Autism Spectrum Disorder for APRNs Nursing CE Course

eritability of conditions is based on twin studies. Twin and family studies strongly suggest that some people have a genetic predisposition to ASD. While identical twin studies have demonstrated ASD occurs in both twins 36% to 95% of the time (NINDS, 2020), recent data from a National Institute of Health (NIH)-funded study (Castelbaum et al., 2020) highlighted the wide variability in symptom degree among twins, despite sharing the same DNA. Castelbaum and colleagues (2020) explored data on 366 identical twin pairs with and without ASD. If one twin had ASD, there was a 96% chance the other twin was also affected; however, their symptoms varied greatly. Non-identical twin studies have shown that if one child has ASD, the other is affected 0% to 31% of the time (NINDS, 2020). Sandin and colleagues (2017) explored ASD heritability utilizing more than 37,000 twin pairs, over 2 million full-sibling pairs, and 800,000 half-sibling pairs. According to their findings, ASD had an overall heritability of 83%, and environmental factors were responsible for the remaining 17%, suggesting that genetic factors play a primary role (Sandin et al., 2017). 

Multiple studies published over the last 10 years have demonstrated an increased incidence of ASD among children born to older parents. For example, a 2017 study in Iceland evaluated the whole-genome sequencing of thousands of people, suggesting that parents in their mid-40s are 5% to 10% more likely to have a child with ASD than 20-year-old parents. According to the researchers, adults develop an increasing number of new gene mutations (de novo) as they age, passing on more of these mutations to offspring conceived in their later years. The findings highlighted that males accumulate de novo mutations four times faster than females; thus, most of the contribution comes from the father (Jonsson et al., 2017). The impact of increased parental age, especially from the father, is one of the most consistent findings in epidemiology research on ASD. Advanced paternal age at the time of conception is also cited as a contributing factor to other mental health conditions, such as schizophrenia and bipolar disorder. It can also impact the child’s future learning potential. While the father's age threshold has not yet been determined, research has suggested a range of 30 to 50 years, with 40 years cited the most frequently (Feinberg et al., 2015; Janeczko et al., 2019). Additionally, in families with one child with ASD, the likelihood of having a second child on the spectrum increases by 2% to 18% (Autism Speaks, n.d.-a). 

According to a large population-based cohort study in Sweden, a history of parental mental illness is associated with an increased likelihood of ASD in a child. Xie and colleagues (2019) evaluated more than 500,000 participants and found that 63.1% of patients with ASD had a parent with a history of mental and/or neurological disorders, compared with 45.4% of those without ASD. In addition, a family history of multiple conditions was associated with a higher odds ratio of ASD, including a history of ASD, intellectual disability, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), schizophrenia, depression, bipolar disorder, personality disorder, cerebral palsy, and epilepsy. Furthermore, the more closely related the affected family member was, the higher the likelihood of ASD became (Xie et al., 2019). Qin and colleagues (2016) performed a systematic review and meta-analysis involving 2,896 participants regarding brain-derived neurotrophic factor (BDNF). They found significantly higher levels of BDNF in peripheral blood samples of patients with ASD versus non-affected controls. BDNF is a prominent, widely expressed neurotrophin that affects neuron survival and growth, synapse formation and plasticity, cell differentiation, and cognitive function (Qin et al., 2016). 

The Childhood Autism Risks from Genetics and the Environment (CHARGE) study was designed to help collect information and research to determine the causes of ASD. A portion of the CHARGE study found more anti-fetal brain autoantibodies in mothers of ASD patients (23%) versus control mothers (1%). These antibodies were also more prevalent among mothers with metabolic conditions such as gestational diabetes, obesity, and hypertension, creating low-grade inflammation and insulin resistance. IgG antibodies—including this specific type—can cross the placenta after 13 weeks of gestation to provide passive immunity to a fetus from various infectious agents. The blood-brain barrier is also more permissive during fetal development (Krakowiak et al., 2016). Finally, ASD is more common in children born prematurely and low birth weight neonates (Autism Speaks, n.d.-a).

Evidence suggests that environmental factors can determine up to 40%–50% of ASD likelihood. The most commonly discussed environmental factor correlated with ASD has been vaccination for more than two decades now. This erroneous connection, spawned from a since-retracted report published in The Lancet by Wakefield and colleagues in 1998, ignited a frenzy over the perceived safety concerns of childhood vaccinations, specifically the measles, mumps, and rubella (MMR) vaccine. Since then, multiple epidemiological studies have demonstrated that neither the MMR nor any other vaccine to prevent childhood infectious diseases increases the likelihood of ASD. In a meta-analysis regarding vaccinations and ASD, Taylor and colleagues (2014) evaluated five cohort studies involving over 1 million children and five case-control studies with almost 10,000 children. They found no association between vaccinations and ASD, including the MMR or vaccinations containing thimerosal or mercury (Taylor et al., 2014). In 2015, Jain and colleagues investigated the MMR further using a retrospective cohort study of over 95,000 siblings of patients diagnosed with ASD. They concluded that the administration of the MMR vaccine was not associated with increased ASD likelihood (Jain et al., 2015). In addition, a 2018 study including more than 81,000 mothers and children found no association between ASD and maternal administration of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine (Becerra-Culqui et al., 2018). Although research continues to demonstrate strong evidence regarding vaccine safety and efficacy and a lack of association between the MMR vaccination (or other vaccines) and ASD, some parents remain reluctant to vaccinate their children, which has led to the recent resurgence of measles (DeStefano & Shimabukuro, 2019).

Many other environmental factors have been studied regarding their potential association to ASD, such as tobacco and alcohol use; exposure to pesticides, phthalates, and bisphenol-A (BPA); decreased maternal consumption of polyunsaturated fatty acids; or increased exposure to air pollution. However, there has been insufficient evidence to establish a clear link between any of these factors and ASD (Lyall et al., 2014). Various studies support the maternal use of prenatal vitamins before and during pregnancy and folic acid supplements during the first month of pregnancy as protective factors to decrease the chance of ASD. This conclusion was partly based on the findings of Levine and colleagues (2018). They analyzed the medical records of 45,300 children and found a statistically significant decrease in the likelihood of ASD when mothers took daily multivitamins and folic acid supplements before and during pregnancy. According to a recent systematic review by Zhong and colleagues (2020), higher or moderate intake of prenatal/multivitamins, folic acid, and vitamin D reduced the likelihood of ASD. However, the results have not been consistent enough for the authors to conclude a causal relationship. An analysis of a series of systematic reviews and meta-analyses by Modabbernia and colleagues (2017) suggested that maternal smoking, thimerosal exposure, and most assisted reproductive technologies do not lead to ASD.  

During pregnancy, maternal use of valproic acid (Depakote) and thalidomide (Thalomid) are known risk factors for ASD. According to multiple epidemiologic studies, exposure to teratogens during the first trimester more strongly increases the likelihood of ASD than exposure during the second or third trimesters (Autism Speaks, n.d.-a; Ornoy et al., 2016). Although research findings are conflicting and remain controversial, selective serotonin reuptake inhibitors (SSRIs) have been flagged for their potential association with ASD. A large, Canadian-based retrospective study including more than 145,000 children found a significant association between maternal use of SSRIs during pregnancy and ASD (Boukhris et al., 2016). Antidepressant use during the second and/or third trimester was associated with ASD. A stronger association was found when SSRI antidepressants or multiple classes of antidepressants were used. Correspondingly, the use of other types of antidepressants (non-SSRIs) during the first trimester or the year before pregnancy was not associated with a greater likelihood of ASD (Boukhris et al., 2016). A 2017 systematic review and meta-analysis assessing the association between ASD and maternal antidepressant medication use during pregnancy found a significant correlation. However, this relationship appeared to be more consistent during the preconception period than during each trimester. Maternal psychiatric disorders in treatment before pregnancy—rather than antenatal exposure to antidepressants—could have a more significant role in ASD (Mezzacappa et al., 2017).

