Abstract:
Background Maintenance of low blood glucose levels approximately 2.6 mmol/L or 47 mg/dL in newborns showed no adverse effects on the neurodevelopment of young children at 2 years (N = 404) and at 4.5 years of age (N = 355) enrolled in the Children with Neonatal Hypoglycaemia and their Later Development (CHYLD) study. However, recent evidence suggests that primary risks of neonatal hypoglycaemia such as gestational diabetes, prematurity, born small or born large might increase the chance of developmental deficits in young children. Guided by the bio-ecological framework, this doctoral thesis evaluates the effect of early cumulative risk and its effect on the neurocognitive and neurobehavioral development in preschool children. Integrative ‘person-focused’ and ‘variable-focused’ strategies were found useful in the evaluation of child neurodevelopment. Methods Six studies were performed in order to determine a) the impact of cumulative risk on child development and b) the developmental trajectory of cognitive constructs in at-risk young children. 1. A cluster analysis of risk factors and outcomes at 2-year and 4.5-year follow-ups in the CHYLD cohort, and validation of the 5-cluster solution. 2. A multivariate analysis to identify group differences in neurodevelopment of at-risk young children at 2 years and at 4.5 years of age. 3. A validation of the 2-cluster solution; the identification of risk predictors and profile of children in more at-risk and less at-risk groups at 4.5 years. 4. Factor analysis of two measures of executive function at 2 years and at 4.5 years of age, and comparison of factor loadings in ‘less at-risk’ children versus ‘more at-risk’ children. 5. A path analytic model to estimate the relationship between general intelligence and executive function, and the cascade impact of cumulative risk on working memory, processing speed, reasoning abilities, and motor development at 4.5 years of age. 6. A path analytic model to estimate the impact of cumulative risk on neurobehaviour and the relationship between ‘parent-rated’ executive function and measures of child psychopathology at 4.5 years of age. Results 1. The use of child risk factors (birth characteristics, primary risk factors of neonatal hypoglycaemia, parent substance use history, socioeconomic status, maternal education) were useful to aggregate patterns of neurodevelopment in at-risk young children at 2 years and at 4.5 years. 2. Significant differences were observed among groups. Neurodevelopmental deficits were observed in groups 1, 2 and 3. These groups of at-risk young children are more likely living in poor family household, lower maternal education, most likely Māori or Pacific ethnicity, and most likely born IDM and/or SGA. 3. Risk status (‘less at-risk’ versus ‘more at-risk’) was validated. Risk status was found related to deprivation, ethnic affiliation, SGA, and head circumference. Risk factors that predicted group membership were: a) prenatal substance exposure, b) postnatal substance exposure, c) SGA and ethnicity, and d) maternal education and SES. 4. ‘More at-risk’ young children had immature inhibition of prepotent responses compared to ‘less at-risk’ children at 2 years, and more immature cognitive flexibility skills at 4.5 years. In the ‘parent-rated’ measure of executive function, ‘more at-risk’ young children have lesser inhibitory skills than ‘less at-risk’ children observed at 2 and at 4.5 years of age. Hypothesised parent-beliefs of child development were significantly influential in the evaluation of executive function in young children at 2 years and at 4.5 years. 5. Intelligence was strongly associated with executive function. However, this relationship was compromised by the effect of cumulative risk. Effects of cumulative risk on verbal reasoning were mediated by working memory, whereas effects of cumulative risk on non-verbal reasoning were mediated by processing speed. Effects of cumulative risk on motor development were mediated by executive function and visuomotor integration. Therefore, the protective role of ‘observed’ executive function in reasoning abilities and motor development were established. 6. Parent-rated executive function was highly correlated with parent reports of child psychopathology. Externalising behaviour was related to inhibitory self-control index, whereas internalising behaviour was related to flexibility and metacognitive indices. Everyday executive function mediated the effects of cumulative risk on child psychopathology. However, executive function only partially mediated the impact of cumulative risk on autism-like behaviours. Therefore, the compensatory role of everyday executive function in child social adjustment was tenable. Conclusions and recommendations Cumulative risk compromises the neural integrity of young children, through a weakening of the global brain efficiency. Subtle traces of neurodevelopmental deficits were observed in areas of language development, inhibition, cognitive flexibility, visuomotor integration and motor development and higher parent reports of hyperactivity, aggressive behaviour, inattention problems and even autism-like behaviours. Moderate neonatal hypoglycaemia was not related to the established risk status in children. However, primary risks such as born small-for-gestation was related to risk status. These findings should be taken in light of the socio-ecological context of risk configuration (SES, maternal education, parent substance use, and ethnicity). Therefore, follow-up assessments and early intervention for the ‘more at- risk’ young children in the CHYLD cohort is highly recommended.