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While benchmark dose (BMD) methodology is well‐established for settings with a single exposure, these methods cannot easily handle multidimensional exposures with nonlinear effects. We propose a framework for BMD analysis to characterize the joint effect of a two‐dimensional exposure on a continuous outcome using a generalized additive model while adjusting for potential confounders via propensity scores. This leads to a dose–response surface which can be summarized in two dimensions by a contour plot in which combinations of exposures leading to the same expected effect are identified. In our motivating study of prenatal alcohol exposure, cognitive deficits in children are found to be associated with both the frequency of drinking as well as the amount of alcohol consumed on each drinking day during pregnancy. The general methodological framework is useful for a broad range of settings, including combinations of environmental stressors, such as chemical mixtures, and in explorations of the impact of dose rate rather than simply cumulative exposure on adverse outcomes. [ABSTRACT FROM AUTHOR]

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

Background: The neurobehavioral health impairments associated with prenatal alcohol exposure are now known to persist through adulthood. However, little is known about how these impairments affect individuals' parenting abilities and the neurobehavioral health of their offspring. This study compares parents with fetal alcohol spectrum disorder (FASD) with socioeconomically matched, nonexposed parents on measures of parenting and family support and assesses the neurobehavioral health of the children in both groups. Methods: Forty‐nine parent–child dyads were recruited from a longitudinal cohort of low socioeconomic status. Measures included the Parenting Styles and Dimensions Questionnaire, Family Support Scale, an in‐depth psychosocial history, the Pediatric Symptom Checklist (PSC; parent and child reports), the Achenbach Child Behavior Checklist (CBCL), a screening psychiatric evaluation of the child, the NIH Toolbox Cognition Battery for Children, The Vineland Adaptive Behavior Scales‐Third Edition caregiver rating form, and the Traumatic Events Screening Inventory (parent and child reports). Results: Cognitive functioning was impaired for both offspring of parents with FASD (x¯ = 81.1, SD = 13.0) and control parents (x¯ = 79.9, SD = 16.1), but despite similar impairments, children of parents with FASD were less likely to have an Individualized Education Plan than controls. Adaptive functioning was adequate for both groups (x¯ = 92.1, SD = 15.4 in exposed vs. x¯ = 94.3, SD = 12.3 in controls) and CBCL and PSC scores in both groups were within normal limits. Parents in both groups showed a predominantly authoritative parenting style. Despite a similar frequency of adverse childhood experiences in both groups, parents with FASD were less likely to recognize their child's adverse experiences. Conclusion: Parents with FASD display notable strengths including a predominantly authoritative parenting style. However, parents with FASD underrecognize child trauma and underutilize developmental services compared to socioeconomically matched controls, despite similar neurocognitive impairments. Impairments in adaptive functioning in parents with FASD may translate into difficulties with child–parent communication and limit both insight into neurobehavioral problems and advocacy skills. There is a need to identify and support parents with FASD to optimize their parenting abilities in the context of their individual strengths and difficulties. [ABSTRACT FROM AUTHOR]

Summary: High levels of prenatal alcohol exposure (PAE) result in significant cognitive deficits in children, but the exact nature of the dose‐response relationship is less well understood. To investigate this relationship, data were assembled from six longitudinal birth cohort studies examining the effects of PAE on cognitive outcomes from early school age through adolescence. Structural equation models (SEMs) are a natural approach to consider, because of the way they conceptualise multiple observed outcomes as relating to an underlying latent variable of interest, which can then be modelled as a function of exposure and other predictors of interest. However, conventional SEMs could not be fitted in this context because slightly different outcome measures were used in the six studies. In this paper we propose a multi‐group Bayesian SEM that maps the unobserved cognition variable to a broad range of observed outcomes. The relation between these variables and PAE is then examined while controlling for potential confounders via propensity score adjustment. By examining different possible dose‐response functions, the proposed framework is used to investigate whether there is a threshold PAE level that results in minimal cognitive deficit. [ABSTRACT FROM AUTHOR]

Background: It is estimated that 1%–5% of children in the United States are affected by prenatal alcohol exposure while only a small percentage are so identified in clinical practice. One explanation for this discrepancy may be the way in which diagnostic criteria are operationalized. Methods: To evaluate the extent to which three commonly used systems for the diagnosis of Fetal Alcohol Spectrum Disorder (FASD) consistently identified children in a community sample, data from the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence (COFASP) study were re‐analyzed. In the data set, there were 2325 children with variables necessary to allow diagnosis by three systems commonly used in North America. These systems were (1) that used by COFASP, which is a revised modification of the Institute of Medicine's recommendations, (2) the 4‐Digit Code, and (3) the most recent Canadian Guidelines. To determine the degree of association among these classifications, the Fleiss Multirater Kappa measure of agreement was applied. Results: Among these three systems, 408 children were classified as FASD, 208 by the CoFASP system, 319 by the 4‐Digit Code, and 28 by the Canadian Guidelines. Agreement among the findings from the three systems varied from slight to fair. Conclusions: These results indicate a lack of consistency in these approaches to FASD diagnosis. Discrepancies result from differences in specifying the criteria used to define the diagnosis, including growth, physical features, neurobehavior, and alcohol‐use thresholds. The question of their relative accuracy cannot be resolved without reference to a measure of validity that does not currently exist, and this suggests the need for a more empirically based diagnostic schema. [ABSTRACT FROM AUTHOR]

Background: The vascular system may be particularly vulnerable to prenatal alcohol exposure (PAE). Alterations in angiogenesis and epigenetic changes to vascular development have been implicated as a probable mechanism for this vulnerability. Methods: We assessed the long‐term impact of prenatal alcohol exposure (PAE) on adult vascular health using a prospective cohort first identified while in utero. Participants with no PAE (n = 37, mean age = 36.7 [SD = 1.6] years) were compared to participants with PAE (n = 51, mean age = 36.3 [SD = 1.7] years). Their vascular health was assessed by arterial blood pressure (BP) and peripheral arterial tonometry, which yields an index of endothelial function (reactive hyperemia index) and a measure of arterial stiffness (augmentation index). Blood samples were collected to assess cholesterol levels and insulin resistance (glucose, hemoglobin A1C, and insulin). Path analysis was used to examine the direct and indirect effects of PAE on vascular health after adjusting for other known physical outcomes. Results: Participants with a history of PAE weighed less, trended towards being shorter, had smaller body mass, and had more alcohol‐related dysmorphic features than those without PAE. Path analysis suggested that the impact of PAE on BP was through its indirect relationships with height, body mass index, and dysmorphic features and resulted in protective effects relative to the Contrast group who were disproportionately overweight. PAE was also found to have a direct negative effect on endothelial function. An index of total alcohol‐related dysmorphic features was negatively had both a direct effect on arterial stiffness and an indirect effect on endothelial function. Conclusions: Prenatal alcohol exposures' impact on vascular function is not independent of other common physical and environmental factors but endothelial function and arterial stiffness seemed most compromised after controlling for these other factors. Level of alcohol‐related dysmorphic features seems to be predictive of more adverse effects than endothelial function and vascular stiffness. [ABSTRACT FROM AUTHOR]

