Heather Carmichael Olson

Magnetic resonance imaging outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders

BACKGROUND Magnetic resonance (MR) technology offers noninvasive methods for in vivo assessment of neuroabnormalities. METHODS A comprehensive neuropsychological/psychiatric battery, coupled with MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessments, were administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and distinguish diagnostic subclassifications across the spectrum. The 4 study groups included: (i) fetal alcohol syndrome (FAS)/partial FAS (PFAS); (ii) static encephalopathy/alcohol exposed (SE/AE); (iii) neurobehavioral disorder/alcohol exposed (ND/AE) as diagnosed with the FASD 4-Digit Code; and (iv) healthy peers with no prenatal alcohol exposure. Presented here are the MRI assessments that were used to compare the sizes of brain regions between the 4 groups. The neuropsychological/behavioral, MRS, and fMRI outcomes are reported separately. RESULTS Progressing across the 4 study groups from Controls to ND/AE to SE/AE to FAS/PFAS, the mean absolute size of the total brain, frontal lobe, caudate, putamen, hippocampus, cerebellar vermis, and corpus callosum length decreased incrementally and significantly. The FAS/PFAS group (the only group with the 4-Digit FAS facial phenotype) had disproportionately smaller frontal lobes relative to all other groups. The FAS/PFAS and SE/AE groups [the 2 groups with the most severe central nervous system (CNS) dysfunction] had disproportionately smaller caudate regions relative to the ND/AE and Control groups. The prevalence of subjects in the FAS/PFAS, SE/AE, and ND/AE groups that had 1 or more brain regions, 2 or more SDs below the mean size observed in the Control group was 78, 58, and 43%, respectively. Significant correlations were observed between size of brain regions and level of prenatal alcohol exposure, magnitude of FAS facial phenotype, and level of CNS dysfunction. CONCLUSIONS Magnetic resonance imaging provided further validation that ND/AE, SE/AE, and FAS/PFAS as defined by the FASD 4-Digit Code are 3 clinically distinct and increasingly more affected diagnostic subclassifications under the umbrella of FASD. Neurostructural abnormalities are present across the spectrum. MRI could importantly augment diagnosis of conditions under the umbrella of FASD, once population-based norms for structural development of the human brain are established.

Prenatal exposure to alcohol and school problems in late childhood: A longitudinal prospective study

The population-based Seattle Longitudinal Prospective Study on Alcohol and Pregnancy unites the fields of developmental psychopathology and behavioral teratology. Examining prenatal biological influences on childhood learning problems, this report is the first to extend earlier findings of alcohol-related deficits into late childhood. This follow-up study of 458 singletons assesses the degree to which childrens classroom behavior and achievement difficulties at age 11 are predicted by prenatal alcohol exposure across the full spectrum of maternal use. Partial least squares statistical techniques are used to summarize complex multiple measures of exposure and outcome as latent variables. Accounting for many factors potentially important in development, analyses reveal a significant and subtle dose-response relationship between prenatal alcohol exposure and childrens school performance a decade later. Maternal binge drinking (five or more drinks per occasion) and drinking during very early pregnancy are particularly salient for childrens poorer school performance. A wide variety of problematic classroom behaviors, including attentional, activity, information-processing, and academic difficulties, are salient for prenatal alcohol exposure. Considered within the body of data on alcohol teratogenesis, these findings suggest that prenatal alcohol exposure has an enduring and predictable relationship with developmental difficulties through late childhood. Clinical, research, and public health implications are discussed.

Responding to the Challenge of Early Intervention for Fetal Alcohol Spectrum Disorders

Prenatal alcohol exposure can lead to significant neurodevelopmental disabilities, now recognized as fetal alcohol spectrum disorders (FASD). This includes both fetal alcohol syndrome, a lifelong birth defect, and a wider range of enduring learning and behavior deficits often called alcohol-related neurodevelopmental disorder (ARND). Diagnostic classification systems have been developed to identify children with FASD, and early interventionists from multiple disciplines can be central in identification and referral for diagnosis, and in providing the known protective influence of intervention early in life. With the recent federal mandates to better address needs of children born prenatally affected by substances, or those impacted by abuse and/or neglect, by referring them for screening and possible early intervention services, there is heightened need for providers to understand FASD. There is a growing body of research data describing the teratogenic effects of alcohol on central nervous system function and physical development, the diversity of children with prenatal alcohol exposure and their families, and the developmental and behavioral characteristics of this clinical population. This article reviews the latest research evidence, bearing in mind what is important to early intervention. This article also gives practical guidance on FASD prevention, methods for early screening, and referral of young children for diagnosis of FASD (and referral for needed services once diagnosed), and how to provide education, support, advocacy assistance, and anticipatory guidance for families raising children with FASD.

