A GWAS for grip strength in cohorts of children-Advantages of analysing young participants for this trait.

Grip strength (GS) is a proxy measure for muscular strength and a predictor for bone fracture risk among other diseases. Previous genome-wide association studies (GWASs) have been conducted in large cohorts of adults focusing on scores collected for the dominant hand, therefore increasing the likelihood of confounding effects by environmental factors. Here, we perform the first GWAS meta-analyses on maximal GS with the dominant (GSD) and non-dominant (GSND) hand in two cohorts of children (ALSPAC, N = 5450; age range = 10.65-13.61; Raine Study, N = 1162, age range: 9.42-12.38 years). We identified a novel significant association for GSND (rs9546244, LINC02465, p = 3.43e-08) and replicated associations previously reported in adults including with a HOXB3 gene marker that shows an expression quantitative trait locus (eQTL) effect. Despite a much smaller sample (~3%) compared with the UK Biobank we replicated correlation analyses previously reported in this much larger adult cohort, such as a negative correlation with coronary artery disease. Although the results from the polygenic risk score (PRS) analyses did not survive multiple testing correction, we observed nominally significant associations between GS and risk of overall fracture, as previously reported, as well ADHD which will require further investigations. Finally, we observed a higher SNP-heritability (24%-41%) compared with previous studies (4%-24%) in adults. Overall, our results suggest that cohorts of children might be better suited for genetic studies of grip strength, possibly due to the shorter exposure to confounding environmental factors compared with adults.

Low-intensity parent- and clinician-delivered support for young autistic children in Aotearoa New Zealand: a randomised controlled trial.

Background: Aotearoa New Zealand does not provide publicly-funded intensive autism support. While parent-mediated supports are promising, children and families may also benefit from direct clinician support. We tested the efficacy of a low-intensity programme involving parent- and clinician-delivered support for autistic children. Methods: This single-blind, two-arm randomised controlled trial assessed outcomes of a six-month low-intensity parent- and clinician-delivered support (2-3 h per week) based on the Early Start Denver Model compared to a control group who received monthly support calls and assistance with referrals. Children aged 1-4.5 years who were autistic or showing signs of autism and their parents were randomised to the low-intensity or control group by a blinded statistician using the Urn minimisation method. Assessments were conducted at baseline and immediately following the support period (24-weeks post-baseline). The primary outcome was child engagement during an interaction with their parent. The trial was pre-registered with ANZCTR: U1111-1260-2529. Findings: From March 2021 to May 2023, 56 families were randomised to either the low-intensity or control group. Following drop-outs, 21 families in the low-intensity group and 24 in the control group were included in analysis. There was large and significantly greater improvement in children's engagement in the low-intensity group compared to the control group (F (1, 43) = 21.47, p < 0.0001, ηp 2 = 0.33). There was one recorded adverse event unrelated to the support and two adverse effects related to the support. Interpretation: A low-intensity parent- and clinician-delivered support can improve engagement between an autistic child and their parent during play. Low-intensity supports may be beneficial in areas where access to clinical autism supports is limited. Funding: Emerging Researcher First Grant from the Health Research Council of New Zealand.

Absence of association between maternal adverse events and long-term gut microbiome outcomes in the Australian autism biobank.

