Sex and age effects on gray matter volume trajectories in young children with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) occurs in ~11% of North American pregnancies and is the most common known cause of neurodevelopmental disabilities such as fetal alcohol spectrum disorder (FASD; ~2-5% prevalence). PAE has been consistently associated with smaller gray matter volumes in children, adolescents, and adults. A small number of longitudinal studies show altered gray matter development trajectories in late childhood/early adolescence, but patterns in early childhood and potential sex differences have not been characterized in young children. Using longitudinal T1-weighted MRI, the present study characterized gray matter volume development in young children with PAE (N = 42, 84 scans, ages 3-8 years) compared to unexposed children (N = 127, 450 scans, ages 2-8.5 years). Overall, we observed altered global and regional gray matter development trajectories in the PAE group, wherein they had attenuated age-related increases and more volume decreases relative to unexposed children. Moreover, we found more pronounced sex differences in children with PAE; females with PAE having the smallest gray matter volumes and the least age-related changes of all groups. This pattern of altered development may indicate reduced brain plasticity and/or accelerated maturation and may underlie the cognitive/behavioral difficulties often experienced by children with PAE. In conjunction with previous research on older children, adolescents, and adults with PAE, our results suggest that gray matter volume differences associated with PAE vary by age and may become more apparent in older children.

Arcuate fasciculus and pre-reading language development in children with prenatal alcohol exposure.

Introduction: Prenatal alcohol exposure (PAE) contributes to widespread neurodevelopmental challenges, including reading, and has been associated with altered white matter. Here, we aimed to investigate whether arcuate fasciculus (AF) development is associated with pre-reading language skills in young children with PAE. Methods: A total of 51 children with confirmed PAE (25 males; 5.6 ± 1.1 years) and 116 unexposed controls (57 males; 4.6 ± 1.2 years) underwent longitudinal diffusion tensor imaging (DTI), for a total of 111 scans from participants with PAE and 381 scans in the unexposed control group. We delineated the left and right AF and extracted mean fractional anisotropy (FA) and mean diffusivity (MD). Pre-reading language ability was assessed using age-standardized phonological processing (PP) and speeded naming (SN) scores of the NEPSY-II. Linear mixed effects models were run to determine the relationship between diffusion metrics and age, group, sex, and age-by-group interactions, with subject modeled as a random factor. A secondary mixed effect model analysis assessed the influence of white matter microstructure and PAE on pre-reading language ability using diffusion metric-by-age-by-group interactions, with 51 age- and sex-matched unexposed controls. Results: Phonological processing (PP) and SN scores were significantly lower in the PAE group (p < 0.001). In the right AF, there were significant age-by-group interactions for FA (p < 0.001) and MD (p = 0.0173). In the left AF, there was a nominally significant age-by-group interaction for MD that failed to survive correction (p = 0.0418). For the pre-reading analysis, a significant diffusion-by-age-by-group interaction was found for left FA (p = 0.0029) in predicting SN scores, and for the right FA (p = 0.00691) in predicting PP scores. Discussion: Children with PAE showed altered developmental trajectories for the AF, compared with unexposed controls. Children with PAE, regardless of age, showed altered brain-language relationships that resembled those seen in younger typically developing children. Our findings support the contention that altered developmental trajectories in the AF may be associated with functional outcomes in young children with PAE.

Factors predicting general health concerns and atypical behaviours in children with prenatal alcohol exposure and other adverse exposures.

Background: Prenatal alcohol exposure (PAE) can have significant negative consequences on the health outcomes of children. Children with PAE often experience other prenatal and postnatal adverse exposures. Increased rates of general health concerns and atypical behaviours are seen in both children with PAE as well as with other patterns of adverse exposures, although these have not been systematically described. The association between multiple adverse exposures and adverse health concerns and atypical behaviours in children with PAE is unknown. Methods: Demographic information, medical history, adverse exposures, health concerns, and atypical behaviours were collected from children with confirmed PAE (n = 22; 14 males, age range = 7.9-15.9 years) and their caregivers. Support vector machine learning classification models were used to predict the presence of health concerns and atypical behaviours based on adverse exposures. Associations between the sums of adverse exposures, health concerns, and atypical behaviours were examined using correlation analysis. Results: All children experienced health concerns, the most common being sensitivity to sensory inputs (64%; 14/22). Similarly, all children engaged in atypical behaviours, with atypical sensory behaviour (50%; 11/22) being the most common. Prenatal alcohol exposure was most important factor for predicting some health concerns and atypical behaviours, and alone and in combination with other factors. Simple associations between adverse exposures could not be identified for many health concerns and atypical behaviours. Conclusion: Children with PAE and other adverse exposures experience high rates of health concerns and atypical behaviours. This study demonstrates the complex effects of multiple adverse exposures on health and behaviour in children.

