Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group

Lancet. 2001 Mar 31;357(9261):989-94. doi: 10.1016/s0140-6736(00)04234-3.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use*
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Therapy, Combination / therapeutic use*
  • Drug Utilization
  • Enterocolitis, Necrotizing / chemically induced
  • Erythromycin / therapeutic use*
  • Female
  • Humans
  • Infant, Newborn
  • Obstetric Labor, Premature / drug therapy*
  • Pregnancy
  • Pregnancy Outcome / epidemiology
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Erythromycin
  • Amoxicillin-Potassium Clavulanate Combination