Defining a Neurobehavioural Phenotype in Fetal Alcohol

Spectrum DisorderNash, K., Greenbaum R., Fantus,

E., Rovet, J., & Koren, G.

What is Fetal Alcohol Spectrum Disorder (FASD)?

• FASD is a neurodevelopmental disorder caused by exposure to alcohol in utero

• Has effects on both brain and behaviour

Diagnostic Criteria

Based on a triad of features Pre and postnatal growth

retardation CNS damage Characteristic facial

dysmorphology

Only a minority of children meet criteria for the full blown syndrome

How do we diagnose without visible signs?

The Motherisk Follow-up Clinic

Began in 1996• Provides a specialized diagnosis in a

central location

Many obstacles exist• Not every child has physical symptoms• Misdiagnosis of ADHD - 70% of children 70% of children

with FASD are diagnosed with with FASD are diagnosed with ADHDADHD

• Long wait lists

The Issue of ADHD

• Children with FASD present with a unique and specific behavioural profile compared to children with ADHD (Greenbaum (2004); Fantus et al., (2004))

0

10

20

30

40

50

60

70

80

OPP HYP PS EM GLB

FASD

ADHD

The Issue of Access

• The majority of children with FASD reside in communities with limited access to a specialized diagnosis

• How do we address this issue?

Aims of the current research

• To identify whether the diagnosis of FASD can be predicted by individual items from a validated questionnaire

• To compare children with FASD to children with ADHD and controls on this questionnaire

• To develop an empirically derived screening tool (Streissguth, 1998)

MethodsParticipants: children between the ages of 6-16

years. FASD (dx; n=30)ADHD (dx; n=30): No exposure historyControls (n= 30): No exposure history, LD, ADHD

Exposure History (FASD): Confirmed by(a) Verbal report of biological parent or relative(b) Knowledge that the child suffered alcohol

withdrawal at birth(c) The child having been place in care because of

maternal alcohol abuse

The Child Behaviour Checklist (CBCL; Achenbach, 1991)

• 113 item parent questionnaire

• T-scores yield:» Competence Scales» 3 Broadband scales» 8 Narrowband scales» DSM Oriented Scales

Item selection

• Selected only 12 based on the work of Greenbaum (2000)

CBCL: 12 Items

• #1 acts to young for his/her age• #3 argues• #8 can’t concentrate/poor attention• # 10 can’t sit still/restless/hyperactive• #16 cruelty/bullying/meanness to others• #22 disobedient at home• #26 no guilt after misbehaving• #41 impulsive/acts without thinking• #43 lying or cheating• #74 showing off/clowning• #81 steals from home• #82 steals outside

Analyses of Data

• Frequency Counts

• Proportions endorsed per group (chi square)

• Endorsement totals per item/group: Discriminant Function Analysis (DFA)

• Sensitivity and Specificity: Receiver Operating Curves (ROC)

Receiver Operating CurvesROC Curve

Diagonal segments are produced by ties.

1 - Specificity

1.00.75.50.250.00

Se

ns

itiv

ity

1.00

.75

.50

.25

0.00

CBCL items involving significant group differences

(Controls & FASD)

0

20

40

60

80

100

120

CBCL Items

% E

nd

ors

ed

FASD

CON

Seven items most strongly differentiating FASD from

control• #1 acts to young for his/her age• #8 can’t concentrate/poor attention• #9 can’t sit still/restless/hyperactive• #22 disobedient at home• #26 no guilt after misbehaving• #41 impulsive/acts without thinking• #43 lying or cheating

ROC Analysis:FASD and Controls

0.0 0.2 0.4 0.6 0.8 1.0

1 - Specificity

0.0

0.2

0.4

0.6

0.8

1.0

Sen

sit

ivit

y

Source of the Curve

discrim

ayimngd

Diagonal segments are produced by ties.

ROC Curve

CBCL items involving significant group differences

(FASD and ADHD)

0

10

20

30

40

50

60

70

80

90

100

ActsYoung

Cruelty No Guilt Lying StealsH StealsO

FASD

ADHD

Six items most strongly differentiating FASD from

ADHD• #1 Acts to young for his/her

age• #16 cruelty/bullying/meanness

to others• #26 no guilt after misbehaving• #43 lying or cheating• #81 steals from home• #82 steals outside

ROC Analysis:FASD and ADHD

0.0 0.2 0.4 0.6 0.8 1.0

1 - Specificity

0.0

0.2

0.4

0.6

0.8

1.0

Se

ns

itiv

ity

Source of the Curve

discrim

noguilt&creul&actsyoung

Diagonal segments are produced by ties.

ROC Curve

Screening checklist for FASD

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

Screening Checklist Continued

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 answers YES to at least 6 out of 7 items this is suggestive of FASD with comorbid ADHD

• If the child does NOT exhibit behaviour consistent with ADHD then they must receive a score of 3 out of 4 on the conduct related items

Step 2: Differentiating FASD from ADHD

i). The child needs to exhibit 2 of the following 31. Does your child lack guilt after misbehaving?2. Does your child act cruel, bully or is mean to others?3. Does your child act young for his/her age?

ORii). 3 of the following 61. Does your child lack guilt after misbehaving?2. Does you child act cruel, bully or is mean to others?3. Does your child act young for his/her age?4. Does your child steal from outside the home?5. Does your child steal from home?6. Does your child lie and cheat?

Clinical Implications

• Address the issue of access

• Spare the long wait times for a diagnosis

• Misdiagnosis of ADHD

Limitations

• Dose and timing of alcohol exposure

• Confounders

• Small sample size

• Clinic referred

Future Directions

• Compare to children diagnosed with conduct disorder

• Replicate and empirically validate

• Neuroimaging and mapping

Acknowledgments

• Rovet Lab: Meagan Williamson, Dina Lafoyannis, Sarah Borokowski, Erin Sheard, Dr. Mary Desrocher, Darlene Walker

• Canadian Institute of Health Research (CIHR)