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

Background: Fetal alcohol spectrum disorders (FASD) are developmental disabilities that are estimated to occur in 2–5% of elementary school children and that negatively impact a child's ability to function without support. Timely diagnosis‐informed interventions are crucial to optimizing the developmental trajectory of children with FASD. The true prevalence of FASD among children receiving services for developmental disabilities is unknown. Methods: An FASD prevalence study was carried out between 2011 and 2014 among a sample of 5‐ to 7‐year‐old children who were receiving services provided by the California State Regional Center for Developmental Disabilities in San Diego County. Children whose parent or caregiver consented were evaluated using the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence study assessment protocol and classification criteria. Results: Among 216 eligible caregiver‐child dyads, 44 completed assessments that were sufficient to obtain a classification for FASD, including fetal alcohol syndrome (FAS), partial FAS, alcohol‐related neurodevelopmental disorder, or no fetal alcohol spectrum disorder. Fifteen children were classified as meeting the criteria for an FASD. A minimum FASD prevalence rate of 69.4 per 1000 (6.9%) among all eligible children was estimated. None of the children classified as FASD were receiving services because of an FASD diagnosis, and none had previously been diagnosed with FASD. Autism was the most common qualifying diagnosis for which children classified as FASD were receiving services. Conclusions: The 6.9% prevalence estimate among Regional Center clients was higher than the prevalence estimate of 2.3% in the same community among 5‐ to 7‐year‐old children in the general population, though the estimate was based on only 20% of eligible dyads. All children in the sample were receiving Regional Center services for another diagnosis. Barriers to eligibility for services for children with FASD may lead to less than optimum care for these children. Study findings support the facilitation of access to developmental services for children with FASD. An FASD prevalence study was carried out among a sample of 5‐7‐year old children receiving services provided by the California State Regional Center for Developmental Disabilities in San Diego County. Among 216 eligible children, 44 completed assessments, and fifteen met criteria for an FASD. A minimum FASD prevalence rate of 69.4 per 1,000 (6.9%) was estimated. None of the children identified had previously been diagnosed with FASD. Study findings support facilitation of access to developmental services for children with FASD. [ABSTRACT FROM AUTHOR]

Background: Although the effects of prenatal alcohol exposure (PAE) have been studied extensively, there is relatively little information available on adult mental health functioning among exposed individuals. The current study compares the self‐reported midlife mental health status of individuals who were prenatally exposed to alcohol and diagnosed in childhood with the effects of this exposure with that of unexposed individuals. Methods: Participants (N = 292) were recruited from two longitudinal cohorts in Atlanta and Seattle and asked to complete an Adult Health Questionnaire that surveyed their current health and mental health status. The questionnaire was completed either in‐person or remotely and included questions about current symptoms of depression and anxiety and mental health disorder diagnoses. The analysis compared a Nonexposed Contrast group to those in two exposure groups: (1) Alcohol Exposed with Fetal Alcohol Effect but not meeting criteria for Fetal Alcohol Syndrome (FAS) and (2) Alcohol Affected and meeting criteria for FAS. Results: Both alcohol‐exposed groups reported higher levels of current depressive symptoms and a higher prevalence of diagnoses of depression, anxiety, bipolar disorder, and/or attention deficit/hyperactivity disorder. No differences were noted for psychotic disorders. PAE was also associated with greater environmental stressors, including higher levels of adverse childhood events and lower current socioeconomic status. Path analyses suggested that PAE was indirectly related to mood disorders with its effects being mediated by other environmental factors. Conclusions: PAE is associated with greater rates of mental health disorders in middle adulthood. These outcomes appear to result from multiple stressors that affect individuals made vulnerable by their early alcohol exposure. Clinical outcomes could be improved by prevention efforts directed at preventing prenatal alcohol use and reducing environmental stressors later in life, and by the early identification of PAE and its effects. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop an efficient and easily calculable risk score that can be used to identify an individual's risk of having been exposed to alcohol prenatally. Methods: Data for this study were collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Phases 2 and 3. Two cohorts (ages 5 to 17 years) completed a comprehensive neurobehavioral battery and a standard dysmorphology exam: a development cohort (DC; n = 325) and a comparative cohort (CC; n = 523). Both cohorts included two groups: those with histories of heavy prenatal alcohol exposure (AE‐DC, n = 121; AE‐CC, n = 177) and a control group that included subjects with minimal or no prenatal alcohol exposure (CON‐DC, n = 204; CON‐CC, n = 346). Behavioral assessments and physical exam data were combined using regression techniques to derive a risk score indicating the likelihood of prenatal alcohol exposure. Subjects were then divided into two subgroups: (1) low risk and (2) high risk. Chi‐square (χ2) determined classification accuracy and ROC curves were produced to assess the predictive accuracy. Correlations between risk scores and intelligence quotient and executive function scores were calculated. Results: Subjects were accurately classified in the DC (χ2 = 78.61, p < 0.001) and CC (χ2 = 86.63, p < 0.001). The classification model also performed well in the DC (ROC = 0.835 [SE = 0.024, p < 0.001]) and CC (ROC = 0.786 [SE = 0.021, p < 0.001]). In the AE‐CC and CON‐CC, there were modest but significant associations between the risk score and executive function (AE‐CC: r = −0.20, p = 0.034; CON‐CC: r = −0.28, p < 0.001) and intelligence quotient (AE‐CC: r = −0.20, p = 0.034; CON‐CC: r = −0.28, p < 0.001). Conclusion(s): The risk score significantly distinguished alcohol‐exposed from control subjects and correlated with important cognitive outcomes. It has significant clinical potential and could be easily deployed in clinical settings. [ABSTRACT FROM AUTHOR]

