Table 2.
The accuracy of MR biomarkers in neonates with neonatal encephalopathy (NE) as predictors of the combined outcome of death and neurodevelopmental disability at 18–30 months of age.
| Scoring System/ Abnormality |
Biomarker cutoff | Design | Ref | Therapy | AUROC (95% CI) |
Sensitivity | Specificity | PPV | NPV |
|---|---|---|---|---|---|---|---|---|---|
| Barkovich (BGT/WS score) | |||||||||
| Any MRI abnormality | BGT or WS ≥ 1 | Prospective, observational | [131] | No TH | 0.63 (0.57–0.68) | 0.92 | 0.33 | 0.44 | 0.88 |
| TH | 0.68 (0.56–0.81) | 0.73 | 0.63 | 0.19 | 0.95 | ||||
| BGT | BGT ≥ WS | No TH | 0.87 | 0.70 | 0.68 | 0.88 | |||
| TH | 0.69 | 0.88 | 0.45 | 0.95 | |||||
| Watershed | WS > BGT | No TH | 0.83 | 0.39 | 0.30 | 0.88 | |||
| TH | 0.33 | 0.69 | 0.05 | 0.95 | |||||
| Rutherford | |||||||||
| PLIC | PLIC equivocal or abn. | Prospective, observational | [42] | No TH | 0.9 | 1.0 | 1.0 | 0.87 | |
| Any mod or severe abnormal. | BGT ≥ 2; WMI = 3 or PLIC | Prospective, RCT substudy | [94] | No TH | 0.81 (0.71–0.91) | 0.94 | 0.68 | 0.74 | 0.92 |
| TH | 0.84 (0.74–0.94) | 0.88 | 0.82 | 0.76 | 0.91 | ||||
| NICHD NRN | Any abn (MRI > 0) | Prospective RCT substudy | [95] | Mixed | 0.90 | 0.65 | 0.62 | 0.91 | |
| Wash U | Total score > 10.5 | Prospective, observational | [96] | TH | 0.72 (0.57–0.86) | 0.77 | 0.46 | 0.47 | 0.76 |
| Weeke | |||||||||
| GM* + MRS | GM w/MRS ≥ 11.5 | Retrospective, multicenter | [97] | TH (Cohort 1) | 0.989 (0.973–1.0) | 0.923 | 0.953 | 0.889 | 0.968 |
| GM* | GM ≥ 9.5 | TH (Cohort 1) | 0.988 (0.973–1) | 0.923 | 0.958 | 0.889 | 0.971 | ||
| TH (Cohort 2) | 0.832 (0.708–0.955) | 0.421 | 0.982 | 0.889 | 0.836 | ||||
| MARBLE | |||||||||
| BGT | BGT ≥ 1# | Prospective, multicenter, observational | [74] | TH | 0.81 (0.75–0.87) | 0.71 | 0.88 | 0.54 | 0.94 |
| Cortex | WS ≥ 1# | 0.67 (0.60–0.73) | 0.48 | 0.81 | 0.33 | 0.89 | |||
| PLIC | PLIC ≥ 1 | 0.82 (0.76–0.87) | 0.71 | 0.90 | 0.58 | 0.94 | |||
| Lac/NAA | Lac/NAA > 0.22 | 0.94 (0.89–0.97) | 0.88 | 0.90 | 0.64 | 0.98 | |||
| NAA | NAA ≤ 5.6 mmol/kg | 0.99 (0.94–1.0) | 1.0 | 0.97 | 0.86 | 1.0 |
Notes:
GM as defined in Weeke scoring system includes BGT, PLIC, brainstem, perirolandic and hippocampus.
MARBLE utilized the Rutherford scoring system above for characterizing BGT and cortical injury on MRI, but applied a different cutoff.
Abbreviations: BGT, Basal Ganglia – Thalamus; GM, gray matter; MARBLE, Magnetic Resonance Biomarkers in Neonatal Encephalopathy; NAA, N-acetylaspartate; NICHD, National Institute of Child Health and Human Development; NRN, Neonatal Research Network; PLIC, posterior limb of the internal capsule; WS, watershed NAA, N-acetylaspartate