Introduction: Maternal immune activation (MIA) and prenatal maternal stress (MatS) are well-studied risk factors for psychiatric conditions such as autism and schizophrenia. Animal studies have proposed the gut microbiome as a mechanism underlying this association and have found that risk factor-related gut microbiome alterations persist in the adult offspring. In this cross-sectional study, we assessed whether maternal immune activation and prenatal maternal stress were associated with long-term gut microbiome alterations in children using shotgun metagenomics. Methods: This cross-sectional study included children diagnosed with autism (N = 92), siblings without a diagnosis (N = 42), and unrelated children (N = 40) without a diagnosis who were recruited into the Australian Autism Biobank and provided a faecal sample. MIA exposure was inferred from self-reported data and included asthma/allergies, complications during pregnancy triggering an immune response, auto-immune conditions, and acute inflammation. Maternal stress included any of up to 9 stressful life events during pregnancy, such as divorce, job loss, and money problems. Data were analysed for a total of 174 children, of whom 63 (36%) were born to mothers with MIA and 84 (48%) were born to mothers who experienced maternal stress during pregnancy (where 33 [19%] experienced both). Gut microbiome data was assessed using shotgun metagenomic sequencing of the children's faecal samples. Results: In our cohort, MIA, but not MatS, was associated with ASD. Variance component analysis revealed no associations between any of the gut microbiome datasets and neither MIA nor MatS. After adjusting for age, sex, diet and autism diagnosis, there was no significant difference between groups for bacterial richness, α-diversity or ß-diversity. We found no significant differences in species abundance in the main analyses. However, when stratifying the cohort by age, we found that Faecalibacterium prausnitzii E was significantly decreased in MIA children aged 11-17. Discussion: Consistent with previous findings, we found that children who were born to mothers with MIA were more likely to be diagnosed with autism. Unlike within animal studies, we found negligible microbiome differences associated with MIA and maternal stress. Given the current interest in the microbiome-gut-brain axis, researchers should exercise caution in translating microbiome findings from animal models to human contexts and the clinical setting.

Behavioural and neuropsychological outcomes in children exposed in utero to maternal labour epidural analgesia.

BACKGROUND: Recent studies report conflicting results regarding the relationship between labour epidural analgesia (LEA) in mothers and neurodevelopmental disorders in their offspring. We evaluated behavioural and neuropsychological test scores in children of mothers who used LEA. METHODS: Children enrolled in the Raine Study from Western Australia and delivered vaginally from a singleton pregnancy between 1989 and 1992 were evaluated. Children exposed to LEA were compared with unexposed children. The primary outcome was the parent-reported Child Behaviour Checklist (CBCL) reporting total, internalising, and externalising behavioural problem scores at age 10 yr. Score differences, an increased risk of clinical deficit, and a dose-response based on the duration of LEA exposure were assessed. Secondary outcomes included language, motor function, cognition, and autistic traits. RESULTS: Of 2180 children, 850 (39.0%) were exposed to LEA. After adjustment for covariates, exposed children had minimally increased CBCL total scores (+1.41 points; 95% confidence interval [CI] 0.09 to 2.73; P=0.037), but not internalising (+1.13 points; 95% CI -0.08 to 2.34; P=0.066) or externalising (+1.08 points; 95% CI -0.08 to 2.24; P=0.068) subscale subscores. Increased risk of clinical deficit was not observed for any CBCL score. For secondary outcomes, score differences were inconsistently observed in motor function and cognition. Increased exposure duration was not associated with worse scores in any outcomes. CONCLUSIONS: Although LEA exposure was associated with slightly higher total behavioural scores, there was no difference in subscores, increased risk of clinical deficits, or dose-response relationship. These results argue against LEA exposure being associated with consistent, clinically significant neurodevelopmental deficits in children.

Investigating Parental Observations of Early Autism Development in Simplex and Multiplex Families.

Past research has highlighted the importance of early identification of developmental differences to improve targeted access to early interventions or supports. As such, it is of particular importance in the context of children at elevated likelihood of autism (such as where an older sibling has a diagnosis of autism), to better understand when and which early concerns are important as predictors of which children will benefit from pre-diagnostic supports. This study explored the number and frequency of retrospective parent reported concerns within the first year of life for children diagnosed with autism, both those who had an older sibling diagnosed with autism and those who did not, as well as for undiagnosed siblings. We found that at both 0-6 and 7-12 months, the only factor related to the presence or absence of early parent reported concerns was child diagnostic status, with the presence of reported early concerns more likely for children with a diagnosis of autism. These findings suggest that for children at elevated likelihood of autism, parents' concerns are driven primarily by developmental differences, with child's birth order and sibling diagnostic status not impacting on parent early concerns.

