Shannon E. Scratch

Neurological Consequences of Diabetic Ketoacidosis at Initial Presentation of Type 1 Diabetes in a Prospective Cohort Study of Children

OBJECTIVE To investigate the impact of new-onset diabetic ketoacidosis (DKA) during childhood on brain morphology and function. RESEARCH DESIGN AND METHODS Patients aged 6–18 years with and without DKA at diagnosis were studied at four time points: <48 h, 5 days, 28 days, and 6 months postdiagnosis. Patients underwent magnetic resonance imaging (MRI) and spectroscopy with cognitive assessment at each time point. Relationships between clinical characteristics at presentation and MRI and neurologic outcomes were examined using multiple linear regression, repeated-measures, and ANCOVA analyses. RESULTS Thirty-six DKA and 59 non-DKA patients were recruited between 2004 and 2009. With DKA, cerebral white matter showed the greatest alterations with increased total white matter volume and higher mean diffusivity in the frontal, temporal, and parietal white matter. Total white matter volume decreased over the first 6 months. For gray matter in DKA patients, total volume was lower at baseline and increased over 6 months. Lower levels of N-acetylaspartate were noted at baseline in the frontal gray matter and basal ganglia. Mental state scores were lower at baseline and at 5 days. Of note, although changes in total and regional brain volumes over the first 5 days resolved, they were associated with poorer delayed memory recall and poorer sustained and divided attention at 6 months. Age at time of presentation and pH level were predictors of neuroimaging and functional outcomes. CONCLUSIONS DKA at type 1 diabetes diagnosis results in morphologic and functional brain changes. These changes are associated with adverse neurocognitive outcomes in the medium term.

Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

Executive function outcome in preterm adolescents

Preterm birth (PT) and low birthweight (LBW) are risk factors for cognitive, academic, and behavioral difficulties. Executive functioning, which is an umbrella term encompassing higher-order problem-solving and goal-oriented abilities, may help to understand these impairments. This review article examines executive functioning in PT and LBW children, with a specific focus on adolescence and the functional consequences of executive dysfunction in this age group. We have focused on adolescence as it is a critical period for brain, cognitive and social-emotional development, and a period of increased autonomy, independence and reliance on executive functioning. While more longitudinal research is required, there is evidence demonstrating that the PT/LBW population is at increased risk for impairments across all executive domains. Emerging evidence also suggests that executive dysfunction may partly explain poorer academic and social-emotional competence in PT/LBW adolescents. In conclusion, PT/LBW adolescents exhibit poorer executive functioning, and close surveillance is recommended for high-risk individuals.

Executive Function in Adolescents Born <1000 g or <28 Weeks: A Prospective Cohort Study

BACKGROUND AND OBJECTIVES: Extremely preterm (EP; <28 weeks) birth and extremely low birth weight (ELBW; <1000 g) are risk factors for poor cognitive outcomes, including in executive function (EF; higher-order cognitive skills necessary for goal-directed, adaptive functioning and important for academic and behavioral-emotional outcomes). We aimed to (1) extend the limited data on EF in EP/ELBW survivors in adolescence compared with normal birth weight controls, and (2) determine changes in EF between ages 8 and 17 years in both groups. METHODS: Two hundred twenty-eight EP/ELBW and 166 control adolescents (mean age, 17 years) from a prospective geographical cohort were assessed with multiple EF tasks, and parent- and self-ratings of behavioral EF. The Rey Complex Figure and Behavior Rating Inventory of Executive Function parent report were also administered at age 8 years, enabling examination of change in scores between childhood and adolescence. RESULTS: EP/ELBW adolescents performed more poorly than controls in verbal processing speed, attentional control, cognitive flexibility, and goal-setting (effect sizes, −0.7 to −0.2 SD), but not psychomotor reaction time. Group differences were of similar magnitude across tasks. From childhood to late adolescence, EP/ELBW children improved their accuracy of the Rey Complex Figure copy more than controls. According to parents, executive behaviors were largely stable over time in both groups. CONCLUSIONS: Adolescents born EP/ELBW have poorer EF skills across multiple domains than controls. From childhood to late adolescence, different aspects of EF improved, but others did not, underscoring the need for multidomain, longitudinal assessments in this high-risk population.

