Autism is the most common neurodevelopmental disorder in the United States. Estimates of the prevalence of ASD suggest that as many as 400,000 individuals in the United States have ASD or a related condition [7]. In the United States, ASD prevalence is 1 in 36 children at 8 years of age and is 3.8 times more common among boys than girls, with male-to-female prevalence ratios was 3.8 [8]. Prevalence estimates among White children (24.3) was lower than prevalence among Black, Hispanic, or Asian/Pacific Islander children (29.3, 31.6, and 33.4, respectively). ASD prevalence among children of two or more races was 22.9, which was not different than among White children but was lower than prevalence among Asian/Pacific Islander, Black, and Hispanic children [8]. In addition, Black children have less access to services than White children with ASD. The overall median age at earliest known ASD diagnosis (49 months of age) is similar by sex and by racial and ethnic groups [8]. Reported rates of ASD have been rising in many countries for more than two decades. Based on a review of epidemiologic studies, the global prevalence of ASD is estimated to be 7.6 cases per 1,000 population [9].

Like ASD itself, the theories of autism are diverse and often overlapping. It was once believed that poor parenting caused autism. The terms "refrigerator mother" or "refrigerator parents" were used to describe emotionally frigid parents who were thought to be too distant, cold, and uncaring to allow the child to bond properly. This view has been referred to as the psychogenic theory of autism; however, it remains unsupported by the scientific and medical communities.

The biologic theory of autism holds that various medical conditions, including gene mutations and/or infections or environmental exposures in genetically predisposed individuals, cause ASD [3]. Studies of have found that certain medical conditions occur with greater frequency in children with ASD than in children without autism. When autism occurs in conjunction with a medical condition that is capable of damaging the nervous system, the medical condition is typically assigned as the cause of autism. Medical conditions that are commonly identified with autism include [17,18,19,20]:

Children with ASD have discreet reductions in plasma levels of cysteine, glutathione, and methionine; reductions in the ratio of the enzymes S-adenosyl-L-methionine (SAMe) to S-adenosyl-L-homocystein (central to the regulation of many biologic processes); and reductions in the ratio of reduced to oxidized glutathione (an antioxidant capable of preventing damage to cellular components) [68]. Reduced concentrations of N-acetylaspartate (NAA) (a metabolite generally abundant in the central nervous system) have been associated with cognitive dysfunction, diminished neuronal activity, and reduced cellular oxidative metabolism. Reduced NAA has been found to diminish neuronal metabolism in boys with ASD in contrast to age-matched controls [65,69]. Metabolic anomalies (e.g., elevated blood serotonin, reduced serum biotinidase), impaired mitochondrial function, and neural inflammation also have been identified in some people with ASD [68,70].

The AAP recommends that all children be screened for developmental delays and disabilities during regular well-child visits at 9, 18, and 30 months of age, with additional screening as needed for children at high risk for developmental problems due to preterm birth or low birth weight. Additionally, all children should be screened specifically for ASD with a standardized tool at 18 and 24 months of age, with ongoing developmental surveillance [10,74]. Developmental surveillance for ASD includes asking caregivers about any concerns they have about their child's development or behavior, informal observation, and monitoring of symptoms in the context of routine health supervision [10].

Many children and adults with ASD have comorbid health conditions. One retrospective study examined the comorbidity burden of ASD in more than 14,000 children and young adults across three general hospitals and one pediatric hospital [88]. Patients with autism had higher than expected rates of all of the medical conditions studied (e.g., eczema, allergies, gastrointestinal problems, seizures, asthma) compared with general patient populations of health centers [88]. Additional studies from the United States, Europe, and Asia confirmed the high prevalence of medical comorbidities among children and young adults with ASD [89,90,91,92]. Medical comorbidities such as epilepsy, gastrointestinal conditions, and respiratory disorders are associated with a mortality rate that is 3 to 10 times higher among patients with ASD than in the general population [93,94].

