UPDATE ON CYSTIC FIBROSIS
NEWBORN SCREENING IN OHIO
Leora Langdon RN, CPNP
Heather Workman, MS
Charlotte Lemming MSW, LISW-S
Robert Fink, M.D.
Update in CF Newborn Screening
• Testing:
• Cystic Fibrosis Testing in NBS Began August 30,2006
– Initially an IRT (testing pancreatic function) >200 was an
abnormal result and triggered DNA test
– DNA Mutation panel tested for 23 CF mutations initially
– Elevated IRT and at least one CF mutation noted on screen
was considered moderate risk for CF and triggered referral to
CF Center
– Elevated IRT of >270 and no mutations also considered
moderate risk for CF and recommendation for redraw of NBS
at 4 weeks of age
Update in CF Newborn Screening
• Testing
• Beginning April 2008, Mutation panel changed to 42
mutations screened and IRT lowered to 140. Value >
270 remained cut off for repeat NBS if no mutation
detected
• Beginning February 2010, The units used for IRT
express the concentration of IRT. IRT >96 Percentile is
evaluated on daily basis and is in the range of 56-65
ng/ml. ( Equivalent to 123-143 previous value)
• Currently IRT value higher than 120 and no mutation
detected, will be noted as moderate risk for CF and
recommend redraw of NBS at 4 weeks of age
Update in CF Newborn Screening
• Process at Dayton Children’s:
• ODH NBS lab fax positive screen report to CF Center and
PMD
• PMD makes initial contact with parent to report positive
screen and need for further evaluation
• PMD then contacts CF Center by phone or fax(Leora Langdon
937-641-5582 or fax 937-641-5390) to notify that parent
contact has been made
• Leora Langdon will then contact parent to schedule testing
and counseling. Initial contact is made within 24-48 hours of
notification with process, testing and counseling, completed
before 1 month of age.
Update in CF Newborn Screening
Process at Dayton Children’s:
- Family arrives at Dayton Children’s lab for sweat testing
and once testing completed they are instructed to go to
pulmonary clinic to meet with Leora Langdon for review of
test results and education.
- Genetic counselor also will meet with family in pulmonary
clinic that same visit.
Update in CF Newborn Screening
• OTHER OHIO CF CENTERS CF NBS PROCESS:
– Schedule sweat testing at around 3-4 weeks of age
– Parent is notified of results at testing visit or within
the same day
– Genetic counseling provided at all CF centers and at
one CF center a CF physician meets with all families
• DIFFERENT STATES:
– Different algorithms based on each states particular
populations as well as consideration of cost, and
resources available for follow up.
Update in CF Newborn Screening
• Screening: From 8/2006 through 8/2011
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CF Carriers = 220
Positive diagnosed with CF = 31
CF Metabolic Syndrome = 13
Referred to other Centers (by physician or parent
choice) = 58
Lost to follow up = 6
Declined follow up = 4
Died = 2
Total = 334 (Received from ODH NBS lab)
Update in CF Newborn Screening
• Positives noted in process:
– Quick scheduling- Able to be tested/seen within 23 weeks of age
– Seen by CF Center Nurse and genetic counselor at
same visit
– If positive testing seen same day by physician
Update in CF Newborn Screening
• Challenges noted in process
– Parental Acceptance
– QNS, quantity not sufficient sweat for testing, and
need for further investigation
Genetic Counseling Appointment
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Overview of cystic fibrosis (CF)
Pregnancy History
Family History
Risk Assessment
Discussion of available tests
Discussion of Options
Summary Letter to Doctor and Patient
Risk Assessment
• Infant suspected to be a carrier (1 mutation)
– No Family history of CF (Caucasian)
• 1 x 1/25 x ¼ = 1/100 ( 1%) ( 1 in 100)
– One parent has a sibling with CF(2/3)
• 1 x 1/25 x ¼ = 1/100 (1%) ( 1 in 100)
• 1 x 2/3 x ¼ = 1/6 (16.67%) ( 1 in 6)
• Notification of additional family members
Risk Assessment
• Infant who has two mutations
(diagnosis of CF)
– Both parents are carriers
– 1 x 1 x ¼ = ¼ (25%) ( 1 in 4)
• Notification of extended family members
Discussion of available tests
• Carrier screening for parents
– ACMG/ACOG recommended 23 mutation panel
– Expanded panels available if clinically indicated
• Testing for future pregnancies
– Chorionic villus sampling (CVS)
– Amniocentesis
– Preimplantation Genetic Diagnosis (PGD)
– Wait until birth
CF carrier screening
Ethnic Group Detection
rate
Ashkenazi
97%
Jewish
Non-Hispanic 90%
Caucasian
African
69%
American
Hispanic
57%
American
Other
Insufficient
data
Before test After - result
1 in 25
1 in 800
1 in 25
1 in 240
1 in 65
1 in 207
1 in 46
1 in 105
2010 National CF Data
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68% Diagnosed by Newborn Screening
15% Diagnosed by Meconium Ileus
Average age at CF Diagnosis < 4 weeks
Homozygous Delta F508 44%
Heterozygous Delta F508 43%
Residual Risk Assessment After Carrier
Screening
•Non-Hispanic Caucasian
1/960 (0.10%) ( 1 in 960)
•African American
1/828 (0.12%) ( 1 in 828)
•Hispanic American
1/420 (0.24%) ( 1 in 420)
•Ashkenazi Jewish
1/3200 (0.03%) ( 1 in 3200)
Long-Term Evaluation of Genetic Counseling Follwing
False-Positive Newborn Screen for Cystic Fibrosis
Cavanagh, et al. 2010
• Parents who received genetic counseling had a
higher level of genetic knowledge 11-14 years
later
– Even parents who had genetic counseling had
misperceptions
– Felt more comfortable discussing the implications
of the NBS with their child
Uptake of Genetic Counseling and CF
Carrier Testing Among Families Seen at
CMC
• Patients who received genetic counseling:
~85%
• Total number of adult parents who received
CF carrier screening: 34 (25%)
• Uptake of CF carrier testing
– 775 eligible, 120 (15.5) had carrier testing
• McClaren, Et al EJHG (2010) 18,0108489
Psychosocial Aspects of
New Born Screening
Charlotte Lemming, MSW, LISW-S
Children’s Medical Center of Dayton
Dayton, Ohio
Pathways
• Illness to diagnosis
• NBS to diagnosis
• NBS to Uncertainty
• How we engage is the key to all the
Pathways
Illness to DX.
