A dose-response analysis of the effects of prenatal alcohol exposure on cognitive development.

BACKGROUND: Most studies of the effects of prenatal alcohol exposure (PAE) on cognitive function have assumed that the dose-response curve is linear. However, data from a few animal and human studies suggest that there may be an inflection point in the dose-response curve above which PAE effects are markedly stronger and that there may be differences associated with pattern of exposure, assessed in terms of alcohol dose per drinking occasion and drinking frequency. METHODS: We performed second-order confirmatory factor analysis on data obtained at school age, adolescence, and early adulthood from 2227 participants in six US longitudinal cohorts to derive a composite measure of cognitive function. Regression models were constructed to examine effects of PAE on cognitive function, adjusted for propensity scores. Analyses based on a single predictor (absolute alcohol (AA)/day) were compared with analyses based on two predictors (dose/occasion and drinking frequency), using (1) linear models and (2) nonparametric general additive models (GAM) that allow for both linear and nonlinear effects. RESULTS: The single-predictor GAM model showed virtually no nonlinearity in the effect of AA/day on cognitive function. However, the two-predictor GAM model revealed differential effects of maternal drinking pattern. Among offspring of infrequent drinkers, PAE effects on cognitive function were markedly stronger in those whose mothers drank more than ~3 drinks/occasion, and the effect of dose/occasion was strongest among the very frequent drinkers. Frequency of drinking did not appear to alter the PAE effect on cognitive function among participants born to mothers who limited their drinking to ~1 drink/occasion or less. CONCLUSIONS: These findings suggest that linear models based on total AA/day are appropriate for assessing whether PAE affects a given cognitive outcome. However, examination of alcohol dose/occasion and drinking frequency is needed to fully characterize the impact of different levels of alcohol intake on cognitive impairment.

Adverse childhood experiences in children with fetal alcohol spectrum disorders and their effects on behavior.

BACKGROUND: Children with fetal alcohol spectrum disorders (FASD) have high rates of adverse childhood experiences (ACEs). ACEs are associated with a wide range of health outcomes including difficulty with behavior regulation, an important intervention target. However, the effect of ACEs on different areas of behavior has not been well characterized in children with disabilities. This study describes ACEs in children with FASD and how they impact behavior problems. METHODS: A convenience sample of 87 caregivers of children (aged 3 to 12) with FASD participating in an intervention study reported on their children's ACEs using the ACEs Questionnaire and behavior problems on the Eyberg Child Behavior Inventory (ECBI). A theorized three-factor structure of the ECBI (Oppositional Behavior, Attention Problems, and Conduct Problems) was investigated. Data were analyzed using Pearson correlations and linear regression. RESULTS: On average, caregivers endorsed 3.10 (SD = 2.99) ACEs experienced by their children. The two most frequently endorsed ACE risk factors were having lived with a household member with a mental health disorder, followed by having lived with a household member with a substance use disorder. Higher total ACEs score significantly predicted a greater overall frequency of child behavior (intensity scale), but not whether the caregiver perceived the behavior to be a problem (problem scale) on the ECBI. No other variable significantly predicted the frequency of children's disruptive behavior. Exploratory regressions indicated that a higher ACEs score significantly predicted greater Conduct Problems. Total ACEs score was not associated with Attention Problems or Oppositional Behavior. DISCUSSION: Children with FASD are at risk for ACEs, and those with higher ACEs had a greater frequency of problem behavior on the ECBI, especially conduct problems. Findings emphasize the need for trauma-informed clinical care for children with FASD and increased accessibility of care. Future research should examine potential mechanisms that underlie the relationship between ACEs and behavior problems to optimally inform interventions.

A hierarchical meta-analysis for settings involving multiple outcomes across multiple cohorts.

