Background: As many as 80% of individuals with fetal alcohol spectrum disorders (FASD) are misdiagnosed or not diagnosed. This study tests the accuracy and validity of a web-based screening tool (the FASD-Tree) for identifying children and adolescents with FASD. Methods:Children with histories of prenatal alcohol exposure (PAE) and controls (N = 302, including 224 with PAE and 78 controls) were examined for physical signs of fetal alcohol syndrome (FAS), and parents completed behavioral questionnaires. Data were entered into the FASD-Tree, a web-based decision tree application. The FASD-Tree provided two outcomes: a dichotomous indicator (yes/no) and a numeric risk score (0 to 5), which have been shown separately to identify children with PAE and neurobehavioral impairment and to correlate with neurobehavioral outcomes. Overall accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the decision tree, risk score, and their combination. Misclassified cases were examined for systematic bias. Results:The FASD-Tree was successful in accurately identifying youth with histories of PAE and the subgroup of individuals with FASD, indicating its validity as an FASD screening tool. Overall accuracy rates for FASD-Tree components ranged from 75.0% to 84.1%, and both the decision tree outcome and risk score, and their combination, resulted in fair to good discrimination (area under the curve = 0.722 to 0.862) of youth with histories of PAE or FASD. While most participants were correctly classified, those who were misclassified differed in IQ and attention. Race, ethnicity, and sex did not affect the results. Conclusion:The FASD-Tree is not a biomarker of PAE and does not provide definitive evidence of prenatal alcohol exposure. Rather it is an accurate and valid screening tool for FASD and can be used by clinicians who suspect that a patient has a history of PAE, even if the exposure is unknown.

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Proprietary genetic datasets are valuable for boosting the statistical power of genome-wide association studies (GWASs), but their use can restrict investigators from publicly sharing the resulting summary statistics. Although researchers can resort to sharing down-sampled versions that exclude restricted data, down-sampling reduces power and might change the genetic etiology of the phenotype being studied. These problems are further complicated when using multivariate GWAS methods, such as genomic structural equation modeling (Genomic SEM), that model genetic correlations across multiple traits. Here, we propose a systematic approach to assess the comparability of GWAS summary statistics that include versus exclude restricted data. Illustrating this approach with a multivariate GWAS of an externalizing factor, we assessed the impact of down-sampling on (1) the strength of the genetic signal in univariate GWASs, (2) the factor loadings and model fit in multivariate Genomic SEM, (3) the strength of the genetic signal at the factor level, (4) insights from gene-property analyses, (5) the pattern of genetic correlations with other traits, and (6) polygenic score analyses in independent samples. For the externalizing GWAS, down-sampling resulted in a loss of genetic signal and fewer genome-wide significant loci, while the factor loadings and model fit, gene-property analyses, genetic correlations, and polygenic score analyses are robust. Given the importance of data sharing for the advancement of open science, we recommend that investigators who share down-sampled summary statistics report these analyses as accompanying documentation to support other researchers' use of the summary statistics.

ObjectivesAdverse childhood experiences (ACEs) are associated with mental health issues and substance use. Having a substance use disorder increases the risk of overdose (OD). Research on ACEs and risk of OD is limited. This study examined the relationship between ACE scores and a self-reported history of OD among patients in an addiction and mental health outpatient setting.MethodsThis single-center, cross-sectional design included adults in a dual-diagnosis addiction and mental health outpatient recovery and treatment program from November 2017 to August 2020. Patients (N = 115) were assessed with self-report questionnaires, which included ACEs and history of OD. Bivariate and multivariable logistic regression was used to determine factors associated with self-reported OD history. We assessed the reliability and validity of the ACEs scale.ResultsOf the 115 participants, 26 (22.6%) reported a past OD at intake. The mean ACE score for participants with an OD history, as compared with those with no history of OD, was 4.0 (standard deviation, 2.7) vs 2.3 (standard deviation, 2.2). In the multivariable regression, a higher ACE score was associated with history of OD (adjusted odds ratio, 1.23; 95% confidence interval, 1.00–1.50; P = 0.0456).ConclusionsGiven the observed association between OD and higher ACE scores, patients presenting for treatment in outpatient dual-diagnosis clinics should be screened for ACEs and OD history, providing the opportunity for treatment with trauma-informed care and/or referral to appropriate services.

PurposeThis study assessed whether the outcome of a screening tool for fetal alcohol spectrum disorders (FASD), the FASD‐Tree, was associated with neuropsychological and behavioral outcomes.MethodsData for this study were collected as part of the fourth phase of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD‐4). Participants (N = 175, 5 to 16 years) with or without histories of prenatal alcohol exposure were recruited from San Diego and Minneapolis. Each participant was screened using the FASD‐Tree and administered a neuropsychological test battery; parents or guardians completed behavioral questionnaires. The FASD‐Tree incorporates physical and behavioral measures and provides an outcome regarding the presence of FASD (FASD‐Positive or FASD‐Negative). Logistic regression was used to test whether the FASD‐Tree outcome was associated with general cognitive ability, executive function, academic achievement, and behavior. Associations were tested in two groups: the whole sample and only correctly classified participants.ResultsResults of the FASD‐Tree were associated with neuropsychological and behavioral measures. Participants classified as FASD‐Positive were more likely than those classified as FASD‐Negative to have a lower IQ score and exhibit poorer performance on measures of executive and academic functions. Behaviorally, participants classified as FASD‐Positive were rated as having more behavior problems and adaptive difficulties. Similar relationships were found for all measures when including only participants correctly classified by the FASD‐Tree screening tool.ConclusionResults from the FASD‐Tree screening tool were associated with neuropsychological and behavioral measures. Participants classified as FASD‐Positive were more likely to have impairment in all domains tested. The results support the effectiveness of the FASD‐Tree as a screening tool for use in clinical settings, providing an efficient and accurate way to identify patients in need of additional evaluation.