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J Pediatr. 2014 Mar;164(3):468-74.e1. doi: 10.1016/j.jpeds.2013.10.067. Epub 2013 Dec 12.

Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy.

Author information

1
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: lina.chalak@utsouthwestern.edu.
2
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX.
3
Department of Clinical Sciences and Statistics, University of Texas Southwestern Medical Center, Dallas, TX.
4
Department of Pediatrics, Brown University, Women & Infants Hospital of Rhode Island, Providence, RI.

Abstract

OBJECTIVE:

To evaluate serum neuronal and inflammatory biomarkers to determine whether measurements of umbilical cords at birth can stratify severity of hypoxic-ischemic encephalopathy (HIE), whether serial measurements differ with hypothermia-rewarming, and whether biomarkers correlate with neurological outcomes.

STUDY DESIGN:

This is a prospective cohort of inborn term newborns with varying degrees of HIE by neurological assessment. Neuronal glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and inflammatory cytokines were measured in serum from umbilical artery at 6-24, 48, 72, and 78 hours of age. Neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-III scales) were performed at 15-18 months.

RESULTS:

Twenty neonates had moderate (n = 17) or severe (n = 3) HIE and received hypothermia; 7 had mild HIE and were not cooled. At birth, serum GFAP and ubiquitin carboxyl-terminal hydrolase L1 increased with the severity of HIE (P < .001), and serial GFAP remained elevated in neonates with moderate to severe HIE. Interleukin (IL)-6, IL-8, and vascular endothelial growth factor were greater at 6-24 hours in moderate to severe vs mild HIE (P < .05). The serial values were unaffected by hypothermia-rewarming. Elevated GFAP, IL-1, IL-6, IL-8, tumor necrosis factor, interferon, and vascular endothelial growth factor at 6-24 hours were associated with abnormal neurological outcomes.

CONCLUSIONS:

The severity of the hypoxic-ischemic injury can be stratified at birth because elevated neuronal biomarkers in cord serum correlated with severity of HIE and outcomes.

PMID:
24332821
PMCID:
PMC4006934
DOI:
10.1016/j.jpeds.2013.10.067
[Indexed for MEDLINE]
Free PMC Article
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