Sensory Processing, School Performance, and Adaptive Behavior of Young School-Age Children with Fetal Alcohol Spectrum Disorders

This study described sensory processing behaviors and sensory-motor abilities in children with fetal alcohol spectrum disorders (FASD) and explored their relationship to home and school function. A clinic-referred sample of 25 children with FASD, ages 5 to 8 years, was compared with 26 children with typical development, balanced for age, gender, and race/ethnicity, on standardized tests examining sensory processing, sensory-motor performance, school performance, and adaptive behavior. Children with FASD scored significantly more poorly on sensory processing, sensory-motor, adaptive, and academic achievement measures, and demonstrated more problem behaviors at home and school. Correlations were significant between measures of sensory processing and sensory-motor performance, adaptive behavior, and some aspects of academic performance. Sensory processing and related foundational sensory-motor impairments should be considered when determining the developmental needs of children with FASD. These impairments may co-occur with and contribute, at least in part, to decreased adaptive and school function.

The Long-Term Neurocognitive Consequences of Prenatal Alcohol Exposure: A 14-Year Study

Prenatal alcohol exposure, at doses not generally associated with maternal alcohol problems, produces a broad array of neurocognitive deficits in offspring even in the absence of effects on growth and morphology. This report presents a summary of neurobehavioral, growth, and morphology findings from long-term follow-up of a birth cohort of 500 from a population-based study that has revealed attention, memory, and information processing deficits from birth through 14 years. Also observed (from school age through 14 years) have been problems with antisocial and delinquent behaviors, and classroom learning and behaviors; some of these problems may be secondary to earlier neurocognitive disabilities. Continuing research in behavioral and neurobehavioral teratology provides important opportunities for the neurosciences and for improved health of future generations.

Magnetic resonance spectroscopy outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders

Magnetic resonance (MR) technology offers noninvasive methods for in vivo assessment of neuroabnormalities. A comprehensive neuropsychological/behavioral, MR imaging (MRI), MR spectroscopy (MRS) and functional MRI (fMRI) assessment was administered to children with fetal alcohol spectrum disorders (FASD) to determine whether global and/or focal abnormalities could be identified and to distinguish diagnostic subclassifications across the spectrum. The four study groups included (1) FAS/partial FAS; (2) static encephalopathy/alcohol exposed (SE/AE); (3) neurobehavioral disorder/alcohol exposed (ND/AE) as diagnosed with the FASD 4-Digit Code; and (4) healthy peers with no prenatal alcohol exposure. Results are presented in four separate reports: MRS (reported here) and neuropsychological/behavioral, MRI and fMRI outcomes (reported separately). MRS was used to compare neurometabolite concentrations [choline (Cho), n-acetyl-aspartate (NAA) and creatine (Cre)] in a white matter region and a hippocampal region between the four study groups. Choline concentration in the frontal/parietal white matter region, lateral to the midsection of the corpus callosum, was significantly lower in FAS/PFAS relative to all other study groups. Choline decreased significantly with decreasing frontal white matter volume and corpus callosum length. These outcomes suggest low choline concentrations may reflect white matter deficits among FAS/PFAS. Choline also decreased significantly with increasing severity of the 4-Digit FAS facial phenotype, increasing impairment in psychological performance and increasing alcohol exposure. NAA and Cre concentrations did not vary significantly. This study provides further evidence of the vulnerability of the cholinergic system in FASD.

Functional magnetic resonance imaging outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders

A comprehensive neuropsychological/psychiatric, MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessment was administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and distinguish diagnostic subclassifications across the spectrum. The four study groups included: 1. FAS/Partial FAS; 2. Static Encephalopathy/Alcohol Exposed (SE/AE); 3. Neurobehavioral Disorder/Alcohol Exposed (ND/AE); and 4. healthy peers with no prenatal alcohol exposure. fMRI outcomes are reported here. The neuropsychological/psychiatric, MRI, and MRS outcomes are reported separately. fMRI was used to assess activation in seven brain regions during performance of N-back working memory tasks. Children across the full spectrum of FASD exhibited significant working memory deficits and altered activation patterns in brain regions that are known to be involved in working memory. These results demonstrate the potential research and diagnostic value of this non-invasive MR tool in the field of FASD.

