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Best Practices: Pediatrics 

Best Practices: Pediatrics

Chapter:
Best Practices: Pediatrics
Author(s):

Mary Catherine Aranda

and Sarah J. Spence

DOI:
10.1093/med/9780195371826.003.0086
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Points of Interest

  • Current recommendations call for developmental surveillance at every well-child check and the use of autism-specific screening tools at 18 months and 24 months of age, as well as when there is any developmental concern.

  • Many resources regarding early detection and management of autism spectrum disorders have been developed in recent years including easy-access internet websites such as www.cdc.gov/autism, www.firstsigns.org, www.aap.org, and www.autismspeaks.org.

  • The primary-care evaluation of a child with an ASD should include a comprehensive history including birth, developmental, medical, and detailed family histories, and a complete physical exam including observations of the child’s interactions, communication, and behaviors.

  • The primary-care physician (PCP) should consider the following medical issues when caring for a child with an ASD: seizures, sleep disturbance, gastrointestinal dysfunction, feeding and nutritional issues, immune problems, tics and Tourette Syndrome, and genetic abnormalities. Children with ASDs are also at increased risk for intellectual disabilities, a history of regression, sensory-motor abnormalities, behavioral problems, and other psychiatric disorders.

  • Research suggests that intensive early intervention can substantially improve outcomes in children with ASDs.

  • Although behavioral and educational therapies are the mainstay of treatments, there is a vast array of therapeutic options currently in practice. Unfortunately, there is very little evidence regarding what therapeutic technique is best for a given child.

Introduction

With the rise in the prevalence of ASDs in the last 20 years to approximately 1 in a 110 children (CDC, 2007; Fombonne, 2009), primary-care pediatricians must rise to meet the challenge of recognizing, screening, evaluating, and managing children with ASDs in their practice. Media concern, parental awareness, and an expanding research agenda have pushed this group of diagnoses to the forefront of child development. Most primary-care providers are aware that autism involves the core deficits of an autism spectrum disorder, which include qualitative impairments in social interaction and communication, and restricted, repetitive, and stereotyped patterns of behavior, interests, and activities (Association, 2000). Because it has been shown that children with ASDs can make significant developmental gains with intense early intervention, parents and pediatric providers must recognize children at risk for ASDs as early as possible, be knowledgeable about intervention, and be able to make proper referrals for further workup and management if necessary.

This chapter is dedicated to the description of what would be considered “best practices” for pediatricians and PCPs. Unfortunately, the state of research into most medical issues in ASD is not well enough developed to have established truly evidence-based practice parameters. Here we summarize much of what has been presented in detail in previous chapters in this volume and synthesize the elements into a guide for caring for a patient on the autism spectrum. We describe the importance of developmental surveillance, the usage and timing of specific ASD screening tools, and the gold standards for diagnosis and thorough assessments. A synopsis of the latest research and best practices for evaluation and management of common medical conditions, psychiatric and cognitive comorbidities, and their workups will also be presented all in the context of providing a medical home for children with ASDs. Finally, we provide brief descriptions of the available interventions so the PCP can be familiar with the family’s options and help them navigate the system.

Developmental Surveillance and Screening

For over 10 years, professional groups have published consensus guidelines, practice parameters, and clinical reports to help PCPs recognize, evaluate, and manage children with suspected ASDs. Although each group has a slightly different focus, there is a clear consensus regarding the role of the PCPs in surveillance and screening. The PCP has a unique role as the point of first contact for most children. The practice of developmental surveillance at every well-child visit and the further use of general and autism-specific screening tools at specific time points is clearly important, but is not in widespread use (Myers & Johnson, 2007). Unfortunately, it is still common to see delays in screening and diagnosis that result in slower referrals to intervention and may adversely affect developmental outcome. Some of these practice recommendations and tools designed to help the PCPs recognize early signs of ASDs are reviewed below.

The first publication regarding guidelines for screening and diagnostic referral came from a meeting of leaders in the research and clinical community sponsored by the Cure Autism Now (CAN) foundation (Geschwind et al., 1998). Shortly thereafter, practice parameters were released by the American Academy of Child and Adolescent Psychiatry (Volkmar et al., 1999), the Child Neurology Society and the American Academy of Neurology (Filipek et al., 2000; Filipek et al., 1999) and the American Academy of Pediatrics (AAP) (AAP, 2001). Most recently the AAP has put out detailed clinical reports regarding identification and evaluation (Johnson & Myers, 2007) and management of children with ASDs (Johnson & Myers, 2007). Each of these publications reviews the current evidence and makes recommendations that can be used in the primary-care setting.

There have been mixed results regarding the accuracy of clinical judgment alone in estimating the developmental progress of a child (Sices et al., 2003; Smith, 1978). In one study, 80% of the children who were eventually diagnosed with ASDs were not initially flagged for concern by their physicians (Robins, 2008). Thus, as the rate of identification of children with ASDs increases, so has the evidence for the importance of screening. Evidence has shown that general screening tools may not be sensitive enough to pick up all ASDs hence the need for ASD-specific screening at specific intervals (Pinto-Martin et al., 2008).

Current recommendations from the AAP call for developmental surveillance to be done at every well-child visit and suggest the use of validated developmental screening tests at specific visits: 9 months, 18 months, and either 24 or 30 months of age (AAP, 2006). Crucial elements of surveillance include careful attention to parental concerns, knowing relevant risk factors, following developmental milestones, and close observation of the child. Risk factors for ASDs include family history of ASD, certain genetic syndromes, or any loss of skills. The AAP report recommends ASD-specific screening testing at the 18-month and 24-month visits, the latter of which is required to identify the child who experienced developmental regression between 18 and 24 months of age (Johnson & Myers, 2007).

