Mental Problems and Disorders in Fetal Alcohol Spectrum Disorders (FASD)

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1 Mental Problems and Disorders in Fetal Alcohol Spectrum Disorders (FASD) Hans-Christoph Steinhausen Universities of Aalborg (DK), Basel (CH) and Zurich (CH) The Berlin FASD Studies N=157 children initially examined between 1977 and

2 Developmental History (N=154) Item n % Prematurity Neonatal complications Sucking problems Failure to thrive Retarded motor development Retarded speech development Mental Disorders Structured psychiatric assessment: Eating disorders Enuresis Encopresis Sleep Disorders Dev.Speech & Language Delay Stereotypies Hyperkinetic Disorders (ADHD) Conduct Disorders Depressive Disorders Anxiety Disorders Subjects with one or more of these diagnoses: 62.8% (N=49/78) 2

3 Mental Disorders Preschool age (N=49) ADHD 51 % Eating disorders 43 % Enuresis 31 % Dev. speech & language delay 31 % Stereotypies 22 % Conduct disorders 16 % Sleep disorders 14 % Anxiety disorders 12 % Affective disorders 10 % Steinhausen et al. 1982, 1993, 1994, Steinhausen 1996, Steinhausen und Spohr 1998 Mental Disorders Early Schoolage (N=50) ADHD 64 % Stereotypies 58 % Dev. speech & language delay 54 % Anxiety disorders 48 % Sleep disorders 36 % Eating disorders 28 % Enuresis 16 % Conduct disorders 15 % Encopresis 10 % Steinhausen et al. 1982, 1993, 1994, Steinhausen 1996, Steinhausen und Spohr

4 Mental Disorders Late schoolage (N=51) Stereotypies 49 % ADHD 45 % Sleep disorders 33 % Dev. speech & langauge delay 27 % Conduct disorders 26 % Eating disorders 10 % Steinhausen et al. 1982, 1993, 1994, Steinhausen 1996, Steinhausen und Spohr 1998 Associations Physical damage predicts mental impairment Steinhausen et al. (1982), JDBP 3,

5 Behavioural profile Steinhausen et al.1993, Steinhausen 1996 Behavioural profile Steinhausen et al.1993, Steinhausen

6 Prenatal Alcohol Exposure Long-term effects after 10 years of follow-up H.-L. Spohr, J. Willms, H.-C. Steinhausen Publication 6

7 Abstract Spohr, Willms & Steinhausen Dysmorphic Features 7

8 Clinical Features Morphometric Variables 8

9 Morphometric Variables Intelligence High frequency of MR/ID at T1 (N=20; 36%) and T2 (N=21; 38%) Intelligence was mostly stable with time 9

10 Intelligence The likelihood of impaired intelligence tended to increase with severity of morphological damage and microcephaly. The association was n.s. in this analysis in contrast to a sign. association in other analyses (Steinhausen et al., 1982,1994) Domestic Arrangements Substantial changes with time. Greater proportions of children were living with parent surrogates, foster parents, and adoptive families 10

11 Prenatal Alcohol Exposure Long-term effects after 20 years of follow-up H.-L. Spohr, J. Willms, H.-C. Steinhausen Publication 11

Sample (N=37) FAS FAE Males Females (N=22) (N=15) (N=20) (N=17) Age at first assessment Mean (years) 3.20 2.34 2.83 2.87 SD (years) 2.76 1.44 1.67 2.98 Age at follow-up Mean (years) 24.71* 21.

12 Sample (N=37) FAS FAE Males Females (N=22) (N=15) (N=20) (N=17) Age at first assessment Mean (years) SD (years) Age at follow-up Mean (years) 24.71* SD (years) Duration of follow-up Mean (years) 21.51* SD (years) * p <.05 Patient with FAS Shown with permission of the patient 12

Patient with FAE Shown with permission of the patient Physical Symptoms at Initial Examination and at Follow-up % of Children with Feature: Initial Examination Follow-up Postnatal growth deficiency