• More traditional medical model
• Families searching for answers
• Child had symptoms of an illness
• Joint effort between family, PMD and CF Care
Team to find solution
NBS to Diagnosis
• Newborn without symptoms
• Informed by PMD to contact CF Care
Team
• Medical Team to provide information to
new parents in first 2-4 weeks of their
lives
NBS to Uncertainty
• Parents informed by PMD to call CF Team
• CF Medical Team unable to provide
resolution to parent’s anxiety.
• “Waiting for the other shoe to drop”
• More tests and delays
Modified Uncertainty Theory
• Based on Mishel’s Uncertainty in Illness
Theory, Studies of NBS have entered this
uncharted territory of degrees of uncertainty
for the parents and affective response over
time.
• Worry and Enduring
• Isolation
• Absence of symptoms is not comforting
Coping with the Uncertainty
• Need to provide information on the roller
coaster of emotions
• Parents remain vigilant and monitoring the
child's progress.
• Relabel – “nonclassic” “double carrier”
• Being health conscious
• Being hopeful
Parents Requests
• Time between first being told and
appointment with CF Center as short as
possible.
• Provide accurate and timely information
• Professionals to recognize the emotional
distress that the parents are under.
2010 National CF Data
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68% Diagnosed by Newborn Screening
15% Diagnosed by Meconium Ileus
Average age at CF Diagnosis < 4 weeks
Homozygous Delta F508 44%
Heterozygous Delta F508 43%
Benefits of CF Newborn Screening
• Weight <3% under age 2 years has decreased
from 30% (2006) to 15% (2010)
• Height <3% under age 2 years has decreased
from 20% (2006) to 10% (2010)
• Prevent fatty liver from malnutrition with
subsequent severe cirrhosis
• Early Detection and Eradication of
Pseudomonas
Risk Factors for Early Lung Disease
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Severe CFTR Mutations
Public Insurance
Mucoid Pseudomonas / MRSA
Low BMI
Hispanic Ethnicity
CF Classification with 2 Mutations
• Cystic Fibrosis – “classic disease”
– Sweat Chloride >60
– PI or PS
– 2 Known Disease Causing Mutations
• CF Metabolic Syndrome
• CF Related Disease
• CBAVD
CF Metabolic Syndrome
• Sweat Chloride 30-59
– < 2 Disease Causing Mutations
– No Clinical Symptoms of CF
• Sweat Chloride <30
– 2 Mutations, 1 is Disease Causing
• Current Problem only 160 out of 2000
Mutations Fully Classified
CF Related Disease - CRD
• CF Metabolic Syndrome who has developed
symptoms typical of CF
• “Easy Symptoms”
– Pseudomonas, Pancreatitis, Bronchiectasis
– Clubbing, Pansinusitis, Rectal Prolapse
• “Tough Symptoms”
– Wheezing, Bronchiolitis, Viral Infections
CF NBS Issues
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State to State Variation
QNS Sweat Tests
Role of Gene Sequencing
Premature Infants (high IRT)
Sweat Test Variability in Infants
Avoid Missing CF Diagnosis - > 5 years of age &
symptoms of cystic fibrosis at any age
CF Newborn Screening
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Complex Program
Very Complex Genetics
Earlier Diagnosis and Treatment
Study Early CF Disease
• Healthier Patients with CF
• Improved Life Expectancy
CF NBS
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Ohio Program – Leora Langdon
Genetic Counseling – Heather Workman
Family Impact – Charlotte Lemming
CF Diagnosis and Care – Bob Fink
Questions??
A Step Towards A Cure
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VX -770 (Ivacaftor) and Mutation G551D
Twice Daily Oral Pill
Decrease Sweat Chloride by 50%
Increase PFT (FEV1) by 20%
10% Weight Gain
Benefits Fully Maintained After 12 Months