Publications by authors named "Julie A Kable"

63 Publications

Partner influence as a factor in maternal alcohol consumption and depressive symptoms, and maternal effects on infant neurodevelopmental outcomes.

Alcohol Clin Exp Res 2021 06 17;45(6):1265-1275. Epub 2021 May 17.

Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.

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.
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http://dx.doi.org/10.1111/acer.14612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254755PMC
June 2021

Measurement of neurodevelopmental effects of prenatal alcohol exposure in Ukrainian preschool children.

Child Neuropsychol 2021 May 13:1-16. Epub 2021 May 13.

Collaborative Initiative for Fetal Alcohol Spectrum Disorders.

Effects of prenatal alcohol exposure (PAE) are rarely measured in preschool children due to relative insensitivity of assessment methods at this age. To examine the potential of a nonverbal battery in early identification of cognitive problems in alcohol-exposed children, 291 prospectively identified Ukrainian children were evaluated using a test battery focusing on early executive functioning (EF) and visuospatial skills, areas of cognitive development particularly sensitive to PAE in older children. Tests included the Differential Ability Scales, 2 Edition (DAS-2) and several NEPSY/NEPSY-II subtests, standardized in the United States. Others were adapted from commonly used non-standardized neuropsychological measures of EF (Preschool Spatial Span, Imitation Hand Game, A not B, Delayed Attention, Subject Ordered Pointing). Children in two sites in Ukraine, Rivne and Khmelnitsky, were tested at 3 ½-4 ½ years to identify effects of PAE. Although most children performed within the average range, Alcohol-Exposed preschoolers had lower scores on DAS-II Summary Scores as well as on specific subtests. To evaluate the effects of alcohol dose during the pre-pregnancy recognition period and during mid-gestation of pregnancy, generalized linear regression models were used controlling for demographic and individual variables. In addition to DAS-II variables, measures reflecting sustained attention, working memory and ability to shift cognitive set were impacted by alcohol dose. Early executive function appears to subsume these performance differences. In conclusion, findings indicate that the effects of PAE can be identified in the preschool period and reliably measured using tests assessing nonverbal and spatial skills supported by executive functioning.
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http://dx.doi.org/10.1080/09297049.2021.1919298DOI Listing
May 2021

Psychopharmacological Treatments in Children with Fetal Alcohol Spectrum Disorders: A Review.

Child Psychiatry Hum Dev 2021 Jan 27. Epub 2021 Jan 27.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Drive NE, Suite 200, Atlanta, GA, USA.

Psychiatric symptoms in children with Fetal Alcohol Spectrum Disorders (FASD) present with high prevalence and morbidity, often across symptom domains, e.g. ADHD-like symptoms, emotional dysregulation and sleep problems. Polypharmacy is often used, but no empirically-based guidelines exist regarding optimal treatment for these children. Moreover, stimulant use in these children is controversial as their responsiveness may be different due to altered neural circuitry associated with prenatal alcohol exposure. The objective of this review is to give an overview of existing data on pharmacological treatments of neurobehavioral symptoms in FASD. Our literature review yielded limited and conflicting clinical data on the effectiveness of pharmacological treatments for psychiatric symptoms in children with FASD, with some symptom domains lacking data altogether. We emphasize the need for clinical trials to guide pharmacological treatments in this complex population.
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http://dx.doi.org/10.1007/s10578-021-01124-7DOI Listing
January 2021

Alterations in Insulin Levels in Adults with Prenatal Alcohol Exposure.

Alcohol Clin Exp Res 2021 03 24;45(3):500-506. Epub 2021 Feb 24.

Department of Psychiatry and Behavioral Science, Emory University School of Medicine, Atlanta, GA, USA.

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/m . 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 1 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.
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http://dx.doi.org/10.1111/acer.14559DOI Listing
March 2021

Validity and Reliability of Executive Function Measures in Children With Heavy Prenatal Alcohol Exposure: Correspondence Between Multiple Raters and Laboratory Measures.

Alcohol Clin Exp Res 2021 03 15;45(3):596-607. Epub 2021 Feb 15.

Center for Behavioral Teratology, San Diego State University, San Diego, CA, USA.

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.
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http://dx.doi.org/10.1111/acer.14547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969422PMC
March 2021

Infant Cardiac Orienting Responses Predict Later FASD in the Preschool Period.

