A 5-year-old boy named J.J. presents to the clinic for his well-child evaluation. His mother reports that J.J. continues to have impressive language abilities; however, she is concerned that he is talking more at people than with people. He does not engage in imaginary play with his peers and does not like to play outside. He persists with eye aversion during conversations, and his mother notices that he rocks back and forth frequently throughout the day. He excels in mathematics and reading; his abilities far exceed that of his prekindergarten class. J.J. has a 3-year-old sister who is with him at the clinic. His mother states that he is a good big brother and plays well with her.
The first article of this series depicted the well-documented concern that pediatric patients with autism spectrum disorder (ASD) are not receiving timely evidence-based care in primary care clinics. A recent estimation in 2016 across 11 sites in the US found the prevalence of ASD among children age 8 years to be 1 in 54.1 Patients should be specifically screened for ASD at age 18 and 24 months. However, despite an increased focus on early diagnosis and treatment, data collected over the past 10 years have shown no improvement in primary care practice of screening for ASD prior to age 3 years, delaying the time in which patients receive a diagnosis and necessary services.1-3 The CDC, the Office of Disease Prevention and Health Promotion (ODPHP), and the World Health Organization (WHO) have set recommendations to improve this disparity.4-6 The initial article in this series argued that the first step to increase access to evidence-based care for pediatric patients with ASD was for primary care providers (PCPs) to accept their role as patients' healthcare team leaders. Such a change in paradigm can ensure improved health outcomes for these patients. After assuming this role, PCPs should move forward and make decisions regarding the patient's plan of care, but at-risk children must be identified at well-child visits before this can occur.
The second installment of this series uses J.J.'s experience, from developmental concern to diagnosis, to illustrate interventions that should be implemented when a patient is identified as at risk for ASD. As with many children on the autism spectrum, J.J. presented symptoms by age 2 years, yet he has still not been evaluated for ASD. The second step in increasing access to evidence-based care for pediatric patients with ASD is for PCPs to accurately use appropriate developmental screening assessments during well-child evaluations.
The CDC recognizes the need for all PCPs to administer developmental screening during well-child evaluations in order to accurately identify and manage the care of pediatric patients with ASD.7 This practice is not occurring consistently in all primary care clinics. Findings in a self-report survey highlighted this concern as it uncovered that approximately half of the participating pediatricians did not regularly use established screening tools for patients younger than 36 months.8 Also, data from the 2016 National Survey of Children's Health revealed that, in the past year, 30.4% of children between the ages of 9 and 35 months were reported by parents to have received a developmental screening, 37.1% were reported to have received developmental surveillance, and only 19.2% were reported to have received both developmental screening and surveillance from a healthcare clinician.9 This healthcare disparity will persist for pediatric patients with ASD until appropriate screening for developmental delays becomes an integral and habitual part of well-child evaluations. Treatment to enhance gross and fine motor skills, improve language disorders, and manage psychiatric and other health comorbidities will remain underutilized because of the omission of accurate developmental screening during well-child exams.
All children ages 9 to 60 months should be screened with an appropriate developmental assessment tool during well-child evaluations.10,11 Additionally, Healthy People 2020 Maternal, Infant, and Child Health (MICH) Objective MICH-29.1 calls for an increase in the number of children ages 10 to 35 months who have been screened for ASD.5 Both the American Academy of Pediatrics (AAP) and the National Institute of Mental Health (NIMH) endorse referral for a more in-depth evaluation if developmental screening flags any concerns.7,11
The CDC recommends that providers discuss all screening results with the child's parents.7 If the child has a negative screening, indicating there is not a concern for developmental delay at that visit, the provider should review the results with the parents to obtain their impression of their child's development. If no further developmental concerns are identified during the visit, no immediate action is required at that time. The child will be screened again at the next well-child exam. If the parent expresses apprehension for developmental delay, providers should listen and work with the parents to create a plan of care that either monitors the child's progression and rescreens at the next well-child visit or refer the child for further evaluation of identified concerns at that time.7
Although there are many other developmental screening tools available, Parents' Evaluation of Developmental Status (PEDS), Ages and Stages Questionnaire, 3rd edition (ASQ-3), and the Modified Checklist for Autism in Toddlers-Revised with Follow-up (M-CHAT-R/F) are the most commonly used tools in primary care.8 In addition to those three, the Infant/Child Development Inventory was evaluated specifically for use in the Access for Autism pilot program, which occurred from 2017 to 2018 and focused on early identification and initial management of pediatric patients at risk for ASD. The pilot program will be discussed in the third article in this series. Therefore, this article will focus on these four screening tools. The AAP endorses the use of screening tools with a reliability value of at least 80% and established validity as measured by a sensitivity and specificity of at least 70%.12 (See Developmental screening tools comparison.)
