Measure what matters: considerations for outcome measurement of care coordination for children with neurodevelopmental disabilities and medical complexity.

Introduction: Care Coordination (CC) is a significant intervention to enhance family's capacity in caring for children with neurodevelopmental disability and medical complexity (NDD-MC). CC assists with integration of medical and behavioral care and services, partnerships with medical and community-based supports, and access to medical, behavioral, and educational supports and services. Although there is some consensus on the principles that characterize optimal CC for children with NDD-MC, challenges remain in measuring and quantifying the impacts of CC related to these principles. Two key challenges include: (1) identification of measures that capture CC impacts from the medical system, care provider, and family perspectives; and (2) recognition of the important community context outside of a hospital or clinical setting. Methods: This study used a multilevel model variant of the triangulation mixed methods design to assess the impact of a CC project implemented in Alberta, Canada, on family quality of life, resource use, and care integration at the broader environmental and household levels. At the broader environmental level, we used linked administrative data. At the household level we used quantitative pre-post survey datasets, and aggregate findings from qualitative interviews to measure group-level impacts and an embedded multiple-case design to draw comparisons, capture the nuances of children with NDD-MC and their families, and expand on factors driving the high variability in outcome measures. Three theoretical propositions formed the basis of the analytical strategy for our case study evidence to explore factors affecting the high variability in outcome measures. Discussion: This study expanded on the factors used to measure the outcomes of CC and adds to our understanding of how CC as an intervention impacts resource use, quality of life, and care integration of children with NDD-MC and their families. Given the heterogeneous nature of this population, evaluation studies that account for the variable and multi-level impacts of CC interventions are critical to inform practice, implementation, and policy of CC for children with NDD-MC.

Frontoparietal and temporal white matter diffusion MRI in children and youth with prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) is associated with brain alterations and neurocognitive deficits, but relationships between brain alterations and neurocognitive deficits remain unclear. METHODS: Diffusion tensor imaging (DTI) data were obtained from 31 participants with PAE and 31 unexposed controls aged 7-15 years. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from the genu, body, and splenium of the corpus callosum (CC), bilateral cingulum, and inferior and superior longitudinal fasciculus (ILF, SLF). Participants completed language subtests from the NEPSY-II. Executive functioning was measured using the Behavior Rating Inventory of Executive Functioning (BRIEF-PR) and verbal learning was assessed using the California Verbal Learning Test-Children's Version (CVLT-C) only in children with PAE. Group differences in diffusion metrics and cognitive scores were tested. Principal component analysis was used to reduce redundancy in cognitive and behavior variables; associations between components and brain measures were then assessed. RESULTS: Children with PAE had lower MD in the right SLF compared with unexposed controls. FA was positively related to age in 6 of 9 tracts and MD negatively related to age in all tracts; there were no significant age-by-group interactions. Participants with PAE scored lower than unexposed peers on the NEPSY-II Comprehension of Instructions and Phonological Processing and above population norms (indicating worse performance) on the BRIEF-PR. Children with PAE had a negative association between a principal component closely associated with Speeded Naming and FA in the left SLF (PAE: p = 0.002) and left ILF (PAE: p = 0.002); unexposed controls showed no significant associations. CONCLUSION: We found widespread cognitive difficulties in children with PAE, but relatively limited differences in brain metrics and associations with age. Different brain-cognitive relationships were found in children with PAE compared with controls. Overall, the results provide additional evidence that PAE may lead to cognitive difficulties and disrupt typical brain-function relationships.

Brain Iron and Mental Health Symptoms in Youth with and without Prenatal Alcohol Exposure.

Prenatal alcohol exposure (PAE) negatively affects brain development and increases the risk of poor mental health. We investigated if brain volumes or magnetic susceptibility, an indirect measure of brain iron, were associated with internalizing or externalizing symptoms in youth with and without PAE. T1-weighted and quantitative susceptibility mapping (QSM) MRI scans were collected for 19 PAE and 40 unexposed participants aged 7.5-15 years. Magnetic susceptibility and volume of basal ganglia and limbic structures were extracted using FreeSurfer. Internalizing and Externalizing Problems were assessed using the Behavioural Assessment System for Children (BASC-2-PRS). Susceptibility in the nucleus accumbens was negatively associated with Internalizing Problems, while amygdala susceptibility was positively associated with Internalizing Problems across groups. PAE moderated the relationship between thalamus susceptibility and internalizing symptoms as well as the relationship between putamen susceptibility and externalizing symptoms. Brain volume was not related to internalizing or externalizing symptoms. These findings highlight that brain iron is related to internalizing and externalizing symptoms differently in some brain regions for youth with and without PAE. Atypical iron levels (high or low) may indicate mental health issues across individuals, and iron in the thalamus may be particularly important for behavior in individuals with PAE.