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

Background: Few studies have investigated the partner's influence on risk factors such as alcohol consumption and depression during pregnancy. Partner substance use and lower relationship satisfaction predict higher maternal alcohol use and depressive symptoms. Because prenatal alcohol use and maternal depression affect infant outcomes, it is imperative to examine how the partner affects these maternal risk factors. The current study examined the effect of a latent construct of partner influence on maternal alcohol use and depressive symptoms, and the effects on infant development of these maternal factors. Methods: Participants were 246 pregnant women from 2 sites in Western Ukraine from whom longitudinal data were collected as part of a multisite study. In the first trimester, mothers reported on relationship satisfaction, partner substance use, and socioeconomic status (SES). In the third trimester, they reported on alcohol use and depressive symptoms. Infants were assessed using the Bayley Scale of Infant Development (average age = 6.93 months). A latent construct titled partner influence was formed using partner substance use and measures of relationship satisfaction, including the frequency of quarreling, happiness in the relationship, and the ease of talking with the partner. Using structural equation modeling, a model was specified in which partner influence and SES predicted maternal alcohol use and depressive symptoms, which in turn predicted infant neurodevelopmental outcomes. Results: Higher partner influence significantly predicted lower prenatal alcohol use and lower depressive symptoms, controlling for the effect of SES. Higher maternal prenatal alcohol use significantly predicted lower infant mental and psychomotor development. Maternal depressive symptoms did not predict infant development over and above the effect of alcohol use. Conclusions: Partner influence is an important contributor to prenatal alcohol use and maternal depressive symptoms, over and above the effect of SES. The significant paths from prenatal alcohol exposure to infant neurodevelopmental outcomes underscore the importance of partner influence during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Evidence suggests that prenatal alcohol exposure (PAE) may adversely impact insulin production and signaling but there is limited information on the range of these effects and their future health consequences. Method: A prospective cohort of predominantly African‐American individuals identified while in utero and followed into adulthood were used to evaluate differences in various indicators of diabetes, including fasting plasma glucose, hemoglobin A1c (HbA1c), and insulin levels. The homeostatic model assessment of insulin resistance (HOMA‐IR) was also computed. Body mass index (BMI) was calculated and normal defined as < 25 kg/m2. Participants were categorized as having PAE (n = 39) if their mothers drank at least 1 ounce of absolute alcohol per week or more during the 1st trimester of pregnancy and as Controls (n = 22) if their mothers reported abstaining from alcohol consumption during pregnancy. Results: Mean age of the sample was 36.0 ± 1.5 years. Indices of glucose metabolism, including fasting plasma glucose and hemoglobin A1c levels, did not vary by group status but insulin levels and HOMA‐IR values varied by group status and BMI level. PAE individuals with a normal BMI had lower insulin levels than Controls. However, in PAE subjects, there was a steeper increase in insulin levels relative to their BMI than in Control subjects. A cluster of 5 PAE cases had low levels of insulin and 4 of the 5 had severe cognitive impairment. Conclusions: The bidirectional effects on insulin level and insulin resistance associated with PAE may indicate differential rates of diabetes disease impact or differential PAE impact in the brain and peripheral areas involved in insulin production and signaling. These alterations may contribute to the metabolic disease risk associated with PAE. [ABSTRACT FROM AUTHOR]

Background: Rating scales are designed to complement traditional performance‐based measures, and both can provide useful information about the functioning of youth with histories of prenatal alcohol exposure. Few studies, however, have compared ratings from multiple informants or the relationship between these subjective rating scale scores and the objective results from laboratory performance‐based scales. Methods: The current study addressed both of these questions in 3 study groups: children with histories of prenatal alcohol exposure (n = 47), attention‐deficit/hyperactivity disorder (ADHD; n = 41), and typically developing controls (CON; n = 73). All subjects completed a standardized neuropsychological test battery, including laboratory measures of executive functioning and a self‐report measure of executive function behaviors. Parents and teachers completed corresponding rating scales of executive function behaviors for each subject. This study assessed the relationship between these behavior rating scales and corresponding neuropsychological tests, and interrater agreement among the multiple informants. Results: Weak correlations were found between the rating scales and laboratory measures, indicating poor convergent validity for the behavior rating scale. Interrater reliability was found but it differed by group. Agreement was found between parent and teacher ratings for children with prenatal alcohol exposure, whereas teacher–child agreement was found for those with ADHD. Conclusions: Findings from this study indicate that behavior ratings can be used to supplement laboratory measures but may not be measuring cognitive abilities regardless of whether a clinical diagnosis is present. A multimethod approach should be used when measuring skills in this domain. This was one of the first studies to examine cross‐informant agreement in a sample of children with prenatal alcohol exposure. Further research is necessary to understand why interrater agreement differed for children with prenatal alcohol exposure and those with ADHD. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) has been identified as one of the leading preventable causes of developmental disabilities, but early identification of those impacted has been challenging. This study evaluated the use of infant cardiac orienting responses (CORs), which assess neurophysiological encoding of environmental events and are sensitive to the impact of PAE, to predict later fetal alcohol spectrum disorder (FASD) status. Methods: Mother–infant dyads from Ukraine were recruited during pregnancy based on the mother's use of alcohol. Participants (n = 120) were then seen at 6 and 12 months when CORs were collected and in the preschool period when they were categorized as having (i) fetal alcohol syndrome (FAS), (ii) partial FAS (pFAS), (iii) alcohol‐related neurodevelopmental disorder (ARND), (iv) PAE and no diagnosis, or (v) no PAE and no diagnosis. To assess CORs, stimuli (auditory tones and pictures) were presented using a fixed‐trial habituation/dishabituation paradigm. Heart rate (HR) responses were aggregated across the first 3 habituation and dishabituation trials and converted to z‐scores relative to the sample's mean response at each second by stimuli. Z‐scores greater than 1 were then counted by condition (habituation or dishabituation) to compute a total risk index. Results: Significant group differences were found on total deviation scores of the CORs elicited from visual but not auditory stimuli. Those categorized as pFAS/FAS had significantly higher total deviation scores than did those categorized as ARND or as having no alcohol‐related diagnosis with or without a history of PAE. Receiver operating characteristic curve analysis of the visual response yielded an area under the curve value of 0.765 for predicting to pFAS/FAS status. Conclusions: A score reflecting total deviation from typical HR during CORs elicited using visual stimuli in infancy may be useful in identifying individuals who need early intervention as a result of their PAE. [ABSTRACT FROM AUTHOR]

Background: In children with prenatal alcohol exposure, spatial working memory is affected and brain regions important for spatial working memory performance exhibit atypical neurodevelopment. We therefore hypothesized that children with prenatal alcohol exposure may also have atypical development of spatial working memory ability. Methods: We examined the relation between spatial working memory and age using a cross‐sectional developmental trajectory approach in youth with and without histories of heavy prenatal alcohol exposure. The Cambridge Neuropsychological Test Automated Battery Spatial Working Memory subtest was administered to children 5.0 to 16.9 years old. Results: While the controls and children with prenatal alcohol exposure showed similar performance at younger ages, larger group differences were observed in older children. This effect was replicated in a separate sample. Conclusions: The atypical brain development that has previously been reported in children with heavy prenatal alcohol exposure may have clinically relevant implications for cognitive development; however, longitudinal cognitive analyses are needed. [ABSTRACT FROM AUTHOR]