Limbic brain subregions associated with mental health symptoms in youth with and without prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) can result in reduced brain volume and an increased risk of mental health challenges. Limbic brain structures such as the hippocampus, thalamus, and amygdala often exhibit smaller volumes in youth with PAE, and similar volume reductions are observed in unexposed youth with symptoms of depression, bipolar disorder, anxiety, and schizophrenia. However, the role of volume reductions in these brain regions in mental health challenges remains unclear for individuals with PAE. METHODS: Thirty-four youth with PAE and 72 unexposed youth aged 7-16 years completed a T1-weighted magnetic resonance imaging scan. FreeSurfer was used to process and extract volumes for hippocampal subfields, thalamic subnuclei, and amygdalar subnuclei. Depression and anxiety symptoms were measured using the Behavioral Assessment System for Children (BASC-2/3-PRS), the Children's Depression Inventory, and the Multidimensional Anxiety Scale for Children. We tested whether limbic subregion volumes differed between youth with and those without PAE and whether volumes were associated with depression and/or anxiety symptoms, controlling for age and gender. RESULTS: Multiple hippocampal and thalamic subregions, but not amygdalar subnuclei, were smaller in individuals with PAE. Multiple group-brain interactions were observed for depression symptoms and subregion volumes. Negative associations between anxiety and limbic subregions were observed across groups. CONCLUSIONS: These findings show extensive volume reductions in the hippocampus and thalamus in youth with PAE. PAE also appears to disrupt the association between depression symptoms and limbic subregions in youth, which may have implications for interventions in these individuals. Anxiety symptoms in youth with and without PAE are similarly associated with limbic volumes.

Improving Care for Families and Children with Neurodevelopmental Disorders and Co-occurring Chronic Health Conditions Using a Care Coordination Intervention.

OBJECTIVE: This clinical intervention study aimed to improve care integration and health service delivery for children with concurrent neurodevelopmental disorders and chronic health conditions. This population has significant unmet needs and disproportionate deficits in service delivery. A lack of coordination across child service sectors is a common barrier to successful treatment and support of children with neurodevelopmental disorders with complex medical needs. METHODS: This project implemented an innovative care coordination model, involving one-on-one supports from a trained care coordinator who liaised with the broader intersectoral care team to improve joint care planning, integration of services, and the experience of both families and care providers. To evaluate the impact of care coordination activities, a single-group interventional study was conducted using a repeated-measures framework (at 0, 6, and 12 months) using previously established outcome measures. RESULTS: Over 2 years, this project provided care coordination to 84 children and their families, with an age range from 2 to 17 years. The care coordination intervention demonstrated positive impacts for children, families, and care teams and contributed to clinical efficiencies. Children had fewer visits to the emergency department and less frequent acute care use. Improvement in access to services, joint care planning and communication across providers, and better linkage with school supports were demonstrated. Families reported that the program decreased their stress around coordinating care for their child. CONCLUSION: This work demonstrated that intersectoral care coordination is attainable through innovative and collaborative practice for children with complex neurodevelopmental and medical needs.

The transition to adult income supports for youth that received special education in British Columbia, Canada: A cohort study.

Youth in special education have complex needs that are supported across multiple systems. Our research investigates the use of adult income assistance, as one structure that supports youth as they transition to adulthood. We created a cohort of youth (5-22 years old) using linked administrative data from British Columbia government ministries from 1996 to 2018. Youth were grouped by their special education funding (most to least; Level 1, Level 2, Level 3, Unfunded, and no special education). We investigated (1) youth characteristics and service use patterns, (2) which youth used income supports after the child-to-adult transition (19-22 years old), and what youth characteristics and service use patterns were associated with use, and (3) how much income support they used (CAD$). Of 174,527 youth, 254 (0.1%) were Level 1, 6020 (3.4%) were Level 2, 4409 (2.5%) were Level 3, 21,232 (12.2%) were Unfunded, and 142,612 (81.7%) were not in special education. Youth assigned higher funding levels, compared to lower levels, generally had increased service use, and in the transition to adult services were more likely to use income supports, and received more income support. An important exception was youth with serious behavioural/mental health special education funding (Level 3), who had increased service use for their level of funding, but received less income support due to a reliance on Temporary versus Disability Assistance. Youth that received an accredited diploma were less likely to use income supports. Factors related to the use of income supports are further described. This study highlights differences in access to income support when youth transition to adult services and considerations around equitable access to support.

Prenatal Exposure And Child brain and mental Health (PEACH) study: protocol for a cohort study of children and youth with prenatal alcohol exposure.

