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Normative MRI Data Increase the Sensitivity to Brain Volume Abnormalities in the Classification of Fetal Alcohol Spectrum Disorder
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Introduction
Fetal alcohol spectrum disorder (FASD), a life-long condition resulting from prenatal alcohol exposure (PAE), is associated with structural brain anomalies and neurobehavioral differences. Evidence from longitudinal neuroimaging suggest trajectories of white matter microstructure maturation are atypical in PAE. We aimed to further characterize longitudinal trajectories of developmental white matter microstructure change in children and adolescents with PAE compared to typically-developing Controls using diffusion-weighted Neurite Orientation Dispersion and Density Imaging (NODDI).
Materials and methods
Participants: Youth with PAE (n = 34) and typically-developing Controls (n = 31) ages 8–17 years at enrollment. Participants underwent formal evaluation of growth and facial dysmorphology. Participants also completed two study visits (17 months apart on average), both of which involved cognitive testing and an MRI scan (data collected on a Siemens Prisma 3 T scanner). Age-related changes in the orientation dispersion index (ODI) and the neurite density index (NDI) were examined across five corpus callosum (CC) regions defined by tractography.
Results
While linear trajectories suggested similar overall microstructural integrity in PAE and Controls, analyses of symmetrized percent change (SPC) indicated group differences in the timing and magnitude of age-related increases in ODI (indexing the bending and fanning of axons) in the central region of the CC, with PAE participants demonstrating atypically steep increases in dispersion with age compared to Controls. Participants with PAE also demonstrated greater increases in ODI in the mid posterior CC (trend-level group difference). In addition, SPC in ODI and NDI was differentially correlated with executive function performance for PAE participants and Controls, suggesting an atypical relationship between white matter microstructure maturation and cognitive function in PAE.
Discussion
Preliminary findings suggest subtle atypicality in the timing and magnitude of age-related white matter microstructure maturation in PAE compared to typically-developing Controls. These findings add to the existing literature on neurodevelopmental trajectories in PAE and suggest that advanced biophysical diffusion modeling (NODDI) may be sensitive to biologically-meaningful microstructural changes in the CC that are disrupted by PAE. Findings of atypical brain maturation-behavior relationships in PAE highlight the need for further study. Further longitudinal research aimed at characterizing white matter neurodevelopmental trajectories in PAE will be important.
Every year, millions of brain MRI scans are acquired in hospitals, which is a figure considerably larger than the size of any research dataset. Therefore, the ability to analyze such scans could transform neuroimaging research. Yet, their potential remains untapped since no automated algorithm is robust enough to cope with the high variability in clinical acquisitions (MR contrasts, resolutions, orientations, artifacts, and subject populations). Here, we present SynthSeg+, an AI segmentation suite that enables robust analysis of heterogeneous clinical datasets. In addition to whole-brain segmentation, SynthSeg+ also performs cortical parcellation, intracranial volume estimation, and automated detection of faulty segmentations (mainly caused by scans of very low quality). We demonstrate SynthSeg+ in seven experiments, including an aging study on 14,000 scans, where it accurately replicates atrophy patterns observed on data of much higher quality. SynthSeg+ is publicly released as a ready-to-use tool to unlock the potential of quantitative morphometry.
Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight ¹ . Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories ² of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones ³ , showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
Background:
As clinicians strive to achieve consensus worldwide on how best to diagnose fetal alcohol spectrum disorders (FASD), the most recent FASD diagnostic systems show convergence and divergence. Applying these systems to a single clinical population illustrates the contrasts between them, but validation studies are ultimately required to identify the best system.
Methods:
The 4-Digit-Code, Hoyme 2016, Canadian 2015 and Australian 2016 FASD diagnostic systems were applied to 1,392 patient records evaluated for FASD at the University of Washington. The diagnostic criteria and tools, the prevalence and concordance of diagnostic outcomes, and validity measures were compared between the systems.
Results:
The proportion diagnosed with fetal alcohol syndrome (FAS) and FASD varied significantly (4-Digit-Code 2.1%, ≤79%; Hoyme 6.4%, 44%, Australian 1.8%, 29%; Canadian 1.8%, 16%). Eighty-two percent were diagnosed FASD by at least one system; only 11% by all four systems. Key factors contributing to discordance include: requiring high alcohol exposure; excluding growth deficiency; relaxing the facial criteria; requiring brain criteria that prevent diagnosis of infants/toddlers; and excluding moderate dysfunction from the spectrum. Primate research confirms moderate dysfunction (1-2 domains ≤-2 standard deviations) is the most prevalent outcome caused by PAE (FAS 5%, severe dysfunction 31%, moderate dysfunction 59%). Only the 4-Digit-Code replicated this diagnostic pattern.
