Severity of hypoxic ischemic encephalopathy correlates with increased expression of angiogenin in neonates.

BACKGROUND: Angiogenin is a small protein encoded by the ANG gene. It is activated by tissue hypoxia, and is known to be a potent stimulator of angiogenesis. The role of angiogenic factors in the pathogenesis of HIE is poorly understood, yet, angiogenin may be part of the molecular mechanisms underlying HIE. OBJECTIVE: Our objective was to explore the predictive value of angiogenin as a biochemical marker in early hypoxic ischemic encephalopathy staging. STUDY DESIGN: We prospectively studied 36 full term HIE neonates and 20 non- asphyxia neonates. Cord blood samples from all subjects immediately at delivery were withdrawn. Neurological examination and grading of HIE were performed during the first day of life. RESULTS: Concentrations of cord blood angiogenin were increased in infants with asphyxia when compared txht o controls (P = 0). Within the asphyxia group, the median cord blood angiogenin was significantly higher in stage III encephalopathy patient compared to stage I and stage II (p = 0). There was a negative correlation between pH, HCo3 level and angiogenin in stage II and stage III. CONCLUSION: Angiogenin helps in assessing the severity of HIE in neonates and is promising marker predicting the stage of hypoxia-ischemia so treatment may be initiated earlier.

Single dose recombinant erythropoietin versus moderate hypothermia for neonatal hypoxic ischemic encephalopathy in low resource settings.

OBJECTIVE: To determine the safety and efficacy of single dose systemic recombinant human erythropoietin (rEPO) in neonates with perinatal hypoxic Ischemic Encephalopathy (HIE), and its effect on serum brain-derived neurotrophic factor (BDNF) and neuron-specific enolase (NSE). METHODS: Forty-five full-term neonates; 30 with perinatal HIE and 15 controls were studied. HIE neonates were randomized into three intervention groups (first 6 h of life): 10 received single subcutaneous 1500 U/kg rEPO at day-1, 10 subjected to hypothermia for 72 h and 10 received supportive care. BDNF and NSE measured during first 6 h and day 5 postnatal. Daily Thompson's score, MRI brain and neuromuscular function scale for survivors at 3 months of age were done. RESULTS: Hypothermia group had best survival especially with stage-II Sarnat scale, followed by rEpo and supportive group. BDNF day-5 was significantly higher in each group compared to controls. MRI score and neuromuscular function score were non-significantly lower in the hypothermia group compared to rEPO. CONCLUSIONS: Therapeutic hypothermia was superior to single dose rEpo for neuro-protection in HIE especially in patients with stage-II Sarnat scale. Therapeutic effect of combined rEPO multiple dosing and modest hypothermia therapy should be studied.

Predictive value of vascular endothelial growth factor in preterm neonates with intraventricular haemorrhage.

OBJECTIVE: Intraventricular haemorrhage (IVH) is a major problem in premature infants. Our objective is to assess the early predictive value of vascular endothelial growth factor (VEGF) for development of IVH and management of its squeal in preterm neonates. METHODS: We prospectively studied 150 preterm neonates (PT) less than 34 weeks gestation. Fifty of them completed the study. 30/50 developed IVH during follow up, and 20 did not. First 24 hours, and 3(rd) day serum samples were collected. Cerebrospinal fluid (CSF) samples were withdrawn for 10 IVH patients. RESULTS: Serum VEGF; both samples were increased in IVH compared to non-IVH group (P=0.001). PHVD-group (n=10) had higher VEGF in both samples than resolved IVH (P=0.004), (P=0.005). While, VEGF increased in the IVH group 2(nd) sample compared to 1(st) (P=0.000), it decreased in non-IVH group, P=0.033). Each 1 unit increase in 1(ST) VEGF increased the risk of occurrence of IVH by 1.6%. 3(rd) day VEGF at a cut-off value of 135 pg/ml is 96% sensitive and 100% specific to predict PHVD. Serum VEGF inversely correlated with TLC, pH, PO(2) and HCO(3), and positively correlated with PCo(2) and FiO(2). CONCLUSION: Serum VEGF predicts development of IVH and PHVD in PT neonates. Also, high CSF level of VEGF could predict the need for permanent shunt placement.