Fetal alcohol spectrum disorder: development of concensus referral criteria for specialist diagnostic assessment in Australia

Background: Fetal alcohol spectrum disorder (FASD) is known to be under-recognised in Australia. The use of standard methods to identify when to refer individuals who may have FASD for specialist assessment could help improve the identification of this disorder. The purpose of this study was to develop referral criteria for use in Australia. Method: An online survey about FASD screening and diagnosis in Australia, which included 23 statements describing criteria for referral for fetal alcohol syndrome (FAS) and FASD based on published recommendations for referral in North America, was sent to 139 health professionals who had expertise or involvement in FASD screening or diagnosis. Survey findings and published criteria for referral were subsequently reviewed by a panel of 14 investigators at a consensus development workshop where criteria for referral were developed.Results: Among the 139 health professionals who were sent the survey, 103 (74%) responded, and 90 (65%) responded to the statements on criteria for referral. Over 80% of respondents agreed that referral for specialist evaluation should occur when there is evidence of significant prenatal alcohol exposure, defined as 7 or more standard drinks per week and at least 3 standard drinks on any one day, and more than 70% agreed with 13 of the16 statements that described criteria for referral other than prenatal alcohol exposure. Workshop participants recommended five independent criteria for referral: confirmed significant prenatal alcohol exposure; microcephaly and confirmed prenatal alcohol exposure; 2 or more significant central nervous system (CNS) abnormalities and confirmed prenatal alcohol exposure; 3 characteristic FAS facial anomalies; and 1 characteristic FAS facial anomaly, growth deficit and 1 or more CNS abnormalities .Conclusion: Referral criteria recommended for use in Australia are similar to those recommended in North America. There is a need to develop resources to raise awareness of these criteria among health professionals and evaluate their feasibility, acceptability and capacity to improve the identification of FASD in Australia

RESEARCH Open Access

Involving consumers and the community in the development of a diagnostic instrument for fetal alcohol spectrum disorders in Australi

Integrating GWAS and Transcriptomics to Identify the Molecular Underpinnings of Thermal Stress Responses in \u3cem\u3eDrosophila melanogaster\u3c/em\u3e

Thermal tolerance of an organism depends on both the ability to dynamically adjust to a thermal stress and preparatory developmental processes that enhance thermal resistance. However, the extent to which standing genetic variation in thermal tolerance alleles influence dynamic stress responses vs. preparatory processes is unknown. Here, using the model species Drosophila melanogaster, we used a combination of Genome Wide Association mapping (GWAS) and transcriptomic profiling to characterize whether genes associated with thermal tolerance are primarily involved in dynamic stress responses or preparatory processes that influence physiological condition at the time of thermal stress. To test our hypotheses, we measured the critical thermal minimum (CTmin) and critical thermal maximum (CTmax) of 100 lines of the Drosophila Genetic Reference Panel (DGRP) and used GWAS to identify loci that explain variation in thermal limits. We observed greater variation in lower thermal limits, with CTmin ranging from 1.81 to 8.60°C, while CTmax ranged from 38.74 to 40.64°C. We identified 151 and 99 distinct genes associated with CTmin and CTmax, respectively, and there was strong support that these genes are involved in both dynamic responses to thermal stress and preparatory processes that increase thermal resistance. Many of the genes identified by GWAS were involved in the direct transcriptional response to thermal stress (72/151 for cold; 59/99 for heat), and overall GWAS candidates were more likely to be differentially expressed than other genes. Further, several GWAS candidates were regulatory genes that may participate in the regulation of stress responses, and gene ontologies related to development and morphogenesis were enriched, suggesting many of these genes influence thermal tolerance through effects on development and physiological status. Overall, our results suggest that thermal tolerance alleles can influence both dynamic plastic responses to thermal stress and preparatory processes that improve thermal resistance. These results also have utility for directly comparing GWAS and transcriptomic approaches for identifying candidate genes associated with thermal tolerance

Messages that increase women’s intentions to abstain from alcohol during pregnancy: results from quantitative testing of advertising concepts

