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. 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

Lina F Chalak  1 , Pablo J Sánchez  2 , Beverley Adams-Huet  3 , Abbot R Laptook  4 , Roy J Heyne  2 , Charles R Rosenfeld  2
Affiliations

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

Lina F Chalak et al. J Pediatr. 2014 Mar.

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.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Umbilical cord plasma GFAP and UCH-L1 and severity of encephalopathy at birth. A box and whisker plot is shown with median as solid line, mean as dotted line, and 25th and 75th quartiles as lower and upper borders. Analyses include neonates with mild (n = 7), moderate (n = 17), and severe (n = 3) HIE. P = .001 (GFAP) and P = .03 (UCH-L1) by Jonckheere-Terpstra test. a, b, and c denote significant differences among each group.
Figure 2
Figure 2
ROC curves of serum biomarkers at 6–24 hours predicting abnormal BSID-III results (<85) at 18–24 months.
See this image and copyright information in PMC

Comment in

References

    1. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–1584. - PubMed
    1. Higgins RD, Raju T, Edwards AD, Azzoparki DV, Bose CL, Clark RH, et al. Hypothermia and other treatment options for neonatal encephalopathy: an executive summary of the Eunice Kennedy Shriver NICHD Workshop. J Pediatr. 2011;159:851.e1–858.e1. - PMC - PubMed
    1. Douglas-Escobar M, Weiss MD. Biomarkers of brain injury in the premature infant. Front Neurol. 2012;3:185. - PMC - PubMed
    1. van der Linden J, Ekroth R, Lincoln C, Pugsley W, Scallan M, Tyden H. Is cerebral blood flow/metabolic mismatch during rewarming a risk factor after profound hypothermic procedures in small children? Eur J Cardiothorac Surg. 1989;3:209–215. - PubMed
    1. Nakamura T, Miyamoto O, Sumitani K, Negi T, Itano T, Nagao S. Do rapid systemic changes of brain temperature have an influence on the brain? Acta Neurochir (Wien) 2003;145:301–307. - PubMed

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