Julie A. Kable

Further Development of a Neurobehavioral Profile of Fetal Alcohol Spectrum Disorders

BACKGROUND Heavy prenatal alcohol exposure (AE) results in a broad array of neurobehavioral deficits. Recent research has focused on identification of a neurobehavioral profile or profiles that will improve the identification of children affected by AE. This study aimed to build on our preliminary neurobehavioral profile to improve classification accuracy and test the specificity of the resulting profile in an alternate clinical group. METHODS A standardized neuropsychological test battery was administered to 3 groups of children: subjects with AE (n = 209), typically developing controls (CON, n = 185), and subjects with attention-deficit/hyperactivity disorder (ADHD, n = 74). We assessed a large sample from 6 sites in the United States and South Africa, using standardized methodology. Data were analyzed using 3 latent profile analyses including (i) subjects with fetal alcohol syndrome (FAS) and controls, (ii) subjects with AE without FAS and controls, and (iii) subjects with AE (with or without FAS) and subjects with ADHD. RESULTS Classification accuracy was moderate but significant across the 3 analyses. In analysis 1, overall classification accuracy was 76.1% (77.2% FAS, 75.7% CON). In the second analysis, overall classification accuracy was 71.5% (70.1% AE/non-FAS, 72.4% CON). In the third analysis, overall classification accuracy was 73.9% (59.8% AE, 75.7% ADHD). Subjects that were misclassified were examined for systematic differences from those that were correctly classified. CONCLUSIONS The results of this study indicate that the neuropsychological effects of AE are clinically meaningful and can be used to accurately distinguish alcohol-affected children from both typically developing children and children with ADHD. Further, in combination with other recent studies, these data suggest that approximately 70% of children with heavy prenatal alcohol exposure are neurobehaviorally affected, while the remaining 30% are spared these often-devastating consequences, at least those in the domains under study. Refining the neurobehavioral profile will allow improved identification and treatment development for children affected by prenatal alcohol exposure.

Math Performance and Behavior Problems in Children Affected by Prenatal Alcohol Exposure: Intervention and Follow-Up

Objective: Fetal alcohol spectrum disorders (FASD), resulting from maternal alcohol use during pregnancy, are associated with significant academic and behavior problems. Although affected children are common in clinical practice, information to guide recommendations about interventions with this high risk group is very limited. This study evaluated the persistence of effects of an intervention on the math performance and behavior of 54 children, 3- to 10-years, diagnosed with fetal alcohol syndrome or FASD. Methods: Children were randomly assigned to a 6-week Math intervention (n = 28) tailored to this clinical group or to a standard psychoeducational contrast group (n = 26). All caregivers received identical educational interventions to promote learning readiness and improve behavioral outcomes. In a previous study, participants were assessed before interventions and immediately following completion. In this follow-up study, participants were recontacted and reassessed at 6 months post completion to determine if positive results on math functioning and child behavior would persist after treatment discontinuation. Results: Focus was on 2 outcomes: (1) Math performance, assessed using standardized measures of math achievement and (2) Behavior problems as reported by caregivers on the Child Behavior Checklist (CBCL) and teachers on the Teacher Report Form (TRF). Experimental-group participants demonstrated significantly greater scores on math outcome measures than Contrast group members and CBCL and TRF behavior was improved over pretest scores in both groups. Conclusion: This 6-month follow-up confirms that both math skills and behavior of alcohol-affected children are improved significantly by interventions designed to meet their specific learning and behavior needs.

Memory and Brain Volume in Adults Prenatally Exposed to Alcohol.

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.

The Impact of Prenatal Alcohol Exposure on Neurophysiological Encoding of Environmental Events at Six Months

