Hyperglycemia occurs in 40-80% of premature, low-birth-weight infants due to immaturity of endogenous regulatory systems and the stress of their condition. Hyperglycemia leads to osmotic diuresis, dehydration and further negative outcomes including increased mortality. In this cohort, typical treatment via calorie restriction reduces the critical substrates required for growth, where the emerging use of insulin carries a significant risk of hypoglycemia.

A metabolic computer system model, clinically validated in adult intensive care unit (ICU) patients and in virtual trials using neonatal ICU (NICU) clinical data, is used to provide tight glycemic control in very low birth weight (VLBW) neonates. Six clinical trials up to 24 hours each were performed based on initial blood glucose over 8 mmol/L to initiate insulin. Median weight was 745g (Range: 540g – 900g). Median gestational age was 25.7 weeks (Range: 24.4 – 27 weeks).

Insulin infusions were modulated to hit a pre-determined target based on measurements every 2-3 hours (max 12 measurements/day). The overall goal was to control blood glucose in a 4-7 mmol/L band. A stochastic model ensured the risk of blood glucose below 4 mmol/L was less than 5% for each intervention. Ethics approval was granted by the South Island Regional Ethics Committee.

Normoglycemia in a 4-7 mmol/L band was achieved in all cases. Median initial blood glucose was 10.1 mmol/L (Range: 7.4 – 14.4 mmol/L). Over all trials median blood glucose was 6.9 (IQR: 5.6 – 7.9, 90%CI: 4.6 – 11.2) mmol/L over 67 measurements. The minimum blood glucose was 3.8 mmol/L. Predicted glucose levels had a median error of 8.3 (IQR: 4.7 – 13.5, 90%CI: 1.2 – 31.1)% compared to the resulting measurement. The median measurement and prediction period was 2.1 hours

Hyperglycemia affects a large proportion of premature infants and is linked to worsened outcomes. A computer model that accurately captures the dynamics of neonatal metabolism provided safe and effective, real-time blood glucose control in 24-hour pilot clinical trials.