Download - Not What We Went Looking For
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Not What We Went Looking ForEthical, Legal, and Social Issues in Identification
of Sex Chromosome Variations
Arlene M. Davis, JD
Assistant ProfessorDepartment of Social Medicine
InvestigatorCenter for Genomics and Society
University of North Carolina, Chapel Hill
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Fellow CGS ResearchersNancy M.P. King, JDDepartment of Social Sciences and Health PolicyWake Forest University School of Medicine
Cynthia M. Powell, MDDepartment of PediatricsUniversity of North Carolina, Chapel Hill
Ian Whitmarsh, PhDDepartment of AnthropologyUniversity of Iowa
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Overview of Presentation• Technologic and societal changes
regarding screening and genetics• Intended or incidental
– Identification of sex chromosome variations (SCVs) in genetic screening
• Data from two interview studies• Implications
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Changing Landscape
• 2006 Supplement to Pediatrics: A Look at Newborn Screening: Today and Tomorrow
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Genetic Screening & SCVs• Detected: incidentally
during prenatal screening or when symptoms are identified
• Proposed NBS methodologies detecting X-linked conditions may also detect SCVs
• Early intervention & detection of medical problems may be beneficial
• Genotype vs. phenotype – wide variation in presentations
• People may do well, whether or not the SCV is ever identified
• Some struggle with life-long medical, learning, & behavioral issues
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Turner (45,X)• 1/4000-1/5000 girls • Symptoms vary and
may include:– Short stature* (4’7”)– Delayed puberty*– Infertility*– Hearing impairment,
lymphedema, cardiac & kidney problems, learning disabilities
• Some never diagnosed
Klinefelter (47,XXY)• 1/1000 boys• Symptoms vary and
may include:– Tall stature– Low testosterone/
puberty*– Infertility– Behavioral problems
& learning disabilities*• 60-70% never diagnosed
Screening May Identify SCVs
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Family Study• 14 families of children
with 45,X and 47,XXY– Parents’ ages: 30s-
50s– Children: 1-16 years– Families with KS: 6– Families with TS: 8
• Questions: diagnosis & care for children and interest/concerns about NBS to identify SCVs
New Mothers’ Study• 28 mothers of infants
– Mothers’ ages:19-45 years
– Infants: 8-12 weeks• Questions: views on
expanding NBS to include specific SCVs
Our Two Interview Studies
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Family Study
• Parents embrace uncertainty about condition, focus on:–Individuality of child–Her accomplishments
• Argue: w/o symptoms, syndrome doesn’t exist
Whitmarsh, I. et al. (2007). A Whitmarsh, I. et al. (2007). A
place for genetic uncertainty. place for genetic uncertainty. SS&M, 65: 1082-1093SS&M, 65: 1082-1093.
New Mothers’ Study• Should SCV screening be
offered? Would you accept? • Would it matter that: – Often no medical treatment
until symptoms develop?– Some show few symptoms
while others have many?– Some may live entire lives
without diagnosis?
Family Study Results Inform Mothers’ Study Questions
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Perceived BenefitsIdentifying SCVs with NBS
Family Study• Early intervention• Have an explanation• Might not be detected
otherwise
New Mothers’ Study• Early intervention• Gives an opportunity to:
– prepare financially– prepare emotionally– research resources
before symptoms arise– learn more about child
• Peace of mind if results are negative
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Perceived Concerns Identifying SCVs with NBSFamily Study
• Increase worry• Increase sense of guilt • Diagnosing all
behaviors• Some families: offer
testing when symptoms arise
• Chromosomal diagnosis=“syndrome”
New Mothers’ Study• Parents might jump to
conclusions about child’s prognosis
• Symptoms may never present
• Offer screening for older babies, not newborns
• Confidentiality breaches• Accuracy and expense
of screening
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
ViewsFamily StudyMother of son with KS on getting diagnosis: •“Well, you find out and then you don’t know any more than you did before you found out.… It’s just, you just know that he has an extra chromosome and that’s as far as it goes.”