Conclusion:
The needs of individuals with FASD are best met when diagnostic systems provide accurate, validated diagnoses across the lifespan, the full spectrum of outcome, the full continuum of alcohol exposure; and utilize diagnostic nomenclature that accurately reflects the association between outcome and alcohol exposure.
The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors' combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism-funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol.
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.
In April 2006, the World Health Organization (WHO) released new international growth charts for children aged 0-59 months. Similar to the 2000 CDC growth charts, these charts describe weight for age, length (or stature) for age, weight for length (or stature), and body mass index for age. Whereas the WHO charts are growth standards, describing the growth of healthy children in optimal conditions, the CDC charts are a growth reference, describing how certain children grew in a particular place and time. However, in practice, clinicians use growth charts as standards rather than references. In 2006, CDC, the National Institutes of Health, and the American Academy of Pediatrics convened an expert panel to review scientific evidence and discuss the potential use of the new WHO growth charts in clinical settings in the United States. On the basis of input from this expert panel, CDC recommends that clinicians in the United States use the 2006 WHO international growth charts, rather than the CDC growth charts, for children aged <24 months (available at https://www.cdc.gov/growthcharts). The CDC growth charts should continue to be used for the assessment of growth in persons aged 2-19 years. The recommendation to use the 2006 WHO international growth charts for children aged <24 months is based on several considerations, including the recognition that breastfeeding is the recommended standard for infant feeding. In the WHO charts, the healthy breastfed infant is intended to be the standard against which all other infants are compared; 100% of the reference population of infants were breastfed for 12 months and were predominantly breastfed for at least 4 months. When using the WHO growth charts to screen for possible abnormal or unhealthy growth, use of the 2.3rd and 97.7th percentiles (or ±2 standard deviations) are recommended, rather than the 5th and 95th percentiles. Clinicians should be aware that fewer U.S. children will be identified as underweight using the WHO charts, slower growth among breastfed infants during ages 3-18 months is normal, and gaining weight more rapidly than is indicated on the WHO charts might signal early signs of overweight.
Prenatal alcohol exposure has numerous effects on the developing brain, including damage to selective brain structure. We review structural magnetic resonance imaging (MRI) studies of brain abnormalities in subjects prenatally exposed to alcohol. The most common findings include reduced brain volume and malformations of the corpus callosum. Advanced methods have been able to detect shape, thickness and displacement changes throughout multiple brain regions. The teratogenic effects of alcohol appear to be widespread, affecting almost the entire brain. The only region that appears to be relatively spared is the occipital lobe. More recent studies have linked cognition to the underlying brain structure in alcohol-exposed subjects, and several report patterns in the severity of brain damage as it relates to facial dysmorphology or to extent of alcohol exposure. Future studies exploring relationships between brain structure, cognitive measures, dysmorphology, age, and other variables will be valuable for further comprehending the vast effects of prenatal alcohol exposure and for evaluating possible interventions.
The caret package, short for classification and regression training, contains numerous tools for developing predictive models using the rich set of models available in R. The package focuses on simplifying model training and tuning across a wide variety of modeling techniques. It also includes methods for pre-processing training data, calculating variable importance, and model visualizations. An example from computational chemistry is used to illustrate the functionality on a real data set and to benchmark the benefits of parallel processing with several types of models.
This multifactorial study investigates the interrelationships between head circumference (HC) and intellectual quotient (IQ), learning, nutritional status and brain development in Chilean school-age children graduating from high school, of both sexes and with high and low IQ and socio-economic strata (SES). The sample consisted of 96 right-handed healthy students (mean age 18.0 +/- 0.9 years) born at term. HC was measured both in the children and their parents and was expressed as Z-score (Z-HC). In children, IQ was determined by means of the Wechsler Intelligence Scale for Adults-Revised (WAIS-R), scholastic achievement (SA) through the standard Spanish language and mathematics tests and the academic aptitude test (AAT) score, nutritional status was assessed through anthropometric indicators, brain development was determined by magnetic resonance imaging (MRI) and SES applying the Graffar modified method. Results showed that microcephalic children (Z-HC < or = 2 S.D.) had significantly lower values mainly for brain volume (BV), parental Z-HC, IQ, SA, AAT, birth length (BL) and a significantly higher incidence of undernutrition in the first year of life compared with their macrocephalic peers (Z-HC > 2S.D.). Multiple regression analysis revealed that BV, parental Z-HC and BL were the independent variables with the greatest explanatory power for child's Z-HC variance (r(2) = 0.727). These findings confirm the hypothesis formulated in this study: (1) independently of age, sex and SES, brain parameters, parental HC and prenatal nutritional indicators are the most important independent variables that determine HC and (2) microcephalic children present multiple disorders not only related to BV but also to IQ, SA and nutritional background.