Autism is increasingly recognized as a whole-body disorder, with the core characteristics commonly attributed to ASD now being attributed to manifestations of a systemic and complex disease process [96]. Study results are challenging the belief that ASD is static, lifelong, and unchangeable, with many results providing evidence that significant improvement is possible following intensive, individualized intervention [98,99,100,101]. It is now established that "specific medical problems are associated with the severity of the condition and that successfully addressing these comorbidities often leads to significant improvement in overall functioning" [96].

The prevalence of seizure disorders is high in people with ASD, and their co-occurrence with ASD contributes to an elevated mortality risk [103]. One meta-analysis of 19 studies found a pooled ASD prevalence of 6.3% in epilepsy. When divided by type, the risks of ASD for general epilepsy, infantile spasms, and focal seizures were 4.7%, 19.9% and 41.9%, respectively [103]. Individuals with epilepsy 18 years of age and younger were found to have a risk of ASD that was 13.2 times greater than that of individuals 18 years of age and older. Individuals with co-occurring intellectual disability had a risk for ASD that was 4.9 times higher than those without intellectual disability. Primary risk factors for epilepsy in patients with ASD include the presence of intellectual disability, female sex, age, and symptomatic etiology of epilepsy [103].

Approximately two-thirds of children with ASD have chronic insomnia [104]. Sleep disturbances can contribute to the psychosocial burden of ASD and exacerbate symptoms such as inattention or irritability [105]. Anxiety and sensory over-responsivity alone are independently associated with a variety of sleep problems (e.g., bedtime resistance, sleep-onset delay, sleep anxiety, night waking), making children with ASD and one or both of these co-occurring conditions particularly predisposed to sleep disturbances [106]. Children's sleep habits and the sensory-processing patterns of avoidance, sensitivity, seeking, and registration were assessed in a cross-sectional study of 231 primary school students 7 to 12 years of age [107]. Each of the sensory-processing patterns was found to have a negative relationship with sleep habits, with a significant difference between children who had more challenges with sleep maintenance compared with those with normal sleep patterns [107].

The goals of treatment for children with ASD are to minimize core deficits; maximize functional independence; and eliminate, minimize, or prevent problem behaviors that may be interfering with the child's functional skills [10]. Intensive, individualized interventions are the most effective treatments for ASD. Early identification increases the likelihood of a favorable outcome; therefore, patients should be referred for specialized diagnostic and therapeutic interventions as soon as signs or symptoms of ASD appear [117,118].

The increased prevalence of ASD has increased the demand for effective treatment options, and intervention science is providing evidence about which practices are effective [124]. A report published in 2013 describes two broad classes of evidence-based interventions: comprehensive treatment models (CTMs) and focused interventions [10,124]. CTMs consist of a set of practices designed to achieve a broad learning or developmental impact on the core characteristics of ASD [124]. Examples of CTMs include Treatment and Education of Autistic and Related Communication-Handicapped Children (TEACCH) and the Early Start Denver Model (ESDM) [124,125,126,127]. As of 2023, an estimated 30 CTM programs are operating in the United States [124].

There is considerable regional variation in the availability of interventions for the management of ASD as well as significant overlap in the methods used. According to the AAP, the common characteristics of effective and empirically supported interventions include [10]:

Neurodiversity is broadly defined as an approach to learning and disability that suggests that diverse neurologic conditions appear as a result of normal variations in the human genome; that these variations should be recognized and respected as any other human variation; and that individuals with these variations are not in need of fixing, but rather should be recognized and respected as a social category on par with gender, ethnicity, sexual orientation, or disability status [135]. Neurodiversity challenges the assumption that ASD is a disease or disorder that needs to be eradicated, prevented, treated, or cured [136]. Self-advocating individuals with autism argue that in "highly social and unpredictable environments some of their differences may manifest as disabilities, while in more autism-friendly environments the disabilities can be minimized, allowing other differences to manifest as talents" [136].

Intensive, individual special education provided by an educator familiar with instructing children with ASD is central to the treatment of ASD [7]. School-aged children with ASD should be enrolled in an appropriate educational program that provides support and promotes language, academic, adaptive, and social skills development. Federal law entitles all students with disabilities to a free and appropriate public education (FAPE) and mandates that these students be placed in the least restrictive environment that allows them to progress toward achieving their goals. These goals must be developed and measured within the framework of an individualized education program (IEP), which is a blueprint for the student's school year. The IEP includes academic and behavioral goals, interventions, modifications, supports, and hands-on learning opportunities that help the student transition from the school years to adulthood. Parents, teachers, and other individuals who work with the student with autism all participate in developing the IEP [140].

Delays in speech onset may be complicated by general developmental delays or by coexisting speech disorders. Up to 30% of children with ASD never acquire verbal speech [145]. Speech-language therapy is the most commonly identified intervention provided for children with ASD [10]. Strategies used include reinforcement of speech sounds and communicative acts, imitation of the child's sounds, and exaggerated imitation and slowed tempo. Augmentative and alternative communication (AAC) is used when there is a deficit in spontaneous speech and includes strategies such as the Picture Exchange Communication System (PECS) and speech-generating devices [146,147]. AAC methods teach the individual to communicate independently [10].

Data from Medicaid and commercial insurers indicate that 56% to 65% of patients with ASD are prescribed psychotropic medications [149,150,151]. One or more medications are prescribed for 1% of children 3 years of age and younger; 10% of children 3 to 5 years of age; 38% to 46% of children 6 to 11 years of age; and 64% to 67% of adolescents 12 to 17 years of age [152,153]. Increased use of medications is attributed to a lower level of cognitive skills and/or intellectual disability, disruptive behavior, or a co-existing diagnosis. A better understanding of the neurobiology of ASD will allow for identification of targeted interventions to better manage co-occurring symptoms and/or address core deficits [10]. As of yet, there is no drug that clearly leads to improvements in the basic symptoms of autism. Drugs are generally prescribed to treat associated behavioral issues and comorbid disorders [7]. Considerations for medication use in treatment of ASD are summarized in Table 6[10,121].

The atypical antipsychotic risperidone has been approved since 1993 for the short-term treatment of adults with schizophrenia and since 2003 for the short-term treatment of adults with acute manic or mixed episodes associated with extreme mood swings. In 2006, the U.S. Food and Drug Administration (FDA) approved the agent for the symptomatic treatment of agitation and irritability in children and adolescents with autism. The approval was the first for the use of a drug to treat behaviors associated with autism in children [158]. The effectiveness of risperidone in ameliorating irritable behavior in children with autism was established in two 8-week, placebo-controlled trials in 156 patients 5 to 16 years of age. These children achieved significantly improved behavioral symptom scores compared with controls [158,159,160]. The most common side effects of risperidone include increased appetite, weight gain, and sedation, with weight gain being the most significant [2,157,159,160]. Aripiprazole, another atypical antipsychotic, also is FDA approved for the treatment of irritability associated with autism [157,161]. In preliminary studies, the atypical antipsychotics olanzapine and ziprasidone have been shown to have similar beneficial effects, but their use in ASD is off-label [157,162,163,164,165]. Although they are effective in controlling behavioral symptoms, olanzapine and ziprasidone are associated with significant adverse effects, including abdominal pain, seizures, and excessive weight gain (olanzapine only) [157,161,162].

Best practices include providing families with contact information for a family support group at the time of diagnosis [10]. Peer support for families of children with ASD has been shown to lessen parental stress, decrease negative mood, and increase positive perceptions [190]. This support may be a local group that provides face-to-face interaction and community activities, or it may be an online community. One study of peer support exchanged via social media found that parents received both informational and emotional support, including discussing and addressing the challenges and difficulties of caring for and raising a child with ASD as well as receiving information about improving children's social lives and self-care routines [191]. Families who do not reach out for support at the time of diagnosis may find the support useful later when they are faced with the transitions from preschool to adolescence to adulthood [10]. National support groups (Resources) and local organizations also are effective in helping families obtain information and feel supported. Clinicians should familiarize themselves with these resources. Additionally, they should advocate for instructional material in English and other languages to support a culturally diverse practice [10].

While it is difficult to project the prognosis and trajectory of development for the child with ASD, most (more than 80%) who are diagnosed with ASD after a comprehensive evaluation at 3 years of age or younger retain their diagnosis [192,193]. If the child has average or above-average cognitive abilities, recognition and diagnosis of ASD can be more difficult.