不同起始时间使用咖啡因对极低出生体质量早产儿呼吸暂停防治作用的系统评价

目的：探讨不同起始时间使用咖啡因防治极低出生体质量早产儿呼吸暂停的疗效和安全性。方法：检索PubMed、Cochrane Library、Embase、中国期刊全文数据库（CNKI）、万方数据、生物医学文献（CBM）及维普等数据库，收集各数据库从建库至2020年6月有关极低出生体质量早产儿早期应用咖啡因防治呼吸暂停的病例对照研究，并采用Cochrane系统评价手册5.1.0和Newcastle-Ottawa量表（NOS）对不同类型研究进行质量评价，采用RevMan 5.3进行系统评价。结果：10项文献中，包括5项随机临床对照研究（RCT）和5项回顾性队列研究，文献质量评价结果显示，5项RCT质量等级为B级，5项回顾性队列研究NOS评分为7～9分。共2 665例患儿，其中早期用药组1 515例，晚期用药1 150例。Meta分析结果显示，早期用药组呼吸暂停（AOP）发生率（RR=0.48，95%CI 0.38～0.60，P<0.01）、吸氧时间（SMD=－0.97，95%CI －1.13～－0.80，P<0.01）、机械通气时间（SMD=－0.82，95%CI －1.06～－0.58，P<0.01）、咖啡因用药时间（SMD=－0.42，95%CI －0.56～－0.28，P<0.01）、支气管肺发育不良（BPD）发生率（RR=0.50，95%CI 0.41～0.60，P<0.01）、动脉导管未封闭（PDA）发生率（RR=0.56，95%CI 0.44～0.70，P<0.01）、早产儿视网膜病（ROP）发生率（RR=0.59，95%CI 0.47～0.74，P<0.01）、脑室内出血（IVH）发生率（RR=0.66，95%CI 0.54～0.81，P<0.01）和坏死性小肠结肠炎（NEC）发生率（RR=0.70，95%CI 0.55～0.91，P<0.01）显著低于晚期用药组，而病死率（RR=1.15，95%CI 0.73～1.81，P=0.55）与晚期用药组比较差异无统计学意义。结论：极低出生体质量早产儿早期使用咖啡因能显著降低呼吸暂停发生率、BPD、ROP、PDA、IVH和NEC发生率，减少机械通气、吸氧和咖啡因用药时间，但对病死率无影响。

Systematically Review on Effect of Caffeine at Different Starting Times on Prevention and Treatment of Apnea in Very Low Birth Weight Preterm Infants

Objective: To probe into the clinical efficacy and safety of caffeine at different starting times on prevention and treatment of apnea in very low birth weight preterm infants. Methods: PubMed, the Cochrane Library, EMBase, CNKI, Wanfang, CMB and VIP database were retrieved to collect the case-control study of caffeine at different starting times on prevention and treatment of apnea in very low birth weight preterm infants. The retrieval time was from the establishment of the database to Apr. 2020. Quality of different types of studies was evaluated by using Cochrane Handbook 5.1.0 and Newcastle Ottawa scale (NOS), RevMan 5.3 was used for Meta-analysis. Results: A total of 10 studies were enrolled, including 5 randomized controlled trials (RCT) and 5 retrospective cohort studies. Results of the literature quality evaluation showed that 5 RCT were of grade B, and 5 retrospective cohort studies had the NOS score from 7 to 9 points. A total of 2,665 children were included, with 1,515 cases in the early administration group and 1,150 cases in the late administration group. Meta-analysis showed that the incidence of apnea (AOP) (RR=0.48, 95%CI from 0.38 to 0.60, P<0.01), duration of oxygen inhalation (SMD=-0.97, 95%CI from -1.13 to -0.80, P<0.01), mechanical ventilation time (SMD=-0.82, 95%CI from -1.06 to -0.58, P<0.01), caffeine administration time (SMD=-0.42, 95%CI from -0.56 to -0.28, P<0.01), incidence of bronchopulmonary dysplasia (BPD) (RR=0.50, 95%CI from 0.41 to 0.60, P<0.01), incidence of patent ductus arteriosus (PDA) (RR=0.56, 95%CI from 0.44 to 0.70, P<0.01), incidence of retinopathy of prematurity (ROP) (RR=0.59, 95%CI from 0.47 to 0.74, P<0.01), incidence of intraventricular hemorrhage (IVH) (RR=0.66, 95%CI from 0.54 to 0.81, P<0.01) and incidence of necrotizing enterocolitis (NEC) (RR=0.70, 95%CI from 0.55 to 0.91, P<0.01) in early administration group were significantly lower than that those in late administration group, while the mortality (RR=1.15, 95%CI from 0.73 to 1.81, P=0.55) was not significantly different. Conclusion: Early administration of caffeine in very low birth weight preterm infants can significantly reduce the incidence of AOP, BPD, ROP, PDA, IVH and NEC, and shorten the mechanical ventilation time, duration of oxygen inhalation and caffeine administration time, which has no effect on mortality.