Supplementary Material for: Clinical Prediction Models and Predictors for Death or Adverse Neurodevelopmental Outcome in Term Newborns with Hypoxic-Ischemic Encephalopathy: A Systematic Review of the Literature

Background: Although many predictive parameters have been studied, an internationally accepted, validated predictive model to predict the clinical outcome of asphyxiated infants suffering from hypoxic-ischemic encephalopathy is currently lacking. The aim of this study was to identify, appraise and summarize available clinical prediction models, and provide an overview of all investigated predictors for the outcome death or neurodevelopmental impairment in this population. Methods: A systematic literature search was performed in Medline and Embase. Two reviewers independently included eligible studies and extracted data. The quality was assessed using PROBAST for prediction model studies and QUIPS assessment tools for predictor studies. Results: A total of nine prediction models were included. These models were very heterogeneous in number of predictors assessed, methods of model derivation, and primary outcomes. All studies had a high risk of bias following the PROBAST assessment and low applicability due to complex model presentation. A total of 104 predictor studies were included investigating various predictors, showing tremendous heterogeneity in investigated predictors, timing of predictors, primary outcomes, results, and methodological quality according to QUIPS. Selected high-quality studies with accurate discriminating performance provide clinicians and researchers an evidence map of predictors for prognostication after HIE in newborns. Conclusion: Given the low methodological quality of the currently published clinical prediction models, implementation into clinical practice is not yet possible. Therefore, there is an urgent need to develop a prediction model which complies with the PROBAST guideline. An overview of potential predictors to include in a prediction model is presented.

背景：尽管已有诸多预测参数得到研究，但目前仍缺乏国际公认且经过验证的预测模型，用以预测罹患缺氧缺血性脑病（hypoxic-ischemic encephalopathy, HIE）的窒息新生儿的临床转归。本研究旨在识别、评价并汇总现有临床预测模型，全面梳理该人群中与死亡或神经发育障碍（neurodevelopmental impairment）转归相关的所有已研究预测因子。
方法：系统检索Medline及Embase数据库。由2名评价者独立筛选符合纳入标准的研究并提取数据；采用PROBAST（预测模型研究偏倚风险评估工具）评估预测模型类研究的质量，采用QUIPS（预后研究质量评价工具）评估预测因子类研究的质量。
结果：最终纳入9项预测模型研究。这些模型在评估的预测因子数量、模型构建方法及主要结局指标方面均存在显著异质性。经PROBAST评估，所有研究均存在较高偏倚风险，且因模型呈现形式复杂导致适用性较低。共纳入104项预测因子研究，涵盖各类预测因子，依据QUIPS评估结果，其在研究的预测因子类型、检测时机、主要结局指标、研究结果及方法学质量方面均存在极大异质性。经筛选的高质量、区分性能优异的研究可为临床医师及研究者提供新生儿缺氧缺血性脑病（HIE）后预后评估相关预测因子的证据图谱。
结论：鉴于当前已发表的临床预测模型方法学质量较低，目前尚无法应用于临床实践。因此，亟需开发符合PROBAST指南规范的预测模型。本研究同时梳理了可纳入预测模型的潜在预测因子清单。