Background: The effects of prenatal alcohol exposure (PAE) are conceptualized as fetal alcohol spectrum disorder, with fetal alcohol syndrome (FAS) as the most severe. Many find it more difficult to characterize behavioral and cognitive effects of exposure on the central nervous system when physical signs are not present. In the current study, an operational definition of alcohol‐related neurodevelopmental disorder (ARND) was examined to determine its usefulness in discrimination of children classified as ARND based on behavior (ARND/B) and cognition (ARND/C) from children in 4 contrast groups: (i) children exposed to study‐defined "risky drinking"; (ii) children with any reported PAE; (iii) children classified as "Higher Risk" for developmental problems; and (iv) children classified as "Lower Risk." Methods: A total of 1,842 children seen as part of a surveillance study (J Am Med Assoc, 319, 2018, 474) were evaluated for alcohol exposure and physical characteristics of FAS, and completed neurodevelopmental testing. Ninety‐one were identified as either ARND/B or ARND/C and contrasted with other groups to further identify distinguishing patterns. Multinomial logistic regression (MLR) was used to examine the accuracy of classification and to identify factors contributing to such classification. Results: Children described as ARND/C were distinct from other groups based on cognition and behavior as well as demographic factors (e.g., age, race, SES), child characteristics (e.g., gestational age; sex), and other drug exposures, while those described as ARND/B differed only on behavior and other drug exposures. MLR models successfully discriminated ARND groups from children in other groups with accuracy ranging from 79% (Higher Risk) to 86.7% (Low Risk). Conclusions: ARND has been a subject of debate. This analysis suggests the effects of alcohol on behavior and cognition even in the absence of the characteristic facial features and growth deficiency that can be identified. The results also indicate that it may be possible to distinguish such children from those in other high‐risk groups. [ABSTRACT FROM AUTHOR]

Background: This study examined the relationship between prenatal exposure to alcohol, manifested through fetal alcohol syndrome (FAS) and pFAS, and hypertension in children and adolescents. Methods: This study was designed to analyze the association between fetal alcohol spectrum disorders (FASD) Status and hypertension status. FAS/pFAS‐diagnosed respondents (n = 125) were collected from a FASD Clinical database in Atlanta, Georgia. Non‐FAS/pFAS respondents (n = 500) were taken from the National Health and Nutrition Examination Survey (NHANES). Chi‐square analyses were used to examine the extent to which FASD status, sex, race/ethnicity, medication use, and obesity status each related to hypertension status. A logistic regression was performed analyzing the relationship between FASD status (y/n: independent) and hypertension status (y/n: dependent) while controlling for age, sex, race/ethnicity, medication use, and obesity status. Results: Univariate relationships between hypertension status and FASD status (OR = 8.46, p < 0.001), medication use (OR = 3.25, p < 0.001), and obesity status (OR = 3.03, p = 0.02) proved to be statistically significant (p < 0.05). FASD status significantly predicted hypertension status (β = 2.31, OR = 10.06, p < 0.001) after accounting for age, sex, race/ethnicity, medication use, and obesity status. Conclusions: The major findings of this study suggest a significant relationship between FASD and hypertension in youth. Race/ethnicity and obesity also proved important in predicting hypertensive blood pressure readings independent of FASD diagnosis. Further research is needed to isolate prenatal alcohol exposure (PAE) as a factor promoting increased hypertension and to assess the risk for hypertension in alcohol‐affected adults. The relationship between FASD and hypertension in clinically‐referred children and adolescents was investigated. Logistic regression indicated a significant predictive relationship between FASD and elevations in both systolic and diastolic blood pressure after controlling for age, sex, race/ethnicity, medication use, and obesity status. Race/ethnicity and obesity also proved significant in predicting hypertension independently of FASD diagnosis. Further research is needed to isolate prenatal alcohol exposure as a factor in youth hypertension and to assess the risk for hypertension in alcohol‐affected adults. [ABSTRACT FROM AUTHOR]

Background: Adaptive function and general intellectual function are two important and often correlated domains. While youth with prenatal alcohol exposure frequently demonstrate impairments in both domains, it is not clear whether the relation between these domains is consistent across levels of ability or whether, for example, adaptive function is less affected by intellectual function at higher ability levels. The aim of the current study was to test this relation in youth with and without prenatal alcohol exposure. Methods: As part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Phase II, subjects with heavy prenatal alcohol exposure (AE) and nonexposed subjects with and without other clinical conditions or concerns (CON) completed a comprehensive neurobehavioral battery. Multiple regression analyses tested the relation between full scale IQ (FSIQ) and overall adaptive function. Interaction terms between Group and each variable were created to formally test for group differences. Three subsequent regression analyses tested which adaptive function domains (Communication, Daily Living Skills, Socialization) significantly contributed to results. Follow‐up analyses examined correlations based on IQ range (low IQ <85; high IQ ≥85). Results: The interaction between FSIQ and Group on overall adaptive function was significant; the relationship between FSIQ and adaptive function was weaker in the AE group than in the CON group. Regarding specific adaptive function domains, the interaction between FSIQ and Group was significant only in the Communication domain. Follow‐up analyses showed, within the low IQ range, the correlation between FSIQ and Communication was stronger in the CON group than the AE group. Within the high IQ range, the correlation between FSIQ and Communication was significant only in the CON group. Conclusions: Although higher intellectual functioning was associated with better adaptive function ability among controls, this was not found among the alcohol‐exposed youth where a general dampening of adaptive ability was noted. Further, the differential relationship between IQ and adaptive function between groups appears to be driven by communication abilities. These findings suggest that level of intellectual functioning of children with prenatal alcohol exposure does not fully account for caregiver‐reported communication and overall adaptive function deficits particularly at higher levels of functioning. [ABSTRACT FROM AUTHOR]

