Factors Associated with a Delayed Autism Spectrum Disorder Diagnosis in Children Previously Assessed on Suspicion of Autism.

This study aimed to investigate factors associated with a delayed autism spectrum (ASD) diagnosis when compared to children with either no or early ASD diagnosis. Among 893 children assessed for ASD before age 8, 39% had no ASD at baseline, of which 21% received a later ASD diagnosis. Autism symptoms, diagnostic history of other developmental disorders, cognitive ability, and socioeconomic factors were associated with delayed ASD. Autism Diagnostic Observation Schedule (ADOS) scores in delayed ASD fell between early and no ASD. Other developmental disorders, time and clinical trends like ADOS use and low parental education distinguished delayed and early ASD, whereas higher frequency of IQ < 70 at baseline and a diagnosis of emotional disorders during follow-up distinguished delayed and no ASD.

Time Trends in Diagnostics and Clinical Features of Young Children Referred on Suspicion of Autism: A Population-Based Clinical Cohort Study, 2000-2010.

The present study aimed to explore clinical trends in the period 2000-2010, along with discriminating clinical factors for autism spectrum disorder (ASD), in young children suspected of ASD. The following trends were observed: (1) a rise in referrals including an increase in referrals among language-abled children, (2) an increase in children assigned an ASD diagnosis after assessment, and (3) a decrease in Autism Diagnostic Observation Schedule total score. The distribution of ASD subtypes and IQ level did not change. Results suggest that a higher proportion of children with less severe autism symptoms were referred and diagnosed. Further, restricted and repetitive behaviors seemed to be a key discriminating factor when distinguishing between ASD and no-ASD children with a discordant symptom profile.

Autism and the right to education in the EU: policy mapping and scoping review of Nordic countries Denmark, Finland, and Sweden.

Introduction: The universal right to education for people with disabilities has been highlighted by the Universal Declaration on Human Rights and the Convention on the Rights of Persons with Disabilities. In this paper, we mapped policies addressing the right to education and special education needs of autistic children in Denmark, Sweden, and Finland. Methods: A policy path analysis was carried out using a scoping review as an underlying framework for data gathering. Policy mapping was performed independently by both lead authors to increase reliability. Results and discussion: The values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities have been closely translated into the respective education systems of the countries under study, offering special education needs services and support in mainstream education with the aim of including as many children into mainstream education as possible. Even though the education systems are comparable, the approaches between the countries under study are slightly different. Denmark and Sweden have passed several policies specifically geared towards special education needs, while Finland incorporates this more in general education policy. Conclusion: All countries under study have incorporated the values of the Universal Declaration of Human Rights and the Convention on the Rights of Persons with Disabilities in their respective education systems while emphasising the need to include as many children in the mainstream system as possible.

Syntax and Morphology in Danish-Speaking Children with Autism Spectrum Disorder.

The current study examined delays in syntax and morphology, and vocabulary, in autism spectrum disorder (ASD). Children ages 4-6 years with ASD (n = 21) and typical development (n = 21), matched on nonverbal mental age, completed five language tasks. The ASD group had significant delays in both syntax and morphology, and vocabulary measures, with significant within-group heterogeneity; furthermore, syntactic and morphological measures were impaired even for subgroups matched on vocabulary. Children in the ASD group without early language delay showed syntactic and morphological impairment, with intact performance on vocabulary and sentence repetition. Findings indicate that syntactic and morphological impairments are a significant concern for high-functioning children with ASD, and may be overlooked if language evaluation focuses exclusively on vocabulary.

Association of Psychiatric and Neurologic Comorbidity With Mortality Among Persons With Autism Spectrum Disorder in a Danish Population.