Alcohol Clin Exp Res 2021 02 6;45(2):386-394. Epub 2021 Jan 6.

Department of Pediatrics (KLJ, WW, ChDC), University of California San Diego, La Jolla, California, USA.

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.
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http://dx.doi.org/10.1111/acer.14525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887046PMC
February 2021

Cross-Sectional Analysis of Spatial Working Memory Development in Children with Histories of Heavy Prenatal Alcohol Exposure.

Alcohol Clin Exp Res 2021 01 6;45(1):215-223. Epub 2021 Jan 6.

From the, Department of Psychology, (EMM, LG, MAI, EPR, SNM), Center for Behavioral Teratology, San Diego State University, San Diego, California.

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.
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http://dx.doi.org/10.1111/acer.14506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875477PMC
January 2021

Best Practices for Engaging Pregnant and Postpartum Women at Risk of Substance Use in Longitudinal Research Studies: a Qualitative Examination of Participant Preferences.

Advers Resil Sci 2020 Oct 28:1-12. Epub 2020 Oct 28.

National Center for Wellness and Recovery, Oklahoma State University Center for Health Sciences, Tulsa, OK USA.

There are significant barriers in engaging pregnant and postpartum women that are considered high-risk (e.g., those experiencing substance use and/or substance use disorders (SUD)) into longitudinal research studies. To improve recruitment and retention of this population in studies spanning from the prenatal period to middle childhood, it is imperative to determine ways to improve key research engagement factors. The current manuscript uses a qualitative approach to determine important factors related to recruiting, enrolling, and retaining high-risk pregnant and postpartum women. The current sample included 41 high-risk women who participated in focus groups or individual interviews. All interviews were analyzed to identify broad themes related to engaging high-risk pregnant and parenting women in a 10-year longitudinal research project. Themes were organized into key engagement factors related to the following: (1) recruitment strategies, (2) enrollment, and (3) retention of high-risk pregnant and parenting women in longitudinal research studies. Results indicated recruitment strategies related to ideal recruitment locations, material, and who should share research study information with high-risk participants. Related to enrollment, key areas disclosed focused on enrollment decision-making, factors that create interest in joining a research project, and barriers to joining a longitudinal research study. With regard to retention, themes focused on supports needed to stay in research, barriers to staying in research, and best ways to stay in contact with high-risk participants. Overall, the current qualitative data provide preliminary data that enhance the understanding of a continuum of factors that impact engagement of high-risk pregnant and postpartum women in longitudinal research with current results indicating the need to prioritize recruitment, enrollment, and retention strategies in order to effectively engage vulnerable populations in research.
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http://dx.doi.org/10.1007/s42844-020-00019-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592139PMC
October 2020

Altered Maternal Plasma Fatty Acid Composition by Alcohol Consumption and Smoking during Pregnancy and Associations with Fetal Alcohol Spectrum Disorders.

J Am Coll Nutr 2020 Mar-Apr;39(3):249-260. Epub 2020 Apr 2.

Department of Nutrition, University of California, Davis, Davis, California, USA.

Polyunsaturated fatty acids are vital for optimal fetal neuronal development. The relationship between maternal alcohol consumption and smoking with third trimester plasma fatty acids were examined and their association with Fetal Alcohol Spectrum Disorders (FASD). Moderate to heavy alcohol-using and low/unexposed comparison women were recruited during mid-pregnancy from two prenatal clinics in Ukraine. The participants' infants underwent physical and neurobehavioral exams prior to one-year of age and classified as having FASD by maternal alcohol consumption and neurobehavioral scores. A subset of mother-child pairs was selected representing three groups of cases and controls: Alcohol-Exposed with FASD (AE-FASD, n = 30), Alcohol-Exposed Normally Developing (AE-ND, n = 33), or Controls (n = 46). Third trimester maternal plasma samples were analyzed for fatty acids and levels were compared across groups. The percent of C18:0 (p < 0.001), arachidonic acid (AA, C20:4n-6, p = 0.017) and C22:5n-6 (p = 0.001) were significantly higher in AE-FASD women than controls or AE-ND women. Alcohol-exposed women who smoked had lower C22:5n-3 (p = 0.029) and docosahexaenoic acid (DHA, C22:6n-3, p = 0.005) and higher C22:5n-6 (p = 0.013) than women consuming alcohol alone or abstainers. Alterations in fatty acid profiles were observed in moderate to heavy alcohol-consuming mothers with infants classified with FASD compared to alcohol-exposed normally developing infants or controls.
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http://dx.doi.org/10.1080/07315724.2020.1737984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011805PMC
June 2021

Characterizing Alcohol-Related Neurodevelopmental Disorder: Prenatal Alcohol Exposure and the Spectrum of Outcomes.

