Stability of executive function in children born at risk of neonatal hypoglycemia

Abstract

Executive function plays an important role in promoting learning and social-emotional development in children. Neonatal hypoglycemia associates with executive function difficulties at 4.5 years, but little is known about the development of executive function over time in children born at risk of neonatal hypoglycemia. We aimed to describe the stability of executive function from early to mid-childhood in children born at risk of neonatal hypoglycemia and its association with neonatal hypoglycemia. Participants in a prospective cohort study of infants born at risk for neonatal hypoglycemia were assessed at ages 2, 4.5, and 9-10 years. We assessed executive function with batteries of performance-based and questionnaire-based measures, and classified children into one of four stability groups (persistent typical, intermittent typical, intermittent difficulty, and persistent difficulty) based on dichotomized scores (typical versus low at each age). Multinomial logistic regression was used to determine the associations between neonatal hypoglycemia and executive function stability groups. Three hundred and nine children, of whom 197 (64%) experienced neonatal hypoglycemia were assessed. The majority of children had stable and typical performance-based (63%) and questionnaire-based (68%) executive function across all three ages. Around one-third (30-36%) of children had transient difficulties, and only a few (0.3-1.9%) showed persistent difficulties in executive function at all ages. There was no consistent evidence of an association between neonatal hypoglycemia and the stability of executive function. Neonatal hypoglycemia does not appear to predict a specific pattern of development of executive function in children born at risk.

Keywords: Self-regulation; infants; longitudinal studies; low blood sugar level; neurocognitive development.

Figure 1. Developmental trajectories of performance-based executive function for children in each stability subgroup.

Z scores, executive function composite z scores; Persistent typical, normal performance (executive function composite score above 1 SD below mean or Global Executive Composite (GEC) <65) at 3 time points; Intermittent typical, at least one low performance at age 2 or 4.5 years but normal performance at age 9-10 years; Intermittent difficulty, at least one normal performance at age 2 or 4.5 years but low performance at age 9-10 years; Persistent difficulty group consisted of children with low performance on executive function at all 3 time points.

Figure 2. Developmental trajectories of questionnaire-based executive function for children in each stability subgroup.

GEC, Global Executive Composite; Persistent typical, normal performance (executive function composite score above 1 SD below mean or Global Executive Composite (GEC) <65) at 3 time points; Intermittent typical, at least one low performance at age 2 or 4.5 years but normal performance at age 9-10 years; Intermittent difficulty, at least one normal performance at age 2 or 4.5 years but low performance at age 9-10 years; Persistent difficulty group consisted of children with low performance on executive function at all 3 time points.

Figure 3. Relationship between neonatal hypoglycaemia and executive function stability groups.

Data are odds ratios and 95% confidence intervals (CI) using the normoglycaemia group as the comparator and adjusted for New Zealand Deprivation Index (NZDep), sex, and primary risk factor for neonatal hypoglycaemia. Perf. EF, Performance-based executive function; Z Score, Executive function composite z score; Ques. EF, Questionnaire-based executive function; GEC, Global Executive Composite; Clin. undetect., Clinically undetected hypoglycaemia. Hypoglycaemia is defined as ≥1 hypoglycaemic event, defined as the sum of nonconcurrent hypoglycaemic and interstitial episodes more than 20 minutes apart; a hypoglycaemic episode is defined as ≥1 consecutive blood glucose concentration <2.6 mmol/L and an interstitial episode as Interstitial glucose concentrations <2.6 mmol/L for 10 minutes; mild hypoglycaemia event is defined as mild hypoglycaemic events ≥2.0 to 2.5 mmol/L only; severe hypoglycaemia event defined as ≥1 severe hypoglycaemic event <2.0 mmol/L; clinically undetected hypoglycaemia, defined as ≥1 hypoglycaemic events but no hypoglycaemic episodes.