Development, implementation, and scalability of the Family Engagement in Research Course: a novel online course for family partners and researchers in neurodevelopmental disability and child health.

Background: Since 2011 when the Canadian Institutes of Health Research launched the Strategy for Patient Oriented Research, there has been a growing expectation to embed patient-oriented research (POR) in the health research community in Canada. To meet this expectation and build capacity for POR in the field of neurodevelopmental disability and child health, in 2017 researchers and family leaders at CanChild Centre for Childhood Disability Research, McMaster University partnered with Kids Brain Health Network and McMaster Continuing Education to develop and implement a 10-week online Family Engagement in Research (FER) Course.

Main Text: From its inception, the FER Course has been delivered in partnership with family leaders and researchers.

Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associated with Risk of FASD Outcomes.

Fetal Alcohol Spectrum Disorder (FASD) is a common neurodevelopmental disorder that affects an estimated 2-5% of North Americans. FASD is induced by prenatal alcohol exposure (PAE) during pregnancy and while there is a clear genetic contribution, few genetic factors are currently identified or understood. In this study, using a candidate gene approach, we performed a genetic variant analysis of retinoic acid (RA) metabolic and developmental signaling pathway genes on whole exome sequencing data of 23 FASD-diagnosed individuals.

Developmental exposure to methylmercury alters GAD67 immunoreactivity and morphology of endothelial cells and capillaries of midbrain and hindbrain regions of adult rat offspring.

Introduction: Methylmercury (MeHg) is an environmental contaminant that is of particular concern in Northern Arctic Canadian populations. Specifically, organic mercury compounds such as MeHg are potent toxicants that affect multiple bodily systems including the nervous system. Developmental exposure to MeHg is a major concern, as the developing fetus and neonate are thought to be especially vulnerable to the toxic effects of MeHg.

Barriers and facilitators to implementation of developmental screening and early intervention in Canadian organizations following completion of a training and coaching model: a thematic analysis.

Introduction: Developmental delay affects approximately 1 in 4 children under 6 years old. Developmental delay can be detected using validated developmental screening tools, such as the Ages and Stages Questionnaires. Following developmental screening, early intervention can occur to address and support any developmental areas of concern.

A tornado in the family: fetal alcohol spectrum disorder and aggression during childhood and adolescence: a scoping review.

Background: Aggression exhibited by children and youth with Fetal Alcohol Spectrum Disorder (FASD) toward family members is a major cause of stress and anxiety for caregivers, but relatively little attention has been directed toward designing interventions specific to this phenomenon. In light of the serious negative impact of this issue for families, a scoping review was undertaken to summarize the evidence available on psychosocial interventions that may mitigate the frequency and severity of aggression exhibited by children and youth with FASD toward family members.

Methods: This review was designed using PRISMA-SCR and JBI scoping review guidelines.

Behavior regulation skills are associated with adaptive functioning in children and adolescents with prenatal alcohol exposure.

Children with prenatal alcohol exposure (PAE) experience a range of adverse outcomes that impact multiple domains of functioning, including cognitive, physical, mental health, behavioral, social-emotional, communication, and learning. To inform tailored clinical intervention, the current study examined the relation between caregiver-reported cognitive skills (executive function; EF) and adaptive functioning. The study conducted a secondary analyses of data provided by caregivers of 87 children and adolescents (aged 5-18 years,  = 11.

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.

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 PedBE clock accurately estimates DNA methylation age in pediatric buccal cells.

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty.

Population-based prevalence of fetal alcohol spectrum disorder in Canada.

Background: Fetal alcohol spectrum disorder (FASD) is one of the most disabling potential outcomes of prenatal alcohol exposure. The population-based prevalence of FASD among the general population of Canada was unknown. The objective of this study was to determine the population-based prevalence of FASD among elementary school students, aged 7 to 9 years, in the Greater Toronto Area (GTA) in Ontario, Canada.

Myelin Water Fraction Imaging of the Brain in Children with Prenatal Alcohol Exposure.

Background: Prenatal alcohol exposure (PAE) is linked to alterations of cerebral white matter, including volume and nonspecific diffusion magnetic resonance imaging (MRI) indices of microstructure in humans. Some animal models of PAE have demonstrated myelination deficiencies, but myelin levels have not yet been evaluated in individuals with PAE. Multiecho T MRI offers a quantitative method to estimate myelin water fraction (MWF; related to myelin content) noninvasively, which was used here to evaluate brain myelination in children with PAE.

Detection of Children/Youth With Fetal Alcohol Spectrum Disorder Through Eye Movement, Psychometric, and Neuroimaging Data.

Fetal alcohol spectrum disorders (FASD) is one of the most common causes of developmental disabilities and neurobehavioral deficits. Despite the high-prevalence of FASD, the current diagnostic process is challenging and time- and money- consuming, with underreported profiles of the neurocognitive and neurobehavioral impairments because of limited clinical capacity. We assessed children/youth with FASD from a multimodal perspective and developed a high-performing, low-cost screening protocol using a machine learning framework.

Effects of placental growth factor deficiency on behavior, neuroanatomy, and cerebrovasculature of mice.

Preeclampsia, a hypertensive syndrome occurring in 3-5% of human pregnancies, has lifelong health consequences for fetuses. Cognitive ability throughout life is altered, and adult stroke risk is increased. One potential etiological factor for altered brain development is low concentrations of proangiogenic placental growth factor (PGF).

