ESPE Yearbook of Paediatric Endocrinology

Arch Dis Child Fetal Neonatal Ed. 2021 Apr 16. Epub ahead of print. doi: 10.1136/archdischild-2020-319926. PMID: 33863775.

This observational study highlights the potential detrimental long-term effects of neonatal hyperglycaemia on neurodevelopmental outcomes in extremely preterm infants, while the benefit of insulin treatment remains unclear.

Hyperglycaemia is common in the extremely preterm infant and has been associated with neurodevelopmental disability. Insulin has been used to treatment the hyperglycaemia in extreme preterm infants with the aim of improving the neurodevelopmental outcome but the results are conflicting. A retrospective study (1) in preterm infants did not observe an association between insulin treatment and neurodevelopmental outcomes at 1 year of age. Another retrospective study (2) observed that infants treated with insulin for neonatal hyperglycaemia had a higher incidence of abnormal neurological development at 2 years of age compared with infants not exposed to hyperglycaemia.

This current study is one of the largest studies conducted in extreme preterm infants investigating the associations between neonatal hyperglycaemia and neurodevelopmental outcomes in childhood. Neonatal hyperglycaemia (defined as blood glucose >8 mmol/l) and longer duration of hyperglycaemia were associated with lower intelligence scores and worse motor outcomes at 6.5 years of age. Insulin treatment in hyperglycaemic infants was not associated with neurodevelopmental outcomes at 6.5 years of age. The mechanisms behind the possible effect of hyperglycaemia on neurocognitive functions are unclear. In rats subjected to hyperglycaemia there is lower brain weight and increased apoptosis especially in the hippocampus region and neonatal hyperglycaemia was found to induce oxidative stress and an increase in inflammatory cytokines, with ensuing microglial activation and astrocytosis (3). Further studies, including adequately powered randomised controlled trials, are needed to better define neonatal hyperglycaemia in preterm infants, to guide its treatment and to clarify its consequences.

Reference: 1. van der Lugt NM, Smits-Wintjens VE, van Zwieten PH. Walther FJ. Short- and long-term outcome of neonatal hyperglycemia in very preterm infants: a retrospective follow-up study. BMC Pediatr 10, 52 (2010). https://doi.org/10.1186/1471-2431-10-52.2. Morgan C. The potential risks and benefits of insulin treatment in hyperglycaemic preterm neonates. Early Hum Dev. 2015;91:655–9.3. Tayman C, Yis U, Hirfanoglu I, Oztekin O, Göktaş G, Bilgin BC. Effects of hyperglycemia on the developing brain in newborns. Pediatr Neurol. 2014 Aug;51(2):239–45.