Investigating the impact of developmental coordination difficulties across home, school, and community settings: Findings from the Australian Impact for DCD survey.

AIM: To evaluate the participation difficulties experienced by children with developmental coordination disorder (DCD) in home, school, and community environments. METHODS: The Impact for DCD survey was completed by primary caregivers of 4-18-year-old children with DCD (or synonymous diagnosis) (n = 429). OUTCOMES AND RESULTS: The greatest participation difficulties experienced at home included dressing, eating with utensils, self-care tasks and drawing/writing reported by over 70% of families. At school, fine motor difficulties were also frequently reported, with additional difficulties keeping up or completing tasks, and not feeling supported at school. Socialisation challenges and bullying were also commonly reported (34.9%). As a result of participation difficulties at school, 5.4% were home schooled. Many children engaged in community activity, with 72.0% currently engaged in at least one organised sports-based activity. CONCLUSIONS AND IMPLICATIONS: Increased recognition of the widespread impact of DCD in a child's life is crucial at an individual and societal level. Parents reported their children experiencing significant participation restrictions and difficulties. The findings of this large-scale study have revealed that most children with DCD are not receiving the support they need to thrive, especially at school. This largely reflects a lack of understanding and recognition of the condition and its associated challenges.

Feasibility of a 2-minute eye-tracking protocol to support the early identification of autism.

We tested the potential for Gazefinder eye-tracking to support early autism identification, including feasible use with infants, and preliminary concurrent validity of trial-level gaze data against clinical assessment scores. We embedded the ~ 2-min 'Scene 1S4' protocol within a comprehensive clinical assessment for 54 consecutively-referred, clinically-indicated infants (prematurity-corrected age 9-14 months). Alongside % tracking rate as a broad indicator of feasible assessment/data capture, we report infant gaze data to pre-specified regions of interest (ROI) across four trial types and associations with scores on established clinical/behavioural tools. Most infants tolerated Gazefinder eye-tracking well, returning high overall % tracking rate. As a group, infants directed more gaze towards social vs. non-social (or more vs. less socially-salient) ROIs within trials. Behavioural autism features were correlated with increased gaze towards non-social/geometry (vs. social/people) scenes. No associations were found for gaze directed to ROIs within other stimulus types. Notably, there were no associations between developmental/cognitive ability or adaptive behaviour with gaze towards any ROI. Gazefinder assessment seems highly feasible with clinically-indicated infants, and the people vs. geometry stimuli show concurrent predictive validity for behavioural autism features. Aggregating data across the ~ 2-min autism identification protocol might plausibly offer greater utility than stimulus-level analysis alone.

Do parent-reported early indicators predict later developmental language disorder? A Raine Study investigation.

