Ohlsson Arne, Shah Vibhuti S, Stade Brenda C
Departments of Paediatrics, Obstetrics and Gynaecology and Institute of Health Policy, Management and Evaluation, University of Toronto, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Cochrane Database Syst Rev. 2014 Dec 14;2014(12):CD003520. doi: 10.1002/14651858.CD003520.pub3.
Although early-onset group B β-hemolytic streptococcus (GBS) infection is rare, it accounts for approximately 30% of neonatal infections, has a high mortality rate, and is acquired through vertical transmission from colonized mothers. Several trials have demonstrated the efficacy of intrapartum antibiotic prophylaxis (IAP) for preventing early-onset disease (EOD). Vaginal disinfection with chlorhexidine during labour has been proposed as another strategy for preventing GBS EOD in the preterm and term neonate. Chlorhexidine has been found to have no impact on antibiotic resistance, is inexpensive, and applicable to poorly equipped delivery sites.
To determine the effectiveness of vaginal disinfection with chlorhexidine during labour in women who are colonized with GBS for preventing early-onset GBS infection in preterm and term neonates.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2014) and reference lists of retrieved studies.
Randomized and quasi-randomized trials comparing vaginal disinfection with chlorhexidine (vaginal wash or gel/cream) versus placebo, or no treatment.
Three review authors independently assessed the trials for inclusion and risk of bias, extracted the data and checked them for accuracy.
We identified no new trials eligible for inclusion in this update. One study was moved from included to excluded studies from the previous version of the review. Four studies, including 1125 preterm and term infants, met the inclusion criteria and reported on at least one of the outcomes of interest. For the comparison chlorhexidine (vaginal wash or gel) versus placebo or no treatment, two studies (n = 987) were pooled. There was no statistically significant difference in early-onset GBS disease (sepsis and/or meningitis) comparing chlorhexidine (vaginal wash or gel/cream) versus placebo or no treatment; risk ratio (RR), 2.32 (95% confidence interval (CI) 0.34 to 15.63); I-squared (I²) = 0% or in GBS pneumonia; RR 0.35 (95% CI 0.01 to 8.6); test for heterogeneity not applicable. The outcome of colonization of the neonate with GBS was reported in three studies (n = 328); RR 0.64 (95% CI 0.40 to 1.01; there was substantial between-study heterogeneity (Chi² = 3.19; P = 0.20; I² = 37%). Maternal mild side effects (stinging or local irritation) (three trials, 1066 women) were more commonly seen in women treated with chlorhexidine (RR 8.50 (95% CI 1.60 to 45.28); there was no heterogeneity (Chi² = 0.01, df = 1 (P = 0.91); I² = 0%). No side effects were reported among the neonates.For the comparison chlorhexidine vaginal wash verus mechanical washing with placebo or no treatment (one study, n = 79), there was a significant reduction in neonatal colonization with GBS; RR 0.32 (95% CI 0.12 to 0.90). Tests for heterogeneity not applicable. There were no other significant results for this comparison.For the comparison chlorhexidine gel or cream versus placebo or no treatment, there were no statistically significant results for the outcomes reported on.The quality of the trials varied and the overall risk of bias was rated as unclear or high. The quality of the evidence using GRADE was very low for the outcomes of the comparison chlorhexidine (vaginal wash or gel/cream) versus placebo or no treatment. These outcomes included: early-onset GBS disease (sepsis and/or meningitis), GBS pneumonia, neonatal colonization with GBS, neonatal mortality due to early-onset GBS infection and adverse (mild) effects in the mother and the neonate.
AUTHORS' CONCLUSIONS: The quality of the four included trials varied as did the risk of bias and the quality of the evidence using GRADE was very low. Vaginal chlorhexidine was not associated with reductions in any of the primary outcomes of early-onset GBS disease (sepsis and/or meningitis) or GBS pneumonia. Vaginal chlorhexidine may reduce GBS colonization of neonates. The intervention was associated with an increased risk of maternal mild adverse effects. The review currently does not support the use of vaginal disinfection with chlorhexidine in labour for preventing early-onset disease. Results should be interpreted with caution as the methodological quality of the studies was poor. As early-onset GBS disease is a rare condition trials with very large sample sizes are needed to assess the effectiveness of vaginal chlorhexidine to reduce its occurrence. In the era of intrapartum antibiotic prophylaxis, such trials may be difficult to justify especially in developed countries.
