Kenyon S L, Taylor D J, Tarnow-Mordi W
Department of Obstetrics and Gynaecology, Leicester Royal Infirmary, UK.
Lancet. 2001 Mar 31;357(9261):979-88. doi: 10.1016/s0140-6736(00)04233-1.
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.
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.
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.
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.
胎膜早破早产（pPROM）是早产最常见的前驱因素，可导致死亡、新生儿疾病及长期残疾。既往针对pPROM的小规模抗生素试验提示对新生儿有一定健康益处，但结果尚无定论。我们开展了一项随机多中心试验以试图解决这一问题。
4826例pPROM女性被随机分配，分别接受每日4次、每次250mg红霉素治疗（n=1197），或325mg阿莫西林克拉维酸钾（250mg阿莫西林加125mg克拉维酸；n=1212），或两者联合治疗（n=1192），或安慰剂治疗（n=1225），持续10天或直至分娩。主要结局指标为新生儿死亡、慢性肺病或出院前超声检查发现的严重脑异常的复合指标。分析采用意向性治疗。
2例女性失访，有15例违反方案。在仅接受红霉素或安慰剂治疗的女性所生的全部2415例婴儿中，红霉素组发生主要复合结局的婴儿较少（1190例中的151例[12.7%] vs 1225例中的186例[15.2%]，p=0.08）。在该比较中的2260例单胎婴儿中，红霉素组发生复合主要结局的婴儿显著较少（1111例中的125例[11.2%] vs 1149例中的166例[14.4%]，p=0.02）。仅使用阿莫西林克拉维酸钾以及阿莫西林克拉维酸钾加红霉素在所有婴儿或仅单胎婴儿中，该结局方面并不优于安慰剂。使用红霉素还与延长孕周、减少新生儿表面活性剂治疗、降低28日龄及以上婴儿的氧依赖、出院前超声检查发现的严重脑异常较少以及血培养阳性较少相关。虽然仅使用阿莫西林克拉维酸钾以及阿莫西林克拉维酸钾加红霉素与延长孕周相关，但也与新生儿坏死性小肠结肠炎发生率显著较高相关。
pPROM女性使用红霉素对新生儿有一系列健康益处，因此可能减少儿童残疾。然而，由于阿莫西林克拉维酸钾与新生儿坏死性小肠结肠炎相关，不能常规推荐用于pPROM。计划对pPROM后的儿童发育和残疾情况进行随访研究。
