Newborn Screening Laboratory Bulletin
II. CDC’s Laboratory Role in Newborn Screening
Overview of the Newborn Screening Quality Assurance Program (NSQAP)
In 1978, CDC established the Newborn Screening Quality Assurance Program (NSQAP) to enhance and maintain the quality of newborn screening tests performed in the United States. NSQAP—housed in CDC’s Environmental Health Laboratory—has grown to become the only comprehensive program in the world devoted to quality assurance of newborn screening tests. Since its inception, NSQAP has steadily added disorders and analytes* (Figs. 1 and 2) to the program and continues to expand the program.† NSQAP provides training, consultation, proficiency testing, guidelines, and reference materials to state public health laboratories and other laboratories responsible for newborn screening in the United States and in several other countries. Because of NSQAP, parents and doctors in the United States can trust the results of newborn screening tests.
*An analyte is a substance that can be measured in the laboratory, and its presence or absence can show abnormal processes resulting in disease. The number of analytes and the number of disorders in newborn screening tests are not identical numbers. The newborn screening tests conducted in laboratories look for analytes that are associated with disorders. Some analytes identify more than one disorder, and some disorders are related to more than one analyte.
†The American College of Medical Genetics (ACMG)recommends that states conduct newborn screening tests for a core panel of 29 disorders (including hearing screening, which does not routinely involve blood spot analysis).ACMG has noted that screening for the core panel will provide data that enable states to include a secondary set of 25 disorders. CDC’s goal is to include primary analytes for the 53 disorders that can be screened using dried blood spots in NSQAP so that it can help the state newborn screening programs meet the ACMG recommendations with confidence and accuracy. NSQAP is currently at 48 disorders plus toxoplasmosis and HIV.
As NSQAP has developed, so have its relationships with public health partners. One of NSQAP’s most important partners is the Association of Public Health Laboratories (APHL) ,which serves as a dynamic interface between CDC and local, state, and territorial public health laboratories. For the past 30 years, APHL has worked closely with NSQAP to assure the highest standards of performance for newborn screening nationwide for public and private laboratories.
Through its Newborn Screening and Genetics in Public Health Committee, APHL is involved in a broad range of issues—including training in laboratory methods using advanced technology, development of policy statements on newborn screening issues, and contingency planning for continued newborn screening in the event of a disaster or other public health emergency. APHL promotes the scientific and technologic expertise of NSQAP to public health officials at the state and federal levels. APHL also provides valuable strategic guidance and expertise to NSQAP. With APHL’s assistance, NSQAP is recognized worldwide and serves as a model program of quality assurance for newborn screening for many other countries.
The birth of Tayla Cunzenheim in Wisconsin on December 23, 2002, was an early Christmas present for her happy parents, Sheryl and Jim. Shortly after they brought Tayla home on Christmas Day, they received a call from the hospital telling them that Tayla’s newborn screening test showed that she had a congenital disorder. Tayla had phenylketonuria (PKU), an inherited and treatable metabolic disorder. With PKU, the body cannot process the amino acid called phenylalanine (Phe), which is in almost all foods that contain protein. If left untreated, the Phe level can get too high in the blood, resulting in mental retardation(3).
When parents are told that their baby has a disorder like PKU, they need to know for certain that the tests are accurate. NSQAP works with all state public health laboratories, including the Wisconsin State Laboratory of Hygiene that analyzed Tayla’s test, to assure that all test results are accurate and that no disorders are missed. In many cases, newborn screening makes the difference between life and death for newborns; in other instances, identifying babies with a disorder means that they can be treated and thus not face life-long disability or cognitive impairment.
The good news for the Cunzenheims is that today Tayla is thriving. The treatment for Tayla involves keeping her on a special diet and special formula. The Cunzenheims worked with a dietician from the Waisman Center at the University of Wisconsin to develop this diet plan. Her parents describe Tayla as “smart as a whip.” She attends school and loves to draw and color. What a gift!
A Snapshot of NSQAP
Newborn screening begins with a heel stick that is done within 24-48 hours of a baby’s birth. A health-care professional collects blood from the baby’s heel onto a filter-paper card, which is the blood-collection device. This card is sent to a newborn screening laboratory for testing.
Working with manufacturers, NSQAP tests all of the filter paper used in the blood-collection devices before they are released for sale. Filter-paper manufacturers provide CDC with sample sets of paper from the beginning, middle, and end of their production lots.
