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Objectives Cortical abnormalities in prenatal alcohol exposure (PAE) are known, including in gyrification (LGI), thickness (CT), volume (CV), and surface area (CS). This study provides longitudinal and developmental context to the PAE cortical development literature. Experimental design Included: 58 children with PAE and 52 controls, ages 6–17 at enrollment, from four Collaborative Initiative on FASD (CIFASD) sites. Participants underwent a formal evaluation of physical anomalies and dysmorphic facial features associated with PAE. MRI data were collected on three platforms (Siemens, GE, and Philips) at four sites. Scans were spaced two years apart. Change in LGI, CT, CS, and CV were examined. Principal observations Several significant regional age-by-diagnosis linear and quadratic interaction effects in LGI, CT, and CV were found, indicating atypical developmental trajectories in PAE. No significant correlations were observed between cortical measures and IQ. Conclusions Regional differences were seen longitudinally in CT, CV, and LGI in those with PAE. The findings represent important insights into developmental trajectories and may have implications for the timing of assessments and interventions in this population. It is noteworthy that cortical metrics did not correlate with IQ, suggesting that more specific aspects of cognitive development may need to be explored to provide further context. [ABSTRACT FROM AUTHOR]

Prenatal cocaine exposure (PCE) is associated with long-term and negative effect on arousal regulation. Recent neuroimaging studies have examined brain mechanisms related to arousal dysregulation with cross-sectional experimental designs; but longitudinal changes in the brain, reflecting group differences in neurodevelopment, have never been directly examined. To directly assess the interaction of PCE and neurodevelopment, the present study used a longitudinal design to analyze functional magnetic resonance imaging (fMRI) data collected from 33 adolescents (21 with PCE and 12 non-exposed controls) while they performed the same working memory task with emotional distracters at two points in time. The mean age of participants was 14.3 years at time_1 and 16.7 years at time_2. With confounding factors statistically controlled, the fMRI data revealed significant exposure-by-time interaction in the activations of the amygdala and default mode network (DMN). For the control adolescents, brain activations associated with emotional arousal (amygdala) and cognitive effort (DMN) were both reduced at time_2 as compared to that at time_1. However, these activation reductions were not observed in the PCE group, indicating persistently high levels of emotional arousal and cognitive effort. In addition, correlations between longitudinal changes in the brain and in behavior have shown that adolescents with persistently high emotional arousal were more likely in need of high cognitive effort; and their cognitive performance was more likely to be affected by distractive challenges. The present results complement and extend previous findings from cross-sectional studies with further evidence supporting the view of PCE associated long-term teratogenic effects on arousal regulation. [ABSTRACT FROM AUTHOR]

Abstract: While prenatal cocaine exposure (PCE) has been associated with arousal dysregulation and attentional impairments in both human and animal studies, the neurobiological bases of these teratogenic effects have not been well characterized. In the current study, we report functional neuroimaging observations of these effects in exposed youth. Using functional magnetic resonance imaging (fMRI), we embedded task-irrelevant emotional distracters in a working memory task to examine the interaction of emotional arousal and memory in 33 PCE and 23 non-exposed adolescents. Though with similar behavioral performance, the two groups exhibited different activation patterns associated with emotion–memory interactions. On the one hand, higher memory load attenuated emotion-related amygdala activation in controls but not in the exposed adolescents; on the other hand, prefrontal activation associated with memory load decreased in the presence of emotional distraction in the controls but increased in the exposed group. These group interaction differences suggest neurobiological substrates for arousal-associated neuronal alterations related to prenatal cocaine exposure. Consistent with previous findings in behavioral and physiological studies, the present neuroimaging data provided more in-depth evidence supporting the view that PCE has significant long-term teratogenic effect on arousal regulation system. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Unintentional injuries are a leading cause of death and disability for children. Those with developmental disabilities, including children affected by prenatal alcohol exposure, are at highest risk for injuries. Although teaching safety skills is recommended to prevent injury, cognitive limitations and behavioral problems characteristic of children with fetal alcohol spectrum disorder make teaching these skills challenging for parents and teachers. In the current study, 32 children, ages 4–10, diagnosed with fetal alcohol syndrome (FAS) and partial FAS, learned fire and street safety through computer games that employed “virtual worlds” to teach recommended safety skills. Children were pretested on verbal knowledge of four safety elements for both fire and street safety conditions and then randomly assigned to one condition. After playing the game until mastery, children were retested verbally and asked to “generalize” their newly acquired skills in a behavioral context. They were retested after 1 week follow-up. Children showed significantly better knowledge of the game to which they were exposed, immediately and at follow-up, and the majority (72%) was able to generalize all four steps within a behavioral setting. Results suggested that this is a highly effective method for teaching safety skills to high-risk children who have learning difficulties. [Copyright &y& Elsevier]

