1 Department of Epidemiology, School of Public Health and Community Medicine and
2 Department of Pediatrics, School of Medicine, University of Washington, Seattle, Washington, USA
Received 18 November 1999; in revised form 24 March 2000; accepted 30 March 2000
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ABSTRACT |
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INTRODUCTION |
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For trained clinicians, dysmorphologists, or clinical geneticists, there is likely to be full agreement on a diagnosis of FAS only when the anomalies in growth, face, and brain are all very extreme and the alcohol exposure is conclusive and substantial. But the features are not dichotomous, that is either normal or clearly abnormal. Rather, the features, and indeed the history of alcohol exposure, all range along separate continua from normal to clearly abnormal and distinctive. In the absence of accurate, precise, and unbiased methods for measuring and recording the severity of exposure and outcome in individual patients, diagnoses will continue to vary widely from clinic to clinic (Chavez et al., 1988; Aase, 1994
; Stratton et al., 1996
). From a clinical perspective, diagnostic misclassification leads to inappropriate patient care, increased risk for secondary disabilities (Streissguth and Kanton, 1997
) and missed opportunities for primary prevention. From a public health perspective, diagnostic misclassification leads to inaccurate estimates of incidence and prevalence (Stratton et al., 1996
). Inaccurate estimates thwart efforts to allocate sufficient social, educational, and healthcare services to this high-risk population and preclude accurate assessment of primary prevention intervention efforts. From a clinical research perspective, diagnostic misclassification reduces the power to identify clinically meaningful contrasts between groups. Non-standardized diagnostic methods prevent valid comparisons between studies.
The primary limitations in the current practice of diagnosing individuals with prenatal alcohol exposure include the following.
Each of these limitations has been largely overcome with the development of a comprehensive manual for the diagnosis of FAS, Diagnostic Guide for Fetal Alcohol Syndrome and Related Conditions (Astley and Clarren, 1999), introducing a new quantitative approach to diagnosis, the 4-Digit Diagnostic Code. The diagnostic method was developed through the combined expertise of the University of Washington FAS Diagnostic and Prevention Network (FAS DPN) multidisciplinary, clinical team and the comprehensive records of 1014 FAS DPN patients (birth to 51 years of age) with reported prenatal alcohol exposure.
The creation of the 4-Digit Diagnostic Code was developed to assure accurate and precise diagnosis of individuals with prenatal alcohol exposure across all seven FAS Clinics in the Washington State FAS DPN (Clarren and Astley, 1997). The FAS DPN (expanded from the CDC-sponsored FAS Clinic at the University of Washington) was mandated by the 1995 Washington State Legislature in response to the high, statewide demand for diagnostic services. The guide was developed to meet the needs of a broad range of professionals in an equally broad range of settings. A core team that includes a physician, a psychologist, a language pathologist and an occupational therapist staffs each clinic, and also a family advocate. Each core team has community based links to alcohol treatment centres, genetics clinics, schools, and social and legal service agencies. The six clinics have been established in the following settings: a children's hospital neurodevelopmental clinic, two public health clinics, an alcohol treatment clinic, a private psychological services clinic paired with an academic institution, and a comprehensive children's medical/ social services centre. These six clinics are led by the FAS DPN core centre at the Center for Human Development and Disability at the University of Washington.
The need to standardize the criteria for FAS was recognized early on by the Fetal Alcohol Study Group of the Research Society on Alcoholism, resulting in published guidelines by Rosett (1980) followed by several efforts to hone, clarify and express concern about the guidelines (Sokol and Clarren, 1989; Aase et al., 1995
; Stratton et al., 1996
). In the absence of specific case definitions, the FAS DPN has responded to both a mandate by its State legislature and recommendations by the Institute of Medicine (Stratton et al., 1996
) to establish a diagnostic method which could be administered accurately and reproducibly.
Below are a brief description of the 4-Digit Diagnostic Code and a comparison of the gestalt (Sokol and Clarren, 1989) and 4-Digit Diagnostic Code outcomes for 454 patients seen in the FAS DPN who received both diagnostic approaches. A more detailed description of the 4-Digit Diagnostic Code can be found in a 111-page manual (Astley and Clarren, 1999
), distributed by the University of Washington in Seattle. The guide includes a standardized FAS Diagnostic Evaluation Form accompanied by instructions, case definitions, normal anthropometric charts, pictorial Likert scales for ranking lip thinness and philtrum smoothness, and a New Patient Information Form which is completed by the patient's family to document the patient's exposure and developmental history. The guide is accompanied by an instructional CD-ROM Fetal Alcohol Syndrome Tutor Medical Training Software (Astley et al., 1999
). We have used the 4-Digit Diagnostic Code to diagnose over 1000 patients and have found the system to be very helpful in clinical and research areas. We describe it here and present preliminary assessments of its accuracy, precision and power, so that others can consider and evaluate its use.
