The Importance of Newborn Screening in Identifying Medical Disorders

According to the Centers for Disease Control and Prevention, more than 13,000 newborn babies are identified with a medical disorder each year. Many of these disorders show no symptoms in the first few weeks of life, meaning a seemingly healthy baby could still have a condition that may affect their mental and physical development or cause early death. Despite this, many such disorders are treatable if identified early enough.

Newborn screening (NBS) is a relatively easy and cost-effective way of improving the overall health of a population by identifying babies with a medical condition in a timely fashion. This allows newborns to receive the treatment they need – which is sometimes as simple as dietary changes or the introduction of a supplement – as quickly as possible and before irreversible damage has developed.

The importance of NBS for detecting inherited conditions

Within the first few days after birth, a healthcare professional will administer a simple heel prick to collect a blood spot sample on a card. The dried blood spot (DBS) card is then shipped to an NBS lab, where it is processed by different technologies that can screen for more than 50 inherited conditions. The scope of the screened conditions will vary depending on the country or region of birth. However, some common diseases are universally screened for, including:

• Congenital hypothyroidism (CH): CH is a thyroid hormone deficiency that can lead to irreversible neurological deficits, as well as poor appetite and breathing problems. The overall incidence of CH ranges from 1 in 3,000 to 1 in 4,000 live births, with variation worldwide among different ethnicities.
• Phenylketonuria (PKU): PKU is caused by a change in phenylalanine hydroxylase that can quickly cause infants to exhibit irritability, posturing, increased deep tendon reflexes, a peculiar “mousy” odor and vomiting. Approximately 1 in 12,000 Caucasians are born with PKU.

There is now momentum to expand screening for other rare diseases at the time of birth. In some instances, states and countries are beginning to build these disorders into their NBS programs:

• Spinal Muscular Atrophy (SMA): SMA is a genetic disorder that affects approximately 1 out of every 10,000 people. Most cases of SMA occur when a segment of a gene called SMN1 is missing. This gene is primarily responsible for making survival motor neuron protein (SMN), which is required to maintain normal motor neuron function. SMA can affect a baby’s ability to swallow, breathe, sit and walk.
• Duchenne Muscular Dystrophy (DMD): DMD is a genetic disorder characterized by progressive muscle degeneration and weakness due to the alteration of a protein called dystrophin, which helps keep muscle cells intact. In Europe and North America, the prevalence of DMD is approximately 6 per 100,000 individuals, with the disease primarily affecting boys.
• Mucopolysaccharidosis type II (MPS II): MPS II (also known as Hunter syndrome) is a rare inherited lysosomal storage disease, mostly found in boys, in which the body lacks iduronate sulfatase, an enzyme needed to break down long chains of sugar molecules called glycosaminoglycans. As a result, the molecules build up in different parts of the body and cause damage.

NBS is a public health success story that benefits both the young children who receive early treatment but also wider society, through the general economic benefits of a healthier population. Naturally, investment into NBS needs to be balanced against other healthcare priorities at the national level. As the NBS expansion continues into new rare disorders, a balance will need to be struck on key criteria such as cost, access to treatment and the proper management of ethical or privacy concerns.

Emerging technologies for expanded disorder detection

NBS is constantly evolving to better screen for new disorders. At present, cutting-edge techniques such as mass spectrometry (MS) and molecular polymerase chain reaction (PCR) are being utilized to screen for disorders in newborns, alongside more traditional screening technology such as immunoassays. The number of disorders screened for varies from country to country – from up to 50 in the US, to 8 in France and just 1 in some developing countries. This difference is guided by incidence rates and the policies set out in individual countries.

Huge strides are continually being made in creating new tools and workflows for future NBS technologies. Next-generation sequencing (NGS), for example, has the potential to revolutionize healthcare. Currently, much second-tier confirmatory testing is done using NGS technologies, which ensure that babies get the correct diagnosis as quickly as possible. However, the scale of NBS means that the market still needs to work out how the infrastructure of a first-tier NGS test for NBS would work in practical terms.

Looking towards the future

NGS is just one exciting development that is emerging in the field. In the short term, NBS is also seeing major advancement in screening for new disorders using pre-existing MS technology, simplified molecular PCR screening systems and innovative new workflow software packages – giving more babies access to screening and the treatment they may need.

All of the technologies, although seemingly not as “space age” as NGS, can deliver a real difference to labs by democratizing screening in ways never seen before.