Long-term neurodevelopmental and metabolic consequences of neonatal hyperglycaemia and early life protein intake

Abstract

Neonatal hyperglycaemia is common in infants born very preterm, and is associated with adverse outcomes. However, it is not clear whether these associations are causal. The incidence of neonatal hyperglycaemia appears to decrease when early life protein intakes are increased, but associations between higher neonatal protein intakes and long-term outcomes are not well studied. Our aim was to test the hypotheses that, in children born very preterm: i) tight glycaemic control for neonatal hyperglycaemia does not change metabolic outcomes compared with standard glycaemic control, but worsens neurodevelopment; ii) neonatal hyperglycaemia is associated with impaired metabolic, body composition and neurodevelopmental outcomes; and iii) increased neonatal protein intake is associated with improved metabolic outcomes, without changing neurodevelopment. Eligible infants were born at <1,500 grams or <30 weeks’ gestation, and admitted to the neonatal intensive care unit, National Women’s Hospital, Auckland, NZ. Neonatal blood glucose concentrations and nutritional intakes were collected. At 7 years’ corrected age children underwent standardised developmental assessments, intravenous glucose tolerance testing, and measurements of growth and body composition. In the neonatal cohort (n=536), neonatal hyperglycaemia was associated with small, sick infants. A total of 129 children were assessed at 7 years’ corrected age. In 57 with neonatal hyperglycaemia and randomised as neonates in a trial of tight vs. standard glycaemic control, tight glycaemic control did not change neurodevelopmental outcomes, but reduced fasting blood glucose concentrations, reduced height, and increased lean mass at 7 years. Children with neonatal hyperglycaemia (n=57) had worse neurodevelopmental outcomes than 54 nonhyperglycaemic matched preterm controls, but this difference did not persist after correction for perinatal characteristics. Higher early protein intakes were associated with an increased risk of cerebral palsy and motor impairment at 7 years. Neonatal hyperglycaemia, as currently managed, is not associated with altered neurodevelopmental outcomes in mid-childhood. A brief period of tight control of neonatal hyperglycaemia alters later growth and body composition, supporting the need for long-term follow up of neonatal interventions. The observed associations between increased early life protein intake and motor impairment in childhood require testing in a randomised control trial.