Resting-state functional connectivity in children born from gestations complicated by preeclampsia: A pilot study cohort.

Background: Individuals (PE-F1s) born from preeclampsia (PE)-complicated pregnancies have elevated risks for cognitive impairment. Intervals of disturbed maternal plasma angiokines precede clinical signs of PE. We hypothesized pan-blastocyst dysregulation of angiokines underlies altered PE-F1 brain vascular and neurological development.

Copy number variation in fetal alcohol spectrum disorder.

Fetal alcohol spectrum disorder (FASD) is characterized by a combination of neurological, developmental, and congenital defects that may occur as a consequence of prenatal alcohol exposure. Earlier reports showed that large chromosomal anomalies may link to FASD. Here, we examined the prevalence and types of copy number variations (CNVs) in FASD cases previously diagnosed by a multidisciplinary FASD team in sites across Canada.

DNA methylation as a predictor of fetal alcohol spectrum disorder.

Background: Fetal alcohol spectrum disorder (FASD) is a developmental disorder that manifests through a range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal alcohol exposure. Although the North American prevalence is currently estimated at 2-5%, FASD has proven difficult to identify in the absence of the overt physical features characteristic of fetal alcohol syndrome. As interventions may have the greatest impact at an early age, accurate biomarkers are needed to identify children at risk for FASD.

Neurological function in children born to preeclamptic and hypertensive mothers - A systematic review.

Background: Offspring whose mothers developed preeclampsia (PE-F1s) show developmental effects that are now being identified, such as cognitive, behavioural, and mood differences compared to offspring from non-complicated pregnancies. We hypothesize that the progressive angiokine dysregulation associated with development of preeclampsia (PE) reflects gene dysregulation in pre-implantation conceptuses, and manifests in all developing fetal tissues rather than exclusively to the placenta. This hypothesis predicts that fetal cerebrovascular and brain development are deviated by fetal-intrinsic, brain-based mechanisms during what is currently considered a placentally-induced maternal disease.

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.

Immediate Neural Plasticity Involving Reaction Time in a Saccadic Eye Movement Task is Intact in Children With Fetal Alcohol Spectrum Disorder.

Background: Saccades are rapid eye movements that bring an image of interest onto the retina. Previous research has found that in healthy individuals performing eye movement tasks, the location of a previous visual target can influence performance of the saccade on the next trial. This rapid behavioral adaptation represents a form of immediate neural plasticity within the saccadic circuitry.

Challenging sleep-wake behaviors reported in informal, conversational interviews of caregivers of children with fetal alcohol spectrum disorder.

Sleep complaints are clinically expected in children exposed to alcohol during pregnancy. We aim to reveal patterns of association among sleep-wake behaviors that are challenging in the life of children with fetal alcohol spectrum disorders (FASD). Through text-mining analyses, we numericized the transcripts of 59 caregiver's informal, conversational interviews.

Ethical Challenges in Contemporary FASD Research and Practice.

Fetal alcohol spectrum disorder (FASD) is increasingly recognized as a growing public health issue worldwide. Although more research is needed on both the diagnosis and treatment of FASD, and a broader and more culturally diverse range of services are needed to support those who suffer from FASD and their families, both research and practice for FASD raise significant ethical issues. In response, from the point of view of both research and clinical neuroethics, we provide a framework that emphasizes the need to maximize benefits and minimize harm, promote justice, and foster respect for persons within a global context.

Diffusion tensor imaging of white matter and correlates to eye movement control and psychometric testing in children with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can cause central nervous system dysfunction and widespread structural anomalies as detected by magnetic resonance imaging (MRI). This study focused on diffusion tensor imaging (DTI) of white matter in a large sample of PAE participants that allowed us to examine correlations with behavioral outcomes. Participants were confirmed PAE (n = 69, mean age = 12.

DNA methylation signature of human fetal alcohol spectrum disorder.

Background: Prenatal alcohol exposure is the leading preventable cause of behavioral and cognitive deficits, which may affect between 2 and 5 % of children in North America. While the underlying mechanisms of alcohol's effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with fetal alcohol spectrum disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date.

Usability Testing of Guided Internet-based Parent Training for Challenging Behavior in Children with Fetal Alcohol Spectrum Disorder (Strongest Families FASD).

Background: In order to meet the need for accessible interventions and support for families affected by fetal alcohol spectrum disorder (FASD), we have developed an Internet-based, distance intervention for caregivers of children with FASD between the ages of four and twelve, called Strongest Families™ FASD.

Objectives: To evaluate the usability of the Strongest Families FASD program content and website in terms of learnability, efficiency and acceptability.

Methods: A remote usability testing approach was conducted in two iterative cycles of participants.

Differential expression of astrocytic connexins in a mouse model of prenatal alcohol exposure.

Maternal alcohol consumption during gestation can cause serious injury to the fetus, and may result in a range of physiological and behavioral impairments, including increased seizure susceptibility, that are collectively termed fetal alcohol spectrum disorder (FASD). The cellular mechanisms underlying increased seizure susceptibility in FASD are not well understood, but could involve altered excitatory coupling of neuronal populations mediated by gap junction proteins. We utilized a mouse model of the prenatal alcohol exposure (PAE) to study the expression pattern of connexin (Cx) major components of gap junctions, and pannexin proteins, which form membrane channels, in the brain of 2-3weeks old PAE and control postnatal offspring.