Genome-wide detection of tandem DNA repeats that are expanded in autism.

Tandem DNA repeats vary in the size and sequence of each unit (motif). When expanded, these tandem DNA repeats have been associated with more than 40 monogenic disorders1. Their involvement in disorders with complex genetics is largely unknown, as is the extent of their heterogeneity. Here we investigated the genome-wide characteristics of tandem repeats that had motifs with a length of 2-20 base pairs in 17,231 genomes of families containing individuals with autism spectrum disorder (ASD)2,3 and population control individuals4. We found extensive polymorphism in the size and sequence of motifs. Many of the tandem repeat loci that we detected correlated with cytogenetic fragile sites. At 2,588 loci, gene-associated expansions of tandem repeats that were rare among population control individuals were significantly more prevalent among individuals with ASD than their siblings without ASD, particularly in exons and near splice junctions, and in genes related to the development of the nervous system and cardiovascular system or muscle. Rare tandem repeat expansions had a prevalence of 23.3% in children with ASD compared with 20.7% in children without ASD, which suggests that tandem repeat expansions make a collective contribution to the risk of ASD of 2.6%. These rare tandem repeat expansions included previously undescribed ASD-linked expansions in DMPK and FXN, which are associated with neuromuscular conditions, and in previously unknown loci such as FGF14 and CACNB1. Rare tandem repeat expansions were associated with lower IQ and adaptive ability. Our results show that tandem DNA repeat expansions contribute strongly to the genetic aetiology and phenotypic complexity of ASD.

Disentangling global and domain-level adaptive behavior trajectories among children with autism spectrum disorder.

BACKGROUND: Heterogeneity in adaptive behavior abilities among people with autism spectrum disorder (ASD) is expressed not only as uneven levels of impairment across domains, but also in the developmental trajectories of adaptive skills. We studied the question of whether, after accounting for global adaptive behavior development, we find evidence of heterogeneity in the trajectories of specific domains of adaptive behavior. METHODS: A sample of 504 children with ASD was obtained by combining data from two independent natural history studies conducted in North America. We used a factor of curves model to explain growth between 36 and 138 months in Vineland Adaptive Behavior Scales, Second Edition (VABS) age equivalents as a function of domain-specific and global growth processes. RESULTS: The domain-specific trajectories in all three domains (Communication, Daily Living Skills, and Socialization) reflected impairment relative to age expectations as well as slower-than-expected growth with age, and the parameters of these trajectories were moderately-to-strongly correlated across domains. The global adaptive behavior trajectory had an initial (36-41 months of age) developmental level of about 22 age-equivalent months, and eventually slowed after initially increasing by about 6 months each year. The global trajectory accounted for the majority of variance in the domain-level processes; however, additional variance remained (14%-38%) in the domain-level intercepts, slopes, and quadratic processes. CONCLUSIONS: These results extend existing theoretical and empirical support for the hierarchical structure of adaptive behavior to include its development over time in clinical samples of children with ASD. A latent global trajectory may be sufficient to describe the growth of adaptive behavior in children with ASD; however, the remaining domain-specific variability after accounting for global adaptive behavior development allows for the possibility that differential effects of intervention on specific domains may be possible and detectable.

Continuity of trajectories of autism symptom severity from infancy to childhood.

BACKGROUND: Behavioral symptom trajectories are informative of the development of young children at increased likelihood for autism spectrum disorder (ASD). METHODS: Developmental trajectories of early signs were examined in a cohort of siblings of children diagnosed with ASD (n = 502) from 6 to 18 months using the Autism Observation Scale for Infants (AOSI), and from 18 months to 5-7 years using the Autism Diagnostic Observation Schedule (ADOS). Diagnostic outcomes for ASD at age 3 confirmed diagnosis for 137 children. We further analyzed the conditional probability of a switch from a trajectory measured with the AOSI to a trajectory measured with the ADOS as well as predictors from age 6 months. RESULTS: We derived three early trajectories of behavioral signs ("Low," "Intermediate," and "Increasing") from 6 to 18 months using the AOSI. We then derived three similar, distinct trajectories for the evolution of symptom severity between 18 and 60-84 months of age (Low, Intermediate, Increasing) using the ADOS. Globally, the Low trajectory included children showing fewer ASD signs or symptoms and the Increasing trajectory included children showing more severe symptoms. We also found that most children in the Low AOSI trajectory stayed in the corresponding ADOS trajectory, whereas children in an Increasing AOSI trajectory tended to transition to an Intermediate or Increasing ADOS trajectory. Developmental measures taken at 6 months (early signs of ASD, Fine Motor, and Visual Reception skills) were predictive of trajectory membership. CONCLUSIONS: Results confirm substantial heterogeneity in the early emergence of ASD signs in children at increased likelihood for ASD. Moreover, we showed that the way those early behavioral signs emerge in infants is predictive of later symptomatology. Results yield clear clinical implications, supporting the need to repeatedly assess infants at increased likelihood for ASD as this can be highly indicative of their later development and behavior.

