Individualized Neuroprognostication in Neonates With Hypoxic-Ischemic Encephalopathy Treated With Hypothermia
Andrea van Steenis, Mehmet Nevzat Çizmeci, Floris Groenendaal, Marianne Thoresen, Frances M. Cowan, Linda S. de Vries, Sylke J. Steggerda
Abstract
Background and Objectives: To determine whether post-rewarming brain MRI enables individualized domain-specific prediction of neurodevelopmental outcomes at 2 years of age in infants treated with hypothermia for hypoxic-ischemic brain injury. Methods: We conducted a retrospective multicenter study of infants with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) treated with hypothermia. Brain MRI abnormalities and the prediction of domain-specific 2-year neurodevelopmental outcomes were scored independently by 2 investigators after which consensus was reached for both imaging findings and outcome prediction. Neuroimaging patterns were categorized as normal, white matter (WM)/watershed-predominant, deep gray matter (DGM)-predominant, and near-total injury. Outcomes were predicted separately for mortality, cerebral palsy (CP) type and severity, cognitive delay, epilepsy, cerebral visual impairment (CVI), and feeding difficulties; these outcomes were predicted as highly unlikely, possible, probable, or highly likely. Results: Of the 152 study infants, 27 (18%) died. The neurodevelopmental outcome at 2 years was available in all 125 survivors. CP was seen in 21 of 125 surviving infants (17%). No infants in the highly unlikely category developed CP while 90% in the highly likely category did. When CP was predicted as possible, 40% developed CP; all were mild and ambulatory. When CP was predicted as probable, 67% developed CP of whom 40% were severe and nonambulatory. Cognitive scores were available in 104 of 125 infants (83%). Cognitive delay was seen in 23 of 104 infants (22%) (15% mild and 7% severe). When cognitive delay was predicted as highly unlikely, 92% did not develop cognitive delay and the delay was mild in those who did. When cognitive delay was considered highly likely, this developed in 100%. When epilepsy, CVI, and feeding problems were predicted as highly unlikely, 98% did not develop epilepsy; for CVI and feeding problems, this was 100% and 97%, respectively. In 27 of 152 infants (18%), the investigators reached consensus that the overall injury was severe enough to consider redirection of care; 21 of 27 infants (78%) died. Of the survivors, 5 infants developed severe CP and 1 had a mild dyskinetic CP with swallowing problems and CVI. Discussion: Individualized domain-specific categorical neuroprognostication mainly based on brain MRI is feasible, reliable, and highly accurate in infants with HIE.