Association of cerebral metabolic rate following therapeutic hypothermia with 18-month neurodevelopmental outcomes after neonatal hypoxic ischemic encephalopathy.
Association of cerebral metabolic rate following therapeutic hypothermia with 18-month neurodevelopmental outcomes after neonatal hypoxic ischemic encephalopathy.
复制标题
治疗性体温过低后脑代谢率与新生儿低氧缺血性脑病后的18个月神经发育结局的关联。
DOI：
10.1016/j.ebiom.2023.104673
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发表时间：
2023-08
期刊：
影响因子：
11.1
通讯作者：
Grant, Patricia E.
中科院分区：
文献类型：
--
作者：
Sutin, Jason;Vyas, Rutvi;Feldman, Henry A.;Ferradal, Silvina;Hsiao, Chuan-Heng;Zampolli, Lucca;Pierce, Lara J.;Nelson, Charles A.;Morton, Sarah U.;Hay, Susanne;El-Dib, Mohamed;Soul, Janet S.;Lin, Pei-Yi;Grant, Patricia E.
关键词：
治疗性低温（TH）是中度至重度新生儿缺氧缺血性脑病（HIE）的标准治疗，但许多幸存者仍然遭受终身残疾，TH对轻度HIE的益处正在积极辩论中。需要发展对轻度HIE敏感的客观诊断，以选择、指导和评估治疗反应。本研究的目的是确定脑氧代谢（CMRO 2）在TH后的日子是否与18个月的神经发育结果相关，作为评估CMRO 2作为HIE诊断潜力的第一步。次要目的是比较与临床检查的相关性，并研究TH期间CMRO 2与温度之间的关系。这是一项前瞻性、多中心、观察性、队列研究，研究对象为2015年12月至2019年10月期间从波士顿儿童医院、布里格姆妇女医院和贝斯以色列女执事医疗中心的三级新生儿重症监护室（NICU）招募的临床诊断为HIE并接受TH治疗的新生儿，随访至18个月。总共有329例胎龄≥34周的新生儿因围产期窒息和疑似HIE入院。179人被接触，103人入组，73人接受TH，64人入选。在NICU床边通过频域近红外和弥散相关光谱法（FDNIRS-DCS）在低温晚期（C）、复温（RW）和恢复正常体温（NT）后测量CMRO 2。其他变量包括体温和临床新生儿脑病（NE）评分，以及磁共振成像（MRI）和波谱（MRS）的结果。主要结局是18个月时的贝利婴幼儿发育量表第三版（BSID-III），标准（SD）为100（15）。58例新生儿的数据质量足以进行分析。相对于NT时的基线，CMRO 2每℃变化14.4%（95%CI，14.2-14.6），而脑组织氧提取分数（cFTOE）每℃变化仅2.2%（95%CI，2.1-2.4），从C到NT的净变化分别为91%和8%。2例随访数据不完整，33例下降，1例死亡，22例参与者（平均[SD]出生后年龄，19.1 [1.2]个月; 11例女性）患有轻度至中度HIE（中位数[IQR] NE评分，4 [3-6]），21例（95%）在18个月时BSID-III评分>85。NT时的CMRO 2与认知和运动综合评分呈正相关（β（SE）= 4.49（1.55）和2.77（1.00）BSID-III分/10−10 moL/dl × mm 2/s，分别为P = 0.009和P = 0.01;线性回归）;其他指标均与神经发育结局无关。在C和RW期间，NICU中CMRO 2的护理点测量显示出巨大的变化和评估个体对TH反应的潜力。TH后CMRO 2在预测轻度至中度HIE 18个月时的认知和运动结局方面优于常规临床评价（NE评分、cFTOE和MRI/MRS），为HIE提供了有希望的客观、基于生理学的诊断。本临床研究由NIH资助（R 01 HD 076258）。
Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO2) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO2's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO2 and temperature during TH. This was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO2 was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15). Data quality for 58 neonates was sufficient for analysis. CMRO2 changed by 14.4% per °C (95% CI, 14.2–14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1–2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3–6]) and 21 (95%) with BSID-III scores >85 at 18 months. CMRO2 at NT was positively associated with cognitive and motor composite scores (β (SE) = 4.49 (1.55) and 2.77 (1.00) BSID-III points per 10−10 moL/dl × mm2/s, P = 0.009 and P = 0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes. Point of care measures of CMRO2 in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO2 following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE. This clinical study was funded by an NIH grant from the (R01HD076258).
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影响因子：
2.1
作者：
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通讯作者：
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DOI：
10.1016/j.jpeds.2019.11.030
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The Journal of pediatrics
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