1 / 36

Update on Newborn Screening for Cystic Fibrosis

Update on Newborn Screening for Cystic Fibrosis. Jacquelyn Zirbes, DNP, RN, CNP, CCRC Stanford University Cystic Fibrosis Center Lucile Packard Children’s Hospital. Discovery of the ∆F508 CFTR Mutation Research teams led by Lap-Chee Tsui, Jack Riordan, and Francis Collins.

ashleyg
Download Presentation

Update on Newborn Screening for Cystic Fibrosis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Update on Newborn Screening for Cystic Fibrosis Jacquelyn Zirbes, DNP, RN, CNP, CCRC Stanford University Cystic Fibrosis Center Lucile Packard Children’s Hospital

  2. Discovery of the ∆F508 CFTR Mutation Research teams led byLap-Chee Tsui, Jack Riordan, and Francis Collins

  3. Newborn Screening Definition * • Population-based public health program applying preventivemedicine in defined regions to reduce infantmorbidity and mortality from certain biochemical and genetic disorders by using presymptomatic detection/diagnosis with dried blood specimens from newborns analyzed in central laboratories employing automated procedures linked to clinical follow-upsystems. Allen and Farrell (1996). Adv Pediatrics 43: 231-270 Allen and Farrell (1996). Adv Pediatrics 43: 231-270

  4. Principles of Achieving Better Outcomes Through Newborn Screening Screening/Follow-up Diagnosis Effective Therapy Death Life Threatening Or Irreversible Disease Biologic Onset Birth Symptomatic Onset Preclinical Stage Time/Event

  5. Diagnosis Through Newborn Screening This ~0.4 ml dried blood specimen supports numerous screening tests!

  6. NBS State Program: Positive Screen Primary Care Provider CF Center Dedicated Line NBS Coordinator Family

  7. California 4-Step CF NBS Model • Immunoreactive Trypsinogen assay (cut-off = 1.6%; projected sensitivity= 95.7%) • DNA analysis with a panel of 40 CFTR mutations (15/23 ACMG* mutations + “minority” alleles) • DNA scanning  sequencing by Ambry • Sweat test when 2 or more mutations detected

  8. California 4-Step Method’s Goals • Use initial dried blood specimen only • Focus on “severe” cases of cystic fibrosis • Identify at least 90% of Hispanic, White, and Black cases • Reduce burden of false positives & negatives, sweat tests, and costs • Achieve efficient reporting of NBS test results • Follow-up and diagnosis of positive screens at CF Centers

  9. SCREENING ≠ DIAGNOSIS (exception: DF508 /DF508 = CF)

  10. Definition of “Screening for Early Detection of Disease” “The screening procedure itself does not diagnose illness.” “Those who test positive are sent for further evaluation by a subsequent diagnostic test or procedure to determine whether they do in fact have the disease.” Hennekens and Buring, Epidemiology in Medicine, p327

  11. California Minimum Guidelines 1.Preparation for Sweat Chloride Test 2. Sweat Chloride Test 3. Laboratory testing at first CF Center visit 4. Family Studies 5. Interpretation of Sweat Chloride Test Results

  12. Throat Culture Results

  13. Updated California Results • 210 infants identified • 13 CF Centers • 27 LPCH ΔF508/ ΔF508 1 ΔF508/other 18 other/other 8

  14. Genotype-Phenotype Relationships* General Principle: genotype determines phenotype (e.g., pancreatic insufficiency vs sufficiency in CF) But, gene modifiers and extrinsic factors contribute also In metabolic disorders such as PKU, mild (non-classical) cases can occur In CF, genotype alone does not determine the pulmonary phenotype * Zielenski J and Tsui LC, Ann Rev Genet 1995; 29:777-807

  15. CA CF NBS Collaborative Network • California Genetic Disease Screening Program • Children’s Hospital of Central California • Children’s Hospital of Los Angeles • Children's Hospital and Research Center at Oakland • Kaiser Permanente Southern California • Loma Linda University Medical Center • Miller Children's at Long Beach Memorial Medical Center • Stanford University • Sutter Sacramento Medical Center • University of California San Diego • University of California San Francisco • Ventura County Medical Center

  16. Advisory Board Frank Accurso, MDUniversity of Colorado Phil Farrell, MD, PhDUniversity of Wisconsin Paul Quinton, PhDUniversity of California San Diego Jeff Wine, PhDStanford University

  17. Specific Aims In a well defined cohort of newborns with fully identified CFTR mutations determine: • 1. The feasibility of applying a uniform infant preparation protocol for sweat testing that includes salt supplementation and adequate fluid intake guidelines • 2. The genotypic determinants of sweat chloride concentration and its longitudinal changes. • 3. The effect of fluid and electrolyte balance on sweat chloride results

  18. Study Outcome Measures -Primary Outcome Measure Sweat chloride concentration at diagnosis. We hypothesize that under the baseline conditions created by the preparation protocol sweat chloride will unequivocally discriminate between varying levels of CFTR dysfunction.