13 Patient with FAE Shown with permission of the patient Physical Symptoms at Initial Examination and at Follow-up % of Children with Feature: Initial Examination Follow-up Postnatal growth deficiency Microcephaly Developmental delay/intellecutal disability Hyperactivity Muscular Hypotonia Short upturned nose Thinned upper lip Maxilla hypoplasia/flat midface

14 Physical Symptoms at Initial Examination and at Follow-up % of Children with Feature: Initial Examination Follow-up Limited joint movement Minor external genital anomalies Cardiac defects Kidney defects Hernias Follow-up of Morphometric Variables First assessment Height Weight Last assessment: < 3rd < 10th < 25th > 25th < 3rd percentile (N=6) < 10th percentile (N=4) < 25th percentile (N=3) > 25th percentile (N=4) < 3rd percentile (N=8) < 10th percentile (N=4) < 25th percentile (N=4) > 25th percentile (N=1) Head Circumference < 3rd percentile (N=31) < 10th percentile (N=6) < 25th percentile > 25th percentile

15 Follow-up of Morphometric Variables Height 90% % of patients below 3rd percentile 80% 70% 60% 50% 40% 30% 20% 10% 0% first assessment follow-up males females whole sample Follow-up of Morphometric Variables Weight 90% % of patients below 3rd percentile 80% 70% 60% 50% 40% 30% 20% 10% 0% first assessment follow-up males females whole sample 15

16 Follow-up of Morphometric Variables Head Circumference 100% % of patients below 3rd percentile 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% first assessment follow-up males females whole sample Follow-up of Morphometric Variables Height Weight 90% 90% % of patients below 3rd percentile 80% 70% 60% 50% 40% 30% 20% 10% % of patients below 3rd percentile 80% 70% 60% 50% 40% 30% 20% 10% 0% first assessment follow-up 0% first assessment follow-up males females whole sample Head Circumference males females whole sample 100% % of patients below 3rd percentile 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% first assessment follow-up males females whole sample 16

17 Intelligence N % Normal (IQ >85) Borderline (IQ 71-85) Mental Retardation Mean SD Intelligence Quotient (IQ) Age at assessment (years) Intelligence by FAS / FAE FAS (N=22) FAE (N=15) N % N % IQ >85 (N=12) IQ (N=10) IQ <70 (N=15) Chi 2 = 2.01; df=2; p=n.s. 17

18 Intelligence by Head Circumference Head Circumference < 3rd perc. > 3rd perc. N % N % IQ >85 (N=12) IQ (N=10) IQ <70 (N=15) Chi 2 = 10.3; df=2; p=.006 Behavioural Profile in FAS and Controls YABCL Profile in FAS and Controls z-scores anxious somatic attention*** aggressive*** w ithdraw n thought*** intrusive*** delinquent* FAS Controls 18

19 Behavioural Profile in FAS / FAE YABCL Profile in FAS / FAE z-scores anxious somatic attention aggressive withdrawn thought intrusive delinquent FAE FAS Behavioural Profile in FAS by Gender YABCL Profile in FAS by Gender z-scores Anxious Somatic Attention*** Aggressive** Withdraw n Thought** Intrusive** Delinquent Boys Girls Total 19

20 Behavioural Profile and Intelligence YABCL Profile and Intelligence z-scores anxious somatic attention aggressive w ithdraw n thought intrusive delinquent IQ > 85 IQ IQ <= 70 Lifetime Domestic Arrangements First assessment Follow-up N % N % Both biological parents Father plus mother surrogate Foster family Adoptive family Institution Dependent living Independent living alone Living with partner Own family

21 Educational Status N % Secondary school level 5 13 Primary school level Special education level Occupational Training (N=36) N % Preparatory Training school based training for a year job training workshops job training in sheltered workshops Occupational training certified apprenticeship apprenticeship without certificaton prematurely terminated *multiple codings 21

22 Occupational Status Total (N=36) N % Employed Temporarily working Household Family business Sheltered workshop Unemployed Disabled Does not apply (age) Psychosocial Functioning Total (N=36) FAS (N=21) FAE (N=15) N % N % N % Meeting People outside the family never less than once a month once a week to once a month more than once a week Independence buying food buying cloth repairing small items financial budget

