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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
  1. Subhabrata Mitra1,
  2. Giles S Kendall2,
  3. Alan Bainbridge3,
  4. Magdalena Sokolska3,
  5. Mary Dinan2,
  6. Cristina Uria-Avellanal1,
  7. David Price3,
  8. Katie Mckinnon2,
  9. Roxana Gunny2,
  10. Angela Huertas-Ceballos2,
  11. Xavier Golay4,
  12. Nicola J Robertson1,5
  1. 1 Institute for Women’s Health, University College London, London, UK
  2. 2 Women and Children, University College London NHS Foundation Trust, London, UK
  3. 3 Medical Physics and Engineering, University College London NHS Foundation Trust, London, UK
  4. 4 Institute of Neurology, Queen Square, University College London, London, UK
  5. 5 Division of Neonatology, Sidra Medicine, Doha, Qatar
  1. Correspondence to Professor Nicola J Robertson, Institute for Women’s Health, University College London, London WC1E 6HX, UK; n.robertson{at}


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.

  • imaging
  • neonatology
  • neurodisability
  • neurodevelopment

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  • Contributors SM, GSK, KM, CU-A recruited the babies and were the clinicians in charge of the clinical safety of the baby during the MRI/MRS study. SM wrote the first draft of the paper. MD assisted with the recruitment and care of the babies undergoing MRI. AB and MS performed the MRS analysis and the mean diffusivity assessment and interpreted the data. DP did the TBSS analysis and interpreted the data. RG scored the MRI images. XG provided advice on the MRI/MRS analysis. AH-C did the Bayley III assessment of the babies in the study. NJR designed and supervised the study and wrote the final drafts of the paper. All authors have been involved in finalising the manuscript and have seen and approved the final version.

  • Funding Funding support for this study was received from UK Department of Health’s NIHR BRC funding scheme.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval University College London Hospital REC.

  • Provenance and peer review Not commissioned; externally peer reviewed.