Background: Of the many negative outcomes associated with gestational alcohol use, one that has received relatively little attention is preterm birth and its possible contribution to effects of prenatal alcohol exposure (PAE) on development. To examine the increased risk for premature delivery associated with PAE and the joint influence of preterm birth and alcohol on child outcomes, analysis was carried out in a longitudinal cohort recruited in Western Ukraine. Methods: Alcohol‐using women and low or nondrinking controls were identified prenatally for a clinical trial of multivitamins and minerals (MVM) in ameliorating effects of PAE. Women were interviewed to provide information about medical and social status and other drug use. At delivery, information was collected about infant (N = 686) status including gestational age (GA) in weeks. Finally, 441 infants were followed to 6 months of age and cognitive (Mental Developmental Index [MDI]) and motor development (Psychomotor Developmental Index [PDI]) (measured using the Bayley Scales of Infant Development, second Ed (BSID‐II). Results: Seven percent infants were born at <37 weeks GA. The odds ratio for preterm delivery for Alcohol Exposed versus Low/No Alcohol was 2.6 (95% Confidence Interval 1.37, 4.94) (p < .003); MVM supplements were associated with a lower rate of preterm delivery overall, but the relative proportion of preterm births did not vary by MVM supplement status between alcohol exposure groups. In mediation models of 6 month cognitive and motor development with reference to Barron and Kenney in 1986, GA significantly mediated alcohol effects (MDI: Z = −2.64, p < .008; PDI: Z = −2.35, p < .02) although PAE independently affected both outcomes (MDI: t = −5.6, p < .000; PDI: t = −3.19, p < .002). Conclusion: Results suggest that PAE is associated with higher rates of preterm birth and that alcohol's effect on development in infancy may be both direct and mediated by shortened length of gestation. [ABSTRACT FROM AUTHOR]

Background: Youth with heavy prenatal alcohol exposure have high rates of behavioral concerns and psychopathology, including increased oppositional and conduct behaviors. The relation between those concerns and executive function (EF) deficits is unknown. We investigated the association of oppositional and conduct behavior and EF in adolescents to inform targeted intervention. Methods: Subjects (N = 267) ages 10 to 17 years comprised 3 groups: alcohol‐exposed with oppositional/conduct behaviors (AE+), alcohol‐exposed without oppositional/conduct behaviors (AE−), and controls (CON). Group differences on direct neuropsychological (Delis‐Kaplan Executive Function System [D‐KEFS]) and indirect parent‐report (Behavior Rating Inventory of Executive Function [BRIEF]) EF measures were tested with multivariate analysis of covariances, followed by univariate analysis of variances and pairwise comparisons. The contribution of attention‐deficit/hyperactivity disorder (ADHD) within the AE groups was assessed in secondary analyses. Results: On the D‐KEFS, there was an omnibus main effect of group, with significant main effects on 3 of 6 variables (CON>AE+, AE−). Within the AE groups, ADHD did not alter the results. On the BRIEF, there was an omnibus significant main effect of group, with significant main effects on all scales (CON

Background Considered the leading cause of developmental disabilities worldwide, fetal alcohol spectrum disorders ( FASD) are a global health problem. To take advantage of neural plasticity, early identification of affected infants is critical. The cardiac orienting response ( COR) has been shown to be sensitive to the effects of prenatal alcohol exposure and is an inexpensive, easy to administer assessment tool. The purpose of this study was to evaluate the COR effectiveness in assessing individual risk of developmental delay. Methods As part of an ongoing longitudinal cohort study in Ukraine, live-born infants of women with some to heavy amounts of alcohol consumption in pregnancy were recruited and compared to infants of women who consumed low or no alcohol. At 6 and 12 months, infants were evaluated with the Bayley Scales of Infant Development- II. CORs were also collected during a habituation/dishabituation learning paradigm. Using a supervised logistic regression classifier, we compared the predictive utility of the COR indices to that of the 6-month Bayley scores for identification of developmental delay based on 12-month Bayley scores. Heart rate collected at each second (Standard COR) was compared to key features (Key COR) extracted from the response. Results Negative predictive values ( NPV) were 85% for Standard COR, 82% for Key COR, and 77% for the Bayley, and positive predictive values ( PPV) were 66% for Standard COR, 62% for Key COR, and 43% for the Bayley. Conclusions Predictive analysis based on the COR resulted in better NPV and PPV than the 6-month Bayley score. As the resources required to obtain a Bayley score are substantially more than in a COR-based paradigm, the findings are suggestive of its utility as an early scalable screening tool based on the COR. Further work is needed to test its long-term predictive accuracy. [ABSTRACT FROM AUTHOR]

Background Prenatal alcohol exposure ( PAE) has been found to impact neurophysiological encoding of environmental events negatively in the first year of life but has not been evaluated in older infants or toddlers. Cardiac orienting responses ( ORs) collected during a habituation/dishabituation learning paradigm were obtained from 12- to 18-month-olds to assess the impact of PAE beyond the first year of life. Methods Participants included women and their toddlers who differed in PAE histories and enrolled in a randomized clinical trial of multivitamin/mineral usage during pregnancy. Those who were randomly assigned to the no intervention group were used for this analysis. The habituation/dishabituation paradigm consisted of 10 habituation and 5 dishabituation trials. Baseline heart rate ( HR) was collected for 30 seconds prior to stimulus onset, and responses to the stimuli were assessed by sampling HR for 12 seconds poststimulus onset. Results The speed of the OR in response to auditory stimuli in the dishabituation condition was found to be altered as a function of maternal alcohol use around conception. For visual stimuli, positive histories of PAE were predictive of the magnitude but not the speed of the response on habituation and dishabituation trials. A history of binge drinking was associated with reduced magnitude of the OR response on visual encoding trials, and level of alcohol exposure at the time of conception was predictive of the magnitude of the response on visual dishabituation trials. Conclusions Cardiac ORs collected in the toddler period were sensitive to the effects of PAE. The magnitude of the OR was more sensitive to the impact of PAE than in previous research with younger infants, and this may be a function of brain maturation. Additional research assessing the predictive utility of using ORs in making decisions about individual risk was recommended. [ABSTRACT FROM AUTHOR]

Background Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented; however, the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Methods Subjects were 407 youth with prenatal alcohol exposure ( n = 192) and controls ( n = 215). Two age groups (child [5 to 7 years] or adolescent [10 to 16 years]) and both sexes were included. All subjects completed standardized neuropsychological testing, and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) multivariate analyses of variance (MANOVAs). Significant effects were followed by univariate analyses. Results No 3-way or 2-way interactions were significant. The main effect of group was significant in all 3 MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on 3 measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual spatial scores and fewer somatic complaints than females. Conclusions Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for nonexposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the 2 age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains. [ABSTRACT FROM AUTHOR]

