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Randomized Controlled Trial
. 2025 Apr 1;179(4):383-395.
doi: 10.1001/jamapediatrics.2024.6209.

NICHD Magnetic Resonance Brain Imaging Score in Term Infants With Hypoxic-Ischemic Encephalopathy: A Secondary Analysis of a Randomized Clinical Trial

Seetha Shankaran  1 , Abbot R Laptook  2 , Carolina Guimaraes  3 , Johnathan Murnick  4 , Scott A McDonald  5 , Abhik Das  6 , Carolyn M Petrie Huitema  6 , Athina Pappas  1 , Rosemary D Higgins  7   8 , Susan R Hintz  9 , Kristin M Zaterka-Baxter  5 , Krisa P Van Meurs  9 , Gregory M Sokol  10 , Lina F Chalak  11 , Tarah T Colaizy  12 , Uday Devaskar  13 , Jon E Tyson  14 , Anne Marie Reynolds  15 , Sara B DeMauro  16   17 , Pablo J Sánchez  18 , Matthew M Laughon  3 , Waldemar A Carlo  19 , Kristi Watterberg  20 , Karen M Puopolo  16   17 , Anna Maria Hibbs  21 , Shannon E G Hamrick  22 , C Michael Cotten  23 , John Barks  24 , Brenda B Poindexter  25 , William E Truog  26 , Carl T D'Angio  27 ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
Collaborators, Affiliations
Randomized Controlled Trial

NICHD Magnetic Resonance Brain Imaging Score in Term Infants With Hypoxic-Ischemic Encephalopathy: A Secondary Analysis of a Randomized Clinical Trial

Seetha Shankaran et al. JAMA Pediatr. .

Abstract

Importance: The neonatal brain injury score on magnetic resonance imaging following moderate or severe hypoxic-ischemic encephalopathy developed by the National Institute of Child Health and Human Development Neonatal Research Network has been revised to separate watershed and basal ganglia or thalamic injury and their associated outcomes.

Objective: To evaluate the association of the injury score with outcomes of death or moderate or severe disability among all infants, and with neurodevelopment among survivors in a trial of deeper and longer cooling.

Design, setting, and participants: In this secondary analysis of a multicenter randomized clinical trial, brain imaging was obtained from infants between October 2010 and November 2013. Infants were followed up to 18 months of age, with follow-up completed in January 2016. Data analysis was performed from August 2021 to September 2024.

Interventions: Infants were assigned to 4 hypothermia groups based on depth and duration of cooling, stratified by center and level of encephalopathy in a 2 × 2 factorial design to cooling at 33.5 °C or 32.0 °C and to 72 or 120 hours. A 10-level brain injury score was examined.

Main outcomes and measures: The primary outcome was death or moderate or severe disability measured by the Bayley Scales of Infant and Toddler Development III, the Gross Motor Function Classification System level, vision, and hearing.

Results: This study included 298 infants who had magnetic resonance imaging (MRI) and primary outcome data among 364 infants of the initial cohort (mean [SD] age at MRI, 9.18 [4.49] days). Death or moderate or severe disability occurred in 72 of 298 infants (24%), and disability occurred in 52 of 278 surviving infants (19%). Death or disability occurred in 12 of 28 infants (43%) with any or predominant watershed injury and in 17 of 46 (37%) of those with any or predominant basal ganglia or thalamic injury. Among the 32 infants with hemispheric devastation, 30 (94%) had death or disability, and 17 (89%) survived with moderate or severe disability. Injury scores of increasing severity were associated with death or disability among all infants (odds ratio, 13.66 [95% CI, 7.47-24.95]; area under the curve, 0.84 [95% CI, 0.78-0.90]) and with disability among surviving infants (odds ratio, 10.52 [95% CI, 5.46-20.28]; area under the curve, 0.80 [95% CI, 0.73-0.88]). There were no differences in the injury score between infants undergoing usual care cooling and those cooled to a greater depth or longer duration.

Conclusions: Among infants with hypoxic-ischemic encephalopathy, outcomes were similar between infants with watershed and basal ganglia injury. Higher imaging scores were associated with risk of death or disability among all infants and with neurodevelopmental disability among surviving infants.

Trial registration: ClinicalTrials.gov Identifier: NCT01192776.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Shankaran reported grants from Wayne State University School of Medicine and funding from NICHD during the conduct of the study. Dr Laptook reported grants from NICHD NRN during the conduct of the study. Dr Das reported grants from NICHD and the National Institutes of Health (NIH) during the conduct of the study. Ms Petrie Huitema reported grants from RTI International during the conduct of the study. Dr Pappas reported grants from NICHD NRN during the conduct of the study. Dr Hintz reported grants from NICHD NRN during the conduct of the study. Dr Van Meurs reported grants from NICHD during the conduct of the study. Dr Sokol reported grants from NIH during the conduct of the study. Dr Reynolds reported grants from NIH during the conduct of the study. Dr DeMauro reported grants from NIH during the conduct of the study; and grants from NIH outside the submitted work. Dr Sánchez reported grants from NICHD NRN during the conduct of the study. Dr Laughon reported grants from NIH during the conduct of the study; and grants from NIH and the US Food and Drug Administration outside the submitted work. Dr Watterberg reported grants from NICHD during the conduct of the study. Dr Hibbs reported grants from NICHD NRN and the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Cotten reported grants from NICHD during the conduct of the study; and personal fees from ReAlta Life Sciences and a patent for Cryo-Cell International with royalties paid from Duke University outside the submitted work. Dr Barks reported grants from Wayne State University as a subcontract from Wayne State University to the University of Michigan during the conduct of the study; and grants from NIH to the University of Michigan and grants from University College London as a grant subcontract to the University of Michigan outside the submitted work. No other disclosures were reported.

References

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