亚低温治疗新生儿缺氧缺血性脑病临床效果的Meta分析

目的总结国内外亚低温治疗新生儿缺氧缺血性脑病（HIE）的研究结果，采用Meta分析方法评价亚低温治疗HIE的临床疗效，探讨亚低温治疗HIE的可行性。方法制定原始文献的纳入标准、排除标准及检索策略，检索PubMed、EMBASE、Ovid、Springer、中国期刊全文数据库、万方数据库及维普中文科技期刊数据库等，获得亚低温治疗HIE的相关文献。使用Cochrane中心推荐的方法进行文献质量评价，采用RevMan 4.22软件对满足纳入标准的有关亚低温治疗HIE的RCT文献进行Meta分析。以病死率、严重神经系统发育障碍（脑瘫、发育迟缓、失明和听力损害）发生率和不良反应发生率作为观察指标，进行定性和定量综合评估。结果共检索到846篇文献，符合纳入标准的9项RCT研究（16篇文献）进入Meta分析，纳入研究均未采用盲法，文献质量评价7项RCT研究为A级，2项为C级，漏斗图检验提示无发表偏倚。Meta分析结果显示，亚低温组和对照组比较：病死率显著降低（RR=0.73，95%CI：0.58~0.91）；随访至18月龄时严重神经系统发育障碍发生率显著降低（RR=0.70，95%CI：0.53~0.92）；脑瘫发生率显著降低（RR=0.72，95%CI：0.53~0.98）；发育迟缓（RR=0.73，95%CI：0.53~0.99）、失明（RR=0.57，95%CI：0.30~1.08）和听力损害（RR=1.52，95%CI：0.71~3.25）发生率差异无统计学意义；不良反应发生率：窦性心动过缓（RR=6.35，95%CI：2.16~18.68）和PLT减少（RR=1.55，95%CI：1.14~2.11）发生率升高，需要治疗的心律失常、凝血功能异常导致的血栓或出血、脓毒症和惊厥发生率差异无统计学意义。结论亚低温治疗可降低HIE患儿的病死率，改善神经系统发育障碍，且具有较好的安全性。

Meta-analysis of clinical efficacy and safety of hypothermia for neonates with hypoxic ischemic encephalopathy

Objective To evaluate the efficacy of therapeutic hypothermia on mortality, long-term neuredevelopmental disability and clinical major side effects in eneephalopathie asphyxiated newborn infants. We summarized the data of hypoxic ischemic encephalopathy (HIE) newborns who were treated with mild hypothermia using meta-analysis method. Methods The standard search strategy of the Neonatal Review Group as outlined in the Cochrane Library ( Issue 2, 2007) was used. RCTs evaluating therapeutic hypothermia in newborns with hypoxic ischemic eneephalopathy were identified by searching the PubMed, EMBASE, Ovid, Springer and CNKI database with the terms "Infant or neonate and asphyxia or hypoxie-ischemic encephalopathy and hypothermia". No language restrictions were applied. RCTs comparing the usage of therapeutic hypothermia with standard care in eneephalopathic newborn infants with evidence of peripartum asphyxia and without recognizable major congenital anomalie s wereincluded. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and other indicators of neurodevelopmental outcome. Two review authors independently selected, assessed the quality of the included studies and extracted data. Authors were contacted for further information. Meta-analysis was performed using relative risk and risk difference for dichotomous data with 95% confidence intervals. Results Nine trials involving 785 neonates were included in the analysis. Cooling techniques and the definition and severity of neuredevelopmental disability differed among studies. Overall, there was evidence of a significant effect of therapeutic hypothermia on the outcomes of mortality ( RR = 0.73, 95% CI: 0. 58 - 0.91 ) and neuredevelopmental disability at 18 to 22 months ( RR = 0. 70,95% CI : 0. 53 - 0. 92). Moreover, hypothermia significantly decreased the incidence of disabling cerebral palsy (RR =0. 72, 95% CI: 0. 53 -0.98).However, hypothermia had no effect on developmental delay ( BR = O. 73, 95% CI : 0.53 - 0.99), blindness ( RR = 0.57, 95% CI: 0.30 - 1.08) and hearing loss ( RR = 1.52, 95% CI: 0.71 - 3.25 ) in newborns with HIE. Adverse effects included benign sinus bradycardia ( RR =6.35, 95% CI: 2. 16 - 18.68 ) and thrombocytopenia ( RR = 1.55, 95% CI: I. 14 - 2. 11 ) without deleterious consequences. Conclusions In general, therapeutic hypothermia seemed to have a beneficial effect on the outcome of neonates with moderate to severe hypoxic ischemic encephalopathy. Despite the methodological differences between trials, wide confidence intervals, and the lack of follow-up data beyond the second year of life, the consistency of the results is encouraging. Further research is necessary to minimize the uncertainty regarding efficacy and safety of any specific technique of cooling for any specific population.