Supplementary Material for: Blood lactate levels during therapeutic hypothermia and neurodevelopmental outcome or death at 18 -24 months of age in neonates with moderate and severe hypoxic-ischemic encephalopathy

Introduction: Blood lactate levels in neonates with hypoxic ischemic encephalopathy (HIE) vary and their impact on neurodevelopmental outcome is unclear. We assessed blood lactate course over time in neonates with HIE during therapeutic hypothermia and investigated if blood lactate values were associated with neurodevelopmental outcome at two years of age. Methods: This is a retrospective cohort study of neonates with HIE born between 2013-2019, treated at the University Children’s Hospital Zurich. We recorded blood lactate values over time and calculated time until lactate was ≤ 2 mmol/L. Neurodevelopmental outcome was assessed at 18 - 24 months of age using the Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) and categorized as favorable or unfavorable. We investigated associations between blood lactate values and outcome using logistic regression and adjusted for Sarnat stage. Results: 33/45 neonates (69%) had a favorable and 14 (31%) an unfavorable neurodevelopmental outcome. Mean initial lactate values were lower in the favorable (13.9 mmol/L, SD 2.9) versus unfavorable group (17.1 mmol/L, SD 3.2; p= 0.002). Higher initial and maximal blood lactate levels were associated with unfavorable outcome, also when adjusted for Sarnat stage (aOR 1.37; 95% CI 1.01-1.88; p= 0.046 and aOR 1.35; 95% CI 1.01-1.81; p= 0.041, respectively). Conclusion: In neonates with HIE receiving TH initial and maximal blood lactate levels were associated with neurodevelopmental outcome at 18 - 24 months of age also when adjusted for Sarnat stage. Further investigations to analyze blood lactate as a biomarker for prognostic value are needed.

引言：缺氧缺血性脑病（hypoxic ischemic encephalopathy, HIE）新生儿的血乳酸水平存在个体差异，其对神经发育结局的影响尚不明确。本研究旨在评估接受治疗性低体温（therapeutic hypothermia, TH）治疗的HIE新生儿的动态血乳酸变化轨迹，并探讨血乳酸水平与患儿2岁时神经发育结局的关联。方法：本研究为回顾性队列研究，纳入2013-2019年间于苏黎世大学儿童医院接受诊疗的HIE新生儿。研究人员记录了受试者的动态血乳酸水平，并计算血乳酸降至≤2 mmol/L所需的时间。采用贝利婴幼儿发育量表第三版（Bayley Scales of Infant and Toddler Development - Third Edition, BSID-III）在受试者18~24月龄时评估其神经发育结局，并将结局划分为良好与不良两类。采用logistic回归分析血乳酸水平与神经发育结局的关联，并校正萨纳特分期（Sarnat stage）的混杂效应。结果：本研究共纳入45例新生儿，其中33例（69%）神经发育结局良好，14例（31%）结局不良。结局良好组的初始血乳酸平均水平为13.9 mmol/L（标准差2.9），低于结局不良组的17.1 mmol/L（标准差3.2；p=0.002）。在校正萨纳特分期后，更高的初始血乳酸水平与最高血乳酸水平均与不良神经发育结局显著相关：初始血乳酸的校正优势比（aOR）为1.37，95%置信区间（CI）为1.01~1.88（p=0.046）；最高血乳酸的校正优势比为1.35，95%置信区间为1.01~1.81（p=0.041）。结论：在接受治疗性低体温治疗的HIE新生儿中，在校正萨纳特分期后，初始与最高血乳酸水平仍与患儿18~24月龄时的神经发育结局显著相关。未来仍需开展进一步研究，以评估血乳酸作为预后生物标志物的临床价值。