Impact of hypoglycaemia on neurodevelopmental outcomes in hypoxic ischaemic encephalopathy: a retrospective cohort study

Background Low blood glucose levels (BGLs) in infants are known to adversely affect neurodevelopmental outcomes. However, this risk is not well explored in infants with hypoxic ischaemic encephalopathy (HIE) that receive therapeutic hypothermia (TH). Additionally, little information is available on the optimal BGLs to target in infants with HIE. Aim To explore the association between hypoglycaemia and neurodevelopmental outcomes at different BGL thresholds (2.6 and 3.0 mmol/L) in neonates with HIE treated with TH. Methods Retrospective cohort study. Clinical information and 2-year neurodevelopmental data using Bayley Scales of Infant Development, third edition (BSID-III) and disabilities were recorded for infants born in Western Australia with HIE and treated with TH between February 2008 and February 2012. Multivariable logistic regression models explored the association between hypoglycaemia and neurodevelopmental outcomes. Results 122 infants underwent a total of 1616 BGL estimations before and during 72 hours of TH. Hypoglycaemia (BGL<2.6 mmol/L) occurred in 38/122 (31%) infants and 11/122 (9%) had recurrent hypoglycaemia (three or more episodes). Infants with recurrent hypoglycaemia (<2.6 mmol/L) had significantly lower mean BSID-III cognitive, language and socioemotional subscale scores. On multivariable analysis, recurrent hypoglycaemia (<2.6 mmol/L) was associated with increased odds of death or disability (adjusted OR 8.15; 95% CI 1.31 to 50.58; p=0.024). Recurrent hypoglycaemia (<3.0 mmol/L) during the first 12 hours of life was also associated with severe disability among survivors (adjusted OR 11.13; 95% CI 2.06 to 59.89; p=0.005). Conclusions Early recurrent hypoglycaemia was associated with increased risk of death or severe disability in neonates undergoing TH for HIE. Prospective studies are needed to identify the ideal target BGL in this population.