Returning to the case scenario, the screening assessment identified developmental delay in gross and fine motor skills along with socialization concerns with J.J. The PCP knows that further investigation is required. The third step in increasing access to evidence-based care for pediatric patients with ASD is for the PCP to analyze the past medical history, social history, and family history of patients identified as at-risk by developmental screening. (See Past medical, family, and social history risk factors associated with ASD.) Of note, the family history should span three generations.26
Evidence-based practice interventions
J.J.'s abnormal developmental screening coupled with the risk factor of having older parents indicated that he was at risk for ASD. The PCP immediately begins a thorough workup. The fourth step in increasing access to evidence-based care for pediatric patients with ASD is for PCPs to implement first-tier interventions that assess for contributing factors for the presenting symptoms. (See Access for ASD Algorithm.)
First-tier interventions. Healthy People 2020 Objective MICH-29.2 aims to increase the number of children with ASD who have had a first evaluation by age 36 months and Objective MICH-29.3 seeks to increase the proportion of children with ASD enrolled in special services by age 48 months.5 The following interventions are recommended by the AAP and NIMH as initial interventions for children with developmental delay concerns. They are considered first-tier interventions as they assess for the presence of common comorbid conditions associated with ASD and differentiate ASD from similar disorders. To meet ODPHP recommendations, these interventions should occur prior to receiving an official diagnosis of ASD.5
Blood tests. Chromosomal microarray (CMA) testing, FMR1 DNA testing, lead screening, and metabolic testing are first-tier lab tests that should occur prior to a diagnosis of ASD.10,26,35,36 These genetic tests can be ordered by most primary care clinicians and do not necessitate referral to a genetic specialist, which avoids unnecessary delays in diagnosis while awaiting a genetic referral.
CMA is the first-tier test for genetic evaluation of a child with ASD.26,35,37 Chromosomal analysis is reserved for exceptions such as a suspected chromosome aneuploidy or family history that suggests chromosomal rearrangements.37
Approximately 1% to 5% of children with ASD have Fragile X as a comorbidity.37 Fragile X should be considered if clinical symptoms, family history, or possibility of genetic inheritance are present.36 First-tier testing for Fragile X should routinely occur in male children with ASD, especially in those who have clinical symptoms or a positive family history.26,36,37 Female children with ASD who also have a compatible Fragile X phenotype; a family history of X-linked neurodevelopmental disorders; or premature ovarian insufficiency, ataxia, or close relatives with tremors should be tested for Fragile X.37 The gold standard of care for testing Fragile X syndrome is the FMR1 DNA test.36
As elevated serum lead levels are a risk factor for developmental delay, children presenting with this concern should be screened for lead exposure.38 Further, children with speech or language dysfunction, attentional or behavioral disorders, or pica should be screened for lead poisoning.26,39 Lead detected in a venous blood sample is more accurate than capillary blood samples, as the latter tend to have false-positive results.39
Metabolic testing is recommended if the following are present: lethargy, ataxia or other movement disorders, cyclic vomiting, unusual odors, early seizures, poor growth, multiple organ involvement, presence of dysmorphic or coarse features, hypotonia, intellectual disability, evidence of storage disease, and inadequate newborn screening.26,40 First-tier recommendations for metabolic testing for global developmental delay include serum ammonia, pyruvate, carnitine, lactate, plasma amino acids, liver and renal function, total homocysteine, acylcarnitine profile, copper, and ceruloplasmin. Urine testing includes evaluating organic acids, purines and pyrimidines, creatine metabolites, oligosaccharides, and glycosaminoglycans.26,40
Audiology evaluation. Audiologic assessment is indicated for any child for whom there is a concern for ASD.10,11,26
Developmental evaluation. Any child who fails developmental screening should be immediately referred to a developmental pediatrician or psychiatrist to obtain a full developmental evaluation.4,11 Waiting to see if a child outgrows the concerning behavior goes against global recommendations and results in poor health outcomes for these children.
