Early Hyperglycemia in Very Preterm Infants Is Associated with Reduced White Matter Volume and Worse Cognitive and Motor Outcomes at 2.5 Years

Abstract

Introduction: Hyperglycemia in very preterm infants is associated with increased morbidity and mortality. We aimed to investigate potential associations between early hyperglycemia, neonatal cerebral magnetic resonance imaging (MRI), and neurodevelopment at 2.5 years.

Methods: The study population included 69 infants with gestational age (GA) 22.3-31.9 weeks (n = 29 with GA <28 weeks), born 2011-2014. Plasma glucose concentrations during the first week were checked according to clinical routines. Hyperglycemia was defined as glucose concentrations above 8.3 mmol/L (150 mg/dL) and above 10 mmol/L (180 mg/dL), respectively, categorized as the highest glucose days 0-2, number of days above 8.3 and 10 mmol/L, and prolonged (yes/no) 2 days or more above 8.3 and 10 mmol/L. The MRI analysis included morphological assessment, regional brain volumes, and assessment of apparent diffusion coefficient (ADC). Neurodevelopmental impairment (NDI) developed in 13 of 67 infants with available outcomes, of which 57 were assessed with the Bayley-III. Univariate and multiple linear and logistic regressions were performed with adjustments for GA, birth weight z-scores, and illness severity expressed as days on mechanical ventilation.

Results: Hyperglycemia above 8.3 mmol/L and 10 mmol/L was present in 47.8% and 31.9% of the infants. Hyperglycemia correlated independently with lower white matter volume, but not with other regional brain volumes, and was also associated with lower ADC values in white matter. Hyperglycemia also correlated with lower Bayley-III cognitive and motor scores in infants with GA <28 weeks, but there was no significant effect on NDI.

Conclusion: Early hyperglycemia is associated with white matter injury and poorer neurodevelopment in very preterm infants.

Keywords: Brain injury; Impairment; Insulin; Magnetic resonance imaging; Neurodevelopment.