Cerebral intracellular lactic alkalosis persisting months after neonatal encephalopathy measured by magnetic resonance spectroscopy

N J Robertson, I J Cox, F M Cowan, S J Counsell, D Azzopardi, A D Edwards

Research output: Contribution to journalArticlepeer-review

Abstract

We have found that cerebral lactate can be detected later than 1 month of age after neonatal encephalopathy (NE) in infants with severe neurodevelopmental impairment at 1 y. Our hypothesis was that persisting lactate after NE is associated with alkalosis and a decreased cell phosphorylation potential. Forty-three infants with NE underwent proton and phosphorus-31 magnetic resonance spectroscopy at 0.2-56 wk postnatal age. Seventy-seven examinations were obtained: 25 aged <2 wk, 16 aged > or = 2 to < or = 4 wk, 25 aged > 4 to < or = 30 wk, and 11 aged > 30 wk. Neurodevelopmental outcome was assessed at 1 y of age: 17 infants had a normal outcome and 26 infants had an abnormal outcome. Using univariate linear regression, we determined that increased lactate/creatine plus phosphocreatine (Cr) was associated with an alkaline intracellular pH (pHi) (p < 0.001) and increased inorganic phosphate/phosphocreatine (Pi/PCr) (p < 0.001). This relationship was significant, irrespective of outcome group or age at time of study. Between outcome groups, there were significant differences for lactate/Cr measured at < 2 wk (p = 0.005) and > 4 to < or = 30 wk (p = 0.01); Pi/PCr measured at < 2 wk (p < 0.001); pHi measured at < 2 wk (p < 0.001), > or = 2 to < or = 4 wk (p = 0.02) and > 4 to < or = 30 wk (p = 0.03); and for N-acetylaspartate/Cr measured at > or = 2 to < or = 4 wk (p = 0.03) and > 4 to < or = 30 wk (p = 0.01). Possible mechanisms leading to this persisting cerebral lactic alkalosis are a prolonged change in redox state within neuronal cells, the presence of phagocytic cells, the proliferation of glial cells, or altered buffering mechanisms. These findings may have implications for therapeutic intervention.

Original languageEnglish
Pages (from-to)287-96
Number of pages10
JournalPediatric Research
Volume46
Issue number3
DOIs
Publication statusPublished - Sep 1999

Keywords

  • Brain/metabolism
  • Brain Diseases/congenital
  • Cytoplasm/metabolism
  • Fetal Hypoxia
  • Humans
  • Infant
  • Infant, Newborn
  • Lactic Acid/analysis
  • Magnetic Resonance Spectroscopy
  • Oxidation-Reduction
  • Regression Analysis
  • Time Factors

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