Description

• Group of neurodevelopmental disorders of early childhood characterized by (i) persistent deficits in social communication and interaction and (ii) restricted, repetitive patterns of behavior, interests, or activities
• Diagnostic and Statistical Manual of Mental Disorders, 5th edition: umbrella term autism spectrum disorder (ASD), which encompasses a group of pervasive developmental disorders with designations for varying severities and associated symptoms
• ASD combines former diagnoses, including autistic disorder, childhood disintegrative disorder, Asperger disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), early infantile autism, childhood autism, Kanner autism, high-functioning autism, and atypical autism, many of which are still used by ICD-10 coding.
• Although symptoms must be present in early development period, they may not be apparent until social demands exceed capacity.
• Symptoms must cause functional impairment. Severity levels:
  • Level 1: requiring support—noticeable impairment
  • Level 2: requiring substantial support—marked deficits
  • Level 3: requiring very substantial support—severe impairments interfering with functionality
• Specifiers for associated symptoms include with catatonia; intellectual impairment; language impairment; known medical or genetic condition; and neurodevelopmental, mental, or behavioral disorders.
• Important to distinguish ASD from symptoms that could be better explained by intellectual disability or global developmental delay

Epidemiology

Onset in early childhood; predominant sex: male > female (approximately 4:1 ratio)

Pediatric Considerations
Symptom onset can often be seen in children <3 years of age but may not become apparent until social demands exceed capacity.

Prevalence

• Estimated prevalence has increased from approximately 1.1% in 2008 to 2.3% in 2018 among children aged 8 years in the United States (1).
• Higher prevalence contributed to changes in diagnostic criteria, increased awareness, improved ascertainment, and access to care (1).
• Higher percentage of ASD is observed in black, Hispanic, and Asian and Pacific Islander children than in white children, which may reflect improvements in identification among these groups (1).

Etiology and Pathophysiology

• No single cause has been identified. Variety of genetic and environmental factors have been associated with ASD but none with absolute specificity for ASD development (1).
• Epidemiologic evidence does not support association between immunizations and ASD.

Genetics

• Genetic concordance: A 2009 Swedish population-based cohort study of 2 million subjects showed a cumulative risk of 59% for monozygotic twins.
• The American College of Medical Genetics and Genomics practice guidelines list the risk of siblings of children diagnosed with ASD without an identifiable cause to be 7% if the affected child is female, 4% if the affected child is male, and >30% if there are two or more affected children.

Risk Factors

• Male sex, advanced paternal age, family history, very low birth weight
• Perinatal insults including toxic exposures, teratogens, prenatal infections, use of selective serotonin reuptake inhibitors (SSRI) or valproate during pregnancy

General Prevention

• Screening for early intervention is associated with improved prognosis, yet median age of diagnosis in the United States is >4 years.
• Routine screening for ASD with a validated tool is recommended at 18- and 24-month well-child visits to assist with early detection.
• Screening is indicated after 24 months if parents or clinician have concerns about ASD as less severe presentations may pass earlier routine screening.
• Children with false positives for ASD frequently have some form of developmental disorder and benefit from early intervention.
• Screening difficult due to variability of signs and symptoms of ASD and lack of unanimous consensus of social developmental milestones, thus leading to delayed diagnosis

Commonly Associated Conditions

• Intellectual disability (seizure in severe cases)
• Attention deficit hyperactivity disorder (ADHD), anxiety, depression, or obsessive behavior
• Motor impairments including hypotonia, apraxia, toe walking, or gross motor delays
• Phenylketonuria (PKU), tuberous sclerosis, fragile X syndrome, Angelman syndrome, Rett syndrome, CHARGE syndrome, Joubert syndrome, Smith-Lemli-Opitz syndrome, Timothy syndrome, and fetal alcohol syndrome (rare)
• Sleep issues: insomnia, circadian rhythm sleep–wake disorder, sleep-related movement disorder
• Change in bowel habits, abdominal pain