Acknowledging that causes of ASD are not well-understood and continually evolving, the National Institute of Environmental Health Sciences (NIEHS, 2021) has listed the following factors as having the most decisive evidence involving the events before and during birth. These factors are unlikely to cause ASD by themselves but appear to facilitate spectrum characteristics when combined with genetic factors (NIEHS, 2021).

• advanced parental age at the time of conception
• prenatal exposure to air pollution or certain pesticides
• maternal obesity, diabetes, or other immune system disorders causing increased inflammation
• extreme prematurity or very low birth weight
• any labor and delivery complication leading to periods of oxygen deprivation (hypoxia) to an infant’s brain (NIEHS, 2021)

Key Features

The hallmark signs of ASD include ongoing social, communication, and interaction challenges and focused or repetitive behaviors and interests. ASD begins in early childhood, affects daily life, and is typically a lifelong condition, although specific symptoms may improve over time. In some children, the social and behavioral characteristics of ASD may manifest during the first year of life. For example, infants and young toddlers may focus intently on specific items, rarely make eye contact, or not meet certain developmental milestones. Other children develop neurotypically until age 2 or 3 and then withdraw, regress, or become indifferent to social interaction. The degree of support needed is primarily influenced by how communication, social functioning, and behaviors impact daily functioning, communication, interpersonal interactions, and development (Autism Speaks, n.d.-a; CDC, 2021c; Koegel et al., 2019; NINDS, 2020).

Verbal and nonverbal communication skills are commonly affected. Most children with ASD will present with delayed onset of verbal communication, which is the most common reason parents seek consultation from a healthcare provider. Healthy developing children typically speak their first words between 10 and 18 months. On average, children with ASD do not achieve this milestone until 36 months. While many children with ASD can communicate verbally, at least one-third have remained nonverbal throughout their lifespan, speaking few or no words (Koegel et al., 2019). People with ASD can have difficulty using and understanding spoken language, gestures, eye contact, facial expressions, tone of voice, idioms, or other figures of speech. Affected persons often feel overwhelmed in social situations, have difficulty gauging personal space, and struggle to recognize and express emotions in themselves and understand the feelings of people around them (Autism Speaks, n.d.-a; NINDS, 2020). 

Repetitive behaviors and focused interests are core features of ASD and can manifest in various ways. These may include body movements, motions with external objects, staring at lights/spinning objects, rituals, and consistent routines (Autism Speaks, n.d.-a; CDC, 2021c). According to the American Academy of Pediatrics (AAP, 2021a), early signs of ASD include the following:

• Age-specific:
  • does not respond to name by 12 months
  • does not point at objects to show interest by 14 months 
  • does not pretend play by 18 months
• General:
  • avoids eye contact 
  • prefers to be alone (e.g., shows little or no interest in playing with peers)
  • has difficulty understanding other people’s feelings or talking about their feelings
  • has delayed speech and language skills
  • exhibits echolalia (i.e., meaningless repetition of words or phrases)
  • gives unrelated answers to questions
  • has unusual reactions to the way things sound, smell, taste, look, or feel
  • is significantly affected by minor changes (e.g., schedule/routine changes; being prevented from following particular rules)
  • has keen focus or interests (e.g., strong memory for specific topics)
  • makes repetitive movements like flapping hands, spinning in circles, or rocking back-and-forth (Hyman et al., 2020)

Table 2 summarizes the core features of ASD grouped into the three major categories of social, communication, and repetitive behaviors. In addition, most people with ASD typically have diverse behaviors, habits, or needs beyond those listed above. Some of the most common include unusual sleeping or eating habits; delayed cognitive, learning, or movement skills; gastrointestinal (GI) issues (e.g., constipation); abnormal fear perception (e.g., lack of fear or excessive fear); anxiety; or hyperactive and impulsive behaviors (CDC, 2021c). 

Screening and Diagnostic Process

The diagnosis of ASD is a clinical one, as there are no laboratory tests or imaging studies to confirm the condition (NINDS, 2020). The DSM is the standard reference healthcare providers use to diagnose ASD, as it outlines the primary diagnostic criteria (see Table 3). However, in clinical practice, an ASD diagnosis is rarely straightforward. Making a definitive diagnosis can be complex and time-consuming. The process starts with screening modalities and typically involves a series of appointments and evaluations by a multidisciplinary healthcare team. The core features of the ASD screening and diagnostic process include the following:

• standardized observations of the child and routine surveillance
• screenings and assessments of their learning and cognitive abilities
• interviews to gather information about their behavior across multiple settings
• a comprehensive review of medical and developmental history (Hyman et al., 2020; Weissman et al., 2021b)

Routine surveillance and developmental screenings are recommended at the 9-, 18-, and 24- or 30-month well-child visits. Along with routine developmental surveillance, the CDC (2020e) and AAP (2021a) recommend all children should be screened for ASD at 18 and 24 months and anytime concerns are raised. The priorities for these visits include asking parents/caregivers about concerns they have about their child’s development or behavior, informal observation, and monitoring of symptoms in the context of routine health supervision. Developmental surveillance is insufficient to identify children who need further evaluation, as children with ASD may not demonstrate all the characteristics in these brief office visits. Parents and caregivers may not volunteer social and emotional concerns unless specifically asked. First-time parents may not be aware that their child’s behavior is abnormal or delayed. Therefore, standardized ASD-specific screening tools are indicated to help identify potential early manifestations and facilitate timely referrals. 

According to Hyman and colleagues (2020), screening is a brief, standardized evaluation to identify abnormalities and deviations from healthy developmental patterns. A screening tool helps detect concerns that may not be readily apparent otherwise. While screening does not confirm a diagnosis, it helps determine whether an additional evaluation is necessary. Healthcare providers are strongly encouraged to promptly refer all toddlers and children anytime an increased likelihood of ASD (or other developmental disorders) is suspected (Hyman et al., 2020).

Various ASD-specific screening tools are available, each targeting a specific age category and based on whether the child is being screened for the first time. First-tier (or level 1) tools are used to screen children for the first time to identify those with a significant chance of ASD from the general population (e.g., those at low-risk), such as in primary care settings. Second-tier (or level 2) screening tools are used for children identified to be at-risk based on developmental surveillance. Second-tier tools are usually more time-consuming, help differentiate ASD from other developmental disorders, and often require more expertise to administer and interpret. Although ASD-specific screening tools are more accurate than general developmental tools for identifying ASD, they are criticized for their limited sensitivity (i.e., imperfect ability to identify young children with ASD) and specificity (i.e., ability to differentiate ASD from other developmental conditions; Hyman et al., 2020; Weissman et al., 2021b).  

The Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) and the M-CHAT-R, with Follow-up (M-CHAT-R/F) are the most frequently used tests in the US. The test carries a sensitivity of 85% and a specificity of 99% and has been validated as a first-tier screening tool for more than 16,000 children in primary care practices (AAP, 2021b; Weissman et al., 2021b). The M-CHAT-R consists of 20 yes/no questions for parents/caregivers, takes 5 to 10 minutes to complete, and can be used for children between 16 and 30 months old. The scoring and follow-up of the M-CHAT-R and M-CHAT-R/F are as follows (AAP, 2021b; Robins et al., 2018):

• A score of 0-2 indicates a low likelihood of ASD. Therefore, no additional intervention is required, and surveillance should continue at subsequent health supervision visits.
• A score of 3-7 denotes a medium likelihood of ASD, and the M-CHAT-R/F is recommended. 
  • M-CHAT-R/F is a healthcare provider-conducted interview using the same 20 questions with additional follow-up inquiries.
• A score of 8-20 indicates a high likelihood of ASD and warrants an immediate referral to a specialist for a diagnostic evaluation and early intervention services. 