Prevalence of fetal alcohol syndrome in a population-based sample of children living in remote Australia: The Lililwan Project

Aboriginal leaders concerned about high rates of alcohol use in pregnancy invited researchers to determine the prevalence of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (pFAS) in their communities.

The Lililwan Project: study protocol for a population-based active case ascertainment study of the prevalence of fetal alcohol spectrum disorders (FASD) in remote Australian Aboriginal communities

Introduction Anecdotal reports suggest that high-risk drinking in pregnancy is common in some remote Australian communities. Alcohol is teratogenic and may cause a range of lifelong conditions termed ‘fetal alcohol spectrum disorders’ (FASD). Australia has few diagnostic services for FASD, and prevalence of these neurodevelopmental disorders remains unknown. In 2009, Aboriginal leaders in the remote Fitzroy Valley in North Western Australia identified FASD as a community priority and initiated the Lililwani Project in partnership with leading research organisations. This project will establish the prevalence of FASD and other health and developmental problems in school-aged children residing in the Fitzroy Valley, providing data to inform FASD prevention and management. Methods and analysis This is a population-based active case ascertainment study of all children born in 2002 and 2003 and residing in the Fitzroy Valley. Participants will be identified from the Fitzroy Valley Population Project and Communicare databases. Parents/carers will be interviewed using a standardised diagnostic questionnaire modified for local language and cultural requirements to determine the demographics, antenatal exposures, birth outcomes, education and psychosocial status of each child. A comprehensive interdisciplinary health and neurodevelopmental assessment will be performed using tests and operational definitions adapted for the local context. Internationally recognised diagnostic criteria will be applied to determine FASD prevalence. Relationships between pregnancy exposures and early life trauma, neurodevelopmental, health and education outcomes will be evaluated using regression analysis. Results will be reported according to STROBE guidelines for observational studies. Ethics and dissemination Ethics approval has been granted by the University of Sydney Human Research Ethics Committee, the Western Australian Aboriginal Health Information and Ethics Committee, the Western Australian Country Health Service Board Research Ethics Committee and the Kimberley Aboriginal Health Planning Forum Research Sub-committee. Results will be disseminated widely through peer-reviewed manuscripts, reports, conference presentations and the media.

Prenatal alcohol exposure, FASD, and child behavior: a meta-analysis

CONTEXT: Fetal alcohol spectrum disorders (FASD) and prenatal alcohol exposure (PAE) are associated with behavioral difficulties, although there are no published systematic reviews that summarize and critique the literature. OBJECTIVE: To describe the behavioral characteristics of children with PAE and/or FASD, assessed using the Achenbach System of Empirically Based Assessments (ASEBA) for school-aged children with parent, teacher, and youth (self-report) forms. DATA SOURCES: Electronic literature databases, reference lists, hand-searches. STUDY SELECTION: peer-reviewed observational studies. DATA EXTRACTION: Study appraisal and data extraction were undertaken by 2 independent assessors. Meta-analyses were performed for parent-rated Internalizing, Externalizing, and Total problems scales. All other ASEBA scales were summarized qualitatively. RESULTS: Included were 23 articles; 16 were used in meta-analyses. Pooled results showed higher Total (mean difference 12.1, 95% confidence interval [95% CI] 7.7–16.5), Internalizing (6.3, 95% CI 3.1–9.5), and Externalizing problems scores (12.5, 95% CI 7.9–17.0) in FASD than No FASD; and greater odds of scoring in the “Clinical” range in FASD. Pooled results demonstrated higher problem scores in children with PAE (P > .05). Qualitative summaries of other scales from parents, teachers, and self-report show poorer behavior ratings in children with FASD and PAE on composite Problem and Competence scores and many Syndrome subscales. LIMITATIONS: Findings were restricted to behaviors assessed using the ASEBA. The published literature was limited, often with only 1 study reporting on a particular scale. CONCLUSIONS: Meta-analysis reveals that FASD and PAE are associated with problematic behavior in many, but not all domains. This clearly affects families, and should be considered in clinical practice by providers.