BACKGROUND: Preterm, prelabour rupture of the fetal membranes (pPROM) is the 
commonest antecedent of preterm birth, and can lead to death, neonatal disease, 
and long-term disability. Previous small trials of antibiotics for pPROM 
suggested some health benefits for the neonate, but the results were 
inconclusive. We did a randomised multicentre trial to try to resolve this 
issue.
METHODS: 4826 women with pPROM were randomly assigned 250 mg erythromycin 
(n=1197), 325 mg co-amoxiclav (250 mg amoxicillin plus 125 mg clavulanic acid; 
n=1212), both (n=1192), or placebo (n=1225) four times daily for 10 days or 
until delivery. The primary outcome measure was a composite of neonatal death, 
chronic lung disease, or major cerebral abnormality on ultrasonography before 
discharge from hospital. Analysis was by intention to treat.
FINDINGS: Two women were lost to follow-up, and there were 15 protocol 
violations. Among all 2415 infants born to women allocated erythromycin only or 
placebo, fewer had the primary composite outcome in the erythromycin group (151 
of 1190 [12.7%] vs 186 of 1225 [15.2%], p=0.08) than in the placebo group. Among 
the 2260 singletons in this comparison, significantly fewer had the composite 
primary outcome in the erythromycin group (125 of 1111 [11.2%] vs 166 of 1149 
[14.4%], p=0.02). Co-amoxiclav only and co-amoxiclav plus erythromycin had no 
benefit over placebo with regard to this outcome in all infants or in singletons 
only. Use of erythromycin was also associated with prolongation of pregnancy, 
reductions in neonatal treatment with surfactant, decreases in oxygen dependence 
at 28 days of age and older, fewer major cerebral abnormalities on 
ultrasonography before discharge, and fewer positive blood cultures. Although 
co-amoxiclav only and co-amoxiclav plus erythromycin were associated with 
prolongation of pregnancy, they were also associated with a significantly higher 
rate of neonatal necrotising enterocolitis.
INTERPRETATION: Erythromycin for women with pPROM is associated with a range of 
health benefits for the neonate, and thus a probable reduction in childhood 
disability. However, co-amoxiclav cannot be routinely recommended for pPROM 
because of its association with neonatal necrotising enterocolitis. A follow-up 
study of childhood development and disability after pPROM is planned.