1
© The Children's Mercy Hospital, 2017
Ibrahim Ahmed, MDJennifer Gannon, MD
Ram Kalpatthi, MDElizabeth Simpson, MD
September 27, 2017
Newborn Screening: 2017 Best Practices Conflict of Interest
Elizabeth Simpson, MD: No conflict of interest
Ram Kalpathi, MD: No conflict of interest
Ibrahim Ahmed, MD: No conflict of interest
Jennifer Gannon, MD: No conflict of interest
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© The Children's Mercy Hospital, 2017 3 © The Children's Mercy Hospital, 2017
Elizabeth Simpson, MDProfessor of Pediatrics
Medical Director of Routine Newborn Services
Truman Medical Center at Hospital Hill
September 27, 2017
Newborn Screening: 2017 Best Practices
More than 12,000 NB (1/800 Screens) are diagnosed with conditions that can cause extreme disability or death if not
treated quickly
© The Children's Mercy Hospital, 2017
Sources: GAO analysis of information from the Advisory Committee on Heritable Disorders in Newborns and Children and selected states. GAO-17-196
Advisory Committee's Newborn Screening Time-Frame Goals and Barriers Identified by States
2
Federal Goals
Goal to have 95% of results reported to pediatricians within five days of birth for babies with the most time-sensitive conditions.
States to have 95% of samples reach their state lab within 24 hours of being collected.
7
Sources: GAO analysis of information from the Advisory Committee on Heritable Disorders in Newborns and Children and selected states. GAO-17-196
Delay in NB Screening Results is Serious Business
8Ellen Gabler , Milwaukee Journal Sentinel Published 7:35 p.m. CT Dec. 17, 2016
State by State Statistics
9Deadly Delays, Journal Sentinel 11/16/2013
The Embarrassing News!
10
Deadly Delays, Journal Sentinel 11/16/2013
11 12
3
© The Children's Mercy Hospital, 2017
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
4
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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
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23
Isoelectric Focusing (IEP)
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Isoelectric Focusing (IEP)
5
25
Missouri Newborn Hemoglobinopathy Screening Results
2013 2014 2015 2016
Total specimens 91218 91425 91650 92118
FS 14 18 24 17
FSC 11 11 13 6
FSA 1 5 5 5
F only - - - -
FAS 1038 993 1071 1114
Slightly elevated Bart’s 12 8 12 3
Highly elevated Bart’s - - 2 1
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Sickle Hemoglobinopathies
HemoglobinopathyEstimated % of
US patientsNBS
patternClinical severity
Hematological Studies
Hb MCV HbA2 HbF
Hb SS 65 FS Severe 6-8 N or ↑ < 3.5% <25%
Hb SC 25 FSC Mild 9-11 ↓ NA <10%
Sickle β+ thalassemia 8 FSA Mild 9-11 ↓ > 3.5% <25%
Sickle β0 thalassemia 2 FS Severe 6-9 ↓ > 3.5% < 25%
HbS-HPFH < 1 FS Mild >11 N or↑ < 2.5% >25%
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Alpha Thalassemia
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Alpha Thalassemia
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Beta Thalassemia
Classification Genotype Clinical Severity Comments
β thalassemia minor or trait
β/β+ , β/β0 MildAsymptomatic
Mild microcytic anemia
β thalassemia intermedia
β+ β+, β+/β0 Moderate Moderate anemia with Hb usually >7
Intermittent blood transfusionsRisk of iron overload
β thalassemia major β0/β0, β+/β+ Severe
Severe anemia early in lifeLifelong blood transfusions
Risk of iron overloadHSCT is curative
Other hemoglobinopathies
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Hemoglobinopathy DefectClinical Severity
Comments
HbE/β0 thalassemia βE/β0 Moderate to severe
Usually β thalassemia intermedia phenotype, Southeast Asian
HbCC βc/βc AsymptomaticUsually no anemia but microcytosis is present.
