Early Cord Metabolite Index and Outcome in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy

Neonatology. 2016;110(4):296-302. doi: 10.1159/000446556. Epub 2016 Aug 3.

Abstract

Background: A 1H-NMR-derived metabolomic index based on early umbilical cord blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE) severity.

Objective: To evaluate whether this metabolite score can predict 3-year neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared with current standard biochemical and clinical markers.

Methods: From September 2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a single maternity hospital. Cord blood was drawn and biobanked at delivery. Neonates were monitored for development of encephalopathy both clinically and electrographically. Neurodevelopmental outcome was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death and cerebral palsy were also considered as abnormal end points.

Results: Thirty-one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42 months. No child had a severely abnormal BSID-III result. The metabolite index significantly correlated with outcome (ρ2 = 0.30, p < 0.01), which is robust to predict both severe outcome (area under the receiver operating characteristic curve: 0.92, p < 0.01) and intact survival (0.80, p = 0.01). There was no correlation between the index score and performance in the individual BSID-III subscales (cognitive, language, motor).

Conclusions: The metabolite index outperformed other standard biochemical markers at birth for prediction of outcome at 3 years, but was not superior to EEG or the Sarnat score.

Trial registration: ClinicalTrials.gov NCT02019147.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asphyxia Neonatorum / metabolism*
  • Asphyxia Neonatorum / physiopathology*
  • Australia
  • Biomarkers / metabolism
  • Cerebral Palsy / diagnosis
  • Child, Preschool
  • Electroencephalography
  • Female
  • Fetal Blood / metabolism*
  • Humans
  • Hypoxia-Ischemia, Brain / metabolism*
  • Hypoxia-Ischemia, Brain / physiopathology*
  • Infant
  • Infant, Newborn
  • Language Development
  • Linear Models
  • Male
  • Metabolomics
  • ROC Curve
  • Severity of Illness Index

Substances

  • Biomarkers

Associated data

  • ClinicalTrials.gov/NCT02019147

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