23 Treatment Effects N % Physiotherapy slight efficiency marked efficiency Occupational therapy slight efficiency marked efficiency missing Speech & language therapy marked efficiency Psychological intervention slight efficiency marked efficiency missing Treatment Effects N % Perceptual training slight efficiency Stimulant treatment marked efficiency Neuroleptic treatment slight efficiency marked efficiency missing Anticonvulsant treatment marked efficiency missing

24 Behavioural Phenotypes Publication 24

25 Abstract DBC profiles 25

26 Behavioural Phenotypes in Four Syndromes Behavioural Phenotypes in Four Syndromes 26

27 Behavioural Phenotypes in Four Syndromes F=11.41, df=3, p<0.001 FAS=FRAX>PWS=TSC Behavioural Phenotypes in Four Syndromes Weighted Raw Scores (N=142) 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 A B C D E F FAS FRAX PWS TSC DBC scales A: disruptive B: self-absorbed C: communication disturbance D: anxious E: autistic relating F: antisocial (N=26) (N=49) (N=39) (N=16) Steinhausen et al., AJMG, 111, ,

28 Book Cambridge University Press 1996; 2011 Review on Neuropsychological and Behavioural Features S.Mattson, N. Crocker and T.T. Nguyen Neuropsychol Rev 21, ,

29 General Intelligence The most common finding is diminished intellectual capacity. However, the majority of individuals with FAS are not intellectually disabled MR/ID is not a necessary criterion of FAS FAS is one of the leading identifiable causes of MR/ID Many affected individuals exhibit impaired intellectual abilities, even in the absence of dysmorphic features and growth retardation However, children with a diagnosis of FAS tend to have more intellectual impairment than those without dysmorhic features but who were exposed prenatally to alcohol General Intelligence The average IQ of individuals with heavy prenatal alcohol exposure is 70 for those with FAS a and 80 for nondysmorphic individuals b The IQ is significantly correlated with psychopathology: children with moderate and severe ID experienced greater mental disturbance IQ scores below 50 indicated poor psychiatric outcome c Discrepant findings on IQ among studies with lower levels of alcohol exposure a Streissguth et al., 1991; b Mattson et al., 1997; c Steinhausen et al.,

30 Executive Functions Higher-order cognitive processes related to frontalsubcortical circuits Alcohol-exposed children are delayed on EF tasks, including measures of problem-solving, planning, concept formation and conceptual set shifting, verbal and non-verbal fluency, response inhibition, and working memory Further Neuropsychological Deficits Learning and memory (verbal and nonverbal) Language Visual-spatial ability Motor function Attention and activity levels Academic impairments 30

31 Behavioural Features Predominantly externalizing behavioural problems (social problems, attention problems, aggressive behaviour) Prenatal alcohol exposure vs. environmental mediation of these problems? Elevated rates of oppositional-defiant disorders, conduct disorders, and ADHD (often also increased rates of internalizing problems / mood disturbances) Persistence of behavioural problems into adulthood Deficits in adaptive functioning and failure of improvement of socialization abilities Systematic Review of Interventions E. Paedon, B. Rhys-Jones, C. Bower C and E.J. Elliott BMC Pediatrics 2009, 9:35 31

32 Review of Interventions Search for clinical studies which evaluated pharmacological, behavioural, speech therapy, occupational therapy, physiotherapy, psychosocial and educational interventions and early intervention programs Participants were under 18 years with a diagnosis of FASD Review of Interventions Twelve studies met the inclusion criteria. Methodological weaknesses were common including small sample sizes, inadequate study design and short-term follow-up. Pharmacological interventions (2 RCT; N=16) showed some benefit from stimulant medication which may decrease hyperactivity and impulsivity but does not improve attention. Some educational and learning strategies (3 RCT) may be beneficial. Social communication and behavioural strategies (2 RCT) may improve social skills. Attention process training may improve attention. Seven RCT that address specific functional deficits are underway or recently completed. 32

33 Conclusions A large proportion of children with intrauterine alcohol exposure suffer from long-lasting negative effects on their development. Intellectual disability or cognitive impairments in association with mental disorders and behavioural abnormalities lead to psychosocial functioning deficits of varying degree. These problems need early identification by skilled experts using adequate assessment tools. Rehabilitation programs should be based on multimodal interventions (e.g. pharmacological, behavioural, speech therapy, occupational therapy, physiotherapy, psychosocial and educational interventions). Varia 33

