Early Magnetic Resonance Imaging Predicts 30-Month Outcomes after Therapeutic Hypothermia for Neonatal Encephalopathy

Ashley M Bach; Annie Y Fang; Sonia Bonifacio; Elizabeth E Rogers; Aaron Scheffler; J Colin Partridge; Duan Xu; A James Barkovich; Donna M Ferriero; Hannah C Glass; Dawn Gano

doi:10.1016/j.jpeds.2021.07.003

Early Magnetic Resonance Imaging Predicts 30-Month Outcomes after Therapeutic Hypothermia for Neonatal Encephalopathy

J Pediatr. 2021 Nov:238:94-101.e1. doi: 10.1016/j.jpeds.2021.07.003. Epub 2021 Jul 6.

Authors

Affiliations

¹ Departments of Neurology and Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Pediatrics, University of California-San Francisco, San Francisco, CA; Department of Neurology, University of California-San Francisco, San Francisco, CA.
² Department of Pediatric Hospital Medicine, Kaiser Permanente, Oakland, CA.
³ Department of Pediatrics, Stanford University, Palo Alto, CA.
⁴ Department of Pediatrics, University of California-San Francisco, San Francisco, CA.
⁵ Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA.
⁶ Department of Radiology, University of California-San Francisco, San Francisco, CA.
⁷ Department of Pediatrics, University of California-San Francisco, San Francisco, CA; Department of Neurology, University of California-San Francisco, San Francisco, CA.
⁸ Department of Pediatrics, University of California-San Francisco, San Francisco, CA; Department of Neurology, University of California-San Francisco, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA.

PMID: 34237346
DOI: 10.1016/j.jpeds.2021.07.003

Abstract

Objective: To evaluate the association of therapeutic hypothermia with magnetic resonance imaging (MRI) findings and 30-month neurodevelopment in term neonatal encephalopathy.

Study design: Cross-sectional analysis of 30-month neurodevelopment (IQR 19.0-31.4) in a prospective cohort of mild-to-severe neonatal encephalopathy imaged on day 4 (1993-2017 with institutional implementation of therapeutic hypothermia in 2007). MRI injury was classified as normal, watershed, or basal ganglia/thalamus. Abnormal motor outcome was defined as Bayley-II psychomotor developmental index <70, Bayley-III motor score <85 or functional motor deficit. Abnormal cognitive outcome was defined as Bayley-II mental developmental index <70 or Bayley-III cognitive score <85. Abnormal composite outcome was defined as abnormal motor and/or cognitive outcome, or death. The association of therapeutic hypothermia with MRI and outcomes was evaluated with multivariable logistic regression adjusted for propensity to receive therapeutic hypothermia.

Results: Follow-up was available in 317 (78%) surviving children, of whom 155 (49%) received therapeutic hypothermia. Adjusting for propensity, therapeutic hypothermia was independently associated with decreased odds of abnormal motor (OR 0.15, 95% CI 0.06-0.40, P < .001) and cognitive (OR 0.11, 95% CI 0.04-0.33, P < .001) outcomes. This association remained statistically significant after adjustment for injury pattern. The predictive accuracy of MRI pattern for abnormal composite outcome was unchanged between therapeutic hypothermia-treated (area under the receiver operating curve 0.76; 95% CI 0.61-0.91) and untreated (area under the receiver operating curve 0.74; 95% CI 0.67-0.81) infants. The negative predictive value of normal MRI was high in therapeutic hypothermia-treated and untreated infants (motor 96% vs 90%; cognitive 99% vs 95%).

Conclusions: Therapeutic hypothermia is associated with lower rates of brain injury and adverse 30-month outcomes after neonatal encephalopathy. The predictive accuracy of MRI in the first week of life is unchanged by therapeutic hypothermia. Normal MRI remains reassuring for normal 30-month outcome after therapeutic hypothermia.

Keywords: hypoxic-ischemic encephalopathy; neonatal neurology; neurodevelopmental outcome.

MeSH terms

Adult
Child, Preschool
Cross-Sectional Studies
Female
Humans
Hypothermia, Induced / methods*
Hypoxia-Ischemia, Brain / diagnostic imaging*
Hypoxia-Ischemia, Brain / therapy
Infant
Infant, Newborn
Infant, Newborn, Diseases / diagnostic imaging
Infant, Newborn, Diseases / therapy
Magnetic Resonance Imaging
Male
Neurodevelopmental Disorders / prevention & control*
Predictive Value of Tests
Pregnancy
Prospective Studies