The amount of paper sent to CDC varies with the size of the production lots; however, thousands of strips of randomly selected paper are tested each year. The filter paper needs to adhere to strict specifications so that the blood can be collected and analyzed correctly.
NSQAP provides quality assurance products, including training, consultation, proficiency testing, guidelines, and reference materials, to state public health laboratories and other laboratories responsible for newborn screening. Currently, NSQAP works with laboratories in every state and U.S. territory as well as with laboratories worldwide.
One of NSQAP’s primary efforts is to prepare dried blood spot reference materials for distribution to laboratories participating in the program’s quality assurance tests.
Each year, NSQAP creates and sends out nearly a million dried blood spot reference specimens. CDC scientists start with prescreened blood from blood banks. They enrich the blood with selected biomarkers (i.e., chemical substances associated with the specific disorders in newborn screening tests).
The blood is then spotted—either by hand or through use of a robot—onto filter paper.
The spots are carefully dried and packed to avoid any degradation and then stored in a freezer until needed for quality control and proficiency tests.
CDC laboratorian stacking racks of blood spot cards to dry so they can be used in quality assurance and proficiency tests.
The quality assurance efforts at CDC involve a continual interaction between NSQAP and the participating laboratories. NSQAP prepares panels of dried blood spot specimens and sends them out to participating labs.
The laboratories analyze the specimens and return their assessments to NSQAP for review. NSQAP then compiles and reports the results to help laboratories maintain accurate and reliable testing practices. The Data Verification and Evaluation reports, along with NSQAP’s dedicated efforts to work with laboratories, help newborn screening laboratories get the right answer every time.
NSQAP monitors newborn screening worldwide so that it can stay on top of new technology and tests. The graphic below lists countries with one or more labs participating in NSQAP.
Since 1978, NSQAP has steadily added laboratories to the program. Whereas only 31 laboratories participated in 1978, nearly 500 labs were enrolled in NSQAP by 2007 (Fig. 3).
Gabriel George was diagnosed with sickle cell disease when he was just three weeks old. Sickle cell disease is a group of inherited red blood cell disorders. Healthy red blood cells are round, and they move through small blood vessels to carry oxygen to all parts of the body. In sickle cell disease, the red blood cells become hard and sticky, and consequently clog the blood flow in small blood vessels. This condition can cause pain and other serious problems, such as anemia and infections(4). NSQAP makes sure that there is sustained quality in newborn screening so that a diagnosis such as Gabriel’s is not missed.
Since his diagnosis, Gabriel’s parents, Charles and Cheryl George, have been actively involved in the Marc Thomas Sickle Cell Foundation in Austin, Texas. Gabriel enjoys reading, riding his bike, and spending time with his brother Nathaniel. Gabriel was named the 2007-2009 poster child for the Sickle Cell Disease Association of America, Inc.
When Jill Levy-Fisch’s third child, Matthew, was born, she knew something was not quite right. He was developmentally delayed, and he never smiled. At age one, Matthew weighed 22 pounds. By the time he reached his second birthday, Matthew still weighed 22 pounds. During the first two and a half years of Matthew’s life, Jill went from doctor to doctor searching for an answer in what is sometimes called a medical diagnostic odyssey. Matthew endured test after test, and the experience was an emotional strain on everyone in the family. At age three-and-a-half, Matthew was finally diagnosed with short chain acyl-CoA dehydrogenase deficiency (SCADD). SCADD is a rare condition that prevents the body from converting certain fats into energy. Some of the symptoms of SCADD include vomiting, low blood sugar, a lack of energy, poor feeding, and failure to gain weight and grow at expected rates. Other features of this disorder may include poor muscle tone, seizures, and developmental delays(5). While there is no standard treatment for SCADD, Matthew has a feeding tube, takes dietary supplements to restore his metabolism, and requires physical therapy. In addition, because of his developmental delay, he visits a reading tutor four days a week.
Newborn screening for SCADD was not available in Matthew’s state at the time of his birth in 2001. Spurred to action, Jill began working for the Save Babies Through Screening Foundation, a volunteer organization that supports newborn screening. She wants to make sure that no family has to endure a medical diagnostic odyssey like her family did. Had Matthew been diagnosed through newborn screening, therapies could have been introduced earlier, and his health outcomes would have been better. While Matthew did not receive the benefit of an accurate, early diagnosis, Jill is thrilled that today her state screens for SCADD and that NSQAP works with her state laboratory to ensure accurate newborn screening tests for SCADD.