UPDATE ON CYSTIC FIBROSIS NEWBORN SCREENING IN OHIO

Leora Langdon RN, CPNPHeather Workman, MS

Charlotte Lemming MSW, LISW-SRobert 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– 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 2-

3 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

• 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 screeningEthnic Group Detection

rateBefore test After - result

Ashkenazi Jewish

97% 1 in 25 1 in 800

Non-Hispanic Caucasian

90% 1 in 25 1 in 240

African American

69% 1 in 65 1 in 207

Hispanic American

57% 1 in 46 1 in 105

Other Insufficient data

2010 National CF Data

• 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 Caucasian1/960 (0.10%) ( 1 in 960)

•African American 1/828 (0.12%) ( 1 in 828)

•Hispanic American1/420 (0.24%) ( 1 in 420)

•Ashkenazi Jewish1/3200 (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) 18,01084-89

Psychosocial Aspects of New Born Screening

Charlotte Lemming, MSW, LISW-SChildren’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

• 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

• 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

• 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

• Complex Program• Very Complex Genetics• Earlier Diagnosis and Treatment• Study Early CF Disease

• Healthier Patients with CF • Improved Life Expectancy

CF NBS• Ohio Program – Leora Langdon• Genetic Counseling – Heather Workman• Family Impact – Charlotte Lemming• CF Diagnosis and Care – Bob Fink

Questions??

A Step Towards A Cure

• 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