Sponsors: Centers for Disease Control and Prevention (CDC) and the
Association of Public Health Laboratories (APHL)
AN OVERVIEW OF THE PROGRAM
A major public health responsibility, newborn screening
for detection of treatable, inherited metabolic diseases is a system
consisting of six parts: education, screening, follow-up, diagnosis,
management, and evaluation. Effective screening of newborns using
dried-blood-spot (DBS) specimens collected at birth, combined with
follow-up diagnostic studies and treatment, helps prevent mental
retardation and premature death. These blood specimens are routinely
collected from more than 95% of all newborns in the United States; state
public health laboratories or their associated laboratories routinely
screen DBS specimens for inborn errors of metabolism and other disorders
that require intervention. For more than 26 years, the Centers for Disease
Control and Prevention (CDC) with its cosponsor, the Association of Public
Health Laboratories (APHL), has conducted research on materials
development and assisted laboratories with the quality assurance (QA) for
these DBS screening tests. All laboratories in the United States that test
DBS specimens participate voluntarily in the Newborn Screening Quality
Assurance Program (NSQAP). The QA services primarily support newborn
screening tests performed by state public health laboratories; however,
CDC also accepts other laboratories and international participants into
the QA program. CDC provides QC materials, proficiency testing (PT)
services, and technical support to 73 domestic screening laboratories, 28
manufacturers of diagnostic products, and 300 laboratories in 53 foreign
countries. This program is a comprehensive provider of QA services for
newborn screening worldwide.
In 1978, the first DBS materials from CDC were distributed for congenital hypothyroidism screening. Currently, the expanded program includes screening for phenylketonuria, galactosemia, congenital adrenal hyperplasia, homocystinuria, and maple syrup urine disease. In 1991, sickle cell disease and other hemoglobinopathies were added to the QA program after studies showed that pneumococcal sepsis in young children with sickle cell disease was reduced by as much as 84% through early identification and treatment; these studies demonstrated the value of newborn screening for this disease. In 1994, the QA program for the DNA confirmatory methods using DBS specimens for sickle cell diseases was added. In 2001, NSQAP operated a pilot PT program for laboratories testing DBS by tandem mass spectrometry (MS/MS) for detection of amino acid metabolic disorders, fatty acid oxidation disorders, and organic acid metabolic disorders. We brought the MS/MS component into a PT evaluation status in 2002 with the application of cutoff decisions and presumptive classifications for grading. In 2002, we began distributing panels of DBS specimens for immunoreactive trypsinogen (IRT) measurements and in 2003 we added DNA confirmatory testing for cystic fibrosis.
The QC program enables screening laboratories to achieve
high levels of technical proficiency and continuity that transcends
changes in commercial assay reagents while maintaining the high-volume
specimen throughput that is required. The PT program provides laboratories
with quarterly panels of blind-coded DBS specimens and gives the
laboratory an independent external assessment of its performance. Each
year several laboratories misclassify at least one PT specimen and are
provided immediate consultation to resolve the analytical problem.
CDC prepares and distributes to national laboratories more than 500,000
DBSs per year. The DBS materials manufactured at CDC must simulate as
closely as possible the actual specimens tested. DBS materials for QC and PT are certified for homogeneity,
accuracy, stability, and suitability for all assays manufactured by
different commercial sources.
Through interactive efforts with state laboratories, NSQAP continues to
strive for improvements in services offered and to meet the growing and
changing needs for newborn screening in the public health community.
PROGRAM OPERATIONS
NSQAP's purpose is to improve interlaboratory
comparability and to work toward interlaboratory harmonization of
newborn screening tests that use DBSs. Current participants include
newborn screening laboratories, confirmatory testing laboratories, diet
monitoring laboratories, and manufacturers.
The QA program consists of two DBS distribution components: QC materials for periodic use and quarterly PT. Laboratories can participate in either or both parts. Results from participating laboratories are identified by laboratory code numbers to ensure confidentiality. For the QC part, NSQAP distributes DBS materials at 6-month intervals. Participants return quantitative results from five different analytical runs of the QC materials. For each 6-month period, NSQAP compiles and distributes the reported results. NSQAP offers QC programs for thyroxine (T4), thyroid-stimulating hormone (TSH), phenylalanine (Phe), total galactose (Gal), 17 alpha-hydroxyprogesterone (17-OHP), leucine (Leu), methionine (Met), tyrosine (Tyr), valine (Val), and citrulline (Cit). We recently began offering QC materials for acylcarnitines (C2, C3, C4, C5, C5DC, C6, C8, C10, C14 and C16).
For the PT part of the program, NSQAP distributes quarterly panels of DBS specimens that participants analyze once. They return their analytical results and qualitative (clinical) assessments for performance grading of the PT specimens. NSQAP prepares PT quarterly reports that show the distributions of analytical values and qualitative assessments reported by participants. NSQAP offers PT programs for T4, TSH, 17-OHP, Total Gal, biotinidase, galactose-1-phosphate uridyltransferase, amino acids (Phe, Leu, Met, Tyr, Val, Cit), acylcarnitines (C3, C4, C5, C5DC, C6, C8, C10, C14, C16), sickle cell disease (SCD) and other hemoglobinopathies. (Currently, the PT panels for SCDs and other hemoglobinopathies are limited to specimens containing hemoglobins related to SCDs, alpha-thalassemia, hemoglobin E-related disorders, and hemoglobins representative of beta-thalassemia in combination with a structural variant.)
At the end of each year, we prepare and distribute to all participants a summary of all PT and QC data reported for that year. There is no fee for participation in the NSQAP. Distributions of PT panels occur in January, April, July, and October. QC materials are distributed in January and July. Packages are shipped by FedEx. There is no cost to the participant for products or shipping. To request products, please download the Request Participation Form (PDF) and fax it to NSQAP at (770) 488-4255. If you have questions about the QA program, please contact:
Newborn Screening Quality Assurance Program
Centers for Disease Control and Prevention (CDC)
4770 Buford Highway N.E., Mailstop F-43
Atlanta, GA 30341-3724 USA
Voice Phone: (770) 488-4582
FAX Number: (770) 488-4255
E-Mail: CBell@cdc.gov
Newborn Screening
Request Participation Form
