An Event‐Related Potential Study of Response Inhibition in ADHD With and Without Prenatal Alcohol Exposure

Background: The attention and cognitive problems seen in individuals with a history of prenatal alcohol exposure often resemble those associated with attention deficit hyperactivity disorder (ADHD), but few studies have directly assessed the unique influence of each on neurobehavioral outcomes. Methods: We recorded event‐related potentials (ERPs) during a Go/No‐go response inhibition task in young adults with prospectively obtained histories of prenatal alcohol exposure and childhood ADHD. Results: Regardless of prenatal alcohol exposure, participants with childhood ADHD were less accurate at inhibiting responses. However, only the ADHD group without prenatal alcohol exposure showed a markedly diminished P3 difference between No‐go and Go, which may reflect a more effortful strategy related to inhibitory control at the neural processing level. Conclusion: This finding supports a growing body of evidence suggesting that the manifestation of idiopathic ADHD symptoms may stem from a neurophysiologic process that is different from the ADHD symptomatology associated with prenatal alcohol exposure. Individuals who have been prenatally exposed to alcohol and present with ADHD symptomatology may represent a unique endophenotype of the disorder, which may require different treatment approaches from those found to be effective with idiopathic ADHD.     

Social Cognitive and Emotion Processing Abilities of Children With Fetal Alcohol Spectrum Disorders: A Comparison With Attention Deficit Hyperactivity Disorder

Background:  Although children with Fetal Alcohol Spectrum Disorders (FASDs) are at high risk of attention deficit hyperactivity disorder (ADHD), direct comparisons show distinct cognitive phenotypes in the 2 diagnoses. However, these groups have not been directly compared for social problems or social cognition, nor has social cognition been directly examined in FASDs.
Objectives:  To compare FASDs and ADHD groups on social cognition tasks and determine whether deficient social cognition and emotion processing predict behavioral problems and social skills.
Methods:  Studied were 33 children with FASDs, 30 with ADHD, and 34 normal controls (NC). All received tasks of social cognition and emotion processing. Parents and teachers rated children on measures of completed questionnaires assessing child's behavioral problems and social skills using the Child Behavior Checklist, Teacher Report Form, and Social Skills Rating Scale. Children received 3 subtests from the Saltzman-Benaiah and Lalonde (2007) Theory of Mind Task as a measure of social cognition and 4 subtests from the Minnesota Test of Affective Processing ( Lai et al., 1991 ) to assess emotion processing.
Results:  Parents and teachers reported more behavior problems and poorer social skills in children in FASD and ADHD than NC groups. FASDs demonstrated significantly weaker social cognition and facial emotion processing ability than ADHD and NC groups. Regression analyses identified social cognition as a significant predictor of behavior problems and emotion processing as a significant predictor of social skills.
Conclusions:  Children with FASDs show a distinct behavioral profile from children with ADHD. Difficulties in social cognition and emotion processing in children with FASDs may contribute to their high incidence of social behavioral problems.     

An fMRI Study of Number Processing in Children With Fetal Alcohol Syndrome

Background: Number processing deficits are frequently seen in children exposed to alcohol in utero. Methods: Functional magnetic resonance imaging was used to examine the neural correlates of number processing in 15 right‐handed, 8‐ to 12‐year‐old children diagnosed with fetal alcohol syndrome (FAS) or partial FAS (PFAS) and 18 right‐handed, age‐ and gender‐matched controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa, using Proximity Judgment and Exact Addition tasks. Results: Control children activated the expected fronto‐parietal network during both tasks, including the anterior horizontal intraparietal sulcus (HIPS), left posterior HIPS, left precentral sulcus, and posterior medial frontal cortex. By contrast, on the Proximity Judgment task, the exposed children recruited additional parietal pathways involving the right and left angular gyrus and posterior cingulate/precuneus, which may entail verbally mediated recitation of numbers and/or subtraction to assess relative numerical distances. During Exact Addition, the exposed children exhibited more diffuse and widespread activations, including the cerebellar vermis and cortex, which have been found to be activated in adults engaged in particularly challenging number processing problems. Conclusions: The data suggest that, whereas control children rely primarily on the fronto‐parietal network identified in previous studies to mediate number processing, children with FAS/PFAS recruit a broader range of brain regions to perform these relatively simple number processing tasks. Our results are consistent with structural neuroimaging findings indicating that the parietal lobe is relatively more affected by prenatal alcohol exposure and provide the first evidence for brain activation abnormalities during number processing in children with FAS/PFAS, effects that persist even after controlling statistically for group differences in total intracranial volume and IQ.     

