Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial
Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial
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DOI：
10.1016/s0140-6736(00)04233-1
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发表时间：
2001-03-31
期刊：
影响因子：
168.9
通讯作者：
Tarnow-Mordi, W
中科院分区：
文献类型：
--
作者：
Kenyon, SL;Taylor, DJ;Tarnow-Mordi, W
背景：早产前胎膜破裂（pPROM）是早产最常见的先兆，可导致死亡、新生儿疾病和长期残疾。以前的小规模抗生素治疗胎膜早破的试验表明对新生儿有一些健康益处，但结果并不确定。我们做了一个随机多中心试验，试图解决这个问题。方法4826名妇女与胎膜早破随机分配250毫克红霉素（n=1197），325毫克复合阿莫西林（250毫克阿莫西林加125毫克克拉维酸; n=1212），两者（n=1192），或安慰剂（n=1225），每天4次，10天或直到分娩。主要结局指标为出院前新生儿死亡、慢性肺部疾病或超声检查显示的主要脑异常的复合指标。结果-两名妇女失去了后续行动，有15个协议违反。在所有2415名仅分配红霉素或安慰剂的妇女所生的婴儿中，红霉素组的主要复合结局少于安慰剂组（151/1190 [12.7%] vs 186/1225 [15.2%]，p=0.08）。在该比较的2260例单例中，红霉素组的复合主要结局显著较少（1111例中的125例[11.2%] vs 1149例中的166例[14.4%]，p=0.02）。在所有婴儿或单胎婴儿中，单用Coamoxiclav和Coamoxiclav+红霉素与安慰剂相比，在这一结局方面没有获益。红霉素的使用还与妊娠期延长、新生儿表面活性剂治疗减少、28天及以上的氧依赖性降低、出院前超声检查显示的主要脑异常减少以及血培养阳性减少相关。虽然共同amoxiclav只有和共同amoxiclav加红霉素与延长妊娠，他们也与新生儿坏死性enterocolitis.Interpretation红霉素的比率显着较高，与妇女的胎膜早破是与一系列的健康福利的新生儿，因此可能减少儿童残疾。然而，由于与新生儿坏死性小肠结肠炎相关，不能常规推荐复方阿莫西林治疗胎膜早破。计划对胎膜早破后儿童发育和残疾进行随访研究。
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 coamoxiclav 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.