IMPORTANCE: Increased mortality has been reported among persons with autism spectrum disorder (ASD), especially among those who also have the comorbid condition of epilepsy or intellectual disability. The effects of psychiatric and neurologic comorbidity on mortality among persons with ASD have not been rigorously examined in large, population-based studies. OBJECTIVE: To investigate the mortality patterns among persons with ASD overall and to assess the associations of comorbid mental, behavioral, and neurologic disorders with mortality among persons with ASD. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study of children born in Denmark during the period from 1980 to 2010 who were alive at 1.5 years of age and followed up through 2013. This population-based sample of children (N = 1,912,904) was identified via linkage between the Danish Civil Registration Service and the Danish Medical Birth Register using a unique 10-digit identifier assigned to all live births and new residents in Denmark. Children were followed up for diagnoses of ASD (International Classification of Diseases, Eighth Revision [ICD-8] codes 299.00, 299.01, 299.02, and 299.03 and ICD-10 codes F84.0, F84.1, F84.5, F84.8, and F84.9) and other mental/behavioral disorders (ICD-8 codes 290-315 and ICD-10 codes F00-F99) in the Danish Psychiatric Central Research Register and for diagnoses of neurologic disorders (ICD-8 codes 320-359 and ICD-10 codes G00-G99) in the Danish National Patient Register. Data analysis was performed in December 2014. MAIN OUTCOMES AND MEASURES: Deaths and causes of death among cohort members were identified via the Danish Civil Registration Service and the Danish Cause of Death Register, respectively. Regressions analyses were performed using Cox regression. RESULTS: Of the 1,912,904 persons included in our study, 20,492 (1.1%) had ASD (15,901 [77.6%] were male). Of the 20,492 persons with ASD, 68 died (0.3%) (57 of 68 [83.8%] had comorbid mental/behavioral or neurologic disorders). The adjusted hazard ratio (aHR) for overall mortality was 2.0 (95% CI, 1.5-2.8) for ASD. The aHRs for ASD-associated mortality among cohort members who did not have neurologic (2.0 [95% CI, 1.4-3.0]) or other mental/behavioral disorders (1.7 [95% CI, 1.0-3.1]) were similar. The co-occurrence of ASD added no additional mortality risk for persons with neurologic (aHR, 0.7 [95% CI, 0.4-1.3]) or mental/behavioral disorders (aHR, 0.8 [95% CI, 0.5-1.2]) compared with persons with these disorders and no ASD. CONCLUSIONS AND RELEVANCE: The mortality risk was 2-fold higher through young adulthood for persons with ASD than for persons without ASD, although mortality affected only 0.3% of persons with ASD. The mechanisms underlying ASD-associated mortality may be mediated through or shared with neurologic or mental/behavioral disorders, thereby providing insights into their potential neurobiological links. Health care professionals and family members should recognize the importance of these disorders with regard to the mortality risk for persons with ASD.

A Danish population-based twin study on autism spectrum disorders.

Genetic epidemiological studies of Autism Spectrum Disorders (ASDs) based on twin pairs ascertained from the population and thoroughly assessed to obtain a high degree of diagnostic validity are few. All twin pairs aged 3-14 years in the nationwide Danish Twin Registry were approached. A three-step procedure was used. Five items from the "Child Behaviour Checklist" (CBCL) were used in the first screening phase, while screening in the second phase included the "Social and Communication Questionnaire" and the "Autism Spectrum Screening Questionnaire". The final clinical assessment was based on "gold standard" diagnostic research procedures including diagnostic interview, observation and cognitive examination. Classification was based on DSM-IV-TR criteria. The initial sample included 7,296 same-sexed twin pairs and, after two phases of screening and clinical assessment, the final calculations were based on 36 pairs. The probandwise concordance rate for ASD was 95.2% in monozygotic (MZ) twins (n=13 pairs) and 4.3% in dizygotic (DZ) twins (n=23 pairs). The high MZ and low DZ concordance rate support a genetic aetiology to ASDs.

Follow-up at mid-school age (9-13 years) of children assessed for autism spectrum disorder before the age of four.

BACKGROUND: Studies of diagnosis and outcome in mid-school age children (9-13 years) referred early in life for a suspected autism spectrum disorder (ASD) are scarce. AIMS: This study aimed to describe outcome, developmental change and the stability of the early diagnosis in mid-school age. METHODS: Children consecutively referred to a specialized autism unit at a regional psychiatric diagnostic centre in Denmark before the age of 4 were contacted in mid-school age (9-13 years). 14 children with ASD and 9 children diagnosed outside the spectrum were included. Current clinical diagnosis, autism characteristics, intellectual abilities and adaptive functioning were assessed at follow-up, and investigated in relation to early measures of intellectual abilities and difficulties in social and communicative situations. RESULTS: The stability of an early ASD diagnosis was confirmed. However, a high degree of change into the autism spectrum was found for children who were initially diagnosed with another developmental disorder. A positive change with regard to IQ level was evident at the individual level. At group level, there was a tendency for lower functioning in the children diagnosed early with ASD. Early measures of intellectual abilities, and of social and communicative difficulties, predicted between 16% and 50% of the variance in intellectual abilities and adaptive functioning. CONCLUSIONS: The findings are in line with follow-up studies in preschool and early school age but highlight the need to monitor early diagnostic decisions, and the need for more nuanced baseline and outcome measures that may help increase our prognostic understanding.