Alcohol Clin Exp Res 2020 06 20;44(6):1245-1260. Epub 2020 May 20.

Departments of Pediatrics and Family Medicine and Public Health, (CDC), University of California San Diego School of Medicine, La Jolla, California.

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.
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http://dx.doi.org/10.1111/acer.14325DOI Listing
June 2020

Immune network dysregulation associated with child neurodevelopmental delay: modulatory role of prenatal alcohol exposure.

J Neuroinflammation 2020 Jan 28;17(1):39. Epub 2020 Jan 28.

Department of Cellular and Physiological Sciences, University of British Columbia, 3307 - 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.

Background: Evidence suggests that cytokine imbalances may be at the root of deficits that occur in numerous neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. Notably, while clinical studies have demonstrated maternal cytokine imbalances with alcohol consumption during pregnancy-and data from animal models have identified immune disturbances in alcohol-exposed offspring-to date, immune alterations in alcohol-exposed children have not been explored. Thus, here we hypothesized that perturbations in the immune environment as a result of prenatal alcohol exposure will program the developing immune system, and result in immune dysfunction into childhood. Due to the important role of cytokines in brain development/function, we further hypothesized that child immune profiles might be associated with their neurodevelopmental status.

Methods: As part of a longitudinal study in Ukraine, children of mothers reporting low/no alcohol consumption or moderate-to-heavy alcohol consumption during pregnancy were enrolled in the study and received neurodevelopmental assessments. Group stratification was based on maternal alcohol consumption and child neurodevelopmental status resulting in the following groups: A/TD, alcohol-consuming mother, typically developing child; A/ND, alcohol-consuming mother, neurodevelopmental delay in the child; C/TD, control mother (low/no alcohol consumption), typically development child; and C/ND, control mother, neurodevelopmental delay in the child. Forty cytokines/chemokines were measured in plasma and data were analyzed using regression and constrained principle component analysis.

Results: Analyses revealed differential cytokine network activity associated with both prenatal alcohol exposure and neurodevelopmental status. Specifically, alcohol-exposed children showed activation of a cytokine network including eotaxin-3, eotaxin, and bFGF, irrespective of neurodevelopmental status. However, another cytokine network was differentially activated based on neurodevelopmental outcome: A/TD showed activation of MIP-1β, MDC, and MCP-4, and inhibition of CRP and PlGF, with opposing pattern of activation/inhibition detected in the A/ND group. By contrast, in the absence of alcohol-exposure, activation of a network including IL-2, TNF-β, IL-10, and IL-15 was associated with neurodevelopmental delay.

Conclusions: Taken together, this comprehensive assessment of immune markers allowed for the identification of unique immune milieus that are associated with alcohol exposure as well as both alcohol-related and alcohol-independent neurodevelopmental delay. These findings are a critical step towards establishing unique immune biomarkers for alcohol-related and alcohol-independent neurodevelopmental delay.
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http://dx.doi.org/10.1186/s12974-020-1717-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988366PMC
January 2020

Neurodevelopmental Outcomes Associated with Prefrontal Cortical Deoxygenation in Children with Fetal Alcohol Spectrum Disorders.

Dev Neuropsychol 2020 Jan-Feb;45(1):1-16. Epub 2020 Jan 8.

Center for Behavioral Teratology and Department of Psychology, San Diego State University, San Diego, California, USA.

