Early diagnosis of autism spectrum disorder: stability and change in clinical diagnosis and symptom presentation

Background: Although a diagnosis of autism spectrum disorder (ASD) appears to be stable in children as young as age three, few studies have explored stability of a diagnosis in younger children. Predictive value of diagnostic tools for toddlers and patterns of symptom change are important considerations for clinicians making early diagnoses. Most findings come from high‐risk samples, but reports on children screened in community settings are also needed. Methods: Stability of diagnosis and Autism Diagnostic Observation Schedule – Toddler Module (ADOS‐T) classifications and scores was examined across two time points in a sample of 82 children identified through the FIRST WORDS^® Project. Children received two comprehensive diagnostic evaluations at average ages of 19.39 (SD = 2.12) and 36.89 (SD = 3.85) months. Results: Stability was 100% when confirming and ruling out a diagnosis of ASD based on a comprehensive diagnostic evaluation that included clinic and home observations, although diagnosis was initially deferred for 17% of the sample. Receiver Operating Characteristic curves revealed excellent sensitivity and acceptable specificity for the ADOS‐T compared to concurrent diagnosis. Logistic regressions indicated good predictive value of initial ADOS‐T scores for follow‐up diagnosis. Finally, both ASD and Non‐ASD children demonstrated a decrease in Social Affect scores (i.e., improvement), whereas children with ASD demonstrated an increase in Restricted and Repetitive Behavior scores (i.e., worsening), changes that were accounted for by nonverbal developmental level in mixed model analyses. Conclusions: Short‐term stability was documented for children diagnosed at 19 months on average, although a minority of children initially showed unclear diagnostic presentations. Findings highlight utility of the ADOS‐T in making early diagnoses and predicting follow‐up diagnoses. Children with ASD demonstrated improvement in social communication behaviors and unfolding of repetitive behaviors, suggesting that certain early patterns of change in symptoms may be characteristic of ASD.     

Development in infants with autism spectrum disorders: a prospective study

BACKGROUND: Autism is rarely diagnosed before three years of age despite evidence suggesting prenatal abnormalities in neurobiological processes. Little is known about when or how development becomes disrupted in the first two years of life in autism. Such information is needed to facilitate early detection and early intervention. METHODS: This prospective study of autism spectrum disorders (ASD) examined development using the Mullen Scales of Early Learning (MSEL) in 87 infants tested at target ages 6, 14, and 24 months. Participants came from infants at high risk (siblings of children with autism) and low risk (no family history of autism) groups. Based on language test scores, Autism Diagnostic Observation Schedule, and clinical judgment at 24 months of age, participants were categorized as: unaffected, ASD, or language delayed (LD). Longitudinal linear regression and ANOVA models were applied to MSEL raw scores, and estimates were compared between the three diagnostic groups. RESULTS: No statistically significant group differences were detected at 6 months. By 14 months of age, the ASD group performed significantly worse than the unaffected group on all scales except Visual Reception. By 24 months of age, the ASD group performed significantly worse than the unaffected group in all domains, and worse than the language delayed group in Gross Motor, Fine Motor, and Receptive Language. The developmental trajectory of the ASD group was slower than the other groups', and showed a significant decrease in development between the first and second birthdays. CONCLUSIONS: Variations from typical and language delayed development are detectable in many children with ASD using a measure of general development by 24 months of age. Unusual slowing in performance occurred between 14 and 24 months of age in ASD.     

Childhood autism spectrum disorder in the Barwon region: a community based study

OBJECTIVE: To establish a community database for children with autism spectrum disorder (ASD) to determine prevalence and identify subgroups based on key intellectual, clinical and family parameters. METHODS: Data were collected for children previously diagnosed with an ASD in the Barwon region using parental interview and review of the child's paediatric and psychological records. Preschool diagnoses were typically made by specialist psychologists and school-age diagnoses made by a multidisciplinary team. RESULTS: One hundred and seventy-seven children in the Barwon region were identified as having ASD (82% response rate). The prevalence of ASD was one per 255 children aged two to 17 years. The prevalence increased 10 fold over a 16-year period and this increase was relatively even across all levels of child intellectual functioning. Forty-two percent of children were intellectually disabled (IQ < 70) and performance IQ was significantly higher than verbal IQ but typical block design-comprehension subtest patterns were not common. Nine sibling pair families were identified, 24% were labelled as having attention deficit hyperactivity disorder (ADHD), 6% had epilepsy, and 18.3% were macrocephalic where data were available. Family difficulty was associated with the degree of obsessions/rituals, frequency and intensity of anger/aggression, and ADHD but overall was not associated with the child's intellectual status. CONCLUSIONS: The relatively rapid increase in prevalence is consistent with overseas studies and suggests significant changes in diagnostic criteria, increasing community awareness and the need for support at all levels of intellectual functioning. Increased occurrence in siblings and relatives gives further evidence for a genetic cause.     