There are a number of standardized screening tests available for use in the primary-care setting (see Chapter 5). Some are general developmental screening tests, including: the Ages and Stages Questionnaire (ASQ), the BRIGANCE Screens, the Child Development Inventories (CDI), and the Parents’ Evaluation of Developmental Status (PEDS). Others are ASD-specific, including: the Modified Checklist for Autism in Toddlers (M-CHAT), the Pervasive Developmental Disorders Screening Test 11 (PDDST-11), and the Social Communication Questionnaire (SCQ).

Increasing Awareness and Knowledge of ASDs

In response to poor consistency in screening for ASDs, several organizations have worked diligently to increase and enhance knowledge for professionals and for parents. These organizations provide valuable tools for use in the primary-care practice.

The Centers for Disease Control and Prevention (CDC) (www.cdc.gov/autism) has been closely tracking the prevalence of ASDs since 1996. A public awareness campaign called “Learn the Signs. Act Early” (www.cdc.gov/actearly) launched in 2004 has reached tens of millions of health-care providers, parents, child-care providers, and community supports. First Signs, an organization begun by a parent of a child with autism, is dedicated to guiding parents and practitioners through developmental monitoring, red flags for ASDs, screening, diagnosis and treatment. In 2007, First Signs and Autism Speaks teamed up to make a very useful ASD video glossary, which has video clips of typically developing children as well as children on the autism spectrum (www.firstsigns.org).

The AAP has released several publications and developed a resource toolkit to educate practitioners in recognizing the early signs of ASDs. They also help practitioners educate parents on both typical and atypical child development by giving them examples of when to be concerned (red flags). The “Autism A.L.A.R.M.” flyer informs primary-care physicians that Autism is prevalent, Listen to parents, Act early, Refer, and Monitor, and includes the AAP surveillance and screening algorithm for ASDs1. With this algorithm, pediatric primary-care providers implement a risk assessment point system to guide proper follow-up and evaluation of children who may have characteristics of an ASD. An AAP introductory booklet, “Understanding Autism Spectrum Disorders,” is also available for parents and primary-care providers. The AAP Autism toolkit (2007)2 is another valuable resource for physicians containing the surveillance and screening algorithm, ASD-specific screening tests, ASD evaluation checklists, physician information sheets, and parent handouts on autism-specific topics such as vaccines, therapies, and complementary therapies.

Autism Speaks (www.autismspeaks.org) is a private foundation dedicated to raising awareness and funding a global biomedical research agenda on the genetics, causes, early detection, diagnosis, and treatment of autism spectrum disorders. Their website is another resource for PCPs with general information about ASDs, reviews of various treatments and therapies, and research updates. They created the “100-Day Kit” for parents, a booklet published in both English and Spanish, which helps families organize and set priorities immediately after an autism diagnosis.

All of these tools are valuable to the PCP for their own use and to share with families.

Diagnosis and Assessment

Following the screening guidelines and employing these tools will allow the PCP to identify children suspected to have an ASD, but what then? Diagnostic criteria delineated in the Diagnostic and Statistical Manual of Mental Disorders from the American Psychiatric Association (DSM-IV or DSM IV-tr) (American Psychiatric Association, 1994 & 2000) can be used to confirm the suspicion or at least to narrow the diagnostic possibilities. In cases where the diagnosis is clear, the child can be immediately referred for early intervention services specific to autism. In other cases, practitioners may feel a referral for further ASD diagnostic testing is necessary but should be simultaneously recommending early intervention services. But PCPs need to understand that because of the heterogeneity of the disorder a diagnosis alone is insufficient. A thorough assessment of each child that can evaluate potential genetic causes, identify comorbid medical conditions, and delineate an individual’s strengths and challenges is often the most important piece for families, and is essential for treatment planning.

The “gold standard” ASD assessments are usually performed at clinical centers that employ a multidisciplinary team of experts in the field. Teams are often comprised of some combination of child psychologists, child psychiatrists, child neurologists, pediatric developmentalists, speech-language pathologists, and occupational therapists. Ideally, in addition to specific ASD diagnostic testing, the assessment should include thorough evaluation of behavior, cognition, speech and language, and sensorimotor function. A medical assessment should also be performed and appropriate referrals to specialists such as in neurology, genetics or gastroenterology can be made. Unfortunately the access to these centers is often limited.

Primary-Care Evaluation for Children with ASDs

The primary-care evaluation of a child with an ASD is based on routine primary-care practice guidelines with special attention to specific issues characteristic of ASDs (see Table 77-1). Ideally, office visits should take into account the child’s core deficits (e.g., poor social communication skills and resistance to change/need for routine) and PCPs should be aware that exams will often be limited by behavioral difficulties and visits may take longer (Myers & Johnson, 2007).