Background Prenatal alcohol exposure (PAE) is an established risk factor for neurodevelopmental deficits in the offspring. Prenatal depression has been associated with neurodevelopmental deficits in the offspring, although investigations into unmedicated prenatal depression have been inconsistent. We hypothesized that unmedicated prenatal depressive symptoms would independently and jointly with PAE predict neurodevelopmental outcomes in infant offspring. Methods We studied 344 participants from a randomized clinical trial of multivitamin supplements in pregnant women in Ukraine. Women were recruited based upon periconceptional alcohol use and followed up to 12 months postpartum. Prenatal depressive symptoms were assessed at approximately 32 weeks of gestation using the Beck Depression Inventory score. Neurodevelopment was assessed with the Bayley Scales of Infant Development II Mental Development Index (MDI) and Psychomotor Development Index (PDI) at 6 and 12 months postpartum. Generalized linear regression models were constructed to assess the independent and joint effects of prenatal depressive symptoms and PAE in models adjusted for sociodemographic and pregnancy characteristics. Results PAE was independently associated with deficits in neurodevelopmental outcomes at 6 and 12 months, however, level of prenatal depressive symptoms was not. We found marginal evidence of synergism of depressive symptoms and PAE, with larger deficits in those with both exposures observed for the PDI-6 months ( p = 0.05) and MDI-12 months ( p = 0.09). Additionally, there was a suggestion of sexual dimorphism; females had stronger deficits from joint exposures than males (depressive symptom [MDI-6 months] female: −8.28, 95% CI −13.06, −3.49; male: 0.68, 95% CI −4.58, 5.94; p for interaction 0.04). While not statistically significant for the MDI or PDI at 12 months, the trend persisted. Conclusions Infants exposed to PAE and prenatal depression may be at an increased risk of neurodevelopmental deficits. Healthcare providers should be aware of this possible synergism in their efforts to mitigate the neurodevelopmental effects of these co-occurring exposures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Fetal alcohol spectrum disorders ( FASD) are often characterized by disruptive behavior problems and there are few effective interventions available. Go FAR is a novel, 3-part intervention designed to improve self-regulation and adaptive living skills of children with FASD by improving metacognitive control of emotions and arousal. Methods The intervention has 3 components: (i) Go FAR: a 'serious game' designed to teach a metacognitive control strategy in a computer game environment; (ii) parent training on child behavioral regulation; and (iii) Behavior Analog Therapy ( BAT) sessions, a practical application of the metacognitive learning methodology by parent and child in the context of learning adaptive skills. The learning strategy ( FAR) teaches the child to Focus and make a plan, Act out the plan, and Reflect back on the plan. Thirty families were randomized to 3 groups: (i) Go FAR ( n = 10); (ii) FACELAND ( n = 10); or (iii) CONTROL ( n = 10). The 2 intervention groups, Go FAR and FACELAND, used computer games to instruct children. Both groups also received 5 sessions of parent training followed by 5 sessions of joint parent/child therapy ( BAT). Assessment of disruptive behavior, including frequency of temper tantrums, frustration tolerance, impulsivity, destructiveness, aggression, and maintaining attention were carried out before enrollment at Mid-Treatment, when game play and parent training were completed, and finally, after completing the BAT sessions. Results Parental report of disruptive behavior overall was significantly reduced in the Go FAR group after the first components, game play and parent training, and after the BAT sessions in the FACELAND group with no changes in the CONTROL group over time. Conclusions The Go FAR® game was well received by children and effective in teaching the required skills. Mastering the FAR metacognitive strategy was associated with a reduction in disruptive behaviors in children with FASD suggesting that effective interventions can improve outcomes for this high-risk group. [ABSTRACT FROM AUTHOR]

Background Heavy prenatal alcohol exposure and attention-deficit/hyperactivity disorder ( ADHD) are associated with adaptive behavior deficits. This study examined the interaction between these 2 factors on parent ratings of adaptive behavior. Methods As part of a multisite study, primary caregivers of 317 children (8 to 16 years, M = 12.38) completed the Vineland Adaptive Behavior Scales-Second Edition ( VABS- II). Four groups of subjects were included: children with prenatal alcohol exposure with ADHD ( AE+, n = 82), children with prenatal alcohol exposure without ADHD ( AE−, n = 34), children with ADHD ( ADHD, n = 71), and control children ( CON, n = 130). VABS- II domain scores (Communication, Daily Living Skills, Socialization) were examined using separate 2 (Alcohol Exposure [ AE]) × 2 ( ADHD diagnosis) between-subjects analyses of covariance. Results There were significant main effects of AE ( p < 0.001) and ADHD ( p < 0.001) on all VABS- II domains; alcohol-exposed children had lower scores than children without prenatal alcohol exposure and children with ADHD had lower scores than those without ADHD. There was a significant AE × ADHD interaction effect for Communication, F(1, 308) = 7.49, p = 0.007, partial η2 = 0.024, but not Daily Living Skills or Socialization domains ( ps > 0.27). Follow-up analyses in the Communication domain indicated the effects of ADHD were stronger in comparison subjects ( ADHD vs. CON) than exposed subjects ( AE+ vs. AE−), and the effects of alcohol exposure were stronger in subjects without ADHD ( AE− vs. CON) than in subjects with ADHD ( AE+ vs. ADHD). Conclusion As found previously, both prenatal alcohol exposure and ADHD increase adaptive behavior deficits in all domains. However, these 2 factors interact to cause the greatest impairment in children with both prenatal alcohol exposure and ADHD for communication abilities. These results further demonstrate the deleterious effects of prenatal alcohol exposure and broaden our understanding of how ADHD exacerbates behavioral outcomes in this population. [ABSTRACT FROM AUTHOR]

