Newborn Screening: 2017 Best Practices Conflict of … Screening: 2017 Best Practices Conflict of Interest ... • Despite newborn screening, ... SCD Thalassemia Major High risk CNS
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Ram Kalpatthi, MDAssociate Professor of Pediatrics
Division of Pediatric Hem/Onc/BMT Children's Mercy Kansas City
UMKC School of Medicine
September 27, 2017
NBS 2017 Best Practice: Hemoglobinopathies Outline
Introduction History of Screening Purpose of screening Methods used in screening Overview of abnormal hemoglobins & diseases Follow up of an abnormal screen Special note on sickle cell trait
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Hemoglobin Development
Hemoglobin Tetromers Newborns Adults
Hb F α2 γ2 70-80% 1-2%
Hb Aα2 β2 20-30% >95%
Hb A2α2 δ2 ~1% <3.5%
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What are “Normal” Hemoglobins
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What are Some “Abnormal” Hemoglobins
HbS HbC HbE HbH Hb Barts
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Abnormal Hemoglobins
Hb S (mutation in β6 Glutamic acid Valine) – Occurs in approximately 8% of African-Americans– In other populations that migrated from near Mediterranean sea
Hb C (mutation in β6 Glutamic acid Lysine) – Occurs in 2-3% of African Americans– Significant clinical condition when double heterozygote with HbS
Hb E (mutation in β26 Glutamic acid Lysine) – Most common abnormal Hb in the world– Occurs in >15% of people of Southeast Asian descent– Significant clinical condition when double heterozygote with β0 thalassemia
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Abnormal Hemoglobins
Hb H (β4 tetramers)– 15-20% in HbH disease– HbH causes hemolysis and Heinz bodies in the erothrocytes
Hb Barts (γ4 tetramers) – 100% in hydrops fetalis– 15-25% in HbH disease– Increased in carries of α thalassemia trait at birth
Approximately 100,000 SCD patients in USA Approximately 2000 babies with SCD per year Infection was the most common cause of death in patients SCD Penicillin prophylaxis in 1986 resulted in dramatic decrease in infection
related mortality Universal NBS for SCD initiated in 1987. Currently all 50 states and the District of Columbia perform NBS for
SCD Other disorders such as α and β thalassemias are increasingly identified
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History of NBS
Identify infants with homozygous SCD and begin penicillin prophylaxis
Identifies infants with other hemoglobinopathieswhom require follow-up
Identifies infants with hemoglobin traits whose families should receive counseling
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Purpose of Screening Methodologies
Isoelectric focusing (IEF) High Performance Liquid Chromatography (HPLC) Cellulose Acetate Electrophoresis (Alkaline) Citrate Agar Electrophoresis (Acid) Capillary Zone Electrophoresis Molecular methods
If Bart’s <10%, patient will need education and genetic counseling
If Bart’s >10%, patient will need further testing for evaluation of HbH disease and hematology referral
1 in 12 African-Americans carry SCT Affects 8% of African-Americans, 0.5% Hispanics & 0.2% Caucasians Mostly asymptomatic with normal life expectancy Complications that can occur in individuals with SCT
– Decreased urine concentration– Hematuria (papillary necrosis)– Increased risk of DVT– Increased risk of renal medullary carcinoma– Risk of sudden death
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Sickle Cell Trait (SCT)
Certain factors can predispose individuals with SCT to have symptoms– High altitude (flying, mountain climbing)– Increased pressure (Scuba diving)– Hypoxemia (when exercising intensely, training for athletic
competitions, military boot camp)– Dehydration
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Sickle Cell Trait (SCT)
• Relatively recent death…freshman defensive back Dale Lloyd at Rice in 2006
• Collapsed after running 16 sprints of 100 yards each• Cause of death was acute rhabdomyolysis• Parents sued Rice and the NCAA• This triggered the NCAA to take a closer look at this issue• 2010: NCAA issued new mandate for SCT screening
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NCAA and SCT
• Identifying SCT particularly important in athletes.• High training expectations, intense workouts can make them more
susceptible to having symptoms from SCT.• Despite newborn screening, many athletes do not know their Sickle
Cell status. • Student Health is an ideal setting to provide screening and
education for SCT SCT is not a contraindication to participate in competitive sports
Most untreated patients die of complications related to brain damage or cardiopulmonary failure in the first decade of life
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MPS-IH: Clinical Course
If there is a suitable donor, HCT is recommended Rx for patients <2 years of age with severe MPS I (Hurler)