In 2016, the US Preventive Services Task Force (USPSTF) announced that there was “insufficient” (“I” statement) evidence to support the universal role of primary care screening for ASD. An I-statement indicates that when the recommendation was synthesized, the literature was insufficient to assess the balance of benefits versus harms in screening for ASD among patients whose parents/caregivers or clinicians have raised no concerns about ASD. However, the USPSTF confirmed the availability of sufficient evidence to support current screening tools (including the M-CHAT-R) as reliable detectors of ASD when concerns arise (Siu et al., 2016). The 2016 I-statement led to controversy among the research and medical communities regarding the risks, benefits, and potential harms of universal screening over the last few years. Still, the AAP, CDC, and other national organizations have not altered their strong recommendations for universal screening, as outlined above. Recently, a press release dated June 4, 2021, announced an update is in progress regarding the USPSTF recommendations for ASD screening of young children (USPSTF, 2021). 

A formal, more thorough, and more structured evaluation of the child’s development is recommended if any screening tool identifies an area of concern. Usually administered by a trained specialist, these more extensive assessments can include observations, structured tests, and additional questionnaires for parents/caregivers. Figure 1 provides an overview of the ASD screening process (Hyman et al., 2020; Weissman et al., 2021b). 

Diagnostic Criteria

According to the CDC (2020e), the final diagnosis of ASD should be made by a developmental pediatrician, pediatric neurologist, pediatric psychologist, or pediatric psychiatrist using the DSM-TR. According to the DSM-5-TR, to be diagnosed with ASD, a child must have persistent needs in all three areas of social communication and interaction (A1 to A3) plus at least two of the four types of focused, repetitive behaviors (B1 through B4) outlined in Table 4 (CDC, 2020d).

Table 4

DSM-5-TR Diagnostic Criteria for ASD

A. Social communication and interaction Current or historical struggles engaging with others across several domains, as seen through all of the following (not exhaustive): building, sustaining, and comprehending relationships challenges with talking and interacting with people back and forth in a group setting body language, reading facial expressions

B. Restricted, repetitive behaviors Actions, thoughts, and attention that are limited and remarkably consistent, sometimes referred to as restricted, repetitive behaviors (RRBs). At least two of the following (previously or currently; examples are illustrative, not exhaustive): curiosity and attention to a limited number of topics patterns of speech and movement that are unchanging significantly increased or decreased response or attention to sights/sounds/smells/touches/feelings from their environment very consistent patterns in daily routines

The ability to perform successfully in crucial environments (home, school, work, friends) is significantly hindered by the condition

Signs may increase with age and elevated communication and interaction requirements but are initially evident at a very young age

Another condition, such as developmental delay or intellectual limitation, does not provide an enhanced reason for the symptoms.

(APA, 2022; CDC, 2020d; Interagency Autism Coordinating Committee [IACC], n.d.)

As highlighted in Table 4, the diagnostic criteria for ASD require clinicians to specify the current extent of symptoms in categories A and B. ASD is graded from 1-3 (see Table 5). 

Common Accompanying Conditions

Several conditions often coexist with ASD, including developmental disorders, genetic disorders, medical illnesses, and mental health conditions. According to Hyman and colleagues (2020), this can prevent clinicians from recognizing the symptoms of ASD during early childhood, as it can be challenging to differentiate between ASD, intellectual developmental disorder, and social communication disorder. Approximately 30% of children with ASD have an intellectual disability (defined by an intelligence quotient [IQ] of < 70) with significant challenges in daily function, and 25% are in the borderline range (IQ 71–85; Autism Speaks, n.d.-a). 

Genetic Disorders

Children with ASD should be evaluated for common coexisting genetic disorders such as Fragile X syndrome, Rett syndrome, and tuberous sclerosis complex (TSC), all linked to an increased likelihood of ASD (see Table 6; CDC, 2021a). Genetic testing is more likely to find a genetic contribution to ASD if the child or another family member has ASD, if a family member has an ASD-related genetic change found through genetic testing, or if multiple family members have ASD. The most common genetic test for patients with ASD is called a chromosomal microarray (CMA), which evaluates chromosomes to identify abnormalities (i.e., extra or missing components) associated with ASD. CMA testing demonstrates a genetic contribution in 5% to 14% of patients with ASD. For patients who test negative for genetic findings on the CMA, whole-exome sequencing may be recommended as the next step in the diagnostic workup. Whole-exome sequencing evaluates for genetic changes in portions of DNA and identifies a contribution in 8% to 20% of people with ASD (CDC, 2021a; Hyman et al., 2020).

Seizures

Children with ASD have an increased risk of seizures and epilepsy even if another genetic condition is not identified. Children whose language skills regress early in life appear to have a higher risk of developing epilepsy or seizure-like brain activity. According to the NINDS (2020), up to 30% of children with ASD develop epilepsy by adulthood, and those diagnosed with both ASD and intellectual disability have the greatest risk of developing a seizure disorder (NINDS, 2020). Many symptoms of seizures overlap with ASD characteristics, making it challenging to differentiate between them. Symptoms also vary based on the type of seizure the child has and which part of the brain was affected; some demonstrate no visible signs at all. According to The Autism Community in Action (TACA), some of the most common seizure symptoms include the following:

• loss of focus
• staring spells
• rapid eye movements/blinking rapidly
• involuntary body movements such as stiffening or muscle twitching
• loss of consciousness
• confusion or disorientation
• anxiousness or mood changes (TACA, 2020)

GI Symptoms

While the etiology remains poorly understood, many children with ASD experience coexisting GI symptoms, such as constipation, diarrhea, nausea, vomiting, and abdominal pain. GI symptoms often correspond to certain behaviors and internalizing symptoms, with a prevalence rate of 9% to 91% (Ferguson et al., 2019). A large survey analysis of electronic medical records including nearly 300,000 children in the US revealed that children with ASD were 67% more likely to have a diagnosis of inflammatory bowel disease (IBD) than children without ASD. IBD consists of Crohn’s disease and ulcerative colitis and is associated with an overactive immune system (Lee et al., 2018). 

Depression and Anxiety

Depression is a relatively common co-occurring mental health in patients with ASD, affecting an estimated 7% of children and 26% of adults (Autism Speaks, n.d.-a). A population-based cohort study in Sweden found that by age 27, almost 20% of patients with ASD were also diagnosed with depression compared to only 6% of the control (non-ASD) population. Researchers found this risk for depression was even higher in patients with ASD without intellectual disability (Rai et al., 2018). Anxiety disorders affect 11% to 40% of children and teens with ASD compared to an estimated 3% to 15% of the general population. Anxiety can be triggered at different times or by various activities and manifest as physiological (e.g., racing heart, stomachache, muscle tightness) or psychological symptoms (e.g., extreme fear of crowds or social situations; Autism Speaks, n.d.-b).