  19. Study Outcome Measures Secondary Outcomes Serum aldosterone, urinary and serum electrolytes. Serum IRT Longitudinal changes in sweat chloride Longitudinal changes in clinical parameters during the first 2 years of life to gain

  20. Study entry criteria Inclusion criteria: • 1) Positive California CF newborn screening result (2 CFTR mutations identified). • 2) Post-menstrual age ≥ 36 weeks • 3) Age at time of first sweat test ≥ 2 weeks old and ≤ 16 weeks old • 4) Weight at time of sweat test ≥ 2 Kg Exclusion criteria: • 1) NICU Hospitalization at the time of diagnosis. • 2) Requiring IV fluids and/or TPN at the time of test. • 3) Diagnosis of hypothyroidism or other endocrinologic/metabolic abnormality. • 4) Presence of any other active medical condition (e.g. congenital heart, liver, or renal disease) that in the opinion of the CF Center would interfere with reliable sweat testing.

  21. Study Protocol Study participation for approximately 2 years Patients will be evaluated 5 times over the 2 year period Family will receive salt supplementation kit (salt packets, instructions and educational material) in anticipation of study visit

  22. Study Procedures

  23. Care of the CF Infant Diagnosed after Newborn Screening CF Foundation Consensus Guidelines are still evolving Need to develop a collaborative care model with PCP-subspecialist partnership An evidence based medicine strategy is very difficult to develop Thus, prudent principles of Dx → Rx based on need should be followed Set high standards such as > 50th percentile growth and normal PFT’s But, avoid overly aggressive clinical management (primum non nocere)

  24. Initiate CF center care in newborns Provide genetic counseling Prevent severe malnutrition • Vitamin E deficiency (hemolytic anemia) • Vitamin A deficiency • Essential fatty acid deficiency • Protein energy malnutrition* • Growth failure Prevent hyponatremia/hypochloremia • Salt loss in sweat* • Associated with breast feeding Prevent early progression of lung disease • Recurrent bacterial infections • Obstructive pulmonary disease • Atelectasis with mucus plugs * Potentially fatal Goals of CF Early Diagnosis & Treatment

  25. The GI/Nutrition Rationale for NBS 1. CF patients are generally well nourished at birth 2. PI will develop in ~90% of patients by ~1 year 3. Severe malnutrition will develop in ~50% untreated 4. PI can be anticipated and malnutrition prevented 5. Long term benefits of normal nutrition are significant

  26. The Pulmonary Rationale for NBS 1. The CF lung is normal at birth, but not for long. 2. Lung disease often develops as early as 2 months. 3. Pseudomonas aeruginosa (PA) colonization may occur in ~1/3 of undiagnosed patients. 4. Transformation from PA to mucoid PA is the greatest long term risk for children.

  27. The 21st Century is aNew Era for Children with CF • An established trend of early diagnosis through NBS • A paradigm shift in therapeutic strategy from the 3 I’s to the 3 P’s • No longer dominated by intervention in individuals with illnesses • But prevention in presymptomatic patients – Prevention of early deaths – Prevention of salt depletion – Prevention of malnutrition and growth failure – Prevention of “cross-infection” – Prevention of chronic PA and early mPA – Prevention of hospitalizations – Prevention (eventually) of lung disease

  28. Summary of Advantages of CF Newborn Screening • Avoid diagnostic quest • Early, specific and proper care • Proactive strategy of care • Prevention • Improved quality of life • Improved parental learning • Reduce costs • Prevent malnutrition and micronutrient deficiencies • Reduce risk of cognitive dysfunction

  29. The Stanford Cystic Fibrosis Center at Lucile Packard Children’s Hospital • Individual Treatment Plan • Collaborative Care • Interdisciplinary Team • Standards of CF Care • Family Centered Care • Emphasis on Family and Primary Provider Education • Research

More Related