Kelly Lauren E, Shivananda Sandesh, Murthy Prashanth, Srinivasjois Ravisha, Shah Prakeshkumar S
Department of Paediatrics, University of Toronto Mount Sinai Hospital, Toronto, Canada.
Cochrane Database Syst Rev. 2017 Jun 28;6(6):CD006183. doi: 10.1002/14651858.CD006183.pub2.
Approximately 1 in 10 pregnancies is affected by meconium passage at delivery, which can result in meconium aspiration syndrome (MAS). MAS can cause respiratory complications and, very rarely, death. Antibiotics have been prescribed for neonates exposed to meconium in amniotic fluid, with the intention of preventing infection due to potential bacterial contaminants.
We conducted this review to assess the efficacy and safety of antibiotics for:1. prevention of infection, morbidity, and mortality among infants born through meconium-stained amniotic fluid (MSAF) who are asymptomatic at birth; and2. prevention of infection, morbidity, and mortality among infants born through MSAF who have signs and symptoms compatible with meconium aspiration syndrome (MAS).
We performed a literature search using the following databases: MEDLINE (1966 to July 2016); Embase (1980 to July 2016); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to July 2016); and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 7) in the Cochrane Library. We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles.
We included randomised and quasi-randomised controlled trials that compared antibiotics administered via any route versus placebo or no treatment for prevention of infection among neonates exposed to MSAF, or who developed MAS. We excluded cohort, case control, and any other non-randomised studies and applied no language restrictions. We included studies of term and preterm infants, and we included studies examining use of any antibacterial antibiotics. We included studies that reported on any outcomes of interest.
We assessed the methodological quality of included trials by reviewing information provided in study reports and obtained by personal communication with study authors. We extracted data on relevant outcomes, estimated effect size, and reported values as risk ratios (RRs), risk differences (RDs), and mean differences (MDs), as appropriate. We conducted subgroup analyses for treatment of MAS and for prophylaxis (asymptomatic neonates exposed to meconium).
Four randomised controlled studies including a total of 695 participants were eligible for inclusion. Three studies evaluated neonates with MAS, and one study assessed asymptomatic neonates exposed to meconium in amniotic fluid. These studies exhibited varying degrees of methodological rigour: Two studies were at low risk of bias, and two were at unclear risk. We graded evidence derived from these studies as low quality. We downgraded overall evidence owing to the large number of participants lost to follow-up in one trial, the small sample sizes of all trials, and unclear methodological details provided for two trials.The primary outcome was risk of early- and late-onset neonatal sepsis. Antibiotics did not decrease the risk of sepsis in neonates with a diagnosis of MAS (RR 1.54, 95% confidence interval (CI) 0.27 to 8.96; RD 0.00, 95% CI -0.02 to 0.03; 445 participants, three studies; I² = 0%) nor in asymptomatic neonates exposed to meconium in amniotic fluid (RR 0.76, 95% CI 0.25 to 2.34; RD -0.01, 95% CI -0.07 to 0.04; 250 participants, one study; I² = 0%). Results show no significant differences in mortality or duration of stay in hospital between groups given antibiotics and control groups of symptomatic and asymptomatic neonates. One study in asymptomatic neonates reported a significant reduction in duration of mechanical ventilation for the control group compared with the antibiotic group (MD 0.26, 95% CI 0.15 to 0.37; 250 participants, one study; I² = 0%).
AUTHORS' CONCLUSIONS: Upon review of available evidence, we found no differences in infection rates following antibiotic treatment among neonates born through meconium-stained fluid and those with meconium aspiration syndrome. The overall quality of evidence is low owing to the small number of included studies. Well-controlled studies of adequate power are needed.
约十分之一的妊娠在分娩时会出现胎粪排出,这可能导致胎粪吸入综合征(MAS)。MAS可引起呼吸并发症,极少数情况下会导致死亡。对于羊水沾染胎粪的新生儿,已开具抗生素处方,目的是预防因潜在细菌污染物导致的感染。
我们进行此项综述以评估抗生素在以下方面的疗效和安全性:1. 预防出生时无症状、经胎粪污染羊水(MSAF)出生的婴儿发生感染、发病和死亡;2. 预防经MSAF出生且有与胎粪吸入综合征(MAS)相符的体征和症状的婴儿发生感染、发病和死亡。
我们使用以下数据库进行文献检索:MEDLINE(1966年至2016年7月);Embase(1980年至2016年7月);护理及相关健康文献累积索引(CINAHL;1982年至2016年7月);以及Cochrane图书馆中的Cochrane对照试验中央注册库(CENTRAL;2016年第7期)。我们还检索了临床试验数据库、会议论文集以及检索到文章的参考文献列表。
我们纳入了随机和半随机对照试验,这些试验比较了通过任何途径给予抗生素与安慰剂或不治疗,以预防暴露于MSAF或发生MAS的新生儿感染。我们排除了队列研究、病例对照研究以及任何其他非随机研究,且不设语言限制。我们纳入了足月儿和早产儿的研究,以及考察任何抗菌抗生素使用情况的研究。我们纳入了报告任何感兴趣结局的研究。
我们通过审查研究报告中提供的信息以及与研究作者进行个人交流获得的信息,评估纳入试验的方法学质量。我们提取了相关结局的数据,估计效应大小,并酌情报告为风险比(RRs)、风险差(RDs)和均值差(MDs)。我们对MAS的治疗和预防(暴露于胎粪的无症状新生儿)进行了亚组分析。
四项随机对照研究共695名参与者符合纳入标准。三项研究评估了患有MAS的新生儿,一项研究评估了羊水沾染胎粪的无症状新生儿。这些研究的方法学严谨程度各不相同:两项研究偏倚风险较低,两项研究偏倚风险不明确。我们将这些研究得出的证据质量评为低质量。由于一项试验中有大量参与者失访、所有试验样本量较小以及两项试验提供的方法学细节不明确,我们对总体证据进行了降级。主要结局是早发性和晚发性新生儿败血症的风险。抗生素并未降低诊断为MAS的新生儿发生败血症的风险(RR 1.54,95%置信区间(CI)0.27至8.96;RD 0.00,95% CI -0.02至0.03;445名参与者,三项研究;I² = 0%),也未降低羊水沾染胎粪的无症状新生儿发生败血症的风险(RR 0.76,95% CI 0.25至2.34;RD -0.01,95% CI -0.07至0.04;250名参与者,一项研究;I² = 0%)。结果显示,给予抗生素的有症状和无症状新生儿组与对照组在死亡率或住院时间方面无显著差异。一项针对无症状新生儿的研究报告称,与抗生素组相比,对照组机械通气时间显著缩短(MD 0.26,95% CI 0.15至0.37;250名参与者,一项研究;I² = 0%)。
通过审查现有证据,我们发现经胎粪污染羊水出生的新生儿与患有胎粪吸入综合征的新生儿在抗生素治疗后的感染率无差异。由于纳入研究数量较少,证据的总体质量较低。需要进行充分有力的对照良好的研究。