OCD

OCD is a mental health condition characterized by obsessive thoughts (e.g., intrusive, unwanted thoughts, urges, or images) that drive compulsive behaviors (e.g., handwashing, checking, doing tasks a certain number of times, arranging things) to decrease or get rid of the obsession. OCD is more prominent in children and teens with ASD than in the general population, affecting 17% to 37% of children and adolescents with ASD. Historically, OCD symptoms have been challenging for clinicians to distinguish from the repeated behaviors and focused interests typical of ASD (Autism Speaks, n.d.-b; Martin et al., 2020).

ADHD

ADHD affects 30% to 60% of children with ASD compared with 6% to 7% of the general population (Autism Speaks, n.d.-b). According to Children and Adults with Attention-Deficit/Hyperactivity Disorder (CHADD, 2018), a national resource center on ADHD funded by the CDC, more than half of all individuals who have been diagnosed with ASD also have signs of ADHD. ADHD is characterized by an unrelenting pattern of inattention, difficulty managing time and organizational tasks, memory deficits, and periods of hyperactivity (high activity levels) or impulsivity that interferes with functioning, learning, and daily life (Autism Speaks, n.d.-b). While these conditions commonly coexist and various symptoms can overlap, the etiology of the relationship is not fully understood. However, both affect brain development in some way. Children receive dual diagnoses more frequently than adults, but one-third to two-thirds of children with ADHD experience symptoms lasting into adulthood (CHADD, 2018). Data from the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome, involving nearly 2,500 children, were reviewed to compare children diagnosed with ADHD and ASD with children with ADHD only. Researchers found that approximately 1 in 8 children currently diagnosed with ADHD was also diagnosed with ASD (Zablotsky et al., 2020). 

Sleep Disturbances

Sleep disturbances—including insomnia, difficulty initiating and maintaining sleep, frequent and prolonged night awakenings, irregular sleep-wake patterns, short sleep duration, and early waking—affect more than 80% of children with ASD. Sleep disturbances are more than twice as common in children with ASD than the general population or those with other developmental conditions not characteristic of ASD (Maxwell-Horn & Malow, 2017; Reynolds et al., 2019). While several studies have demonstrated a clear link between sleep disturbances and ASD, the etiology of this relationship remains unclear. The influences that contribute to sleep problems in patients with ASD are multifactorial and may include sensory over-responsiveness, abnormal melatonin production, ADHD, and mood disorders. Research has also revealed mutations in gene expression related to irregular, delayed sleep phases and sleep problems in some children and adults with ASD. Abnormalities in gene expression regulating melatonin pathways may also be responsible for low melatonin levels and circadian sleep disturbances. Furthermore, medications to treat common coexisting conditions such as ADHD can impair regular sleep-wake cycles (Carmassi et al., 2019; Maxwell-Horn & Malow, 2017).

Obesity

According to Autism Speaks (n.d.-a), ASD-associated health problems affect patients across the lifespan, from infancy to older adulthood. A study led by the CDC and the Health Resources and Services Administration revealed that adolescents with ASD were more than twice as likely to be obese than adolescents without developmental differences (31.8% versus 13.1%, respectively; CDC, 2019a).

Allergies

Skin and food sensitivities and allergies more commonly affect people with ASD than those without ASD. In a population-based cross-sectional study in the US, researchers used data involving nearly 200,000 children from the National Health Interview Survey (NHIS). They found that 11.25% of children with ASD had a food allergy, compared to 4.25% of children without ASD. Furthermore, they noted a 6% increased prevalence of all three types of allergies among patients with ASD versus those without (Xu, Snetselaar, et al., 2018). In another study examining data on parent-reported food allergies in children with ASD from the NHIS survey, for study years 2011-2015, researchers found that food allergies were practically 2.5 times more common in children with ASD (13.1%) than in children without ASD (5.4%; Tan et al., 2019). 

Risky Behaviors

Additional characteristics, risky behaviors, and challenges associated with ASD do not necessarily fit into the above categories. Some of the most common include the following (Autism Speaks, n.d.-a):

• Almost half of those with ASD wander or bolt from safety.
• More than 25% of 8-year-olds with ASD engage in self-injurious behaviors, such as biting, headbanging, and skin scratching.
• Approximately two-thirds of children with ASD between 6 and 15 years are bullied.
• Drowning is a leading cause of death for children with ASD, accounting for about 90% of deaths associated with wandering or bolting among those aged 14 and younger.

Treatment Options

While there is no cure for ASD, various treatments can help with many distressing symptoms. There are two primary treatment categories: educational and behavioral interventions (including communication approaches) and pharmacological therapy. Therapies and behavioral interventions (i.e., nonpharmacological treatments) are designed to treat the support needs of ASD to build skills and minimize potential gaps in development. Since the manifestations of ASD can overlap with other disorders, treatment must focus on each individual’s specific needs and not their diagnostic label. Therefore, treatment plans should be individualized, developmentally appropriate, and intensive, with a metric for periodically evaluating each patient’s response to ensure interventions are adjusted accordingly. While most people with ASD will benefit from treatment regardless of their age at diagnosis, it is generally accepted that the earlier these therapies are initiated, the better the outcomes (CDC, 2019b; National Institute of Child Health and Human Development [NICHD], 2021; NINDS, 2020). 

As outlined by Hyman and colleagues (2020), the three primary goals of treatment for children with ASD consist of the following:

• support the child’s core needs and associated co-occurring impairments (social communication, interaction, and restricted or repetitive behaviors and interests) 
• maximize functional independence by facilitating learning and adaptive skills
• eliminate, minimize, or prevent specific behaviors that may interfere with functional skills

Nonpharmacological Therapies: Educational and Behavioral Interventions

In the US, educational law mandates the use of practices supported by evidence-based research. As outlined by the US Department of Education, the laws and guidelines regarding children with ASD include the following:

• Individuals with Disabilities Education Improvement Act (IDEA) of 2004 (Public Law 108–446)
• No Child Left Behind Act of 2001 (Public Law 107–110) 
• Every Student Succeeds Act of 2015 (Public Law 114–95; US Department of Education, n.d.)

Therapy Options

Therapies that begin when the child is younger than 3 years old are referred to as early intervention services (EIS) and are typically organized through the state, local government, or school systems under part C of IDEA. IDEA guarantees free and appropriate education for every child with a disability (including ASD). Each state or territory develops individual policies for implementing IDEA (Hyman et al., 2020; US Department of Education, n.d.). EIS has effectively improved behavior, functional skills, and communication in children with ASD. The goal of EIS is to support each child’s needs over time to enhance functioning. In a small percentage of patients, areas of concern may be minimized to the extent that they no longer cause disability. While treatment strategies vary based on each child’s age, functioning, and individual needs, EIS typically includes the following core therapy groups: speech and language therapy (SLP), physical therapy (PT), occupational therapy (OT), and social skills training (SST; see Table 7). These core groups are traditionally integrated as vital components of ASD behavioral and communication therapies (Steinbrenner et al., 2020).

Services can be provided by an early intervention program, school-based education program, or private practice. The program should be reviewed and modified as the child's needs change over time (Weissman et al., 2021a). According to a review of EIS literature over the last 15 years, Landa (2018) described compelling evidence that young children with ASD benefit from these services. Furthermore, parents learn to implement child-responsive engagement strategies when a parent-coaching intervention is provided. The evidence supports combining parent-mediated and direct clinician-implemented interventions to maximize each child’s developmental gains (Landa, 2018). In a 2019 cohort study involving children in an urban EIS program, McManus and colleagues found that only 73% of referred patients initiated services, and only 43% successfully started services within the federally mandated deadline of 45 days. The researchers also concluded that one additional hour of therapy per month was associated with a 3-point functional gain on the Child Outcomes Summary score (McManus et al., 2019). Improved outcomes are seen if interventions are started before the age of 4, including decreased severity scores, increased IQ scores, and enhanced adaptive skills. Researchers revealed significant lifetime savings in a 2017 Canadian study when patients with ASD began intensive behavioral interventions without any waiting period (Piccininni et al., 2017).

