Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group.

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 i...

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Publicado en:Lancet Vol. 357; no. 9261; pp. 979 - 989
Autores principales: Kenyon SL, Taylor DJ, Tarnow-Mordi W, Kenyon, S L, Taylor, D J, Tarnow-Mordi, W
Formato: clinical trial research tables/charts Journal Article
Publicado: Lancet 3/31/2001
Acceso en línea:Ver este registro en EBSCOhost
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        atl: Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group.
      aug:
        au:
          Kenyon SL
          Taylor DJ
          Tarnow-Mordi W
          Kenyon, S L
          Taylor, D J
          Tarnow-Mordi, W
        affil: Department of Obstetrics and Gynaecology, Leicester Royal Infirmary, UK
      sug:
        subj:
          Fetal Membranes, Premature Rupture Drug Therapy
          Labor, Premature Drug Therapy
          Antibiotics Therapeutic Use
          Erythromycin Therapeutic Use
          Amoxicillin Therapeutic Use
          Antibiotics, Combined Therapeutic Use
          Pregnancy
          Pregnancy Outcomes
          Enterocolitis, Necrotizing Chemically Induced
          Treatment Outcomes
          Clinical Trials
          Placebos
          T-Tests
          Mann-Whitney U Test
          Female
          Funding Source
          Human
          Female
      ab: 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.
      pubtype: Academic Journal
      doctype:
        clinical trial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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