Evidence from animal models and epidemiological studies has linked prenatal alcohol exposure (PAE) to a broad range of long-term cognitive and behavioural deficits. However, there is a paucity of evidence regarding the nature and levels of PAE associated with increased risk of clinically significant cognitive deficits. To derive robust and efficient estimates of the effects of PAE on cognitive function, we have developed a hierarchical meta-analysis approach to synthesize information regarding the effects of PAE on cognition, integrating data on multiple outcomes from six U.S. Iongitudinal cohort studies. A key assumption of standard methods of meta-analysis, effect sizes are independent, is violated when multiple intercorrelated outcomes are synthesized across studies. Our approach involves estimating the dose-response coefficients for each outcome and then pooling these correlated dose-response coefficients to obtain an estimated "global" effect of exposure on cognition. In the first stage, we use individual participant data to derive estimates of the effects of PAE by fitting regression models that adjust for potential confounding variables using propensity scores. The correlation matrix characterizing the dependence between the outcome-specific dose-response coefficients estimated within each cohort is then run, while accommodating incomplete information on some outcome. We also compare inferences based on the proposed approach to inferences based on a full multivariate analysis.

Initial Feasibility of the "Families Moving Forward Connect" Mobile Health Intervention for Caregivers of Children With Fetal Alcohol Spectrum Disorders: Mixed Method Evaluation Within a Systematic User-Centered Design Approach.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are prevalent neurodevelopmental conditions. Significant barriers prevent family access to FASD-informed care. To improve accessibility, a scalable mobile health intervention for caregivers of children with FASD is under development. The app, called Families Moving Forward (FMF) Connect, is derived from the FMF Program, a parenting intervention tailored for FASD. FMF Connect has 5 components: Learning Modules, Family Forum, Library, Notebook, and Dashboard. OBJECTIVE: This study assesses the feasibility of FMF Connect intervention prototypes. This includes examining app usage data and evaluating user experience to guide further refinements. METHODS: Two rounds of beta-testing were conducted as part of a systematic approach to the development and evaluation of FMF Connect: (1) an iOS prototype was tested with 20 caregivers of children (aged 3-17 years) with FASD and 17 providers for the first round (April-May 2019) and (2) iOS and Android prototypes were tested with 25 caregivers and 1 provider for the second round (November-December 2019). After each 6-week trial, focus groups or individual interviews were completed. Usage analytics and thematic analysis were used to address feasibility objectives. RESULTS: Across beta-test trials, 84% (38/45) of caregivers and 94% (17/18) of providers installed the FMF Connect app. Technological issues were tracked in real time with updates to address problems and expand app functionalities. On use days, caregivers averaged 20 minutes using the app; most of the time was spent watching videos in Learning Modules. Caregiver engagement with the Learning Modules varied across 5 usage pattern tiers. Overall, 67% (30/45) of caregivers posted at least once in the Family Forum. Interviews were completed by 26 caregivers and 16 providers. App evaluations generally did not differ according to usage pattern tier or demographic characteristics. Globally, app users were very positive, with 2.5 times more positive- than negative-coded segments across participants. Positive evaluations emphasized the benefits of accessible information and practical utility of the app. Informational and video content were described as especially valuable to caregivers. A number of affective and social benefits of the app were identified, aligning well with the caregivers' stated motivators for app use. Negative evaluations of user experience generally emphasized technical and navigational aspects. Refinements were made on the basis of feedback during the first beta test, which were positively received during the second round. Participants offered many valuable recommendations for continuing app refinement, which is useful in improving user experience. CONCLUSIONS: The results demonstrate that the FMF Connect intervention is acceptable and feasible for caregivers raising children with FASD. They will guide subsequent app refinement before large-scale randomized testing. This study used a systematic, user-centered design approach for app development and evaluation. The approach used here may illustrate a model that can broadly inform the development of mobile health and digital parenting interventions.

Effects of prenatal alcohol exposure on cognitive and behavioral development: Findings from a hierarchical meta-analysis of data from six prospective longitudinal U.S. cohorts.

