Mercer B M, Miodovnik M, Thurnau G R, Goldenberg R L, Das A F, Ramsey R D, Rabello Y A, Meis P J, Moawad A H, Iams J D, Van Dorsten J P, Paul R H, Bottoms S F, Merenstein G, Thom E A, Roberts J M, McNellis D
University of Tennessee, Memphis 38103, USA.
JAMA. 1997 Sep 24;278(12):989-95.
Intrauterine infection is thought to be one cause of preterm premature rupture of the membranes (PPROM). Antibiotic therapy has been shown to prolong pregnancy, but the effect on infant morbidity has been inconsistent.
To determine if antibiotic treatment during expectant management of PPROM will reduce infant morbidity.
Randomized, double-blind, placebo-controlled trial.
University hospitals of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
A total of 614 of 804 eligible gravidas with PPROM between 24 weeks' and 0 days' and 32 weeks' and 0 days' gestation who were considered candidates for pregnancy prolongation and had not received corticosteroids for fetal maturation or antibiotic treatment within 1 week of randomization.
Intravenous ampicillin (2-g dose every 6 hours) and erythromycin (250-mg dose every 6 hours) for 48 hours followed by oral amoxicillin (250-mg dose every 8 hours) and erythromycin base (333-mg dose every 8 hours) for 5 days vs a matching placebo regimen. Group B streptococcus (GBS) carriers were identified and treated. Tocolysis and corticosteroids were prohibited after randomization.
The composite primary outcome included pregnancies complicated by at least one of the following: fetal or infant death, respiratory distress, severe intraventricular hemorrhage, stage 2 or 3 necrotizing enterocolitis, or sepsis within 72 hours of birth. These perinatal morbidities were also evaluated individually and pregnancy prolongation was assessed.
In the total study population, the primary outcome (44.1 % vs 52.9%; P=.04), respiratory distress (40.5% vs 48.7%; P=.04), and necrotizing enterocolitis (2.3% vs 5.8%; P=.03) were less frequent with antibiotics. In the GBS-negative cohort, the antibiotic group had less frequent primary outcome (44.5% vs 54.5%; P=.03), respiratory distress (40.8% vs 50.6%; P=.03), overall sepsis (8.4% vs 15.6%; P=.01), pneumonia (2.9% vs 7.0%; P=.04), and other morbidities. Among GBS-negative women, significant pregnancy prolongation was seen with antibiotics (P<.001).
We recommend that women with expectantly managed PPROM remote from term receive antibiotics to reduce infant morbidity.
宫内感染被认为是胎膜早破早产（PPROM）的原因之一。抗生素治疗已被证明可延长孕周，但对婴儿发病率的影响并不一致。
确定PPROM期待治疗期间使用抗生素是否会降低婴儿发病率。
随机、双盲、安慰剂对照试验。
国立儿童健康与人类发展研究所母胎医学单位网络的大学医院。
804例符合条件的PPROM孕妇中，共有614例，孕周在24周0天至32周0天之间，被认为有延长孕周的可能，且在随机分组前1周内未接受过促进胎儿成熟的皮质类固醇或抗生素治疗。
静脉注射氨苄西林（每6小时2克剂量）和红霉素（每6小时250毫克剂量）48小时，随后口服阿莫西林（每8小时250毫克剂量）和红霉素碱（每8小时333毫克剂量）5天，与匹配的安慰剂方案进行对比。识别并治疗B族链球菌（GBS）携带者。随机分组后禁止使用宫缩抑制剂和皮质类固醇。
综合主要结局包括至少合并以下情况之一的妊娠：胎儿或婴儿死亡、呼吸窘迫、重度脑室内出血、2期或3期坏死性小肠结肠炎，或出生后72小时内发生败血症。还分别评估了这些围产期发病率，并评估了孕周延长情况。
在整个研究人群中，抗生素组的主要结局（44.1%对52.9%；P = 0.04）、呼吸窘迫（40.5%对48.7%；P = 0.04）和坏死性小肠结肠炎（2.3%对5.8%；P = 0.03）的发生率较低。在GBS阴性队列中，抗生素组的主要结局（44.5%对54.5%；P = 0.03）、呼吸窘迫（40.8%对50.6%；P = 0.03）、总体败血症（8.4%对15.6%；P = 0.01）、肺炎（2.9%对7.0%；P = 0.04）及其他发病率较低。在GBS阴性女性中，抗生素治疗可显著延长孕周（P < 0.001）。
我们建议对孕周距足月尚远的PPROM期待治疗的女性使用抗生素以降低婴儿发病率。