Background This study examined prevalence of psychiatric disorders and behavioral problems in children with and without prenatal alcohol exposure ( AE) and attention-deficit/hyperactivity disorder ( ADHD). Methods Primary caregivers of 344 children (8 to 16 years, M = 12.28) completed the Computerized Diagnostic Interview Schedule for Children- IV ( C- DISC-4.0) and the Child Behavior Checklist ( CBCL). Subjects comprised 4 groups: AE with ADHD ( AE+, n = 85) and without ADHD ( AE−, n = 52), and nonexposed with ADHD ( ADHD, n = 74) and without ADHD ( CON, n = 133). The frequency of specific psychiatric disorders, number of psychiatric disorders (comorbidity), and CBCL behavioral scores were examined using chi-square and analysis of covariance techniques. Results Clinical groups had greater frequency of all psychiatric disorders, except for anxiety, where the AE- and CON groups did not differ. There was a combined effect of AE and ADHD on conduct disorder. For comorbidity, children with ADHD had increased psychiatric disorders regardless of AE, which did not have an independent effect on comorbidity. For CBCL scores, there were significant main effects of AE and ADHD on all scores and significant AE × ADHD interactions for Withdrawn/ Depressed, Somatic Complaints, Attention, and all Summary scores. There was a combined effect of AE and ADHD on Externalizing, Total Problems, and Attention Problems. Conclusions Findings indicate that ADHD diagnosis elevates children's risk of psychiatric diagnoses, regardless of AE, but suggest an exacerbated relation between AE and ADHD on conduct disorder and externalizing behavioral problems in children. Findings affirm a poorer behavioral prognosis for alcohol-exposed children with ADHD and suggest that more than 1 neurobehavioral profile may exist for individuals with AE. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Pearson's 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure (PAE) is associated with various adverse effects on human brain and behavior. Recently, neuroimaging studies have begun to identify PAE effects on specific brain structures. Investigation of such specific PAE effects is important for understanding the teratogenic mechanism of PAE on human brain, which is critical for differentiating PAE from other disorders. In this structural MRI study with young adults, PAE effects on the volumes of automatically segmented cortical and subcortical regions of interest (ROIs) were evaluated both through a group difference approach and a parametric approach. In the group difference approach (comparing among two PAE and a control groups), a disproportionate PAE effect was found in several occipital and temporal regions. This result is inconsistent with previous studies with child samples. Moreover, a gender difference in PAE effect was shown in some cortical ROIs. These findings suggest that sampling and gender may be important factors for interpreting specific PAE effects on human brain. With the parametric approach, it was demonstrated that the higher the PAE level, the smaller the entire brain, the lower the IQ. Several cortical and subcortical ROIs also exhibited a negative correlation between the PAE level and ROI volume. Furthermore, our data showed that the PAE effect on the brain could not be interpreted by the PAE effect on general physical growth until the young adult age. This study provides valuable insight into specific effects of PAE on human brain and suggests important implications for future studies in this field. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article presents a study which compared the negative activations in the default mode network (DMN) between the prenatal cocaine exposure (PCE) and nonexposed adolescents during a verbal working memory task. The researchers observed that PCE subjects to be more sensitive to salient stimuli in the environment and that they are more easily disturbed during sleep. Also, they found PCE children to have a higher daydreaming score.

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. [ABSTRACT FROM AUTHOR]

Background: Increased systemic oxidant stress contributes to a variety of maternal complications of pregnancy. Although the antioxidant glutathione (GSH) and its oxidized component glutathione disulfide (GSSG) have been demonstrated to be significantly altered in the adult alcoholic, the effects of maternal alcohol use during pregnancy on oxidant stress in the postpartum female remain under investigation. We hypothesized that maternal alcohol use would increase systemic oxidant stress in the pregnant female, evidenced by an oxidized systemic GSH redox potential. Methods: As a subset analysis of a larger maternal language study, we evaluated the effects of alcohol consumption during pregnancy on the systemic GSH redox status of the postpartum female. Using an extensive maternal questionnaire, postpartum women where queried regarding their alcohol consumption during pregnancy. Any drinking, the occurrence of drinking >3 drinks/occasion, and heavy drinking of >5 drinks/occasion during pregnancy were noted. Using HPLC, maternal plasma samples were analyzed for GSH, oxidized GSSG and the redox potential of the GSH/GSSG antioxidant pair calculated. Results: Maternal alcohol use occurred in 25% (83/321) of our study sample. Two in ten women reported consuming >3 drinks/occasion during pregnancy, while 1 in 10 women reported consuming alcohol at >5 drinks/occasion. Any alcohol use during pregnancy significantly decreased plasma GSH ( p < 0.05), while alcohol at >3 drinks/occasion or >5 drinks/occasion significantly decreased plasma GSH concentration ( p < 0.05), increased the percent of oxidized GSSG ( p < 0.05), and substantially oxidized the plasma GSH redox potential ( p < 0.05). Conclusions: Alcohol use during pregnancy, particularly at levels >3 drinks/occasion, caused significant oxidation of the systemic GSH system in the postpartum women. The clinical ramifications of the observed alcohol-induced oxidation of the GSH redox system on high risk pregnancies or on the exposed offspring require more accurate identification and further investigation. [ABSTRACT FROM AUTHOR]

Background: While behavioral studies have established that prenatal alcohol exposure (PAE) can result in diminished arithmetic processing capability, the underlying neural correlates of this deficit are still unclear. The aim of the present study was to use functional magnetic resonance imaging to determine the effect of PAE on neuronal activation during a subtraction task. Methods: Participants were young adults from a low socio-economic status population who were identified prenatally; the sample consisted of healthy unexposed controls ( n = 17) and PAE who were subdivided based on the presence ( n = 19) or absence of physical dysmorphic signs ( n = 18). Multiple regression analysis was used to determine extent of activation and percent signal change during arithmetic processing, using a letter-matching task as the baseline. Region of interest analysis of activation was performed in the native space and normalized for each individual to compensate for the considerable variability in head size observed in the alcohol-exposed population. Results: An exposure-dependent response was observed in task performance and neuronal activation. Dysmorphic PAE individuals showed significantly lower task-related performance and activation in regions known to be associated with arithmetic processing, including left superior and right inferior parietal regions and medial frontal gyrus, while the nondysmorphic PAE group was generally intermediate but not significantly different from the control group in task performance and activation. Conclusions: Results indicate that there is a range of effects of PAE on arithmetic processing and that the severity of this deficit may be dependent on degree of impairment demonstrated by the exposed individual. Evidence of physical dysmorphia may be indicative of functional damage to regions associated with arithmetic calculation, resulting in markedly impaired neuronal recruitment. [ABSTRACT FROM AUTHOR]

Cocaine-exposed infants have been found to have altered arousal responses but little is known about such responses in later childhood. Physiological responses to stressors were used to assess the arousal modulation of school-aged, cocaine-exposed children (n = 73) and two contrast groups, socioeconomically-matched controls (n = 58) and children with behavioral disturbance (n = 35). The behaviorally disturbed group had the highest heart rate across conditions but demonstrated a pattern of hyporesponsiveness to the stressors. They had the smallest decrement in skin conductance response at baseline and the least recovery of skin conductance response following exposure to stressors. Cocaine-exposed children demonstrated greater acceleratory responses to the stressors as indexed by their skin conductance level and were intermediate between the socioeconomically-matched controls and children with behavioral disturbance in recovery of skin conductance response following stressors. Altered arousal responses associated with prenatal cocaine exposure persisted into middle childhood but were different from those found in behaviorally disturbed children. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 251–265, 2008. [ABSTRACT FROM AUTHOR]

