Predictors of Developmental Outcomes in Hypoxic-ischemic Encephalopathy Treated with Hypothermia

Background: The efficacy of therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy is well-established. However, the impact of perinatal and neonatal factors on long-term developmental outcomes in this population is still limited. We sought to assess perinatal and neonatal characteristics associated with developmental outcomes following hypoxic-ischemic encephalopathy.

Methods: 66 infants with moderate to severe HIE who underwent therapeutic hypothermia were enrolled between 2010 and 2015. Perinatal and neonatal characteristics including birth anthropometrics, gestational age, gender, pH and base excess (cord or within the first hour of life), APGAR scores at 1 and 5 minutes of life, brain MRI, and peak creatinine and alanine transaminase levels in the first 24 hours were included as predictors. Discharge feeding classifications of oral feeds, gavage feeds (NG/NJ tube), G-tube feeds or combined were included as predictors, as was presence and absence of G-tube feeding. Developmental outcomes at 24 months of age were measured via Capute and Mullen scores, as well as Gross Motor Function Classification, and scores across all measures were uniformly classified as typical development, or mild, moderate or severe developmental impairment.

Results: Birth head circumference and MRI NICHD grades were significant predictors of mild developmental impairment at 24 months (p = 0.018 and p=0.016 respectively), which persisted after adjustment for gender and median income (p = 0.035 and p=0.016 respectively). APGAR scores at 1 minute of life were significantly associated with mild developmental impairment at 24 months (p=0.025). MRI NICHD grades and pH were significantly associated with mild or moderate developmental impairment (p < 0.001 and p=0.022 respectively), which persisted after adjusting for gender and median income (p=0.003 and p=0.015 respectively). Birth length and weight were not associated with developmental outcomes at 24 months.

Conclusion: There was a significant association between early factors including birth head circumference, pH and MRI NICHD grade with developmental outcomes at the two-year visit in infants with HIE treated with hypothermia. This study is amongst the first to describe the relationship between head circumference and developmental outcomes and adds to the growing body of literature on long-term outcomes in infants who have undergone therapeutic hypothermia.