Pfister Robert H, Soll Roger, Wiswell Thomas E
Division of Neonatal Perinatal Medicine, Fletcher Allen Health Care, Smith #582, 111 Colchester Avenue, Burlington, VT, USA, 05401.
Cochrane Database Syst Rev. 2009 Oct 7(4):CD006180. doi: 10.1002/14651858.CD006180.pub2.
Respiratory distress syndrome (RDS) is a significant cause of morbidity and mortality in preterm infants. RDS is caused by a deficiency, dysfunction, or inactivation of pulmonary surfactant. Numerous surfactants of either animal extract or synthetic design have been shown to improve outcomes. New surfactant preparations that include peptides or whole proteins that mimic endogenous surfactant protein have recently been developed and tested.
To assess the effect of administration of synthetic surfactant containing surfactant protein mimics compared to protein free synthetic surfactant on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having RDS.
Standard search methods of the Cochrane Neonatal Review Group were used. The search included MEDLINE (1966 - March 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) in all languages.
Randomized and quasi-randomized controlled clinical trials were considered for this review. Studies that enrolled preterm infants or low birth weight infants at risk for or having RDS who were treated with either a synthetic surfactant containing surfactant protein mimics or a protein free synthetic surfactant were included for this review. Studies of treatment or prevention of respiratory distress syndrome were included.
Data regarding mortality, chronic lung disease and multiple secondary outcome measures were abstracted by the review authors. Statistical analysis was performed using Review Manager software. Categorical data were analyzed using relative risk, risk difference, and number needed to treat. 95% confidence intervals reported. A fixed effects model was used for the meta-analysis. Heterogeneity was assessed using the I(2) statistic.
One study was identified that compared protein containing synthetic surfactants (PCSS) to protein free synthetic surfactants. Infants who received protein containing synthetic surfactant compared to protein free synthetic surfactant did not demonstrate significantly different risks of prespecified primary outcomes: mortality at 36 weeks postmenstrual age (PMA) [RR 0.89 (95% CI 0.71, 1.11)], chronic lung disease at 36 weeks PMA [RR 0.89 (95% CI 0.78, 1.03)], or the combined outcome of mortality or chronic lung disease at 36 weeks PMA [RR 0.88 (95% CI 0.77, 1.01)]. Among the secondary outcomes, a decrease in the incidence of respiratory distress syndrome at 24 hours of age was demonstrated in the group that received PCSS [RR 0.83 (95% CI 0.72, 0.95).
AUTHORS' CONCLUSIONS: In the one trial comparing protein containing synthetic surfactants compared to protein free synthetic surfactant for the prevention of RDS, no statistically different clinical differences in death and chronic lung disease were noted. Clinical outcomes between the two groups were generally similar although the group receiving protein containing synthetic surfactants did have decreased incidence of respiratory distress syndrome. Further well designed studies comparing protein containing synthetic surfactant to the more widely used animal derived surfactant extracts are indicated.
呼吸窘迫综合征（RDS）是早产儿发病和死亡的重要原因。RDS是由肺表面活性物质缺乏、功能障碍或失活引起的。许多动物提取物或合成设计的表面活性物质已被证明可改善预后。最近已开发并测试了包括模拟内源性表面活性蛋白的肽或全蛋白的新型表面活性物质制剂。
评估与不含蛋白的合成表面活性物质相比，给予含表面活性蛋白模拟物的合成表面活性物质对有发生RDS风险或已发生RDS的早产儿死亡率、慢性肺病及其他与早产相关疾病的影响。
采用Cochrane新生儿综述组的标准检索方法。检索包括所有语言的MEDLINE（1966年 - 2009年3月）和Cochrane对照试验中心注册库（CENTRAL，Cochrane图书馆）。
本综述纳入随机和半随机对照临床试验。纳入对有发生RDS风险或已发生RDS的早产儿或低出生体重儿进行治疗的研究，这些患儿接受含表面活性蛋白模拟物的合成表面活性物质或不含蛋白的合成表面活性物质治疗。纳入呼吸窘迫综合征治疗或预防的研究。
综述作者提取有关死亡率、慢性肺病及多个次要结局指标的数据。使用Review Manager软件进行统计分析。分类数据采用相对风险、风险差异和需治疗人数进行分析。报告95%置信区间。荟萃分析采用固定效应模型。使用I²统计量评估异质性。
确定了一项将含蛋白合成表面活性物质（PCSS）与不含蛋白合成表面活性物质进行比较的研究。与接受不含蛋白合成表面活性物质的婴儿相比，接受含蛋白合成表面活性物质的婴儿在预设主要结局方面未显示出显著差异：孕龄36周时的死亡率[相对风险0.89（95%置信区间0.71，1.11）]、孕龄36周时的慢性肺病[相对风险0.89（95%置信区间0.78，1.03）]或孕龄36周时死亡率或慢性肺病的综合结局[相对风险0.88（95%置信区间0.77，1.01）]。在次要结局中，接受PCSS的组在24小时龄时呼吸窘迫综合征的发生率有所降低[相对风险0.83（95%置信区间0.72，0.95）]。
在一项比较含蛋白合成表面活性物质与不含蛋白合成表面活性物质预防RDS的试验中，未发现死亡和慢性肺病在统计学上有不同的临床差异。两组间的临床结局总体相似，尽管接受含蛋白合成表面活性物质的组呼吸窘迫综合征的发生率有所降低。需要进一步开展设计良好的研究，将含蛋白合成表面活性物质与使用更广泛的动物源性表面活性物质提取物进行比较。
