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Perinatal Asphyxia and Erythropoietin and VEGF: Serial Serum and Cerebrospinal Fluid Responses
Deirdre U Sweetman1, Chike Onwuneme, William R Watson
1Neonatology, National Maternity Hospital, Dublin, Ireland.
Insights
Erythropoietin (Epo) and vascular endothelial growth factor (VEGF) in infant serum may indicate the severity of hypoxic-ischaemic brain injury. Elevated Epo and decreased VEGF correlate with neonatal encephalopathy and adverse outcomes.
Area of Science:
- Neonatalogy
- Neurology
- Biochemistry
Background:
- Neonatal encephalopathy (NE) in infants stems from hypoxic-ischaemic injury, potentially causing inflammation and excessive cytokine release.
- Systemic inflammation is common in NE, prompting investigation into hypoxia-associated cytokines like vascular endothelial growth factor (VEGF) and erythropoietin (Epo).
Purpose of the Study:
- To examine the relationship between Epo, VEGF levels, brain injury, and outcomes in term infants experiencing perinatal asphyxia (PA) compared to controls.
- To assess the potential of Epo and VEGF as biomarkers for hypoxic-ischaemic injury in newborns.
Main Methods:
- Serum and cerebrospinal fluid (CSF) samples were collected from term infants exposed to PA and controls over days 1-4.
- Multiplex immunoassays were used to measure VEGF and Epo levels, comparing them to encephalopathy severity, MRI findings, and mortality.
- 94 infants provided 247 serum samples and 34 CSF samples; 12 were controls and 82 were exposed to PA.
Main Results:
- Infants exposed to PA had significantly higher serum Epo levels on days 1 and 2 compared to controls.
- Grade II/III NE was linked to elevated day 2 Epo and decreased day 1 VEGF. Elevated Epo correlated with severe MRI abnormalities.
- Mortality was associated with elevated day 3 Epo and decreased day 1 VEGF. CSF Epo and VEGF levels did not significantly correlate with outcomes.
Conclusions:
- Serum Epo and VEGF show promise as indicators of hypoxic-ischaemic injury severity and brain damage in neonates.
- These cytokines are closely linked to hypoxic exposure, suggesting their utility in assessing neonatal outcomes.
Background:
Infants with neonatal encephalopathy (NE) of hypoxic-ischaemic origin are at risk of oxidative and ischaemia-reperfusion injury, which may induce abnormal inflammatory responses involving excessive cytokine production and release in serum and cerebrospinal fluid (CSF). Systemic inflammation is found in infants with NE, and we therefore were interested in cytokines associated with hypoxia, including vascular endothelial growth factor (VEGF) and erythropoietin (Epo).
Objective:
To investigate the relationship between Epo, VEGF levels, brain injury and outcome in a group of term infants exposed to perinatal asphyxia (PA) compared to controls.
Methods:
Serum and CSF biomarkers associated with hypoxia (VEGF, Epo) were serially measured using multiplex immunoassays over days 1-4 in term infants exposed to PA including infants with NE and controls. Results were compared to severity of encephalopathy, MR brain imaging and mortality.
Results:
Ninety-four infants had 247 serum samples collected (n = 12 controls, 82 exposed to PA with 34 CSF samples), and 4 infants died. Controls had significantly lower serum Epo levels on days 1 and 2 compared to those exposed to PA (p = 0.02). Grade II/III NE was significantly associated with elevated day 2 Epo and decreased day 1 VEGF (p < 0.05; day 2 Epo AUC = 0.74, cut-off 10.05 IU/ml). Elevated serum Epo was associated with severely abnormal MRI. Mortality was associated with elevated day 3 Epo and decreased day 1 VEGF. CSF levels were all after hypothermia and were not significantly associated with outcome.
Conclusion:
Serum Epo and VEGF may be markers of severity of hypoxia-ischaemia and brain injury as they are closely related to hypoxic exposure.
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