Occasionally mild anemia present. African origin
HbEE βE/βE MildMild microcytic anemia. Southeast Asian,
Southern Chinese
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NBS Pattern & Interpretation
NBS pattern Interpretation Comments
FA Normal None
Fβ thalassemia major
PrematurityRepeat testing, education, genetic counseling, confirmatory testing and hematology referral
AF Likely post-blood transfusion Repeat testing 3-4 months after the last transfusion
FSHbSS disease
Sickle β0 thalassemiaSickle HPFH
Confirmatory testing, education, genetic testing, and hematology referral
FSASickle β+ thalassemia, SCD with
transfusion
Confirmatory testing, education, genetic testing, and hematology referral. Repeat testing in 3-4 months if
transfused
FAS Sickle cell trait Education and genetic counseling
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NBS Pattern & Interpretation
NBS pattern Interpretation Comments
FSC HbSC diseaseConfirmatory testing, education, genetic counseling,
and hematology referral
FCHb C disease
Hb Cβ+ thalassemiaConfirmatory testing, education, genetic counseling,
and hematology referral
FEHb E disease
Hb Eβ+ thalassemiaConfirmatory testing, education, genetic counseling,
and hematology referral
FA+ variant Hb variant traitConfirmatory testing, education, genetic counseling,
and hematology referral if needed
FA Bart’s
Silent α thalassemia carrierα thalassemia trait
HbH diseaseHbH Constant Spring disease
Hydrops fetalis
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
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Athletes and SCT
7
© The Children's Mercy Hospital, 2017 © The Children's Mercy Hospital, 2017
Ibrahim Ahmed, MDDivision of Pediatric Hem/Onc/BMT
Children's Mercy Kansas CityAssociate Professor of Pediatrics
UMKC School of Medicine
September 27, 2017
NBS 2017 best practice: What's the BMT role?
Objectives
What is Blood and Marrow Transplant? Overview of BMT role in SCID Overview of BMT role in metabolic
disorders
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MO/KS Newborn Screening Disorders Tested
Biotinidase Deficiency (BIOT) Classical Galactosemia (GALT) Congenital Adrenal Hyperplasia (CAH) Congenital Primary Hypothyroidism (CH) Cystic Fibrosis (CF) Severe Combined Immunodeficiency (SCID) ** Amino Acid Disorders Fatty Acid Disorders Organic Acid Disorders Hemoglobinopathies: Sickle cell disease & Beta-thalassemia Lysosomal Storage Disorders: Fabry (GLA); Gaucher (GBA); Hurler/MPS-I (IDUA);Krabbe
(GALC) ** ; Pompe (GAA) Point of Care Screening: Critical Congenital Heart Defects (CCHD) Hearing
** Currently conducting statewide pilot/implementation testinghttp://health.mo.gov/lab/newborn/pdf/MissouriDisorderList.pdf
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Allogeneic Blood and Marrow Transplntation
41
BMT
Leukemia and Lymphoma
Rescue Marrow (Auto-HCT)
Marrow Failure Syndromes
Severe Aplastic Anemia
Metabolic Syndromes(Enzyme replacement)
Rescue for SCID and other PIDs
Hemoglobinopathies
ALL, AML, MDS, JMML, CML, HL*
FA, CT, DK
SCID,
Hurler Syndrome (MPS-I)
SCDThalassemia Major
High risk CNS cancer, NB, HL (R), NHL (R),
ES (R), WT (R)WAS, Bare cell syndrome, …
Time Health status Benefit/Risk ratio Expectations and Outcome
42
Allogeneic Blood and Marrow Transplntation
8
Severe Combined Immune Deficiency
Disturbed cellular and humoral immunity that may lead to early death from overwhelming infections
43https://www-uptodate-com.ezproxy.cmh.edu/contents/image?imageKey=ALLRG%2F77023&topicKey=ALLRG%2F3912&source=see_link
RAG1/RAG2 (T-B-NK+)Artemis DNA-PKcs
X-SCID (T-B+NK-)JAK3 deficiency
ADA (10-15%)Reticular dysgenesisMTHFD1(T-B-NK-)
CD45 deficiencyCD3 pathway deficiencies(T-B+NK+)
SCID: Presentation & Diagnosis
Family History Healthy child and +ve NBS
– T cell receptor excision circle (TREC) assay
Omenn Syndrome: – Autoimmunity (Erythroderma, Alopacia, HSM, lymphadenopathy)
Present at few months of age with:– Life threattening infections (viral/PJP/bacterial)/complications– Failure to thrive / diarrhea
44
45Cutoff: TREC <95 copies/punch
Cost: € 1.83 / sample +
Cost: € 1.15 / sample +
Personelcost: € 0.8 /
sample
Date of download: 9/4/2017Copyright © 2014 American Medical Association. All rights
reserved.