The diagnosis of fetal alcohol spectrum disorder (FASD) is complex and guidelines are warranted. A subcommittee of the Public Health Agency of Canada's National Advisory Committee on Fetal Alcohol Spectrum Disorder reviewed, analysed and integrated current approaches to diagnosis to reach agreement on a standard in Canada. The purpose of this paper is to review and clarify the use of current diagnostic systems and make recommendations on their application for diagnosis of FASD-related disabilities in people of all ages. The guidelines are based on widespread consultation of expert practitioners and partners in the field. The guidelines have been organized into 7 categories: screening and referral; the physical examination and differential diagnosis; the neurobehavioural assessment; and treatment and follow-up; maternal alcohol history in pregnancy; diagnostic criteria for fetal alcohol syndrome (FAS), partial FAS and alcohol-related neurodevelopmental disorder; and harmonization of Institute of Medicine and 4-Digit Diagnostic Code approaches. The diagnosis requires a comprehensive history and physical and neurobehavioural assessments; a multidisciplinary approach is necessary. These are the first Canadian guidelines for the diagnosis of FAS and its related disabilities, developed by broad-based consultation among experts in diagnosis.
Accurate and early diagnosis of the fetal alcohol syndrome is important for secondary prevention, intervention, and treatment, yet many pediatricians lack expertise in recognition of the characteristic features of this disorder. After a structured training program for pediatricians, we examined the ability to accurately diagnose fetal alcohol syndrome.
Two dysmorphologists conducted a 2-day training program in the diagnosis of the physical features of fetal alcohol syndrome for 4 pediatricians in Moscow. Dysmorphologists and pediatricians worked in teams to examine children, demonstrate techniques, and validate that pediatricians could identify physical features of this disorder under direct observation. Subsequently, pediatricians independently evaluated children in 41 boarding schools and orphanages. Those children diagnosed with fetal alcohol syndrome or deferred (possible fetal alcohol syndrome) by the pediatricians were then evaluated by the dysmorphologists. Accuracy of the diagnosis of fetal alcohol syndrome or deferred was assessed, as well as the interrater agreement for specific selected features of the disorder.
A total of 110 children were examined by both the pediatricians and the dysmorphologists. Of these, 79 were identified with fetal alcohol syndrome by the pediatricians; in 66 (83.5%) of these children, the diagnosis was confirmed by the dysmorphologists. Among 31 children who were classified as deferred by the pediatricians, 21 (67.7%) were confirmed with either fetal alcohol syndrome or deferred by the dysmorphologists. With respect to selected structural features characteristic of fetal alcohol syndrome, good interrater agreement was noted for height and head circumference < or = 10th centile, whereas moderate-to-fair agreement was noted for smooth philtrum, long philtrum, presence of "hockey-stick" palmar crease, and palpebral fissure length < or = 10th centile. Poor agreement was noted for thin upper lip.
After a relatively short training session, pediatricians were reasonably accurate in diagnosing fetal alcohol syndrome on the basis of physical features and in recognizing most of the selected specific features associated with the disorder.
To quantify the relationship between brain volume and head circumference from early childhood to adulthood, and quantify how this relationship changes with age.
Whole-brain volume and head circumference measures were obtained from MR images of 76 healthy normal males aged 1.7 to 42 years.
Across early childhood, brain volume and head circumference both increase, but from adolescence onward brain volume decreases while head circumference does not. Because of such changing relationships between brain volume and head circumference with age, a given head circumference was associated with a wide range of brain volumes. However, when grouped appropriately by age, head circumference was shown to accurately predict brain volume. Head circumference was an excellent prediction of brain volume in 1.7 to 6 years old children (r = 0.93), but only an adequate predictor in 7 to 42 year olds.
