Courtney R. Green

Executive Function Deficits in Children with Fetal Alcohol Spectrum Disorders (FASD) Measured Using the Cambridge Neuropsychological Tests Automated Battery (CANTAB).

BACKGROUND Chronic prenatal alcohol exposure causes a spectrum of deleterious effects in offspring, collectively termed fetal alcohol spectrum disorders (FASD), and deficits in executive function are prevalent in FASD. The goal of this research was to test the hypothesis that children with FASD exhibit performance deficits in tasks that assess attention, planning and spatial working memory. METHODS Subjects (8-15 years male and female children) with a diagnosis of fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND), and age- and sex-matched controls, completed four tasks selected from the Cambridge Neuropsychological Tests Automated Battery (CANTAB). RESULTS Compared with age-matched control children (n = 92), subjects with FASD (n = 89) exhibited longer reaction and decision times (effect size range; Cohens d = .51 to .73), suggesting deficits in attention. Children with FASD demonstrated deficits in planning and spatial working memory that became more pronounced when task difficulty increased. The largest effect size in this study population (Cohens d = 1.1) occurred in the spatial working memory task. Only one outcome measure revealed differences across the diagnostic subgroups, although all groups were different from control. CONCLUSION This study demonstrates that deficits in multiple executive function domains, including set shifting, planning and strategy use, attention and spatial working memory, can be assessed in children with FASD using an easy to administer, brief battery of computer-based neuropsychological tasks. The tasks appear to be equally sensitive for brain injury resulting from prenatal exposure to alcohol, regardless of the presence of facial dysmorphology.

Oculomotor control in children with fetal alcohol spectrum disorders assessed using a mobile eye‐tracking laboratory

Prenatal exposure to alcohol can result in a spectrum of adverse developmental outcomes, collectively termed fetal alcohol spectrum disorders (FASDs). This study evaluated deficits in sensory, motor and cognitive processing in children with FASD that can be identified using eye movement testing. Our study group was composed of 89 children aged 8–15 years with a diagnosis within the FASD spectrum [i.e. fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), and alcohol‐related neurodevelopmental disorder (ARND)], and 92 controls. Subjects looked either towards (prosaccade) or away from (antisaccade) a peripheral target that appeared on a computer monitor, and eye movements were recorded with a mobile, video‐based eye tracker. We hypothesized that: (i) differences in the magnitude of deficits in eye movement control exist across the three diagnostic subgroups; and (ii) children with FASD display a developmental delay in oculomotor control. Children with FASD had increased saccadic reaction times (SRTs), increased intra‐subject variability in SRTs, and increased direction errors in both the prosaccade and antisaccade tasks. Although development was associated with improvements across tasks, children with FASD failed to achieve age‐matched control levels of performance at any of the ages tested. Moreover, children with ARND had faster SRTs and made fewer direction errors in the antisaccade task than children with pFAS or FAS, although all subgroups were different from controls. Our results demonstrate that eye tracking can be used as an objective measure of brain injury in FASD, revealing behavioral deficits in all three diagnostic subgroups independent of facial dysmorphology.

Chronic prenatal ethanol exposure and increased concentration of fatty acid ethyl esters in meconium of term fetal Guinea pig.

In humans, the occurrence of prenatal exposure to ethanol is difficult to validate objectively. Increased concentration of fatty acid ethyl esters (FAEE) in the meconium of the newborn may be a biomarker of prenatal ethanol exposure. The validity of this proposed biomarker was tested in pregnant guinea pigs that received chronic oral administration of 4 g ethanol/kg maternal body weight/day (n=8), isocaloric-sucrose/pair-feeding (n=8) or water (n=2) throughout gestation. At gestational day 65 (term, gestational day 66 to 69), each dam and her offspring were euthanized, and meconium was collected from the term fetal large intestine. Eight individual FAEE (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linolenic and arachidonic AEE) were measured by gas chromatography––flame ionization detection and confirmed by gas chromatography––mass spectrometry. The chronic maternal ethanol regimen decreased fetal body weight and brain weight. There was virtually no measurable FAEE in the meconium for the water group (n=3 fetuses). For meconium of the ethanol offspring (n=25 fetuses) compared with the sucrose offspring (n=23 fetuses), the total FAEE concentration was 8-fold higher; and lauric, palmitic, stearic and oleic AEE concentrations were at least 5-fold higher for the ethanol group. The data indicate that fetal meconium FAEE constitute a biomarker of prenatal ethanol exposure for a maternal ethanol regimen that restricts fetal development, with an inverse relationship between meconium total FAEE concentration and both body weight and brain weight.

