Effect of Therapeutic Hypothermia on the Outcome in Term Neonates with Hypoxic Ischemic Encephalopathy-A Randomized Controlled Trial.

OBJECTIVE: To assess the effect of therapeutic hypothermia on the outcome in term neonates with hypoxic ischemic encephalopathy (HIE). METHODS: A randomized controlled trial was conducted in a tertiary care teaching hospital in south India. Term infants with moderate to severe HIE were randomized to be treated with normothermia or hypothermia. Mortality, neurological abnormality or normal outcome was recorded at hospital discharge or 28 days of age, whichever was earlier, and at 18 months of age. RESULTS: The baseline maternal and neonatal characteristics in the two groups were similar. The 78 infants in the hypothermia group had more normal survivors at discharge (38%) than the 84 infants in the normothermia group (30%), ratio 1.29 (95% confidence interval 0.84-1.99), and at 18 months of age (65% vs. 42%), ratio 1.54 (1.13-2.10). When these results were combined with those of a previous randomized trial in the same neonatal unit, there were significantly more normal survivors with hypothermia compared to normothermia at discharge, ratio 1.49 (1.18-1.88) and at 6-18 months of age, ratio 1.37 (1.17-1.60). CONCLUSION: In term infants with HIE, therapeutic hypothermia reduced mortality and neurological abnormalities, and resulted in more normal survivors. LAY SUMMARY: Babies who do not breathe immediately after they are born are likely to die or have brain damage. Previous studies have suggested that cooling these babies after birth might reduce the number who die or have brain damage. In this resource-limited setting, babies who were cooled were less likely to die or survive with brain damage.

Neuronal Biomarkers in Predicting Neurodevelopmental Outcome in Term Babies with Perinatal Asphyxia.

OBJECTIVE: To assess whether serum levels of neuronal biomarkers (S100 calcium-binding protein B and Neuron specific enolase) correlate with the neurodevelopmental outcome of term neonates at 18 mo who had hypoxic ischemic encephalopathy and underwent therapeutic hypothermia. METHODS: This randomized controlled trial was conducted in a tertiary care teaching hospital, south India. There were 162 term infants with moderate to severe hypoxic ischemic encephalopathy who were randomized into 2 groups (Group A and B). Neonates in Group A and B received normothermia and therapeutic hypothermia respectively. Serum levels of neuronal biomarkers were estimated at 0, 24 (±1) and 72 (±1) h after birth using sandwich ELISA in both groups. All neonates were carefully monitored till discharge. Infants who survived the neonatal period were followed up in the high risk clinic for 18 mo and neurodevelopmental assessment was done using Developmental Assessment Scale for Indian Infants (DASII). Neurodevelopmental outcomes between the two groups were compared using Chi square test and neuronal biomarker levels between the groups were compared using Mann Whitney test. RESULTS: The baseline maternal and neonatal characteristics in both groups were comparable. There was statistically insignificant lesser mortality in therapeutic hypothermia group compared to normothermia group with Risk Ratio (RR): 0.82 (28.2% vs. 34.5%, 95% CI: 0.52-1.29, p = 0.38). Among the survivors, children in therapeutic hypothermia group had better motor and mental scores compared to those in normothermia group at 18 mo. There was no significant correlation between S100B and Neuron specific enolase levels and neurodevelopmental outcome. CONCLUSIONS: Serum levels of neuronal biomarkers (S100B and Neuron specific enolase) do not correlate with the long term neurodevelopmental outcome among these infants.