Relationships between neurodevelopmental functioning and hemodynamic changes in the prefrontal cortex (PFC) were contrasted between children with prenatal alcohol exposure (PAE) and children who differed relative to their history of PAE and the presence of other neurodevelopmental impairment. For all groups, deoxygenated hemoglobin (HBR) levels in the medial PFC area were negatively related to externalizing problems and levels in the medial and right lateral PFC were positively related to errors on a cognitive inhibition task. Hemodynamic changes in the medial and right lateral PFC of children with PAE demonstrated stronger relationships to aspects of executive functioning relative to contrast groups.
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http://dx.doi.org/10.1080/87565641.2020.1712604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080191PMC
June 2020

Relation Between Oppositional/Conduct Behaviors and Executive Function Among Youth with Histories of Heavy Prenatal Alcohol Exposure.

Alcohol Clin Exp Res 2019 06 30;43(6):1135-1144. Epub 2019 Apr 30.

Center for Behavioral Teratology and Department of Psychology , San Diego State University, San Diego, California.

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
Conclusions: EF deficits in youth with histories of prenatal alcohol exposure were confirmed using direct and indirect measures. Oppositional/conduct behaviors related to EF deficits on indirect but not direct EF measures. Greater understanding of the contribution of concurrent psychopathology to long-term outcomes for alcohol-exposed youth requires further investigation.
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http://dx.doi.org/10.1111/acer.14036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551300PMC
June 2019

Relation between adaptive function and IQ among youth with histories of heavy prenatal alcohol exposure.

Birth Defects Res 2019 07 4;111(12):812-821. Epub 2019 Feb 4.

Center for Behavioral Teratology and Department of Psychology, San Diego State University, San Diego, California.

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.
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http://dx.doi.org/10.1002/bdr2.1463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650363PMC
July 2019

The Use of Functional Near-Infrared Spectroscopy to Differentiate Alcohol-Related Neurodevelopmental Impairment.

Dev Neuropsychol 2019 Mar-Apr;44(2):203-219. Epub 2019 Jan 20.

a Department of Psychiatry and Behavioral Science , Emory University School of Medicine , Atlanta , GA , USA.

Oxygenated (HBO) and deoxygenated hemoglobin (HBR) levels in the prefrontal cortex (PFC) were measured using functional near-infrared spectroscopy (fNIRS) to determine if PFC activity during a cognitive inhibition task distinguishes children with prenatal alcohol exposure (PAE, n = 26) from both typically developing controls (n = 19) and a contrast group of children with other neurobehavioral problems (n = 14). Despite showing evidence of increased PFC activity in the non-inhibitory condition relative to controls, children in the PAE group displayed reduced PFC HBO and increased HBR relative to both other groups in the inhibitory condition, suggesting reduced PFC activity but increased oxygen consumption without sufficient oxygen replacement.
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http://dx.doi.org/10.1080/87565641.2019.1567734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423538PMC
June 2019

Patterns of Prenatal Alcohol Use That Predict Infant Growth and Development.

Pediatrics 2019 02 4;143(2). Epub 2019 Jan 4.

Departments of Pediatrics and.

Background: Previous studies have had inconsistent findings regarding the quantity and frequency of prenatal alcohol exposure (PAE) that lead to deficits in growth and neurodevelopment. This may be due to imprecise methods of exposure classification. Our objective in this study was to employ longitudinal trajectory modeling of maternal drinking patterns associated with infant growth or neurodevelopmental deficits to a homogenous sample of mothers and infants.

Methods: From a sample of 471 pregnant women prospectively enrolled in a longitudinal study in the Ukraine, we performed a longitudinal cluster analysis of drinking patterns across gestation. We employed multivariable regression analyses to determine if each trajectory group was associated with infant weight, length, or head circumference at birth or psychomotor or mental deficits in infancy.

Results: We identified 5 distinct PAE trajectory groups: minimal or no PAE throughout gestation, low-to-moderate PAE with discontinuation early in gestation, low-to-moderate PAE sustained across gestation, moderate-to-high PAE with reduction early in gestation, and high PAE sustained across gestation. The highest-trajectory group was associated with deficits in infant weight and length at birth and deficits in psychomotor and mental performance at 6 to 12 months of age. Although confidence intervals overlapped, low-to-moderate sustained use was more strongly associated with most negative infant outcomes than moderate-to-high PAE with early reduction.

Conclusions: With these findings, we confirm that high, sustained PAE confers the highest risk for adverse infant outcomes but demonstrate that even low-to-moderate PAE continued across gestation is associated with certain deficits. This approach may be used to help clinicians identify high-risk infants for targeted early intervention.
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http://dx.doi.org/10.1542/peds.2018-2399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361345PMC
February 2019

Developmental Outcomes in Duarte Galactosemia.

