Abstract
Aim: To investigate the relationship between cytokines associated with innate immune cell activation and brain injury and outcome in infants with NE compared to neonatal controls.Methods: Serum and CSF biomarkers associated with activated neutrophils and monocytes [Interleukin-8 (IL-8) and Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF)] were serially measured using duplex immunoassays on days 1, 3 and 7 in term newborns with NE and controls. Results were compared to grade of encephalopathy, seizures, MRI brain imaging, mortality and Bayley Score of Infant and Toddler Development (Bayley-III) at 2 years of age.Results: Ninety-four infants had serum samples collected with 34 CSF samples. NE Grade II/III was significantly associated with elevated on day 2 serum IL-8. Mortality was best predicted by elevated day 1 IL-8. GM-CSF was initially elevated on day 1 and abnormal MRI imaging was associated with decreased day 2 GM-CSF. Elevated GM-CSF at day of life 6–7 correlated negatively with composite cognitive, language and motor Bayley-III scores at 2 years.Conclusion: Moderate or severe NE and mortality was associated with elevated IL-8. Day 2 GM-CSF could predict abnormal MRI results in NE and Bayley-III. Therefore, these cytokines are altered in NE and may predict early outcomes and further implicate inflammatory processes in NE.
Highlights
Neonatal encephalopathy (NE) can result in long-term neurodevelopmental impairment in term infants
The study enrolled a total of 94 term neonates including controls (n = 12) and infants exposed to perinatal asphxia with NE 0III (n = 82)
There were no significant differences between controls and NE cases with regard to gestational age, birth weight, gender or outborn status
Summary
Neonatal encephalopathy (NE) can result in long-term neurodevelopmental impairment in term infants. Systemic inflammation and a dysregulated immune response are features of NE [4, 5]. Elevated leukocytes are associated with adverse neurodevelopmental outcome in infants with NE [6]. Infants with NE present systemic inflammation, we were interested in cytokines associated with innate immune cell activation such as Interleukin-8 (IL-8) and granulocytemacrophage colony-stimulating factor (GM-CSF). IL-8 and GMCSF stimulate neutrophils and monocytes in both adults and neonates [8]. IL-8 is a chemotactic cytokine that mainly facilitates neutrophil recruitment and activation during immunological responses at the site of inflammation [9]. IL-8 concentrations in the serum of neonates with perinatal asphyxia are significantly higher than levels in control newborns on day 1 of life and has been suggested as a suitable candidate biomarker in NE [10,11,12]
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