TABLE 77–1. Keys to history and physical exam in a child with an ASD

Thorough history

Query medical and behavioral issues past and present

Query developmental history

Query family history to include a three-generation pedigree

Complete physical exam

Observe child in exam room

Measure growth parameters, especially head circumference

Conduct dysmorphology evaluation

Evaluate skin with Wood’s lamp

Conduct neurological exam

Studies for all children with developmental delays

Conduct audiologic evaluation

Screen for lead

Studies to consider in ASD

Genetic testing

Metabolic testing

EEG

MRI

A comprehensive history includes a developmental history and three-generation pedigree. A complete medical history should include the typical review of systems but with special focus on problems that appear to be increased in children with ASDs: neurological issues (i.e., seizures), sleep difficulties, and GI problems. Birth history is also important because babies with prematurity, low birth weight, and perinatal difficulties appear to be at increased risk (Limperopoulos et al., 2008). Developmental history needs to query more than the simple language and motor milestones and should focus on social communication skills (e.g., back and forth sharing of sounds, eye contact, responding to name, imitating others, pointing) as well as any maladaptive behaviors (e.g., rocking, hand or finger mannerisms, spinning). Any sensory difficulties (e.g., sensitivity to loud noises, certain textures, certain tastes) should be elicited from the parent. A history of any loss of any skills or regression should be documented. Given the strong genetic component of autism, the child’s family history should be queried for any ASD diagnosis, genetic disorder, neurological disorders (seizures), psychiatric history (obsessive-compulsive disorder, anxiety or mood disorders), language delay or disability, and other learning difficulties.

Beyond its importance for routine health care, a physical exam is an opportunity for direct observation of a child’s behavior allowing a preliminary assessment of eye contact, joint attention, and the child’s main form of communication and expressive language skills. Any repetitive or stereotyped behaviors in the exam room should also be recorded. Noting the presence or absence of certain physical findings is essential. Although macrocephaly is not specific to autism, providers should be aware that this is overrepresented in this disorder with 20% showing head circumferences above the 98% (Fombonne et al., 1999). Examining the child for any dysmorphic features (face, limbs, stature, genitalia) can also yield clues to various genetic syndromes and diagnoses associated with ASDs. Because there is a higher incidence of autism in children with tuberous sclerosis, a careful evaluation of a child’s skin for neurocutaneous lesions such as hypopigmented macules or ash-leaf spots (using a Wood’s lamp or ultraviolet light source) is important. A neurological exam focusing on reflexes, abnormal movements, strength, tone, and coordination will assist the physician in ruling out neurological and muscle disorders that may be contributing to the core deficits of an ASD.

There are certain studies and labs that should be done in every child with developmental delay including an ASD. A formal audiologic hearing evaluation is recommended for all children with developmental delays (ASHA, 2004) to rule out hearing problems that could contribute to communication deficits. Lead screening is also recommended for all child showing signs of developmental delay, even if the child does not have pica or an oral fixation (CDC, 1997). Although not implicated in causing autism, lead poisoning can lead to learning disabilities, cognitive deficits, and behavioral problems. Many children on the autism spectrum, especially children with intellectual disabilities, remain in the oral-motor phase of development, placing them at a higher risk for lead poisoning (Cohen et al., 1976; Shannon & Graef, 1996).

Recommendations regarding additional medical testing are inconsistent (Johnson & Myers, 2007) and often based on clinical practice experience and expertise. PCPs need to recognize that further workup may have two different functions: diagnostic testing warranted by current health-related issues and testing for possible etiologies. This latter issue is often the most important to parents.

Tests to consider include EEG, MRI, and genetic testing. Some neurologists will use EEG for routine screening although the practice standards only call for it if there is a clinical suspicion of seizures or developmental regression. Brain MRIs are currently only recommended in the case of an abnormal neurological exam (Filipek et al., 2000). Many of the existing practice guidelines call for basic genetic testing in ASDs including high-resolution chromosome analysis and DNA for Fragile X. Many will also do fluorescence in situ hybridization (FISH) for the 15q region looking for duplication. The newer microarray technology is more sensitive in identifying abnormalities in individuals with ASDs (Shen et al., 2010) and is likely to replace karyotypes in the very near future. The presence of moderate to severe intellectual disability and syndromic features greatly increases the yield of genetic testing. Discovery of a genetic abnormality is especially important because of genetic counseling implications.

Although any additional testing may not be done in a primary-care setting, it is important for practitioners to be aware of the possible comorbidities in this disorder and to have a low threshold for making subspecialty referrals appropriate for each child. All too often, issues are ignored because they are simply attributed to “the autism.”

Establishment of a Medical Home

Despite the fact that a child may receive the diagnosis of an ASD outside of his primary care, a child’s medical home will usually continue to remain with his PCP. For this reason, patients and families will be greatly benefited by a provider who is knowledgeable about ASDs. Navigating the world of autism can be extremely difficult for parents and children. They deserve to have a primary-care physician who will recognize and manage common medical problems seen with ASDs, facilitate early intervention and school issues, help sort through various therapies and treatments, and ultimately aid in planning for various transitions such as entering school, beginning adolescence, and venturing into adulthood.

It is especially important to remember that these children need the same standard of care as children with typical development. They need to be treated for the same childhood illnesses, receive appropriate anticipatory guidance, and have their immunizations kept up-to-date.

Medical Issues to Consider

Seizures

One of the most frequent medical comorbidities is epilepsy. It is commonly stated that 1/3 of individuals with ASDs will have seizures, although reported rates are variable, probably resulting from sample ascertainment differences. Large population-based samples show rates ranging from 5 to 26% (Fombonne, 1999). Risk factors for epilepsy include moderate to severe intellectual disability, comorbid neurological and neurogenetic conditions (e.g., cerebral palsy, Tuberous Sclerosis Complex, 15q duplication syndrome), and female gender (Spence & Schneider, 2009). Age of seizure onset is bimodal (early childhood vs. adolescence or early adulthood) (Volkmar & Nelson, 1990), and there is variability in the type and severity of seizures.

