1. University of Nevada Reno Division of Health Sciences Nevada State Public Health Laboratory Newborn Screening (NBS) Program

2.  Screens for congenital and heritable disorders  These disorders may cause severe mental retardation, illness, or death if not treated early in life  If treated, infants may live relatively normal lives  Resulting in medical costs savings over time PURPOSE OF NEWBORN SCREENING

3. Result In:  Growth problems  Developmental delays  Behavioral/emotional problems  Deafness or blindness  Organ Damage  Retardation  Seizures  Coma, sometimes leading to death If Untreated, Disorders Can

4.  Newborn screening has been performed on Nevada infants since the early 1980’s; however, Nevada was sending the testing to the Oregon Public Health Laboratory for analyses  In 2011, legislation was modified to have the testing preferably done in Nevada. The Nevada State Public Health Laboratory was chosen to perform the testing  On July 1, 2014, the Nevada State Public Health Laboratory began screening all Nevada newborns for >40 disorders History of Newborn Screening in Nevada

5.  No funding was provided to the NSPHL to implement newborn screening. Existing staff validated and implemented the new methodologies and technologies associated with newborn screening  The NSPHL was fortunate to have a donor, Mick Hitchcock PhD, provide over $1 million dollars to purchase the highly complex and technical mass spectrometry instrumentation for the newborn metabolic testing  Experienced staff were hired as the NSPHL approached the July 1, 2014 live date to perform the daily testing and follow- up duties that would be required  On July 1, 2014, the Nevada State Public Health Laboratory began screening all Nevada newborns for >40 disorders Implementation of Newborn Screening in Nevada

6.  Utilizing existing employees for instrument setup, training and validation  Validated assays in phases to reduce the personnel needs/costs  Modified workflow schedules to incorporate NBS validation testing and routine NSPHL work with existing staff Absorbing the Cost of Laboratory Startup

7.  Nevada is 1 of 14 states currently requiring 2 NBS tests per infant. Many states recommend a 2 nd NBS test; but do not require it  NBS Programs identify approximately 10% of diagnosed cases on the 2 nd NBS sample  The NSPHL processes 200-600 specimens per day analyzing for >40 disorders per sample received Nevada Newborn Screening Program

8.  NBS cards are punched and tested on the day received  Normal results are mailed within 24 hours by regular postal service  Abnormal results are called, faxed and mailed to the hospital and Attending Physician within 48 hours of sample receipt Timeliness Abnormal/Normal Results

9.  The NSPHL and Follow-up staff have streamlined the workflow to ensure results are reported within 24-48 hours after sample receipt  “Panic” results are given priority and Specialists, the Attending Physician and hospital staff are notified immediately to assure appropriate medical care is administered to the baby Nevada Workflow

10.  The first screen at 24-48 hours or before leaving hospital, whichever is first  The second screen is recommended at 10-14 days of age  Premature and low birth weight babies (Neonatal Intensive Care [NICU]) are required to have three screens, one at NICU admission, 48-72 hours post NICU admission and at 28 days or at discharge  Take first screen before any medical treatment, TPN feeding or transfusion Nevada Babies are Mandated to Have Two Newborn Screens performed

12. NBS Screening Card

13. Newborn Screening Card - NICU

14. Newborn Screening Card – Single Used for a lost 2 nd screen card, unsuccessful NBS submission or for PKU monitoring testing

15. NBS Data Required for Sample Linking and Result Interpretation

16.  Linking of multiple specimens from same baby  Points assigned to each information  Demographic information of the mother and baby must match and must meet a minimum score for data system to automatically link  If below minimum score, put on a list for review and manually linked Specimen Linking

17. NBS Sample Collection

18. Current Sample Transport mechanisms in use to send samples to the NSPHL:  FedEx  UPS  US Mail  Local & Hospital Couriers Specimen Transport to NSPHL

19. Out-of-State Specimens

22. Nevada NBS Monthly Sample Volumes

23. Organic Acid Conditions: Beta-ketothiolase deficiency (BKD) Glutaric acidemia, Type I (GA I) Isobutyryl CoA dehydrogenase deficiency (IBD) Isovaleric acidemia (IVA) Malonic aciduria Maple syrup urine disease (MSUD) Methylmalonic acidemias (MMA/8 types) Propionic acidemia (PA) 3-Hydroxy-3-methylglutaryl CoA lyase deficiency (HMG) 2-Methyl-3-hydroxybutyryl CoA dehydrogenase deficiency (MBHD) 2-Methylbutyryl CoA dehydrogenase deficiency (2MBC) 3-Methylcrotonyl CoA carboxylase deficiency (3MCC) 3-Methylglutaconyl CoA hydratase deficiency (3MGH) Multiple carboxylase deficiency UreaCycle Conditions: Arginase deficiency Argininosuccinate lyase deficiency (ASA) Citrullinemia Other Conditions: Biotinidase deficiency Galactosemia Lysosomal storage diseases IMMUNODEFICIENCY STATES SCID – Target Implementation 2017 CYSTIC FIBROSIS ENDOCRINE CONDITIONS: Congenital adrenal hyperplasia (CAH) Congenital hypothyroidism HEMOGLOBIN CONDITIONS: HEMOGLOBIN CONDITIONS: Sickle cell disease and other hemoglobinopathies METABOLIC CONDITIONS: Amino Acid Conditions: Amino Acid Conditions:Homocystinuria Hyperphenylalanemia, including phenylketonuria (PKU) Tyrosinemia Fatty Acid Oxidation Conditions: Fatty Acid Oxidation Conditions: Carnitine uptake defect Carnitine palmitoyl transferase I deficiency (CPT I) Carnitine palmitoyl transferase II deficiency (CPT II) Multiple acyl-CoA dehydrogenase deficiency (MADD) Short chain acyl-CoA dehydrogenase deficiency (SCAD) Medium chain acyl-CoA dehydrogenase deficiency (MCAD) Long chain 3 hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) Very long chain acyl-CoA dehydrogenase deficiency Newborn Diseases Evaluated

