EVALUATION OF GLIAL FIBRILLARY ACIDIC PROTEIN LEVELS IN PREDICTING PROGNOSIS IN PERINATAL ASPHYXIA- HYPOXIC ISCHEMIC ENCEPHALOPATHY

Abstract

Background: Perinatal asphyxia is a condition characterized by an impairment of oxygen exchange at birth resulting in hypoxemia and metabolic acidosis. Perinatal asphyxia affects virtually every organ of the body including kidneys, heart, respiratory and gastrointestinal systems; however, CNS is the most frequently involved organ in perinatal asphyxia. While the majority of organ involvement may be reversible, CNS involvement in perinatal asphyxia may be progressive and lead to an evolving encephalopathy called Hypoxic Ischemic Encephalopathy (HIE) with long-term ramifications including visual and hearing loss, seizures, autism, ADHD, neurodevelopmental delay, and cerebral palsy.

Objectives:

(i) To study the levels of GFAP in neonates affected with perinatal asphyxia.

(ii) To study the possible role of GFAP in predicting neurodevelopmental outcome in perinatal asphyxia complicated by hypoxic encephalopathy.

(iii) To guide the optimal timing in relation to the detection of GFAP after an acute perinatal hypoxic event.

Methods: The study was a prospective case-control study conducted in the Department Of Pediatrics, SKIMS. 35 newborns fulfilling the ACOG criteria for perinatal asphyxia were included in our study as cases and an equal no of controls were taken. The GFAP levels were compared in the cases at 12 and 48 hours of life and similarly in controls. The relative levels were then compared between cases and controls at the same time points i.e. at 12 and 48 hours of life.  The cases were periodically followed up after discharge and evaluated at 3 & 6 months for neurodevelopmental outcomes by using the Hammersmith Infant Neurodevelopmental Scale (HINE). The GFAP levels (at 12 & 48 hours) in cases were correlated to the neurodevelopmental outcomes as assessed by the HINE scoring.

Results: The mean serum GFAP level in the HIE group(n=35) was 0.253 ng/mL while the mean serum GFAP level in the control group(n=35) was 0.056 ng/mL at 12 hours of life. The mean serum GFAP level in the HIE group was 0.285 ng/mL while the mean serum GFAP level in the control group was 0.050 ng/mL at 48 hours of life. 7 patients in the HIE group died due to complications in the neonatal period. We found that 12/12(100%) patients with abnormal neurodevelopmental outcome had GFAP levels above 0.24 ng/mL at both 12 and 48 hours of life inferring that a cut off value of 0.24 ng/mL has 100% sensitivity in patients with abnormal neurodevelopmental outcome. 14/16 (87.5%) of patients with normal neurodevelopmental outcome at 3 and 6 months of life had GFAP levels below 0.24 ng/mL at 12 hours of life. Thereafter, at 48 hours of life , 15/16(93.7%) of patients with normal neurodevelopmental outcome had GFAP levels below 0.24 ng/mL showing specificity of 87.5% and 93.7% at 12 and 48 hours of life respectively. Our study suggests that a GFAP cut-off value of 0.24 ng/mL at 12 hours may predict with a sensitivity and specificity of 100% and 87.5% respectively abnormal outcome in Hypoxic Ischemic encephalopathy. At 48 hours the sensitivity of a GFAP cut-off value of 0.24 ng/mL remains 100% but specificity increases to 93.7%.

Conclusion: To conclude, in our study, we found that Glial fibrillary acidic protein levels were considerably higher in patients with Hypoxic Ischemic Encephalopathy compared to controls. Glial fibrillary acidic protein levels are negatively correlated to and can be used to predict the neurodevelopmental outcome.