The diagnosis of epilepsy is made more challenging because the behavior exhibited during a seizure can be confused with typical ASD behaviors. For instance, absence (petit mal) and complex partial seizures are characterized by periods of unresponsiveness. However, failing to answer to your name is one of the hallmarks of ASD behavior. Complex partial seizures can also demonstrate behavioral automatisms that could be confused with autistic stereotypical behaviors.

Any suspicion of seizures should prompt a neurology referral for further workup including EEG. Although a prolonged or overnight EEG (including natural sleep) is more sensitive to abnormalities than a routine office study, these are often more difficult to obtain in children with behavioral difficulties. Seizure treatment in ASD has the same goals as for all pediatric epilepsy: the best efficacy with the lowest side-effect profile; but with special consideration of behavioral side effects of anticonvulsants, both negative (behavioral dysregulation) and positive (mood stabilization).

Finally, there is growing awareness and interest in the occurrence of background EEG abnormalities—especially epileptiform discharges—in ASDs, even in the absence of clinical seizures. Some studies have shown epileptiform discharges in up to 60% of individuals (Chez et al., 2006; Kim et al., 2006). What to do about these abnormalities is not yet known but there are practitioners prescribing anticonvulsant medication based on the idea that discharges could negatively affect cognition or behavior. Although there are some small studies from other childhood epilepsy syndromes that suggest that these treatments could be beneficial (Spence & Schneider, 2009), more empiric data are needed to determine if these will eventually be considered among best practices in ASD.

Sleep Issues

Parents report significant sleep disorders as one of the most common comorbidities in ASDs. Sleep problems include insomnia, delayed sleep onset, sleep fragmentation, and early-morning awakening (Johnson & Malow, 2008) and appear to occur more frequently in children with ASDs than typical children (DeVincent et al., 2007; Polimeni et al., 2005). Although problems may be even more common in ASD children with comorbid intellectual disability, they are also prevalent for those with normal intelligence (Malow et al., 2006). PCPs must consider the multitude of causes for sleep difficulty including comorbid medical issues (seizures, gastrointestinal disturbance) or psychiatric issues (anxiety), medications (stimulants, asthma treatments) and/or behavioral/environmental issues. Finding the cause (s) and offering appropriate treatment may significantly improve daytime functioning (Johnson & Malow, 2008).

Gastrointestinal Dysfunction

Results from studies investigating the relationship between gastrointestinal (GI) symptoms and ASDs have been conflicting, leading to much discussion and debate. Initial reports of significant GI symptoms in children with ASDs (e.g., frequent constipation, loose stools or diarrhea, reflux, abdominal pain and bloating) suffered from selection bias and lack of control populations, calling into question whether this is an issue unique to autism. But a more recent study demonstrated significantly higher symptom rates in the ASD children compared to those with typical development and other developmental disabilities (70% versus 28% and 42%, respectively) (Valicenti-McDermott et al., 2006), supporting the idea that GI dysfunction is an associated condition of ASDs.

There have also been reports of abnormalities on endoscopy. In a now infamous study3 published in the Lancet in 1998, a group of GI specialists performed endoscopy in a small number of patients with ASDs and reported ileal lymphoid hyperplasia in these children (Wakefield et al., 1998b). Another group found esophagitis, gastritis, and duodenitis (Horvath et al., 1999). Further studies from the Wakefield group have postulated an immune-mediated pathology (Furlano et al., 2001; Torrente et al., 2002). However, interpretation of the findings is limited by lack of proper controls and biased recruitment of children with known GI symptoms, which may not be representative of the general population of children with ASDs. There is further disagreement regarding whether these histological changes are specific to ASDs or even pathological (MacDonald & Domizio, 2007).

At this time, there are no specific recommendations regarding GI workup or treatment in children with an ASD diagnosis. However, the Autism Speaks’ Autism Treatment Network, a group of clinicians from 15 hospitals serving children with autism, is currently developing guidelines for GI assessment in autism. For ASD patients with GI symptoms, a closer evaluation of the GI system is certainly warranted. Dependent on the severity of the condition, a GI referral may be necessary. Anecdotal evidence suggests that GI discomfort can contribute to aberrant behavior and that behavioral improvement can be seen with proper medical treatment.

Feeding and Nutritional Issues

Food selectivity is frequently described in children with ASDs. Sensory as well as behavioral issues and rigid mealtime routines have been implicated. However, data on nutrient intake of these children is both limited and conflicting. One study demonstrated no differences in nutrient intake between children with and without ASDs (Lockner et al., 2008). Another showed inadequate vitamin intake in children with ASDs (Cornish, 1998). Anecdotally the authors have seen patients where strict food preferences have actually contributed to malnutrition and required intervention via tube feeding.

Many children with ASDs will be placed on modified diets and/or given supplements (Hanson et al., 2007; Levy & Hyman, 2003). Concern for food allergies may drive special diet choices but there has been limited research proving any overlap of non-IgE-mediated food allergies and autism (Jyonouchi, Geng, Ruby, Reddy, et al., 2005; Jyonouchi, Geng, Ruby, & Zimmerman-Bier, 2005). Families may confuse what they see as adverse behavioral reactions to a given food with a true allergy. This is not to say that children with ASDs never have food allergies, but these may not be related to the autism diagnosis (Murch, 2005). The pediatrician should be aware of the child’s diet and should help supervise any exclusion diet or vitamin supplementation to ensure there are no significant nutritional deficiencies or significant side effects from high doses of vitamins. If close monitoring of diet and supplements is beyond the scope of practice for the practitioner, a referral to a nutritionist might be beneficial.

