Hypoglycaemia in preterm infants and subsequent neurodevelopmental

Project Coordinators Robert Hume and Fiona Williams 

Methodology

Design Cohort study / case: comparison

Setting: 8 neonatal intensive care units in Scotland

Subjects: neonates <35 weeks gestation

Exclusion criteria: HIV/Hepatitis B/C positive or at high risk of being

Procedures: All infants will be recruited and investigated in the neonatal unit in the week prior to discharge home.  Thus all infants will be stable and well; in our previous studies such infants were around 37-38 weeks corrected gestation.  All infants will have blood glucose levels measured 4 hours after their last feed, the subsequent scheduled feed will be omitted, and their blood glucose levels measured again at 2 hours.  We are defining severe hypoglycaemia as one blood glucose measurement <2.2 mmol/litre; mild hypoglycaemia is defined as one measurement of blood glucose between 2.2-2.6 mmol/litre; and normoglycaemia as blood glucose measurements both >2.6 mmol/litre.  We will provide an algorithm that all units will be advised to follow for the further investigation and clinical management of infants with hypoglycaemia.  Data on the known causes and confounders of neurodevelopment will be collected.  Neurodevelopmental status will be assessed at 2 years corrected age.

Sample size: We shall recruit 2400 infants over 24 months which will enable us to detect an incidence of severe hypoglycaemia of 5%, mild hypoglycaemia of 11%. This study has sufficient numbers to allow the neurodevelopmental assessment in 100 infants in each of the outcome groups: normoglycaemic, mildly hypoglycaemic and severely hypoglycaemic.    Assuming a recruitment rate of 80% this will result in 100 infants in the severe group (and proportionally larger numbers in the other two groups) which has sufficient power (80%) to enable a difference (p=5%) of Mental Development and Psychomotor Development Indices, MDI and PDI, of 7 points to be detected between the normoglycaemic group and the hypoglycaemic groups.

Outcome measures: In the days immediately prior to discharge home, blood glucose levels will be measured 4 hours after the last feed, the scheduled feed omitted, and blood glucose measured again at 2 hours.  Neurodevelopment will be assessed with Bayley Scales (MDI and PDI) at 2 years correct age.  

Analyses Adjusted odds ratios will be calculated for severe hypoglycaemia, mild hypoglycaemia and normoglycaemia.