新生儿血型不合溶血病丙种球蛋白治疗安全性和有效性的Meta分析

Meta analysis of the effect of immunoglobulin infusion on neonatal isoimmune hemolytic disease caused by blood group incompatibility

目的 新生儿母婴血型不合溶血病仍是新生儿早期高胆红素血症的主要病因,严重者需要光照及交换输血治疗.早期静脉使用丙种球蛋白可以在一定程度上阻断溶血.本研究通过Meta分析评价静脉滴注丙种球蛋白对新生儿血型不合溶血病的治疗作用及安全性.方法 使用相关检索词检索MEDLINE、Cochrane Library、EMBASE、CNKI及CBM数据库,获得关于静脉滴注丙种球蛋白治疗新生儿Rh及ABO血型不合溶血病的临床随机对照试验,采用Review Manager 4.2统计软件对数据进行Meta分析.结果 共纳入6篇文献、456例溶血病新生儿.其中4篇文献纳入Rh血型不合溶血病患儿,共109例;4篇文献纳入ABO血型不合溶血病患儿,共347例.各研究中丙种球蛋白治疗组和对照组新生儿的胎龄、体重及性别等均无统计学差异.静脉滴注丙种球蛋白联合光疗组新生儿相对于单纯光疗组新生儿,平均光疗时间缩短（加权均数差-15.42,95%可信区间-29.00～-1.85）,换血人数比率明显减少（相对危险度0.25,95%可信区间0.17～0.39）,平均住院时间缩短（加权均数差-25.44,95%可信区间-36.93～-13.94）,但是对降低血清最高胆红素值的效果不明显（加权均数差-29.91,95%可信区间-78.24～18.42）,对晚期贫血的发生也无明显作用.没有研究发现静脉应用丙种球蛋白有明显的不良反应.结论 Meta分析支持静脉滴注丙种球蛋白对新生儿血型不合溶血病有一定治疗效果,可缩短光疗时间,减少换血次数,但还需要更严格设计的大样本双盲随机对照试验,并应进行较长期的随访研究.

Objective Neonatal isoimmune hemolytic disease is still one of the major causes of neonatal hyperbilirubinemia.The infants with severe hemolysis even need phototherapy and exchange transfusion.Early intravenous immunoglobulin infusion may block hemolysis to some extent.This study aimed to investigate the efficacy and safety of immunoglobulin infusion on neonatal isoimmune hemolytic disease by meta analysis.Method All randomized controlled trials on the effect of immunoglobulin infusion on neonatal Rh and ABO incompatible hemolytic disease obtained by searching MEDLINE,Cochrane Library,EMBASE,CNKI and CBM were included.Meta analysis was done by Review Manager 4.2software.Results Six trials with totally 456 neonates were included.There were 109 infants with Rh blood group incompatible hemolysis in 4 studies and 347 infants with ABO blood group incompatible hemolysis in 4 studies.There was no significant difference in gestational age,weight and sex between the immunoglobulin infusion and control groups.Compared with those neonates treated with only phototherapy,the infants treated with immunoglobulin and phototherapy had shorter duration of phototherapy（weighted mean difference,WMD - 15.42,95% CI - 29.00 to - 1.85）,less chance to be given exchange transfusion（RR 0.25,95% GI 0.17 to 0.39）and shorter duration of hospitalization（WMD - 25.44,95% GI - 36.93 to- 13.94）.While intravenous immunoglobulin could not decrease the maximum serum bilirubin level（WMD -29.91,95%CI -78.24 to 18.42）.There was no significant difference in the incidence of late anemiabetween the two groups.No adverse reaction was found in neonates who received immunoglobulin.Conclusions The results of this meta analysis support that the intravenous immunoglobulin had some therapeutic effect on neonatal isoimmune hemolytic disease.The infants who received immunoglobulin had shorter duration of phototherapy and less chance to be given exchange transfusion.Well designed,double blind and randomized controlled trials with large sample size and long-term follow-up are needed for further evaluation of the efficacy and safety of the immunoglobulin therapy.