Hyperglycaemia in infants with hypoxic-ischaemic encephalopathy is associated with improved outcomes after therapeutic hypothermia: a post hoc analysis of the CoolCap Study

Abstract

Objective: To investigate whether glycaemic profile is associated with multiorgan dysfunction and with response to hypothermia after perinatal hypoxic-ischaemic encephalopathy (HIE).

Design: Post hoc analysis of the CoolCap Study.

Setting: 25 perinatal centres in UK, USA and New Zealand during 1999-2002.

Patients: 194/234 (83%) infants of ≥36 weeks' gestation with moderate-to-severe HIE enrolled in the CoolCap Study with documented plasma glucose levels and follow-up outcome.

Intervention: Infants were randomised to head cooling for 72 hours starting within 6 hours of birth or standard care. Plasma glucose levels were measured at predetermined time intervals after randomisation.

Main outcome measure: Unfavourable primary outcome was defined as death and/or severe neurodevelopmental disability at 18 months. Glycaemic profile (hypoglycaemia (≤40 mg/dL, ≤2.2 mmol/L), hyperglycaemia (>150 mg/dL, >8.3 mmol/L) and normoglycaemia) during 12 hours after randomisation was investigated for association with multiorgan dysfunction or risk reduction of primary outcome after hypothermia treatment.

Results: Hypoglycaemia but not hyperglycaemia was associated with more deranged multiorgan function parameters (mean pH 7.23 (SD 0.16) vs 7.36 (0.13), p<0.001; aspartate transaminase 2101 (2450) vs 318 (516) IU/L, p=0.002; creatinine 1.95 (0.59) vs 1.26 (0.5) mg/dL, p<0.001) compared with normoglycaemia. After adjusting for Sarnat stage and 5 min Apgar score, only hyperglycaemic infants randomised to hypothermia had reduced risk of unfavourable outcome (adjusted risk ratio: 0.80, 95% CI 0.66 to 0.99), whereas hypoglycaemic and normoglycaemic infants did not.

Conclusions: Early glycaemic profile in infants with moderate-to-severe HIE may help to identify risk of multiorgan dysfunction and response to therapeutic hypothermia.

Trial registration number: NCT00383305.

Keywords: CoolCap Study; hyperglycaemia; hypoglycaemia; neonatal hypoxic ischaemic encephalopathy; response to hypothermia treatment.