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METHODS |
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Preliminary assessments of precision, accuracy, and power are presented to assist the reader in their evaluation of this new diagnostic method. The diagnostic evaluation forms of 20 patients were randomly selected from the 736 patients who received a 4-Digit Diagnostic Code 1 to 4 years ago at the University of Washington FAS DPN Clinic by S.K.C. and S.J.A. The standardized diagnostic forms document the clinical and psychometric data that were available for the patients at the time of their diagnoses. The 4-Digit Diagnostic Codes were deleted from the forms by the research assistant and rederived by S.K.C. and S.J.A. independently. Inter-rater reliability between S.K.C. and S.J.A. was assessed by comparing their rederived 4-Digit Diagnostic Codes. Intra-rater reliability was assessed by comparing the rederived codes to the original 4-Digit Diagnostic Codes. An additional assessment of inter-rater reliability was conducted on all 16 patients who had received 4-Digit Diagnostic Codes from one of the six FAS DPN clinics without consultation with the FAS DPN Core team at the University of Washington. The level of agreement between the 4-Digit Diagnostic Codes derived by the Network and University of Washington clinical teams was assessed. The -statistic was computed to test intra- and inter-rater agreement. Accuracy (the degree to which a measurement represents the true value of the parameter that is being measured) was assessed by comparing the 4-Digit Diagnostic Code outcomes to the gestalt diagnostic outcomes of the 454 patients who were diagnosed by both methods. Each of the diagnostic outcomes was also compared to the published diagnostic guidelines (Sokol and Clarren, 1989
) available when the gestalt diagnoses were made. Power, the probability of detecting an effect in a study sample if an effect of a specified size or greater truly exists in the population, was computed using SamplePower (SPSS Inc., 1997).
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RESULTS |
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Clinical nomenclature
There are 256 possible 4-Digit Diagnostic Codes ranging from 1111 to 4444. Each 4-Digit Diagnostic Code falls into one of 22 unique clinical diagnostic categories (labelled A to V) (Table 1). The 22 diagnostic categories are named to reflect the Likert ranking of each digit in the 4-Digit Diagnostic Code. The names are constructed sequentially from four terms: sentinel physical findings, neurobehavioural disorder, static encephalopathy, and alcohol exposure status as presented in Fig. 1
and Table 1
. Note that the names for diagnostic categories EJ, KP, and QV only differ by alcohol exposure, thus there are essentially only nine unique diagnostic outcome categories ranging from no cognitive/ behavioural or sentinel physical findings detected to FAS. This is in contrast to the five diagnostic outcome categories (FAS, partial FAS, ARBD, ARND, and FAE) currently in use across the various gestalt guidelines (Clarren and Smith, 1978
; Sokol and Clarren, 1989
; Stratton et al., 1996
).
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Case defining the growth component of the 4-Digit Diagnostic Code
Age- and gender-adjusted height- and weight-centiles are ranked by circling A, B or C in the ABC score table (Table 2A). The HeightWeight ABC score recorded in Table 2A
is converted to a 4-Digit Diagnostic Code rank using Table 2B
. The 4-Digit Diagnostic Code rank is transferred to the 4-Digit Diagnostic Code grid (Fig. 1
). Detailed instructions are provided in the diagnostic guide for FAS (Astley and Clarren, 1999
) for ranking growth when growth measures are available at more than one time point.
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Case-defining the brain damage/dysfunction component of the 4-Digit Diagnostic Code
Brain damage/dysfunction is the most significant disability for individuals damaged by prenatal alcohol exposure. Ethanol alters the developing brain in a variety of ways, from structural to gross anomalies of grey and/or white matter and/or to subtle alterations in neurochemical levels (West, 1986). Accurately quantifying and qualifying brain damage/dysfunction is important for both diagnosis and treatment planning. Brain damage can be defined in a large number of ways that are each associated with a broad spectrum of disability. The four-point Brain Damage Likert Scale (Table 4
) allows the clinician to separate patients with clear evidence of brain damage (Likert rank 4) from patients with no evidence of brain damage (Likert rank 1). The 4-Digit Diagnostic Code rank for brain does not rank the severity of structural, neurological or functional problems faced by the patient. Rather, it ranks the strength of evidence supporting the presence of an organic cause for cerebral/cerebellar dysfunction.