Diagnosis of autism spectrum disorders in 2‐year‐olds: a study of community practice

Background: Longitudinal research studies have demonstrated that experienced clinicians using standardized assessment measures can make a reliable diagnosis of autism spectrum disorders (ASDs) in children under age 3. Limited data are available regarding the sensitivity and specificity of these measures in community settings. The aims of this study were to determine how well a standardized diagnostic observational measure (Autism Diagnostic Observation Schedule – ADOS) functions alone, and with a brief parent measure within a community setting when administered by community clinicians. Methods: Clinical records for 138 children between the ages of 24 and 36 months of age who were evaluated for possible ASD or social/language concerns at a hospital‐based developmental evaluation clinic were examined. Evaluations were conducted by community‐based clinical psychologists. Classification results obtained from standardized diagnostic measures were compared with case reviewer diagnosis, by reviewers blind to scores on diagnostic measures, using The Records‐based Methodology for ASD Case Definition that was developed by the Metropolitan Atlanta Developmental Disabilities Surveillance Program. Results: When compared with case review diagnosis, the ADOS demonstrated strong sensitivity and specificity for both Autism versus Not Autism and ASD versus Nonspectrum (NS) diagnoses in this young sample. The Social Communication Questionnaire (SCQ), using the lower cutoff of ≥12, had adequate sensitivity when differentiating Autism from Not Autism, but weak sensitivity when differentiating ASD from NS, missing about 80% of the children with pervasive developmental disorder – not otherwise specified. Using either the Modified Checklist for Autism in Toddlers or the SCQ in combination with the ADOS did not result in improved specificity over the ADOS alone and led to a drop in sensitivity when differentiating ASD from NS disorders. Conclusions: These results demonstrate that following best practice guidelines, the ADOS can be successfully incorporated into clinical practice with relatively good sensitivity and specificity, and worked well with a referred sample of 2‐year‐olds. A parent questionnaire did not lead to any improvement in diagnostic classification above the ADOS used in isolation.     

Toxicity biomarkers in autism spectrum disorder: A blinded study of urinary porphyrins

Background: Recent studies suggest that children diagnosed with an autism spectrum disorder (ASD) have significantly increased levels of urinary porphyrins associated with mercury (Hg) toxicity, including pentacarboxyporphyrin (5cxP), precoproporphyrin (prcP), and coproporphyrin (cP), compared to typically developing controls. However, these initial studies were criticized because the controls were not age‐ and gender‐matched to the children diagnosed with an ASD. Methods: Urinary porphyrin biomarkers in a group of children (2–13 years of age) diagnosed with an ASD (n= 20) were compared to matched (age, gender, race, location, and year tested) group of typically developing controls (n= 20). Results: Participants diagnosed with an ASD had significantly increased levels of 5cxP, prcP, and cP in comparison to controls. No significant differences were found in non‐Hg associated urinary porphyrins (uroporphyrins, hexacarboxyporphyrin, and heptacarboxyporphyrin). There was a significantly increased odds ratio for an ASD diagnosis relative to controls among study participants with precoproporphyrin (odds ratio = 15.5, P < 0.01) and coproporphyrin (odds ratio = 15.5, P < 0.01) levels in the second through fourth quartiles in comparison to the first quartile. Conclusion: These results suggest that the levels of Hg‐toxicity‐associated porphyrins are higher in children with an ASD diagnosis than controls. Although the pattern seen (increased 5cxP, prcP, and cP) is characteristic of Hg toxicity, the influence of other factors, such as genetics and other metals cannot be completely ruled out.     

Service utilization in a sample of preschool children with autism spectrum disorder: A Canadian snapshot

OBJECTIVE:

To describe services received by preschool children diagnosed with autism spectrum disorder (ASD) during the five-year period following their diagnosis.