Longitudinal associations between early childhood irritability and adolescent depression symptoms in autistic children are mediated by peer relationships but not educational engagement.

In the general population, irritability is associated with later depression. Despite irritability being more prevalent in autistic children, the long-term sequelae are not well explored. We tested whether irritability in early childhood predicted depression symptoms in autistic adolescents, and whether associations could be explained by difficulties in peer relationships and lower educational engagement. Analyses tested the longitudinal associations between early childhood irritability (ages 3-5) and adolescent depression symptoms (age 14) in a prospective inception cohort of autistic children (N = 390), followed from early in development shortly after they received a clinical diagnosis. Mediators were measured in mid-childhood (age 10) by a combination of measures, from which latent factors for peer relationships and educational engagement were estimated. Results showed early childhood irritability was positively associated with adolescent depression symptoms, and this association remained when adjusting for baseline depression. A significant indirect pathway through peer relationships was found, which accounted for around 13% of the association between early childhood irritability and adolescent depression, suggesting peer problems may partially mediate the association between irritability and later depression. No mediation effects were found for education engagement. Results highlight the importance of early screening and intervention for co-occurring irritability and peer problems in young autistic children.

Developmental cascades between insistence on sameness behaviour and anxiety symptoms in autism spectrum disorder.

Autistic children experience high rates of anxiety. Insistence on sameness behaviour (IS) is a core feature of autism that appears correlated with anxiety severity. The objective of this study was to examine the longitudinal relations between anxiety and IS in autistic children using a developmental cascade model. A longitudinal cohort of 421 autistic children was followed between 4 and 11 years of age. Anxiety was quantified using items from the Anxiety Problems subscale of the Child Behavior Checklist; sameness behaviours were measured using the Repetitive Behavior Scale-Revised, Ritualistic/sameness subscale (both parent-report measures). Structural equation modelling was used to examine the longitudinal and directional associations between anxiety and IS at four time-points, through cross-lagged panel models (CLPM) with and without a random-intercepts component (RI-CLPM). Both the CLPM and the RI-CLPM had good fit. Significant directional associations were detected whereby elevated or increasing IS preceded elevated or increasing anxiety symptoms 1-2 years later, respectively. Stable baseline tendencies towards anxiety and IS as between-person traits (intercepts) were strongly associated (standardized estimate = 0.69, p < 0.001). The magnitude of the cross-sectional associations between anxiety and IS appeared to lessen with age. IS and anxiety symptoms in autism are closely related. They appear to be shared traits that mirror each other particularly in younger children. Increasing IS may be a sign of emerging future anxiety. Interventions that target IS to reduce or prevent anxiety amongst school-aged autistic children merit further study.

Predictors of language regression and its association with subsequent communication development in children with autism.