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A rank of 3 is reserved for patients who present with psychometric evidence of brain damage. Clearly, there are patients who have organic brain damage at a level not detectable by the current technology that allows us to derive a rank 4. In the absence of advanced technology, we feel it is important to identify patients who present with cognitive/ behavioural dysfunction as measured on standardized psychometric tests. At this time, we case define rank 3 to mean that a patient has had an age-appropriate battery of tests in the areas of intelligence, adaptation, academic achievement, language, and neuropsychology. The pattern of abnormality on the test battery, when taken as a whole, must be clinically interpreted by the assessing team to strongly support abnormal brain function. Patients who do not meet the criteria for a rank 4, yet have psychometric test outcomes that document abnormal brain function (greater than 2 SD below the mean) across three or more areas listed above, receive a rank 3. Although there are no scientific data to support that a criterion of three or more failures is more reflective of brain damage than a criterion of one or two failures, our experience with over 1000 patients has demonstrated that the criteria we have selected have good face validity (e.g. the team is more likely to clinically interpret the battery as a whole as strongly supporting abnormal brain function when there are three or more failures). We anticipate that further clinical research coupled with rapidly advancing technology is likely to provide more objective scientific data from which to judge the validity of these criteria. It is important to note that it is possible for a patient to meet the criteria for both a rank 3 and rank 4, since these are not mutually exclusive categories. If this occurs, the higher rank (rank 4) is inserted into the 4-Digit Diagnostic Code, because, for diagnostic purposes, it reflects the strongest clinical evidence of brain damage. The psychometric outcomes, whether normal or abnormal, facilitate the development of the treatment plan for all patients.
Likert rank 2 is given to two subgroups of patients. All patients in rank 2 should have histories of behavioural and/or cognitive problems that strongly suggest underlying brain dysfunction. One group of patients has not yet had the types of testing that would move them into rank 3 or 4, if positive. The reason for this lack of testing is usually because the patients are too young to be reliably or conclusively tested (i.e. less than 6 years of age). The other group of patients includes those who have had testing that did not reveal compelling evidence for rank 3 or 4 classification, and yet, in the clinician's judgement, a strong possibility of brain damage cannot be entirely dismissed. Alternative testing and/or follow-up testing should usually be considered. If adequately sensitive and appropriate testing has been carried out without clear evidence of brain dysfunction, it is unlikely a rank 2 classification would be given.
Patients are classified as rank 1 when no structural, neurological or cognitive/behavioural problems measured by clinical/ psychometric assessment or caregiver interview are discerned.
Case defining the gestational alcohol exposure component of the 4-Digit Diagnostic Code
Alcohol exposure is ranked according to the quantity, timing, frequency, and certainty of exposure during pregnancy (Table 5). The case definitions address the facts that exposure information is often unavailable and/or inaccurate and a clear consensus is not available concerning the amount of alcohol that can actually be toxic to each individual foetus (Stratton et al., 1996
). The case definitions differentiate four clinically meaningful exposure groups (4: confirmed high exposure; 3: confirmed exposure, but level is low or unknown; 2: unknown exposure; 1: confirmed absence of exposure).
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Other prenatal and postnatal exposures/experiences
A comprehensive diagnostic process must take into consideration the risks associated with prenatal and postnatal exposures and experiences other than prenatal alcohol exposure. Most of the features associated with FAS are not specific to prenatal alcohol exposure. A variety of prenatal (poor prenatal care, prenatal complications, familial genetics, and exposure to other potentially teratogenic agents, etc.) and/or postnatal (physical/sexual abuse, disrupted placement histories, head injuries, chronic substance abuse by the patient, etc.) events could explain all or some of the symptoms presented by the patient. The 4-Digit Diagnostic Code method requires the clinician to record pertinent prenatal and postnatal exposures and events on the standardized FAS Diagnostic Evaluation Form, rank their severity using case defined four-point Likert scales and report them in the standardized medical summary template provided in the diagnostic guide for FAS (Astley and Clarren, 1999).
Comparison of the gestalt and 4-Digit Diagnostic Code Methods
The gestalt (Sokol and Clarren, 1989) and 4-Digit Diagnostic Code outcomes for 454 patients who initially received gestalt diagnostic evaluations at the University of Washington FAS DPN clinic are compared in Tables 6 and 7
. Table 6
presents a cross-tabulation of the gestalt and 4-Digit Diagnostic Code outcomes. Table 7
illustrates the variable magnitude of expression of the key diagnostic features of FAS (growth, face, brain, and alcohol) for the three gestalt diagnostic outcomes (FAS, PFAS, and PFAE) and for the equivalent 4-Digit Diagnostic Code categories (categories A and B are equivalent to the gestalt FAS; category C is equivalent to the gestalt PFAS; and categories EI would be equivalent to the gestalt category of PFAE). The study population was 57.7% male, ranged in age from birth to 51 years old with a mean ± SD of 10.1 ± 7.0 years and had the following racial distribution: Caucasian (57.5%), African American (9.0%), Native American/Alaskan (14.1%), other (19.4%). Race, age, and gender were equally distributed across the 4-Digit Diagnostic Code and gestalt diagnostic categories.