A review of social skills deficits in individuals with fetal alcohol spectrum disorders and prenatal alcohol exposure: profiles, mechanisms, and interventions

Background: Individuals gestationally exposed to alcohol experience a multitude of sociobehavioral impairments, including deficits in adaptive behaviors such as social skills. Methods: The goal of this report is to critically review research on social skills deficits in individuals with prenatal alcohol exposure, including individuals with and without fetal alcohol spectrum disorders (FASD). Results: Social deficits are found in alcohol‐exposed children, adults, and adolescents with and without a clinical presentation. These deficits tend to persist across the lifespan and may even worsen with age. Social deficits in this population appear to be independent of facial dysmorphology and IQ and are worse than can be predicted based on atypical behaviors alone. Abnormalities in neurobiology, executive function, sensory processing, and communication likely interact with contextual influences to produce the range of social deficits observed in FASD. Conclusions: Future investigations should strive to reconcile the relationship between social skills deficits in FASD and variables such as gender, age, cognitive profile, and structural and functional brain impairments to enable better characterization of the deficits observed in this population, which will enhance diagnosis and improve remediation.     

Implicit strategy affects learning in children with heavy prenatal alcohol exposure

BACKGROUND: Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re-analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention. METHODS: The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9-16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test-Children's Version; CVLT-C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL-WRAML). RESULTS: Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT-C compared with the VL-WRAML. Groups also showed comparable rates of retention after a delay on the CVLT-C. In contrast, on the VL-WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT-C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level. CONCLUSIONS: The finding of spared retention of verbal information on the CVLT-C in our earlier studies may be related to test characteristics of the CVLT-C rather than a finding of spared verbal retention per se, given that spared retention was not found on a separate test of verbal learning and memory without an implicit learning strategy. These results suggest that the use of an implicit strategy positively affected the ability of alcohol-exposed children to learn and retain new verbal information.     

Executive functioning in children with heavy prenatal alcohol exposure

BACKGROUND: Children with heavy prenatal alcohol exposure have well documented deficits in overall cognitive ability. Recently, attention has turned to the executive function (EF) domain in this population. Until recently, comprehensive measures of EF have not been available within one test battery. This study used a battery of tests to assess four domains of EF in alcohol-exposed children. METHODS: The Delis-Kaplan Executive Function Scale was used to evaluate EF in 18 children with heavy prenatal alcohol exposure, with and without a diagnosis of fetal alcohol syndrome (FAS), and 10 nonexposed controls. Children ranged in age from 8 to 15 years. Measures from four domains of executive functioning were analyzed: planning ability, cognitive flexibility, selective inhibition, and concept formation and reasoning. Tasks consisted of primary EF measures as well as measures of secondary component skills. RESULTS: Alcohol-exposed children were deficient on EF measures compared with nonexposed controls. Furthermore, in most cases, children with and without the FAS diagnosis did not differ from one another. These deficits were not entirely explainable by concomitant deficits on component skills. Specific impairments were identified within the domains of planning and response inhibition, with additional deficits in abstract thinking and flexibility. CONCLUSIONS: Deficits in executive functioning were observed in alcohol-exposed children with or without the diagnosis of FAS and in the absence of mental retardation. Performance on these EF tasks provides insight into the cognitive processes driving overall performance and has implications for adaptive and daily functions. These results are consistent with anecdotal and empirical reports of deficits in behavioral control and with neuroanatomical evidence of volumetric reductions in structures within the frontal-subcortical system in children with heavy prenatal alcohol exposure.     

Auditory and visual sustained attention in adolescents prenatally exposed to alcohol

BACKGROUND: Sustained attention problems and impulsivity are reported in association with prenatal alcohol exposure and fetal alcohol syndrome, but research in this area is limited and contradictory. METHODS: Auditory and visual sustained attention were investigated in 265 low-income, predominantly African-American, adolescents (mean age, 15.12 years; SD, 0.92). Included were 53 unexposed controls and 128 exposed to alcohol and other drugs prenatally, with 46 of these exhibiting dysmorphic features and growth retardation, as well as a special-education contrast group (n = 84). Sustained attention was measured with "AK" subtests from a commercially available Continuous Performance Task program. Outcomes included total correct, total errors, omissions, commissions, preservations, hit rate, false alarms, reaction time, and response sensitivity (d'). A repeated-measures multivariate analysis of variance procedure was used with the exposure group (four groups) as the independent variable and presentation mode (visual or auditory) and trial block (four blocks) as within-subject repeated measures. RESULTS: There was an interaction of group with presentation mode for total correct, errors, error type, hit rate, and d'. Most groups processed visual information more effectively than auditory information. In contrast, dysmorphic adolescents performed as effectively when presented with auditory stimuli but were less efficient in processing visual information. Significantly higher error rates, particularly omission errors [F(3,261) = 7.16; p < 0.000], as well as lower d' [F(3,261) = 5.77; p < 0.001], were noted in this group. CONCLUSIONS: These results suggest that there may be specific patterns to the effect of prenatal alcohol exposure on cognitive performance that can be identified during adolescence. In this study of sustained attention, processing in the visual modality was more affected than that in the auditory modality. Deficits in visual processing seemed to result from insensitivity to target stimuli.     

