Practice parameter: evaluation of the child with global developmental delay.

Objective: To make evidence-based recommendations concerning the evaluation of the child with a nonprogressive global developmental delay. Methods: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. Results: Global developmental delay is common and affects 1% to 3% of children. Given yields of about 1%, routine metabolic screening is not indicated in the initial evaluation of a child with global developmental delay. Because of the higher yield (3.5% to 10%), even in the absence of dysmorphic features or features suggestive of a specific syndrome, routine cytogenetic studies and molecular testing for the fragile X mutation are recommended. The diagnosis of Rett syndrome should be considered in girls with unexplained moderate to severe developmental delay. Additional genetic studies (e.g., subtelomeric chromosomal rearrangements) may also be considered in selected children. Evaluation of serum lead levels should be restricted to those children with identifiable risk factors for excessive lead exposure. Thyroid studies need not be undertaken (unless clinically indicated) if the child underwent newborn screening. An EEG is not recommended as part of the initial evaluation unless there are historical features suggestive of epilepsy or a specific epileptic syndrome. Routine neuroimaging, with MRI preferred to CT, is recommended particularly if abnormalities are found on physical examination. Because of the increased incidence of visual and auditory impairments, children with global developmental delay may undergo appropriate visual and audiometric assessment at the time of diagnosis. Conclusions: A specific etiology can be determined in the majority of children with global developmental delay. Certain routine screening tests are indicated and depending on history and examination findings, additional specific testing may be performed. NEUROLOGY 2003;60:367–380 Developmental disabilities are a group of related chronic disorders of early onset estimated to affect 5% to 10% of children.1,2 Global developmental delay is a subset of developmental disabilities defined as significant delay in two or more of the following developmental domains: gross/fine motor, speech/language, cognition, social/personal, and activities of daily living.3-7 Global developmental delay describes QSS Educational Statement: The Quality Standards Subcommittee (QSS) of the American Academy of Neurology seeks to develop scientifically sound, clinically relevant practice parameters for the practice of neurology. Practice parameters are strategies for patient management that assist physicians in clinical decision making. They consist of one or more specific recommendations based on analysis of evidence of a specific clinical problem. These might include diagnosis, symptoms, treatment, or procedure evaluation. From the Departments of Neurology/Neurosurgery and Pediatrics (Dr. Shevell) and School of Physical & Occupational Therapy (Dr. Majnemer), McGill University; Division of Pediatric Neurology (Dr. Shevell), Montreal Children’s Hospital, Montreal, Canada; Department of Pediatrics (Dr. Ashwal), Loma Linda University, Loma Linda, CA; private practice (Dr. Donley), Traverse City, MI; Division of Psychiatry (Dr. Flint), Wellcome Trust Centre for Human Genetics, University of Oxford, UK; private practice (Dr. Gingold), Morgantown, WV; National Institute of Neurological Disorders and Stroke (Dr. Hirtz), National Institutes of Health, Bethesda, MD; Departments of Pediatrics & Neurology (Dr. Noetzel), Washington University School of Medicine, St. Louis, MO; and Departments of Pediatrics & Neurology (Dr. Sheth), University of Wisconsin at Madison. This statement has been endorsed by the Child Neurology Society. Approved by the AAN Quality Standards Subcommittee April 16, 2002. Approved by the AAN Practice Committee August 3, 2002. Approved by the AAN Board of Directors October 19, 2002. Received May 15, 2002. Accepted in final form July 16, 2002. Address correspondence and reprint requests to Dr. Stephen Ashwal, Department of Pediatrics, Loma Linda University School of Medicine, 11175 Coleman Pavilion, Loma Linda, CA 92350; e-mail: [email protected]; or Wendy Edlund, American Academy of Neurology, 1080 Montreal Avenue, St. Paul, MN 55116; e-mail: [email protected] Copyright © 2003 by AAN Enterprises, Inc. 367 a clinical presentation that has a heterogeneous etiologic profile and is associated with age-specific deficits in adaptation and learning skills. Those deficits are evident in comparison with the skills attainment of chronological peers. Significant delay is defined as performance two standard deviations or more below the mean on age-appropriate, standardized normreferenced testing. The term global developmental delay is usually reserved for younger children (i.e., typically less than 5 years of age), whereas the term mental retardation is usually applied to older children when IQ testing is more valid and reliable.4-13 A child with the clinical picture of global developmental delay is not necessarily destined to be mentally retarded. Infants and children