Biomarkers for Severity of Neonatal Hypoxic-Ischemic Encephalopathy and Outcomes in Newborns Receiving Hypothermia Therapy

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• 作者：Lina F. Chalak ; MD ; MSCS¹ ; ^{lina.chalak@utsouthwestern.edu" class="auth_mail} ; Pablo J. Sá ; nchez ; MD¹ ; Beverley Adams-Huet ; MS² ; Abbot R. Laptook ; MD³ ; Roy J. Heyne ; MD¹ ; Charles R. Rosenfeld ; MD¹
• 关键词：BSID-III ; Bayley Scales of Infant and Toddler Development-III ; GFAP ; Glial fibrillary acidic protein ; HIE ; Hypoxic-ischemic encephalopathy ; IL ; Interleukin ; MRI ; Magnetic resonance imaging ; NICHD ; Eunice Kennedy Shriver National Institute of Child Health and Human Development ; ROC ; Receiver-operating characteristic ; UCH-L1 ; Ubiquitin carboxyl-terminal hydrolase L1 ; VEGF ; Vascular endothelial growth factor
• 刊名：The Journal of Pediatrics
• 出版年：March, 2014
• 年：2014
• 卷：164
• 期：3
• 页码：468-474.e1
• 全文大小：453 K

文摘

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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.