BACKGROUND: Cognitive and behavioral sequelae of prenatal alcohol exposure (PAE) continue to be prevalent in the United States and worldwide. Because these sequelae are also common in other neurodevelopmental disorders, researchers have attempted to identify a distinct neurobehavioral profile to facilitate the differential diagnosis of fetal alcohol spectrum disorders (FASD). We used an innovative, individual participant meta-analytic technique to combine data from six large U.S. longitudinal cohorts to provide a more comprehensive and reliable characterization of the neurobehavioral deficits seen in FASD than can be obtained from smaller samples. METHODS: Meta-analyses were performed on data from 2236 participants to examine effects of PAE (measured as oz absolute alcohol/day (AA/day)) on IQ, four domains of cognition function (learning and memory, executive function, reading achievement, and math achievement), sustained attention, and behavior problems, after adjusting for potential confounders using propensity scores. RESULTS: The effect sizes for IQ and the four domains of cognitive function were strikingly similar to one another and did not differ at school age, adolescence, or young adulthood. Effect sizes were smaller in the more middle-class Seattle cohort and larger in the three cohorts that obtained more detailed and comprehensive assessments of AA/day. PAE effect sizes were somewhat weaker for parent- and teacher-reported behavior problems and not significant for sustained attention. In a meta-analysis of five aspects of executive function, the strongest effect was on set-shifting. CONCLUSIONS: The similarity in the effect sizes for the four domains of cognitive function suggests that PAE affects an underlying component or components of cognition involving learning and memory and executive function that are reflected in IQ and academic achievement scores. The weaker effects in the more middle-class cohort may reflect a more cognitively stimulating environment, a different maternal drinking pattern (lower alcohol dose/occasion), and/or better maternal prenatal nutrition. These findings identify two domains of cognition-learning/memory and set-shifting-that are particularly affected by PAE, and one, sustained attention, which is apparently spared.

A Mobile Health Intervention for Fetal Alcohol Spectrum Disorders (Families Moving Forward Connect): Development and Qualitative Evaluation of Design and Functionalities.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) affect approximately 2% to 5% of the US population. However, most families are unable to access FASD-informed interventions. Barriers to care include the lack of a knowledgeable and skilled workforce and family-level barriers such as limited financial resources, inability to access childcare, and stigma. As a result, families often try peer-to-peer and self-help support strategies. However, they often take these strategies from disparate sources, which have quite variable intervention quality and empirical support. OBJECTIVE: This study aimed to initiate systematic development and evaluation of a mobile health intervention (app) for caregivers raising children with FASD. Focus groups were conducted to elicit participant perspectives on app design and functionalities to inform further app development. METHODS: The app, called FMF Connect, was derived from the scientifically validated Families Moving Forward (FMF) Program, a clinician-delivered behavioral consultation intervention. FMF Connect was intended for caregiver self-delivery and included five main components: (1) Learning Modules, (2) Family Forum, (3) Library, (4) Notebook, and (5) Dashboard. Focus group methods were used to solicit perspectives from diverse families during the early stages of app development. Questions were asked about interface design, relevance of components and content, and perceived barriers and facilitators of use. A total of 25 caregivers participated in 7 focus groups across 5 US cities. Data were analyzed thematically. RESULTS: Focus group participants were generally enthusiastic about the app interface design and components. Four global positive impression themes emerged, including (1) ease of access, (2) how the app guides and organizes information, (3) connection to other users and information, and (4) ability to share some content with others. Themes arose not only in discussions relating to positive app features but also when participants were asked about motivators for app use. Participants related how these positive global themes could address some system-level barriers, such as limited access to services, feeling isolated, and increased advocacy needs related to the societal lack of FASD knowledge. Participants identified many positive features about individual app components and functionalities. They also communicated potential barriers to use and raised important concerns and considerations relating to several app components. These included recognizability of the app based on the logo, and the balance of following the planned intervention sequence versus obtaining immediate answers. Also mentioned were privacy and dynamics within the Family Forum. CONCLUSIONS: FMF Connect is a promising novel intervention with potential to reach many families in need and reduce significant barriers to care, resulting in a broader public health impact. Study findings will guide further app development both in terms of content and technological advances to optimize intervention effects. FMF Connect app development provides useful directions for other apps aimed at changing parenting practices.

