Broad-Spectrum Antibiotics for Spontaneous Preterm Labour: The ORACLE II Randomised Trial

Abstract

Summary Background Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue. Methods 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. 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 None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5·6%], co-amoxiclav 76 [5·0%], both antibiotics 91 [5·9%], vs placebo 78 [5·0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection. Interpretation This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.