Since the introduction of Guthrie filter paper testing for phenylketonuria in the early 1960s, newborn screening has continued to grow. The first significant expansion took place with introduction of tandem mass spectrometry in the late 1990s and early 2000s. More recently, availability of screening methods for immunological, lysosomal storage, and peroxisomal disorders has prompted further expansion. As the cost and availability of molecular screening has become more mainstream, it is also becoming a part of newborn screening in some state programs. Changes to newborn screening are taking place so rapidly, it is challenging for providers to keep pace.
The Advisory Committee for Heritable Diseases in Newborns and Children (Committee) advises the Secretary, U.S. Department of Health and Human Services (Secretary) about newborn screening and inclusion of heritable conditions to the Recommended Uniform Screening Panel (RUSP). Although newborn screening remains state-based and varies across the country, the RUSP serves as a guide to help standardize newborn screening at the national level. The charge of the Committee is to provide recommendations to enhance, expand, and standardize newborn screening across state lines to reduce infant and childhood morbidity and mortality. To that end, the Committee reviews the available evidence on nominated conditions and weighs the risk benefit ratio of screening, including early diagnosis and availability of treatments. Based on these findings, the Committee makes recommendations to the Secretary regarding whether the condition should be screened and based on those findings, the Secretary determines whether the condition will be included in the RUSP.
As of July 2017, most states were screening for the majority (32-33) of the 34 core conditions as recommended on the RUSP including critical congenital cyanotic heart disease and severe combined immunodeficiency syndrome. Core conditions are those for which the natural history is well understood, there is a reliable screening test and available and effective treatments, and timely identification may influence reproductive decision-making. Some states also screen for an additional 26 secondary conditions. These conditions are not the primary targets of screening, but can be identified by biochemical abnormalities used to identify a core condition and for which reporting of the results may prove beneficial. Some states screen for conditions for which screening methods are available but are not included on the RUSP, in addition to the core and/or secondary conditions. Conditions that meet these criteria include glucose-6-phosphate dehydrogenase deficiency (G6PD), HIV, globoid cell leukodystrophy (Krabbe) disease, and several other lysosomal storage disorders.
After careful vetting, recent additions to the RUSP include two lysosomal storage disorders, glycogen storage type II (Pompe) and mucopolysaccharidosis type 1 diseases, and a peroxisomal disease, X-linked adrenoleukodystrophy. Other conditions nominated for inclusion to the RUSP without success include guanidinoacetate methyltransferase deficiency, 22q.11.2 deletion syndrome, Fabry disease, hemoglobin H, Krabbe, neonatal hyperbilirubinemia, Niemann-Pick disease, and spinal muscle atrophy. Of note, even though these conditions have been nominated for inclusion and not approved, it does not preclude a state from adding the condition to the panel or for the condition to be nominated again as the methodologies and treatment options evolve over time. For example, New York paved the way for lysosomal storage disease screening by adding Krabbe to the state newborn screening panel. As methodology became more commercially available, this prompted expansion of newborn screening for several lysosomal storage diseases in Illinois and Missouri, and other states that will soon follow suit. As diagnostic testing and treatments emerge, conditions can be nominated for inclusion more than once. For example, the initial nomination for Pompe disease in 2008 was declined. As treatment options improved and outcomes became available, subsequent nomination prompted committee review and RUSP inclusion was recommended by the Committee in 2015.
With the expansion of newborn screening from 1 to approximately 60 conditions in the last half century, the majority of which has occurred in the last 15 years, there is no doubt newborn screening is rapidly growing and screening is taking place for conditions that are not well known or well understood. There are differences between states that raise challenges for providers in referral centers or that serve neighboring states. As such, it is imperative providers remain abreast of RUSP recommendations as well as the conditions screened at the state level to provide accurate and current education to parents in the prenatal and postnatal settings, inform parents about positive and negative results of newborn screening, and understand when and to which specialist infants who screen positive need to be referred for evaluation and confirmatory testing for these rare conditions.
Recommended Resources
* Baby's First Test. Retrieved from http://www.babysfirsttest.org/
* NewSTEPS. Retrieved from https://www.newsteps.org/
* U.S. Department of Health and Human Services, Advisory Committee on Heritable Disorders in Newborns and Children. Recommended Uniform Screening Panel (2016, November). Retrieved from https://www.hrsa.gov/advisorycommittees/mchbadvisory/heritabledisorders/recommen