Hippocampal volume and memory and learning outcomes at 7 years in children born very preterm.

Using magnetic resonance imaging, this study compared hippocampal volume between 145 very preterm children and 34 children born full-term at 7 years of age. The relationship between hippocampal volume and memory and learning impairments at 7 years was also investigated. Manual hippocampal segmentation and subsequent three-dimensional volumetric analysis revealed reduced hippocampal volumes in very preterm children compared with term peers. However, this relationship did not remain after correcting for whole brain volume and neonatal brain abnormality. Contrary to expectations, hippocampal volume in the very preterm cohort was not related to memory and learning outcomes. Further research investigating the effects of very preterm birth on more extensive networks in the brain that support memory and learning in middle childhood is needed.

Free Thyroxine Levels After Very Preterm Birth and Neurodevelopmental Outcomes at Age 7 Years

BACKGROUND AND OBJECTIVES: Preterm infants commonly have transient hypothyroxinemia of prematurity after birth, which has been associated with deficits in general intellectual functioning, memory, attention, and academic achievement. However, research has predominantly focused on thyroxine levels in the first 2 weeks of life and outcomes are limited to the preschool period. Our objective was to evaluate the relationships between free thyroxine (fT4) levels over the first 6 weeks after very preterm (VPT) birth with cognitive functioning and brain development at age 7 years. METHODS: A total of 83 infants born VPT (<30 weeks’ gestation) had fT4 concentrations measured postnatally and 2- and 6-week area under the curve (AUC) summary measures were calculated. Follow-up at age 7 years included a neuropsychological assessment and brain MRI. Univariable and multivariable regression modeling was used where AUC for fT4 was the main predictor of neurodevelopmental outcome at age 7 years. RESULTS: Multivariable modeling revealed that higher, not lower, postnatal fT4 levels (2-week AUC) were associated with poorer cognitive performances at age 7 years on tasks of verbal learning (P = .02), verbal memory (P = .03), and simple reaction time (P < .001). A similar pattern of results was found when the 6-week AUC was examined. No significant associations between postnatal fT4 levels and brain volumes at age 7 years were identified. CONCLUSIONS: Results are contradictory to previous observations and suggest that after adjustment for confounders, higher postnatal fT4 levels in VPT infants, rather than lower levels, may be a marker of adverse neuropsychological development in childhood.

A randomized controlled trial of cognitive behaviour therapy to improve glycaemic control and psychosocial wellbeing in adolescents with type 1 diabetes

We evaluated a cognitive behaviour therapy–based programme to improve glycaemic control and psychosocial wellbeing in adolescents with type 1 diabetes. A total of 147 adolescents aged 13–16 years were randomized to the intervention (n = 73) or standard care (n = 74). The primary outcome was glycaemic control at 3 and 12 months post randomization, and secondary measures were stress, self-efficacy and quality of life. Mixed-effects regression models were used to assess differences in means between groups at each time point. There was little evidence of differences in glycaemic control between groups. However, psychosocial wellbeing improved in the intervention group compared to the control group. Recommendations for future programmes are discussed. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12608000368336).

Clinical utility of mental state screening as a predictor of intellectual outcomes 6 months after diagnosis of type 1 diabetes.

Screening tests of basic cognitive status or ‘mental state’ have been shown to predict mortality and functional outcomes in adults. This study examined the relationship between mental state and outcomes in children with type 1 diabetes.

Accelerated corpus callosum development in prematurity predicts improved outcome

To determine: (1) whether corpus callosum (CC) size and microstructure at 7 years of age or their change from infancy to 7 years differed between very preterm (VP) and full‐term (FT) children; (2) perinatal predictors of CC size and microstructure at 7 years; and (3) associations between CC measures at 7 years or trajectories from infancy to 7 years and neurodevelopmental outcomes.

Reducing and preventing internalizing and externalizing behavior problems in children with type 1 diabetes: a randomized controlled trial of the Triple P-Positive Parenting Program

Children with type 1 diabetes are at increased risk of mental health problems, which in turn are associated with poor glycemic control, diabetes‐related complications, and long‐term psychiatric morbidity. We tested the efficacy of the Triple P‐Positive Parenting Program in reducing or preventing mental health problems and improving glycemic control in children with type 1 diabetes in a randomized controlled trial.