New Mothers’ StudyNew mothers regarding some have few symptoms while others have many:•“I am interested in knowing if she has it, not in how severe it may be.”•“That’s the one where it makes me wish that we just wait and get him screened if he had any symptoms.”
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
ViewsFamily StudyGrandmother of a teenager with Klinefelter:•“He’s really not a full blown Klinefelter, he’s just a borderline….You know, he’s just a little Klinefelter’s, he’s not a lot Klinefelter’s.”Father of girl with Turner:•“I don’t think Turner’s exists without some of the physical aspects of it.”
New Mothers’ StudyNew mothers regarding some live their entire lives without a diagnosis:•“If he does not have symptoms, and I do not have a reason to think he has it, there is no reason to do this test.”•“The possibility that she would have severe symptoms [is] enough to make me want to know.”
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
ConclusionsNew Mothers’ Study
• Most said they would want screening for SCVs. • “If it’s there, you would want to know about it.
Even if it’s mild or asymptomatic. I mean, I would still want to know about it.”
• They believed diagnosis would provide access to early intervention services they thought would be beneficial.
• Some viewed screening as peace of mind, assuming the results would be negative.
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
ImplicationsOur Views of Screening and Genetic Variation
Who Controls Meaning of Genetic Information?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
One Presentation of Our Future
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Enrollment of Children in a Study of Huntington's
Disease
Leon S. Dure, MD
Bew White Professor of Pediatrics and NeurologyThe University of Alabama at Birmingham
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Clinical Features of HD • Prevalence 4 – 10/100,000• Inheritance Dominant
High penetranceExpansion of htt gene
• Age of onset 35 – 45 yrs (range 2 – 80)<10% under 18 yrs
• Duration 15 – 30 yrs
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
HD Genetics
• Expansion of translated CAGn, chromosome 4p– Polyglutamate motif (similar to MCD, SCA-1, etc.)– CAG > 39 correlated with clinical disease– Age of onset inversely related to CAG expansion– Testing easily done – not highly accessed
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Clinical Presentation of HD• Initial signs and symptoms
– Chorea, incoordination, personality changes– Psychiatric diagnoses common
• Later signs and symptoms– Progressive chorea, dystonia– Dysarthria– Dementia, ongoing psychiatric disturbances– Early death
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
HSG - COHORT“Framingham study for HD”
• Scientific rationale• Innovations
– Inclusion of spouses and 1º relatives– Inclusion of minors– Biobank repository– Comprehensive environmental history
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Concerns for COHORT• HD family attitudes
– Clinical research in general– Research involving minors
• Logistics of assent and consent– Departure for HSG– Age and development specific process– Practical question – what and how are children to be
approached?• When do they know about HD?• What do they know?• What would be the effect of participation on children?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Dataset Development• Pilot Internet survey targeting HD families
– HDSA website– HSG website
• Advantages– Inexpensive– Anonymous
• Disadvantages– How representative are responses?– Limited information
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
HD Parent Survey• 6 months duration• 249 respondents• Survey design
– Basic demographics– Gene status– Family information – children, risk,
understanding– Attitudes regarding research for adults
and children
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Respondent Characteristics• Gender – 81% female• Mean Age – 42 yrs (F = 40y, M = 48y)• Gene status
– 42% not at risk/gene negative– 37% at risk– 18% gene positive
• Clinical research– 84% never participated in HD clinical research
• Children of respondents– 225 reported from 75% of respondents– Mean age 11yrs
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Informing Children• 62% had provided information of
some type– Average age of respondent = 47y– < 50% of AR parents had informed
• Age of children– Current average = 14y– Age informed = 12y
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Uninformed Children• Average age = 7y• Gene status of parents
– AR = 47%– NEG = 35%– POS = 18%
• Reasons for not informing– Age– Sparing distress
• Appropriate age to inform– Wait until adulthood – 8%– 15-18y – 44%– 10-14y – 26%– 5-9y – 16%
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Attitudes Towards Research• Adults regarding themselves
– 88% Agree/Strongly agree that symptomatic and at-risk persons should participate
– No major differences regarding gene status• Adults regarding children
– 55% agree that children should participate– 35% neutral– 10% disagree with participation
• Age for participation– 51% greater than 14yrs– 29% 10-14yrs– 20% less than 10yrs
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Adult/Parental Concerns• Adult participation
– Insurance– Confidentiality
• Child participation– Child’s understanding of the study– Most commonly cited – “psychological
effect of participation”
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Clinical Activities in COHORT• Yearly neurologic examination
– 63% supportive– Age – 47% 15-18y
• Blood specimen for research and “DNA testing”– 49% supportive– Age – 45% 15-18y
• Statistically, AR group was least likely to be supportive of examination/blood specimen
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Summary/Conclusions• Parental support for inclusion of children in
COHORT– Older children– Informed children
• Importance of family composition/gene status/symptom presence– Not all families inform children at the same time– Clinical activities of COHORT will need to be tailored to
parental concerns• Need to develop strategies to assess childhood
understanding of HD
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Genetic Screening in CVID:What are we looking for?