INTRODUCTION: Fetal alcohol spectrum disorder (FASD), which is caused by prenatal alcohol exposure (PAE), affects an estimated 4% of North Americans, and is the most common preventable cause of intellectual disability. Mental health problems, including anxiety and depression, are experienced by nearly all individuals with FASD. However, there is very limited knowledge about effective mental health treatments for individuals with FASD; effective treatments are hindered in part due to a lack of understanding of the basic neurobiology underlying internalising disorders in youth with FASD. METHODS AND ANALYSIS: The Prenatal Exposure And Child brain and mental Health (PEACH) study includes children aged 7-18 years. We will use longitudinal neuroimaging (anatomical T1-weighted, diffusion and passive viewing function MRI) and mental health assessments (Behaviour Assessment Scale for Children, Multi-dimensional Anxiety Scale for Children, Children's Depression Inventory (CDI-2), Kiddie Scale of Affective Disorders) to: (1) characterise brain development trajectories in youth with FASD, (2) determine whether brain alterations mediate increased anxiety and depression in youth with FASD and (3) identify baseline brain features that predict changes of anxiety and depression symptoms over the next 2 years. All of this will be done while considering sex and adverse postnatal experiences, which can significantly impact mental health and brain outcomes. This project will forge new understanding of FASD and mental health from a neurobiological perspective, highlighting key time periods (ie, sensitive windows) and brain regions (ie, that may be susceptible to neurostimulation), while identifying factors that predict individual trajectories of anxiety and depression symptoms. ETHICS AND DISSEMINATION: This study was approved by the University of Calgary Conjoint Health Research Ethics Board and the University of Alberta Health Research Ethics Board. Study results will be disseminated in peer-reviewed journals, at relevant conferences and in conjunction with our knowledge mobilisation partners.

White matter alterations in young children with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can lead to cognitive, behavioural, and social-emotional challenges. Previous neuroimaging research has identified structural brain alterations in newborns, older children, adolescents, and adults with PAE; however, little is known about brain structure in young children. Extensive brain development occurs during early childhood; therefore, understanding the neurological profiles of young children with PAE is critical for early identification and effective intervention. We studied 54 children (5.21 ± 1.11 years; 27 males) with confirmed PAE (94% also had other prenatal exposures, 74% had adverse postnatal experiences) compared with 54 age- and sex-matched children without PAE. Children underwent diffusion tensor imaging between 2 and 7 years of age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were obtained for 10 major white matter tracts. Univariate analyses of covariance were used to test group differences (PAE vs. control) controlling for age and sex. The PAE group had higher FA in the genu of the corpus callosum and lower MD in the bilateral uncinate fasciculus. The PAE group also had lower tract volume in the corpus callosum, the bilateral inferior fronto-occipital fasciculi, and the right superior longitudinal fasciculus. Our findings align with studies of newborns with PAE reporting lower diffusivity, but contrast those in older populations with PAE, which consistently report lower FA and higher MD. Further research is needed to understand trajectories of white matter development and how our results of higher FA/lower MD in young children connect with lower FA/higher MD observed at older ages.

Different brain profiles in children with prenatal alcohol exposure with or without early adverse exposures.

Prenatal alcohol exposure (PAE) can alter brain development and impact mental health outcomes, and often occurs in conjunction with postnatal adversity (e.g., maltreatment). However, it is unclear how postnatal adverse exposures may moderate mental health and brain outcomes in children with PAE. T1-weighted and diffusion magnetic resonance imaging were obtained from 66 participants aged 7-16 years. Twenty-one participants had PAE and adverse postnatal exposures (PAE+), 12 had PAE without adverse postnatal exposures (PAE-), and 33 were age- and gender-matched controls unexposed to either prenatal alcohol or postnatal adversity. Internalizing and externalizing mental health symptoms were assessed using the Behavioral Assessment System for Children II, Parent-Rating Scale. ANCOVAs were used to compare mental health symptoms, limbic and prefrontal cortical volumes, and diffusion parameters of cortico-limbic white matter tracts between groups, and to assess brain-mental health relationships. Both PAE groups had worse externalizing behavior (higher scores) than controls. The PAE- group had lower fractional anisotropy (FA) in the bilateral cingulum and left uncinate fasciculus, and smaller volumes in the left anterior cingulate cortex than controls and the PAE+ group. The PAE- group also had higher mean diffusivity (MD) in the left uncinate than the PAE+ group, and smaller right anterior cingulate and superior frontal gyrus volumes than controls. These findings show different brain structure and mental health symptom profiles in children with PAE with and without postnatal adversity, highlighting the need to consider adverse postnatal exposures in individuals with PAE.

Dietary and Supplement-Based Complementary and Alternative Medicine Use in Pediatric Autism Spectrum Disorder.