BACKGROUND: Developmental language disorder (DLD) is one of the most common neurodevelopmental conditions. Due to variable rates of language growth in children under 5 years, the early identification of children with DLD is challenging. Early indicators are often outlined by speech pathology regulatory bodies and other developmental services as evidence to empower caregivers in the early identification of DLD. AIMS: To test the predictive relationship between parent-reported early indicators and the likelihood of children meeting diagnostic criteria for DLD at 10 years of age as determined by standardized assessment measures in a population-based sample. METHODS: Data were leveraged from the prospective Raine Study (n = 1626 second-generation children: n = 104 with DLD; n = 1522 without DLD). These data were transformed into 11 predictor variables that reflect well-established early indicators of DLD from birth to 3 years, including if the child does not smile or interact with others, does not babble, makes only a few sounds, does not understand what others say, says only a few words, says words that are not easily understood, and does not combine words or put words together to make sentences. Family history (mother and father) of speech and language difficulties were also included as variables. Regression analyses were planned to explore the predictive relationship between this set of early indicator variables and likelihood of meeting DLD diagnostic criteria at 10 years. RESULTS: No single parent-reported indicator uniquely accounted for a significant proportion of children with DLD at 10 years of age. Further analyses, including bivariate analyses testing the predictive power of a cumulative risk index of combined predictors (odds ratio (OR) = 0.95, confidence interval (CI) = 0.85-1.09, p = 0.447) and the moderating effect of sex (OR = 0.89, CI = 0.59-1.32, p = 0.563) were also non-significant. CONCLUSIONS: Parent reports of early indicators of DLD are well-intentioned and widely used. However, data from the Raine Study cohort suggest potential retrospective reporting bias in previous studies. We note that missing data for some indicators may have influenced the results. Implications for the impact of using early indicators as evidence to inform early identification of DLD are discussed. WHAT THIS PAPER ADDS: What is already known on the subject DLD is a relatively common childhood condition; however, children with DLD are under-identified and under-served. Individual variability in early childhood makes identification of children at risk of DLD challenging. A range of 'red flags' in communication development are promoted through speech pathology regulatory bodies and developmental services to assist parents to identify if their child should access services. What this paper adds to the existing knowledge No one parent-reported early indicator, family history or a cumulation of indicators predicted DLD at 10 years in the Raine study. Sex (specifically, being male) did not moderate an increased risk of DLD at 10 years in the Raine study. Previous studies reporting on clinical samples may be at risk of retrospective reporting bias. What are the potential or actual clinical implications of this work? The broad dissemination and use of 'red flags' is well-intentioned; however, demonstrating 'red flags' alone may not reliably identify those who are at later risk of DLD. Findings from the literature suggest that parent concern may be complemented with assessment of linguistic behaviours to increase the likelihood of identifying those who at risk of DLD. Approaches to identification and assessment should be considered alongside evaluation of functional impact to inform participation-based interventions.

Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits.

BACKGROUND: The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta-genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). METHODS: We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months), and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism-based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models. RESULTS: Early-life vocabulary size was modestly heritable (SNP-h2 = 0.08-0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (rg = -0.74), highlighting developmental heterogeneity. CONCLUSIONS: The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.

Categorical versus dimensional structure of autism spectrum disorder: A multi-method investigation.

Background: A key question for any psychopathological diagnosis is whether the condition is continuous or discontinuous with typical variation. The primary objective of this study was to use a multi-method approach to examine the broad latent categorical versus dimensional structure of autism spectrum disorder (ASD). Method: Data were aggregated across seven independent samples of participants with ASD, other neurodevelopmental disorders (NDD), and non-ASD/NDD controls (aggregate Ns = 512-16,755; ages 1.5-22). Scores from four distinct phenotype measures formed composite "indicators" of the latent ASD construct. The primary indicator set included eye gaze metrics from seven distinct social stimulus paradigms. Logistic regressions were used to combine gaze metrics within/across paradigms, and derived predicted probabilities served as indicator values. Secondary indicator sets were constructed from clinical observation and parent-report measures of ASD symptoms. Indicator sets were submitted to taxometric- and latent class analyses. Results: Across all indicator sets and analytic methods, there was strong support for categorical structure corresponding closely to ASD diagnosis. Consistent with notions of substantial phenotypic heterogeneity, the ASD category had a wide range of symptom severity. Despite the examination of a large sample with a wide range of IQs in both genders, males and children with lower IQ were over-represented in the ASD category, similar to observations in diagnosed cases. Conclusions: Our findings provide strong support for categorical structure corresponding closely to ASD diagnosis. The present results bolster the use of well-diagnosed and representative ASD groups within etiologic and clinical research, motivating the ongoing search for major drivers of the ASD phenotype. Despite the categorical structure of ASD, quantitative symptom measurements appear more useful for examining relationships with other factors.

The first six months of life: A systematic review of early markers associated with later autism.