No single therapy has been proven to be the most effective for ASD. In addition to varying by a child’s age and developmental level, interventions differ in their theoretical approach, delivery modality, and targets. According to Hyman and colleagues (2020), the most effective behavioral and communication techniques provide structure, direction, and organization for a child and their family. While numerous behavioral interventions and treatment programs are available, certain therapies have more robust evidence supporting their efficacy (Hyman et al., 2020; Weissman et al., 2021). The core features of effective ASD educational and behavioral programs include the following: 

• low staff-to-student ratio (1:1 or 1:2)
• individualized program tailored to meet the needs of each child
• teachers with specialized experience working with children with ASD and a highly supportive teaching environment
• at least 25 hours per week of services
• curriculum emphasizing attention, imitation, communication, play, social interaction, regulation, and self-advocacy
• predictability and structure
• functional analysis of behavior needs
• transition planning
• family/caregiver involvement
• close monitoring, ongoing program evaluation, and adjustment based on each child's evolving needs (Weissman et al., 2021a)

Wong and colleagues (2015) defined two categories of evidence-based interventions: a comprehensive treatment model (CTM) and focused interventions, both of which have been widely adopted and supported by evidence-based practice guidelines (Steinbrenner et al., 2020) and the AAP (Hyman et al., 2020). These interventions can be offered in several settings (e.g., classroom, home-based, or community) and individual or group sessions. CTMs consist of a set of practices designed to achieve a broad learning or developmental impact on several core features of ASD. CTMs can address multiple therapeutic goals over a defined period. In contrast, focused interventions target a single skill or goal. These interventions are operationally defined, address specific learner outcomes, and tend to occur over a shorter period than CTMs (i.e., until the objective is achieved). Focused interventions are the key components of educational programs for children and youth with ASD, and they may be effective for promoting skill development and communication (Hyman et al., 2020; Steinbrenner et al., 2020; Wong et al., 2015).

Two primary evidence-based approaches utilized in current practice include naturalistic developmental behavioral interventions (NDBI) and applied behavior analysis (ABA). NDBI incorporates ABA and developmental principles, emphasizing developmentally based learning objectives and foundational social learning skills. NDBI typically fosters a flow of social engagement patterns between a child and their provider (typically a therapist or behavioral interventionist). The goal is to promote child engagement and skill development, expanding the child’s communication, social cues, and play interactions. NDBI employs turn-taking during play, child-initiated teaching episodes, and naturally occurring opportunities to engage in clear and developmentally appropriate cues (e.g., antecedents) to elicit specific behaviors and consequences (e.g., rewards/reinforcement; Hyman et al., 2020; Landa, 2018). 

Most evidence-based treatment models for ASD are based on ABA, the most well-cited and widely researched behavioral intervention for ASD. ABA was developed in the late 1960s and defined as “the process of applying sometimes tentative principles of behavior to the improvement of specific behaviors, and simultaneously evaluating whether or not any changes noted are indeed attributable to the process of application—and if so, to what parts of that process” (Baer et al., 1968, p. 91). Hyman and colleagues (2020) currently define ABA as “the process of systematical interventions based upon the principles of learning theory to improve socially significant behaviors to a meaningful degree, and to demonstrate that the interventions employed are responsible for the improvement in behavior” (p. 22). ABA is offered to young children with EIS and used among older children, adolescents, and adult populations. ABA employs an operant conditioning model, a method of learning that uses rewards and punishments for behavior. It encourages positive behavior through rewards and discourages negative or unwanted behavior by ignoring it. This method seeks to associate a behavior and a direct consequence (either positive or negative) for the specific behavior (Autism Speaks, n.d.-c; Hyman et al., 2020; Landa, 2018).

In contrast to NDBI, ABA promotes a more straightforward, decontextualized, and highly structured approach. ABA aims to help improve the child’s communication, attention, focus, memory, and academics while decreasing specific problem behaviors. ABA is flexible: it can be performed in any setting as an individualized, one-on-one treatment or within a group. It typically occurs for 25-40 hours per week and can last for 1-3 years. It breaks the learning process down into the ABCs: antecedent, behavior, and consequence (Autism Speaks, n.d.-c; Hyman et al., 2020; Landa, 2018). There are various forms of ABA, and some prime examples are outlined below (Autism Speaks, n.d.-c; CDC, 2019b; NICHD, 2021):

• Discrete Trial Training (DTT): a style of teaching that utilizes a series of trials to teach specific steps of a desired behavior or response. Lessons are separated into simple fragments, and positive reinforcement is used to reward appropriate answers and behaviors. Incorrect answers are ignored.
• Early Intensive Behavioral Intervention (EIBI): a highly structured teaching approach that targets 3- to 5-year-olds to build positive behaviors (e.g., social communication) and reduce unwanted behaviors (e.g., self-injury, tantrums, and aggression). EIBI requires a one-on-one adult-to-child environment under the supervision of a trained professional.
• Early Start Denver Model (ESDM): used for 12- to 48-month-old children, focusing on play to build positive relationships and joint activities to help children expand their language, social, and cognitive abilities. 
• Pivotal Response Training (PRT): attempts to increase a child’s motivation to learn, monitor their behavior, and initiate communication with others through positive reinforcement. It targets “pivotal areas” such as the initiation of social interactions and self-management. PRT is play-based and child-led and can be implemented in the child’s environment at home. 
• Verbal Behavior Intervention Therapy (VB or VBI): focuses on teaching verbal communication skills. It helps children connect words with their use or purpose to help children understand why we need to use words and how they can be helpful.
• Positive Behavior Support (PBS): seeks to determine the cause of negative or unwanted behaviors, change the environment, and then teach skills regarding the correct or desired behavior as a replacement. 

In addition to NDBI and ABA, other evidence-based interventions for ASD are described in Table 8.

Family Involvement in Behavioral Therapy

Much of the success experienced by patients with ASD relies on the skills, capabilities, education, investment, and training of their parents/caregivers and family unit. A growing body of evidence reveals that focused interventions delivered by trained parents or caregivers are an important component of the treatment program. Families should be involved in the selection of intervention approaches and participate in all educational and therapeutic decisions. By law, students with ASD must receive an appropriate educational program, although it may not include all of the components desired by the family (Eidson et al., 2020). According to Hyman and colleagues (2020), parent management training consists of 2 categories: parent support and parent-mediated interventions. Parent support interventions are knowledge-focused, indirectly benefit the child, and include care coordination and psychoeducation. Parent-mediated interventions are technique-focused and directly benefit the child. They focus on the core needs of ASD and are often based on ABA principles. Studies demonstrate that parent-mediated interventions significantly impact both parental and child behaviors (Tabatabaei et al., 2020). 

The Preschool Autism Communication Trial (PACT), a randomized controlled trial employing a parent-mediated social communication intervention for children with ASD aged 2 to 4 years, was designed to work with parents to help improve parent-child communication at home. The researchers found a statistically significant overall improvement in support needs throughout the trial and long-term (6 years) within the parent-driven early intervention group. The treatment effect was apparent across social-communication and repetitive need domains (Pickles et al., 2016). In a 2017 systematic review, Parsons and colleagues (2017) identified preliminary evidence that parent-mediated intervention training delivered remotely (i.e., via self-guided websites, written training manuals, videoconferencing, or other audiovisual training) improves parent knowledge, increases parent commitment, and enhances social behavior and communication skills for children with ASD. These findings reveal the potential to reach and positively impact the outcomes of more patients and families using technology (Parsons et al., 2017). In addition, when a parent training program was directly compared with parent education only (i.e., the same information was offered regarding their child and their condition but no coaching on specific behavioral management techniques), Bearss and colleagues (2015) found significantly fewer problem behaviors at 24 weeks in the training group versus the education-only group.

