONS: 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.
TRIAL REGISTRATION: