Two-Year Neurodevelopmental Outcomes After Mild Hypoxic Ischemic Encephalopathy in the Era of Therapeutic Hypothermia
Two-Year Neurodevelopmental Outcomes After Mild Hypoxic Ischemic Encephalopathy in the Era of Therapeutic Hypothermia
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DOI：
10.1001/jamapediatrics.2019.4011
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发表时间：
2020-01-01
期刊：
影响因子：
26.1
通讯作者：
Hallberg, Boubou
中科院分区：
文献类型：
--
作者：
Finder, Mikael;Boylan, Geraldine B.;Hallberg, Boubou
重要性：治疗性低温降低了中度至重度缺氧缺血性脑病（HIE）婴儿的死亡和残疾风险。到目前为止，治疗性低温的随机临床试验尚未包括轻度HIE婴儿，因为他们认为预后良好。目的验证轻度HIE患儿神经发育结局较健康同龄人差的假设。设计、环境和参与者：对2007年1月至2015年8月在爱尔兰科克和瑞典斯德哥尔摩进行的4项前瞻性队列研究的汇总数据进行分析。数据分析日期为2017年9月至2019年6月。随访时间为18 ~ 42个月。在这项多中心队列研究中，所有儿童均在爱尔兰科克大学妇产医院或瑞典斯德哥尔摩卡罗林斯卡大学医院的三级中心出生或接受治疗。总共有690名儿童符合这项研究的条件。出院时，使用改良的Sarnat评分将所有儿童分为以下5组：健康对照组、围产期窒息（PA）、轻度HIE、中度HIE和重度HIE。使用Bayley婴幼儿发展量表第三版（BSITD-III）评估认知、语言和运动发育。BSITD-III评分被标准化为100（15）的平均值，分数越低表明存在发育迟缓的风险。结果：在690名符合研究条件的儿童中，有471名儿童获得了2年随访数据（随访时平均[SD]年龄为25.6[5.7]个月，男性占54.8%），其中包括152名对照组，185名PA无HIE儿童和134名HIE儿童，其中14名死亡。与对照组相比，轻度HIE婴儿（n=55）的认知综合评分较低，平均（SD）为97.6（11.9）比103.6 (14.6)；粗平均差值为-6.0 (95% CI, -9.9 ~ -2.1)，调整后平均差值为-5.2 （95% CI, -9.1 ~ -1.3）。未经治疗的轻度HIE患儿（n=47）与经治疗性低温治疗的幸存的中度HIE患儿（n=53）的平均认知综合评分无显著差异，轻度与中度的粗平均差异为-2.2 （95% CI, -8.1至3.7）。结论和相关性本研究结果表明，在2岁时，轻度HIE病史儿童的认知综合评分可能低于同期对照组，与治疗性低温治疗的中度HIE幸存者的认知综合评分可能没有显著差异。
IMPORTANCE Therapeutic hypothermia reduces risk of death and disability in infants with moderate to severe hypoxic ischemic encephalopathy (HIE). Randomized clinical trials of therapeutic hypothermia to date have not included infants with mild HIE because of a perceived good prognosis.OBJECTIVE To test the hypothesis that children with mild HIE have worse neurodevelopmental outcomes than their healthy peers.DESIGN, SETTING, AND PARTICIPANTS Analysis of pooled data from 4 prospective cohort studies in Cork, Ireland, and Stockholm, Sweden, between January 2007 and August 2015. The dates of data analysis were September 2017 to June 2019. Follow-up was performed at age 18 to 42 months. In this multicenter cohort study, all children were born or treated at the tertiary centers of Cork University Maternity Hospital, Cork, Ireland, or Karolinska University Hospital, Stockholm, Sweden. In all, 690 children were eligible for this study.EXPOSURES At discharge, all children were categorized into the following 5 groups using a modified Sarnat score: healthy controls, perinatal asphyxia (PA) without HIE, mild HIE, moderate HIE, and severe HIE.MAIN OUTCOMES AND MEASURES Cognitive, language, and motor development were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III). The BSITD-III scores are standardized to a mean (SD) of 100 (15), with lower scores indicating risk of developmental delay.RESULTS Of the 690 children eligible for this study, 2-year follow-up data were available in 471 (mean [SD] age at follow-up, 25.6 [5.7] months; 54.8% male), including 152 controls, 185 children with PA without HIE, and 134 children with HIE, of whom 14 had died. Infants with mild HIE (n=55) had lower cognitive composite scores compared with controls, with a mean (SD) of 97.6 (11.9) vs 103.6 (14.6); the crude mean difference was -6.0 (95% CI, -9.9 to -2.1), and the adjusted mean difference was -5.2 (95% CI, -9.1 to -1.3). There was no significant difference in the mean cognitive composite scores between untreated children (n=47) with mild HIE and surviving children with moderate HIE (n=53) treated with therapeutic hypothermia, with a crude mean difference for mild vs moderate of -2.2 (95% CI, -8.1 to 3.7).CONCLUSIONS AND RELEVANCE This study's findings suggest that, at age 2 years, the cognitive composite scores of children with a history of mild HIE may be lower than those of a contemporaneous control group and may not be significantly different from those of survivors of moderate HIE treated with therapeutic hypothermia.