University of Nevada Reno Division of Health Sciences

Nevada State Public Health LaboratoryNewborn Screening (NBS) Program

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

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

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

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

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

Nevada is 1 of 14 states currently requiring 2 NBS tests per infant. Many states recommend a 2nd NBS test; but do not require it

NBS Programs identify approximately 10% of diagnosed cases on the 2nd NBS sample

The NSPHL processes 200-600 specimens per day analyzing for >40 disorders per sample received

Nevada Newborn Screening Program

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

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

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

NBS Screening

Card

NewbornScreening

Card - NICU

Newborn Screening Card – SingleUsed for a lost 2nd screen card,

unsuccessful NBS submission or for PKU monitoring testing

NBS Data Required for Sample Linking and Result Interpretation

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

NBS Sample Collection

Current Sample Transport mechanisms in use to send samples to the NSPHL:

FedEx

UPS

US Mail

Local & Hospital Couriers

Specimen Transport to NSPHL

Out-of-State Specimens

Hospitals/Clinics/Midwives

NSPHL

Blood Spot Test

Result Within Cutoff Value

Mail/Fax Report to Submitter

Result Outside Cutoff Value

Specimen retested to verify initial result

Borderline

Request for another

specimen

Presumptive Positive

Report to Follow-up

Coordinator

Coordinator contacts PCP, Specialist and

Diagnostic Lab

Normal

Mail/Fax Report to Submitter

Normal

Newborn Screening Workflow

Nevada NBS Monthly Sample Volumes

Organic Acid Conditions: Beta-ketothiolase deficiency (BKD)Glutaric acidemia, Type I (GA I)Isobutyryl CoA dehydrogenase deficiency (IBD)Isovaleric acidemia (IVA)Malonic aciduriaMaple 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 deficiencyArgininosuccinate lyase deficiency (ASA)Citrullinemia

Other Conditions: Biotinidase deficiencyGalactosemiaLysosomal storage diseases

IMMUNODEFICIENCY STATESSCID – Target Implementation 2017

CYSTIC FIBROSIS

ENDOCRINE CONDITIONS:Congenital adrenal hyperplasia (CAH)Congenital hypothyroidism

HEMOGLOBIN CONDITIONS: Sickle cell disease and other hemoglobinopathies

METABOLIC CONDITIONS: Amino Acid Conditions: HomocystinuriaHyperphenylalanemia, including phenylketonuria (PKU)TyrosinemiaFatty Acid Oxidation Conditions: Carnitine uptake defectCarnitine 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

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

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

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

Received a 2-year CDC Grant to implement SCID testing in Nevada:

1st year – FY2016: Purchase equipment for validation and personnel training – In progress

2nd 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

Normal Result Report

Abnormal Result Report

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

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)

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

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 ActivitiesFollow-up Coordinator located in Las Vegas, NV

Nevada Statewide Medical ConsultantsNicola Longo, MD, PhD University of Utah Genetics/PediatricsMetabolic 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 DisordersHemoglobinopathy Consultant (Sickle cell diseases)

Craig Nakamura, MD Children’s Lung Specialists, LTD Pulmonary Consultant (Cystic Fibrosis)

Nevin W. Wilson, MD & Mary Beth Hogan, MDUniversity of Nevada School of Medicine - PediatricsImmunology-SCID Consultants

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

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 1st and 2nd 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

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State

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

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

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 BILLIONFrom Buist et al., June 2009

Final Words About Cost

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 CommitteeMeet Quarterly via Video Conference

Reno & Las Vegas Locations

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

Stephanie Van Hooser, MBA, MT(ASCP), CLSNV State Public Health LaboratoryAdministrative Directorsvanhooser@medicine.nevada.edu775-682-6205

Bonifacio (Jojo) Dy, MDNV State Public Health LaboratoryNewborn Screening Manager bdy@medicine.nevada.edu775-682-6238

Contact Information

Questions?