may have global developmental delay owing to conditions such as cerebral palsy, certain neuromuscular disorders, and other conditions such as early environmental deprivation, yet when they are old enough to measure cognitive level they do not score in the mentally retarded range. The diagnosis of mental retardation, according to the American Association of Mental Retardation8 and the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision,11 requires accurate and valid assessment of intelligence, which is generally not possible in infants and young children8 in addition to deficits in adaptive function. Available valid instruments for assessing intelligence (such as the Stanford-Binet or Wechsler Preschool Primary Scale of Intelligence) are not generally applicable under age 3 years.12 The precise prevalence of global developmental delay is unknown. Estimates of 1% to 3% of children younger than 5 years are reasonable given the prevalence of mental retardation in the general population.14 Based on approximately 4 million annual births in the United States and Canada, between 40,000 and 120,000 children born each year in these two countries will manifest global developmental delay. Developmental surveillance is recognized as an integral component of pediatric care.15 Professional organizations dedicated to the medical care of children recommend routine monitoring of a child’s developmental progress.15,16 Formal screening, together with reliance on parental reporting measures, constitutes the primary means by which children with global developmental delay are identified.17 In addition, children possessing either biologic or social risk factors for later developmental delay are often targeted through specific follow-up programs that incorporate routine periodic assessments evaluating developmental performance.18 Environmental influences such as culture, parental skills, neglect, and opportunity may modify the cause’s expression as well as the detection and diagnosis of global developmental delay. Accumulating evidence also demonstrates the benefits of early intervention through a variety of programs (e.g., Head Start) with respect to shortterm outcomes19 and suggests that early diagnosis of a child with global delay may improve outcome. Initial screening is important not only in identifying children with developmental delay but also is the first step in determining whether a child has global delay, a language disorder, or an autistic spectrum disorder. This parameter is focused specifically on the child who has global developmental delay. Previous parameters have reviewed the evaluation of children and adolescents with language disorders20 and autistic spectrum disorders.21 Identification of a globally delayed young child by routine pediatric screening in the first years of life mandates a careful search for an underlying etiology.22 This search is usually initiated by the primary care physician and frequently requires referral to either a child neurologist or developmental pediatrician.7,23 Accurate etiologic determination, despite the fact that many disorders have no specific therapeutic interventions, has specific implications regarding treatment, prognosis, ongoing medical management of associated conditions, assessment of recurrence risk, counseling of families if there is a risk of recurrence, and implementation of prevention programs.7,14,24 Determining causality also empowers the affected family in planning for their child and limits further unnecessary testing.25 Estimates of the etiologic yield (10% to 81%) in children with global developmental delay/mental retardation are highly variable.7,14,24-29 The reported variability in diagnostic yield can be attributed to differences in a variety of factors including sample population characteristics, severity of delay in the children studied, extent of diagnostic investigations, and technological advances over time, especially with respect to genetic and neuroimaging techniques. Considerable uncertainty exists among practitioners evaluating young children with global developmental delay with respect to the appropriate extent of laboratory investigations and referral for ancillary services.24,30,31 Laboratory investigations should be undertaken only after a comprehensive history and physical examination are undertaken. One prospective (17.2% yield) and two retrospective (19.1%, 34.2%) studies have shown that the etiology of developmental delay can be established on the basis of the history and examination.7,28,29 This practice parameter reviews available evidence concerning the value of diagnostic testing in the initial evaluation of a young child with a global developmental delay that is static, nonprogressive, and has no clear etiology. Based on this evidence, specific recommendations for each testing modality are provided. Description of process. Literature searches were conducted with the assistance of the University of Minnesota Biomedical Information Services for relevant articles published from 1980 to 2000. Databases searched included MEDLINE, Healthstar, ERIC, and CINAHL. Depending on the particular diagnostic test/ ancillary