Kristen Hayward, MDFellow, Pediatric Rheumatology
Seattle Children’s Hospital
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
the Case16 m.o. F presents for immune work-up
Past Medical History:term, healthy2 infections treated with oral antibiotics mild eczema
Family History:Dad: immunodeficiency syndrome (CVID)
•sepsis, anemia, thrombocytopenia•splenectomy, steroids, IV immunoglobulin
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
the Case(continued)
Physical Exam:normal growth & developmentnormal exam
Labs:mild anemianormal vaccine responsesnormal antibody levels
Mom’s concern:Should we send a genetic test for CVID?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
What is CVID?Common Variable Immunodeficiency
Incidence: 1/10,000 – 50,000 in U.S. Presents in 2nd – 3rd decade of life
•recurrent bacterial infections•chronic lung disease•autoimmune phenomena•malignancies
Inheritance: • 90% sporadic
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
What is CVID?Treatment:
• replacement immunoglobulins (IVIG)• timely antibiotics
Prognosis:• mortality 20-30% over 30 years
Diagnosis:• clinical and laboratory criteria
So what about genetic testing?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Genetic Testing in CVID?TACI gene:
mutation in 7-10% of CVID casesgood biologic plausibilitysame change found in
asymptomatic family members
Father’s TACI gene analysis:single amino acid substitutiondescribed on OMIM, not validated
mutation or variation?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Back to the CASE…
Should we test our patient
for a TACI mutation?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
How do we decide?Burke, Pinsky & Press framework
Yes No
High
Low
Burke, Pinsky, Press, American Journal of Medical Genetics 106 (2001), pp. 233–240
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Clinical Validity? Genetic test for CVID
“Positive” result
- Unclear if causative- Unclear penetrance- Unclear age of onset
“Negative” result
- Unclear if causative- Baseline risk based
on family history
Indeterminant clinical validity
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Effective Treatmentfor CVID?
No preventative therapiesNo cure
Supportive care:- Timely antibiotics can be life saving- IVIg may improve outcomes
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
What are the issues?
Labeling Effects
Health Outcomes
Vulnerable child?Future insurability?
Closer follow-up?Earlier detection?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
What would YOU do?
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
the Case What happened?
Patient underwent genetic testing:same TACI sequence as her father
26 months: developed arthritis in multiple jointsstarted treatment within 8 weeks
36 months: low WBC, low antibodiesstarted replacement IVIG
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
What was the family’s perspective?
Testing was a good thing
Altered perception of child- Convinced that child had disease
Value of information- Empowered to seek appropriate care
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Provider’s perspective?More questions than answersTest may be more valuable in timeTreatment dilemmas:
- Usual medications?- Increased risk of malignancy, infection?