The diagnoses included within the umbrella term fetal alcohol spectrum disorders (FASD), are based on the documentation of prenatal alcohol exposure (PAE), growth deficits and a pattern of dysmorphic physical features and neurobehavioral impairments. Although 3 key facial features (short palpebral fissures, a smooth philtrum and a thin vermilion of the upper lip) are the only dysmorphic features taken into account for the diagnosis of Fetal Alcohol Syndrome (FAS) or partial FAS (pFAS), several other features are commonly seen in individuals with these diagnoses. The goals of our study were to determine if some of these secondary physical features also occur more frequently in children with alcohol-related neurodevelopmental disorder (ARND) relative to controls, and if a cluster of these features combined in a dysmorphology score could be used to identify those negatively impacted by PAE but who do not have the cardinal physical features that led to a diagnosis of FAS or pFAS. Among 2681 children recruited for the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence (CoFASP) study, 1726 had an FASD or sufficient evidence of PAE having occurred or not in their pregnancy. Children were then categorized into groups using the modified Hoyme diagnostic criteria (FAS (n = 24), pFAS (n = 99) and ARND (n = 87), and No FASD (n = 1516), including those with No FASD and a history of PAE (No FASD/PAE, n = 498) and those with No FASD and no history of PAE (No FASD/No PAE, n = 1018). The frequencies of 26 secondary dysmorphic features were compared among these groups, both individually and combined in non-weighted and weighted dysmorphic scores. Correlations of the total dysmorphic scores with an index of overall cognitive ability were also compared by group status. Several of these features were significantly more frequent in children with FAS than in those with No FASD diagnosis with or without PAE but not in comparison to those with ARND. The number of features was also significantly higher in the FAS group as compared to all other groups for both weighted and unweighted dysmorphology scores but were not higher in the group with ARND when compared to the groups with No FASD either in the presence or absence of PAE. Although not diagnostic, higher total dysmorphology scores were predictive of lower general cognitive abilities in the group with ARND, suggesting severity of alcohol-related dysmorphology is predictive of severity of alcohol-related neurobehavioral impairment. Secondary physical features were not more frequent in children with ARND compared to children without an FASD diagnosis but were a marker for lower cognitive function. The use of secondary physical features to support a diagnosis of ARND was not supported in this sample. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a hierarchical decision tree model that combines neurobehavioral and physical measures to identify children affected by prenatal alcohol exposure even when facial dysmorphology is not present.Study Design: Data were collected as part of a multisite study across the US. The model was developed after we evaluated more than 1000 neurobehavioral and dysmorphology variables collected from 434 children (8-16 years of age) with prenatal alcohol exposure, with and without fetal alcohol syndrome, and nonexposed control subjects, with and without other clinically-relevant behavioral or cognitive concerns. The model subsequently was validated in an independent sample of 454 children in 2 age ranges (5-7 years or 10-16 years). In all analyses, the discriminatory ability of each model step was tested with logistic regression. Classification accuracies and positive and negative predictive values were calculated.Results: The model consisted of variables from 4 measures (2 parent questionnaires, an IQ score, and a physical examination). Overall accuracy rates for both the development and validation samples met or exceeded our goal of 80% overall accuracy.Conclusions: The decision tree model distinguished children affected by prenatal alcohol exposure from nonexposed control subjects, including those with other behavioral concerns or conditions. Improving identification of this population will streamline access to clinical services, including multidisciplinary evaluation and treatment. [ABSTRACT FROM AUTHOR]

Introduction Few studies have focused on the transition to adulthood in adults with prenatal alcohol exposure (PAE). In this study, we examine the occurrence of problem behavior at this transition, including mental health problems, substance use, and difficulties with the legal system. The sample is prospective and provides an opportunity to examine effects of a wide range of prenatal exposure. Adults with PAE were expected to show more problem behavior; the impact of level of exposure was examined as well. Method The sample was drawn from a predominantly low-income, African-American population. Mothers of the alcohol-exposed participants (n = 123) and those in the non-exposed SES-Control group (CONT) (n = 59) were recruited at a prenatal visit when information on alcohol and drug use during pregnancy was collected. A disability contrast group (n = 54) was recruited at adolescence. The adults with PAE were assigned to three groups varying in physical and cognitive effects of exposure. This report is based on the adults' responses to interviews or questionnaires on problem behavior and laboratory tests related to substance use. Results Adults with PAE showed more problem behavior in all three areas than adults from the CONT group. For mental health problems, the exposed group showing cognitive, but not physical effects, had the highest scores; their scores were similar, however, to those of the disability contrast group on several scales. Results for outcomes on substance use and legal difficulties were less consistent, but, when significant effects occurred, the group that was exposed, but neither physically nor cognitively affected, was more likely to show negative outcomes. Males in this group were most involved in these behaviors. Conclusion Effects of PAE continue into early adulthood and affect mental health problems, substance use, and interactions with the legal system. Adults who are exposed, but less physically affected, seem to be the most involved in problem behavior. More research is necessary to examine environmental effects in conjunction with PAE on these outcomes and to provide a basis for developing potential interventions. [ABSTRACT FROM AUTHOR]

