Newborn Screening Data Standards Update

1. Newborn Screening Data Standards Update Swapna Abhyankar, MD National Library of Medicine June 5, 2014 LOINC Committee Meeting

2. Outline • Brief overview of newborn screening (NBS) • NBS data standards • Implementation efforts • Current issues

3. Overview of newborn screening (NBS) • Public health program • Almost every infant born in U.S. is screened • Goal is to identify healthy-appearing infants with conditions for which early intervention is available and can prevent significant morbidity and mortality

4. NBS timeline • 1960s - screening for phenylketonuria (PKU) • 1970s-80s – addition of galactosemia, congenital hypothyroidism, and sickle cell disease screening • 1990s - introduction of tandem mass spectrometry for NBS • Measures amino acids, carnitines, acylcarnitines • Disorders are identified based on patterns of analytes and analyte ratios (many:many relationship)

5. Recommended Uniform Screening Panel (RUSP) • Through early 2000s, no uniformity in the number of disorders each state screened for • Effort by the AAP, HRSA and ACMG to create a recommended panel • 2006 – RUSP approved by the Secretary of HHS; had 29 core, 25 secondary conditions • 2014 – 31 core, 26 secondary conditions • 29 of the core are lab tests • Most use MS/MS, few simple chemistry tests – TSH, galactose, 17-OHP • 2 are point-of-care

7. Data and messaging standards • NLM collaborated with multiple agencies to create: • Comprehensive LOINC panel for NBS • Analyte codes (LOINC) • Interpretation codes with answer lists (LOINC, SNOMED CT) • Card variables (LOINC) • Annotated HL7 message that NBS programs can use as a template for their own messages • Approved by the HHS Secretary’s Advisory Committee on Heritable Disorders’ Laboratory Standards and Procedures Subcommittee

8. 54089-8 Newborn screening panel • Nested panel structure • Report summary panel • Card data panel • Test results panel - DBS • Amino acid panel • Acylcarnitine panel • Hemoglobinopathies panel • Endocrine panel • Congenital hypothyroidism panel • Congenital adrenal hyperplasia panel • Test results panel – POC • Hearing screening panel • Critical congenital heart disease panel

10. http://newbornscreeningcodes.nlm.nih.gov

11. Analyte view

12. State implementation efforts • Several states are in the process of implementing electronic messaging of NBS orders and results • We are helping map their local terms to LOINC/SNOMED CT and build their HL7 messages • Creating new terms/codes where gaps are found • Some are in the testing stage, are exchanging HL7 messages between the NBS lab and local hospitals/health information exchanges • States we know are using LOINC for NBS: • Kentucky, Washington, Oregon (+5), Illinois, Florida, Texas, Delaware, Michigan, California, Colorado, Ohio, Massachusetts, Pennsylvania, Utah

13. Adoption of NBS LOINC codes outside state programs • NBS long-term follow-up datasets • Over 50 NBS and other conditions • Goal is to make these data sets available to researchers • Virtual repository of dried blood spots • Pilot program - real data from CA, MI, NY, IA • Represents >2.2 million DBS specimens • Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs) • Centralized data repository, information about NBS programs themselves + aggregate results

14. Continuous evolution • Since the original panel was created, we have developed new codes for severe combined immunodeficiency, 5 lysosomal storage diseases, and critical congenital heart disease • We devised a new, simple and sustainable method for reporting hemoglobinopathy screening results • Terms and variables are periodically updated based on feedback from stakeholders • Beyond NBS • Therapeutic diet monitoring for patients with phenylketonuria and tyrosinemia diagnosed with NBS • Confirmatory and diagnostic testing, short/long-term followup

15. Current issues – MS/MS • Isobaric peaks • If a state reports a leucine result, what is it really reporting? • Leucine? • Leucine+isoleucine+alloisoleucine+valine? • Should we have some indicator that the result is an isobaric peak in the LOINC term? Peak 1: valine, leucine, isoleucine

16. Current issues – MS/MS (cont.) • Derivatizedvsnon-derivatizedmethods • Is it important for the LOINC term to include whether a derivatized or non-derivatized method was used? Derivatized kit Non-derivatized kit

17. Current issues – genetic testing • Genetic testing results • If a result is “no mutations found” how do we know how many/which mutations they looked for? • Different states user different commercial or custom assays with 1 to 40+ mutations

19. Current issues – genetics (cont.) • Similar to hemoglobin problem • Different states use different methods/controls, can identify variable number of hemoglobin types • From the result, we know the hemoglobins that were identified, but we don’t know which ones were not identified, not because they weren’t there, but because they don’t look for them • Hemoglobin solution – report the hemoglobins found AND the hemoglobins that can currently be identified by that lab

21. Current issues (cont.) • Screening versus diagnostic testing • Some programs are using genetic tests or other tests traditionally considered diagnostic as part of their screening protocol, either as first-line or second tier • Are these screening tests? • Do we include them in the NBS panel?

22. Partnerships with the NBS community • State NBS programs and laboratories • NBS laboratory system vendors • American College of Medical Genetics • Health Resources and Services Administration • Centers for Disease Control and Prevention • National Institute for Child Health and Development • Lab Standards and Procedures Subcommittee for HHS Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children • Association of Public Health Laboratories • NewSTEPs • Genetic Alliance

23. Thank you! Questions? Contact information: Swapna Abhyankar, MD swapna.abhyankar@nih.gov 301.594.7974