Immune Problems

Involvement of the immune system in autism is currently a very active research area (see Chapter 24), but most of the work has been done in the basic science arena investigating etiology. From a clinical perspective the data are limited. Counter to anecdotal reports, there is no evidence for increased rates of infection in the early lives of children with autism (Rosen et al., 2007). Some studies have suggested higher rates of autoimmune disorders in family members of children with autism (Sweeten et al., 2003). Immunological profiling of children with ASDs has yielded inconsistent evidence of immune dysregulation (Ashwood & Van de Water, 2004) and the clinical significance of this remains unknown. Because auto-immunity has been implicated (Wills et al., 2007), some practitioners are advocating immune-mediated treatments (steroids or intravenous immunoglobulins). Although this may eventually prove to be an important treatment mechanism in ASDs, at this time there is scant evidence to support efficacy.

Tics and Tourette Syndrome

Studies have shown significantly higher rates of tics and Tourette Syndrome in individuals with ASDs than would be expected by chance co-occurrence alone. In samples of ASD patients tics have been reported in up to 22% and Tourette Syndrome in 8 to 20% (Baron-Cohen et al., 1999; Burd et al., 1987; Canitano & Vivanti, 2007).

One difficulty for practitioners is to differentiate tics (especially complex tics) from the motor and vocal stereotypies seen in ASDs. Tics tend to be brief and occur abruptly out of the context of typical or normal behavior. Stereotypies such as hand flapping, spinning, and hopping are repetitive or ritualistic movements that are typically more rhythmic and continuous than tics. Tics tend to have a waxing and waning course and can change in type and frequency while stereotypies will often remain constant for many years. Although children with autism will likely have stereotypies, it is important for pediatricians to be aware of the increased risk of tics and Tourette syndrome in ASDs because of the treatment implications. Children on the autism spectrum with comorbid tic disorders may have worsening tics when started on stimulant medications. Neuroleptic medications, often used in patients with a primary tic disorder, may be beneficial to the child on the spectrum with comorbid tics but will likely be less effective for the stereotypies.

Genetic Abnormalities

Although the etiology of autism remains largely unknown, it is clear that there is a strong genetic component, and recurrence risk within families is estimated at approximately 10%. Certain genetic syndromes or neurogenetic disorders are also known to be overrepresented in individuals with ASDs. Neurological or genetic disorders may account for up to 10 to 20% of autism cases (Barton & Volkmar, 1998; Kielinen et al., 2004; Oliveira et al., 2007) and chromosomal abnormalities are present in 3 to 9% using standard cytogenetic testing (karyotyping) (Fombonne et al., 1997; Wassink et al., 2001). Newer genetic testing methodologies using microarrays are now able to detect copy number variations (CNVs), which demonstrate microdeletion and duplications in the genome, postulated to be etiologically related to ASDs in a subset of patients (Sebat et al., 2007; Szatmari et al., 2007).

The most frequent associations are with Fragile X Syndrome, Tuberous Sclerosis Complex, and 15q duplication syndrome, each of which is thought to be present in 1 to 3% of individuals with autism. Rett Syndrome also shares phenotypic features with autism (at least at the early stages) and should especially be considered in girls with regression. A microdeletion and/or duplication syndrome involving a region on chromosome 16 (16p11) has also been reported (Kumar et al., 2008; Weiss et al., 2008). Autism has also been seen in patients with other neurogenetic syndromes, including: Neurofibromatosis, Hypomelanosis of Ito, Moebius Syndrome, Prader-Willi and Angelman, Joubert, Down Syndrome, Williams Syndrome, Sotos Syndrome; muscular dystrophy, Cowden Syndrome, Cohen Syndrome, Velocardiofacial Syndrome, ARX mutations, and Timothy syndrome (Spence, 2004). Obviously each of these syndromes must be considered in the context of its typical clinical presentation beyond autism symptoms.

There are also reports of an autism phenotype in some patients with metabolic disorders such as untreated Phenylketonuria (PKU) (Baieli et al., 2003), disorders of purine metabolism, biotinidase deficiency, disorders of cerebrospinal fluid (CSF) neurotransmitters including deficiency of folic acid (Moretti et al., 2008), and Smith-Lemli-Opitz syndrome (SLOS) (Tierney et al., 2001), and others (Manzi et al., 2008). Although these are rare conditions, detection is crucial because they may represent treatable entities.

There has also been interest in the overlap between mitochondrial disorders and ASDs, which is highlighted in a case report questioning the role of vaccines in the autistic regression of a child later found to have an underlying mitochondrial disorder (Poling et al., 2006). Published literature would suggest that these cases are rare, but clues to possible mitochondrial dysfunction include significant hypotonia, seizures, and severe delays (Filiano et al., 2002; Oliveira et al., 2005).

Other Associated Conditions

Intellectual Disabilities

Historically the literature has stated that approximately 70% of individuals with autism have comorbid intellectual disability (Fombonne, 1999; Rapin, 1997). However, there have been more recent studies that have shown lower rates (Fombonne, 2009) and this may result from the inclusion of children on the milder end of the autism spectrum, availability of intervention, and improved testing of cognitive abilities in nonverbal children.