test most appropriate for research setting
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Summary Become familiar applying the
Burke, Pinsky, & Press model to evaluate genetic tests for pediatric diseases
Identify dilemmas arising from genetic tests with low or indeterminate clinical validity
Recognize differences between provider and family perceptions of genetic testing
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Thank youTruman Katz Center
for Pediatric Bioethics-Doug Diekema-Doug Opal
UW Public Health Genetics -Kelly Fryer-Edwards
Pediatric Rheumatology and Immunology Departments
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Attitudes toward carrier testing of minors
A study of families with X-linked & autosomal recessive diseases
Cynthia A. James, ScM, PhD
Genetic CounselorJohns Hopkins ARVD Program
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Purpose of the studyTo investigate the desirability of and
rationale for/against carrier testing of minors among members of families affected by X-linked (XL) and autosomal recessive (AR) conditions– Attitudes of adolescent and adult
siblings– Influence of mode of inheritance of the
disease on attitudes
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Chronic granulomatous disease
• Primary immunodeficiency disorder characterized by recurrent fungal and catalase positive bacterial infections
• Incidence: 1/200,000• Mortality: 2- 5% per year• 2/3 XL, 1/3 AR
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Duchenne & Becker muscular dystrophy• X-linked• Duchenne
– Diagnosis age 3-5– Loss of ambulation age 9-12– Death in 20’s - early 30’s
• Becker– Diagnosis around age 12 (varied)– Loss of ambulation in 20’s– Survival well into adulthood
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Spinal muscular atrophy (II & III)• Autosomal recessive• Type II
– Onset < 18 months– Children learn to sit unaided +/- walk – Death late adolescence / young adulthood
• Type III– Onset > age 2– Loss of ambulation variable - adolescence /
adulthood– Normal lifespan
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Recruitment• CGD
– Registry of U.S. Residents Affected by CGD of the Immune Deficiency Foundation
– NIH Clinical Center intramural studies on CGD• Neuromuscular conditions
– Maryland/Southern Delaware and Washington DC Chapters of the Muscular Dystrophy Association
• Mailed invitations to participate
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Methodology overview• Interview phase
– Semi-structured telephone interviews with 14 parents and 9 adolescent sisters (age 12-15) from 10 families with CGD
– Qualitative analysis (template analysis)• Questionnaire phase
– Mailed questionnaires completed by 206 (54% response rate) parents, adult siblings, and adults with CGD, muscular dystrophy and SMA
– Quantitative analysis
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Interviews• Semistructured telephone interviews• 20 - 90 minutes• Topics
– Family and medical history of CGD– Impact of CGD on the family– Perceptions of genetics of CGD– Perceptions of reproductive risks– Family communication– Attitudes toward carrier testing of minors
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Perceptions of the “best” age for carrier testing
Age Parents Sisters**(n =14) (n = 9)
Young as possible 4 0Puberty 8 3Mid-teens 1 118 or older* 1 4
* Parents were significantly more likely than girls tofavor carrier testing before age 18 (p<0.05)
**One girl thought there was no ideal age for carrier testing
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
• Test prior to adolescence– Parental role both in caring for child both
medically “a good parent knows as much health information as
possible” (mother, AR)– & emotionally
“I would want to cultivate a positive attitude about the news as early as possible” (mother, AR)
Risks and benefits of carrier testing - parents
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
• Test at adolescence– It is vital to know carrier status before
becoming sexually active and may affect choices re. sexual activity
“If a girl knows at 14 – hey, I could get mixed up with the wrong guy and end up with a child of my own, like my brother – maybe she would think twice…” (mother, AR)
– Girls are ready to understand both intellectually and emotionally the meaning of test results
– Adolescents have the right to know their carrier status
“They grow up with CGD in the family, it’s their right to know whether they are carriers” (mother, XL)
Risks and benefits of carrier testing - parents
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
• Girls believed it important to have access to carrier testing for reproductive decision-making
• Girls were more cognizant of psychological risks– “Around 18, because when you’re younger it’s probably
harder to take the news and you’d be worried about ever having a husband because you’d be like ‘oh what would we think if we had a child like that? Would he still like me?’” (XL – age 12)
