Haemodynamic and neurophysiological assessments for 2-year outcome prediction in neonates with hypoxic-ischaemic encephalopathy treated with therapeutic hypothermia: a systematic review and meta-analysis

Objective To evaluate the prognostic accuracy of amplitude-integrated electroencephalography (aEEG), cerebral near-infrared spectroscopy (cNIRS) and targeted neonatal echocardiography (TnECHO) for predicting 2-year outcomes (neurodevelopment and/or death) in infants with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). Design Systematic review and meta-analysis. Data sources MEDLINE, Embase, CINAHL and the Cochrane Library (2002–16 April 2025). PROSPERO registration: CRD42023387592. Eligibility criteria Prognostic studies including infants ≥35 weeks’ gestation with HIE treated with whole-body TH and reporting neurodevelopmental impairment at 18–24 months and/or death. Data extraction and synthesis Data were extracted independently. Risk of bias was assessed using Quality in Prognosis Studies. Pooled sensitivity, specificity, diagnostic ORs (DORs) and area under the curve (AUC) estimates were calculated using random-effects models. Results 37 studies (n=2721) were included; 24 (n=1989) contributed to meta-analysis. Abnormal aEEG background at 36 hours predicted adverse 2-year outcomes with sensitivity 0.83 (95% CI 0.70 to 0.92), specificity 0.88 (95% CI 0.79 to 0.93), DOR 33.06 (95% CI 12.87 to 84.94), AUC (0.88). Absence of sleep–wake cycling had high specificity 0.93 (95% CI 0.88 to 0.96), DOR 30.19 (95% CI 14.47 to 63.01) and AUC 0.88. Abnormal cNIRS demonstrated potential prognostic value at 36–48 hours with specificity 0.97 (95% CI 0.13-1.00), DOR 26.74 (95% CI 4.55 to 157.14) and AUC (0.86) at 36 hours. Acute pulmonary hypertension showed low overall discrimination, DOR 2.17 (95% CI 1.35 to 3.47) and (AUC 0.40). Right ventricular dysfunction showed higher specificity but substantial heterogeneity. Conclusions Abnormal aEEG background at 36 hours provides reliable bedside prognostic information for 2-year outcomes in HIE. cNIRS may offer complementary value, whereas there is limited evidence supporting the utility of TnECHO alone. Multimodal methods may improve early prognostication.