Cognitive abilities can be difficult to measure because of behavioral difficulties that interfere with testing and the fact that tests often rely heavily on language, a core deficit in this disorder. Therefore, low scores may not be completely reflective of true deficits. In tests that attempt to separate out nonverbal and verbal abilities, there is often a significant discrepancy between verbal and nonverbal scores. Although the trend has been either similar scores on these domains or higher scores on the nonverbal domains (Munson et al., 2008), higher verbal scores have been found in some studies of children with high-functioning autism or Asperger Disorder (Miller & Ozonoff, 2000).

Knowing the cognitive level of an individual with an ASD impacts several factors, including diagnostic clarity, treatment, and prognosis. Clinicians often have a difficult time differentiating autism core features in a child with severe intellectual disability. Because children with very low IQs will often be nonverbal and have limited social awareness, one might confuse this with autism. Therefore, clinicians must evaluate a child’s social abilities in relation to their developmental age before diagnosing an ASD.

Individuals with ASDs and intellectual disability also have an increased risk of comorbid disorders such as epilepsy (Spence & Schneider, 2009), psychiatric disorders (attention-deficit/hyperactive disorder, mood disorders, catatonia) (McCarthy, 2007) and genetic syndromes (especially in dysmorphic individuals) (Battaglia & Carey, 2006; Miles & Hillman, 2000; Shevell et al., 2001). Furthermore, correct assessments of cognitive abilities are crucial for educational planning. Overall intelligence and particularly nonverbal cognitive ability tends be one of the strongest predictors of outcomes in general (Helt et al., 2008), in studies investigating pretreatment variables in predicting the success of behavioral treatments (Howlin et al., 2009), and in studies extending to adulthood (Howlin et al., 2004).

There are children on the autism spectrum with extraordinary splinter skills in areas such as math or art who may be considered savants, but these situations are rare and poorly understood.

Regression

Approximately 1/5 to 1/3 of children with ASDs will experience some type of regression of previously acquired skills. This typically occurs between 15 and 24 months of age (Turner et al., 2006; Werner & Dawson, 2005). Severe regression occurring after a 2-year period of typical development is diagnostic of Childhood Disintegrative Disorder, a rare pervasive developmental disorder (Association, 1994; Mouridsen, 2003).

Regression can be in the form of loss of verbal skills, loss of social skills (eye contact, play behaviors) or loss of gestural communication (waving bye-bye, pointing) (Lord et al., 2004; Meilleur & Fombonne, 2009; Stefanatos et al., 2002) and can occur in children with typical development or even more often, in the setting of already delayed milestones (Meilleur & Fombonne, 2009). Some studies have suggested a poorer cognitive outcome for children with ASDs and regression, with these children having more intellectual disability (Hoshino et al., 1987; Kobayashi & Murata, 1998).

The astute clinician should not automatically attribute signs of regression to psychosocial stressors (such as a family move or a new sibling), but rather further investigate the nature and severity of the regression. Epileptic disorders such as infantile spasms or Landau-Kleffner Syndrome or rare metabolic disorders need to be considered in the differential diagnosis.

Sensory-Motor Abnormalities

Although not part of the core features of autism, sensory and motor dysfunction is common in children with ASDs. Odd behaviors appear to indicate either decreased or increased interest or sensitivity to the sensory world (Rogers et al., 2003). These occur in all senses, including visual (close visual inspection, peering out of the corners of the eyes), auditory (intolerance to noises, holding hands over the ears), somatosensory (repetitive feeling of surfaces, intolerance to certain sensations) or olfactory systems (needing to sniff objects).

More interest is also being paid to subtle motor deficits in these children. There have been reports of motor delays (Mayes & Calhoun, 2003), hypotonia (Ming et al., 2007), gait and balance issues (Kielinen et al., 2004; Minshew et al., 2004), clumsiness (Ghaziuddin & Butler, 1998), and dyspraxia (Dziuk et al., 2007; Mandelbaum et al., 2006) in individuals with ASDs (see Chapter 22).

Behavior Problems

Many children with ASDs have challenging behaviors such as significant tantrums, aggression toward others, and self-injury, which often interfere with educational programs, community involvement, and family life. These may be more prevalent in individuals with comorbid intellectual disability (Bodfish et al., 2000; Schroeder et al., 2001).

A role for the PCP is to evaluate the child for medical reasons that may be contributing to these behaviors (Bosch et al., 1997), as a number of medical problems may negatively influence behavior. A careful history and examination is essential for their identification, especially because individuals with autism may not be able to communicate specific symptoms. The following medical issues should be considered: infections (otitis media, pharyngitis, dental abscess, UTI, URI); GI problems (constipation, reflux); sleep disturbances; undetected injuries (even fractures); hormonal fluctuations during puberty. Those medical issues that are amenable to treatment should be treated accordingly. In addition to common medical issues, medications or supplements that the child may be taking may produce behavioral side effects. Finally, possible environmental or situational causes of the behaviors should be explored with the family. As with typically developing children, transitions, family events, certain places, and new siblings can be possible reasons for exacerbation of problem behaviors.

PCPs can also help families with behavioral intervention by requesting a functional behavioral analysis to be accomplished by a child psychologist or qualified professional in the school system. This analysis should not only assist in discovering the antecedents and triggers for the behaviors, but should also facilitate a behavioral plan to decrease and/or manage behaviors. In severe cases, physicians should consider referral to a specialist for medication management (a developmental-behavioral pediatrician, child psychiatrist, or child neurologist).