Pharmacological Therapy

While medications cannot treat the core needs of ASD, they may be used to manage some of the medical or mental health comorbidities and symptoms. The Autism Speaks Autism Treatment Network (ATN) consists of hospitals, physicians, researchers, and families across the US and Canada, supported by a cooperative agreement with the US Department of Health & Human Services. The ATN (n.d.-a) has developed a tool kit to guide clinicians on the safe and judicious use of medications for children with ASD. While medications can help some children, medication is not suitable for everyone. The ATN (n.d.-a) recommends that medication therapy be suggested only after behavioral and educational methods have been unsuccessful in meeting certain behaviors and needs. Moreover, once medication therapy is initiated, ongoing behavioral therapies are still essential. Despite these recommendations, no formal guidelines preclude the early use of medication therapy. Medication use should be based on shared decision-making between the prescriber, the patient, and their family. The medication recommended will depend on the child’s primary needs, as each drug treats different targets. Before prescribing, APRNs should be transparent with families about treatment goals and the possible risks and benefits. APRNs are responsible for teaching families about monitoring for effectiveness and side effects of medications. This section will review some of the most commonly prescribed medications in ASD, but it is not a comprehensive list (ATN, n.d.-a).  

Second-Generation/Atypical Antipsychotics (SGAs)

Risperidone (Risperdal) and aripiprazole (Abilify) are the only US Food & Drug Administration (FDA)-approved medications for the treatment of ASD-associated irritability (Autism Speaks, n.d.-a). While both of these drugs are most commonly used to treat schizophrenia, they work differently. Risperidone (Risperdal) antagonizes dopamine and serotonin receptors in the brain, essentially rebalancing dopamine and serotonin levels in the brain to improve thinking, mood, and behavior (National Alliance on Mental Illness [NAMI], 2020c). Aripiprazole (Abilify) functions as a partial dopamine and serotonin 5-HT1A agonist and 5-HT2A antagonist, rebalancing dopamine and serotonin to improve mood, thinking, and behavior (NAMI, 2020a).

Risperidone (Risperdal) is indicated to treat irritability associated with ASD for children and adolescents aged 5 to 16 years. According to the FDA, this indication includes aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods. Risperidone (Risperdal) is weight-based and prescribed at a starting dose of 0.25 mg/day for patients weighing under 20 kg and 0.5 mg/day for patients weighing 20 kg or more. The dose can be titrated by 0.25 to 0.5 mg at 2 weeks to achieve the target dose. The effective dose range is 0.5 to 3 mg/day, but the dose should be individualized to the response and tolerability of each patient. The total dose can be administered once daily or twice daily in divided doses. Once a sufficient clinical response is achieved and maintained, consideration should be given to lowering the dose gradually to achieve the optimal balance of efficacy, safety, and side effects. Dose adjustment is required for patients with creatinine clearance (CrCl) below 30mL/min or severe hepatic impairment. The most common adverse drug reactions (ADRs) include somnolence, increased appetite, fatigue, rhinitis, fever, upper respiratory infection (URI), coughing, vomiting, urinary incontinence, increased saliva, and constipation. Less common ADRs include anxiety, tremor, dizziness, dry mouth, nausea, tachycardia, skin rash, and weight gain. In clinical trials, some patients experienced dystonia (hypertonia, involuntary muscle contractions, tetany, tongue paralysis) and Parkinsonism (extrapyramidal disorder, hypokinesia, bradycardia). APRNs should counsel patients and parents/caregivers that somnolence has an early onset with a peak incidence during the first 2 weeks of treatment and a median duration of 16 days. Persistent somnolence can be managed by administering a once-daily dose at bedtime, giving half the daily dose twice daily (instead of once daily), or reducing the dose (FDA, 2009). 

Aripiprazole (Abilify) is indicated to treat irritability associated with ASD for children and adolescents aged 6 to 17 years. The starting dose of aripiprazole (Abilify) is 2 mg/day, the recommended dose ranges from 5 to 10 mg/day, and the maximum daily dose is 15 mg/day. According to the prescribing guidelines, aripiprazole (Abilify) dosing adjustments should be limited to 5 mg/day and should occur gradually, at intervals of no less than 1 week. Patients should be routinely reassessed to determine their ongoing need for maintenance treatment. Increased appetite and weight gain are more common with aripiprazole (Abilify) than risperidone (Risperdal). Aripiprazole (Abilify) can also increase fasting blood glucose, cholesterol, and triglycerides levels. Sleepiness/sedation and drooling are common. Other reported ADRs include vomiting, somnolence, tremor, pyrexia, drooling, decreased appetite, salivary hypersecretion, extrapyramidal disorder, and lethargy (FDA, 2016; NAMI, 2020a).

Movement disorders are a rare but sometimes serious ADR associated with SGAs. These symptoms can occur immediately after starting the medication, following dose increases, after taking it for an extended period, or after it is discontinued. Movement disorders may manifest in various ways, but all typically include changes in body or muscle movements. Since movement disorders can be severe, APRNs who are prescribing risperidone (Risperdal), aripiprazole (Abilify), or any other SGA should counsel parents/caregivers on monitoring and promptly reporting these symptoms to their healthcare provider (ATN, n.d.-a). Some of the most common signs of movement disorder include the following:

• rigid muscles accompanied by a high fever or a change in alertness, heart rate, or breathing
• muscle spasms or cramping
• slowed movements of the body
• pacing or restlessness
• staring episodes, rapid eye blinking, and unusual eye movements or closing
• unusual mouth or tongue movements
• changes in walking, tremors, repetitive movements the child cannot control that are distinct from their baseline behaviors (ATN, n.d.-a)

While only two medications are FDA-approved for ASD-related irritability, several other drugs are used off-label to manage depression, anxiety, ADHD, or OCD symptoms. According to the Agency for Healthcare Research and Quality (AHRQ, 2015), off-label use means that while the drug is approved by the FDA, it has not been FDA-approved for the specific indication or condition for which it is being given. Off-label prescribing is a widespread and legal practice in the US. Approximately 1 in 5 medications are prescribed for off-label use (AHRQ, 2015).

Stimulants

Stimulant medications can reduce hyperactivity symptoms, improve focus, extend attention span, or manage impulsive behaviors. Medications for ADHD can effectively help diminish impulsivity and hyperactivity symptoms when it coexists with ASD (NINDS, 2020). Stimulants heighten the central nervous system (CNS) response, typically by increasing catecholamine levels in the brain. Catecholamines refer to a group of neurotransmitters that are endogenously released into the bloodstream in response to stress. The primary catecholamines are dopamine, epinephrine (adrenaline), and norepinephrine (Farzam et al., 2021). Some of the most commonly used stimulant medications in children with ASD include the following:

• methylphenidate (Ritalin, Concerta)
• dexmethylphenidate (Focalin)
• dextroamphetamine/amphetamine (Adderall)
• dextroamphetamine (Dexedrine)
• lisdexamfetamine (Vyvanse; ATN, n.d.-a)

Stimulants can cause many side effects such as sleep disturbances (especially difficulty falling asleep), anorexia, irritability, and emotional outbursts. Less commonly, patients may experience involuntary tics, depression, anxiety, headaches, repetitive behaviors and thoughts, diarrhea, or social withdrawal. In addition, CNS stimulants carry a risk for serious cardiovascular reactions, including changes in heart rate, abnormal cardiac rhythm, and increased blood pressure. Sudden death, stroke, and myocardial infarction have been reported in adults taking CNS stimulants at the recommended doses. Furthermore, these medications can induce psychosis and paranoia or exacerbate behavioral disturbance and thought disorder for patients with preexisting psychotic disorders (FDA, 2019). 