Speech therapy evaluation. The NIMH advocates for speech-language therapy referral if ASD is suspected.11 Speech-language therapists are vital members of the interdisciplinary team caring for a child with ASD. They assess for receptive and expressive language disorders; literacy skills; initiation of communication; social reciprocity and the range of communicative functions; sharing affect; play behaviors; use of gestures; speech prosody; and conversational skills including topic management, turn-taking, and providing appropriate amounts of information in conversational contexts.41
Physical therapy evaluation. Many children with ASD experience below average gross motor function compared with their neurotypical peers. A physical therapy evaluation and services are recommended to reduce developmental and functional obstacles to increase inclusion in peer group activities. This is essential as there is an association between gross motor disabilities and impaired socialization skills.42 Children with ASD may experience postural, motor, and functional delays including atypical motor development. Delay in motor milestones attainment such as asymmetry, oral-motor problems, repetitive motor movements, dyspraxia, motor coordination, movement preparation reaction, and motor milestone delays are also noted.43
Occupational therapy evaluation. Occupational therapy concentrates on a combination of cognitive, physical, and motor skills. Occupational therapists assist the child in attaining self-care skills, including community living and safety procedures; behavioral challenges in social and learning situations; and fine motor skills development.44
Psychiatric/psychological therapy evaluation. Both psychiatrists and psychologists manage the mental health aspect of ASD. Children with ASD experience a higher rate of psychiatric disorders than neurotypical children, including attention-deficit and hyperactivity disorder (ADHD), depression, bipolar disorder, and anxiety.45 Seventy percent of children with ASD have also been evaluated and diagnosed with one or more psychiatric disorders; the most frequent being anxiety, ADHD, and oppositional defiant disorder.46 Both psychiatrists and psychologists can receive training in diagnosing ASD, and most interdisciplinary diagnostic teams are comprised of one or both specialists.
Early intervention evaluation. Approximately 15% of children experience developmental disability during childhood.47,48 Evaluation at an early intervention office is a free service for children of age 3 years and younger in the US. Treatments may include speech and physical therapy along with assistance for families.7 Data from 2014 revealed that early intervention services are underutilized as only 2% to 3% of all children in the US are enrolled in early childhood intervention programs by age 3 years.47
Follow-up evaluation. A follow-up evaluation should occur 1 month after the initial well-child evaluation. During this visit, providers should discuss all obtained and pending evaluations. Also, since pediatric ASD is associated with financial burdens and stress to families, providers should supply information on advocacy and support groups that can help alleviate these concerns.49 Referral to a social worker may also be considered. Lastly, providers should consider recommending genetic counseling for children with global delay, intellectual disabilities, seizures, or dysmorphic physical features.50
The fifth step in increasing access to evidence-based care for pediatric patients with ASD is for PCPs to consider second-tier interventions to assess for comorbid conditions. Comorbid conditions can contribute to some behavioral challenges associated with ASD.25 The following interventions are considered second tier as they are based on documented risk factors or concerns that could be expressed while obtaining the medical history or found during the physical exam but are not always present in pediatric ASD.
