Newborn screening explained: The science, impact, and outlook of early detection

What is newborn screening (NBS)?

Newborn screening (NBS) is a crucial public health program that tests infants shortly after birth for rare but serious genetic and metabolic disorders. Analyzing a dried blood spot (DBS) sample collected by a heel prick for various biomarkers allows for the detection of conditions like phenylketonuria (PKU), maple syrup urine disease, spinal muscular atrophy (SMA), and other inborn errors of metabolism before symptoms appear. Early detection is vital, as it allows for prompt intervention, potentially preventing severe developmental delays, health complications, or even death. 

Why is NBS so important for public health?

Firstly, it allows for early detection and treatment of serious conditions that may not be immediately apparent at birth, enabling timely treatment and significantly improving outcomes for affected infants. By identifying these conditions before symptoms appear, healthcare providers can initiate treatment when it's most effective.

Secondly, early detection and treatment often result in better health outcomes and reduced healthcare costs over the child's lifetime. As a result, NBS is a cost-effective way to improve population health. In the United States, it is estimated to save about 1 billion dollars annually.¹ While the conditions screened for are rare individually, collectively they affect a significant number of newborns. It is estimated that over 40,000 lives are saved every year thanks to NBS.

Lastly, NBS programs provide valuable data for research and public health planning, helping to improve our understanding of these conditions and refine screening and treatment protocols over time.

What are the global differences in NBS?

Global differences in NBS are significant and reflect a complex interplay of economic, cultural, and healthcare system factors. Alarmingly, only 1 in 3 children worldwide receive any form of newborn screening, highlighting a major global health disparity.

Developed countries typically have more comprehensive NBS programs, but the number of conditions screened for can vary significantly. For instance, the United States recommends screening for 35 core conditions and consideration of 26 secondary conditions, with many states screening for far more, while the United Kingdom screens for only 9 disorders.

These differences reflect varying approaches to healthcare delivery, resource allocation, and risk assessment. For example, some countries may prioritize conditions that are more prevalent in their population or those for which they have established treatment protocols, while others focus on the ethical implications and overall impact on the healthcare system. Additionally, cultural attitudes towards genetic testing and data privacy also play a role in shaping these policies.

Moreover, the infrastructure required for follow-up care and treatment of identified conditions is a crucial consideration. A country might choose not to screen for a condition if it lacks the resources to provide appropriate care for affected infants.

Therefore, while the number of conditions screened can be an indicator of a program's comprehensiveness, it's essential to consider the broader context of each country's healthcare system, population needs, and ethical frameworks when evaluating NBS programs.

What makes a successful NBS screening program? 

A successful NBS program is characterized by several key factors, with speed, security, connectiveness, and the ability to expand being crucial elements. 

• Speed: Receiving rapid results is critical in NBS programs. Programs must have efficient sample collection, transportation to the laboratory, analysis, and reporting. Ideally, results should be available within 5–7 days of birth. This speed allows for early intervention in affected infants, which can be lifesaving in many cases.
• Security: Given the sensitive nature of genetic information, robust data security measures are essential. This includes secure handling of physical samples, encrypted data transmission, and strict access controls for patient information. Programs must comply with relevant data protection regulations and maintain patient confidentiality.
• Connectiveness: A well-connected system ensures seamless communication between various stakeholders — hospitals, laboratories, primary care providers, and specialists. Integrated health information systems can facilitate rapid result reporting and initiation of follow-up care. This connectedness also supports tracking of long-term outcomes, which is crucial for program evaluation and improvement.
• Ability to expand: Flexibility to incorporate new screenings as scientific knowledge advances is vital. This includes the capacity to adapt to new technologies, such as genomic sequencing, and the ability to add new conditions to the screening panel. A scalable infrastructure that can accommodate increased testing volume and complexity is key to a program's long-term success. 

What are the latest advances in NBS? 

The field of NBS has seen significant advancements in recent years, particularly in testing methodologies and the range of detectable conditions. Two notable advances are:

• Mass Spectrometry for expanded screening panels such as lysosomal storage disorders and amino acid disorders: Tandem mass spectrometry (MS/MS) has revolutionized NBS for many previously un-detectable disorders. This technology allows for the simultaneous detection of multiple disorders from a single dried blood spot sample. MS/MS can measure enzyme activities or specific biomarkers such as Pompe disease, Fabry disease, and Gaucher disease. The high sensitivity and specificity of MS/MS have made it possible to include these rare but serious conditions in NBS panels, enabling early detection and treatment.
• Molecular Testing for Spinal Muscular Atrophy (SMA): The introduction of molecular testing for SMA in NBS programs allows for the detection of deletions or mutations in the SMN1 gene, which is responsible for SMA. Early detection of SMA is crucial because new treatments, such as gene therapy, are most effective when administered before symptoms appear. 

What could be the future of NBS? 

The future of NBS is poised for significant advancements, with newborn genetic sequencing emerging as a potentially transformative technology. Newborn sequencing can be approached either by sequencing the entire genome or exome, or through a specified panel of genetic conditions. Despite their abilities to detect a much broader range of genetic conditions than current screening methods, sequencing has yet to replace the simpler biochemical approaches.

Other future changes include expanding the number and types of diseases that are being screened for; integrating the genetic information gathered at birth to inform personalized health strategies throughout an individual's life; improving the accuracy of testing; and working toward standardizing NBS practices globally to ensure that more children have access to comprehensive screening regardless of where they are born. All of these potential advancements need to be carefully considered as to their ethical and safety implications, including data privacy, informed consent, and the right not to know certain genetic information.

How does NBS fit within reproductive health as a whole?

NBS is an integral part of a broader continuum of reproductive health care that spans from preconception through pregnancy and into early childhood. Information learned from NBS could show increased risks for having a child with certain genetic conditions. This information could then inform decisions regarding carrier screening, prenatal testing, and/or the desire to have additional children for the couple and their extended family. Additionally, NBS serves as a crucial bridge between prenatal care and pediatric care. It complements prenatal testing by detecting conditions that may not be identifiable prenatally or by identifying conditions that develop or become detectable only after birth, in order to allows for early interventions and ongoing pediatric care.

NBS ensures that health risks are monitored and addressed at multiple stages, while the early identification of issues allow for parents to make more informed choices about their child's healthcare.