Stimulants have a boxed warning regarding their high potential for abuse and dependence. Prescribers must assess the risk of abuse before prescribing and monitor patients for signs of abuse and dependence while on therapy. Abuse is characterized by impaired control over drug use despite harm and cravings. The most common signs and symptoms of stimulant abuse include an increased heart rate, respiratory rate, and blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; loss of coordination; tremors; flushed skin; and vomiting. In rare cases, anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed. Tolerance refers to a state of adaptation in which exposure to a drug reduces the drug’s desired and/or undesired effects; it can occur during chronic therapy with these medications. Physical dependence occurs when the abrupt cessation of the drug produces withdrawal symptoms. Finally, stimulants have been associated with acute overdose, which can be fatal as the CNS is overstimulated. Symptoms of overdose can include GI distress (e.g., nausea/vomiting), restlessness, agitation, anxiety, tremors, hyperreflexia (overactive reflexes), muscle twitching, convulsions, euphoria, confusion, hallucinations, delirium, sweating, palpitations, cardiac arrhythmias, hypotension, tachypnea, mydriasis (pupil dilation), rhabdomyolysis (breakdown of muscle tissue causing the leakage of damaging proteins into the blood), and coma (Farzam et al., 2021; FDA, 2019).

Antidepressants

Antidepressants may be prescribed for depression, anxiety, panic disorders, repetitive thoughts or behaviors, or aggressive behavior. Most FDA-approved prescription medications for depression target three neurotransmitters: serotonin, norepinephrine, and dopamine. SSRIs work by increasing serotonin levels and are usually the safest initial choice of antidepressants because they tend to cause the least side effects. The most common drugs prescribed for ASD, including the following:

• fluoxetine (Prozac)
• fluvoxamine (Luvox)
• sertraline (Zoloft)
• paroxetine (Paxil)
• citalopram (Celexa)
• escitalopram (Lexapro; ATN, n.d.-a; National Institute of Mental Health [NIMH], 2016)

Antidepressants usually take 2 to 4 weeks to achieve their optimal effect. Symptoms pertaining to sleep, appetite, and concentration often improve before a notable change in mood. Due to their side effect profiles, most antidepressants need to be tapered up slowly when starting therapy and tapered down gradually when stopping treatment. If stopped abruptly, some antidepressants pose a risk for withdrawal-like symptoms such as dizziness, headache, flu-like syndrome (tiredness, chills, muscle aches), agitation, irritability, insomnia, nightmares, diarrhea, and nausea. The most common side effects include GI problems (nausea, vomiting, constipation), headaches, difficulty falling asleep, sleepiness, and weight gain. All patients taking SSRIs are at risk for an ADR called serotonin syndrome, characterized by agitation, anxiety, confusion, high fever, sweating, tremors, a lack of coordination, dangerous fluctuations in blood pressure, and rapid heart rate. Serotonin syndrome is a potentially life-threatening condition for which patients must seek immediate medical attention. While antidepressants typically do not require routine laboratory monitoring or drug levels, prescribers should remain alert to the potential side effects and adverse effects outlined above. SSRIs are rarely associated with hyponatremia, bleeding, and decreased bone mineral density (Mayo Clinic, 2019; NIMH, 2016).

Antidepressants that target the neurotransmitter norepinephrine may be used to treat ADHD, but they are not FDA-approved for this indication and are considered off-label. Bupropion (Wellbutrin) is a norepinephrine and dopamine reuptake inhibitor (NDRI) that helps improve concentration and focus and reduces hyperactivity; it is regularly prescribed for ADHD. Since bupropion (Wellbutrin) does not influence serotonin, it works differently than the antidepressants outlined above. The most common side effects include headaches, weight loss, dry mouth, insomnia, nausea, dizziness, constipation, tachycardia, and a sore throat. These side effects typically improve over the first 1 to 2 weeks on the medication. Rare but potentially serious side effects affecting under 10% of patients include skin rash, sweating, ringing in the ears (tinnitus), stomach pain, muscle pain, thought disturbances, anxiety, or angle-closure glaucoma (e.g., eye pain, changes in vision, swelling or redness in or around the eye). Bupropion (Wellbutrin) is also associated with an increased risk for seizures in people susceptible to them. This is particularly important for children with ASD due to the high prevalence of coexisting seizure disorders. Thus, it is recommended that bupropion (Wellbutrin) is not prescribed to children with coexisting epilepsy or those who have experienced recurrent seizures (NAMI, 2020b).

In 2004, the FDA required a warning to be printed on the labels of all antidepressant medications regarding the risk for increased suicidality among children and adolescents taking these medications. A few years later, the warning was expanded to all young adults, especially those under 25, stating that these individuals may experience increased suicidal thoughts or behaviors during the first few weeks on antidepressants and warning clinicians to monitor patients for this effect. The FDA also requires manufacturers to provide a Patient Medication Guide (MedGuide) to patients (or parents/caregivers) to advise them of the risks of suicide and precautions that can be taken. Furthermore, prescribers are advised to ask patients about suicidal thoughts before prescribing antidepressants to young persons (FDA, 2018). APRNs should counsel families on the heightened importance of monitoring for these symptoms in patients with ASD, particularly those with significant communication needs. Table 9 lists the points that must be included in the boxed warning.

Anticonvulsants

Anticonvulsants, also referred to as antiepileptic drugs (AEDs), are first-line treatments for seizures. To date, no AED has been explicitly studied regarding its efficacy in treating seizures in ASD. Still, AEDs are prescribed off-label for mood stabilization, aggression, and self-injury for children with ASD. Some of the most commonly prescribed anticonvulsants for children with ASD include the following:

• carbamazepine (Tegretol)
• valproic acid (Depakote)
• lamotrigine (Lamictal)
• oxcarbazepine (Trileptal)
• topiramate (Topamax; ATN, n.d.-a; TACA, 2020)

AED dosing for children is weight-based, and doses are titrated slowly based on tolerance and response. Patients and their caregivers should be counseled on the importance of taking medications at the same time every day. Consistency is vital to maintain a therapeutic blood concentration of the drug. Patients and caregivers should be reminded never to stop the medication without the prescriber's awareness and direction, as most options must be tapered to avoid withdrawal symptoms or increased seizure activity. Common side effects include sleepiness or drowsiness, nausea/vomiting, dizziness, and memory problems. Less commonly, patients can experience pancreatitis, liver failure, bone marrow suppression, tremors, hepatitis, and rashes (ATN, n.d.-a). According to TACA (2020), patients taking AEDs often experience one or more of the following:

• neurological side effects (e.g., ataxia, tremor, nystagmus)
• behavioral side effects (e.g., agitations, hyperactivity, aggression)
• GI side effects (e.g., nausea, abdominal pain)

Complementary and Alternative Medicine (CAM)

CAM treatments are non-mainstreamed practices implemented in the place of conventional options or alongside evidence-based treatments. Many CAM treatments have little or no scientific evidence supporting their efficacy but are widely available and used. CAM therapies are often considered attractive options for families because they focus on support needs (CDC, 2019b). Between 28% and 74% of children with ASD receive at least one CAM. According to Hyman and colleagues (2020), CAM therapies can be grouped into three major categories as follows:

