Background Clinical grading of HIE correlates with outcome. TH improves survival and neurodevelopment in HIE. Aim: To review the effect of TH on the prognostic value of clinical grading of HIE and its course.

Methods Systematic review and meta-analysis of studies on the ability of Sarnat stage at defined times to predict death/disability at ≥18 m in normothermia and TH-treated term neonates with HIE. Pooled risks were estimated, with random effect models, according to HIE stage and treatment.

Results Data on encephalopathy stage at <6 h were available from seven TH trials including 1214 newborns with moderate/severe HIE. Post-hoc studies of two trials (381 infants) provided 72 h data.

The proportion of infants with moderate encephalopathy at <6 h who had poor outcome was 52% (95% CI:44–60; I² = 48%) in normothermia-treated and 35% (95% CI:28–41; I² = 51%) in TH-treated neonates. The proportion for severe encephalopathy was 83% (95% CI:72–93; I² = 81%) in normothermia and 67% (95% CI:58–76; I² = 74%) in TH. At <6 h, the OR for severe vs moderate HIE to predict unfavourable outcome was 4.14 (95% CI:2.40–7.13; I² = 35%) in normothermia and 3.77 (95% CI:2.62–5.41; I² = 0%) in TH.

TH did not affect HIE grade at 72 h. No improvement of encephalopathy at 72 h increased the risk of poor outcome (OR 8.21, 95% CI:2.01–33.6; I² = 74%). The ORs for persistent moderate and severe encephalopathy at 72 h to predict unfavourable outcome were 5.09 (95% CI:1.53–16.92; I² = 66%) and 42.83 (95% CI:13.55–135.37; I² = 44%).

Conclusions While TH has changed the predictive values of initial HIE grades, clinical staging at <6 h correlates with outcome. The course of encephalopathy throughout TH is valuable in outcome prediction.