Pediatrics 2019 01;143(1)

Departments of Human Genetics,

: media-1vid110.1542/5849572227001PEDS-VA_2018-2516 OBJECTIVES: For decades, infants with Duarte galactosemia (DG) have been identified by newborn screening (NBS), but whether they should be treated with dietary restrictions of galactose has remained unknown. To clarify, we conducted a study of dietary and developmental outcomes in 206 children with DG (case patients) and 144 controls, all of whom were 6 to 12 years old.

Methods: We recruited case patients from states where they were identified by NBS; unaffected siblings served as controls. Diet in infancy was ascertained by retrospective parent surveys; developmental outcomes were assessed in 5 domains, yielding 73 outcome measures for each child. We divided subjects randomly into independent discovery ( = 87) and validation ( = 263) sets. We tested the discovery set to order the 73 outcome measures by ascending values and tested the 10 outcomes with the lowest values for possible association with DG in the validation set. We also tested these same 10 outcomes for possible association with milk exposure in infancy among case patients in the validation set.

Results: None of the 73 outcomes tested in the discovery set revealed significant association with DG, and none of the 10 outcomes tested in the validation set revealed either significant association with DG or significant association with milk exposure among children with DG.

Conclusions: Through our results, we demonstrated that there were no significant differences in outcomes tested between case patients and controls or among case patients as a function of milk exposure in infancy. In this study, we provide a long-needed foundation of knowledge for health care providers, families, and NBS professionals seeking to make evidence-based decisions about DG.
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http://dx.doi.org/10.1542/peds.2018-2516DOI Listing
January 2019

Gestational age and socioeconomic status as mediators for the impact of prenatal alcohol exposure on development at 6 months.

Birth Defects Res 2019 07 31;111(12):789-796. Epub 2018 Oct 31.

Department of Pediatrics, University of California at San Diego, San Diego, California.

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.
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http://dx.doi.org/10.1002/bdr2.1408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494703PMC
July 2019

Executive Functioning Correlates With Communication Ability in Youth With Histories of Heavy Prenatal Alcohol Exposure.

J Int Neuropsychol Soc 2018 11 16;24(10):1026-1037. Epub 2018 Oct 16.

1Center for Behavioral Teratology and Department of Psychology,San Diego State University,San Diego,California.

Objectives: Caregivers of youth with heavy prenatal alcohol exposure report impaired communication, which can significantly impact quality of life. Using data collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), we examined whether cognitive variables predict communication ability of youth with histories of heavy prenatal alcohol exposure.

Methods: Subjects (ages 10-16 years) comprised two groups: adolescents with heavy prenatal alcohol exposure (AE) and non-exposed controls (CON). Selected measures of executive function (NEPSY, Delis-Kaplan Executive Function System), working memory (CANTAB), and language were tested in the child, while parents completed communication ratings (Vineland Adaptive Behavior Scales - Second Edition). Separate multiple regression analyses determined which cognitive domains predicted communication ability. A final, global model of communication comprised the three cognitive models.

Results: Spatial Working Memory and Inhibition significantly contributed to communication ability across groups. Twenty Questions performance related to communication ability in the CON group only while Word Generation performance related to communication ability in the AE group only. Effects remained significant in the global model, with the exception of Spatial Working Memory.

Conclusions: Both groups displayed a relation between communication and Spatial Working Memory and Inhibition. Stronger communication ability related to stronger verbal fluency in the AE group and Twenty Questions performance in the CON group. These findings suggest that alcohol-exposed adolescents may rely more heavily on learned verbal storage or fluency for daily communication while non-exposed adolescents may rely more heavily on abstract thinking and verbal efficiency. Interventions aimed at aspects of executive function may be most effective at improving communication ability of these individuals. (JINS, 2018, 24, 1026-1037).
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http://dx.doi.org/10.1017/S1355617718000772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237635PMC
November 2018

Altered maternal immune networks are associated with adverse child neurodevelopment: Impact of alcohol consumption during pregnancy.

Brain Behav Immun 2018 10 5;73:205-215. Epub 2018 May 5.

Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.