– “ I don’t think they should do it when they are real young, I think about my age (15) is good – if they are young and they found out about it then they will worry about it a whole lot” (XL – age 15)
Risks & benefits of testing - adolescents
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Desirability of hypothetical test
• 5/6 untested girls had clear ideas on whether they would want testing were it hypothetically offered “tomorrow”
• Among the 9 parents, 4 had discordant views from their daughters on the desirability of the girl having the test “tomorrow”
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Parental Predictions• 5/11 predictions (4 from fathers) of whether
their children would say they wanted testing were incorrect“I would think she would (want carrier testing)… She’s an
extrovert… and she’s not bashful about those things. And I think she’d want to know once she understood the magnitude of…. what it could mean to her in the long run” (father, XL)
“ I want to know for myself but I don’t think I want to know now. I don’t want it to overpower my life. I don’t want to stay up nights thinking,… OK from this point on I’m not going to have kids…” (age 12, XL)
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Questionnaires• Mail questionnaires• Administered to parents, adult siblings, and adults
with CGD, MD, SMA. (9 versions)• 30 minutes• Topics:
– Family history– Clinical severity & perceived severity– Understanding of inheritance & reproductive risks– Parental guilt and blame– Stigma– Attitudes toward carrier testing of minors
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
100
80
60
40
20
0
% w
ho w
ould
test
dau
ghte
r
3 year-old 13 year-old
XL CGD AR CGD XL neuro (MD) AR neuro (SMA)
“Imagine you had a 3/13 year-old daughter who had a chance of being a carrier. Also imagine the carrier test is a blood test and is 100% accurate. Would you have her tested at age 3/13?”
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Logistic regression - carrier testing for a minor daughter
Three-year oldVariable Coefficient Odds ratio p-value
(SE) (95% CI) (<)Mode of inheritance 0.96 (0.38) 2.6 (1.2-5.5) 0.05(0=XL)Condition 1.5 (0.39) 4.6 (2.1-9.9) 0.001(0=CGD)
Thirteen-year oldVariable Coefficient Odds ratio p-value
(SE) (95% CI) (<)Mode of inheritance 1.5 (0.51) 4.6 (1.7-12.4) 0.01(0=XL)Condition 0.99 (0.53) 2.7 (0.96-7.6) 0.1(0=CGD)
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Reasons for/against testing“How important would each of the
following reasons be in your decision of whether or not to have her tested at age 3/13?”
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Rationale for Testing
Parental Role3yo (%)
13yo(%)
I could make plans to tell her about her genetic risk 98 94
As a parent, testing would give me peace of mind 94 83
A good parent knows as much as possible about anything related to the health of their child
94 98
She could be raised (go through her teens) knowing her carrier status. I could help her adjust to her genetic risk
91 100
I would be able to answer questions about whether or not she is a carrier when she asks them
90 99
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Rationale for testing
Psychosocial Risks3yo (%)
13yo(%)
She might experience insurance, educational, or job discrimination someday if she is a carrier
44 35
Learning she is a carrier too early could scare her 39 37
Other people might treat her differently if they find out she is a carrier
31 20
Testing might damage her self-image and self-esteem
32 27
I might treat her differently if she is a carrier 23 18
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Rationale for testing
Reproductive issues3yo (%)
13yo(%)
She would be certain to know and understand her genetic risk before she becomes sexually active
96 98
She would be able to start a romantic relationship knowing whether she is a carrier
86 90
Finding out whether or not someone is a carrier is only important when they could have/are planning children. The test results wouldn’t be important at her age.
30 43
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Rationale for testing
Informed consent3yo (%)
13yo(%)
A person should have a say in making a decision about whether to know their carrier status and a 3 year-old is too young to provide an opinion / at 13 she would be old enough to help make the decision
26 66
She would be too young / old enough to understand what the results mean
33 85
A person has the right to decide as an adult whether to find out if they are a carrier. If I tested her I would take away that right.
13 21
A blood test is painful. 10 7
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Rationale for NOT Testing
Informed consent3yo (%)
13yo(%)
A person should have a say in making a decision about whether to know their carrier status and a 3 year-old is too young to provide an opinion / at 13 she would be old enough to help make the decision
78 46
She would be too young / old enough to understand what the results mean
80 65
A person has the right to decide as an adult whether to find out if they are a carrier. If I tested her I would take away that right.