The brain's functional connectome in young children with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can lead to altered brain function and structure, as well as lifelong cognitive, behavioral, and mental health difficulties. Previous research has shown reduced brain network efficiency in older children and adolescents with PAE, but no imaging studies have examined brain differences in young children with PAE, at an age when cognitive and behavioral problems often first become apparent. The present study aimed to investigate the brain's functional connectome in young children with PAE using passive viewing fMRI. We analyzed 34 datasets from 26 children with PAE aged 2-7 years and 215 datasets from 87 unexposed typically-developing children in the same age range. The whole brain functional connectome was constructed using functional connectivity analysis across 90 regions for each dataset. We examined intra- and inter-participant stability of the functional connectome, graph theoretical measurements, and their correlations with age. Children with PAE had similar inter- and intra-participant stability to controls. However, children with PAE, but not controls, showed increasing intra-participant stability with age, suggesting a lack of variability of intrinsic brain activity over time. Inter-participant stability increased with age in controls but not in children with PAE, indicating more variability of brain function across the PAE population. Global graph metrics were similar between children with PAE and controls, in line with previous studies in older children. This study characterizes the functional connectome in young children with PAE for the first time, suggesting that the increased brain variability seen in older children develops early in childhood, when participants with PAE fail to show the expected age-related increases in inter-individual stability.

Comparing Attentional Networks in fetal alcohol spectrum disorder and the inattentive and combined subtypes of attention deficit hyperactivity disorder.

The Attention Network Test (ANT) was used to examine alerting, orienting, and executive control in fetal alcohol spectrum disorder (FASD) versus attention deficit hyperactivity disorder (ADHD). Participants were 113 children aged 7 to 10 years (31 ADHD-Combined, 16 ADHD-Primarily Inattentive, 28 FASD, 38 controls). Incongruent flanker trials triggered slower responses in both the ADHD-Combined and the FASD groups. Abnormal conflict scores in these same two groups provided additional evidence for the presence of executive function deficits. The ADHD-Primarily Inattentive group was indistinguishable from the controls on all three ANT indices, which highlights the possibility that this group constitutes a pathologically distinct entity.

Differentiating attention deficits in children with fetal alcohol spectrum disorder or attention-deficit-hyperactivity disorder.

AIM: The attention and inhibition problems found in children with attention-deficit-hyperactivity disorder (ADHD) are also common in children with fetal alcohol spectrum disorders (FASDs). Attempts to distinguish ADHD from FASDs in terms of these deficits are rare and were pursued in this study. METHOD: A total of 116 children (47 with ADHD, 31 males, 16 females; 30 with FASDs, 17 males, 13 females; and 39 comparison children, 20 males, 19 females) participated. The mean age was 9 years 4 months (SD 1y 8mo) in the ADHD groups, 8 years 10 months (SD 1y 2mo) in the FASD group, and 9 years 1 month (SD 1y 1mo) in the comparison group. Sustained attention was tested with a slow event rate continuous performance task (CPT). Inhibitory control was tested with both a slow and fast event rate Go/No-Go task. RESULTS: On the CPT task, children with ADHD, combined type (ADHD-C), ADHD, primarily inattentive type (ADHD-PI), and FASDs showed greater declines in task performance as a function of time than comparison children, suggesting sustained attention problems in all clinical groups. Children's Go/No-Go performance was event-rate dependent, with the ADHD-C group being affected in the slow condition and the ADHD-PI and FASD groups having problems with the fast condition. INTERPRETATION: Children with ADHD-C are typically impaired in handling understimulation, while children with FASDs may have problems with overstimulation. The dissociation in responsivity to event rate between groups may have significant differential diagnostic value.

Can attention deficit hyperactivity disorder and fetal alcohol spectrum disorder be differentiated by motor and balance deficits?

There is an ongoing debate regarding the diagnostic overlap between Attention Deficit Hyperactivity Disorder (ADHD) and Fetal Alcohol Spectrum Disorder (FASD). Differential diagnosis is important because of treatment implications. Children aged 7-10years (47 ADHD, 30 FASD, 39 controls) participated. The Movement Assessment Battery for Children (M-ABC) and the Clinical Observations of Motor and Postural Skills (COMPS) were used. Force plate and electromyography data were collected during static balance and balance perturbation. On the M-ABC both children with ADHD and FASD had more motor problems than controls. The ADHD-Combined and the ADHD-Predominantly Inattentive subgroups were similarly affected in their fine motor skills. On the COMPS, the majority of children in both groups performed in the normal range, but for those children clinically affected, it was the children with ADHD who were more likely to be severely impaired. The children with ADHD were characterized by early onset latencies of the tibialis anterior muscles and increased amplitudes of the gastrocnemius muscles. Difficulty scaling muscle force reflecting medial cerebellar involvement may be the key problem in ADHD. Cerebellar involvement in the postural instability in FASD awaits further study.