预防性应用茶碱类药物对围生期窒息后新生儿肾功能影响的Meta分析

Prophylactic Use of Theophylline on the Prevention of Renal Dysfunction in after Perinatal Asphyxia Neonates:a Meta-analysis

目的系统性评价预防性应用茶碱(ThP)类药物对围生期窒息(PA)后新生儿肾功能异常(RD)的影响。方法计算机检索Pub Med、Medline、Web of Science、Cochrane图书馆、中国生物医学文献数据库、中国知网和万方数据知识服务平台,检索时间为建库至2017-07-31,收集关于PA后新生儿预防性应用ThP类药物干预评价RD的随机对照试验,对纳入文献进行质量评价和数据提取,采用Rev Man 5.2.6软件对RD发生率、血肌酐(Scr)水平、肾小球滤过率(GFR)、尿β2微球蛋白(β2M)水平、病死率进行分析。结果共纳入6篇文献,378例患儿,其中干预组190例,对照组188例。纳入文献均为中度偏倚文献。Meta分析结果显示,干预组RD发生率低于对照组[RR=0.35,95%CI(0.25,0.49),P<0.000 01]。干预组第1天Scr水平与对照组比较,差异无统计学意义[WMD=0,95%CI(-0.08,0.07),P=0.910 00];干预组第3、5天Scr水平均低于对照组[WMD=-0.57,95%CI(-0.68,-0.46),P<0.000 01;WMD=-0.35,95%CI(-0.53,-0.16),P=0.000 20]。干预组第1天GFR与对照组比较,差异无统计学意义[WMD=1.68,95%CI(-1.05,4.41),P=0.230 00];干预组第3、5天GFR均高于对照组[WMD=14.30,95%CI(11.73,16.87),P<0.000 01;WMD=10.59,95%CI(7.72,13.47),P<0.000 01]。干预组第1天尿β2M水平低于对照组[WMD=-7.23,95%CI(-8.65,-5.81),P<0.000 01]。干预组病死率与对照组比较,差异无统计学意义[RR=0.92,95%CI(0.54,1.55),P=0.750 00]。干预剂量为8、5 mg/kg的干预组RD发生率均低于对照组[RR=0.37,95%CI(0.22,0.62),P=0.000 20;RR=0.34,95%CI(0.22,0.52),P<0.000 01]。RD发生率的漏斗图左右对称性可,未见明显发表偏倚。结论预防性应用ThP类药物对PA后新生儿肾功能具有保护作用,但由于样本量不足及缺乏远期神经系统评价,目前仍不能常规应用于临床。

Objective To systematically assess the effect of prophylactic use of theophylline（ThP） for the prevention of renal dysfunction（RD） in after perinatal asphyxia（PA）neonates.Methods We searched Pub Med,Medline,Web of Science,Cochrane Library,CBM,CNKI and Wanfang Data Knowledge Service Platform databases for randomized controlled trials assessing the effect of prophylactic use of ThP for the prevention of RD in neonates after PA collected as of July 31,2017.We assessed the quality of the included articles and extracted needed information from them.Incidence of RD,serum creatinine（Scr） level,glomerular filtration rate（GFR）,urinary β2-microglobulin（β2M） level and fatality rate were analyzed by Rev Man 5.2.6 software.Results Six randomized controlled trials with moderate biases were included.Three hundred and seventy-eight neonates receiving either ThP（intervention group,n=190） or placebo（control group,n=188） were analyzed.Compared with placebo,ThP treatment was associated with lower incidence of RD[RR=0.35,95%CI（0.25,0.49）,P〈0.000 01].Scr level was similar on the 1 st day after PA[WMD=0,95%CI（-0.08,-0.07）,P=0.910 00]betweengroups but declined on the 3 rd and 5 th days after PA in the intervention group [WMD=-0.57,95%CI（-0.68,-0.46）,P〈0.000 01;WMD=-0.35,95%CI（-0.53,-0.16）,P=0.000 20,respectively].GFR showed no difference between groups on the 1 st day after PA[WMD=1.68,95%CI（-1.05,4.41）,P=0.230 00],but it was significantly higher on the 3 rd and 5 th days after PA in intervention group than those in the control group[WMD=14.30,95%CI（11.73,16.87）,P〈0.000 01;WMD=10.59,95%CI（7.72,13.47）,P〈0.000 01,respectively].ThP treatment was associated with lower level of urinary β2M on the 1st day after PA[WMD=-7.23,95%CI（-8.65,-5.81）,P〈0.000 01].There was no significant difference in fatality rate between two groups [RR=0.92,95%CI（0.54,1.55）,P=0.750 00].Both 8 mg/kg and 5 mg/kg ThP significantly decreased the incidence of RD [RR=0.37,95%CI（0.22,0.62）,P=0.000 20;RR=0.34,95%CI（0.22,0.52）,P〈0.000 01].The funnel plot graph of incidence of RD showed good symmetry,indicating no obvious publishing bias.Conclusion Prophylactic use of ThP has a protective effect on preventing after PA neonatal RD.However,due to the limitation of sample size and without evaluation of long-term neurodevelopmental outcome,it is not yet to recommend the routine prophylactic use of ThP in after PA neonates.