Moderate neonatal hypoglycemia and adverse neurological development at 2-6 years of age

To determine whether moderate neonatal hypoglycemia in otherwise healthy infants is associated with adverse neurodevelopmental outcome in pre-school children. Population-based cohort study with prospectively collected register data from Sweden. All singletons born July 1st 2008 through December 31st 2012 (n = 101,060) in the region were included. Infants with congenital malformations, infants treated in neonatal intensive care unit, infants with inborn errors of metabolism and infants to mothers with diabetes were excluded. Infants were followed-up until 2014, at 2-6 years of age. Exposure was neonatal moderate hypoglycemia. Main outcomes were a compiled neurological or neurodevelopmental outcome; any developmental delay; motor developmental delay; and cognitive developmental delay. In adjusted regression analyses, the odds ratio (OR) of any neurological or neurodevelopmental outcome was 1.48 (95% confidence interval: 1.17-1.88) in hypoglycemic compared to normoglycemic infants. The adjusted risk of any developmental delay was more than doubled (OR 2.53 [1.71-3.73]), the adjusted risk of motor developmental delay was almost doubled (OR: 1.91 [1.06-3.44]) and the adjusted risk of cognitive developmental delay was almost tripled (OR 2.85 [1.70-4.76]). Infants with early neonatal hypoglycemia (< 6 h) had a double risk (OR 1.94 [1.30-2.89]) of any neurological or neurodevelopmental outcome and a tripled risk of cognitive developmental delay (OR 3.17 [1.35-7.43]), compared to normoglycemic infants. In the first population-based study on this topic, we show that moderate neonatal hypoglycemia is associated with increased risks of impaired neurodevelopment. Current treatment routines for uncomplicated hypoglycemia should be followed.