Math Abilities Among Children with Neurodevelopmental Difficulties: Understanding Cognitive Factors and Evaluating a Pilot Intervention.

Math development in children relies on several underlying cognitive functions, including executive functions (EF), working memory (WM), and visual-motor abilities, such as visual-motor integration (VMI). Understanding how these cognitive factors contribute to children's math performance is critical to supporting math learning and long-term math success. The present quasi-experimental waitlist control study (N = 28) aimed to (a) examine the unique contributions of EF, WM, and VMI to math abilities among children ages 5-8 years old with neurodevelopmental difficulties; (b) determine whether a math intervention (the Mathematics Interactive Learning Experience; MILE) that supports these cognitive processes was effective when modified to be delivered to small groups in a school setting, and (c) examine whether any participant characteristics, such as age or IQ, were correlated with post-intervention math score changes. At baseline, participants' math scores were significantly below the normative mean in all math content areas (ps < .01). EF, WM, and VMI were highly correlated with math ability; however, verbal WM was the only unique predictor of math ability in regressions analysis. Compared to a waitlist control group, children in the immediate MILE intervention group achieved significantly greater math gains overall. When all children who ultimately completed the intervention were considered together, significant improvement was observed in more than half of math content areas. Furthermore, at the individual level, 85.7% of participants showed reliable change in at least one math content area. Implications for supporting math learning in children with neurodevelopmental difficulties are discussed.

Adaptive behavior, sleep, and physical activity in adolescents with fetal alcohol spectrum disorder.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is broadly associated with impairments to adaptive behavior and dysfunctional sleep. Associations between sleep, adaptive behavior, and physical activity are frequently drawn in discussions of typical development and other clinical conditions. AIMS: In this study, we sought to characterize patterns of sleep, adaptive behavior, and physical activity in adolescents with FASD. We also investigated the associations between sleep, adaptive behavior, and physical activity within this population. METHODS AND PROCEDURES: Twenty-seven adolescents aged 11- to 17-years with a diagnosis of FASD and their caregivers participated in this study. All participants completed parent and youth questionnaires on adaptive behavior, sleep, and physical activity. OUTCOMES AND RESULTS: Adolescents with FASD displayed significant impairments to all domains of adaptive behavior and considerable sleep disturbance. Worse sleep was associated with older age and sleep-related breathing disturbances were associated with poorer social adaptive behavior. Participation in physical activity, particularly organized sport, was strongly associated with better adaptive behavior. CONCLUSIONS AND IMPLICATIONS: Adolescents with FASD experience considerable challenges with regards to sleep and adaptive behavior. Physical activity, particularly organized sport, may provide opportunities for the improvement of adaptive behavior in this population.

Prioritizing a Research Agenda of Transitional Care Interventions for Childhood-Onset Disabilities.

Transitional care interventions have the potential to optimize continuity of care, improve health outcomes and enhance quality of life for adolescents and young adults living with chronic childhood-onset disabilities, including neurodevelopmental disorders, as they transition to adult health and social care services. The paucity of research in this area poses challenges in identifying and implementing interventions for research, evaluation and implementation. The purpose of this project was to advance this research agenda by identifying the transitional care interventions from the scientific literature and prioritize interventions for study. A modified-Delphi approach involving two rounds of online surveys followed by a face-to-face consensus meeting with knowledge users, researchers and clinician experts in transitional care (n = 19) was used. A subsequent virtual meeting concluded the formulation of next steps. Experts rated 16 categories of interventions, derived from a systematic review, on importance, impact, and feasibility. Seven of the 16 interventions categories received a mean score rating of ≥7 (out of 10) on all three rating categories. Participants then rank ordered the reduced list of seven interventions in order of priority and the top four ranked interventions advanced for further discussion at a consensus meeting. Using the Template for Intervention Description and Replication (TIDieR) checklist as a guide, the participants identified that a study of a peer system navigator was worthy of future evaluation. This study highlighted that transitional care interventions are complex and multifaceted. However, the presence of a peer to support system navigation, advocacy and individual and family education was considered the most ideal intervention addressing the current gap in care. Future research, which aims to engage patients and families in a co-design approach, is recommended to further develop this intervention.