METHOD:

An inception cohort of preschoolers diagnosed with ASD from Halifax (Nova Scotia), Montreal (Quebec), Hamilton (Ontario), Edmonton (Alberta) and Vancouver (British Columbia) were invited to participate. Parents/caregivers (n=414) described the services provided to their children at four time points: baseline (T1; within four months of diagnosis; mean age three years); six months later (T2); 12 months later (T3); and at school entry (T4). Data were first coded into 11 service types and subsequently combined into four broader categories (no services, behavioural, developmental and general) for analysis.

RESULTS:

More than 80% of children at T1, and almost 95% at T4 received some type of service, with a significant number receiving >1 type of service at each assessment point. At T1, the most common service was developmental (eg, speech-language therapy). Subsequently, the most common services were a combination of behavioural and developmental (eg, intensive therapy based on applied behaviour analysis and speech-language therapy). Service provision varied across provinces and over time.

DISCUSSION:

Although most preschool children with ASD residing in urban centres were able to access specialized services shortly after diagnosis, marked variation in services across provinces remains a concern.     

Social and behavioural outcomes in children diagnosed with autism spectrum disorders: a longitudinal cohort study

Objective: To compare social and behavioural outcomes between children formally diagnosed with autism spectrum disorders (ASD) with those of children who displayed autistic traits at preschool age, but remained undiagnosed as teenagers. Method: A secondary analysis of data from a birth cohort study, the Avon Longitudinal Study of Parents and Children (N = 13,944), in SW England. Children clinically diagnosed with ASD were identified from their medical records (n = 71). A comparison group, who displayed autistic traits at age 3–4, but without ASD diagnosis were also identified (n = 142). Social and behavioural outcomes in adolescence were compared between the two groups. Results: Children with ASD diagnoses were more impaired as teenagers that those in the comparison group on a range of measures of autistic‐like behaviour. The developmental trajectory of prosocial behaviour showed that differences between the case and comparison groups increased dramatically in the preschool and early primary years, but that after 6 years the trajectories were similar. Conclusions: The divergence of the clinically diagnosed group and the nondiagnosed group in measures of autistic‐like behaviour increased with age. This study provides evidence that it may be difficult to distinguish preschool age children who exhibit autistic‐like symptoms but improve, from those who go on to develop lifelong impairment.     

孤独症谱系障碍儿童的诊断年龄及其影响因素

目的 研究孤独症谱系障碍（ASD）儿童的诊断年龄,探讨ASD诊断年龄的影响因素。方法 收集2011年2月至2017年7月于重庆医科大学附属儿童医院首次就诊后确诊为ASD的1691例儿童的临床资料。应用多元线性回归模型分析影响ASD诊断年龄的相关因素。结果 ASD诊断年龄平均为35±17个月（范围9~175个月）,其中24~35个月获得确诊者占比最高（46.13%,780/1 691）,其次为≥ 36个月（33.41%,565/1 691）。多元线性回归分析显示,有语言障碍、居住在主城区、父母学历高的ASD儿童诊断年龄较早（P < 0.05）。结论 儿童ASD的诊断年龄多在24~35个月。ASD诊断年龄与个体主要症状、居住地区和父母文化程度有关。     

Pathways in ASD Study Team. Service utilization in a sample of preschool children with autism spectrum disorder: A Canadian snapshot.

OBJECTIVE:

To describe services received by preschool children diagnosed with autism spectrum disorder (ASD) during the five-year period following their diagnosis.

METHOD:

An inception cohort of preschoolers diagnosed with ASD from Halifax (Nova Scotia), Montreal (Quebec), Hamilton (Ontario), Edmonton (Alberta) and Vancouver (British Columbia) were invited to participate. Parents/caregivers (n=414) described the services provided to their children at four time points: baseline (T1; within four months of diagnosis; mean age three years); six months later (T2); 12 months later (T3); and at school entry (T4). Data were first coded into 11 service types and subsequently combined into four broader categories (no services, behavioural, developmental and general) for analysis.

RESULTS:

More than 80% of children at T1, and almost 95% at T4 received some type of service, with a significant number receiving >1 type of service at each assessment point. At T1, the most common service was developmental (eg, speech-language therapy). Subsequently, the most common services were a combination of behavioural and developmental (eg, intensive therapy based on applied behaviour analysis and speech-language therapy). Service provision varied across provinces and over time.

