Kelly Nash The Ontario Institute for Studies in Education of the University of Toronto and the Hospital for Sick Children September, 24, 2008

Transcription

1 Comparing the Behavioural Profiles of Children with Fetal Alcohol Spectrum Disorders, Attention Deficit Hyperactivity Disorder (ADHD), and Oppositional Defiant Conduct Disorder (ODD/CD): Working Towards Differential Diagnosis. Kelly Nash The Ontario Institute for Studies in Education of the University of Toronto and the Hospital for Sick Children September, 24, 2008

2 Executive Summary Fetal Alcohol Spectrum Disorders (FASDs) are a critical mental health issue that is both prevalent and costly. The diagnostic criteria of FASDs include a history of gestational drinking, pre- and postnatal growth retardation, characteristic facial features, and a complex and pervasive pattern of neurobehavioural anomalies. The full blown syndrome, characterized by hallmark facial features occurs in the minority of affected children. Children with FASDs suffer a wide range of challenges ranging from behavioural disturbances to severe developmental delays and a high proportion of children with FASD go on to require mental health services as adults. The associated costs are staggering as it is estimated that Canada spends $344 million annually on youth with FASDs. Most estimates are conservative because they exclude incarceration and difficult to measure costs such as lost productivity, and poor quality of life. Although the disabilities of FASDs are debilitating and lifelong, they can be alleviated with early intervention. This is an especially difficult task as the diagnostic procedure for FASDs is complex as most children with FASD do not present with the full-blown facial features. Because the the diagnostic procedure involves a specialized team of professionals which include, psychometrists, psychologists and pediatricians, the wait lists are extensive. Moreover, the behavioural features of FASDs can be seen in other disorders, such as Attention Deficit Disorder (ADHD), Conduct Disorder, learning disabilities, communication disorders, which make the diagnosis more difficult. Furthermore, since the bulk of children with prenatal alcohol exposure reside in areas with limited access to full diagnostic work-ups many will not have the opportunity to see a mental health professional until it is too late. Thus, there is an urgent need to develop a screening tool for identifying children at high risk for FASDs. Based on this gap in our knowledge, the present work developed a screening tool that was be able to differentiate children with FASDs from children who share similar behavioural profiles, namely children with ADHD and Oppositional Defiant/Conduct Disorder. Behavioural profiles between groups were measured using individual items from a parent/guardian respondent questionnaire. This screening tool can be administered and scored by frontline personnel who work with children with FASD. Results from this study are being adapted into the Canadian Association of Pediatric Health Centre s (CAHPC) Nation Screening Tool Development Kit for Fetal Alcohol Spectrum Disorders. It is our hope that this screening tool will advance efforts at early identification and treatment, and ultimately help to circumvent many of the devastating problems affecting these individuals and their families. Table of Contents Alcohol is a powerful teratogen causing significant brain impairment, facial and other dysmorphologies and retarded growth. The consequences of prenatal alcohol exposure (PAE) are not benign, with most affected children showing reduced IQ as well as significant cognitive and learning disabilities and severe behaviour problems. By adulthood, nearly every individual exposed in utero to alcohol experiences some form of secondary psychological disturbance, which includes substance abuse and trouble with the law (Olson, Morse & Huffine, 1998; Mattson & Riley, 1998; Sampson, Streissguth, Bookstein, Little, Clarren, Dehaene, Hanson & Graham, 1997). Surprisingly, however, research to date on children with PAE has focused on the cognitive aspects of this disorder to the exclusion of the socioemotional aspects. Therefore, very little is known about the full spectrum of sociobehavioural disturbances affecting children with PAE, creating difficulties in how to best to diagnose and treat the disorder. The condition involving neurobehavioural deficits and specific physical dysmorphology following PAE is known as FAS while the presence of neurobehavioural defects in the absence of characteristic dysmorphology is referred to as Alcohol Related Neurodevelopmental Disorder (ARND). To account for the wide range of impairments that arise from PAE the nondiagnostic 20