BACKGROUND: Language regression, broadly defined as the loss of acquired language skills in early childhood, is a distinctive feature of autism. Little is known about the factors underlying regression or the prognosis of children who exhibit regression. We examine potential predictors of language regression and test its association with language development in a prospective longitudinal sample of children with autism spectrum disorder (ASD) from diagnosis to age 10 years. METHODS: We analysed data from Pathways in ASD, a prospective longitudinal study of 421 children enrolled around the time of an autism diagnosis between 2 and 5 years. Autism Diagnostic Interview-Revised data were available for 408 children, of whom 90 (22%) were classified as having language regression. RESULTS: Demographic and other health factors including caregiver education, family income, child sex, reported seizures, and age of enrolment did not differ between children with and without language regression. Children with language regression walked earlier and attained first words sooner than those without regression. However, both groups attained phrase speech at comparable ages. Those with regression exhibited greater delays in expressive and receptive communication over the follow-up period, although this effect was attenuated when accounting for baseline differences in motor and cognitive ability. Overall, those with language regression continued to exhibit expressive but not receptive communication delay compared to those without regression. Communication trajectories were heterogeneous to age 10 years, irrespective of regression status. CONCLUSIONS: Although language regression can be alarming, our findings confirm that its occurrence does not necessarily foreshadow worse developmental outcomes relative to those without regression. Although a discrepancy in age-equivalent communication skills may persist, this can be expected to be of less practical importance with rising average levels of skills. Future studies need to account for the significant variability in language trajectories by considering factors beyond developmental regression.

Middle-childhood executive functioning mediates associations between early-childhood autism symptoms and adolescent mental health, academic and functional outcomes in autistic children.

BACKGROUND: Executive functioning (EF) varies in children with autism spectrum disorder (ASD) and is associated with clinical symptoms, academic, and adaptive functioning. Here, we examined whether middle-childhood EF mediates associations between early-childhood autism symptoms and adolescent outcomes in children with ASD. METHODS: The Pathways in ASD Cohort comprising children recruited at the time of ASD diagnosis (at 2-4 years-of-age) and followed prospectively across eight subsequent timepoints over ~10 years was used. A subset of Pathways participants (n = 250) with Behavior Rating Inventory of Executive Function (BRIEF)-Parent Form data from at least one timepoint when participants were school-aged was analyzed. A mediation framework was used to examine whether BRIEF-measured EF across age 7-10 years (middle-childhood) mediated associations between early-childhood autism symptoms (measured using the parent-report Social Responsiveness Scale across age 2-6 years) and clinical, academic, and functional outcomes, indexed at age >10-11.8 years (early-adolescence) using the Child Behavior Checklist (CBCL)-Internalizing and Externalizing Scales, Academic Performance from the Teacher's Report Form, and Vineland Adaptive Behavior Scales. Models were rerun substituting clinician-rated and teacher-rated measures, where possible. RESULTS: Mediation models indicated a significant indirect effect of middle-childhood EF on associations between early-childhood autism symptoms and externalizing behavior, academic performance, or adaptive functioning in early adolescence; kappa squared (κ2 ) effect sizes ranged from large to small. Model findings were stable across raters. Middle-childhood EF did not mediate associations between early-childhood autism symptoms and adolescent internalizing behavior. CONCLUSIONS: Among children with an ASD diagnosis, middle-childhood EF may be one pathway through which early-childhood autism symptoms influence a variety of outcomes in early-adolescence. An experimental study targeting middle-childhood EF to improve adolescent academic, emotional/behavioral, and adaptive functioning is needed to evaluate the clinical meaningfulness of these findings.

Precursors of self-regulation in infants at elevated likelihood for autism spectrum disorder.

Research concerning temperament in children and adults with autism spectrum disorder (ASD) has suggested a consistent profile of low positive affect, high negative affect, and low regulation (Visser et al., 2016). One area receiving less attention is individual differences among children diagnosed with ASD. The primary objective of this study was to use a person-centered approach to explore heterogeneity of early temperament precursors of regulation in a large sample of infants with elevated familial likelihood of ASD. Early precursors of regulation included temperament assessed at 6, 12, and 24 months whereas outcome measures were diagnosis of ASD, cognitive ability and adaptive behavior at 36 months. Participants included 176 low-likelihood and 473 elevated-likelihood infants, 129 of whom were diagnosed with ASD at 3 years. Results supported a three-profile solution: a well-regulated profile (high positive affect and high attentional focus and shifting), a low attention focus profile (higher attentional shifting compared to attentional focus), and a low attention shifting profile (higher attentional focus compared to attentional shifting). A higher proportion of children diagnosed with ASD were classified into the low attention shifting profile. Furthermore, children with the well-regulated profile were differentiated from the other profiles by a pattern of higher social competence and lower dysregulation whereas children with the low attention focus profile were distinguished from the other profiles by higher cognitive ability at 3 years. The findings indicate that the combination of early positive affect with attention measures may provide an enhanced tool for prediction of self-regulation and later outcomes.

