不同时间窗全身亚低温治疗新生儿缺氧缺血性脑病疗效观察

The efficacy of systemic hypothermia therapy initiated at different times on neonatal hypoxic-ischemic encephalopathy

目的探讨不同时间窗全身亚低温治疗新生儿缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)患儿的临床效果、安全性及近期预后。方法回顾性分析2013年1月至2018年8月湖南省儿童医院新生儿重症监护病房收治的生后12 h内入院、诊断新生儿中重度HIE并完成治疗的足月新生儿,根据亚低温治疗开展情况分为生后6 h内亚低温组(TH1组)、6~12 h亚低温组(TH2组)和常规治疗组(对照组)。收集3组患儿围产期和住院期间临床资料及6个月时的随访资料,应用SPSS 25.0统计软件对数据进行分析,比较不同时间窗亚低温治疗与常规治疗患儿的转归及近期神经发育结局。结果共纳入147例中重度HIE患儿,111例完成72 h亚低温治疗,TH1组79例,TH2组32例,对照组36例。日龄10 d左右时TH1组新生儿神经行为测定评分高于对照组,差异有统计学意义(P<0.05);TH2组与TH1组和对照组比较,差异均无统计学意义(P>0.05)。TH1组和TH2组颅脑MRI损伤情况均轻于对照组,差异有统计学意义(P<0.05);TH1和TH2组差异无统计学意义(P>0.05)。随访至6个月时,100例患儿完成了贝利婴幼儿智能发展量表检查,21例异常,3组患儿运动发育指数分布差异无统计学意义(P>0.05);TH1组和TH2组智力发育指数<70分比例低于对照组,差异有统计学意义(P<0.05);TH1组和TH2组智力发育指数比较,3组PDI比较,差异均无统计学意义(P>0.05)。6个月时对照组病死率(32.1%,9/28)高于TH1组(6.6%,4/61),差异有统计学意义(P<0.05);TH2组与TH1组和对照组比较,差异均无统计学意义(P>0.05)。结论HIE患儿的全身亚低温治疗是安全的,延长HIE患儿亚低温治疗时间窗至生后6~12 h仍能在一定程度上降低患儿病死率、改善神经发育结局。

Objective To study the clinical efficacy,safety and prognosis of systemic hypothermia therapy on neonatal hypoxic-ischemic encephalopathy(HIE)initiated at different times after birth.Method From January 2013 to August 2018,term neonates(within 12 hours after birth)diagnosed with neonatal moderate to severe HIE and received systemic treatment in the neonatal intensive care unit of our hospital were retrospectively included.According to the starting time of hypothermia therapy,the neonates were assigned into three groups:within 6 h after birth(TH1 group),6〜12 h(TH2 group)and conventional treatment group(control group).Their clinical data during perinatal period,hospitalization period and follow-up at 6-month were reviewed.Their clinical and neurodevelopmental outcomes were compared using SPSS 25.0 statistical software.Result A total of 147 neonates with moderate to severe HIE were enrolled.Ill received 72-hour hypothermia therapy,including 79 in the TH1 group;32 in the TH2 group and 36 in the control group.The neurobehavioral test scores at 10-day of life in the TH1 group were significantly higher than the control group(P<0.05).No significant differences existed among the TH2 group,the TH1 group and the control group(P>0.05).The brain magnetic resonance imaging(MRI) showed injuries in the TH1 group and the TH2 group were significantly milder than the control group(P<0.05).No significant differences of brain injuries existed between TH1 group and TH2 group(P>0.05).100 patients completed Bailey Infant Intelligence Development Scale at 6-month follow-up.21 had abnormal scores.No statistically significant differences existed in the psychomotor development index(PDI)scores among the three groups(P>0.05).TH1 and TH2 groups had significantly fewer cases with mental development index(MDI)<70 points than the control group(P<0.05).No statistically significant differences existed of MDI scores between the TH1 group and the TH2 group(P>0.05).No statistically significant differences existed of PDI scores among the 3 groups(P>0.05).At 6-month,the mortality rate of the control group(32.1%,9/28)was significantly higher than the TH1 group(6.6%,4/61)(P<0.05).No significant differences existed of mortality rate at 6-month among the TH2 group,the TH1 group and the control group(P>0.05).Conclusion Systemic hypothermia therapy for neonatal HIE is safe.Starting systemic hypothermia therapy at 6-12-hour after birth may also be effective in reducing mortality rate and improving neurodevelopmental outcome.