3 term Fetal Alcohol Spectrum Disorders (FASDs) is now widely used (Chudley, Conry, Cook, Loock, Rosales, LeBlanc, et al., 2005; Spohr, Willms and, Steinhausen, 2007; Niccols, 2007). A proper diagnosis of FASds includes understanding the neurobehavioural characteristics and requires a specialized professional team consisting of psychiatrists, psychologists, and pediatricians. However such diagnostic procedures are costly, encompass long wait lists, do not account for risk factors associated with the disorder, and do not adequately serve children living in remote areas where access to full diagnostic services and mental health professionals is limited. Additionally, FASDs are often comorbid with other psychiatric disorders, such as Attention Deficit Hyperactivity Disorder (ADHD), seen in as many as 70% of children with FASD (Nanson and Hisock, 1997), and Oppositional Defiant/Conduct Disorder (ODD/CD). Because children with FASDs are often diagnosed and treated for the comorbid disorders, the FASDs themselves are often overlooked. Therefore the appropriate tools to make a differential diagnosis on the FASD spectrum and to distinguish FASDs from other psychiatric disturbances of childhood are vital, but nonexistent. Thus, a primary focus in FASD research must be the development of new and improved methods for early identification of children with FASDs. These methods need to discriminate children with FASDs from children with ADHD and ODD/CD and to be applicable in remote areas where services are restricted or lacking. To address these issues the present study was designed (i) to investigate whether children with FASDs show a distinctive behavioural profile relative to children with ADHD and ODD/CD and (ii) to use this information to develop an empirically derived FASD screening tool. The present study is therefore intended to address a critical issue, first comparing children with FASDs to children with similar clinical profiles and second, by studying their socioemotional rather than cognitive functioning. Methodology Participants The study cohort consisted of 220 children aged 6 to 17 years who belonged to one of three clinical groups (FASD, ADHD, or CD/ODD) or to a normal control group without a clinical diagnosis (NC). In accordance with the Research Ethics Boards at The Hospital for Sick Children and the Centre for Addiction and Mental Health, informed consent was obtained from parents or legal guardians while assent was obtained from those children 7 years of age and older. Data were collected by chart review of the four groups and extraction of the CBCL and items as well as background information such as maternal Learning Disability (LD), paternal substance abuse, maternal psychiatric history, paternal psychiatric history, adopted, in foster care, number of foster care placements, abuse, neglect, and SES (derived using the Hollingshead index). The FASD group consisted of 56 children with a documented history of exposure to alcohol during pregnancy and a diagnosis of FAS/ARND received through the Motherisk Follow-up Clinic at the Hospital for Sick Children. The majority of children investigated in this clinic were brought mainly by foster or adoptive parents for concerns about suspected alcohol exposure. A small proportion was brought by a biological parent or relative who reported they, or the child s mother, had abused alcohol during pregnancy. In all cases, exposure history was confirmed by one of three criteria: (i) verbal report of the biological parent or relative, (ii) the child suffered alcohol withdrawal at birth, or (iii) the child was placed in care because of maternal alcohol abuse. For a detailed description of the Motherisk diagnostic process see Greenbaum, Nulman, Rovet, and Koren (2002). The ADHD group was comprised of 50 children who were recruited from a pre-existing data pool in our laboratory (Greenbaum, 2004; Hepworth, 2004). Files were reviewed retrospectively and children with a confirmed diagnosis of ADHD and no history of prenatal drug or alcohol exposure were included in the study. Whenever possible, information pertaining to the source of the ADHD 21

