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Plasma neurofilament light protein predicts cerebral tissue injury in cooled babies

Presented as a poster at the Neonatal Society 2016 Summer Meeting.

Shah DK, Ponnusamy V, Evanson J, Kapellou O, Ekitzidou G, Gupta N, Clarke P, Michael-Titus A, Yip PK

Royal London Hospital, Ashford and St Peter’s Hospitals, Homerton University Hospital, Southampton University Hospitals, Norfolk and Norwich University Hospitals, Queen Mary University of London

Background: Hypoxic-ischaemic encephalopathy (HIE) in the newborn remains an important problem globally. Mild therapeutic hypothermia (TH) has been shown to be safe and effective in preventing death and disability. There are no early tissue biomarkers for selection of newborns for TH or for prognosticating outcome. Hypothesis: Plasma neurofilament light (NfL) protein, an important cytoskeleton component of neurons are raised in relation to severity of brain injury in newborns after HIE as noted on MRI.

Methods: Plasma samples from 37 newborns were studied; 11 newborns with mild HIE who did not fulfil cooling criteria and were managed conservatively and 26 newborns with moderate-severe HIE who were treated with TH for 72 hours, half of whom had a cerebral MRI predictive of an unfavourable outcome (1). Infants treated with TH had up to three serial specimens (Figure); S1 after the infant had reached target temperature, S2 prior to commencing rewarming and S3 after completing rewarming. Infants with mild HIE had a single specimen taken. Plasma from the newborns was tested for NfL protein using an enzyme-linked immunosorbent assay (ELISA). Cooled newborns had cerebral MR images independently rated by two raters with expertise.

Results: There was a statistically significant difference in NfL levels between the three groups (mild HIE, favourable TH and unfavourable TH) for sample S1 (F=5.13, p=0.01). Cooled newborns who had MRIs predictive of unfavorable (blue) outcome had significantly higher NfL levels than those with MRIs predictive of favorable (red) outcomes (F=27.63, p<0.001) (Figure). NfL levels were raised in the unfavorable group within 24 hours.

Plasma neurofilament light protein predicts cerebral tissue injury in cooled babies

Conclusion: We demonstrate that it is feasible to study NfL in the plasma of newborns. NfL may be an effective early biomarker for stratifying babies to additional neuroprotective interventions as well as prognosticating longer term outcomes. Larger studies are required to confirm this preliminary work.

Corresponding author: divyen.shah@bartshealth.nhs.uk

References
1. Rutherford et al. Lancet Neurology. 2010

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