Genomic Sequencing of all newborns? Good or Bad?

Published On: October 14th, 2022>By Frank Adamo, CEO Add Your Labs>Last Updated: March 5th, 2023>Categories: General>

Update in Diagnostic and Clinical lab testing

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I have seen several recent articles from around the world discussing the utilization of genomic sequencing in newborns (refs 4-12). One specific application discussed was in Newborn Screening (NBS) (ref 1). In the U.S., NBS is run by each State. Most new parents in the U.S. are not even aware that their newborn is being screened for very rare, but sometimes deadly diseases.

NBS labs are high-volume ‘screening’ labs that test a total of ~4M babies each year across 37 labs. Screening newborns for treatable disorders has proven effective in preventing or dramatically ameliorating the severe consequences of these specific conditions.

Currently, NBS labs typically screen for 29-50 rare disorders for each baby, depending on the state (ref 2). However, there are over 7,000 rare diseases that have been identified to date. With the rapid progress of technology and genomics, it seems possible to be able to screen for additional disorders. But are there unintended costs associated with genetic discovery in newborns? Ethicists have debated the cost-benefit analysis in identifying additional genetic diseases.

Advances in DNA sequencing (i.e. next generation sequencing) has made genetic analysis in newborns more of a reality. Studies have been underway for years. However, the criteria that exists to determine if babies should be screened for specific disorders hasn’t changed that much.

Bick, et. al. (ref 1) recently published commentary that addresses the opportunities and challenges of genomic sequencing as part of newborn screening programs.

Below are summary points of the publication:

1. Genomic Technology in Newborn Screening

a. Can screen for many disorders at a very low cost per disease

b. Gene panels, whole exome, and whole genome sequencing are potential options that are being researched

c. Genomic technological advances have allowed greater sequencing coverage which can identify different structural variants, such as small nucleotide variants (SNVs), small indels, and copy number variants (CVNs). This means that they can now more easily sequence through the parts of the genome that were traditionally difficult to sequence through.

2. How do you choose which Conditions, Genes, and Variants for Screening?

a. Using the HRSA Recommended Uniform Screening Panel (RUSP) (ref 13) panel as a guide (paper discussed Wilson and Junger Principles), which has served as a recommendation for NBS programs. Each state in the US decides on which disorders to screen for

b. In 2003, the ACMG (American College of Medical Genetics) developed the criteria that is used to determine if a disorder should be add to the RUSP (ref 2). The below are high level criteria that is used to determine if a condition should be added to NBS panels.

i. Is the condition an Important Health Problem

ii. Is the Natural History of the Condition Adequately Understood. Note: Natural history of disease refers to the progression of a disease process in an individual over time, in the absence of treatment3.

iii. Is the condition not easily recognizable in the Latent or Early Symptomatic Stage of the condition. NOTE: will your pediatrician identify the condition upon regular examination, which they may not typically be looking for signs of the conditions.

iv. Is there a suitable screening method to easily find the condition. Example, can you test for the condition on a dried-blood spot (DBS) from the baby.

v. Will the test be able to find the condition among the general population being served, knowing that there are biochemical and genetic differences among people.

vi. There Should Be an Agreed Policy on Whom to Treat as Patients

vii. There should be acceptable (i.e. effective and safe) treatment if the condition is discovered

viii. If a condition is found, are there reasonable facilities and specialist providers that can Diagnosis (i.e. confirm) and Treat the condition

ix. Are the costs to our healthcare system acceptable if population-based screening of the condition starts. This includes the diagnosis and treatment of patients.

c. Ethical, Communication, Data, Management and Sharing, Legal, and Social Implications

i. Genetic evaluations to screen newborns bring additional complexity and the potential for unintended consequences. Therefore, its critically important to ensure that the rules that have been set can fairly and safely be applied to genomic sequencing methods.

ii. Things to consider ethically

1. Informed consent – from whom? What constitutes adequate consent?

2. Potential of discrimination if genetic information is stored

3. Psycho-social impacts on parent-child relationships

4. Adult vs newborn disease onset

a. Should parents know if their newborn may have a condition that manifests in adulthood

b. Will the newborn want to learn about adult-onset disease when they get older? Not all people want to know that they may or may not get a disease as an adult

iii. Communication and Transparency

1. People must understand what their being told

2. Can cause unnecessary anxiety

Potential Benefits of Genomic Sequencing of Newborns

The authors point out several benefits of adding this genomic technology to NBS including:

Identification of many additional conditions (or risk of condition) and not limited to just 29-50 conditions, depending on the state you live in
Revisit genomic data in the future. New genes or variants are being discovered all the time. The additional knowledge can help identify disease-causing genetic changes that were not previously understood
New treatments become available, which can treat these

Conclusion

So, this is the debate: Do the benefits of adding additional conditions on NBS panels with the utilization of DNA sequencing outweigh the risks? Or vice versa?

While research is still ongoing to determine if additional conditions ‘could’ be screened for with DNA sequencing, the ethical determinations have not been resolved or agreed upon, regarding if they ‘should’ be.

What do you think? Do you think the benefits of DNA sequencing outweigh the potential risks? I would love to hear your thoughts!

References:

Genomic Sequencing of all newborns? Good or Bad?

Update in Diagnostic and Clinical lab testing

Add Your Labs provides updates on hot or interesting topics in Diagnostics, with an emphasis on clinical lab testing.

Potential Benefits of Genomic Sequencing of Newborns

Conclusion

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