service of interest, key words/phrases included the following: mental retardation, developmental delay, developmental disability, neurodevel368 NEUROLOGY 60 February (1 of 2) 2003 opmental delay, physical therapy, occupational therapy, speech therapy, audiology, ophthalmology, and psychometric evaluation. Searches were restricted to the English language under the subheading of infant and child. Individual committee members reviewed titles and abstracts so identified for content and relevance. Articles dealing with investigations in developmental delay with reference to determining a possible etiology were selected for further detailed review. From the bibliographies of several articles selected for review, additional articles thought to be relevant were identified at the discretion of committee members. A bibliography of the 160 articles identified and reviewed for preparation of this parameter is available at the American Academy of Neurology website (http://www.aan.com/). Relevant position papers were also sought from professional organizations, including the consensus statement of the American College of Medical Genetics on the evaluation of mental retardation.32 Each article was reviewed, abstracted, and classified by a committee member. A four-tiered classification scheme for diagnostic evidence recently approved by the Quality Standards Subcommittee was utilized as part of this assessment (Appendix 2). Depending on the strength of this evidence it was decided whether specific recommendations could be made, and if so, the level of strength of these recommendations (Appendix 3). Evidence pertinent to each diagnostic test followed by the committee’s evidenced-based recommendations are presented. The committee selected a value of 1% as a clinically meaningful cutoff point for diagnostic yield. Thus if the diagnostic yield of a test was less than 1% it was felt that this test should not be performed on a routine basis whereas tests with yields greater than 1% should be considered. What is the diagnostic yield of metabolic and genetic investigations in children with global developmental delay? Evidence. Laboratory investigations relevant to the possible ascertainment of an underlying etiology include metabolic studies that screen for specific inborn errors of metabolism, cytogenetic and molecular tests that employ various techniques, and screening for chronic lead poisoning and hypothyroidism. Metabolic studies. Two class III studies (table 1) involving 2,655 patients have evaluated the diagnostic yield of screening for metabolic disorders in institutionalized populations of individuals with presumed significant global developmental delay or mental retardation.34,35 A diagnostic yield of 0.6%34 and 1.3%35 was obtained utilizing nonselective screening protocols. A class II population-based study from Finland on four successive birth cohorts of children born between 1969 and 1972 employed a standardized metabolic screening protocol in children identified to have severe mental retardation.33 The results yielded a frequency of 5% for identified inherited metabolic diseases, attributed by the study’s authors to the patient’s “Finnish disease heritage,” which may be specific to a relatively homogeneous and isolated population. A class III study from Israel36 and a class IV study of heterogeneous North American children with global developmental delay7 highlighted that the diagnostic yield for metabolic testing was about 1% even within the context of a history or examination suggestive of a possible underlying metabolic disorder. A more recent class II prospective study from the same group of investigators confirmed a yield of less than 5% even on an indicated (i.e., family history, parental consanguinity) basis.28 Typically metabolic screening in these studies involved amino and organic acids together with a determination of serum ammonia and lactate levels. Neonatal screening programs for metabolic disorders (varying in testing but typically involving amino and organic acids and thyroid function) identify infants with conditions that are associated with global developmental delay.32 These have decreased the number of children who present with undiagnosed global developmental delay and thus decrease the yield of metabolic testing in this particular population done later in life. The advent of tandem mass spectrometry has further increased the yield of neonatal screening programs (i.e., universal newborn screening).38-40 Although the yield from metabolic testing is low, one issue that needs consideration is whether a treatable condition that was not detected using a neonatal screening program would be missed. Most children with an inborn error of metabolism have other symptoms (e.g., failure to thrive, developmental regression, episodic decompensation) or physical findings (e.g., hepatosplenomegaly, coarse facial features) that prompt diagnostic testing, making the likelihood of not diagnosing a treatable condition presenting just with symptoms of global developmental delay quite low.32,35 In addition, nonspecific and nondiagnostic abnormalities are freTable 1 Metabolic testing in children with global