The progressive replacement of enzyme-deficient hematopoietic cells with donor-derived enzyme-competent cells in vascular and extravascular compartments of the body
Importance in predicting the risk for most prevalent and severe orthopedic complications: – the leukocyte IDUA level obtained post-HCT – age at HCT– follow-up age – follow-up center
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Hurler Syndrome (MPS-IH)
Mieke Aldenhoven et al. Blood 2015;125:2164-2172
The long-term prognosis of patients with MPS-IH receiving HCT can be improved by:– reducing the age at HCT through earlier diagnosis, – using exclusively noncarrier donors – achieving complete donor chimerism
Clinical Biochemical GeneticistDivision of Clinical Genetics
Children’s Mercy Kansas CityClinical Assistant Professor, UMKC School of Medicine
NBS 2017 Best Practice
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Learning Objective
Describe experiences of PCPs and families Know what educational resources are available Incorporate practical information about
evaluating abnormal NBS into daily care of patients.
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Disclosing NBS Results
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PCP Experience
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Pediatrics, 2006:118;1836-1841
Pediatricians’ Reported Barriers Percent agreed
CF CH Sickle Cell
PKU MCAD
Not competent to discuss 13.2 8.8 8.8 22.6 75.0
Uncertain what confirmatory test 20.8 5.6 6.3 39.2 67.7
No convenient laboratory 10.1 2.1 3.5 13.7 17.2
Uncertain how to interpret 15.7 7.0 7.7 30.3 49.5
Uncertain who to refer to if confirmed 4.4 2.1 1.4 7.4 17.2
PCP Experience of NBS Disclosure
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Clinical Pediatrics 2015;54:67-75
Difficulties with being first point of contact: Management of result
Content of conversation
Addressing parents’ questions
Managing parental anxiety
PCPs recommendations to state NBS labs: Fax communication alone might not be enough
Providing handout for PCP to share with family
Training on “breaking bad news” or handout with common questions
Effect of false positive NBS result
Families with FP for IEM vs. normal result – Mothers had higher scores on Parental Stress Index and Parent-
Child Dysfunction subscale (Waisbren et al, 2003)
FP for MCAD deficiency– Infants with FP had more visits to PCP and >2x as many
hospitalizations in first year of life vs. infants with normal NBS (Karaceper et al, 2016)
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Parents’ Experiences
203 parents, positive NBS CF or CH– Infants confirmed as TP or carrier
Self-described reactions varied– “Very scary” to “not too concerned”– Significant emotional stress, fear of child dying– Guilt– Rollercoaster of emotions
Who in your practice contacts family? How will you provide information, answer
questions? Evaluate wellness of infant
– If infant is ill, diagnostic testing is warranted
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Appropriate Reasons to Repeat NBS
Reasons states ask for a repeat:– Unsatisfactory sample– Screen performed too early (<24 hrs)– Infant too young for test (LSDs)– History of transfusion (Hb, GALT)– “Low risk” result for certain conditions
Don’t repeat unless asked to Repeating NBS = betting that it will be
normal
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Risks of Repeating Screen on a Referral
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Delay of diagnosis Delay of treatment Missed diagnosis One analyte = multiple conditions
– Additional tests to differentiate
Repeat NBS = entire screen
Summary
Evaluation of abnormal NBS stressful for everyone Workup algorithms are available Educational materials are available NBS allows for prompt initiation of evaluation and
treatment
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Acknowledgements
Bryce Heese, MD
Uttam Garg, PhD
Emily Barr, RD
Hilary Boorstein, PhD
Randi Hanson, MS CGC
Nikki Lewis, RN
Kelly Neuburger, MSW
Meghan Strenk, MS, CGC
Kasey Rowzer, RD
Tarine Weihe, RD
Missouri Department of Health and Senior Services NBS Lab
Kansas Department of Health and Environment NBS Lab
Newborn Screening: 2017 Best Practices Just getting the results is not the end of the problem
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A Journal Sentinel Special ReportThe price of being wrongNewborn screening saves babies, but lives can be shattered when state labs ignore science and common sense.By Ellen Gabler of the Milwaukee Journal Sentinel 12/9/2016
In Summary, What We Did at TMC
Big QI Project Designated only certain collection hours Hired a courier for weekends State of MO passed a law to improve
turnaround time but didn’t fund it
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Action Steps for Your Practice?