Parental age and autism spectrum disorders.

PURPOSE: We sought to study the possible association between parental age and autism spectrum disorder (ASD) by using both a cohort design and a sibling design. METHODS: Our cohort included all singleton births in Denmark from January 1, 1980, through December 31, 2003, a total of 1,311,736 children. Cases of ASDs were obtained from the Danish National Psychiatric Register using International Classification of Diseases (ICD)-8 and ICD-10. RESULTS: A total of 9556 children were diagnosed with an ASD. Both maternal and paternal age were associated with a greater risk of ASD in the offspring (hazard ratios ranging from 1.21 (1.10-1.34) to 1.65 (1.09-2.48) depending on combinations of parental age categories; <35, 35-39, and 40+ years). For mothers younger than 35 years, the risk of ASD increased with increasing father's age group. For fathers younger than 35 years, the risk of ASD increased with increasing maternal age. CONCLUSIONS: We found an association between parental age and ASD in the cohort study, but the combined underlying mechanisms through which paternal and maternal age impact ASD risk do not seem to act synergistically. The results of the sibling analysis suggest that the association between parental age and ASD found in the cohort study cannot be accounted for by common genetic and environmental factors.

Validity of childhood autism in the Danish Psychiatric Central Register: findings from a cohort sample born 1990-1999.

The purpose of this study was to assess the validity of the diagnosis of childhood autism in the Danish Psychiatric Central Register (DPCR) by reviewing medical records from 499 of 504 total children with childhood autism born 1990-1999. Based on review of abstracted behaviors recorded in case records from child psychiatric hospitals, case status determination was performed using a standardized coding scheme. In 499 children diagnosed with childhood autism in the DPCR, the diagnosis could be confirmed in 469 children (94%). Of the 30 non-confirmed cases, five were classified by the reviewers as non-autistic cases and the remaining 25 cases were either classified with another ASD diagnosis or the specific diagnosis was not possible to determine.

A population-based association study of glutamate decarboxylase 1 as a candidate gene for autism.

Linkage studies, genome-wide scans and screening of possible candidate genes suggest that chromosome 2q31 may harbour one or more susceptibility genes for autism. The glutamate decarboxylase gene 1 (GAD1) located within chromosome 2q31 encodes the enzyme, GAD67, catalyzing the production of gamma-aminobutyric acid (GABA) from glutamate. Numerous independent findings have suggested the GABAergic system to be involved in autism. The present study investigates a Danish population-based, case-control sample of 444 subjects with childhood autism and 444 controls. Nine single nucleotide polymorphisms (SNPs) comprising the GAD1 gene and the microsatellite marker D2S2381 were examined for association with autism. We found no association between childhood autism and any single marker or 2-5 marker haplotypes. However, a rare nine-marker haplotype was associated with childhood autism. We cannot exclude neither GAD1 as a susceptibility gene nor the possibility of another susceptibility gene for autism to be located on chromosome 2q31.

What distinguishes autism spectrum disorders from other developmental disorders before the age of four years?

The increasing recognition of the benefits of early intervention for children with autism spectrum disorder (ASD) stresses the importance of early identification of children who might benefit from those programs. However, in the early years of life it may be difficult to distinguish children with ASD from children with other developmental disorders. The aim of the present study was to identify behavioural patterns that could facilitate this differentiation. Prior to diagnostic assessment, 2- and 3-year-old children (n=30), all referred to a clinic for "possible autism", were observed in a semi-structured play interaction, and their parents were interviewed about the children's early development from 0 to 24 months. Following diagnostic assessment, the 17 children fulfilling the ICD-10 criteria for ASD were compared to the 13 children diagnosed with other developmental disorders (outside the autism spectrum). On the basis of parent reports only a few distinguishing signs of ASD were found before 24 months of age. On the basis of professional observations in a semi-structured play interaction several distinguishing signs were found for the 2- and 3-year-olds; smiles in response, responds to name, follows pointing, looks to "read" faces, initiates requesting verbal and nonverbal behaviours, and functional play.