Other Psychiatric Disorders

It is important for the PCP to be aware that children with autism can and do present with comorbid psychiatric disorders. Although current DSM criteria preclude a diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) in the setting of ASD, it is clear that many children on the spectrum have significant difficulty with attention and hyperactivity. Similarly, mood disorders and anxiety can be common. Given the complexities of teasing out behaviors that result from the autism vs. these other disorders, most PCPs will want to consider referral to a child psychiatrist for further evaluation and treatment. (See Chapters 1518, 20, 22, 69, and 76 for more detail.)

Interventions

As soon as a child is suspected of having an ASD, early intervention services should be initiated as research suggests that intensive early intervention substantially improves outcomes (Sallows & Graupner, 2005). A panel convened by the National Research Council defined intensive early intervention as at least 25 hours per week of instruction with year-round services (Lord & McGee, 2001). Although a PCP may not be responsible for setting up therapy, understanding the options and educating families on their rights is important. A brief overview is presented below.

Navigating the Educational System

Federal regulations ensure that all children with disabilities be offered funded educational programming either through an Individualized Family Service Plan (IFSP) or an Individualized Education Plan (IEP). A state-funded IFSP will document and guide the early-intervention process for the family with a child under 3 years old with a suspected or diagnosed ASD. When the child turns 3 years old, the local school system takes over the child’s educational services. IEPs outline the education services to include needed therapies (behavioral, speech, occupational, physical) for learning purposes as well as specific short-term and long-term goals for the child with an ASD. However, these programs are not mandated to offer the 25 hours per week of instruction or year-round services, so the child’s pediatrician should be aware of other community services and therapies to supplement the child’s early-intervention experience. Local programs vary tremendously and many families will choose to go beyond the funded programs to obtain more intensive or different services.

Available Behavioral Interventions

Behavioral and educational therapies are the mainstay of treatments. Unfortunately, the literature regarding the efficacy of various therapies lags behind the growing number of children needing services. Although there are certainly differences between treatment programs in technique and even underlying theory (e.g., strict behaviorist vs. more developmental or naturalistic), there is some agreement on some common elements including the need for: immediate access, intensive therapy, low student–teacher ratios, parent training, exposure to typically developing peers, frequent evaluation, structure and predictability, and opportunities for generalization (Myers & Johnson, 2007). (For more detail on these therapies, see Chapter 5866, and 75 in this volume.)

Applied Behavior Analysis (ABA) techniques have been the best-studied and have demonstrated efficacy for creating significant developmental and cognitive gains (Lovaas, 1987; McEachin et al., 1993; Sallows & Graupner, 2005). ABA therapy strives to increase and enhance social communication as well as teach cognitive skills and decrease problem behaviors through a variety of behavioral analytic methods to include, but not limited to: repetition, positive reinforcement, shaping, prompting, and fading.

The Treatment and Education of Autistic and Related Communication-Handicapped Children (TEACCH) program is a special education model tailored to the individual’s needs, similar to ABA. The focus of TEACCH is a structured physical, social, and communicating environment, especially helpful for the visual learner (www.teacch.com). Another team-based educational model is Social Communication, Emotional Regulation and Implementing Transactional Supports (SCERTS). This model uses a variety of behavioral interventions including ABA, visual supports, and augmentative communication (www.scerts.com).

The Developmental, Individual-difference, Relationship-based (DIR) model contains “Floor-time” therapy. The Floor-time model involves the parent engaging the child at his or her current developmental level and allowing the child to lead the interaction (www.floortime.org). The Relationship Development Intervention (RDI) method is another parent-based therapy (Gutstein et al., 2007) with a goal of having the child make social improvements in everyday functioning and relationships through a variety of social activities (www. rdiconnect.com). These interventions, although popular, have not yet been empirically validated to be efficacious.

Responsive teaching (RT) (Mahoney & Perales, 2005) and Pivotal Response Training (PRT) (Koegel et al., 2001) are intervention models that encourage parents to be the primary interventionists and are applied in the child’s natural environment, such as home and school.

Other approaches to augment behavioral therapies are also frequently employed. Speech and language therapy works on verbal and nonverbal skills as well as teaching other modalities of communication such as sign language or use of augmentative communication devices or systems. For children with fine motor delays, delayed self-help skills, or significant sensory issues, occupational therapy may be beneficial. Therapists often use sensory integration therapy for children with ASDs and sensory issues, although efficacy data are lacking. Another commonly used technique (especially for higher-functioning children) is social skills training, which may help with joint attention, social communication, and understanding of nonverbal cues.

The bulk of published evidence supports the efficacy of early intervention based on applied behavior analysis. Unfortunately, there is very little evidence regarding what therapeutic technique is best for a given child. This leaves many families struggling with which model to choose or being forced to go with what is available in their community.

Psychopharmacological Treatment

Although pediatricians may not be prescribing medications, they should be aware of those agents in most common usage for individuals with ASDs. Treatments are currently targeted on specific symptoms and medication choices are based on usage in other childhood psychiatric disorders. But as reviewed in this volume (see Chapter 69 and 76) there is limited empiric evidence for efficacy specifically in autism. At the same time, psychoactive medication usage is very common and increasing over time in this population with reported rates over 50% (Aman et al., 2003; Mandell et al., 2008; Oswald & Sonenklar, 2007).

Stimulants and alpha-adrenergic blockers target hyperactivity and attentional problems. Antidepressants (especially serotonergic) are commonly used for mood, anxiety, and the obsessive-compulsive type behaviors (restricted interests, repetitive behaviors). Various mood stabilizers (including anticonvulsants) are used for mood lability and outbursts. Antipsychotic or neuroleptic agents are most often employed for aggression and irritability. In fact, risperidone is currently the only agent with specific FDA approval for use in ASDs. Melatonin and a variety of sedative agents have been used for sleep problems.