Behavioral and physiological differences during an emotion-evoking task in children at increased likelihood for autism spectrum disorder.

Literature examining emotional regulation in infants with autism spectrum disorder (ASD) has focused on parent report. We examined behavioral and physiological responses during an emotion-evoking task designed to elicit emotional states in infants. Infants at an increased likelihood for ASD (IL; have an older sibling with ASD; 96 not classified; 29 classified with ASD at age two) and low likelihood (LL; no family history of ASD; n = 61) completed the task at 6, 12, and 18 months. The main findings were (1) the IL-ASD group displayed higher levels of negative affect during toy removal and negative tasks compared to the IL non-ASD and LL groups, respectively, (2) the IL-ASD group spent more time looking at the baseline task compared to the other two groups, and (3) the IL-ASD group showed a greater increase in heart rate from baseline during the toy removal and negative tasks compared to the LL group. These results suggest that IL children who are classified as ASD at 24 months show differences in affect, gaze, and heart rate during an emotion-evoking task, with potential implications for understanding mechanisms related to emerging ASD.

Co-occurring trajectories of anxiety and insistence on sameness behaviour in autism spectrum disorder.

BACKGROUND: Children with autism spectrum disorder (ASD) have increased susceptibility to anxiety disorders. Variation in a common ASD symptom, insistence on sameness behaviour, may predict future anxiety symptoms. AIMS: To describe the joint heterogeneous longitudinal trajectories of insistence on sameness and anxiety in children with ASD and to characterise subgroups at higher risk for anxiety. METHOD: In a longitudinal ASD cohort (n = 421), insistence on sameness behaviour was measured using the Autism Diagnostic Interview-Revised at approximately ages 3, 6 and 11 years. Anxiety was quantified at 8 time points between ages 3 and 11 years using the Child Behavior Checklist (CBCL) (parent report). Clusters of participants following similar trajectories were identified using group-based and joint trajectory modelling. RESULTS: Three insistence on sameness trajectories were identified: (a) 'low-stable' (41.7% of participants), (b) 'moderate-increasing' (52.0%) and (c) 'high-peaking' (i.e. increasing then stabilising/decreasing behaviour) (6.3%). Four anxiety trajectories were identified: (a) 'low-increasing' (51.0%), (b) 'moderate-decreasing' (16.2%), (c) 'moderate-increasing' (19.6%) and (d) 'high-stable' (13.1%). Of those assigned to the 'high-peaking' insistence on sameness trajectory, 95% jointly followed an anxiety trajectory that surpassed the threshold for clinical concern (T-score >65) by middle childhood (anxiety trajectories 3 or 4). Insistence on sameness and anxiety trajectories were similar in severity and direction for 64% of the sample; for 36%, incongruous patterns were seen (e.g. decreasing anxiety and increasing insistence on sameness). CONCLUSIONS: The concurrent assessment of insistence on sameness behaviour and anxiety in ASD may help in understanding current symptom profiles and anticipating future trajectories. High preschool insistence on sameness in particular may be associated with elevated current or future anxiety symptoms.

Symptom trajectories in the first 18 months and autism risk in a prospective high-risk cohort.

BACKGROUND: Although early autism spectrum disorder (ASD) detection strategies tend to focus on differences at a point in time, behavioral symptom trajectories may also be informative. METHODS: Developmental trajectories of early signs of ASD were examined in younger siblings of children diagnosed with ASD (n = 499) and infants with no family history of ASD (n = 177). Participants were assessed using the Autism Observation Scale for Infants (AOSI) from 6 to 18 months. Diagnostic outcomes were determined at age 3 years blind to previous assessments. RESULTS: Semiparametric group-based modeling using AOSI scores identified three distinct trajectories: Group 1 ('Low', n = 435, 64.3%) was characterized by a low level and stable evolution of ASD signs, group 2 ('Intermediate', n = 180, 26.6%) had intermediate and stable levels, and group 3 ('Inclining', n = 61, 9.3%) had higher and progressively elevated levels of ASD signs. Among younger siblings, ASD rates at age 3 varied by trajectory of early signs and were highest in the Inclining group, membership in which was highly specific (94.5%) but poorly sensitive (28.5%) to ASD. Children with ASD assigned to the inclining trajectory had more severe symptoms at age 3, but developmental and adaptive functioning did not differ by trajectory membership. CONCLUSIONS: These prospective data emphasize variable early-onset patterns and the importance of a multipronged approach to early surveillance and screening for ASD.

