What disorders do newborn screening programs typically include?

While there are no universal criteria for selecting disorders for newborn screening programs, there is consensus that included disorders should have a relatively high frequency in the general population, a well-defined natural history, and high mortality and morbidity rates when left untreated. Importantly, effective treatments and tests for these disorders should also be available.

The number of disorders screened varies from state to state and also between countries. Newborn screening programs in the U.S. tend to screen for the 61 conditions that are currently on the Recommended Uniform Screening Panel developed by the Health Resources and Services Administration. Out of these 61 conditions, 49 are metabolic disorders, and 12 are other types of disorders, including two (critical congenital heart disease and hearing loss) that are not screened for with clinical laboratory tests. Most of the metabolic disorders are classed as organic acidurias, amino acid disorders, and fatty acid oxidation defects.

What does the process of newborn screening and follow-up entail?

Newborn screening is usually a state-mandated program that various federal and professional bodies guide. It is not just a laboratory test but a complete process that begins with sample collection, transportation, and laboratory testing, and then proceeds to results notification, patient treatment and education, and finally, the evaluation of the patient’s long-term outcome.

To start, healthcare providers collect a heel-prick blood sample on filter paper from an infant and send it to a screening laboratory for testing—which for metabolic disorders is primarily done with tandem mass spectrometry. After testing, the lab then categorizes results as either low or high risk. For low-risk cases, the newborn screening laboratory generally contacts the primary care provider to collect an additional sample for repeat testing. For high-risk cases, in addition to contacting the primary care provider, the lab also notifies a specified genetic center with specialized care providers for immediate follow-up. Either the primary care provider or genetic center then contacts the patient for clinical evaluation and additional laboratory testing for confirmation of screen-positive results. This needs to be done in a timely manner, as most metabolic disorders require immediate patient management and treatment. Lastly, to close the circuit, the newborn screening laboratory is notified, usually by the genetic center, of confirmation results for quality control and assurance.

What are the challenges of following up on newborn screen positive results?

Coordinating a patient’s clinical evaluation and follow-up testing for result confirmation can be challenging due to the limited availability of specialized healthcare providers and laboratories, particularly for patients living in remote areas. This may delay the initial management and treatment of an infant with a serious disorder. Some confirmation tests also require a large volume of either blood or another sample type such as urine, cerebro¬≠spinal fluid, or fibroblasts, all of which are difficult to collect in newborns. Additionally, almost all of the methods used in the confirmation of metabolic disorders are laboratory-developed tests. This leads to significant variation in results from different labs.

As newborn screening programs continue to advance, these challenges should be kept in mind and addressed so that all newborns benefit from prompt and proper follow-up of screen-positive results.

Dr. Garg will delve further into this topic during two roundtable talks (session numbers 42112 and 52212) at the 71st AACC Annual Scientific Meeting on Monday, August 5 at the Anaheim Convention Center in California.

Uttam Garg, PhD, DABCC, FAACC, is director of the division of laboratory medicine and professor of pediatric pathology at Children’s Mercy Hospital and University of Missouri School of Medicine in Kansas City. +Email: ugarg@cmh.edu