Acquisition and retention of verbal and nonverbal information in children with heavy prenatal alcohol exposure

BACKGROUND: Memory deficits are reported commonly in children with fetal alcohol syndrome. However, little is known about nonverbal memory performance in this population. METHODS: The current study examined learning and memory abilities in alcohol-exposed children and nonexposed controls. Multiple verbal and nonverbal measures were used that incorporated repeated learning trials and delayed recall trials. The alcohol-exposed group included children with heavy prenatal alcohol exposure with and without fetal alcohol syndrome. Children ranged in age from 8 to 16 years, and groups were matched on age, sex, ethnicity, and socioeconomic status. RESULTS: Children with heavy prenatal alcohol exposure displayed deficits in learning and recall of verbal and nonverbal information across all measures. On learning trials, they recalled fewer words and displayed a lower rate of acquisition. However, when we analyzed delayed verbal recall data after controlling for initial verbal learning, group differences were not apparent. The same pattern did not occur for nonverbal information; children with prenatal alcohol exposure recalled less on delayed recall even when we accounted for initial learning. CONCLUSIONS: These data are consistent with previous studies that indicate immediate memory deficits but suggest that, at least for verbal information, delayed recall deficits in this population are better accounted for by deficits in initial learning. Importantly, a different pattern of results was demonstrated for verbal versus nonverbal information, which suggests the need for additional research in this area.     

Applying a Developmental Framework to the Self‐Regulatory Difficulties of Young Children with Prenatal Alcohol Exposure: A Review

Prenatal alcohol exposure (PAE) can be associated with significant difficulties in self‐regulatory abilities. As such, interventions have been developed that focus on improving varying aspects of self‐regulation for this population. The application of a multilevel theoretical framework that describes the development of self‐regulation during early childhood could further advance the field. First, this framework could assist in elucidating mechanisms in the trajectories of early adjustment problems in this population and, second, informing the development of more precise assessment and interventions for those affected by PAE. The aims of the current review were to provide an overview of the self‐regulatory framework proposed by Calkins and colleagues (e.g., Calkins, 2007; Calkins and Fox, 2002); examine the self‐regulatory difficulties that are commonly experienced during infancy (i.e., 0 to 2 years) and early childhood (i.e., 3 to 8 years) in children with PAE in the context of the developmental framework; and describe how the framework can inform the development of future assessment and intervention provision for young children with PAE. The application of a developmental framework, such as proposed by Calkins and colleagues, allows for a systematic and theoretically driven approach to assessment and intervention programs for young children with PAE.     

Interhemispheric transfer in children with heavy prenatal alcohol exposure

BACKGROUND: Prenatal alcohol exposure has long been associated with alterations in brain structure and behavioral changes. The corpus callosum can be affected by heavy prenatal alcohol exposure, and agenesis (absence) of this structure occurs more often in children with fetal alcohol syndrome than in the general population or in other developmentally delayed populations. Although the majority of children with fetal alcohol syndrome do not have agenesis of the corpus callosum, callosal area is reduced in this population, particularly in the anterior and posterior regions. However, the functional implication of these size reductions has not been examined. METHODS: The current study used a finger localization task to measure the transfer of information across the corpus callosum in children and adolescents with histories of heavy prenatal alcohol exposure and age- and sex-matched controls. In a subset of children, correlational analysis was also conducted between behavioral data and cross-sectional area of the corpus callosum. RESULTS: When compared with nonexposed controls, alcohol-exposed children made more errors on trials for which information had to cross the corpus callosum ("crossed" trials) than on trials for which it did not ("uncrossed" trials), and they also made more errors as the task increased in complexity. Additionally, correlations with magnetic resonance imaging data in a subset of children revealed that impairment in interhemispheric transfer was related to reductions in the size of the corpus callosum. These correlations were independent of effects expected from the relationship between corpus callosum size and general intellectual functioning alone. CONCLUSIONS: These findings suggest that children with heavy prenatal alcohol exposure display subtle deficits in the interhemispheric transfer of information in the somatosensory domain. Such deficits in interhemispheric transfer are likely to be related to the myriad of other behavioral and cognitive impairments observed in these children.     

