3 - Multimodal Neuromonitoring in Neonatal Hypoxic-Ischemic Encephalopathy and the Association with Neurodevelopmental Outcomes: A Multicenter Study

Publication Number: 1002.3

Celina L. Brunsch, University Medical Center Groningen, Groningen, Groningen, Netherlands; Sara De Crescenzo, Università degli Studi di Bologna- Alma Mater Studiorum, Bologna, Emilia-Romagna, Italy; Linda C.. Meiners, University Medical Center Groningen, Groningen, Groningen, Netherlands; Hendrik Ter Horst, Beatrix children’s hospital, UMCG, GRONINGEN, Groningen, Netherlands; vittoria Paoletti, Neonatal Intensive Care Unit - IRCCS AOUBO, Bologna, Emilia-Romagna, Italy; Claudia Pizzoli, IRCCS ISNB Ausl Bologna, Bologna, Emilia-Romagna, Italy; Duccio Cordelli, University of Bologna, Bologna, Emilia-Romagna, Italy; Monica Maffei, ISNB IRCCS BOLOGNA, BOLOGNA, Emilia-Romagna, Italy; Anne E.. den Heijer, University Medical Center Groningen, Haren, Groningen, Netherlands; Topun Austin, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom; Luigi Corvaglia, IRCCS AOUBO, Bologna, Emilia-Romagna, Italy; Elisabeth M.W.. Kooi, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, Groningen, Netherlands; Silvia Martini, IRCCS AOUBO, Bologna, Emilia-Romagna, Italy

Background: Hypoxic-ischemic encephalopathy (HIE) is still associated with adverse neurodevelopmental outcomes (NDO), despite the use of therapeutic hypothermia. Early clinical prognosis is largely based on magnetic resonance imaging (MRI), which is usually performed after rewarming.

Objective: We aimed to assess whether multimodal neuromonitoring, using near-infrared spectroscopy and amplitude-integrated electroencephalography (aEEG), is associated with cerebral injury on MRI and later NDO.

Design/Methods: Neonates born at >35 weeks gestational age and >1800 gram birth weight undergoing therapeutic hypothermia were included in this prospective-retrospective multicenter study. The aEEG pattern, cerebral tissue oxygenation, burden of hyperoxia, arterial blood pressure, heart rate, and cerebrovascular autoregulation were monitored during therapeutic hypothermia and rewarming, averaged over epochs from 0-24h, 24-48h, 48-72h, and 72-96h. Early cerebral MRI was assessed using a validated quali-quantitative score. NDO was assessed using Bayley Scales of Infant Development (BSID-III) cognitive and motor scores at 24 months.

Results: We included 128 neonates with a median Thompson score of 9. Among the multimodal monitoring modalities, a greater seizure burden (B24-48h = 3.21, 95%CI [2.01, 4.41]), absent sleep-wake-cycling (B24-48h = -5.53, 95%CI [-8.29, -2.77]), and a higher burden of hyperoxia (B0-24h = 0.34, 95%CI [0.07, 0.61]), were associated with worse cerebral injury on MRI. BSID-III cognitive and/or motor scores inversely correlated with aEEG abnormalities, cerebral tissue oxygenation, burden of hyperoxia and the absence of sleep-wake-cycling, whereas higher arterial blood pressures between 0-24h were associated with higher NDO scores.

Conclusion(s): Monitoring of aEEG features, including the seizure burden and the absence of sleep-wake-cycling, and hemodynamic features, especially cerebral hyperoxiam showed a significant association with brain injury on MRI and with later NDO in neonates with HIE. Multimodal monitoring may provide valuable clinical and prognostic information in these patients and could be applied in future studies to identify infants who may benefit most from adjuvant therapies.