Proton magnetic resonance spectroscopy lactate/N-acetylaspartate within 2 weeks of birth accurately predicts 2-year motor, cognitive and language outcomes in neonatal encephalopathy after therapeutic hypothermia

Arch Dis Child Fetal Neonatal Ed. 2019 Jul;104(4):F424-F432. doi: 10.1136/archdischild-2018-315478. Epub 2018 Oct 15.

Abstract

Objective: Brain proton (1H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) 1H MRS Lac/NAA for the prediction of Bayley III outcomes at 2 years using optimised metabolite fitting (Tarquin) with threonine and total NAA; (2) prediction of motor outcome with diffusion-weighted MRI; (3) BGT Lac/NAA correlation with the National Institute of Child Health and Human Development (NICHD) MRI score.

Subjects and methods: 55 (16 inborn, 39 outborn) infants at 39w+5 d (35w+5d-42w+0d) with NE admitted between February 2012 and August 2014 to University College London Hospitals for therapeutic hypothermia underwent MRI and 1H MRS at 3T on day 2-14 (median day 5). MRIs were scored. Bayley III was assessed at 24 (22-26) months.

Results: 16 babies died (1 inborn, 15 outborn); 20, 19 and 21 babies had poor motor, cognitive and language outcomes. Using a threshold of 0.39, sensitivity and specificity of BGT Lac/NAA for 2-year motor outcome was 100% and 97%, cognition 90% and 97% and language 81% and 97%, respectively. Sensitivity and specificity for motor outcome of mean diffusivity (threshold 0.001 mm2/s) up to day 9 was 72% and 100% and fractional anisotropy (threshold 0.198) was 39% and 94%, respectively. Lac/NAA correlated with BGT injury on NICHD scores (2A, 2B, 3).

Conclusion: BGT Lac/NAA on 1H MRS at 3T within 14 days accurately predicts 2-year motor, cognitive and language outcome and may be a marker directing decisions for therapies after cooling.

Keywords: imaging; neonatology; neurodevelopment; neurodisability.

MeSH terms

  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Cognitive Dysfunction / etiology*
  • Humans
  • Hypothermia, Induced / methods*
  • Hypoxia-Ischemia, Brain / complications
  • Hypoxia-Ischemia, Brain / diagnostic imaging*
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / therapy*
  • Infant
  • Infant, Newborn
  • Language Development Disorders / etiology*
  • Male
  • Prognosis
  • Proton Magnetic Resonance Spectroscopy

Substances

  • Aspartic Acid
  • N-acetylaspartate