Complementary and Alternative Medicine (CAM)

It is imperative for the pediatrician to appreciate the high rate of CAM use in individuals with ASDs. Studies estimate that up to 75 to 95% of ASD families may be using some form of CAM (Harrington et al., 2006; Levy & Hyman, 2003; Wong & Smith, 2006). So in order to provide optimal care, physicians need to be asking families about CAM use. One role for the PCP is to encourage families to carefully evaluate the scientific evidence (or lack thereof) for these treatments and to point out those with “red flags” that would make us question their validity, such as claims of immediate benefit, cure, and total lack of side effects (Myers & Johnson, 2007). Parents also need to know that so-called “natural” treatments may produce adverse effects and affect other medications that the child is taking. Although a full review of the available CAM therapies is beyond the scope of this chapter (see Chapter 71 for a complete review), awareness of the most common treatments is important.

The gluten-free casein-free diet is one of the most commonly used special diets. Anecdotally parents report not only improved GI symptoms, but also improved behavior and communication skills. Unfortunately, this diet has not yet been rigorously tested for efficacy and small studies show conflicting results (Elder et al., 2006; Knivsberg et al., 1995; Knivsberg et al., 2002). Parents need to know that this diet is still unproven in children with ASDs.

Supplements are another common CAM therapy. There are a multitude of products marketed for children with autism, including vitamins, minerals, fatty acids and amino acids, and even enzyme preparations. Some are recommended in homeopathic doses, others in supratherapeutic amounts. Again, there are very few studies to support their use, but the PCP must be aware of what patients are taking and educate families on possible side effects such as those seen with high doses of certain vitamins (e.g., A, D, E, B-3, B-6, and C) (Rosenbloom, 2007).

Practitioners and families may find the National Center for Complementary and Alternative Medicine (NCCAM, www.nccam.nih.gov) to be a helpful resource for investigating various alternative therapies for ASDs.

Conclusions

Given the prevalence of autism, PCPs will inevitably be taking care of patients on the autism spectrum. Best practices would dictate that the child with an ASD is cared for in the context of a medical home where the practitioner is knowledgeable about everything from screening and diagnosis, to workup and management, to interventions and family support. This is obviously a lofty goal for many primary-care providers in the current practice setting but we hope the information provided in this chapter can get them closer to a realization of this goal.

Unfortunately, the state of the scientific literature is not at the point where truly evidence-based practice parameters can be devised for most of the problems encountered by individuals with ASDs in the primary-care setting, but we should be heartened by the fact that there are groups working on this issue. As mentioned above, the Autism Treatment Network4 is a collection of autism centers around the country and in Canada that is dedicated to collecting the data necessary to create practice parameters for medical workup and treatment of children with ASDs. As data are collected, practice standards and, later, true evidence-based practice parameters will be created and shared with the primary-care community. Until that time, PCPs are left with the enormous challenge of keeping up-to-date with a fast-moving and complex field.

Challenges and Future Directions

  • Creation of a medical home in the primary-care setting for all individuals with autism that would greatly improve care practices for children and their families.

  • Improved access to autism diagnosis and evaluation centers and subspecialty referrals for all families to reduce burden on primary-care providers.

  • Improved data on prevalence of various medical and other comorbidities in ASDs that would allow for better education for families on the risks of these entities.

  • Establishment of practice standards and eventually evidence-based practice parameters for management of medical issues in ASDs.

Suggested Reading

Johnson, C. P., & Myers, S. M. (2007). Identification and evaluation of children with autism spectrum disorders. Pediatrics, 120 (5), 1183–1215.Find this resource:

Myers, S. M., & Johnson, C. P. (2007). Management of children with autism spectrum disorders. Pediatrics, 120 (5), 1162–1182.Find this resource:

Acknowledgments

The authors wish to thank Susan Swedo, Audrey Thurm, and Geoff Smith for helpful comments on this manuscript.

Disclaimer: This work was written as part of our official duties as Government employees. The article is freely available for publication without a copyright notice, and there are no restrictions on its use, now or subsequently. The views expressed in this chapter are the private views of the authors and are not to be construed as official or reflecting the views of the NIMH, NIH, HHS, Department of the Army, Department of Defense, or the United States Government.

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              Notes:

              3 The real controversy came with the comment that these children had experienced a behavioral regression after their MMR vaccine, implying that the vaccination may have been causally related to autism (Kawashima et al., 2000; Wakefield et al., 1998a), a controversy that played out in the media. However, in 2004 allegations of scientific misconduct were brought to the Lancet editors (Horton, 2004) and a partial retraction was printed by 10 of 13 authors (S. H. Murch et al., 2004). Many further studies have failed to demonstrate a causal relationship between MMR and ASD (Chen, Landau, Sham, & Fombonne, 2004; Dales, Hammer, & Smith, 2001; DeStefano, Bhasin, Thompson, Yeargin-Allsopp, & Boyle, 2004; Hornig et al., 2008; Richler et al., 2006; Taylor et al., 1999). Unfortunately, because of the media frenzy, there are still concerns about the possible link between the MMR and autism in the lay community.

              4. Website: http://www.autismspeaks.org/science/programs/atn/. Funded by Autism Speaks and a grant from the Health Resources and Services Administration (HRSA).