Cytokines and chemokines are potent modulators of brain development and as such, dysregulation of the maternal immune system can result in deviations in the fetal cytokine balance, altering the course of typical brain development, and putting the individual on a "pathway to pathology". In the current study, we used a multi-variate approach to evaluate networks of interacting cytokines and investigated whether alterations in the maternal immune milieu could be linked to alcohol-related and alcohol-independent child neurodevelopmental delay. This was achieved through the measurement of 40 cytokines/chemokines from maternal blood samples collected during the second and third trimesters of pregnancy. Importantly, during the second trimester we identified network enrichment in levels of cytokines including IFN-ɣ, IL-10, TNF-β, TNF-α, and CRP associated with offspring neurodevelopmental delay. However, as elevations in levels of these cytokines have previously been reported in a wide range of neurodevelopmental disorders including autism spectrum disorder and schizophrenia, we suggest that this cytokine profile is likely not disorder specific, but rather may be an indicator of neurodevelopmental delay in general. By contrast, distinct clusters of activated/inhibited cytokines were identified based on maternal alcohol consumption and child neurodevelopmental outcome. Specifically, cytokines including IL-15, IL-10, MDC, and members of the VEGF sub-family were highest in alcohol-consuming mothers of children with neurodevelopmental delay and were identified in both network analyses and examination of individual cytokines, whereas a differential and unique cytokine profile was identified in the case of alcohol-independent child neurodevelopmental delay. We propose that the current findings could provide a critical step towards the development of early biomarkers and possibly interventions for alcohol-related neurodevelopmental delay. Importantly, the current approach could be informative for understanding mechanisms linking maternal immune system dysfunction and adverse child outcomes in a range of other neurodevelopmental disorders.
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http://dx.doi.org/10.1016/j.bbi.2018.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344127PMC
October 2018

Two-year cortical trajectories are abnormal in children and adolescents with prenatal alcohol exposure.

Dev Cogn Neurosci 2018 04 21;30:123-133. Epub 2018 Feb 21.

University of Minnesota, Twin Cities, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.dcn.2018.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949095PMC
April 2018

Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities.

JAMA 2018 02;319(5):474-482

University of Arizona College of Medicine, Tucson.

Importance: Fetal alcohol spectrum disorders are costly, life-long disabilities. Older data suggested the prevalence of the disorder in the United States was 10 per 1000 children; however, there are few current estimates based on larger, diverse US population samples.

Objective: To estimate the prevalence of fetal alcohol spectrum disorders, including fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder, in 4 regions of the United States.

Design, Setting, And Participants: Active case ascertainment methods using a cross-sectional design were used to assess children for fetal alcohol spectrum disorders between 2010 and 2016. Children were systematically assessed in the 4 domains that contribute to the fetal alcohol spectrum disorder continuum: dysmorphic features, physical growth, neurobehavioral development, and prenatal alcohol exposure. The settings were 4 communities in the Rocky Mountain, Midwestern, Southeastern, and Pacific Southwestern regions of the United States. First-grade children and their parents or guardians were enrolled.

Exposures: Alcohol consumption during pregnancy.

Main Outcomes And Measures: Prevalence of fetal alcohol spectrum disorders in the 4 communities was the main outcome. Conservative estimates for the prevalence of the disorder and 95% CIs were calculated using the eligible first-grade population as the denominator. Weighted prevalences and 95% CIs were also estimated, accounting for the sampling schemes and using data restricted to children who received a full evaluation.

Results: A total of 6639 children were selected for participation from a population of 13 146 first-graders (boys, 51.9%; mean age, 6.7 years [SD, 0.41] and white maternal race, 79.3%). A total of 222 cases of fetal alcohol spectrum disorders were identified. The conservative prevalence estimates for fetal alcohol spectrum disorders ranged from 11.3 (95% CI, 7.8-15.8) to 50.0 (95% CI, 39.9-61.7) per 1000 children. The weighted prevalence estimates for fetal alcohol spectrum disorders ranged from 31.1 (95% CI, 16.1-54.0) to 98.5 (95% CI, 57.5-139.5) per 1000 children.