To use head circumference as an accurate indication of abnormal brain volume in the clinic or research setting, the patient's age must be taken into account. With knowledge of age-dependent head circumference-to-brain volume relationship, head circumference (particularly in young children) can be an accurate, rapid, and inexpensive indication of normalcy of brain size and growth in a clinical setting.
The Human Connectome Projects in Development (HCP-D) and Aging (HCP-A) are two large-scale brain imaging studies that will extend the recently completed HCP Young-Adult (HCP-YA) project to nearly the full lifespan, collecting structural, resting-state fMRI, task-fMRI, diffusion, and perfusion MRI in participants from 5 to 100 + years of age. HCP-D is enrolling 1300 + healthy children, adolescents, and young adults (ages 5-21), and HCP-A is enrolling 1200 + healthy adults (ages 36-100+), with each study collecting longitudinal data in a subset of individuals at particular age ranges. The imaging protocols of the HCP-D and HCP-A studies are very similar, differing primarily in the selection of different task-fMRI paradigms. We strove to harmonize the imaging protocol to the greatest extent feasible with the completed HCP-YA (1200 + participants, aged 22-35), but some imaging-related changes were motivated or necessitated by hardware changes, the need to reduce the total amount of scanning per participant, and/or the additional challenges of working with young and elderly populations. Here, we provide an overview of the common HCP-D/A imaging protocol including data and rationales for protocol decisions and changes relative to HCP-YA. The result will be a large, rich, multi-modal, and freely available set of consistently acquired data for use by the scientific community to investigate and define normative developmental and aging related changes in the healthy human brain.
The fetal alcohol spectrum of disorders (FASD) includes four diagnostic categories for the clinical consequences of prenatal alcohol exposure (PAE) in the unborn child. Physical features are necessary for the diagnosis of the fetal alcohol syndrome (FAS) and partial pFAS. Moreover, these features are specific and a diagnosis of FAS can be made even in the absence of knowledge of PAE. Not only growth deficits, microcephaly and the 3 facial features (short palpebral fissures, smooth philtrum and narrow vermillion of the upper lip) are characteristic, since other dysmorphic features particularly in the hands are key to the recognition of FAS. Most features can be explained by the damage to the brain during pregnancy and can be replicated in animal models. Many different diagnostic guidelines are used for the diagnosis of FASD and the physical features are considered differently in each of them. There is a need for universal clinical criteria for the diagnosis of FASD if our goal is to favor universal recognition.
Background:
Despite the prevalence of fetal alcohol spectrum disorders (FASD) and the importance of accurate identification of patients, clinical diagnosis may not be consistent across sites due to the heterogeneous nature of FASD and the characteristics of different diagnostic systems used. Here, we compare 5 systems designed to operationalize criteria recommended for the diagnosis of effects of prenatal alcohol exposure (PAE). We determined the extent of consistency among them as well as factors that may reduce intersystem reliability. Compared are: Emory Clinic, Seattle 4-Digit System (Diagnostic Guidelines for Fetal Alcohol Spectrum Disorders: The 4-Digit Diagnostic Code, Seattle, WA, University Publication Services, 2004), Centers for Disease Control and Prevention (Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis, Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA, 2004), Canadian Guidelines (CMAJ, 172, 2005, S1), and the Hoyme Modifications (Pediatrics, 115, 2005, 39).
Methods:
Subjects were 1,581 consecutively registered patients applying for evaluation at a university-based clinic treating alcohol and drug-exposed children. Records of the multidisciplinary evaluation (pediatric, social, psychological) were abstracted. Diagnostic criteria for all 5 systems were applied, and patients were diagnosed according to each of the systems. We compared results using Cohen's Kappa to evaluate the extent of agreement.
Results:
Percent of individuals diagnosed with FASD ranged from 4.74% (CDC) to 59.58% (Hoyme). Examination using Cohen's Kappa found modest agreement among systems, particularly when individual diagnoses, Fetal Alcohol Syndrome (FAS), partial FAS (pFAS), and Alcohol-Related Neurodevelopmental Disorder (ARND) were used. Examination of diagnostic criteria found almost perfect agreement on growth (weight; height), with limited overlap for physical features (palpebral fissures, hypoplastic philtrum, upper vermillion) and for neurobehavioral outcomes. Child's race and age influenced agreement among systems, with African American and older children more frequently diagnosed.
Conclusions:
Results suggest problems in convergent validity among these systems, as demonstrated by a lack of reliability in diagnosis. Absence of an external standard makes it impossible to determine whether any system is more accurate, but outcomes do suggest areas for future research that may refine diagnosis.