Children's Sleep During COVID-19: How Sleep Influences Surviving and Thriving in Families.

OBJECTIVE: The COVID-19 pandemic has the potential to disrupt the lives of families and may have implications for children with existing sleep problems. As such, we aimed to: (1) characterize sleep changes during the COVID-19 pandemic in children who had previously been identified as having sleep problems, (2) identify factors contributing to sleep changes due to COVID-19 safety measures, and (3) understand parents' and children's needs to support sleep during the pandemic. METHODS: Eighty-five Canadian parents with children aged 4-14 years participated in this explanatory sequential, mixed-methods study using an online survey of children's and parents' sleep, with a subset of 16 parents, selected based on changes in their children's sleep, participating in semi-structured interviews. Families had previously participated in the Better Nights, Better Days (BNBD) randomized controlled trial. RESULTS: While some parents perceived their child's sleep quality improved during the COVID-19 pandemic (14.1%, n = 12), many parents perceived their child's sleep had worsened (40.0%, n = 34). Parents attributed children's worsened sleep to increased screen time, anxiety, and decreased exercise. Findings from semi-structured interviews highlighted the effect of disrupted routines on sleep and stress, and that stress reciprocally influenced children's and parents' sleep. CONCLUSIONS: The sleep of many Canadian children was affected by the first wave of the COVID-19 pandemic, with the disruption of routines influencing children's sleep. eHealth interventions, such as BNBD with modifications that address the COVID-19 context, could help families address these challenges.

Assessment of Autism Symptoms From 6 to 18 Months of Age Using the Autism Observation Scale for Infants in a Prospective High-Risk Cohort.

The objectives were to characterize behavioral signs of autism spectrum disorder (ASD) in younger siblings of diagnosed children (high-risk; HR) and examine classification features of the Autism Observation Scale for Infants (AOSI). Participants (501 HR and 180 low-risk [LR]) were assessed between 6 and 18 months using the AOSI and at age 3 for ASD diagnoses. Total AOSI scores differentiated HR infants later diagnosed with ASD starting at 12 months. ROC analyses identified 12- and 18-month cutoff scores associated with 0.52 sensitivity and 0.74 specificity and 0.73 sensitivity and 0.65 specificity, respectively. Although classification accuracy does not support use as a standalone screen, the AOSI identifies features associated with ASD starting at 6 months and differentiates HR infants with ASD by 12 months.

Profiles and Predictors of Academic and Social School Functioning among Children with Autism Spectrum Disorder.

Objective: The purpose of the study was to identify profiles and predictors of academic and social functioning in a sample of school-age children with autism spectrum disorder.Method: The study included 178 children (88% boys, 75% Caucasian, ages 10-11) who completed a standardized measure of academic skills and whose teachers completed a related measure. Measures of both academic and social performance were used to construct profiles of school functioning. Measures of language, nonverbal IQ, autism symptom severity, behavior difficulties, and early social-communication skills between ages 3 and 4 were used to examine predictors of profile membership. Latent Profile Analysis was used to identify and describe profiles of children's academic and social school functioning. Profile membership was then regressed on each of the predictors using a series of multinomial logistic regression models. Finally, a multivariate model that included all significant predictors was built to examine the best fitting constellation of profile predictors.Results: Four profiles - reflecting variation in academic achievement, school engagement, socialization skills, pragmatic language use, and social relationships - captured the diverse school functioning outcomes of the sample. Profile membership was predicted by variation in imitation, responding to joint attention, language ability, nonverbal IQ and behavior difficulties between ages 3 and 4 years. However, in a multivariate model, only language and behavior difficulties emerged as significant predictors.Conclusions: A person-centered approach to targeted early intervention that reduces behavior difficulties and enhances social-communication and language abilities may prove especially important for the promotion of later academic and social functioning at school.