Conclusions And Relevance: Estimated prevalence of fetal alcohol spectrum disorders among first-graders in 4 US communities ranged from 1.1% to 5.0% using a conservative approach. These findings may represent more accurate US prevalence estimates than previous studies but may not be generalizable to all communities.
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http://dx.doi.org/10.1001/jama.2017.21896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839298PMC
February 2018

GoFAR: improving attention, behavior and adaptive functioning in children with fetal alcohol spectrum disorders: Brief report.

Dev Neurorehabil 2018 Jul 9;21(5):345-349. Epub 2018 Jan 9.

c Do2learn.com , Raleigh , NC , USA.

Objective: This brief report describes the GoFAR intervention designed to improve attention, behavior, and adaptive functioning in children with FASD, ages 5 to 10 years.

Methods: Thirty children were randomized to one of three conditions: GoFAR; FACELAND, and CONTROL; 25 completed the interventions. Over 10 sessions children and caregivers learned a metacognitive strategy (FAR) designed to improve cognitive control of behavior and adaptive functioning and practiced it during behavior analog therapy. Attention, behavior problems, and adaptive skills were measured pre- and post-intervention.

Results: From pre- to post-testing the GoFAR intervention group improved on the Test of Variables of Attention (TOVA). Both intervention groups improved in Daily Living Skills.

Conclusion: This pilot study demonstrated that children with FASD and their caregivers benefit from a focused intervention designed to improve effortful control of behavior. The study suggests the need for a larger clinical trial to evaluate the intervention's effectiveness.
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http://dx.doi.org/10.1080/17518423.2018.1424263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314185PMC
July 2018

Effects of prenatal alcohol exposure in a prospective sample of young adults: Mental health, substance use, and difficulties with the legal system.

Neurotoxicol Teratol 2017 Nov 3;64:50-62. Epub 2017 Oct 3.

Center for Maternal Substance Abuse and Child Development, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park Drive NE, Suite 200, Atlanta, GA 30329, United States.. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ntt.2017.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739524PMC
November 2017

Prefrontal cortical responses in children with prenatal alcohol-related neurodevelopmental impairment: A functional near-infrared spectroscopy study.

Clin Neurophysiol 2017 11 2;128(11):2099-2109. Epub 2017 Sep 2.

Departments of Psychiatry and Behavioral Science, Emory University School of Medicine, Atlanta, GA 30329, USA; Pediatrics, Emory University School of Medicine, Atlanta, GA 30329, USA.

Objective: Disruption in the neural activation of the prefrontal cortex (PFC) in modulating arousal was explored in children with heavy prenatal alcohol exposure (PAE), who have known neurobehavioral impairment.

Methods: During a task that elicits frustration, functional near-infrared spectroscopy (fNIRS) was used to measure PFC activation, specifically levels of oxygenated (HBO) and deoxygenated (HBR) hemoglobin, in children with PAE (n=18) relative to typically developing Controls (n=12) and a Clinical Contrast group with other neurodevelopmental or behavioral problems (n=14).

Results: Children with PAE had less activation during conditions with positive emotional arousal, as indicated by lower levels of HBO in the medial areas of the PFC and higher levels of HBR in all areas of the PFC sampled relative to both other groups. Children in the Control group demonstrated greater differentiation of PFC activity than did children with PAE. Children in the Clinical Contrast group demonstrated the greatest differences in PFC activity between valences of task conditions.

Conclusions: Specific patterns of PFC activation differentiated children with PAE from typically developing children and children with other clinical problems.

Significance: FNIRS assessments of PFC activity provide new insights regarding the mechanisms of commonly seen neurobehavioral dysfunction in children with PAE.
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http://dx.doi.org/10.1016/j.clinph.2017.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675790PMC
November 2017

Neural correlates of verbal memory in youth with heavy prenatal alcohol exposure.

Brain Imaging Behav 2018 Jun;12(3):806-822

Center for Behavioral Teratology, Department of Psychology, San Diego State University, 6330 Alvarado Court, Suite 100, San Diego, CA, 92120, USA.

