Chapter 25: Autism Spectrum Disorder

I. Intensive and convalescent care

1. Definition

   1. Autism spectrum disorder (ASD), as defined by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition, (DSM-V) is a complex heterogeneous neurodevelopmental disorder with two main distinguishing features.

      1. Impaired social communication and social interaction

      2. Narrow or restricted and repetitive behaviors and interests

   2. In contrast to the previous edition, in DSM-V ASD can be comorbid with other developmental disorders such as attention deficit hyperactivity disorder (ADHD), developmental coordination disorder (DCD), specific language impairment (SLI), and intellectual disability (ID).

   3. ASD typically emerges by 3 years but rarely before 10 months of age. Some information provided below applies to follow-up care but is included here as a general introduction.

2. Incidence/prevalence

   1. Reported prevalence of ASD has increased over the past 30 years from 1:1000 to ~1:88.

   2. ASD prevalence associated with obstetric and neonatal factors that result in NICU admission is estimated to be between 1:32 and 1:77.

   3. Severity of CNS injury and most clinical risk factors are individually associated with ASD risk, but are highly intercorrelated and likely reflected in the twofold increased risk of ASD if born preterm.

   4. Since NICU admissions account for about 1/8 of live births with preterm birth a major cause, from 10% to 25% of all ASD cases are likely to be NICU graduates.

3. Pathophysiology

   In summary, studies of the pathophysiology of ASD point to developmental disruption experienced early, most likely in the first trimester when CNS organization undergoes large developmental changes. First trimester abnormalities have cascading consequences for second trimester development, with long-term negative consequences expressed years later as ASD. These early adverse effects are not necessarily apparent as hemorrhage or other detectable injury on MRI, CT, or CUS after delivery, but may be visible only on autopsy, or possibly as brain volumetric deficiencies or neural track abnormalities.

   1. The pathophysiology of ASD is assumed to be related to abnormal brain development.

      1. Brain imaging links numerous brain centers and their interconnections with ASD, including regions in the cortex, cerebellum, limbic system, thalamus, and brainstem.

      2. MRI studies show different developmental trajectories for both subcortical and cortical brain volume growth overall and in specific areas associated with ASD at least through 7 years and in some areas into adolescence.

      3. A difference in growth trajectory, with increased head size associated with ASD, may indicate abnormalities in apoptosis and neuronal pruning that affect developing neural pathways.

      4. Volumetric MRI of the brainstem, by contrast, indicates smaller volumes at birth, only reaching normal levels by adolescence.

      5. Postmortem studies show abnormalities in cell development, migration, and connectivity in multiple brain regions linked to the serotonin system, oxidative stress, and associated factors.

   2. Prenatal (first and second trimester) abnormalities

      1. Placental abnormalities

         • ASD-associated placental abnormalities primarily involve lack of synchrony and poor arborization of the arterial system branching from central to peripheral areas of the placenta, suggesting poor fetal oxygenation and/or perfusion.

         • These first trimester disorganizing effects have multiple causes, including early infection, diabetes, and hypertension, and are coincident ...