尽管早发型B族β溶血性链球菌（GBS）感染罕见，但它约占新生儿感染的30%，死亡率高，且是通过定植母亲垂直传播获得的。多项试验已证明产时抗生素预防（IAP）对预防早发型疾病（EOD）的有效性。分娩期间用氯己定进行阴道消毒已被提议作为预防早产和足月新生儿GBS-EOD的另一策略。已发现氯己定对抗生素耐药性无影响，价格低廉，且适用于设备简陋的分娩场所。
确定GBS定植的产妇在分娩期间用氯己定进行阴道消毒对预防早产和足月新生儿早发型GBS感染的有效性。
我们检索了Cochrane妊娠与分娩组试验注册库（2014年10月31日）以及检索到的研究的参考文献列表。
比较氯己定（阴道冲洗或凝胶/乳膏）与安慰剂或不治疗的阴道消毒的随机和半随机试验。
三位综述作者独立评估试验是否纳入及偏倚风险，提取数据并检查其准确性。
我们未识别出符合本次更新纳入标准的新试验。一项研究从之前版本的综述中的纳入研究变为排除研究。四项研究，包括1125例早产和足月婴儿，符合纳入标准并报告了至少一项感兴趣的结局。对于氯己定（阴道冲洗或凝胶）与安慰剂或不治疗的比较，两项研究（n = 987）进行了合并。在早发型GBS疾病（败血症和/或脑膜炎）方面，氯己定（阴道冲洗或凝胶/乳膏）与安慰剂或不治疗相比无统计学显著差异；风险比（RR）为2.32（95%置信区间（CI）0.34至15.63）；I² = 0%，在GBS肺炎方面；RR为0.35（95%CI 0.01至8.6）；异质性检验不适用。三项研究（n = 328）报告了新生儿GBS定植的结局；RR为0.64（95%CI 0.40至1.01；研究间存在显著异质性（Chi² = 3.19；P = 0.20；I² = 37%）。产妇轻度副作用（刺痛或局部刺激）（三项试验，1066名女性）在接受氯己定治疗的女性中更常见（RR为8.50（95%CI 1.60至45.28）；无异质性（Chi² = 0.01，自由度 = 1（P = 0.91）；I² = 0%）。未报告新生儿有副作用。对于氯己定阴道冲洗与用安慰剂或不治疗进行机械冲洗的比较（一项研究，n = 79），新生儿GBS定植显著减少；RR为0.32（95%CI 0.12至0.90）。异质性检验不适用。该比较无其他显著结果。对于氯己定凝胶或乳膏与安慰剂或不治疗的比较，所报告的结局无统计学显著结果。试验质量各不相同，总体偏倚风险被评为不明确或高。对于氯己定（阴道冲洗或凝胶/乳膏）与安慰剂或不治疗的比较结果，使用GRADE的证据质量非常低。这些结局包括：早发型GBS疾病（败血症和/或脑膜炎）、GBS肺炎、新生儿GBS定植、早发型GBS感染导致的新生儿死亡以及母亲和新生儿的不良（轻度）影响。
纳入的四项试验质量各不相同，偏倚风险和使用GRADE的证据质量也非常低。阴道氯己定与早发型GBS疾病（败血症和/或脑膜炎）或GBS肺炎的任何主要结局的减少均无关联。阴道氯己定可能会减少新生儿GBS定植。该干预措施与产妇轻度不良反应风险增加有关。本综述目前不支持在分娩时使用氯己定进行阴道消毒来预防早发型疾病。由于研究的方法学质量较差，结果应谨慎解释。由于早发型GBS疾病是一种罕见情况，需要非常大样本量的试验来评估阴道氯己定减少其发生的有效性。在产时抗生素预防时代，尤其是在发达国家，这样的试验可能难以证明其合理性。