Cognition is 1 of 4 domains measured by the NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIH-TB), and complements modules testing motor function, sensation, and emotion. On the basis of expert panels, the cognition subdomains identified as most important for health, success in school and work, and independence in daily functioning were Executive Function, Episodic Memory, Language, Processing Speed, Working Memory, and Attention. Seven measures were designed to tap constructs within these subdomains. The instruments were validated in English, in a sample of 476 participants ranging in age from 3 to 85 years, with representation from both sexes, 3 racial/ethnic categories, and 3 levels of education. This report describes the development of the Cognition Battery and presents results on test-retest reliability, age effects on performance, and convergent and discriminant construct validity. The NIH-TB Cognition Battery is intended to serve as a brief, convenient set of measures to supplement other outcome measures in epidemiologic and longitudinal research and clinical trials. With a computerized format and national standardization, this battery will provide a "common currency" among researchers for comparisons across a wide range of studies and populations. Neurology (R) 2013; 80 (Suppl 3):S54-S64
The Human Connectome Project (HCP) faces the challenging task of bringing multiple magnetic resonance imaging (MRI) modalities together in a common automated preprocessing framework across a large cohort of subjects. The MRI data acquired by the HCP differ in many ways from data acquired on conventional 3 Tesla scanners and often require newly developed preprocessing methods. We describe the minimal preprocessing pipelines for structural, functional, and diffusion MRI that were developed by the HCP to accomplish many low level tasks, including spatial artifact/distortion removal, surface generation, cross-modal registration, and alignment to standard space. These pipelines are specially designed to capitalize on the high quality data offered by the HCP. The final standard space makes use of a recently introduced CIFTI file format and the associated grayordinate spatial coordinate system. This allows for combined cortical surface and subcortical volume analyses while reducing the storage and processing requirements for high spatial and temporal resolution data. Here, we provide the minimum image acquisition requirements for the HCP minimal preprocessing pipelines and additional advice for investigators interested in replicating the HCP's acquisition protocols or using these pipelines. Finally, we discuss some potential future improvements to the pipelines.
The physical features of fetal alcohol syndrome include smooth philtrum, thin vermillion border, short palpebral fissures, microcephaly, and growth deficiencies on weight and height. However, little is known about the specific quantities of alcohol exposure, pattern of drinking, timing of exposure, and magnitude of risk for each of these features.
Using data on 992 subjects collected prospectively in California between 1978 and 2005, we examined the patterns and timing of alcohol exposure in relation to these features. Structural features were assessed by a dysmorphologist who performed a blinded physical examination of all infants. Patterns of drinking were evaluated by drinks per day, number of binge episodes, and maximum number of drinks. Timing of exposure was evaluated 0 to 6 weeks postconception, 6 to 12 weeks postconception, first trimester, second trimester, and third trimester.
Higher prenatal alcohol exposure in every pattern was significantly associated with the incidence of smooth philtrum but not with short palpebral fissures. The strongest associations were with timing of exposure in the second half of the first trimester (RR 1.25, 95% CI 1.14 to 1.36 for average number of drinks per day; RR 1.17, 95% CI 1.09 to 1.26 for maximum number of drinks in 1 episode). Similarly, thin vermillion border was most strongly associated with exposure in the second half of the first trimester. Findings with respect to timing of exposure were similar for microcephaly and reduced birth weight. However, reduced birth length was increased with exposure in any trimester. These associations were linear, and there was no evidence of a threshold.
Reduced birth length and weight, microcephaly, smooth philtrum, and thin vermillion border are associated with specific gestational timing of prenatal alcohol exposure and are dose-related without evidence of a threshold. Women should continue to be advised to abstain from alcohol consumption from conception throughout pregnancy.
The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) was created in 2003 to further understanding of fetal alcohol spectrum disorders. Clinical and basic science projects collect data across multiple sites using standardized methodology. This article describes the methodology being used by the clinical projects that pertain to assessment of children and adolescents. Domains being addressed are dysmorphology, neurobehavior, 3-D facial imaging, and brain imaging. (c) 2010 Elsevier Inc. All rights reserved.