24.  Disorder occurs with significant frequency  Test are inexpensive and reliable  Effective treatment/intervention exists  If untreated, baby may die or develop severe retardation  Affected baby may appear normal at birth  American College of Medical Genetics guidelines Criteria for Screened Disorders

25. Number of Confirmed Cases: 115 Number of Babies Screened: 61,172 Number of Tests Performed: 5,338,298

26.  The Nevada NBS Program will identify approximately 300-500 infants with Sickle Cell Trait per year  Cases are referred to a Hematologist Consultant to explain the significance to parents and provide genetic counseling  Sickle Cell Disease cases are discussed at the quarterly Newborn Screening Advisory Committee meetings Sickle Cell Trait

27. Received a 2-year CDC Grant to implement SCID testing in Nevada:  1 st year – FY2016: Purchase equipment for validation and personnel training – In progress  2 nd year – FY2017: Purchase additional equipment to implement statewide screening and “go live”  A fee increase will be required to support testing long-term SCID Screening

28. Normal Result Report

29. Abnormal Result Report

30.  Hardcopy Reports – Mailed  Faxing individual reports upon request  Automated Faxing by Client – in development  Implementing eReports:  Client can login to the Nevada NBS System to view/print reports  In the future, link to Nevada’s Health Information Exchange (HIE) for report access Reporting Mechanisms

31. Monthly reports are provided to submitters reporting on:  Sample Card Transit Times  Demographic Errors  Specimen Collection Errors  Unsatisfactory Samples Submitted for Testing Practice Profile Reports (Continuous Quality Improvement Monitor)

32. Confirmatory Testing is coordinated by the short-term follow-up personnel in conjunction with the Medical Consultant and Attending Physician. Confirmatory testing generally uses a different sample type and testing methodology than the screening assay Confirmatory Testing

33.  Receives the initial presumptive positive screening test from the laboratory and makes appropriate notifications to manage the case  Notifies the appropriate Newborn Screening Consultant  Determines confirmatory testing to be performed in conjunction with the appropriate NBS Consultant  Arranges for baby’s confirmatory sample to be collected and sent to a designated confirmatory lab  Assures results are received timely and newborns receive the appropriate care Follow-up Activities Follow-up Coordinator located in Las Vegas, NV

34. Nevada Statewide Medical Consultants Nicola Longo, MD, PhD University of Utah Genetics/Pediatrics Metabolic Consultant (Biotinidase Deficiency, Galactosemia, Organic Acidemias, Urea Cycle, Amino Acid, Fatty Acid Oxidation Disorders) Consultation & Clinics Northern and Southern Nevada Alexandra Aguilar, MD Endocrinology Consultant (Hypothyroidism, Congenital Adrenal Hyperplasia) Jonathan Bernstein, MD Children’s Center for Cancer and Blood Disorders Hemoglobinopathy Consultant (Sickle cell diseases) Craig Nakamura, MD Children’s Lung Specialists, LTD Pulmonary Consultant (Cystic Fibrosis) Nevin W. Wilson, MD & Mary Beth Hogan, MD University of Nevada School of Medicine - Pediatrics Immunology-SCID Consultants

35.  This is a screen. There are presumptive positives reported that are “true positives” & some “false positives” - Confirmation is required to distinguish  The newborn screen is designed to detect babies at risk before they have signs and symptoms  Early detection and treatment results in prevention of irreversible complications  There is often no family history. Siblings may not have history of any screened disorders Things Parents Should Know About Abnormal Screens

36.  Nevada’s fee for NBS laboratory testing is part of the birth registry fee defined in NAC 440.210. The fee is currently $81 for both the 1 st and 2 nd sample testing  Plans are underway to remove the NBS fee from the birth registry fee and obtain the fee through an alternate mechanism Newborn Screening Fee

37. NBS Fee by State (April 2016) Source: NewSTEPs – Association of Public Health Laboratories

38.  The NBS Fee payment protocol may change in the future as the NBS fee is removed from the birth registry payment system  With Newborn Screening Panel test expansion in Nevada, fees will increase to sustain the program expansion and assure care of infants NBS Fee Adjustment

39. In 2011, the National PKU Alliance published a monograph on the collective cost of treating just PKU in USA:  About 4 Million babies screened per year  Collective national cost of such: $200M  Annual cost PER PERSON of special formula: $7,100  Nursing care in a long term setting: ~$100,000  Cost of managing disabilities, “treated too late” $1 – 2 BILLION From Buist et al., June 2009 From Buist et al., June 2009 Final Words About Cost

40.  Provides program review for dried blood spot and hearing screenings  Provides a voice for consumers  Discuss newborn screening best practices  Promotes advocacy  Review proposals for addition of NBS tests  Provide recommendations Nevada NBS Advisory Committee Meet Quarterly via Video Conference Reno & Las Vegas Locations

41.  NBS Pamphlets (English & Spanish)  Collection and Newborn Screening Program Video  Collection posters  NBS website  Power Point presentations of NBS Collection  Online Provider Education  On-site In-Service trainings Resources for Providers

42. Stephanie Van Hooser, MBA, MT(ASCP), CLS NV State Public Health Laboratory Administrative Director svanhooser@medicine.nevada.edu775-682-6205 Bonifacio (Jojo) Dy, MD NV State Public Health Laboratory Newborn Screening Manager bdy@medicine.nevada.edu775-682-6238 Contact Information

43. Questions?