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Precision: inter- and intra-rater reliability
The 4-Digit Diagnostic Codes of 20 randomly selected patient files were rederived by S.K.C. and S.J.A. independently while masked to the original 4-Digit Diagnostic Code that had been derived 1 to 4 years ago by the University of Washington clinical team. The codes rederived by S.K.C. and S.J.A. matched the original 4-Digit Diagnostic Codes across all four digits for all 20 subjects (inter- and intra-rater reliability was 100%, = 1.0, P = 0.000). The 4-Digit Diagnostic Codes for the 20 randomly selected patients spanned the entire spectrum of normal to FAS (1124 to 1444). Inter-rater reliability between the six FAS DPN regional clinics and the University of Washington FAS DPN core clinic resulted in an exact match across all four digits on 15 of 16 (94%) patients (
= 0.93, P = 0.000) and an exact match on diagnostic category on all 16 (100%) of the patients (
= 1.0, P = 0.000). The one 4-Digit Diagnostic Code that did not match was coded by the regional FAS DPN clinic as 1223 and the University FAS DPN clinic as 1123. The mismatch in the facial score was due to the network physician not pulling the epicanthal fold back before measuring the PFL, resulting in an underestimate of the length.
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POWER |
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DISCUSSION |
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The 4-Digit Diagnostic Code presents with many strengths. It offers an intuitively logical digital approach to reporting outcomes and exposure that reflects the true diversity and continuum of disability associated with prenatal alcohol exposure. Preliminary assessments of precision, accuracy and power appear to be greatly increased over the gestalt method of diagnosis. This can be attributed, in large part, to the use of objective, ordinal and continuous measurement scales, specific, comprehensive case definitions (Polit and Hungler, 1995), and the use of a multidisciplinary clinical team approach. This study as well as others (Abel, 1990
; Hannigan et al., 1992
) have demonstrated that the current gestalt approach to diagnosis can often lead to diagnoses of FAS made solely on exposure, made in the absence of CNS dysfunction or made when only a single facial anomaly is present. The 4-Digit Diagnostic Code prevents this from occurring. Outcomes and exposures are reported independently so as not to imply that an individual's disabilities and/or anomalies are confirmed to be caused by their prenatal alcohol exposure. The 4-Digit Diagnostic Code serves as a standardized, descriptive language that will allow clinicians and researchers to communicate clearly and objectively the exposures and outcomes of their patients. Although the FAS DPN has gone one step further and clinically categorized and labelled the codes, use of the 4-Digit Diagnostic Code is independent of this step, much like measuring and reporting birth weight in grams and centiles is independent of defining the cut-off for low birth weight. Failure to reach consensus on the categorization and labelling of the codes need not prevent the use of the 4-Digit Diagnostic Code. The 4-Digit Diagnostic Code is fully comprehensive. It can be used to diagnose individuals of all ages and races who present across the full spectrum of exposure and outcomes. This is achieved by directing the clinician to age-, gender-, and race-adjusted anthropometric and psychometric measures when available and appropriate. The availability and reliability of outcome and exposure information varies across patients. The derivation of the 4-Digit Diagnostic Code addresses this reality by encoding both the presence and absence of outcome and exposure information. This method can be taught to a wide array of healthcare and social service providers, thus greatly expanding the availability of diagnostic services. Multidisciplinary clinical teams from six States in the USA and three Canadian Provinces have been trained to use the 4-Digit Diagnostic Code to date.
Although the 4-Digit Diagnostic Code was developed for prospective use in a fully staffed, multidisciplinary clinic, it can also be used in active and passive screening and surveillance efforts. Surveillance generally uses methods distinguished by their practicality, uniformity, and frequently their rapidity, rather than by complete accuracy (Last, 1988). A key feature of the 4-Digit Diagnostic Code is that it not only documents exposure and outcome, but also documents how much data were available (or not available) to support the diagnostic outcome. The standardized FAS Diagnostic Evaluation Form served as an efficient tool for conducting the retrospective chart review on the 736 patients whose gestalt diagnoses were upgraded to 4-Digit Diagnostic Codes. The method provides an efficient and reproducible tool for conducting retrospective chart reviews, a process that is the very essence of passive surveillance. The computerized facial analysis component of the 4-Digit Diagnostic Code also serves as an efficient and highly effective photographic method for screening for FAS (Astley et al., 1999
). This method is currently being used to screen all children entering foster care in one county in Washington State.
Meaningful progress in the areas of screening, diagnosis, intervention, surveillance, and primary prevention all hinge on development of an accurate, precise, valid, and efficient method for identification of individuals damaged by prenatal alcohol exposure. The 4-Digit Diagnostic Code was developed to achieve that goal in Washington State.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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REFERENCES |
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