Comments and Reflections on Ethics in Screening for Biomarkers of Prenatal Alcohol Exposure

Early identification of and intervention for fetal alcohol spectrum disorder (FASD) has been shown to optimize outcomes for affected individuals. Detecting biomarkers of prenatal alcohol exposure (PAE) in neonates may assist in the identification of children at risk of FASD enabling targeted early interventions. Despite these potential benefits, complicated ethical issues arise in screening for biomarkers of PAE and these must be addressed prior to the implementation of screening programs. Here, we identify and comment, based on a North American perspective, on concerns raised in the current ethical, social, and legal literature related to meconium screening for PAE. Major ethical concerns revolve around the targeting of populations for PAE screening, consent and respect for persons, stigma and participation rates, the cost-benefit analysis of a screening program, consequences of false-positive and false-negative test results, confidentiality and appropriate follow-up to positive screen results, and the use of screen results for criminal prosecution. We identify gaps in the literature on screening for PAE, most notably related to a lack of stakeholder perspectives (e.g., parents, healthcare providers) about screening and the ethical challenges it presents.

Diffusion Tensor Imaging Correlates of Saccadic Reaction Time in Children with Fetal Alcohol Spectrum Disorder

BACKGROUND Eye movement tasks provide a simple method for inferring structural or functional brain deficits in neurodevelopmental disorders. Oculomotor control is impaired in children with fetal alcohol spectrum disorder (FASD), yet the neuroanatomical substrates underlying this are not known. Regions of white matter have been shown by diffusion tensor imaging (DTI) to be different in FASD and thus may play a role in the delayed saccadic eye movements. The objective of this study was to correlate oculomotor performance with regional measures of DTI-derived white matter anisotropy in children with FASD. METHODS Fourteen children (8 to 13 years) with FASD were recruited for oculomotor assessment and DTI. Eye movement control was evaluated using the pro- and antisaccade tasks, in which subjects look at (prosaccade) or away from (antisaccade) a peripheral target. Saccadic reaction time (SRT; time for subjects to move their eyes after the target appears) and direction errors (saccades made in the incorrect direction relative to the instruction) were measured and correlated to fractional anisotropy (FA) on a voxel-by-voxel basis across the whole brain white matter. RESULTS A significant positive correlation was observed between antisaccade SRT and FA in a large cluster containing anterior and posterior sections of the corpus callosum just to the right of the midline; prosaccade SRT and FA correlated positively in the genu of the corpus callosum and the right inferior longitudinal fasciculus (ILF), and correlated negatively in the left cerebellum. CONCLUSIONS The negative correlation for prosaccade SRT and cerebellum demonstrated that individuals with slower reaction times had lower FA values relative to their faster responding counterparts, a finding that implicates cerebellar dysfunction as a significant contributor to deficits in oculomotor control. The higher FA in the corpus callosum and ILF corresponding to longer reaction times for both pro- and antisaccade was opposite to what was expected, but nonetheless implies that altered brain structure in these regions underlies deficits in oculomotor control.