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Examine Your Existing Process
Designate someone at your hospital and in your office to help follow up on screens Periodically re-evaluate how you are doing Be sure to reach out if you have problems
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Don’t forget Hearing Screens
1-6/1000 with Real Loss Repeat Screen at 1 month Diagnose by 3 months Amplify by 6 months OAE is not enough
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Resources/References
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• ACTion Sheets and Algorithms: https://www.ncbi.nlm.nih.gov/books/NBK55827/
• Advisory Committee on Heritable Disorders in Newborns and Children: https://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/index.html
• Baby’s First Test: http://www.babysfirsttest.org/
• STAR-G: http:// www.newbornscreening.info
• Genetics Home Reference: https://ghr.nlm.nih.gov/
• Davis TC, Humiston SG, Arnold CL, et al. Recommendations for effective newborn screening communication: results of focus groups with parents, providers, and experts. Pediatrics. 2006;117(5 pt 2):S326-S340.
• Farrell MH, Christopher SA, Tluczek A, et al. Improving communication between doctors and parents after newborn screening. WMJ. 2011;110:221-227.
• Finan C, Nasr SZ, Rothwell E, Tarini B. Primary care providers’ experiences notifying parents of cystic fibrosis newborn screening results. Clin Pediatr (Phila). 2015;54:67-75.
• Gennaccaro M, Waisbren SE, Marsden D. The knowledge gap in expanded newborn screening: survey results from paediatriciansin Massachusetts. J Inherit Metab Dis. 2005;28:819-824.
• Gurian EA, Kinnamon DD, Henry JJ, Waisbren SE. Expanded newborn screening for biochemical disorders: the effect of a false-positive result. Pediatrics. 2006;117:1915-1921.
Resources/References
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• Gurian EA, Kinnamon DD, Henry JJ, Waisbren SE. Expanded newborn screening for biochemical disorders: the effect of a false-positive result. Pediatrics. 2006;117:1915-1921.
• Hinton CF, Neuspiel DR, Gubernick S et al. Improving Newborn Screening Follow-up in Pediatric Practices: Quality Improvement Innovation Network. Pediatrics. 2012;130:e669-e675.
• Kemper AR, Uren RL, Moseley KL, Clark SJ. Primary care physicians’ attitudes regarding follow-up care for children with positivenewborn screening results. Pediatrics. 2006;118:1836-1841.
• Salm N, Yetter E, Tluczek A. Informing parents about positive newborn screening results: parents’ recommendations. J Child Health Care. 2012;16:367-381.
• Tluczek A, Koscik RL, Farrell PM, Rock MJ. Psychosocial risk associated with newborn screening for cystic fibrosis: parents’ experience while awaiting the sweat-test appointment. Pediatrics. 2005;115:1692-1703.
• Tluczek A, Orland KM, Cavanaugh L. Psychosocial consequences of false-positive newborn screens for cystic fibrosis. QualHealth Res. 2011;21:174-186.
• Waisbren SE, Albers S, Amato S et al. Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress. JAMA. 2003;290:2564-2572.
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