There is now good evidence that behavioural signs of autism spectrum conditions (autism) emerge over the first two years of life. Identifying clear developmental differences early in life may facilitate earlier identification and intervention that can promote longer-term quality of life. Here we present a systematic review of studies investigating behavioural markers of later autism diagnosis or symptomology taken at 0-6 months. The following databases were searched for articles published between 01/01/2000 and 15/03/2022: Embase, Medline, Scopus, PubMed, PsycINFO, CINAHL, Web of Science and Proquest. Twenty-five studies met inclusion criteria: assessment of behaviour at 0-6 months and later assessment of autism symptomology or diagnosis. Studies examined behaviours of attention, early social and communication behaviours, and motor behaviours, as well as composite measures. Findings indicated some evidence of measures of general attention, attention to social stimuli, and motor behaviours associated with later autism diagnosis or symptomology. Findings were inconsistent regarding social and communication behaviours, with a lack of repeated or validated measures limiting drawing firm conclusions. We discuss implications of the findings and suggest recommendations for future research.

Neurodevelopmental outcomes in children after prenatal marijuana exposure.

BACKGROUND: The effect of prenatal marijuana exposure (PME) on child neurodevelopment remains poorly understood. Prior studies have demonstrated inconsistent results. OBJECTIVES: This study evaluated the association between PME and neuropsychological test scores in late childhood and early adulthood, accounting for a wide range of parental characteristics. METHODS: This study evaluated participants from the Raine Study, a cohort of 2868 children born between 1989 and 1992. Children whose mothers provided information on marijuana use during pregnancy were included. The primary outcome was the Clinical Evaluation of Language Fundamentals (CELF) at age 10. Secondary outcomes included the Peabody Picture Vocabulary Test (PPVT), Child Behaviour Checklist (CBCL), McCarron Assessment of Neuromuscular Development (MAND), Coloured Progressive Matrices (CPM), Symbol Digit Modality Test (SDMT) and Autism Spectrum Quotient (AQ) scores. Exposed and unexposed children were matched by propensity score using optimal full matching. Missing covariate data were imputed using multiple imputation. Inverse probability of censoring weighting (IPCW) was used to adjust for missing outcome data. Linear regression within matched sets, adjusted by IPCW, evaluated score differences between exposed and unexposed children. As a secondary analysis, modified Poisson regression, adjusted by match weights and IPCW, evaluated the risk of clinical deficit in each outcome following PME. RESULTS: Of the 2804 children in this cohort, 285 (10.2%) had PME. After optimal full matching and IPCW, exposed children scored similarly on CELF Total (-0.33 points, 95% confidence interval [CI] -4.71, 4.05), Receptive (+0.65 points, 95% CI -4.08, 5.38) or Expressive (-0.53 points, 95% CI -5.07, 4.02). PME was not associated with secondary outcomes or risks of clinical deficit in any neuropsychological assessments. CONCLUSIONS: After adjusting for sociodemographic and clinical covariates, PME was not associated with worse neuropsychological test scores at age 10 or autistic traits at 19-20.

Arriving at the empirically based conceptualization of restricted and repetitive behaviors: A systematic review and meta-analytic examination of factor analyses.

An empirically based understanding of the factor structure of the restricted and repetitive behaviors (RRB) domain is a prerequisite for interpreting studies attempting to understand the correlates and mechanisms underpinning RRB and for measurement development. Therefore, this study aimed to conduct a systematic review and meta-analysis of RRB factor analytic studies. Sets of meta-analyses were performed to examine (a) the factor structure of individual RRB instruments, (b) associations between RRB subdomains across instruments, and (c) the association between RRB factors and other variables. Searches for peer-reviewed articles evaluating the factor structure of the RRB domain were performed in PsycINFO (Ovid), Medline (Ovid), and Embase (Ovid). No age, measurement, or informant-type limits were imposed. Quality and risk of bias for individual studies were assessed using relevant COSMIN sections. Among the 53 studies retained for review, 41 examined RRB factor structures among individuals with autism spectrum disorder (ASD) and 12 among non-ASD samples. Meta-analysis of factor correlations provided evidence that the RRB domain encompasses the following eight specific factors: repetitive motor behaviors, insistence on sameness, restricted interests, unusual interests, sensory sensitivity, and repetitive, stereotyped language. Although interrelated, RRB factors were distinct, showing a unique pattern of associations with demographic, cognitive, and clinical correlates. Meta-analyses of the associations between RRB factors and specific correlates, specifically adaptive functioning and communication impairments, should be considered preliminary due to the limited number of studies. Despite limitations, this review provides important insights into the factor structure of the RRB domain and highlights critical conceptual, measurement, and methodological limitations of the current research that will need to be addressed in order to improve our understanding of RRB.