BACKGROUND Using methodologies from developmental studies on infant information-processing skills, early manifestations of later long-term neurocognitive effects of prenatal alcohol exposure can be explored by assessing primary cognitive processes, including attentional regulation and processing speed. METHODS One hundred eighteen 6-month-old infants (18 high risk, 100 low risk) from a longitudinal study of moderate prenatal alcohol exposure and intrauterine growth retardation were presented with both auditory (400 and 1000 Hz pure tones) and visual stimuli (chromatic Caucasian faces) in an information-processing paradigm with cardiac response as the dependent variable. The first three habituation trials were analyzed to assess neurophysiological encoding of environmental events in infants categorized as high and low risk based on status of maternal drinking. Specific indexes of the cardiac response were used to assess the infants (1). speed of initiating attention, (2). sustained attention, and (3). shifting attention after stimulus offset. RESULTS Infants identified as high risk based on a cumulative risk index for prenatal alcohol exposure responded more slowly to stimuli and were rated as significantly higher in arousal level across the three trials but did not display differences in their sustained deceleration responses or responses to stimulus-offset. CONCLUSIONS Less efficient neurophysiological encoding was observed among high-risk infants, suggesting that prenatal alcohol exposure may disrupt fundamental components of the attentional system responsible for regulating the bodys responses to environmental events. Slower neurophysiological responses involved in encoding environmental stimuli and initiating attention and higher levels of behavioral arousal suggest that these infants may have had difficulties with regulating the interactions between arousal level and the attentional system needed to provide optimal efficiency in processing environmental events. These outcomes suggest that prenatal alcohol exposure results in specific impairments in early attentional regulation, which may influence subsequent cognitive development and behavioral outcomes dependent on these primary cognitive processes.

Impact of a camp experience on phenylalanine levels, knowledge, attitudes, and health beliefs relevant to nutrition management of phenylketonuria in adolescent girls.

OBJECTIVE To evaluate the effectiveness of an education intervention in a summer camp setting on knowledge, attitudes, and health beliefs regarding metabolic control of phenylketonuria and dietary compliance. DESIGN An observational study of a weeklong metabolic camp for adolescent girls with phenylketonuria (PKU) who were followed up over the course of 1 year. Observations also were made in 3 subsequent years of camp. INTERVENTION The camp experience consisted of diet and disease education, sessions on reproductive development, and recreation. Group discussions on attitudes and perceptions about PKU related to dietary compliance were held with nutritionists and a pediatric psychologist. OUTCOME MEASURES Biochemical and psychological data were collected on the first and last days of the camp to assess short-term effects of the intervention, then at quarterly intervals during the year to determine the long-term impact of the camp. Precamp and Postcamp plasma amino acid data for the subsequent 3 years were also collected. SUBJECTS/SETTING Analyses were based on 13 adolescent girls with PKU in the first year of a camp at Emory University in Atlanta, Ga, and compared with data from 11 additional campers enrolled the second year, 8 in the third year, and 7 in the fourth year. Mean age +/- standard deviation of first-year campers was 13 +/- 2 years, mean IQ +/- standard deviation was 98 +/- 16, and 9 of 13 girls had menstruated. STATISTICAL ANALYSES PERFORMED Short-term effects of the intervention were computed by comparing mean levels of response from the baseline period to those from the last day of camp using t tests for dependent samples. Repeated-measures analysis of variance was used to assess the long-term effects of the camp experience over the course of a year at regular quarterly intervals. RESULTS Short-term effects of the education intervention were significant reductions in dietary phenylalanine intake, plasma phenylalanine levels, and perceived isolation. However, these effects progressively returned to baseline levels over the course of a year. The significant short- and long-term effects of increased knowledge of diet and disease persisted throughout the study period. APPLICATIONS/CONCLUSIONS Short-term effects of the education intervention resulted in improved metabolic control associated with improved attitudes, increased knowledge of diet and disease, increased perceived support, and decreased barriers to dietary compliance in a camp setting.

Executive function predicts adaptive behavior in children with histories of heavy prenatal alcohol exposure and attention-deficit/hyperactivity disorder.

BACKGROUND Prenatal exposure to alcohol often results in disruption to discrete cognitive and behavioral domains, including executive function (EF) and adaptive functioning. In the current study, the relation between these 2 domains was examined in children with histories of heavy prenatal alcohol exposure, nonexposed children with a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and typically developing controls. METHODS As part of a multisite study, 3 groups of children (8 to 18 years, M = 12.10) were tested: children with histories of heavy prenatal alcohol exposure (ALC, n = 142), nonexposed children with ADHD (ADHD, n = 82), and typically developing controls (CON, n = 133) who did not have ADHD or a history of prenatal alcohol exposure. Children completed subtests of the Delis-Kaplan Executive Function System (D-KEFS), and their primary caregivers completed the Vineland Adaptive Behavior Scales-II. Data were analyzed using regression analyses. RESULTS Analyses showed that EF measures were predictive of adaptive abilities, and significant interactions between D-KEFS measures and group were present. For the ADHD group, the relation between adaptive abilities and EF was more general, with 3 of the 4 EF measures showing a significant relation with adaptive score. In contrast, for the ALC group, this relation was specific to the nonverbal EF measures. In the CON group, performance on EF tasks did not predict adaptive scores over the influence of age. CONCLUSIONS These results support prior research in ADHD, suggesting that EF deficits are predictive of poorer adaptive behavior and extend this finding to include children with heavy prenatal exposure to alcohol. However, the relation between EF and adaptive ability differed by group, suggesting unique patterns of abilities in these children. These results provide enhanced understanding of adaptive deficits in these populations, as well as demonstrate the ecological validity of laboratory measures of EF.