Characterizing adverse childhood experiences among children and adolescents with prenatal alcohol exposure and Fetal Alcohol Spectrum Disorder.

BACKGROUND: Individuals with Fetal Alcohol Spectrum Disorder (FASD) and prenatal alcohol exposure (PAE) face elevated rates of postnatal environmental adversity across the lifespan. OBJECTIVE: We explored early adversity among children and adolescents with PAE. PARTICIPANTS AND SETTING: Our sample included 333 children and adolescents with PAE assessed at a Canadian FASD diagnostic clinic, 66% of whom were diagnosed with FASD. METHODS: Data were collected retrospectively via record review, and adversity was measured using the Adverse Childhood Experiences Questionnaire (ACE-Q). RESULTS: Participants experienced high levels of adversity (mean ACE score of 3.4), which increased with age, mental health comorbidity, and number of living placements. Common ACEs included: not being raised by both biological parents (97.3%), caregiver disruption (88.5%), and exposure to household substance use (69.7%). Females had significantly higher rates of sexual abuse than males (p < .001, ø = -0.18). There was no difference in total ACE scores between participants diagnosed with FASD versus those not diagnosed, but participants with FASD were less likely to live with both biological parents (p < .001, ø = .19) or to have been exposed to household mental health problems (p = .007, ø = -0.15). CONCLUSIONS: Children and adolescents with PAE experience high rates of early adversity. Practice and policy initiatives are needed to improve early detection of ACEs among children with PAE, and of PAE among children with ACEs. Targeted supports are needed to strengthen the early caregiving environment and mitigate the risks of adversity to support healthy outcomes for individuals with PAE and FASD.

Transitional Care Interventions for Youth With Disabilities: A Systematic Review.

CONTEXT: Transition from the pediatric to the adult health care system is a complex process that should include medical, psychosocial, educational, recreational, and vocational considerations. OBJECTIVE: In this systematic review, we aim to synthesize the evidence on transitional care interventions (TCIs) to improve the quality of life (QoL) for adolescents and young adults with childhood-onset disabilities, including neurodevelopmental disorders. DATA SOURCES: Four electronic databases (Medline, Embase, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature) were searched. STUDY SELECTION: In the included studies, researchers examined TCIs for adolescents and young adults (12-24 years of age) with childhood-onset disabilities. Studies were experimental, quasi-experimental, and observational studies published in the last 26 years. DATA EXTRACTION: Two reviewers independently completed study screening, data extraction, and risk-of-bias assessment. RESULTS: Fifty-two studies were included. Five studies reported on QoL, but statistically significant improvements were noted in only 1 of these studies. Significant improvements were also found in secondary outcomes including disability-related knowledge and transitional readiness. TCIs targeted patients, families and/or caregivers, and health care providers and exhibited great heterogeneity in their characteristics and components. LIMITATIONS: Inconsistent reporting on interventions between studies hindered synthesis of the relationships between specific intervention characteristics and outcomes. CONCLUSIONS: Although there is limited evidence on the impact of TCIs on the QoL for youth with childhood-onset disabilities, there is indication that they can be effective in improving patient and provider outcomes. The initiation of transition-focused care at an early age may contribute to improved long-term health outcomes in this population.

Current Socioeconomic Status Correlates With Brain Volumes in Healthy Children and Adolescents but Not in Children With Prenatal Alcohol Exposure.

