Prognostic value of haemodynamic and neurophysiological assessments in newborns with hypoxic-ischaemic encephalopathy undergoing whole-body therapeutic hypothermia: a systematic review and meta-analysis of short-term outcomes

OBJECTIVE: To evaluate the prognostic value of amplitude-integrated electroencephalography (aEEG), cerebral near-infrared spectroscopy (cNIRS) and targeted neonatal echocardiography (TnECHO) for predicting short-term outcomes in neonates with hypoxic-ischaemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, CINAHL and the Cochrane Library were searched to 16 April 2025. The review was registered on PROSPERO (CRD42023387592). ELIGIBILITY CRITERIA: Prognostic studies of neonates ≥35 weeks' gestation with HIE treated with TH, reporting short-term outcomes: death, abnormal brain MRI or a composite of both. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently. Risk of bias was assessed using the Quality in Prognosis Studies tool. Pooled sensitivity, specificity, diagnostic OR (DOR) and area under the curve (AUC) were calculated using a random-effects model. RESULTS: Thirty-seven studies (n=2836) were included; 26 (n=2268) contributed to meta-analyses. Abnormal aEEG background at 24 hours predicted abnormal MRI with sensitivity 0.76 (95% CI 0.38 to 0.94), specificity 0.70 (95% CI 0.43 to 0.87), DOR 5.91 (95% CI 2.00 to 17.49) and AUC 0.72. Abnormal cNIRS at 48 hours showed comparable prediction with sensitivity 0.77 (95% CI 0.57 to 0.89), specificity 0.61 (95% CI 0.19 to 0.91), DOR 8.38 (95% CI 2.02 to 34.66) and AUC 0.79. TnECHO-detected pulmonary hypertension had limited prognostic value with DOR 2.08 (95% CI 0.36 to 11.9) and AUC 0.62. Right ventricular function measures showed substantial heterogeneity in sensitivity and DOR. CONCLUSIONS: aEEG and cNIRS between 24 hours and 48 hours could offer reasonable prognostic value for detecting brain injury in HIE. TnECHO has limited predictive utility in isolation. Multimodal approaches may enhance early risk stratification and should be explored in future studies.