Introduction Although many studies have demonstrated effects of prenatal alcohol exposure (PAE) on physical, cognitive, and behavioral development in children, few have focused on the long term effects on adults. In this study, data are presented on adaptive function and entry into adult roles in a community sample of young adults with PAE. The expectation was that prenatally exposed adults would show lower adaptive functioning and more difficulty with entry into adult roles than the non-exposed control group and that these effects would be related to the severity of PAE effects. Method The predominantly African-American, low income sample included adults with a wide range of prenatal exposure (n = 123) as well as control groups for socioeconomic (SES) (n = 59) and disability (n = 54) status. The mothers of the alcohol-exposed and SES-control group participants were recruited before birth and offspring have been followed up periodically. The disability control group was recruited in adolescence. The adults were interviewed about adaptive function in day-to-day life and adult role entry. Collateral adults who were well-acquainted with each participant were interviewed concerning adaptive function. Results Results showed that adults who were dysmorphic and/or cognitively affected by PAE had difficulty with adaptive function and entry into adult roles. Males showing cognitive effects with no physical effects were the most severely affected. Results for exposed adults not showing physical or cognitive effects were similar to or more positive than those of the control group for most outcomes. Conclusion PAE has long-term effects on adaptive outcomes in early adulthood. Additional research should focus on possible interventions at this transition and on factors contributing to the adjustment of the exposed, but unaffected participants. [ABSTRACT FROM AUTHOR]

Abstract: Prenatal cocaine exposure (PCE) is associated with arousal dysregulation, and alterations of amygdala activity in response to emotional arousal have previously been reported. However, voluntary regulation of emotional affect, enabling appropriate neural response to different streams of stimuli, must also engage prefrontal regions, yet the impact of PCE on these prefrontal mechanisms has not been investigated. Recent neuroimaging studies have shown the involvement of ventral prefrontal cortex (vPFC) in the modulation of amygdala reactivity and the mediation of effective emotional regulation. Based on these findings, using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), the present study compared functional activations of the vPFC as well as its structural connectivity with the amygdala between groups of PCE and control adolescents. In a working memory task with emotional distracters, the PCE adolescents exhibited less capability of increasing their vPFC activation in response to increased memory load, which corresponded with their less suppressed amygdala activation. Reduced structural connectivity between the vPFC and the amygdala was also observed from DTI measurement in the PCE group. In addition, correlations between amygdala activation and (i) vPFC activation, as well as (ii) amygdala-vPFC structural connectivity, were observed in the control but not in the PCE group. These data complement previous findings of the impact of PCE on the activity of the amygdala and extend our understanding of the neurobiological mechanisms underlying the effect of PCE on arousal dysregulation reported in human and animal studies. [Copyright &y& Elsevier]

Abstract: This study examined the associations between prenatal cocaine exposure and quality of mother–infant play interactions at 13months of infant ages. We investigated whether maternal psychological distress and infant reactivity mediated or moderated this association. Participants consisted of 220 (119 cocaine exposed and 101 non-cocaine exposed) mother–infant dyads participating in an ongoing longitudinal study of prenatal cocaine exposure. Results indicated that mothers who used cocaine during pregnancy displayed higher negative affect and lower sensitivity toward their infant during play interactions at 13months, and that their infants were less responsive toward them. Contrary to hypothesis, this association was not mediated by maternal psychological distress or by infant reactivity. However, results for both the cocaine and non-cocaine exposed infants were supportive of a transactional model where lower maternal sensitivity at 1month was predictive of higher infant reactivity at 7months, which in turn was predictive of lower maternal warmth/sensitivity at 13months, controlling for potential stability in maternal behavior. Results also indicated that as hypothesized, infant reactivity moderated the association between maternal cocaine use during pregnancy and maternal warmth/sensitivity at 13months of age. Cocaine-using mothers who experienced their infants as being more reactive in early infancy were less warm/sensitive toward them in later infancy. Results have implications for parenting interventions that may be targeted toward improving maternal sensitivity among cocaine-using mothers with more reactive infants. [ABSTRACT FROM AUTHOR]