Parent-Child Interactions May Help to Explain Relations Between Parent Characteristics and Clinically Observed Child Autistic Behaviours.

The importance of supporting parent-child interactions has been noted in the context of prodromal autism, but little consideration has been given to the possible contributing role of parental characteristics, such as psychological distress. This cross-sectional study tested models in which parent-child interaction variables mediated relations between parent characteristics and child autistic behaviour in a sample of families whose infant demonstrated early signs of autism (N = 103). The findings suggest that associations between parent characteristics (psychological distress; aloofness) and child autistic behaviours may be mediated by the child's inattentiveness or negative affect during interactions. These findings have important implications in developing and implementing interventions in infancy which target the synchrony of parent-child interaction with the goal to support children's social communication development.

Interactions between the lipidome and genetic and environmental factors in autism.

Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.

Reliability of the Commonly Used and Newly-Developed Autism Measures.

PURPOSE: The aim of the present study was to compare scale and conditional reliability derived from item response theory analyses among the most commonly used, as well as several newly developed, observation, interview, and parent-report autism instruments. METHODS: When available, data sets were combined to facilitate large sample evaluation. Scale reliability (internal consistency, average corrected item-total correlations, and model reliability) and conditional reliability estimates were computed for total scores and for measure subscales. RESULTS: Generally good to excellent scale reliability was observed for total scores for all measures, scale reliability was weaker for RRB subscales of the ADOS and ADI-R, reflecting the relatively small number of items for these measures. For diagnostic measures, conditional reliability tended to be very good (> 0.80) in the regions of the latent trait where ASD and non-ASD developmental disability cases would be differentiated. For parent-report scales, conditional reliability of total scores tended to be excellent (> 0.90) across very wide ranges of autism symptom levels, with a few notable exceptions. CONCLUSIONS: These findings support the use of all of the clinical observation, interview, and parent-report autism symptom measures examined, but also suggest specific limitations that warrant consideration when choosing measures for specific clinical or research applications.

Estimated Therapy Costs and Downstream Cost Consequences of iBASIS-Video Interaction to Promote Positive Parenting Intervention vs Usual Care Among Children Displaying Early Behavioral Signs of Autism in Australia.