Individuals with prenatal alcohol exposure (PAE) exhibit neurological deficits associated with brain injury including smaller brain volumes. Additional risk factors such as lower socioeconomic status (SES) may also have an impact on brain development for this population. This study examined how brain volumes are related to SES in both neurotypically developing children and adolescents, and those with PAE. 3D T1-weighted MPRAGE images were acquired from 69 participants with PAE (13.0 ± 3.2 years, range 7.1-18.8 years, 49% female) and 70 neurotypical controls (12.4 ± 2.9 years, range 7.0-18.5 years, 60% female) from four scanning sites in Canada. SES scores calculated using Hollingshead's Four-Factor Index of Social Status from current caregiver placement were not significantly different between groups, though more children with PAE had lower SES scores compared to controls. Psychometric data comprised 14 cognitive measures, including executive functioning, attention and working memory, memory, math/numerical ability, and word reading. All cognitive scores were significantly worse in children with PAE compared to controls, though SES was not correlated with cognitive scores in either group after correction for multiple comparisons. All 13 brain volumes were smaller in children with PAE compared to children in the control group. Higher SES was associated with larger hippocampus and amygdala volumes in controls, but there were no such associations in children with PAE. Direct evaluation of the interaction between SES and diagnostic group did not show a significant differential impact of SES on these structures. These findings support previous links between SES and brain volumes in neurotypically developing children, but the lack of such a relationship with SES in children with PAE may be due to the markedly smaller brain volumes resulting from the initial brain injury and postpartum brain development, regardless of later SES.

Pragmatic trial evaluating the effectiveness of a patient navigator to decrease emergency room utilisation in transition age youth with chronic conditions: the Transition Navigator Trial protocol.

INTRODUCTION: Transition to adult care is a challenging and complex process for youth with special healthcare needs. We aim to compare effectiveness of a patient navigator service in reducing emergency room (ER) use among adolescents with chronic health conditions transitioning to adult care. METHODS AND ANALYSIS: Pragmatic randomised controlled trial parallel group design comparing ER visit rates between patients with access to a personalised navigator intervention compared with usual care. Unit of randomisation is the patient. Treatment assignment will not be blinded. Embedded qualitative study to understand navigator's role and cost analysis attributable to the intervention will be performed. Patients aged 16-21 years, followed within a chronic disease clinic, expected to be transferred to adult care within 12 months and residing in Alberta during study period will be recruited from three tertiary care paediatric hospitals. Sample size will be 300 in each arm. Navigator intervention over 24 months is designed to assist participants in four domains: transition preparation, health system brokering, socioeconomic determinants of health and self-management. Primary outcome is ER visit rate during observation period. Secondary outcomes are ambulatory and inpatient care utilisation measures, as well as Transition Readiness Assessment Questionnaire score, and Short-Form Health Survey 12 (SF-12) score at 6 and 18 months post-randomisation. Poisson regression will compare rates of ER/urgent care visits between navigator and control participants, using intention to treat principle. Cost analysis of the intervention will be conducted. Thematic analysis will be used to identify perceptions of stakeholders regarding the role of navigators. ETHICS AND DISSEMINATION: Ethics approval was obtained from the University of Calgary Conjoint Health Research Ethics Board (REB #162561) and the University of Alberta Health Research Ethics Board (Pro00077325). Our team is composed of diverse stakeholders who are committed to improving transition of care who will assist with dissemination of results. TRIAL REGISTRATION NUMBER: NCT03342495.

The cost-effectiveness of screening tools used in the diagnosis of fetal alcohol spectrum disorder: a modelled analysis.

BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is characterized by physical and neurological abnormalities resulting from prenatal alcohol exposure. Though diagnosis may help improve patient outcomes, the diagnostic process can be costly. Subsequently, screening children suspected of FASD prior to diagnostic testing has been suggested, to avoid administering testing to children who are unlikely to receive a diagnosis. The present study set out to assess the cost-effectiveness of currently recommended FASD screening tools. METHODS: The screenings tools evaluated were chosen from Children's Healthcare Canada's National Screening Toolkit for Children and Youth Identified and Potentially Affected by FASD and include meconium testing of fatty acid ethyl esters (meconium testing) and the neurobehavioral screening tool (NST). An economic model was constructed to assess cost-effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of findings. Costs reflect 2017 Canadian dollars and the perspective is the public healthcare system. RESULTS: Both screening tools evaluated resulted in reduced costs and fewer diagnosed years of life than a no screening strategy in which all children suspected of FASD receive diagnostic testing. The model predicts that screening newborns with meconium testing results in a reduced cost of $89,186 per 100 individuals screened and 38 fewer diagnosed years of life by age 18, corresponding to an incremental cost-effectiveness ratio (ICER) of $2359. Screening children with the NST resulted in a reduced cost of $183,895 per 100 individuals screened and 77 fewer diagnosed years of life by age 18, corresponding to an ICER of $2390. CONCLUSION: Findings suggest that screening is associated with less use of healthcare recourses but also fewer years of life with an FASD diagnosis over a no screening strategy. Since diagnosis can be key to children receiving timely and appropriate health and educational services, cost-savings must be weighed against the fewer years of life with a diagnosis associated with screening.

Health care stakeholder perspectives regarding the role of a patient navigator during transition to adult care.

BACKGROUND: Transition to adult care represents a vulnerable period for young people with special health care needs as they navigate multiple life transitions and developmental issues. Patient navigators are a promising intervention designed to facilitate the transfer from pediatric to adult care. However, consistent definitions, key tasks, roles and responsibilities are lacking in guiding the scope of practice and the implementation of patient navigators. METHODS: Fundamental qualitative description was utilized in this study to identify perceptions from health care providers about implementing a patient navigator service for young people with special health care needs in transition to adult care. A purposive sample of health care providers with a variety of backgrounds within pediatric and adult systems in Alberta, Canada were recruited. Semi-structured interviews with participants were analyzed using thematic analysis to inductively identify perceptions regarding the role of patient navigators. RESULTS: A total of 43 health care providers highlighted the need for a patient navigator service to encompass 4 key stages for young people with special health care needs transitioning from pediatric to adult services: (1) identification of young people with special health care needs and families requiring support, (2) preparation for transfer, (3) health system navigation and, (4) post-transfer support. CONCLUSIONS: The results of this qualitative study provide guidance for the development of patient navigator interventions for young people with special health care needs, as well as provide support for current transition services offered across Canada.

Deferred diagnosis in children assessed for fetal alcohol spectrum disorder.

Early intervention for individuals with FASD is paramount, thus exploring factors that affect the diagnostic process is critical. This process can be complicated by challenges gathering background information, accurately evaluating higher-level cognitive skills across ages, and teasing apart the impact of life adversities from the effects of prenatal alcohol exposure. This study is a retrospective file review of 154 children (44% female; mean age 8.4 years, range 1.0 to 16.9) deferred at their first FASD assessment, and 51 (43% female; mean 9.9 years, range 2.7 to 17.2) who returned for a second assessment. Data was collected from three Canadian FASD clinics to explore reasons for deferral, the clinical profile of deferred children, why some returning children were diagnosed while others were not, and changes between assessments. Results suggest that deferred children initially lacked evidence of abnormalities sufficient for a diagnosis, presented with areas of relative neurobehavioral strength and difficulty, and children eventually diagnosed with FASD showed significantly more impaired brain function (p < 0.001, ηp2 = 0.547), postnatal risk (p = 0.021, ηp2 = 0.121), and comorbidities (p = 0.038, ηp2 = 0.085) than undiagnosed children. These findings provide important insights into the process of clinical assessment for FASD.

Mathematics intervention for children with fetal alcohol spectrum disorder: A replication and extension of the math interactive learning experience (MILE) program.