4 diagnosis and a list of any attention related medications tried in the past or at the time of testing was also obtained. At the time of recruitment 38 children were taking medication, 4 were not, and for 8 participants no information was provided regarding medication status. All ADHD diagnoses were made by qualified professionals including developmental pediatricians, psychologists, and psychiatrists. The ODD/CD cohort was comprised of 60 children admitted to the Acute Intensive Care Unit (AICU) at Youthdale Treatment Centre between January 2004 and March The AICU is a temporary treatment program for adolescents experiencing a psychiatric emergency with problems ranging from suicidality, severe aggression, and psychosis. Youthdale is a non-profit, charitable community agency funded by the Ministry of Community, Family and Children s Services. Youthdale operates four treatment residences in Toronto and one in York Region (Aurora). Files were reviewed retrospectively and children with a confirmed primary diagnosis of ODD or CD and no history of prenatal drug or alcohol exposure were included in the study. All ODD/CD diagnoses were made by a psychiatrist or psychologist. Thirty-one children in this cohort were also diagnosed with ADHD, 25 children were taking medication for attention problems and 43 were taking medication for behaviour problems. Normal controls were 53 participants in previous studies in our laboratory (Hepworth, 2004; Greenbaum, 2004). They were recruited through postings to the general public, information distributed to parents of students within the Toronto Catholic District School Board, or through families in the clinical groups who were willing to enroll non-exposed siblings or acquaintances of FASD or ADHD children. Tests and Measures The Child Behaviour Checklist (CBCL; Achenbach and Rescorla, 2001) is a widely used instrument with strong reliability and validity that assesses social competencies and behaviour problems in children 6 to 18 years of age. The CBCL is comprised of both a series of open-ended questions and a rating scale of 113 behavioural descriptors scored on a 3-point scale from 0=not true, 1= sometimes true, and 2=often true. Computer scoring of the CBCL yields a Total Behavior Problems score, three broad-band scores assessing Internalizing, Externalizing and Total behavior problems, and eight narrow-band scales assessing Withdrawn/Depressed, Somatic Complaints, Anxious/Depressed, Social, Thought, Attention, Rule-Breaking Behaviour, and Aggressive problems. Additionally, the CBCL provides five scales that are consistent with DSM-IV diagnostic categories which include: Affective problems, Anxiety Problems, Somatic Problems, ADHD Problems, Oppositional Defiance, and Conduct Problems. These scales were uniquely designed to assess how similar a child s profile is to another child with a DSM-IV diagnosis. The narrow-band syndrome scales can be viewed as subtypes of the broad-band syndromes. The problem scales are scored negatively with higher T-scores reflecting more problems. On narrow-band and DSM-IV problem scales T-scores between 65 and 70 represent the borderline range and scores 70 and above are considered clinical. On broad-band scales, T-scores between 60 and 63 are considered borderline and scores 64 or above are considered clinically significant. Results Demographic Information: Maternal and Child Characteristics Demographic characteristics are summarized in Table 1. Children in this study range from 6-16 years of age with an average age of 10.8 years for the total sample. It should be noted that while the male to female ratio was disproportionately high in the ADHD group (4:1), this ratio is not deemed problematic as it accurately reflects prevalence rates in the general population. Family levels of SES differed across the groups with FASD children coming from largely adoptive and foster middle-class families. Children with ODD/CD and ADHD tended to be from more middle- 22

5 to upper-class families and were mostly living with their biological parents. In contrast children in the NC group were all living with their biological parents and the majority of children had high SES levels. However, because SES was not strongly correlated (R =.48) with the main outcome measure (Total Problems), it was not used as a covariate in subsequent analyses. A relatively high proportion of mothers in the FASD group smoked cigarettes in addition to drinking alcohol during pregnancy in contrast to mothers in the ADHD, ODD/CD and NC groups. Approximately equal numbers of children in the FASD, ADHD, ODD/CD groups were taking medication for attention problems compared to no children in the NC group. A disproportionately high number of children in the ODD/CD group were taking psychotropic medication and this likely reflects the severity of the social and emotional problems seen in this study group. Group differences in behavioural functioning A series of one-way MANOVA s were conducted on different groups of CBCL scales to determine the effect of clinical group membership on parent-rated behaviour on the CBCL. On the Broad Band scales a significant omnibus group difference was found between the groups, Wilks Lambda =.21, F (9,521) = 52.44, p <.00. Univariate analyses revealed all three scales to be statistically significant (p <.00). Post hoc analyses to the MANOVA were conducted to determine specific univariate group differences on the Broad Band scales. Each pairwise comparison was conducted using the Tukey method. Results revealed significant group differences between children with FASD and controls on all 3 scales. Compared to children with ADHD, children with FASDs presented with significantly elevated Externalizing Problems. Compared to children with ODD/CD, children with FASDs presented with significantly fewer problems on the Total Problems and Internalizing Problems scales. Analysis of the Narrow Band scales also revealed a significant omnibus group difference on all six scales, Wilks Lambda =.21, F (24,607) = 18.4, p <.00. Univariate analyses revealed significant group differences on all scales (p <.00) with post hoc analyses showing the children with FASDs differed from controls. Compared to children with ADHD, children with FASDs presented with significantly more problems on the following scales: Externalizing Problems, Rule Breaking Behaviour, and Aggressive Behaviour. However, children with ODD/CD presented with significantly more clinical elevations than children with FASDs on the following scales: Withdrawn, Somatic Complaints, Anxiety/Depression, Thought Problems, Rule Breaking Behaviour, Aggressive Behaviour. Lastly, analysis of the DSM-IV scales also revealed a significant omnibus group difference on all 5 scales, Wilks Lambda =.22, F (15,586) = 28.32, p <.00. Univariate analyses revealed significant group differences on all 5 scales (p <.00). Results revealed significant group differences between children with FASDs and control s on all 5 scales. Compared to children with ADHD, children with FASDs presented with significantly more problems on the following DSM- IV scales: ODD Problems and Conduct Problems. However, children with ODD/CD presented with significantly more clinical elevations than children with FASD on the following DSM-IV scales: Affective Problems, Anxiety Problems, Somatic Problems, ODD Problems and Conduct Problems. The magnitude of the problems in the clinical groups is exemplified by the following findings; 66% of the ADHD sample, 77% of the FASD sample and 98% of the ODD/CD sample were identified as having Total Problems scores in the clinical range (T-scores > 64). The severity of the problems in the ODD/CD group, compared to the other two groups is emphasized by the following comparisons on the Internalizing Problems scale demonstrating that 89% of children in the ODD/CD had scores in the clinical range, compared to 34% of children with FASD and 50% of children with ADHD. On the Externalizing subscale, 95% of children in the ODD/CD group had 23