56 47
A blood test is painful. 33 7
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Rationale for NOT testing
Psychosocial Risks3yo (%)
13yo(%)
She might experience insurance, educational, or job discrimination someday if she is a carrier
53 43
Learning she is a carrier too early could scare her 83 60
Other people might treat her differently if they find out she is a carrier
44 50
Testing might damage her self-image and self-esteem
50 58
I might treat her differently if she is a carrier 13 14
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Conclusions• There is widespread support of carrier
testing of minors among adult members of families affected by XL and AR genetic conditions– Fulfilling parental role– Protection from uninformed reproductive
decision-making• Adolescent and adult family members
perceive the risks and benefits of carrier testing differently– Adolescents perceive more psychosocial risks
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Recommendations• Maintain current policies regarding
deferring carrier testing of minors• Genetic counseling and other
medical sessions should attend to perceived benefits of carrier testing of minors.
• Further research into the experiences of adolescent family members
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
AcknowledgementsJohns HopkinsNeil A. Holtzman, MD MPHJerry A. Winkelstein, MDKarl Broman, PhDKathy DeVet, PhDDave Valle, MDCrystal Tichnell, MSHugh Calkins, MD
NIHDon Hadley, MS (NHGRI)Harry Malech, MD (NIAID)Steve Holland, MD (NIAID)John Gallin, MD (NIAID)
Muscular Dystrophy Association
Immune Deficiency Foundation
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
The Public Health Value of Prenatal Screening
Victoria Seavilleklein, PhD
Clinical and Organizational Ethics FellowJoint Centre for Bioethics
University of Toronto, Canada
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Prenatal Screening (PNS)• Multiple marker screening (maternal serum
screening and nuchal translucency screening)
• Used to detect likelihood of conditions• Positive screen → CVS/amniocentesis →
abortion• Traditionally:
– Down syndrome, open neural tube defects, Trisomy 18
– Offered to ‘high-risk’ women
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Overview• Prenatal screening is expanding• Autonomy and public health relied
upon to justify PNS and its expansion• Argue that PNS isn’t justified on the
basis of public health
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Public Health• Multiple definitions, no single field,
discipline or methodology• “The science and art of promoting
health, preventing disease, prolonging life and improving quality of life through the organized efforts of society.” (Health Canada 2003)
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
PNS as a Public Health Initiative
• Offered population-wide• Coordinated by health clinics and
hospitals, often provincially funded• Intended to reduce the incidence of
illness and disability, thereby improving population health
• Broadly recognized by PH agencies, clinicians, in conferences & literature
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Challenges to PNS as a Public Health Strategy
1) Morally problematic definition of ‘prevention’
2) Contested benefit/burden ratio3) Limited effectiveness4) Negative consequences for people
with disabilities and society
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
1) Definition of ‘prevention’• Preventing the person, not the
condition• No ‘treatments’ or ‘cures’, just
abortion• Morally problematic because it
devalues people with disabilities• Poor track record of discrimination,
past and present
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
2) Burdens and Benefits• Ideally, those who suffer the burdens of PH
initiatives will benefit from them– Not always the case with women and fetuses
• To justify a population screen, “the disease or condition should be an important public health burden to the target population in terms of illness, disability, and death” (Khoury et al., 2003, 55). – The burden of people with disabilities is
debated
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
3) Limited Effectiveness• ~5% of disability due to genetics
– Most common causes: Low birth weight and prematurity
• Cost-effectiveness– Based on the abortion of fetuses with
projected disabilities– Challenges with cost-benefit analyses
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
4) Negative Consequences• For people with disabilities
– Reinforces a medical model of disability – Focus on avoidance, less on integration
• For mothers and families– Increased care responsibilities
• For society– Discrimination, social justice– Public policy message of devaluation– Socioeconomic disparities
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Conclusion• Public health resources would be better
spent elsewhere– Morally problematic definition of ‘prevention’– Contested benefit/burden ratio– Limited effectiveness– Negative consequences
• Routinely offering PNS isn’t justified according to the value of public health
Treuman Katz Center for Pediatric Bioethics - 2008 Conference
Thank you!Questions?