Preschool autism services: A tale of two Canadian provinces and the implications for policy.

For children with autism spectrum disorder (ASD), a lifelong neurodevelopmental condition, assessment and treatment services vary widely across Canada-potentially creating inequities. To highlight this, the Preschool Autism Treatment Impact study compared children's services and outcomes in New Brunswick (NB) and Nova Scotia (NS). Diagnostic practices, service delivery models, wait times, and treatment approaches differed, as did children's 1-year outcomes and costs for families and the public sector. Considering NB and NS strengths, we suggest that an optimal system would include: rapid access to high-quality diagnostic and intervention services; adherence to research-informed practice guidelines; interventions to enhance parents' skills and self-efficacy; and measures to minimize financial burdens for families. Our results also suggest that provinces/territories must do more to ensure equitable access to effective services, including sharing and reporting on national comparative data. Canadian children with ASD deserve access to effective and consistent services, no matter where they live.

Predictors of longer-term development of expressive language in two independent longitudinal cohorts of language-delayed preschoolers with Autism Spectrum Disorder.

BACKGROUND: Studies estimate that 30% of individuals with autism are minimally verbal. Understanding what factors predict longer-term expressive development in children with language delays is critical to inform identification and treatment of those at-risk for persistent language impairments. The present study examined predictors of expressive language development in language-delayed preschoolers followed through later school-age and young adulthood. METHODS: Children using single words or less on the Autism Diagnostic Observation Schedule (ADOS) at approximately 3 years old were drawn from the Early Diagnosis (EDX) and Pathways in ASD longitudinal cohorts. Age-3 predictors of Age-19 ADOS language level were identified using Classification and Regression Trees (CART) in the EDX sample. Linear mixed models examined the effects of CART-identified predictors on Vineland expressive communication (VExp) trajectories from Age-3 to Age-19. The same linear mixed models were examined in the Pathways sample, identifying predictors of VExp from ages 3 to 10.5 years. RESULTS: Significantly delayed fine motor skills (T-score < 20) was the strongest CART predictor of Age-19 language. In the linear mixed models, time, Age-3 fine motor skills and initiation of joint attention (IJA) predicted VExp trajectories in the EDX sample, even when controlling for Age-3 visual receptive abilities. In the Pathways sample, time and Age-3 fine motor skills were significant predictors of VExp trajectories; IJA and cognitive skills were not significant predictors. CONCLUSIONS: Marked deficits in fine motor skills may be a salient proxy marker for identifying language-delayed children with ASD who are at risk for persistent language impairments. This finding adds to the literature demonstrating a relation between motor and language development in ASD. Investigating individual skill areas (e.g., fine motor and nonverbal problem-solving skills), rather than broader indices of developmental level (e.g., nonverbal IQ) may provide important cues to understanding longer-term language outcomes that can be targeted in early intervention.

The association between social emotional development and symptom presentation in autism spectrum disorder.

Understanding differences in social-emotional behavior can help identify atypical development. This study examined the differences in social-emotional development in children at increased risk of an autism spectrum disorder (ASD) diagnosis (infant siblings of children diagnosed with the disorder). Parents completed the Brief Infant-Toddler Social-Emotional Assessment (BITSEA) to determine its ability to flag children with later-diagnosed ASD in a high-risk (HR) sibling population. Parents of HR (n = 311) and low-risk (LR; no family history of ASD; n = 127) children completed the BITSEA when their children were 18 months old and all children underwent a diagnostic assessment for ASD at age 3 years. All six subscales of the BITSEA (Problems, Competence, ASD Problems, ASD Competence, Total ASD Score, and Red Flags) distinguished between those in the HR group who were diagnosed with ASD (n = 84) compared to non-ASD-diagnosed children (both HR-N and LR). One subscale (BITSEA Competence) differentiated between the HR children not diagnosed with ASD and the LR group. The results suggest that tracking early social-emotional development may have implications for all HR children, as they are at increased risk of ASD but also other developmental or mental health conditions.