Prenatal alcohol exposure patterns and alcohol-related birth defects and growth deficiencies: a prospective study

Background: 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. Methods: 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. Results: 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. Conclusions: 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.     

Genetic and developmental modulation of cardiac deficits in prenatal alcohol exposure

BACKGROUND: Increasing evidence demonstrates that genetic background is an important modulator of alcohol's effects on the developing fetus. Such effects are separable from maternal ethanol metabolism. Here, we study ethanol's effects on cardiogenesis in an avian model that shows strong cell death within neuronal and neural crest precursors following ethanol exposure. METHODS: The study design tested the hypothesis that ethanol-induced losses of cardiac neural crest populations would disrupt outflow tract development and thus contribute to the valvuloseptal deficits observed in prenatal alcohol exposure. Three chick strains were exposed to alcohol at gestational windows between gastrulation and early heart septation (day 3 incubation), and then hearts were examined at the completion of morphogenesis (day 10 incubation). RESULTS: Ethanol's impact on cardiac development was influenced by fetal genetics. The B300 x Hampshire Red cross exhibited pronounced cell death within cardiac neural crest populations but had normal development of the heart and aortic arches. Neural crest migration and differentiation into the distal outflow tract were also normal in these embryos, which suggested a capacity to repair earlier losses. The DeKalb White x Hampshire Red cross also did not exhibit cardiac defects. Hearts of the B300 strain had a unique phenotype with respect to ethanol exposure and exhibited a thin ventricular compact layer, dilatation, and reduced myosin/deoxyribonucleic acid and myosin/protein content, a phenotype that indicates disrupted myocardial maturation and inductive cues. The deficit was only observed when ethanol exposure occurred at stages 15 or 18 and apparently was independent of neural crest cell death. Such ventricular thinning might go undetected in the absence of extensive screening. CONCLUSIONS: Results add to the increasing evidence that genetic background strongly modulates the effects of prenatal alcohol exposure. The results also suggest that embryos have a varying capacity to repair and recover from earlier neural crest losses.     

Biomarkers for the Detection of Prenatal Alcohol Exposure: A Review

Alcohol exposure during pregnancy can cause adverse effects to the fetus, because it interferes with fetal development, leading to later physical and mental impairment. The most common clinical tool to determine fetal alcohol exposure is maternal self‐reporting. However, a more objective and useful method is based on the use of biomarkers in biological specimens alone or in combination with maternal self‐reporting. This review reports on clinically relevant biomarkers for detection of prenatal alcohol exposure (PAE). A systematic search was performed to ensure a proper overview in existing literature. Studies were selected to give an overview on clinically relevant neonatal and maternal biomarkers. The direct biomarkers fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulfate, and phosphatidylethanol (PEth) were found to be the most appropriate biomarkers in relation to detection of PAE. To review each biomarker in a clinical context, we have compared the advantages and disadvantages of each biomarker, in relation to its window of detectability, ease of collection, and the ease and cost of analysis of each biomarker. The biomarkers PEth, FAEEs, and EtG were found to be applicable for detection of even low levels of alcohol exposure. Meconium is an accessible matrix for determination of FAEEs and EtG, and blood an accessible matrix for determination of PEth.     

Children with heavy prenatal alcohol exposure demonstrate deficits on multiple measures of concept formation

Background:  Children with heavy prenatal alcohol exposure have documented impairments in executive functioning (EF). One component of EF, concept formation, has not been well studied in this group.
Methods:  Children (8 to 18 years) with histories of heavy prenatal alcohol exposure, with and without fetal alcohol syndrome (FAS), were compared to typically developing controls on 2 measures of concept formation and conceptual set shifting: the Wisconsin Card Sorting Test and the Card Sorting Test from the Delis–Kaplan Executive Functioning System. In addition to between-group comparisons, performance relative to overall intellectual functioning was examined.
Results:  Children with histories of heavy prenatal alcohol exposure showed impairment on both tests of concept formation compared to non-exposed controls. These deficits included difficulty generating and verbalizing concepts, increased error rates and perseverative responses, and poorer response to feedback. However, in comparison to controls, alcohol-exposed children performed better on measures of concept formation than predicted by their overall IQ scores. Exploratory analyses suggest that this may be due to differences in how the measures relate at different IQ levels and may not be specific to prenatal alcohol exposure.
Conclusions:  Deficits in concept formation and conceptual set shifting were observed in alcohol-exposed children with or without the diagnosis of FAS and in the absence of mental retardation. These deficits likely impact problem solving skills and adaptive functioning and have implications for therapeutic interventions in this population.