Effects of chronic prenatal ethanol exposure on mitochondrial glutathione and 8-iso-prostaglandin F2α concentrations in the hippocampus of the perinatal guinea pig

It is hypothesised that oxidative stress is a key mechanism of ethanol neurobehavioural teratogenicity, resulting in altered endogenous antioxidant status and increased membrane lipid peroxidation in the hippocampus of chronic prenatal ethanol exposure (CPEE) offspring. To test this hypothesis, timed pregnant guinea-pigs (term, approximately gestational day (GD) 68) received chronic daily oral administration of (i) 4 g ethanol kg(-1) maternal bodyweight, (ii) isocaloric sucrose with pair feeding, or (iii) water. At GD 65 (term fetus) and postnatal day (PD) 0 (neonate), individual offspring were killed, the brain was excised and the hippocampi were dissected. Glutathione (GSH) concentration was measured in the cytosolic and mitochondrial fractions of hippocampal homogenate. The occurrence of lipid peroxidation was determined by measuring the concentration of 8-iso-prostaglandin F2+/- (8-iso-PGF2+/-). There was CPEE-induced decreased brain weight and hippocampal weight at GD 65 and PD 0, decreased mitochondrial GSH concentration in the hippocampus at PD 0, with no change in mitochondrial GSH concentration at GD 65 or cytosolic GSH concentration at GD 65 or PD 0, and no change in mitochondrial or whole-homogenate 8-iso-PGF2+/- concentration in the hippocampus at GD 65 or PD 0. The data demonstrate that CPEE produces selective mitochondrial dysfunction in the hippocampus of the neonatal guinea-pig, involving GSH depletion.

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.

Guided Internet-Based Parent Training for Challenging Behavior in Children With Fetal Alcohol Spectrum Disorder (Strongest Families FASD): Study Protocol for a Randomized Controlled Trial

Background Fetal alcohol spectrum disorder (FASD) is a term used to encompass the full range of neurobehavioral and cognitive dysfunction that may occur as a consequence of prenatal alcohol exposure. There is relatively little research on intervention strategies that specifically target the behavioral problems of children with FASD. Availability and access to services are barriers to timely and effective care for families. The Strongest Families FASD intervention was recently adapted from the Strongest Families “Parenting the Active Child” program to include FASD-specific content delivered via an Internet-based application in conjunction with 11 telephone coaching sessions. Objective Our objectives are to (1) evaluate the effectiveness of Strongest Families FASD in reducing externalizing problems (primary outcome), internalizing problems, and parent distress (secondary outcomes) in children aged between 4 and 12 years diagnosed with FASD when compared to a control group with access to a static resource Web page; (2) evaluate the effectiveness of Strongest Families FASD in improving social competence (secondary outcome) in school-aged children aged between 6 and 12 diagnosed with FASD when compared with an online psychoeducation control; and (3) explore parental satisfaction with the Strongest Families FASD online parenting program. Methods Parents and caregivers (N=200) of children diagnosed with FASD who have significant behavioral challenges, ages 4-12, are being recruited into a 2-arm randomized trial. The trial is designed to evaluate the effectiveness of the Web-based Strongest Families FASD parenting intervention on child behavior and caregiver distress, compared to a control group receiving access to a static resource Web page (ie, a list of FASD-specific websites, readings, videos, and organizations). Results The primary outcome will be externalizing problems measured by the Child Behavior Checklist (CBCL). Secondary outcomes include (1) internalizing problems and (2) social competence, both measured by the CBCL; and (3) parental distress measured by the Depression Anxiety Stress Scale-21. The Client Satisfaction Questionnaire-8 (CSQ-8) and the Satisfaction Survey are completed by the intervention group at the end of session 11. Results will be reported using the standards set out in the Consolidated Standards of Reporting Trials (CONSORT) Statement. Conclusions It is hypothesized that the Strongest Families FASD intervention group will improve child behavior and parental distress. Caregiver satisfaction is anticipated to be positive. Advancing evidence on the effectiveness and acceptance of distance services can inform policy and adoption of eHealth programs. ClinicalTrial ClinicalTrials.gov NCT02210455; https://clinicaltrials.gov/ct2/show/NCT02210455 (Archived by WebCite at http://www.webcitation.org/6bbW5BSsT)