The best possible start: A qualitative study on the experiences of parents of young children with or at risk for fetal alcohol spectrum disorders.

BACKGROUND: The developmental outcomes and life course trajectories of young children with or at-risk for fetal alcohol spectrum disorders (FASD) can be optimized when individual and family needs are identified early and met with family-centered early intervention (EI) services. However, little is known about access to and quality of EI services with this high-needs population. METHOD: Twenty-five biological or adoptive parents of children with or at high risk for FASD, living in the greater area of Seattle, Washington participated in this qualitative study. Three focus groups were conducted using a semi-structured interview guide. Participants described their experience with EI, as well as other supports and challenges faced in their child's first three years of life. Interviews were audio recorded, transcribed verbatim and coded using phenomenological methods. Themes that were consistent across participant groups emerged from the data, as well as themes that showed differences among participant experiences. RESULTS: Common EI supports and needs between biological and adoptive parent groups were identified. In addition, perspectives and needs unique to each parent group were revealed. Themes were identified and organized into three categories: (1) child needs; (2) parent needs and priorities; and (3) EI capacity. When parents talked about their child's cognitive, physical, communication or adaptive development, they all discussed how EI was meeting those needs. In contrast, when parents expressed concern for their child's social-emotional development, a description of how EI was supporting these needs was missing from the conversation. Parents appreciated when EI providers were truthful, provided anticipatory guidance, and connected them with supports for their own social-emotional well-being. Yet there were unmet needs for respite care, and parents expressed that support for basic needs related to child or family survival was not consistently recognized as a top priority for families. This high-risk group of young children and their parents also encountered a multitude of transitions in their child's early years and later. Parents wanted more support navigating these transitions as they entered or moved through different systems of care. CONCLUSIONS: Parents appreciated and endorsed the importance of EI with its provision of individualized, family-centered supports and resources. Examination of the gaps and unmet needs that are common and distinct underscore the importance of an FASD-informed approach to EI. Study findings provide insight into areas for which EI enhancements could be developed in order to tailor supports for the complex needs of this diverse population of children and parents.

An investigation of intra-individual variability in children with fetal alcohol spectrum disorder (FASD).

Intra-individual variability (IIV) is defined as systematic within-person variation in performance either across test sessions (e.g., test/retest performance on the same task) or in one session (e.g., variations in performance on multiple trials of a single task). Higher levels of IIV have been noted as a characteristic of neurodevelopmental disorders such as attention deficit/hyperactivity disorder​ (ADHD), but IIV is yet to be investigated in fetal alcohol spectrum disorder (FASD). FASD is a term used to describe a range of conditions resulting from prenatal exposure to alcohol. As part of a comprehensive neuropsychological battery, four study groups (1. fetal alcohol syndrome/partial fetal alcohol syndrome; 2. static encephalopathy/alcohol exposed; 3. neurobehavioral disorder/alcohol exposed as diagnosed using the University of Washington FASD 4-Digit Code; 4. typically-developing (TD) age-matched children with no prenatal alcohol exposure) were administered measures of motor response and inhibitory control, attention, and adaptive behavior. The results indicate increased levels of IIV in those with FASD compared to the TD controls. It was found that IIV uniquely contributes to predicting adaptive behavior above and beyond attention, while attention partially mediates the relationship between IIV and adaptive behavior. This is the first study to the authors' knowledge to show the presence of increased IIV in children with FASD. It additionally provides evidence that IIV measures some inherent variability in performance independent of poor attention in children with FASD.

Understanding and managing sleep disruption in children with fetal alcohol spectrum disorder.