DISCUSSION:

Although most preschool children with ASD residing in urban centres were able to access specialized services shortly after diagnosis, marked variation in services across provinces remains a concern.     

The evolution of diagnostic trends in congenital heart disease: A population-based study

OBJECTIVE: To analyse historical trends in diagnosis of congenital heart disease (CHD) in all diagnosed cardiac malformations born between 1945 and 1994 in a population-based study, the first of its type. METHODOLOGY: Retrospective analysis of age and mode of diagnosis was carried out in 953 patients with CHD, in the setting of a regional hospital providing diagnostic and follow up services for all of Malta. Main outcome measures were age at diagnosis, cumulative percentage diagnosis by age and mode of diagnosis. RESULTS: A significant negative correlation of age at diagnosis with time was found for both lesions not requiring intervention, and requiring intervention (P < 0.0001). Cumulative percentage diagnosis by age increased progressively with time. Echocardiography increased the birth prevalence of definitively diagnosed defects, particularly of lesions not requiring intervention. The annual number of cardiac catheters for these conditions has decreased with an increased number and proportion of interventional catheters. The current catheterization rate for CHD is 6.1/100 000 population. CONCLUSION: Echocardiography has led to an increase in the diagnosis in the birth prevalence of CHD, and provided early diagnosis, supplanting cardiac catheterization as a primary diagnostic tool.     

孕期多环芳烃暴露与幼儿孤独症谱系障碍相关行为关系的出生队列研究

目的 探讨母孕期多环芳烃（PAHs）暴露与幼儿孤独症谱系障碍（ASD）相关行为的相关性。方法 采用出生队列研究,选择已进行脐带血PAH-DNA加合物测定并完成36月龄幼儿行为问题评估的348名幼儿作为研究对象。采用2~3岁儿童行为量表（CBCL）、孤独症行为评定量表（ABC）评定36月龄幼儿行为问题。分析脐带血PAH-DNA加合物浓度与36月龄幼儿CBCL量表、ABC量表得分间的相关性。结果 新生儿脐带血PAH-DNA加合物的检出率为52.3%,浓度中位数为0.68 ng/mL。CBCL量表总得分中位数为23分,ABC量表总得分中位数为8分。PAH-DNA加合物浓度与36月龄幼儿CBCL量表中社交退缩得分呈正相关（r_s=0.205,P < 0.05）,与ABC量表总分、生活自理能力得分呈正相关（分别r_s=0.412、0.355,均P < 0.05）。PAH-DNA加合物浓度与36月龄幼儿ABC量表总分密切相关（β=0.122,P < 0.05）。结论 母孕期PAHs暴露是儿童发生ASD相关行为的危险因素。有效降低母孕期PAHs暴露,开展新生儿脐带血PAH-DNA加合物检测,对ASD的早期预防、筛查及干预工作具有重要意义。     

专业人员指导下孤独症谱系障碍儿童家长执行的家庭康复疗效观察的前瞻性研究

目的 探讨专业人员指导下,由家长执行的家庭康复对孤独症谱系障碍（autism spectrum disorder,ASD）儿童的治疗作用。 方法 前瞻性选取ASD儿童60例（月龄24~60个月）,随机分为观察组和常规组。常规组儿童仅对家长进行线上理论培训。观察组儿童家长,除线上理论培训外,还进行专业人员团队指导下由家长执行的家庭康复。采用心理教育评估第3版（Psycho-Education Profile Third Edition,PEP-3）、儿童期孤独症评定量表（Childhood Autism Rating Scale,CARS）评估两组儿童干预前、干预后能力变化情况。 结果 经6个月干预后,观察组PEP-3量表各维度和常规组大部分维度得分较干预前提高（P<0.01）;两组CARS量表得分较干预前降低（P<0.05）。与常规组相比,干预后观察组儿童PEP-3量表语言理解、语言表达、大肌肉、小肌肉、个人自理、适应行为维度得分提高（P<0.05）,CARS量表得分降低（P<0.05）。 结论 对家长培训,由家长执行的干预可以提升ASD儿童的能力,改善其核心临床症状;但以专业人员组成的团队为资源平台,以家长为主要干预力量的家庭康复服务模式,对提升ASD儿童语言、运动等能力,改善其症状严重程度的效果更为显著。