Newborn screening began in other countries in the early 1960s. It started with detecting inherited metabolic diseases such as phenylketonuria. In 1961, Dr. Robert Guthrie, a pediatrician and a microbiologist, developed a special strain of bacteria that thrives in the presence of certain amino acids. He developed a method to screen large numbers of samples by placing a dried blood spot (DBS) from a newborn on a piece of filter paper, drying it, and placing it on a medium containing this special strain.

Although this method is now obsolete and historical, it was used to begin newborn screening across the U.S. in 1963, starting with phenylketonuria. This was followed by the inclusion of foliar diabetes mellitus and homocystinuria. 

Starting in the early 1970s, newborn screening expanded to encompass congenital hypothyroidism and congenital adrenal hyperplasia, as it became evident that endocrine metabolites remained stable in filter paper bloodstains.

In Korea, all newborns have been screened for phenylketonuria and congenital hypothyroidism for free since 1997. In 2006, four more items (homocystinuria, diabetes insipidus, congenital adrenal hyperplasia, and galactosemia) were added to make it six. Since 2019, about 20 inherited metabolic diseases have been screened for free using a method called Tandem Mass.

In order for a specific test or condition to be included in a newborn screening program, it must meet the following requirements. 

First, the condition being screened for must be relatively common. Second, the condition must be difficult to diagnose before symptoms appear, even for the most experienced physicians. Third, the condition should be serious enough that a delayed diagnosis could result in irreversible brain damage or death. Fourth, the disease is treatable and has a very good prognosis if diagnosed early. (It is important to note that a screening test is not a definitive test.) Sixth, the cost of screening and confirmatory testing, as well as the cost of lifetime treatment, will be significantly less than the cost of untreated (left without early diagnosis) and therefore cost-effective.

Phenylketonuria is one of the classic conditions that fulfills all of these requirements very well. In the U.S., the incidence is about 1 in 15,000 newborns, while in Korea it is about 1 in 50,000. The most common condition is congenital hypothyroidism, which occurs at a frequency of 1 in 3,000 newborns.

Early newborn screening programs primarily included rare inherited endocrine and metabolic disorders, but the increasing number of rare genetic disorders for which treatments are being developed has led to the inclusion of disorders other than inherited endocrine and metabolic disorders.

Examples include immune system disorders such as severe immunodeficiency, neuromuscular disorders such as spinal muscular atrophy and adrenoleukodystrophy, and special blood disorders (hemoglobin abnormalities). Experts meet regularly to discuss the conditions that should be included in the newborn screening test based on the aforementioned criteria. The list of core diseases, secondary conditions, and conditions not recommended for inclusion is constantly being revised and updated.

However, there are several unfortunate problems with the current newborn screening programs in Korea. 

First, there is no official expert organization to discuss which diseases should be included. The frequency of rare diseases varies from country to country, as well as the level of laboratories and access to treatments, making it difficult to apply foreign examples. 

More importantly, Korea has too many laboratories, different disease categories, and poor test quality control.

In other words, newborn screening is too decentralized. The annual number of newborns has plummeted to about 250,000. In other countries, one or two large laboratories are sufficient to test all newborns, but in Korea, screening tests are performed in more than 10 laboratories. However, unless there are only one or two centralized laboratories, it is difficult to control the quality of the test, and it is difficult to track the diagnosis and treatment of patients. This inevitably leads to difficulties in determining the exact frequency of each disease in Korea, accurate and fast early diagnosis, and quick referral to specialists.

In addition, screening tests must be redone at a certain rate. In order to set the cut-off value of test results for retesting, it must be based on big data. Since most of the diseases we screen for are late-stage diseases, it is important to move quickly from diagnosis to treatment. A series of networks and algorithms are needed to quickly contact the parents of newborns who need to be retested, recommend a hospital for diagnosis, recommend a specialist for treatment, and monitor the progress of treatment.

I believe that this process should be managed directly by the state. The cost is too high for the state to stay negligent under the pretext of recognizing the private sector’s autonomy. 

Lastly, I want to emphasize the importance of the management of filter papers (DBS), which are used for testing and contain blood from newborns. They are often discarded by each laboratory after a certain period of time. However, bloodstained filter papers can be stored for decades. This is an invaluable asset that can be used for a variety of studies and tests (e.g., to find missing children). With parental consent, leftover filter papers should be stored and centrally managed at the Korean Bioinformation Center. 

Recently, a civilian company said it wanted to collect, store, and manage them, but this is absurd. There are some things that should be left to the autonomy of the private sector and some things that should be managed directly by the state, and newborn screening tests fall into the latter category.

This contribution was originally published in Korea Healthlog, a sister paper of Korea Biomedical Review, on May 16, 2023. -- Ed.