• natural products (e.g., herbs, vitamins and minerals, and probiotics)
• mind and body practices (e.g., yoga, chiropractic care, massage, acupuncture, progressive relaxation, and guided imagery)
• other therapies (e.g., traditional medicine and naturopathy)

The National Center for Complementary and Integrative Health (NCCIH) maintains a website regarding novel CAM therapies for patients with ASD. The NCCIH (2017) acknowledges the lack of high-quality research on CAM treatments for ASD and makes the following statements and recommendations regarding current CAM approaches:

• There is no scientific evidence that chelation therapy (a treatment to remove certain heavy metals like lead from the blood and body) helps patients with ASD. On the contrary, it can even be harmful.
• Hyperbaric oxygen therapy (HBOT) provides a higher concentration of oxygen delivered in a chamber containing higher-than-sea-level atmospheric pressure. Since HBOT potentially increases cerebral perfusion, it has been proposed that children with ASD might benefit from this treatment. However, randomized controlled trials have not demonstrated clinically significant evidence supporting the benefit of HBOT for ASD. 
• There is no scientific evidence supporting the use and efficacy of oxytocin (a hormone and neurotransmitter involved in childbirth and breastfeeding that can modulate human social behavior and cognition). Moreover, it may even be harmful as there is no long-term evidence supporting the safety of this treatment. 
• Secretin (a digestive hormone released to regulate gastric acid secretion and pH levels in the duodenum) has been reported to improve GI dysfunction and reduce behavior needs in patients with ASD. However, secretin has no evidence supporting its efficacy in ASD, can have significant adverse effects, and is not recommended. 
• It is unclear whether acupuncture, mindfulness-based practices, and massage therapy can improve ASD symptoms, and they should not be used in place of conventional treatments.

Music therapy may positively affect social interaction, communication, and behavioral skills in children with ASD. According to Hyman and colleagues (2020), there is limited and conflicting evidence regarding the efficacy of other widely used CAM therapies, such as massage, chiropractic care, yoga, and equine-assisted therapy. However, unlike the CAM interventions described above, these options have little to no potential adverse effects. While further research is necessary to establish their clinical utility and efficacy, these interventions may be beneficial adjunct therapies for children with ASD, mainly when used with evidence-based treatments. There are numerous other CAM therapies not reviewed in this section. Regardless of the treatment, APRNs must encourage parents/caregivers to discuss all therapeutic options with their child’s healthcare provider before starting (CDC, 2019b; NCCIH, 2017, 2021). 

Dietary Interventions

Dietary interventions are often used to ameliorate the core needs and problem behaviors of ASD. Dietary adjustments are perceived as beneficial by many parents/caregivers because they are considered natural. The most common nutritional change is the elimination of dairy, sugar, gluten, and casein-containing food. To date, clinical trials have not demonstrated statistically significant treatment effects with these dietary adjustments (Hyman et al., 2020). The impact of novel diets, such as the ketogenic diet (which causes the body to break down fats instead of carbohydrates), is not fully understood. The ketogenic diet has been marketed toward controlling seizures associated with ASD, but there is minimal data that this high-fat, low-carbohydrate diet is advantageous. Evolving evidence has also demonstrated the side effects and health consequences of ketogenic diets in children, such as constipation, vomiting, a lack of energy, hunger, hyperuricemia, hyperlipidemia, and kidney stones. According to Li and colleagues (2021), the most severe side effect of the ketogenic diet in children is the suppression of physical development and impaired growth. While specific dietary changes may help improve problem behaviors in some children with ASD, their nutritional needs must be monitored to avoid harmful health consequences, especially dangerous vitamin, mineral, and nutrient deficiencies and growth retardation. Nutritional counseling is strongly recommended for parents/caregivers who want their child to try a special diet to manage ASD-related needs (Li et al., 2021; NCCIH, 2017). 

Supplements

Dietary supplements are readily available over-the-counter (OTC) and represent various substances ranging from vitamins and minerals to enzymes, probiotics, and botanicals. These are used for diverse indications, such as managing symptoms or enhancing wellness, and are available in various forms (e.g., pills, gummies, powders, bars, drinks). Most supplements and herbal preparations have not undergone rigorous scientific testing for safety or effectiveness. While the FDA regulates prescription and other OTC medications to ensure their safety and efficacy, dietary supplements are not subjected to the same scrutiny and oversight. The lack of FDA oversight and regulation of these agents poses concerns regarding their consistency, ingredient purity, and safety profiles. They often contain hidden ingredients that may not be appropriate for all consumers (Katzung, 2018; NCCIH, 2017). 

Popular dietary and vitamin supplements for ASD include melatonin, omega-3 fatty acids (fish or algae oil), amino acids, dimethylglycine, vitamin D, and vitamin B6 with magnesium. Despite their widespread use, there is limited high-quality research regarding the efficacy of these agents for children with ASD. The NCCIH (2017, 2021) supports the use of melatonin for sleep disturbances associated with ASD, as available research indicates that melatonin may be beneficial and carries minimal risks. Several studies have examined the role of omega-3 fatty acids for ASD, but it is not fully clear whether they improve symptoms. Therefore, the NCCIH (2017) advises against using omega-3 fatty acids in place of conventional treatment. 

No conclusive evidence demonstrates that children or adults with ASD require a higher vitamin intake than the daily recommendations for the general population. Some vitamins and dietary supplements can cause dangerous side effects and interactions when taken with other supplements or prescription medications. Taking too much of a supplement or vitamin or substituting supplements for prescription medicines can be harmful, causing severe side effects and dangerous drug interactions; in some cases, the consequences can even be life-threatening. Furthermore, the long-term risks of high-dose vitamin supplementation have not been studied in children with ASD. APRNs should counsel parents/caregivers on the safety hazards of initiating unproven therapies without speaking to their child’s healthcare provider (CDC, 2019b; Hyman et al., 2020; NINDS, 2020).

For more information on dietary supplements, refer to the Dietary Supplements NursingCE course.

Parent/Caregiver Education and Resources

It is challenging to predict the outcomes for children with ASD, especially those younger than 3 years. Some children will sustain the diagnosis, whereas others may no longer meet diagnostic criteria for ASD as they age. Typically, children who no longer meet the diagnostic criteria for ASD continue to demonstrate residual social, communication, and/or behavioral needs during adulthood. APRNs serve central roles in educating parents/caregivers on the signs of ASD to facilitate early recognition and intervention (Hyman et al., 2020; Shulman et al., 2019). 

APRNs should use each routine well-child healthcare visit as an opportunity to educate parents/caregivers on the early warning signs of ASD. According to the CDC (2020e), parents should take two priority actions if they suspect their child might have or is likely to develop ASD:

• First, talk to their child’s healthcare provider about their concerns.
• Second, call their local Early Intervention program or school system for a free evaluation of their child.

The CDC (2021b) offers a free, user-friendly Milestone Tracker app to makes it easy for parents/caregivers to track, support, and discuss their young child’s development with their child’s healthcare provider (https://www.cdc.gov/ncbddd/actearly/index.html). The ATN (n.d.-b) has compiled a decision aid for parents/caregivers to help them assess their personal beliefs on using medications for challenging ASD-related behaviors, providing information regarding the possible risks and benefits of different agents. This resource promotes collaboration with the child’s healthcare provider to choose a treatment that matches their personal needs, values, and treatment goals (ATN, n.d.-b).

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