Genetics evaluation. Evidence supports the role of genetics in the etiology of ASD.37 A groundbreaking study evaluating patients with ASD in five countries revealed that variation in occurrence of ASD is highly dependent on genetic composition.51 This study reports that 80% of the overall risk for developing ASD is attributed to genetic factors, establishing genetic composition as the predominant influence in ASD as compared with environmental or maternal circumstances. Common genetic disorders associated with ASD include Fragile X syndrome, tuberous sclerosis complex, Angelman syndrome, Bannayan-Riley-Ruvalcaba syndrome, Smith-Lemli-Opitz syndrome, Down syndrome, Rett syndrome, and mitochondrial disorders.11,26 Karyotype evaluation, MECP2 gene mutation and sequence analysis, and PTEN gene mutation and sequence analysis should be considered based on family history and physical examination.26
Sleep evaluation. As many as 80% of children with ASD experience sleep disturbances.52 The most common sleep disturbances found in children with ASD are difficulty falling asleep and repeated awakenings during the night.53 Sleep disturbances can augment detrimental behavioral patterns, especially daily living skills, social cognition, social communication, and intelligence quotient, and should be assessed and treated as soon as they are detected.54,55
Gastrointestinal evaluation. Chronic gastrointestinal (GI) concerns are common in children with ASD. A survey including a large nationally representative sample found that children with ASD were 7 times more likely than children without developmental disabilities to have frequent diarrhea/colitis and 2.4 times more likely to have a food allergy.56 Diarrhea, constipation, and abdominal pain are identified as the most prevalent GI issues noted in children with ASD.57,58 Also, a survey in China found that significant social, communication, and behavioral challenges that are associated with ASD were heightened when comorbid GI symptoms were present.55,59
Neurologic evaluation. ASD commonly co-occurs with other developmental, psychiatric, neurologic, chromosomal, and genetic diagnoses. The co-occurrence of one or more non-ASD developmental diagnoses is 83%, with the co-occurrence of one or more psychiatric diagnoses being 10%.60 Anxiety, depression, and ADHD are common comorbid psychiatric conditions.59 Seizure disorder has been linked to increased morbidity and mortality among people with ASD.61,62
There are conflicting reports regarding the efficacy of complementary and alternative medicine (CAM) treatments in patients with ASD. High use of CAM, such as special or elimination diets, has been estimated to occur in 52% to 74% of families with children who have ASD.63 At the time of publication, further research is needed to ascertain which alternative therapies can be proven effective to improve core ASD symptoms in pediatric patients. This research is an essential guide for parents and providers determining treatments that are worth the investment of their time, money, and effort.
Case scenario resolution
J.J.'s provider used her knowledge of first- and second-tier interventions to guide her discussion with his mother. Concerns for sleep disruption and obsessive-compulsive behaviors were identified. J.J. lives in a state that requires an evaluation from a physician, psychologist, and speech therapist for a diagnosis. J.J.'s provider referred him to a developmental pediatrician. The waiting time for an initial ASD evaluation with this provider was 18 months. J.J.'s provider initiated other referrals while awaiting the official diagnosis of ASD. She referred him to a speech therapist for evaluation and treatment of reciprocal language disorder and oral-motor sensitivity. J.J. was also referred to an occupational therapist for dyspraxia and a physical therapist for generalized weakness combined with gross motor skill delay. J.J.'s family history was negative for genetic rearrangements. He did not present with symptoms of a metabolic disorder and his head circumference was normal. J.J. was referred to an audiologist to test his hearing, due to his mom's concern that J.J. seemed to not hear her or sometimes responded inappropriately to her requests. The provider used the Autism Speaks Sleep Toolkit to guide his mom through some strategies to improve J.J.'s sleep.64A follow-up visit was scheduled in 4 weeks to discuss the results of the referrals and to reassess J.J.'s sleep patterns.
This article covered the initial process of providing evidence-based care to pediatric patients at risk for ASD in a primary care setting. The procedure involves taking one step at a time. The first step is for PCPs to accept their role as the leader of the patient's healthcare team. The second step is to appropriately use a developmental screening tool at well-child evaluations. The third step is to analyze the past medical history, social history, and family history for risk factors. The fourth and fifth steps involve referring at-risk patients to healthcare specialists to obtain a definitive diagnosis and to begin treatment for comorbid conditions. (See Key concepts.) The final article of this series will detail the results of a pilot program that aimed to enhance the care provided to pediatric patients identified as being at risk for ASD. Implications for future studies and practical advice for PCPs will be included.
- Appropriate developmental assessments should be implemented during well-child visits.
- The past medical history, social history, and family medical history should be analyzed for risk factors of ASD.
- Evidence-based first-tier interventions should be initiated prior to obtaining an official ASD diagnosis for at-risk patients.
- PCPs should evaluate for and intervene if common comorbidities associated with ASD are present.
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