Verbal and nonverbal memory in adults prenatally exposed to alcohol.

BACKGROUND Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains. METHODS In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic group, n = 47); Exposed individuals without such effects (n = 74). Contrast groups included: Controls (n = 59) matched for ethnicity, socioeconomic status, and hospital of birth; Special Education contrast group (n = 54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval, and learning over trials as indexed by slope. RESULTS Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance. CONCLUSION These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.

The impact of maternal smoking on fast auditory brainstem responses.

Deficits in auditory processing have been posited as one of the underlying neurodevelopmental consequences of maternal smoking during pregnancy that leads to later language and reading deficits. Fast auditory brainstem responses were used to assess differences in the sensory processing of auditory stimuli among infants with varying degrees of prenatal cigarette exposure. Maternal report of consumption of cigarettes and blood samples were collected in the hospital to assess exposure levels and participants were then seen at 6-months. To participate in the study, all infants had to pass the newborn hearing exam or a clinically administered ABR and have no known health problems. After controlling for participant age, maternal smoking during pregnancy was negatively related to latency of auditory brainstem responses. Of several potential covariates, only perinatal complications and maternal alcohol use were also related to latency of the ABR responses and maternal smoking level accounted for significant unique variance after controlling for these factors. These results suggest that the relationship between maternal smoking may lead to disruption in the sensory encoding of auditory stimuli.

Prenatal Alcohol Exposure, Attention-Deficit/Hyperactivity Disorder, and Sluggish Cognitive Tempo

BACKGROUND Children with heavy prenatal alcohol exposure often meet criteria for attention-deficit/hyperactivity disorder (ADHD). ADHD research has examined subtype differences in symptomatology, including sluggish cognitive tempo (SCT). This construct is defined by behavioral symptoms including hypoactivity and daydreaming and has been linked to increased internalizing behaviors. The current study examined whether similar findings are displayed in children with prenatal alcohol exposure. METHODS As part of a multisite study, caregivers of 272 children (8 to 16 years) completed the SCT Scale and Child Behavior Checklist (CBCL). Four groups were included: alcohol-exposed children with ADHD (ALC+; n = 75), alcohol-exposed children without ADHD (ALC-; n = 35), nonexposed children with ADHD (ADHD; n = 60), and nonexposed children without ADHD (CON; n = 102). SCT and CBCL scores were analyzed using 2 (exposure) × 2 (ADHD) analyses of variance. Pearsons correlations measured the relationships between SCT, CBCL, and Full Scale IQ (FSIQ). Discriminant function analysis examined whether SCT items could accurately classify groups. RESULTS Analyses revealed significant main effects of exposure and ADHD on SCT and internalizing and externalizing scores and significant interaction effects on SCT and internalizing scores. SCT significantly correlated with internalizing, externalizing, and attention ratings in all groups and with FSIQ in ALC+. Discriminant function analysis indicated that specific SCT items could distinguish ALC- from CON. CONCLUSIONS Alcohol-exposed children exhibited elevated SCT scores. Elevations were related to increased parent ratings of internalizing and externalizing behaviors and attention. These findings are observed in alcohol-exposed children regardless of ADHD symptoms and specific SCT items proved useful in distinguishing exposed children, suggesting clinical utility for this measure in further defining the neurobehavioral profile related to prenatal alcohol exposure.

A Comparison Among 5 Methods for the Clinical Diagnosis of Fetal Alcohol Spectrum Disorders

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 Cohens 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 Cohens 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. Childs 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.