Importance: The growing global prevalence of autism spectrum disorder (ASD) is associated with increasing costs for support services. Ascertaining the effects of a successful preemptive intervention for infants showing early behavioral signs of autism on human services budgets is highly policy relevant. Objective: To estimate the net cost impact of the iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP) intervention on the Australian government. Design, Setting, and Participants: Infants (aged 12 months) showing early behavioral indicators of autism were recruited through community settings into the multicenter Australian iBASIS-VIPP randomized clinical trial (RCT), a 5- to 6-month preemptive parent-mediated intervention, between June 9, 2016, and March 30, 2018, and were followed up for 18 months to age 3 years. This economic evaluation, including cost analysis (intervention and cost consequences) and cost-effectiveness analyses of iBASIS-VIPP compared with usual care (treatment as usual [TAU]), modeled outcomes observed at age 3 through to 12 years (13th birthday) and was conducted from April 1, 2021, to January 30, 2023. Data analysis was conducted from July 1, 2021, to January 29, 2023. Exposures: iBASIS-VIPP intervention. Main Outcomes and Measures: To project the diagnostic trajectory and associated disability support costs drawing on the Australian National Disability Insurance Scheme (NDIS), the main outcome was the differential treatment cost of iBASIS-VIPP plus TAU vs TAU and disability-related government costs modeled to age 12 years, using a clinical diagnosis of ASD and developmental delay (with autism traits) at 3 years. Costs were calculated in Australian dollars and converted to US dollars. Economic performance was measured through the following: (1) differential net present value (NPV) cost (iBASIS-VIPP less TAU), (2) investment return (dollars saved for each dollar invested, taking a third-party payer perspective), (3) break-even age when treatment cost was offset by downstream cost savings, and (4) cost-effectiveness in terms of the differential treatment cost per differential ASD diagnosis at age 3 years. Alternate values of key parameters were modeled in 1-way and probabilistic sensitivity analysis, the latter identifying the likelihood of an NPV cost savings. Results: Of the 103 infants enrolled in the iBASIS-VIPP RCT, 70 (68.0%) were boys. Follow-up data at age 3 years were available for 89 children who received TAU (44 [49.4%]) or iBASIS-VIPP (45 [50.6%]) and were included in this analysis. The estimated mean differential treatment cost was A $5131 (US $3607) per child for iBASIS-VIPP less TAU. The best estimate of NPV cost savings was A $10 695 (US $7519) per child (discounted at 3% per annum). For each dollar invested in treatment, a savings of A $3.08 (US $3.08) was estimated; the break-even cost occurred at age 5.3 years (approximately 4 years after intervention delivery). The mean differential treatment cost per lower incident case of ASD was A $37 181 (US $26 138). We estimated that there was an 88.9% chance that iBASIS-VIPP would deliver a cost savings for the NDIS, the dominant third-party payer. Conclusions and Relevance: The results of this study suggest that iBASIS-VIPP represents a likely good-value societal investment for supporting neurodivergent children. The estimated net cost savings were considered conservative, as they covered only third-party payer costs incurred by the NDIS and outcomes were modeled to just age 12 years. These findings further suggest that preemptive interventions may be a feasible, effective, and efficient new clinical pathway for ASD, reducing disability and the costs of support services. Long-term follow-up of children receiving preemptive intervention is needed to confirm the modeled results.

Language and reading impairments are associated with increased prevalence of non-right-handedness.

Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6-19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases  = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06-1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.

Parent-child interaction and developmental outcomes in children with typical and elevated likelihood of autism.

BACKGROUND: Early parent-child interactions have a critical impact on the developmental outcomes of the child. It has been reported that infants with a family history of autism and their parents may engage in different patterns of behaviours during interaction compared to those without a family history of autism. This study investigated the association of parent-child interactions with child developmental outcomes of those with typical and elevated likelihood of autism. METHOD: This longitudinal study investigated the relationship between global attributes of parent-child interaction and the developmental outcomes of infant siblings with elevated likelihood (EL: n = 29) or typical likelihood (TL: n = 39) of developing autism. Parent-child interactions were recorded during a session of free-play when the infants were six months of age. Developmental assessments were carried out when the children were 12 and 24 months of age. RESULTS: The intensity of mutuality was significantly higher in the TL group than in the EL group, and developmental outcomes were poorer in the EL group when compared to the TL group. Positive associations between parent-child interaction scores at six months and developmental outcomes at 12 months were observed only in the TL group. However, in the EL group, higher levels of infant positive affect and attentiveness paid to the caregiver is associated with lower autism symptoms. Due to the sample size and design of the study, the findings must be viewed as indicative. CONCLUSION: This preliminary investigation demonstrated differences in the association between parent-child interaction quality and developmental outcomes for children with typical and elevated likelihood for autism. Future studies should combine micro-analytic and macro-analytic approaches to parent-child interaction to further examine the nature of this relationship.