34 Fetal Alcohol Syndrome Maternal alcohol consumption and its relation to the outcome of pregnancy and child development at 18 months CONCLUSIONS The results are consistent with previous published work in showing an ssociation between infants body size and maternal alcohol consumption either before or in early pregnancy at levels of about 140g/week or more. Drinking only one standard drink a day in early pregnancy does not appear to have a detrimental effect on fetal growth. There was no evidence that the development of children of mothers who drink at the levels observed in the studies was impaired either mentally or physically at age 18 months. On the basis of our findings and a consideration of the literature, we recommend that women do not drink alcoholic beverages during pregnancy, but if this is not possible because of social pressures, cosumption should be restricted to no more than one standard drink a day. The Euromac Project Group. Florey C du V, Taylor D, Bolumar F, Kaminski M, Olsen J (eds). International Journal of Epidemiology 1992, 21 Suppl.1 Fetal Alcohol Syndrome Long-Term Psychopathological and Cognitive Outcome of Children with Fetal Alcohol Syndrome ABSTRACT Objective: The long-term outcome of a large cohort of children suffering from fetal alcohol syndrome was studied. Method: Structured psychiatric interviews, behavior checklists for parents and teachers, and intelligence tests were used. Assessments took place during preschool age, early school age (6 to 12 years), and late school age ( 13 years). Results: There was an excess of psychopathology with a wide variety of psychiatric stereotypies persisted over time. Interview findings were largely in accordance with parents and teachers questionnaire findings. Intelligence test findings included a large proportion of mentally retarded children and displayed high stability at follow-up. Conclusions: The development of children suffering from fetal alcohol syndrome is jeopardized by a high rate of persistent psychiatric and cognitive impairments. H.-C. Steinhausen, J. Willms & H.-L. Spohr 34

35 Fetal Alcohol Syndrome Alcohol Teratogenicity Critical Periods: Threshold: - entire pregnancy - probably > one standard drink per day - binge drinking more deleterious than continuous drinking H.-L. Spohr, J. Willms, H.-C. Steinhausen Fetal Alcohol Syndrome Definition of FAS The diagnosis can only be made when the patient has signs of abnormality in each of three categories: 1. Prenatal and / or postnatal growth retardation (weight and / or length below the tenth percentile when corrected for gestational age) 2. Central nervous system involvement (including neurological abnormality, developmental delay, intellectual impairment and / or structural abnormalities, such as microcephaly (head circumference below the third percentile) or brain malformations found on imaging studies or autopsy) 3. A characteristic face, currently qualitatively described as including short palpebral fissures, an elongated midface, a long and flattened philtrum, thin upper lip, and flattened maxilla. FAS Group of the Research Society on Alcoholism 35

36 Fetal Alcohol Syndrome Rehabilitation Structure the environment Strategies (i.e., home; work space; routines; school) Help with sleep disturbances (e.g., consistent bedtime routines; use of white noise in the bedroom) Deal with eating problems (e.g., allowing ample time to eat; having reasonable expectations on portion size) Provide early intervention programs Rehabilitation Auswertung von 5 Studien in den USA. Erfolge von Interventionen beginnen sich abzuzeichnen, zumal in 4 Studien signifikante Verbesserungen bei Verhalten und Fertigkeiten beobachtet wurden. Elterntraining und Fertigkeitstrainings tragen zum Erfolg bei. (Bertrand, Res Dev Disabil 2009, 30, ) Untersuchung von 10 Interventionsstudien. Die wissenschaftliche Evidenz für wirksame Interventionen bei FASD ist begrenzt. (Premji et al., Child Healh Care Dev 2007, 33, ) Intensive Forschung ist dringend geboten. 36

Fetal Alcohol Exposure

Fetal Alcohol Exposure Fetal alcohol exposure occurs when a woman drinks while pregnant. Alcohol can disrupt fetal development at any stage during a pregnancy including at the earliest stages before a