From: Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States
JAMA. 2014;312(7):729-738. doi:10.1001/jama.2014.9132
Date of download: 9/4/2017Copyright © 2014 American Medical Association. All rights
reserved.
From: Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States
JAMA. 2014;312(7):729-738. doi:10.1001/jama.2014.9132
Classification of Conditions With Low T-Cell Receptor Excision Circles and Low T-Cell Numbers Found by Newborn Screening
48Dorsey et al, J ALLERGY CLIN IMMUNOL; MARCH 2017
9
Protection / Isolation
Intravenous immunoglobulin (IVIG) and Abx/PJP prophylaxis
Confirmatory work-up
Blood and marrow transplant => produce normally functioning T cells and probably B cells
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Management and Treatment
50Pai et al. N ENGL J MED 371;5 NEJM.ORG JULY 31, 2014
Severe Combined Immune Deficiency
TREC in NBS stands for:a. The Real State Councilb. T cell Receptor Excision Circlec. Transdisciplinary Research on Energetics and
Cancerd. Translating Research in Elder Care
51
Q Hurler Syndrome (MPS-IH)
Incidence 1:100.000
AR
Lysosomal storage disease, due to α-L-iduronidaseinsufficiency => dermatan and heparan sulfate substrates accumulation
52Journal of Pediatric Orthopaedics, 24(1), January/February 2004
Multisystem disease: Coarse facial features, corneal clouding, hepatosplenomegaly, cardiorespiratory failure, progressive intellectual deterioration, sensorineural hearing loss, and a generalized characteristic skeletal dysplasia
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
54
Hurler Syndrome (MPS-IH)
10
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Mieke Aldenhoven et al. Blood 2015;125:2164-2172©2015 by American Society of Hematology
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Mieke Aldenhoven et al. Blood 2015;125:2164-2172©2015 by American Society of Hematology
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
57
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
58Blood, 125(13), 2164-2172
Hurler Syndrome (MPS-IH)
© The Children's Mercy Hospital, 2017 © The Children's Mercy Hospital, 2017
Managing Abnormal Newborn ScreensJennifer Gannon, MD, FAAP, FACMG
Clinical Biochemical GeneticistDivision of Clinical Genetics
Children’s Mercy Kansas CityClinical Assistant Professor, UMKC School of Medicine
NBS 2017 Best Practice
11
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.
61
Disclosing NBS Results
62
PCP Experience
63
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
64
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
66http://cdn-img.essence.com/sites/default/files/images/em
Salm N, Yetter E, Tluczek A. J Child Health Care. 2012;16:367-381.
12
Parents’ Recommendations: Themes
Knowledgeable
Known to family
Effective communicator
Calm, reassuring
Answer and encourage questions
Make sure parents understand
Be honest
Be sensitive
Use simple language, don’t overwhelm
Characteristics in PCP PCP approach to disclosure
67Salm N, Yetter E, Tluczek A. J Child Health Care. 2012;16:367-381.Baby-healthguru.com-jpg
ACT SHEET
ACMG
Actions to take
Diagnostic evaluation
Clinical considerations
Additional resources
68https://www.ncbi.nlm.nih.gov/books/NBK55827/
Algorithm
Analyte(s) flagged
Confirmatory labs
Interpretation of results
Next steps
69https://www.acmg.net/docs/ACT%20Sheets/Algorithms/Visio-C8_%20C6_C10.pdf Accessed 06/24/2017
Educational Materials
Baby’s First Test– Conditions by State– Links to State NBS Brochures
STAR-G Genetics Home Reference
70
Opportunity for QI Projects
71
Practical Considerations
72
13
Notification of Treatment Center
Kansas – Lab does not notify Missouri – Lab does notify
– Exception: SCID – PCP must contact Immunology at treatment center
Contacting treatment center recommended
73http://randommization.com/2013/08/02/the-element-of-confusion-tee/
When contacting family:
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
75
http://www.ggc.org/images/DSB_Sample_Collection__Requirements.pdfhttp://i.dailymail.co.uk/i/pix/2010/10/18/article-1321698-0BAA9B22000005DC-712_468x484.jpghttp://livesstar.com/wp-content/uploads/2017/02/prematurity-for-child_2.jpg
Repeat Screens
Don’t repeat unless asked to Repeating NBS = betting that it will be
normal
76
Risks of Repeating Screen on a Referral
77
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
78
14
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
Patients and Families
79 80
© The Children's Mercy Hospital, 2017
Elizabeth Simpson, MDProfessor of Pediatrics
Medical Director of Routine Newborn Services
Truman Medical Center at Hospital Hill
September 27, 2017
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?