Accumulating evidence has revealed high rates of sleep disruption among children with fetal alcohol spectrum disorder (FASD). Multiple animal and clinical studies have found a clear association between sleep problems and prenatal alcohol exposure, and recent research is beginning to characterize the types and extent of sleep disruption in FASD. Nevertheless, sleep disruption in children with FASD often goes unrecognized or is treated without referring to an evidence base. Children's disrupted sleep interferes with parental sleep and increases caregiver burden, which is of particular importance for families raising children with FASD, a group with very high levels of caregiving stress. The literature supporting an association between sleep problems and deficits in emotional, behavioral, and cognitive function in children is compelling, but needs further investigation in children with FASD. This paper will review the current state of knowledge on sleep in FASD and recommend a rational approach to sleep interventions for affected children and their families.

Prevalence and profile of Neurodevelopment and Fetal Alcohol Spectrum Disorder (FASD) amongst Australian Aboriginal children living in remote communities.

BACKGROUND: Despite multiple risk factors for neurodevelopmental vulnerability, few studies have assessed neurodevelopmental performance of Australian Aboriginal children. An important risk factor for neurodevelopmental vulnerability is prenatal alcohol exposure (PAE), which places children at risk for Fetal Alcohol Spectrum Disorder (FASD). AIMS: This study assesses neurodevelopment outcomes in a population of Australian Aboriginal children with and without PAE. METHODS AND PROCEDURES: Children born in 2002/2003, and living in the Fitzroy Valley, Western Australia between April 2010 and November 2011, were eligible (N=134). Sociodemographic and antenatal data, including PAE, were collected by interview with 127/134 (95%) consenting parents/caregivers. Maternal/child medical records were reviewed. Neurodevelopment was assessed by clinicians blinded to PAE in 108/134 (81%) children and diagnoses on the FASD spectrum were assigned. OUTCOMES AND RESULTS: Neurodevelopmental disorder was documented in 34/108 children (314.8 per 1000). Any diagnosis on the FASD spectrum was made in 21/108 (194.4 per 1000) children (95% CI=131.0-279.0). CONCLUSIONS AND IMPLICATIONS: Neurodevelopmental impairment with or without PAE is highly prevalent among children in the Fitzroy Valley. Rates of diagnoses on the FASD spectrum are among the highest worldwide. Early intervention services are needed to support developmentally vulnerable children in remote communities.

Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE): Proposed DSM-5 Diagnosis.

Over the past 40 years, a significant body of animal and human research has documented the teratogenic effects of prenatal alcohol exposure (PAE). Neurobehavioral Disorder associated with PAE is proposed as a new clarifying term, intended to encompass the neurodevelopmental and mental health symptoms associated with PAE. Defining this disorder is a necessary step to adequately characterize these symptoms and allow clinical assessment not possible using existing physically-based diagnostic schemes. Without appropriate diagnostic guidelines, affected individuals are frequently misdiagnosed and treated inappropriately (often to their considerable detriment) by mental health, educational, and criminal justice systems. Three core areas of deficits identified from the available research, including neurocognitive, self-regulation, and adaptive functioning impairments, are discussed and information regarding associated features and disorders, prevalence, course, familial patterns, differential diagnosis, and treatment of the proposed disorder are also provided.

Functional handwriting performance in school-age children with fetal alcohol spectrum disorders.

Handwriting is a critical skill for school success. Children with fetal alcohol spectrum disorders (FASD) often present with fine motor and visual-motor impairments that can affect handwriting performance, yet handwriting skills have not been systematically investigated in this clinical group. This study aimed to comprehensively describe handwriting skills in 20 school-age children with FASD. Children were tested with the Process Assessment of the Learner, 2nd Edition (PAL-II), and the Visuomotor Precision subtest of NEPSY, a developmental neuropsychological assessment. Participants performed below average on PAL-II measures of handwriting legibility and speed and on NEPSY visual-motor precision tasks. In contrast, PAL-II measures of sensorimotor skills were broadly within the average range. Results provide evidence of functional handwriting challenges for children with FASD and suggest diminished visual-motor skills and increased difficulty as task complexity increases. Future research is needed to further describe the prevalence and nature of handwriting challenges in this population.

Sleep problems in children with fetal alcohol spectrum disorders.