Prenatal alcohol exposure can impact both brain development and neurobehavioral function, including verbal learning and recall, although the relation between verbal recall and brain structure in this population has not been examined fully. We aimed to determine the structural neural correlates of verbal learning and recall in youth with histories of heavy prenatal alcohol exposure using a region of interest (ROI) approach. As part of an ongoing multisite project, subjects (age 10-16 years) with prenatal alcohol exposure (AE, n = 81) and controls (CON, n = 81) were tested using the CVLT-C and measures of cortical volume, surface area, and thickness as well as hippocampal volume were derived from MRI. Group differences in brain and memory indices were tested with ANOVA. Multiple regression analyses tested whether brain ROIs significantly predicted memory performance. The AE group had lower scores than the CON group on all CVLT-C variables (ps ≤ .001) and volume and surface area (ps < .025), although results varied by ROI. No group differences in cortical thickness were found. The relations between cortical structure and memory performance differed between group among some ROIs, particularly those in the frontal cortex, generally with smaller surface area and/or thinner cortex predicting better performance in CON but worse performance in AE. Cortical surface area appears to be the most sensitive index to the effects of prenatal alcohol exposure, while cortical thickness appears to be the least sensitive. These findings also indicate that the neural correlates of verbal memory are altered in youth with heavy prenatal alcohol exposure compared to controls.
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http://dx.doi.org/10.1007/s11682-017-9739-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745322PMC
June 2018

Evidence Supporting the Internal Validity of the Proposed ND-PAE Disorder.

Child Psychiatry Hum Dev 2018 04;49(2):163-175

Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 12 Executive Park, Atlanta, GA, 30329, USA.

The internal validity of the proposed Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE) was evaluated in children diagnosed with either Fetal Alcohol Syndrome (FAS) or partial FAS who were 3-10 years of age and had enrolled in a math intervention study. Symptoms were coded as present or absent using assessments conducted in the study, including standardized measures of neurocognitive and behavioral functioning, parent interview, and direct observations of the child. The number of endorsed ND-PAE symptoms was not related to environmental factors but was moderately related to the child's age. ND-PAE symptoms were highly consistent and this did not vary by age. Evidence suggested the ND-PAE adaptive symptoms may be too restrictive and only one symptom from this domain may be sufficient. Impulsiveness was not related to an endorsement of the ND-PAE disorder but research is needed with other clinical groups to establish the discriminative validity of this symptom.
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http://dx.doi.org/10.1007/s10578-017-0738-8DOI Listing
April 2018

Cortical gyrification is abnormal in children with prenatal alcohol exposure.

Neuroimage Clin 2017 22;15:391-400. Epub 2017 May 22.

University of Minnesota, Twin Cities, United States. Electronic address:

Objectives: Prenatal alcohol exposure (PAE) adversely affects early brain development. Previous studies have shown a wide range of structural and functional abnormalities in children and adolescents with PAE. The current study adds to the existing literature specifically on cortical development by examining cortical gyrification in a large sample of children with PAE compared to controls. Relationships between cortical development and intellectual functioning are also examined.

Experimental Design: Included were 92 children with PAE and 83 controls ages 9-16 from four sites in the Collaborative Initiative on FASD (CIFASD). All PAE participants had documented heavy PAE. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Cortical gyrification was examined using a semi-automated procedure.

Principal Observations: Whole brain group comparisons using Monte Carlo z-simulation for multiple comparisons showed significantly lower cortical gyrification across a large proportion of the cerebral cortex amongst PAE compared to controls. Whole brain comparisons and ROI based analyses showed strong positive correlations between cortical gyrification and IQ (i.e. less developed cortex was associated with lower IQ).

Conclusions: Abnormalities in cortical development were seen across the brain in children with PAE compared to controls. Cortical gyrification and IQ were strongly correlated, suggesting that examining mechanisms by which alcohol disrupts cortical formation may yield clinically relevant insights and potential directions for early intervention.
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http://dx.doi.org/10.1016/j.nicl.2017.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447653PMC
March 2018

Response to Astley's Letter to the Editor.

Alcohol Clin Exp Res 2017 01 26;41(1):219. Epub 2016 Nov 26.

Department of Pediatrics, University of California at San Diego, La Jolla, California.

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http://dx.doi.org/10.1111/acer.13271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537735PMC
January 2017

The Use of Cardiac Orienting Responses as an Early and Scalable Biomarker of Alcohol-Related Neurodevelopmental Impairment.

Alcohol Clin Exp Res 2017 01 24;41(1):128-138. Epub 2016 Nov 24.

Department of Pediatrics, University of California, San Diego, La Jolla, California.

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.
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http://dx.doi.org/10.1111/acer.13261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5205554PMC
January 2017
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