Value of Biochemical Markers for Outcome in Term Infants With Asphyxia

Abstract

Perinatal asphyxia remains a common cause of neonatal deaths and morbidity as well as long-term neurologic disability. Numerous biochemical markers have been proposed for evaluating infants having perinatal asphyxia. This prospective study evaluated 3 putative markers of outcome in term infants with perinatal asphyxia: interleukin-6 (IL-6), neuron-specific enolase (NSE), and the urinary uric acid/creatinine ratio (UA/Cr ratio). Marker levels were estimated simultaneously in blood and cerebrospinal fluid (CSF) within 1 to 3 days after birth in 21 infants with hypoxic\Nischemic encephalopathy (HIE). They subsequently were monitored for development and neurologic function over the first 2 years of life using the Denver Developmental Screening Test II. Twelve infants were diagnosed as having mild and 9 moderate to severe HIE. Two infants died in the neonatal intensive care unit. The overall outcome was thought to be adverse in 7 infants (33%). Five surviving infants, all of whom had moderate to severe HIE, developed severe motor deficits (spastic hemiparesis in 3 infants and spastic diapiresis and spastic hemiparesis in 1 infant each). Four of the 21 infants had postneonatal seizures. Of 7 infants with moderate to severe HIE, 9 (78%) had an adverse outcome, whereas all of those with mild HIE had a favorable outcome. Levels of IL-6 in both serum and CSF were significantly higher in infants with moderate to severe HIE than in the mildly affected infants. Moderate to severe HIE invariably predicted higher IL-6 levels in CSF. Serum and CSF concentrations of IL-6 correlated to a high degree. Levels of NSE in CSF were significantly higher in cases of moderate to severe HIE than in mildly affected infants. Serum NSE levels did not correlate significantly with the degree of HIE. CSF levels of NSE correlated relatively strongly with CSF levels of IL-6. UA/Cr ratios did not correlate significantly with the degree of HIE. Of all the parameters, IL-6 in CSF best predicted the outcome at age 2 years. A cutoff value of 25.9 pg/mL was 100% sensitive and 79% specific for an adverse outcome, and had positive and negative predictive values of 100% and 86%, respectively. Levels of NSE in CSF also had high predictive value They were 86% sensitive and 64% specific, with positive and negative predictive values of 90% and 55%, respectively. Neither serum NSE nor the urinary UA/Cr ratio was a good predictor of adverse outcomes. Should these predictive markers of later neurodevelopmental outcome be found accurate in further samples of infants in the neonatal intensive care unit, they might become a routine part of the workup of infants having perinatal asphyxia.