Supplementary Material for: Are Simple Magnetic Resonance Imaging Biomarkers Predictive of Neurodevelopmental Outcome at Two Years in Very Preterm Infants?

Background: Preterm infants are at increased risk of neurodevelopmental impairment due to the vulnerability of the immature brain. Early risk stratification is necessary for predicting outcome in the period of highest neuroplasticity. Several biomarkers in magnetic resonance imaging (MRI) at term equivalent age (TEA) have therefore been suggested. Objective: To assess the predictive value of simple brain metrics and the total abnormality score (TAS) – a modified score for brain injury and growth – in relation to neurodevelopmental outcome of very preterm infants in MRI at TEA. Methods: Single-centre cohort study including preterm infants with gestational age (GA) ≤32 weeks and birth weight ≤1,500 g. Biparietal width (BPW), interhemispheric distance, transcerebellar diameter (TCD) and TAS were assessed. To detect subtle haemorrhages, additional susceptibility-weighted imaging (SWI) was used in addition to conventional MRI to evaluate its clinical relevance. Neurodevelopment was tested by the Mental and Psychomotor Developmental Index (MDI/PDI) of the Bayley Scales of Infant Development II at a corrected age of 24 months. Results: One hundred twenty-nine children with median GA of 28.1 weeks and median birth weight of 980 g were included. BPW significantly correlated with PDI (p= 0.01, R2 = 0.06) and TCD with MDI (p < 0.01, R2 = 0.05) and PDI (p < 0.01, R2 = 0.06) but explained variances were low. TAS was not predictive of neurodevelopmental outcome. By using SWI, additional 4 cases of low grade haemorrhages were identified compared to conventional sequences. In one case this additional information was clinically relevant (MDI/PDI below average). Conclusion: Simple brain metrics and TAS did not reliably predict neurodevelopmental outcome in a cohort with low prevalence of high grade brain injury. The additional value of SWI is yet to be determined in larger cohorts. The combination of imaging and functional biomarkers may be advisable for the prediction of neurodevelopmental outcome.

背景：由于未成熟大脑的脆弱性，早产儿罹患神经发育障碍（neurodevelopmental impairment）的风险显著升高。在神经可塑性最高的时期开展早期风险分层，对预测预后至关重要。因此，学界已提出多项基于校正胎龄（term equivalent age, TEA）时磁共振成像（magnetic resonance imaging, MRI）的生物标志物。
研究目的：评估校正胎龄时磁共振成像中，简易脑测量指标与总异常评分（total abnormality score, TAS）——一种针对脑损伤与脑发育的改良评分——对极早产儿神经发育结局的预测价值。
研究方法：本研究为单中心队列研究，纳入胎龄（gestational age, GA）≤32周、出生体重≤1500g的早产儿。对双顶骨间径（biparietal width, BPW）、半球间距离、小脑上径（transcerebellar diameter, TCD）以及总异常评分进行评估。为检测隐匿性出血，本研究在常规磁共振成像基础上额外采用磁敏感加权成像（susceptibility-weighted imaging, SWI），以评估其临床相关性。在校正年龄24月龄时，采用贝利婴儿发育量表第二版（Bayley Scales of Infant Development II）的精神发育指数（Mental Developmental Index, MDI）与精神运动发育指数（Psychomotor Developmental Index, PDI，合称MDI/PDI）对受试者的神经发育状况进行测评。
研究结果：本研究共纳入129例受试者，其胎龄中位数为28.1周，出生体重中位数为980g。双顶骨间径与精神运动发育指数呈显著相关（p=0.01，R²=0.06）；小脑上径与精神发育指数（p<0.01，R²=0.05）及精神运动发育指数（p<0.01，R²=0.06）均呈显著相关，但解释的变异度均较低。总异常评分无法有效预测神经发育结局。相较于常规磁共振序列，磁敏感加权成像额外检出4例轻度出血病例，其中1例的额外检出信息具有临床意义（该受试者精神发育指数与精神运动发育指数均低于平均水平）。
研究结论：在重度脑损伤患病率较低的队列中，简易脑测量指标与总异常评分无法可靠预测神经发育结局。磁敏感加权成像的额外临床价值仍需在更大样本的队列中进一步验证。未来可考虑结合影像学指标与功能生物标志物，以实现神经发育结局的精准预测。