BACKGROUND: Individuals with fetal alcohol spectrum disorders (FASD) experience deficits in behavior, cognition, and academic functioning resulting from prenatal alcohol exposure (PAE). Although receiving intervention for developmental disabilities is a strong protective factor against negative outcomes in FASD, intervention research in this population is in its infancy. AIMS: The purpose of this study was to replicate and extend a mathematics intervention, the Math Interactive Learning Experience (MILE) program, which was developed in the USA specifically for children with FASD. METHODS: Twenty-eight Canadian children aged 4-10 years with confirmed PAE or an FASD diagnosis were assigned to either the MILE intervention or a contrast intervention. RESULTS: Following a relatively brief, individualized, one-on-one intervention, children in the MILE group demonstrated significantly greater changes in math achievement compared to the contrast group. Significant changes in other cognitive functions were not observed. Older age, lower IQ, and confirmed PAE but no FASD diagnosis were associated with greater math achievement change in the MILE group. CONCLUSIONS: The replication and extension of the math intervention appears to have significant, positive impact on mathematics achievement scores of children with PAE and FASD.

Preserved cortical asymmetry despite thinner cortex in children and adolescents with prenatal alcohol exposure and associated conditions.

Prenatal alcohol exposure (PAE) is associated with reduced overall brain volume. Although this has been reported consistently across studies, the status of cortical thickness after PAE is more variable. The cortex is asymmetric in typical controls, but it is unclear whether the left and right counter parts of the cortical gray matter are unevenly influenced in postpartum brain development after PAE. Brain MRI was acquired in a newly recruited sample of 157 participants (PAE: N = 78, 5.5-18.9 years, 40 females and controls: N = 79, 5.8-18.5 years, 44 females) across four Canadian sites in the NeuroDevNet project. The PAE group had other confounds such as psychiatric co-morbidity, different living environment, and so on, not present in the control group. In agreement with previous studies, the volumes of all brain structures were reduced in PAE compared to controls, including gray and white matter of cerebrum and cerebellum, and all deep gray matter including the hippocampus, amygdala, thalamus, caudate, putamen, and pallidum. The PAE group showed reductions in global and regional cortical thickness, while the pattern and degree of cortical thickness asymmetry were preserved in PAE participants with the greatest rightward asymmetry in the lateral parietal lobe and the greatest leftward asymmetry in the lateral frontal cortex. This persistent asymmetry reflects that the homologous left and right cortical regions followed typical relative developmental patterns in the PAE group despite being thinner bilaterally than controls. Hum Brain Mapp 39:72-88, 2018. © 2017 Wiley Periodicals, Inc.

Sexual dimorphism of volume reduction but not cognitive deficit in fetal alcohol spectrum disorders: A combined diffusion tensor imaging, cortical thickness and brain volume study.

Quantitative magnetic resonance imaging (MRI) has revealed abnormalities in brain volumes, cortical thickness and white matter microstructure in fetal alcohol spectrum disorders (FASD); however, no study has reported all three measures within the same cohort to assess the relative magnitude of deficits, and few studies have examined sex differences. Participants with FASD (n = 70; 30 females; 5-32 years) and healthy controls (n = 74; 35 females; 5-32 years) underwent cognitive testing and MRI to assess cortical thickness, regional brain volumes and fractional anisotropy (FA)/mean diffusivity (MD) of white matter tracts. A significant effect of group, age-by-group, or sex-by-group was found for 9/9 volumes, 7/39 cortical thickness regions, 3/9 white matter tracts, and 9/10 cognitive tests, indicating group differences that in some cases differ by age or sex. Volume reductions for several structures were larger in males than females, despite similar deficits of cognition in both sexes. Correlations between brain structure and cognitive scores were found in females of both groups, but were notably absent in males. Correlations within a given MRI modality (e.g. total brain volume and caudate volume) were prevalent in both the control and FASD groups, and were more numerous than correlations between measurement types (e.g. volumes and diffusion tensor imaging) in either cohort. This multi-modal MRI study finds widespread differences of brain structure in participants with prenatal alcohol exposure, and to a greater extent in males than females which may suggest attenuation of the expected process of sexual dimorphism of brain structure during typical development.

Effects of working memory training on children born preterm.