6 scores in the clinical range compared to 84% of children in the FASD group and 50% of children in the ADHD group. Chi Square analysis revealed significant group differences between FASD and ADHD on Externalizing Problems χ2(1) = 14.0, p <.00 and between FASD and ODD/CD on Internalizing χ2(1)= 37.6, p <.00, Externalizing χ 2 (1)= 5.6, p <.02 and Total χ2(1)= 15.9, p <. 00 Problems. Group difference on individual items from the CBCL Children with FASD differed significantly from controls on all 12 items. Endorsement rates were significantly higher among children with FASD than ADHD for acts young (χ 2 (1) = 5.0, p<.02), cruelty/bullying/meanness to others (χ 2 (1) =5.2, p<.00), doesn t seem guilty after misbehaving (χ 2 (1) = 17.7, p<.00), steals from home (χ 2 (1) = 17.0, p<.00), and steals outside (χ 2 (1) = 9.7, p<.00). Endorsement rates were significantly higher for children with ODD/CD for cruelty/bullying/meanness to others (χ 2 (1) = 5.2, p<.02), and disobedient at home (χ 2 (1) = 8.0, p<.01), than children with FASD, whereas children with FASD received significantly more endorsements for acts young (χ 2 (1) = 7.2, p<.01) than children with ODD/CD. In view of the fact that acts young may represent the unique arrested social development documented in children with FASD, the Social Problems subscale was visually examined across each age group in each of the four groups, since results could not be analyzed for significance due to the unequal distribution of children in each age group. Visual examination of the pattern of results seems to indicate that social development may be arrested in children with FASDs compared to NC s, and children with ADHD and ODD/CD. Typically developing children show a normal development trend, with parent-rated social problems peaking around adolescence. For children with ADHD and ODD/CD parent-rated social problems appear to improve with maturation, whereas for children with FASDs it is quite evident that, with age, parent-rated social problems increase. However the extent to which these results are correlated with IQ could not be determined as an IQ measure was not available for every child. ROC analyses The items found to be significant in the chi square analyses were submitted to ROC analysis. A comparison between children with FASDs and NC s revealed that the largest Area Under the Curve (AUC) was achieved with.970 (p <.00). With a cutoff of 3 out of 12 items, a sensitivity of 98% and specificity of 42% was achieved. Comparison between children with FASDs and ADHD revealed that the largest AUC was achieved with.78 (p <.00). With a cutoff of 2 out of 5 items, a sensitivity of 89% and specificity of 54% was achieved. Comparisons between children with FASDs and ODD/CD were not conducted due to the lack of items that differentiated the two groups on the chi square analysis. We presently propose the following FASD screening tool (see Table 1), which involves a 3-step approach. The first step identifies behaviours suggestive of FASD, the second discriminates children with FASD from children with ADHD and the final step discriminating children with FASD from children with ODD/CD. Step 1 is based on parents /caregivers responses to the 12 questions shown in Table 1. If the parent answers yes to at least three of items 1 to 7, this is suggestive of an FASD with 98% specificity and 42% sensitivity. However if the child does not exhibit behaviour consistent with ADHD (i.e. the answer is negative to items 2, 6, 7), then the child must receive a score of 3 or more on items 1, 3, 4, and 5. In Step 2, which serves to rule out ADHD alone, the child must receive a score of 2 or more for items 1 through 5. Because acts young was the only item to discriminate children with FASDs from children with ODD/CD, it also must be endorsed for children in both steps for a child to have suspected FASD. Importantly, as in any case investigating potential FASDs, confirmation that the mother indeed consumed alcohol during pregnancy is required. 24