Developmental trajectories of adaptive behavior in autism spectrum disorder: a high-risk sibling cohort.

BACKGROUND: Children with autism spectrum disorder (ASD) often experience impairments in adaptive behavior. METHODS: Developmental trajectories of adaptive behavior in ASD were examined in children from high-risk (siblings of children diagnosed with ASD, n = 403) and low-risk (no family history of ASD, n = 163) families. Children were assessed prospectively at 12, 18, 24, and 36 months of age using the Vineland Adaptive Behavior Scales and underwent a blind independent diagnostic assessment for ASD at 36 months of age. RESULTS: The semi-parametric group-based modeling approach using standard scores on the Adaptive Behavior Composite revealed three distinct developmental trajectories: (a) Group 1 (21.2% of sample) showed average performance at 12 months and a declining trajectory; (b) Group 2 (52.8% of the sample) showed average performance at 12 months with a slightly declining trajectory; and (c) Group 3 (26.0% of the sample) showed a higher level of adaptive behavior at 12 months and a stable trajectory. The Mullen Scales of Early Learning Early Learning Composite and the Autism Observation Scale for Infants total score at 6 and 12 months predicted trajectory membership. CONCLUSIONS: The results emphasize heterogeneous development associated with ASD and the need for interventions tailored to individual presentations.

Developmental Trajectories of Feeding Problems in Children with Autism Spectrum Disorder.

OBJECTIVE: Although feeding problems are a common concern in children with autism spectrum disorder (ASD), few longitudinal studies have examined their persistence over time. The purpose of this study was to examine the developmental progression of feeding problems across four time points in preschoolers with ASD. METHODS: Group-based trajectory analyses revealed four distinct trajectories of feeding problems in our sample (N = 396). RESULTS: The majority of children showed levels of feeding problems that were low from the outset and stable (Group 1; 26.3%) or moderate and declining over time (Group 2; 38.9%). A third group (26.5%) showed high levels of feeding problems as preschoolers that declined to the average range by school age. Few participants (8.3%) showed evidence of severe chronic feeding problems. Feeding problems were more highly correlated with general behavior problems than with autism symptom severity. CONCLUSIONS: Overall, our findings demonstrated that in our sample of children with ASD, most feeding problems remitted over time, but a small subgroup showed chronic feeding problems into school age. It is important to consider and assess feeding problems in ASD against the backdrop of typical development, as many children with ASD may show improvement with age.

Developmental functioning and symptom severity influence age of diagnosis in Canadian preschool children with autism.

BACKGROUND: Early diagnosis of autism spectrum disorder (ASD) is essential in most Canadian jurisdictions to access interventions that improve long-term child outcomes. Our main objective was to identify factors associated with timing of ASD diagnosis in five provinces across Canada. METHODS: Factors influencing age of diagnosis were assessed in the analyses of an inception cohort of children diagnosed with ASD between ages 2 and 5 years. We examined bivariate associations and using a series of multiple variable regression models, evaluated the unique contributions of developmental functioning, ASD symptoms and demographic variables. Children with known genetic abnormalities, or severe sensory or motor impairments interfering with assessment were excluded. RESULTS: Participants were 421 children (84.6% boys). The mean age of diagnosis was 38.2 months (SD=8.7), an average of 19 months after parents identified initial concerns. Factors associated with later diagnosis included more advanced language and cognitive skills, and higher levels of restricted repetitive behaviour symptoms. Child sex and family demographics were not associated with age of diagnosis. In regression analyses, language and cognitive skills accounted for 6.8% of variance in age of diagnosis and ASD symptoms contributed an additional 5.5%. Provincial site accounted for 4.0% of variance in age of diagnosis, independent of developmental skills and ASD symptoms. INTERPRETATION: Diagnosis of ASD occurred, on average, 19 months after parents' initial concerns. Language and cognitive skills, symptom severity and provincial site accounted for variation in age of ASD diagnosis in this Canadian cohort. Variable presentation across the developmental continuum must be considered in planning assessment services to ensure timely ASD diagnosis so that outcomes can be improved. Policy and practice leadership is also needed to reduce interprovincial variability.