Abstract: Women giving birth to children with fetal alcohol syndrome have a higher risk of early mortality. However, the risk of increased mortality associated with drinking at lower levels during pregnancy has not been evaluated previously. Accordingly, mortality at 20 years post recruitment was examined in a sample (N =570) of women recruited between 1980 and 1986, who drank more than 1 ounce of absolute alcohol per week (oz AA/wk) during pregnancy and compared to that in abstainers from the same low socioeconomic, African-American population. Using data from archival information and state mortality records, Cox proportional hazards survival models were constructed to determine whether alcohol use, cigarette use, infant birth weight, infant dysmorphia, and alcohol use and abuse by the woman''s own mother (family history positive) were associated with increased risk for mortality. At follow-up (in 2003), 9.5% of the sample had died, with the rate for controls being 3.6%, for those alcohol users who stopped during pregnancy, 12.7%, and for the alcohol users who continued drinking throughout pregnancy, 12.5%. Thus, women using alcohol in pregnancy, whether they stopped or continued to use, were significantly (χ 2 (2)=12.1, P <.01) more likely than abstainers to have died before follow-up. Nondrinkers'' mortality rate was lower than that of other women from this low-income, high-risk population, whereas the drinkers'' rate was 2.7 times higher. In a multivariate analysis, factors contributing to mortality risk included alcohol use and cigarette smoking, but not infant birth weight. Drinking at any level during pregnancy should be regarded as a risk factor for the mother as well as for offspring. Health care professionals working with such women should provide counseling and support for abstinence. [Copyright &y& Elsevier]

Background: Individuals with fetal alcohol spectrum disorders (FASD) experience deficits in behavior, cognition, and academic functioning resulting from prenatal alcohol exposure (PAE). Although receiving intervention for developmental disabilities is a strong protective factor against negative outcomes in FASD, intervention research in this population is in its infancy.Aims: The purpose of this study was to replicate and extend a mathematics intervention, the Math Interactive Learning Experience (MILE) program, which was developed in the USA specifically for children with FASD.Methods: Twenty-eight Canadian children aged 4-10 years with confirmed PAE or an FASD diagnosis were assigned to either the MILE intervention or a contrast intervention.Results: Following a relatively brief, individualized, one-on-one intervention, children in the MILE group demonstrated significantly greater changes in math achievement compared to the contrast group. Significant changes in other cognitive functions were not observed. Older age, lower IQ, and confirmed PAE but no FASD diagnosis were associated with greater math achievement change in the MILE group.Conclusions: The replication and extension of the math intervention appears to have significant, positive impact on mathematics achievement scores of children with PAE and FASD. [ABSTRACT FROM AUTHOR]

This study examined the association between fetal tobacco exposure (FTE) and focused attention at 9 months of child age, and the role of child sex and infant behavioral reactivity as potential moderators of this association. Data were obtained from 203 mothers and their infants (105 fetally exposed and 98 non-exposed) on infant focused attention and behavioral reactivity to a frustration task. FTE was ascertained via nicotine metabolites in infant meconium, reflecting primarily third trimester fetal exposure. Results demonstrated a main effect of FTE on focused attention, such that exposed infants exhibited lower levels of focused attention than non-exposed infants. Behavioral reactivity, but not infant sex, moderated the relationship between FTE and focused attention, such that exposed infants who were highly reactive to frustration had the lowest levels of focused attention. Results suggest that smoking interventions, even in the third trimester, may have a positive impact on attentional outcomes for infants. [ABSTRACT FROM AUTHOR]

The Math Interactive Learning Experience (MILE), a program designed to address academic and behavioral problems found in children with Fetal Alcohol Spectrum Disorders (FASD), was found to be effective in a randomized clinical trials with results that persisted at a 6-month follow-up. The current study evaluated the effectiveness of a community translation, in partnership with several community sites in the metropolitan Atlanta area. A total of 60 participants were randomly assigned to one of the three treatment groups: the MILE program administered at a specialty care center (Center MILE) or in the community (Community MILE), or to parent math instruction only (Parent Instruction). This study evaluated instructor satisfaction with the training program, knowledge related to FASD and the MILE program, adherence to the MILE teaching methodology, participant math outcomes, and parents’ satisfaction with their treatment experience. Instructors reported a high degree of satisfaction with the overall training and mean site fidelity ratings were positively correlated with change in math performance. Those in the MILE intervention groups demonstrated more positive gains in math skills than those in the Parent Instruction group but did not differ from each other. Parents in the Parent Instruction group reported less satisfaction with their intervention than those assigned to the Center MILE group but satisfaction ratings did not differ between those in the MILE intervention groups. These results indicate that the community translation and the MILE instructor training program developed as part of this process were well-received and effective in producing positive treatment outcomes. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]