Newborn screening (NBS) is a system that has been called one of the greatest public health programs in the United States.1  Each year, >98% of ∼4 million newborns in the United States are screened, and >12 500 are diagnosed with a condition.2  Gauging its success has been limited by lack of data regarding long-term outcomes of identified patients. In this issue of Pediatrics, Mütze et al3  report long-term clinical outcomes in 306 patients with inborn errors of metabolism (IEM) identified between 1999 and 2016 through NBS in the laboratory at the University Hospital Heidelberg by using tandem mass spectroscopy. Patients were followed at 5 sites in Germany until a median age of 6.2 years (ranging from 1 to 17.4 years). The cohort of patients had 10 of the 12 IEMs on the national NBS panel in Germany, all of which are on the core or secondary list of the Recommended Uniform Screening Panel of the US Department of Health and Human Services.4  The authors report the incidence of acute metabolic decompensation in their cohort, a risk factor in many of the IEMs, as well as hospitalization rates and long-term outcomes. Assessments included structured clinical examination, medical history, analysis of medical records, and neuropsychological testing obtained at defined ages. More than 95% of individuals attended regular kindergarten or primary school and had age-appropriate development quotients or intelligent quotients. Without NBS, most of these patients would have permanent developmental and intellectual disability, chronic neurologic dysfunction, or would not have survived.

The NBS system is complex, with multiple components that must work optimally to allow early diagnosis of conditions and institution of appropriate treatment before onset of symptoms. For metabolic, respiratory, endocrine, neuromuscular, and hematologic disorders that require dried blood spot analysis, these components include the birth center where the initial blood spots are obtained, transport to the NBS laboratory, the laboratory, communication of results to the provider and patient, confirmatory testing, and long-term follow-up care by primary care providers and specialty teams. Mütze et al3  analyzed the NBS process quality between 2003 and 2016 and report the time required from initial DBS sampling to the reporting of results, which decreased until 2007 but remained stable after that despite time improvements in sampling and laboratory reporting, because of an increase in time for shipment of the samples by the national mail service in Germany. This highlights the critical importance of what may seem a simple part of the process, particularly in the age of overnight delivery for basic household items. For those patients reported with neonatal metabolic decompensation, these occurred in the first 5 days of life and none after NBS results were reported, demonstrating the importance of optimizing and decreasing turnaround times.

Long-term follow-up data for patients with conditions identified through NBS is critical for understanding the impact of early identification and treatment, developing appropriate treatment protocols, and assessing outcomes. In their study, Mütze et al3  examine this area, as also recommended in the previous publication in Pediatrics by Kemper et al,5  although there clearly is more work to be done. There are numerous challenges to collecting such data. There is lack of interoperability between the health care and public health systems that impedes clinical data sharing. In the United States, NBS programs are unique to each state. Currently, only a few states track patients beyond the initial short-term follow-up period. There is limited funding for long-term follow-up tracking and data entry, and patient tracking is difficult. Many of the new conditions that are being added to NBS panels have forms with onset in later childhood or adulthood. If a patient moves to a different state, they may be lost to follow-up.

Germany currently includes 14 disorders on their national NBS panel,3  and the United States has 35 on the core Recommended Uniform Screening Panel.4  It is estimated that there are 9600 rare diseases, at least half affect children, and ≤5% have an approved treatment.6,7  The Orphan Drug Act and similar international legislation has incentivized development of therapeutics, and discovery has been accelerated. Early diagnosis and treatment can often improve outcomes. These factors combined with the use of genomic sequencing for rapid identification will likely lead to an exponential increase in the numbers of conditions meeting criteria for NBS8  and an even greater need for surveillance and tracking systems.

National registries and flow of data from electronic medical record systems to public health NBS programs would optimize the ability to track patient outcomes, establish evidence-based best practices, improve quality of care, and assess the needs of patients and families. A framework for assessing outcomes from NBS has been proposed,9  but only through acknowledgment of the importance of this within the larger context of improving health outcomes of children and its implementation will the true benefits of NBS be realized. Mütze et al3  provide an excellent example in this important article of how such data can be used to evaluate the health benefits and demonstrate the positive impact of NBS.

Opinions expressed in these commentaries are those of the author and not necessarily those of the American Academy of Pediatrics or its Committees.

FUNDING: No external funding.

COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/2020-0444.

NBS

newborn screening

IEM

inborn errors of metabolism

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The author has indicated she has no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The author has indicated she has no financial relationships relevant to this article to disclose.