Background: Fetal alcohol syndrome (FAS) has been recognized as a disabling condition with a significant impact on the neurobehavioral functioning of affected individuals, including cognition, behavior, and academic functioning, but little research has been performed on targeted interventions for these children. Methods: A socio-cognitive habilitative program focused on improving behavior and math functioning in children 3 to 10 years of age ( n=61) was developed and evaluated. The intervention provided parental instruction on FAS, advocacy, and behavioral regulation via workshops and interactive math tutoring with children. All families received parental instruction and were then randomly assigned to either the math instruction or standard psychoeducational care groups. Results: Satisfaction with workshops was very high, with over 90% agreeing that trainers were knowledgeable and materials easy to understand and helpful. Significant gains in knowledge were found for information provided in the instructional groups. At posttesting, caregivers reported fewer problem behaviors on the Achenbach Child Behavior Checklist, Internalizing Problem Behavior, Externalizing Problem Behavior, and Total Problem Behavior summary scales. After 5 months, both groups of children demonstrated gains in math knowledge but significantly higher gains were found in the group receiving direct math instruction. The math treatment group was also more likely to demonstrate a gain of over 1 standard deviation on any of the 4 math outcome measures used. Conclusions: These findings suggest that parents of children with fetal alcohol spectrum disorders (FAS(D)) benefit from instruction in understanding their child's alcohol-related neurological damage and strategies to provide positive behavioral supports and that targeted psychoeducational programs may be able to remediate some of the math deficits associated with prenatal alcohol exposure. [ABSTRACT FROM AUTHOR]

This study examined the association between prenatal exposure to cocaine and autonomic regulation at 7 months of age. Heart rate (HR) and respiratory sinus arrhythmia (RSA) were obtained from 154 (79 exposed, and 75 nonexposed) infants during baseline and tasks designed to elicit positive and negative affect. Cocaine-exposed infants had higher HR during the positive affect task. There was a significant suppression of RSA during the negative affect task for nonexposed infants but not for exposed infants. Fetal growth and maternal caregiving behavior did not mediate or moderate this association. These results provide additional support for an association between prenatal cocaine exposure and dysregulation during infancy. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 276–289, 2007. [ABSTRACT FROM AUTHOR]

Effects of prenatal cocaine exposure and parental versus nonparental care on outcome at 2 years of age were examined. The sample included 83 cocaine-exposed and 63 nonexposed children and their caregivers; 49 and 34 of the cocaine-exposed children experienced parental and nonparental care, respectively. Prenatal drug exposure was not related directly to children's outcome at 2 years of age. However, compared with cocaine-exposed children in parental care, those in nonparental care experienced a more optimal environment and performed better in several developmental domains at 2 years of age in spite of being at greater neonatal risk. Further analyses suggested that this protective effect of nonparental care was in part due to nonkin rather than kin care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A Structured Clinical Interview (SCI) was used to assess both proximal characteristics of the rearing environments of prenatally polydrug exposed infants in a low SES sample and infant behavioral characteristics (e.g., feeding, sleeping, self-regulation). The 95-item questionnaire systematized collection of developmental history and caregiving environment for 132 infant–caregiver dyads who were seen for follow-up at 6, 12, and 24 months. Outcome data were indexed in five theoretically based areas: Caregiving Instability, Problems with Social Routine, Dysregulation, Infant Feeding Problems and Infant Sleeping Problems. Main effects were found in the Caregiving Instability and Sleeping Problems Index scores for drug exposure but not gestational age. Chronological age and drug interactions were found for Feeding Problems and Sleeping Problems Index scores, with those in the drug group having persistent difficulties in these areas. Additionally, there was a term and drug interaction effect in the Problems with Social Routine Index. In all of these areas, prenatal drug exposure was associated with less optimal scores. The SCI proved to be a useful tool in studying this high-risk population and may be useful in research and clinical settings. Future instrument development is planned. © 2001 Michigan Association for Infant Mental Health. [ABSTRACT FROM AUTHOR]

Prenatal exposure to cocaine, as well as other drugs, has been linked with “dysregulation,” usually defined as problems in arousal and/or behavioral regulation. This study was designed to describe the physiological basis of dysregulation as a function of prenatal cocaine/polydrug exposure and term status. Eight-week-old infants were selected because they are just developing the ability to modulate arousal. One hundred-eighteen infants (23 preterm control, 27 preterm drug-exposed, 29 full-term control, and 39 full-term drug-exposed) completed a protocol during which heart rate (HR) and respiratory rate (RR) were measured. Drug group differences were found in baseline, arousal (response to stress), and arousal modulation (recovery from stress). A hierarchical multiple regression analysis was conducted to determine the portion of variance attributable to postnatal caregiving environment, term status, and specific drug exposure. Term status accounted for significant variance in arousal (both RR and HR), and in arousal modulation (only RR). Prenatal exposure to cocaine contributed a significant amount of unique variance in HR arousal whereas tobacco contributed significantly to HR arousal modulation. Prenatal drug exposure and preterm status contributed differently to dysregulation as measured by physiological responses. © 2000 John Wiley & Sons, Inc. Dev Psychobiol 36: 194–212, 2000 [ABSTRACT FROM AUTHOR]

Behavioral deficits are often noted in children with fetal alcohol syndrome (FAS) and other individuals with prenatal alcohol exposure, including mental retardation, learning problems, social problems, and deficits in attention. Because attention deficit, hyperactivity disorder (ADHD) has been diagnosed so frequently in children with FAS and other alcohol related birth defects, there has been speculation that alcohol is an etiological factor in ADHD. To examine the relationship between behavior characteristics of children with fetal alcohol exposure and those seen in children with a diagnosis of ADHD, 149 low socioeconomic status (SES), African-American children (mean age = 7.63 years) were given a battery of neuropsychological and behavioral tests. One hundred and twenty-two were a sub-sample from a longitudinal study of prenatal alcohol exposure, whereas twenty-seven were identified in an ADHD Clinic. Children were given two sets of tests: (1) 'traditional model' of conventional behavioral and psychiatric measures of ADHD and externalizing behavior; and (2) measures of neurocognitive functioning reflecting a four-factor model of the neurological basis of the components of attention (Mirsky AF, in Integrated Theory and Practice in Clinical Neuropsychology, Hillsdale, NJ, Lawrence Erlbaum Associates, 1989). Results indicated that children with the physical characteristics associated with prenatal alcohol exposure and those with a diagnosis of ADHD had equivalent intellectual abilities with both clinical groups performing more poorly than contrast children from the same SES and ethnic groups. However, there were clear distinctions on behavioral and neurocognitive measures between the two clinical groups with those with ADHD performing more poorly on conventional tests sensitive to attentional problems and conduct disorder. When these two groups were compared on measures designed to measure the model of the four factors of attention by Mirsky, they were noted to have distinct patterns of deficits. These results suggested that the alcohol-affected children did not have the same neurocognitive and behavioral characteristics as children with a primary diagnosis of ADHD. [ABSTRACT FROM AUTHOR]

A response from the author of the article regarding the methods used in the diagnosis of fetal alcohol spectrum disorder (FASD) is presented.