7 Conclusion & Recommendations/Next Steps The present study has highlighted multiple findings, such as the finding that a potential screening tool may exist for children with FASDs that discriminates them from children with ADHD and ODD/CD as well as the finding that environmental risk factors do not appear to influence the behavioural profile of children with FASDs. The current study has also identified several several gaps that still exist in our knowledge about the FASD profile. On a general level, the field of alcohol teratogenicity would greatly benefit from research examining how the dose and timing of alcohol exposure, prenatal care, maternal health, genetic susceptibility, and concomitant exposure contribute to FASD. Additionally, little is known about the influence of paternal factors on the developing fetus. Since many children with FASD are fostered or adopted, perhaps the responsibility of collecting this crucial developmental history should lie with the child protection agencies as they represent the first and most consistent line of contact with the birth and adoptive/foster families of these children. The next step in investigating the proposed screening tool is on an epidemiological scale so that adequate reliability and validity can be determined. Additionally, this would allow for important age, gender, geographical and cultural considerations to be made. Both clinicians and researchers working with children with FASDs have struggled to find intervention strategies that are successful for children with FASDs on both cognitive and behavioural levels. Despite being recognized in a speech from the throne in 2004 as a Canadian public health concern, there are few programs in Canada for specifically treating children with FASDs. This may stem, in part, from the fact that FASDs are less well understood than other psychopathological conditions. Additionally there is no available source of systematically compiled information describing the number of people with FASDs in Canada, the services they are receiving, or the effectiveness of these services. Such an oversight highlights the crucial need for future studies to carefully scrutinize the FASD profile alongside other developmental disorders. Research examining the FASD profile has evolved tremendously since FAS was first introduced into the medical literature in the 1960 s. Nevertheless, we are far from understanding the full spectrum of strengths and weaknesses that typify individuals with FASDs, thus impeding our ability to identify a specific neurobehavioural phenotype. As has been demonstrated, identifying the phenotype is further complicated by the fact that many children with FASDs also share profiles or co-morbid diagnoses of children with other clinical conditions, such as ADHD, ODD, CD, mental retardation and language impairments. Therefore, it will be especially important for future research to delineate the FASD profile from these other childhood conditions. Due to the complexity of this disorder, until a differential approach is adopted, developing interventions that specifically target FASDs will be difficult. On a societal level, with the cost estimated to be up to 1.4 million dollars in intervention across the lifespan of an individual with an FASD (Streissguth et al., 1991), FASDs remain a critical public health concern that can only be alleviated with early intervention initiatives. In both economic and individual terms, the costs of the impact of the disorder on the families of individuals with FASDs are immeasurable. Consequently, and in so far as possible, the primary goal of research efforts should be to provide hope for individuals with FASDs and their families. Knowledge exchange plan The results of the present study are being used to create a National Screening Tool for FASDs that will be part of a kit comprised of behavioural markers, such as the proposed tool, as well as biomarkers. The next step will be to test this kit at an epidemiological level. The work has already 25

8 been presented at the International Neuropsychological Society s annual meeting (2008) as well as to an expert panel of health care workers as part of the CAHPC s mandate (2007). 26

9 Table 1. Screening Checklist for FASD Behavioral Phenotype Step 1: Identifying behaviour suggestive of FASD The following questions should be asked of the child s parent/guardian to determine whether the child s behaviour is suggestive of FASD. 1. Does your child act too young for his/her age? 2. Does your child have difficulty concentrating, and can t pay attention for long? 3. Is your child disobedient at home? 4. Does your child lie or cheat? 5. Does your child lack guilt after misbehaving? 6. Does your child act impulsively and without thinking? 7. Does your child have difficulty sitting still/is restless/hyperactive? If the parent/caregiver answers yes to at least any three out of seven items this is suggestive of FASD with 42% sensitivity and 98% specificity. Step 2: Differentiating FASD from ADHD The child needs to exhibit any 2 of the following 5 1. Does your child experience lack guilt after misbehaving? 2. Does your child display acts of cruelty, bullying or meanness to others? 3. Does your child act young for his/her age? 4. Does your child steal from home? 5. Does your child steal outside of home?

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