Previous literature has shown that complementary and alternative medicine (CAM) is steadily increasing in autism spectrum disorder (ASD). However, little data is currently available regarding its use, safety, and efficacy in children with ASD. Thus, the purpose of this study is to describe the use of supplement-based CAM therapies in children between the ages of 4 to 17 years with ASD. This population-based, cross-sectional study evaluated children with ASD regarding supplement use. A total of 210 participants were recruited from a variety of sources including educational and physical activity programs, and social media to complete a questionnaire. Primary caregivers provided information on current supplement based CAM use. Data evaluated the proportion of children that used supplement therapies, the types of supplements used, reasons for use, perceived safety, and demographic factors associated with use (e.g. income, parental education, severity of disorder). Seventy-five percent of children with ASD consumed supplements with multivitamins (77.8%), vitamin D (44.9%), omega 3 (42.5%), probiotics (36.5%), and magnesium (28.1%) as the most prevalent. Several supplements, such as adrenal cortex extract, where product safety has not yet been demonstrated, were also reported. A gluten free diet was the most common specialty diet followed amongst those with restrictions (14.8%). Health care professionals were the most frequent information source regarding supplements; however, 33% of parents reported not disclosing all their child's supplements to their physician. In conclusion, the use of supplement therapies in children with ASD is endemic and highlights the need for further research concerning public health education surrounding safety and efficacy.

Characterizing adverse prenatal and postnatal experiences in children.

BACKGROUND: Prenatal and postnatal adversities, including prenatal alcohol exposure (PAE), prenatal exposure to other substances, toxic stress, lack of adequate resources, and postnatal abuse or neglect, often co-occur. These exposures can have cumulative effects, or interact with each other, leading to worse outcomes than single exposures. However, given their complexity and heterogeneity, exposures can be difficult to characterize. Clinical services and research often overlook additional exposures and attribute outcomes solely to one factor. METHODS: We propose a framework for characterizing adverse prenatal and postnatal exposures and apply it to a cohort of 77 children. Our approach considers type, timing, and frequency to quantify PAE, other prenatal substance exposure, prenatal toxic stress, postnatal threat (harm or threat of harm), and postnatal deprivation (failure to meet basic needs) using a 4-point Likert-type scale. Postnatal deprivation and harm were separated into early (<24 months of age) and late (≥24 months) time periods, giving seven exposure variables. Exposures were ascertained via health records, child welfare records, interviews with birth parents, caregivers, and/or close family/friends. RESULTS: Nearly all children had co-occurring prenatal exposures, and two-thirds had both prenatal and postnatal adversities. Children with high PAE were more likely to experience late postnatal adversities, and children with other prenatal substance exposure were more likely to have early postnatal deprivation. Postnatal adversities were more likely to co-occur. CONCLUSION: This framework provides a comprehensive picture of a child's adverse exposures, which can inform assessment and intervention approaches and policy and will be useful for future research.

Weighted vests' effect on social attention for toddlers with Autism Spectrum Disorders.

BACKGROUND: There is limited research validating the use of weighted vests for problem behaviours/social attention in toddlers with autism spectrum disorders (ASD) although vests are commonly used in early intervention to improve attention. PURPOSE: The effect of weighted vests on competing behaviours and joint attention (a pivotal skill for development and a core deficit for toddlers with ASD) in semistructured play with their mothers was investigated. METHODS: A multiple baseline design that included generalization probes to provide evidence of treatment effects across adult female play partners. Unambiguous definitions were created for competing behaviours and joint attention resulting in good inter-observer reliability. Mothers' morale was measured pre- and post-intervention. FINDINGS: There were no replicated effects of vests on competing behaviours or joint attention. Mothers experienced increased morale in spite of null effects of the intervention. IMPLICATIONS: The findings suggest needed re-evaluation of the use of weighted vests with toddlers.

Medication effects on symptoms of attention-deficit/hyperactivity disorder in children with fetal alcohol spectrum disorder.

Attention-deficit/hyperactivity disorder (ADHD) may be the most common mental health disorder in children with fetal alcohol spectrum disorders (FASD). Despite this, little information is available regarding the effectiveness of ADHD treatment in this population. This study, conducted within a clinical service, aimed to assess the impact of medication on symptoms of ADHD in children with FASD by determining (a) the extent of change in ADHD symptoms with medication, and (b) whether differences in improvement are seen between symptom domains. Data were extracted from the medical records of 27 children with FASD who had been referred to an ADHD medication service at the Alberta Children's Hospital in Canada. Participants were primarily male and ranged in age from 5 years 6 months to 14 years 5 months. Teacher MTA-SNAP-IV scores were the primary outcome measure. Baseline, best, and change scores across three symptom domains (inattention, hyperactivity/impulsivity, and opposition/defiance) were determined. A total of 41 medication trials was conducted. More children obtained normalized best scores for hyperactivity/impulsivity (n = 18) and opposition/defiance (n = 19) than for inattention (n = 9) across medication trials. These findings suggest that inattention may be less responsive to ADHD medication. Replication in larger samples with a placebo-controlled design is required.