Researchers have reported benefits of working memory training in various populations, however, the training gains in preterm population is still inadequately studied. This study aimed to investigate the transfer and lasting effects of an online working memory training program on a group of preterm children aged between 4 and 6 years (mean gestational age = 28.3 weeks; mean birth weight = 1153 grams). Children were asked to perform the Cogmed JM at home for approximately 15 minutes a day, 5 days a week for 5 weeks. Their nontrained working memory and attention were assessed pre-training, post-training, and at 5-week follow-up. Parent ratings on children's executive functions were obtained at the three time points. Results revealed that significant improvements in verbal working memory was emerging in preterm children at 5-week follow-up, while significant gains in visuospatial working memory was found post-training and at 5-week follow-up in age-matched term-born children. These results indicated that working memory training has benefits on preterm children; however, the gains are different from those observed in term-born children. No significant differences in attention and parent-rated EF were found in either group across time. The possible explanations for the training benefits observed in preterm children were discussed.

Intervention recommendations and subsequent access to services following clinical assessment for fetal alcohol spectrum disorders.

BACKGROUND: Children with fetal alcohol spectrum disorders (FASD) and prenatal alcohol exposure (PAE) experience multiple difficulties requiring various interventions. Researchers have called for investigation into service use with respect to clinically recommended interventions. AIMS: To examine intervention recommendations for children with FASD/PAE and subsequent access to these recommended interventions. METHODS AND PROCEDURES: Intervention recommendations following FASD assessment were examined for children (1-17 years). Recommendations were compared according to diagnostic status and demographic and environmental variables. Subsequent access to several interventions was examined for 45 participants. OUTCOMES AND RESULTS: A variety of recommendations were given. Children with FASD received more recommendations overall and received more education, anticipatory guidance, family support, and safety recommendations than undiagnosed children with PAE. Undiagnosed children received more mental health and reassessment recommendations. Older children received fewer family support and developmental therapy recommendations but more mental health recommendations than younger age groups. Many families accessed modified school programming, developmental therapy, psychiatry, child counseling, and parent support as recommended. CONCLUSIONS AND IMPLICATIONS: Children with FASD and PAE have extensive needs and should receive individualized recommendations. An assessment is valuable even without an FASD diagnosis. Areas of high/low service access may provide insight into accessibility and perceived importance of interventions. WHAT THIS PAPER ADDS: This study responds to important research questions regarding the intervention needs of individuals with FASD. It is novel in its exploration of intervention recommendations given to children prenatally exposed to alcohol without an FASD diagnosis (rather than only children with FASD) and in its examination of post-assessment service use patterns specifically in relation to clinical recommendations.

Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity.

The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5-18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA.

Caregiver needs and stress in caring for individuals with fetal alcohol spectrum disorder.

OBJECTIVE: Individuals with FASD experience neurodevelopmental impairments and adverse outcomes, which can result in stress on the caregiver. However, there is little research on the needs of caregivers supporting individuals with FASD and whether they are associated with caregiver stress. METHOD: 125 caregivers of individuals with FASD completed a survey with questions adapted from the Family Caregiver Survey and the Perceived Stress Scale. RESULTS: Caregivers reported a range of needs and concerns, and high levels of stress. In many areas of caregiver well-being concerns tended to be higher among caregivers with adolescents and adults compared to those with children. Foster parents reported fewer well-being concerns than biological/kinship and adoptive parents. Caregivers who cared for the individuals for longer periods of time reported the most well-being concerns and lowest satisfaction with supports. Caregivers with the lowest income reported higher levels of stress than those with higher incomes. Higher reported stress was highly correlated with more needs/concerns. CONCLUSIONS: Caregivers of individuals with FASD have multiple areas of need and concern, and experience high levels of stress. Reducing demands on caregivers and providing resources may help reduce caregiver needs and stress, particularly for those caring for adolescents and adults, and those with lower incomes.

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level.

Genomic characterization of chromosome 8 pericentric trisomy.

We present a patient with trisomy 8p11.21q11.21 associated with language, gross motor, fine motor, and cognitive delay. Furthermore, using array-based comparative genomic hybridization, we identify the specific genes duplicated in our patient.