84
15
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
85
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
86
Resources/References
87
• 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.
Hemoglobinopathies: Current practices for screening, confirmation and follow-up, CDC 2015
Chandrakasan S, Kamat D. An overview of hemoglobinopathies and the interpretation of newborn screening results. Pediatr Ann. 2013;42:502-8
Hoppe CC. Newborn screening for non-sickling Hemoglobinopathies. Hematology Am SocHematol Educ Program. 2009:19-25
https://www.cdc.gov/ncbddd/sicklecell/index.html
http://health.mo.gov/living/families/genetics/newbornscreening/factsheets.php
Naik RP, Haywood C. Sickle cell trait diagnosis: clinical and social implications. Hematology Am Soc Hematol Educ Program. 2015;2015:160-7
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References
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09/01/17 Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, Abbott JK, Baker M, Ballow M, Bartoshesky LE, Bonagura VR, Bonilla FA, Brokopp C, Brooks E,
Caggana M, Celestin J, Church JA, Comeau AM, Connelly JA, Cowan MJ, Cunningham-Rundles C, Dasu T, Dave N, De La Morena MT, Duffner U, Fong C, Forbes L, Freedenberg D, Gelfand EW, Hale JE, Hanson IC, Hay BN, Hu D, Infante A, Johnson D, Kapoor N, Kay DM, Kohn DB, Lee R, Lehman H, Lin Z, Lorey F, Abdel-Mageed A, Manning A, McGhee S, Moore TB, Naides SJ, Notarangelo LD, Orange JS, Pai S, Porteus M, Rodriguez R, Romberg N, Routes J, Ruehle M, Rubenstein A, Saavedra-Matiz CA, Scott G, Scott PM, Secord E, Seroogy C, Shearer WT, Siegel S, Silvers SK, Stiehm ER, Sugerman RW, Sullivan JL, Tanksley S, Tierce ML, Verbsky J, Vogel B, Walker R, Walkovich K, Walter JE, Wasserman RL, Watson MS, Weinberg GA, Weiner LB, Wood H, Yates AB, Puck JM. Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States. JAMA. 2014;312(7):729–738. doi:10.1001/jama.2014.9132
Laura Tagliaferri , Joachim B. Kunz , Margit Happich , Susanna Esposito , Thomas Bruckner , Daniel Hübschmann , Jürgen G. Okun , Georg F. Hoffmann , AnsgarSchulz , Judit Kappe , Carsten Speckmann , Martina U. Muckenthaler , Andreas E. Kulozik. Newborn screening for severe combined immunodeficiency using a novel and simplified method to measure T-cell excision circles (TREC). Clinical Immunology 175 (2017) 51–55
Dorsey, Morna J., MD, MMSc; Dvorak, Christopher C., MD; Cowan, Morton J., MD; Puck, Jennifer M., MD. Treatment of infants identified as having severe combined immunodeficiency by means of newborn screening. J Allergy Clin Immunol. 2017 Mar;139(3):733-742. doi: 10.1016/j.jaci.2017.01.005.
Weisstein JS, Delgado E, Steinbach LS, Hart K, Packman S. Musculoskeletal manifestations of Hurler syndrome: long-term follow-up after bone marrow transplantation. J Pediatr Orthop. 2004 Jan-Feb;24(1):97-101.
Aldenhoven, M., Wynn, R. F., Orchard, P. J., O’Meara, A., Veys, P., Fischer, A., Valayannopoulos, V., Neven, B., Rovelli, A., Prasad, V. K., Tolar, J., Allewelt, H., Jones, S. A., Parini, R., Renard, M., Bordon, V., Wulffraat, N. M., de Koning, T. J., Shapiro, E. G., Kurtzberg, J., & Boelens, J. J. (2015). Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood, 125(13), 2164-2172. Accessed September 05, 2017. https://doi.org/10.1182/blood-2014-11-608075.
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References
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Of Course, Our Babies are Worth It!
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Thank you