Background: Public awareness-raising campaigns targeting alcohol use during pregnancy are an important part of preventing prenatal alcohol exposure and Fetal Alcohol Spectrum Disorder. Despite this, there is little evidence on what specific elements contribute to campaign message effectiveness. This research evaluated three different advertising concepts addressing alcohol and pregnancy: a threat appeal, a positive appeal promoting a self-efficacy message, and a concept that combined the two appeals. The primary aim was to determine the effectiveness of these concepts in increasing women’s intentions to abstain from alcohol during pregnancy.Methods: Women of childbearing age and pregnant women residing in Perth, Western Australia participated in a computer-based questionnaire where they viewed either a control or one of the three experimental concepts. Following exposure, participants’ intentions to abstain from and reduce alcohol intake during pregnancy were measured. Other measures assessed included perceived main message, message diagnostics, and potential to promote defensive responses or unintended consequences.Results: The concepts containing a threat appeal were significantly more effective at increasing women’s intentions to abstain from alcohol during pregnancy than the self-efficacy message and the control. The concept that combined threat and self-efficacy is recommended for development as part of a mass-media campaign as it has good persuasive potential, provides a balance of positive and negative emotional responses, and is unlikely to result in defensive or unintended consequences.Conclusions: This study provides important insights into the components that enhance the persuasiveness and effectiveness of messages aimed at preventing prenatal alcohol exposure. The recommended concept has good potential for use in a future campaign aimed at promoting women’s intentions to abstain from alcohol during pregnanc

A modified Delphi study of screening for fetal alcohol spectrum disorders in Australia

Background: There is little reliable information on the prevalence of fetal alcohol spectrum disorders (FASD) in Australia and no coordinated national approach to facilitate case detection. The aim of this study was to identify health professionals’ perceptions about screening for FASD in Australia. Method: A modified Delphi process was used to assess perceptions of the need for, and the process of, screening for FASD in Australia. We recruited a panel of 130 Australian health professionals with experience or expertise in FASD screening or diagnosis. A systematic review of the literature was used to develop Likert statements on screening coverage, components and assessment methods which were administered using an online survey over two survey rounds. Results: Of the panel members surveyed, 95 (73%) responded to the questions on screening in the first survey round and, of these, 81 (85%) responded to the second round. Following two rounds there was consensus agreement on the need for targeted screening at birth (76%) and in childhood (84%). Participants did not reach consensus agreement on the need for universal screening at birth (55%) or in childhood (40%). Support for targeted screening was linked to perceived constraints on service provision and the need to examine the performance, costs and benefits of screening. For targeted screening of high risk groups, we found highest agreement for siblings of known cases of FASD (96%) and children of mothers attending alcohol treatment services (93%). Participants agreed that screening for FASD primarily requires assessment of prenatal alcohol exposure at birth (86%) and in childhood (88%), and that a checklist is needed to identify the components of screening and criteria for referral at birth (84%) and in childhood (90%). Conclusions: There is an agreed need for targeted but not universal screening for FASD in Australia, and sufficient consensus among health professionals to warrant development and evaluation of standardised methods for targeted screening and referral in the Australian context. Participants emphasised the need for locally-appropriate, evidence-based approaches to facilitate case detection, and the importance of ensuring that screening and referral programs are supported by adequate diagnostic and management capacity

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia

EEG power at 3 months in infants at high familial risk for autism

Background: Alterations in brain development during infancy may precede the behavioral manifestation of developmental disorders. Infants at increased risk for autism are also at increased risk for other developmental disorders, including, quite commonly, language disorders. Here we assess the extent to which electroencephalographic (EEG) differences in infants at high versus low familial risk for autism are present by 3 months of age, and elucidate the functional significance of EEG power at 3 months in predicting later development. Methods: EEG data were acquired at 3 months in infant siblings of children with autism (high risk; n = 29) and infant siblings of typically developing children (low risk; n = 19) as part of a prospective, longitudinal investigation. Development across multiple domains was assessed at 6, 9, 12, 18, 24, and 36 months. Diagnosis of autism was determined at 18–36 months. We assessed relationships between 3-month-olds’ frontal EEG power and autism risk, autism outcome, language development, and development in other domains. Results: Infants at high familial risk for autism had reduced frontal power at 3 months compared to infants at low familial risk for autism, across several frequency bands. Reduced frontal high-alpha power at 3 months was robustly associated with poorer expressive language at 12 months. Conclusions: Reduced frontal power at 3 months may indicate increased risk for reduced expressive language skills at 12 months. This finding aligns with prior studies suggesting reduced power is a marker for atypical brain function, and infants at familial risk for autism are also at increased risk for altered developmental functioning in non-autism-specific domains