STUDY OBJECTIVES: Sleep problems in children with fetal alcohol spectrum disorders (FASD) are reportedly common but not well characterized. Objectives were to: (1) assess sleep concerns in children with FASD using a caregiver-report survey, the Children's Sleep Habits Questionnaire (CSHQ); (2) compare CSHQ results with those of previously reported community sample; and (3) describe pilot polysomnography findings in children with FASD. METHODS: Children with FASD were recruited from a behavioral intervention study, and participating caregivers completed the CSHQ. CSHQ results were compared with the original data from a previously published community sample of similar age. Participants with FASD and elevated CSHQ scores were offered overnight polysomnography. RESULTS: Thirty-three children with FASD (4.1-12.1 years) were enrolled; 85% of children with FASD scored above the clinical cutoff Total Score of 41, reflecting marked sleep disturbance. Elevated subdomain scores occurred primarily in areas concerning for pediatric insomnia. Those with comorbid ADHD had elevated CSHQ on additional subdomains with no difference in Total Scores. Compared with the community sample, children with FASD had higher Total Scores on the CSHQ (52 vs. 39, p < 0.001). Polysomnography, completed in 5 subjects, revealed mild sleep disordered breathing and fragmented sleep with elevated non-respiratory arousal indices. CONCLUSIONS: Clinically significant sleep problems are present in children with FASD on both subjective and objective measures. Further investigation is needed to better describe these sleep disturbances and their impact on overall health and daytime neurobehavioral problems in this clinical population.

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.

"Family matters:" fetal alcohol spectrum disorders and the family.

Information about "family matters" is vital to developing targeted interventions, reducing placement disruption, and enhancing outcome in fetal alcohol spectrum disorders (FASD). The quality of the caregiving environment and family function are associated with long-term outcome in natural history study of individuals with FASD. This article integrates multiple information sources to better understand the role of family factors in the outcome of individuals with FASD, and how the family is affected by raising a child with this lifelong condition. A brief description of the useful informal literature is brought together with a review of the surprisingly limited body of systematic research findings on FASD and caregiver/family function, and new data describing children with FASD and characteristics of their caregivers. Directions for future data-gathering and intervention development emerge from combining what is already known with an exploration of what can be learned from a highly targeted review of family-related data in the wide-ranging, general literature on developmental disabilities, and use of a proposed conceptual framework that joins a developmental systems perspective with a family systems approach.

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.

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.

Neuropyschological and behavioral outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders.

BACKGROUND: Clinical and research advancements in the field of fetal alcohol spectrum disorders (FASD) require accurate and valid identification of FASD clinical subgroups. OBJECTIVES: A comprehensive neuropsychological battery, coupled with magnetic resonance imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) were administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified across the spectrum, and distinguish diagnostic subclassifications within the spectrum. The neuropsychological outcomes of the comprehensive neuroimaging study are presented here. METHODS: The study groups included: 1) FAS/Partial FAS; 2) Static Encephalopathy/Alcohol Exposed (SE/AE); 3) Neurobehavioral Disorder/Alcohol Exposed (ND/AE) as diagnosed by an interdisciplinary team using the FASD 4-Digit Code; and 4) healthy peers with no prenatal alcohol. A standardized neuropsychological battery was administered to each child and their primary caregiver by a psychologist. RESULTS: Use of the 4-Digit Code produced three clinically and statistically distinct FASD clinical subgroups. The three subgroups (ND/AE, SE/AE and FAS/PFAS) reflected a linear continuum of increasing neuropsychological impairment and physical abnormality, representing the full continuum of FASD. Behavioral and psychiatric disorders were comparably prevalent across the three FASD groups, and significantly more prevalent than among the Controls. All three FASD subgroups had comparably high levels of prenatal alcohol exposure. CONCLUSIONS: Although ND/AE, SE/AE, and FAS/PFAS are distinct FASD subgroups, these groups are not distinguishable solely by their neuropsychological profiles. While all children within a group shared the same magnitude of neuropsychological impairment, the patterns of impairment showed considerable individual variability. MRI, MRS and fMRI further distinguished these FASD subgroups.