PIP
Case histories are presented of 8 unrelated children born to mothers who were chronic alcoholics. These children showed a similar pattern of craniofacial, limb, and cardiovascular defects associated with prenatal-onset growth deficiency and developmental delay. This is the 1st report to document an association between maternal alcoholism and aberrant morphogenesis in the offspring. The mean duration of maternal alcoholism was 9.4 years. 3 of the cases were black, 3 were Native American, and 2 were white. The mean gestational age was 38 weeks. The degree of linear growth deficiency was more severe than the deficit of weight at birth, suggesting that a factor other than maternal undernutrition alone affected prenatal growth. Developmental delay, prenatal and postnatal growth deficiency, and short palbebral fissures were observed in all 8 children. 7 of the 8 children also demonstrated microcephaly and maxillary hypoplasia with relative prognathism. 6 had an altered palmar crease pattern, 5 showed cardiac and joint anomalies, and 4 had epicanthal folds. Although adequate nutrition was provided to the children during hospital admission and/or foster care placement, no catch-up growth was observed. After 1 year, the average linear growth rate was 65% of normal and the average rate of weight gain was only 38% of normal. By 1 year, head circumference fell below the 3rd percentile for height and chronological age in 5 of the 6 children in whom measurements were taken. Fine motor dysfunction was present in 5 of the 6 children tested, and most were delayed in gross motor performance as well. The similarity in pattern of malformation noted among these 8 children suggests a singular mode of etiology related to an as yet unknown effect of maternal alcoholism. Direct ethanol toxicity is the most likely possibility.
Several properties of the cerebral cortex, including its columnar and laminar organization, as well as the topographic organization of cortical areas, can only be properly understood in the context of the intrinsic two-dimensional structure of the cortical surface. In order to study such cortical properties in humans, it is necessary to obtain an accurate and explicit representation of the cortical surface in individual subjects. Here we describe a set of automated procedures for obtaining accurate reconstructions of the cortical surface, which have been applied to data from more than 100 subjects, requiring little or no manual intervention. Automated routines for unfolding and flattening the cortical surface are described in a companion paper. These procedures allow for the routine use of cortical surface-based analysis and visualization methods in functional brain imaging.
Fetal alcohol syndrome (FAS) results from maternal alcohol use during pregnancy and carries lifelong consequences. Early recognition of FAS can result in better outcomes for persons who receive a diagnosis. Although FAS was first identified in 1973, persons with this condition often do not receive a diagnosis. In 2002, Congress directed CDC to update and refine diagnostic and referral criteria for FAS, incorporating recent scientific and clinical evidence. In 2002, CDC convened a scientific working group (SWG) of persons with expertise in FAS research, diagnosis, and treatment to draft criteria for diagnosing FAS. This report summarizes the diagnostic guidelines drafted by the SWG, provides recommendations for when and how to refer a person suspected of having problems related to prenatal alcohol exposure, and assesses existing practices for creating supportive environments that might prevent long-term adverse consequences associated with FAS. The guidelines were created on the basis of a review of scientific evidence, clinical expertise, and the experiences of families affected by FAS regarding the physical and neuropsychologic features of FAS and the medical, educational, and social services needed by persons with FAS and their families. The guidelines are intended to facilitate early identification of persons affected by prenatal exposure to alcohol so they and their families can receive services that enable them to achieve healthy lives and reach their full potential. This report also includes recommendations to enhance identification of and intervention for women at risk for alcohol-exposed pregnancies. Additional data are needed to develop diagnostic criteria for other related disorders (e.g., alcohol-related neurodevelopmental disorder).
Prenatal alcohol exposure may adversely affect fetal development, causing growth restriction, distinctive craniofacial anomalies, and central nervous system dysfunction. The continuum of associated adverse fetal outcomes is most accurately termed fetal alcohol spectrum disorders (FASD). The purpose of this study was to further clarify the relationship between dysmorphic features and general cognitive capacity in a study on Finnish children with FASD. Forty-eight 8- to 16-year-old children with FASD underwent a dysmorphology examination and an assessment of cognitive capacity. Dysmorphic features and growth deficiency were quantified by assigning each child a total dysmorphology score (TDS). Six subtests from the Wechsler Intelligence Scale for Children (WISC-III) were used for assessment of general cognitive capacity. Our results show a significant correlation between the TDS and cognitive capacity was found, suggesting that children with more severe growth deficiency and dysmorphic features have more cognitive limitations. Birth measures of length and weight correlated with general cognitive capacity. Head circumference correlated only with Performance IQ. These findings imply an inverse relationship between growth deficiency/dysmorphic features and cognitive function in children with FASD. Although the correlations are significant, the data suggest that in individual cases, the TDS cannot reliably predict cognitive function in later life.
Wechsler intelligence scale for children-fifth edition (WISC-V). Pearson Education
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