Importance of neonatal genetic screening

Recent advances in the development of large-scale genomic sequencing now allow its application in neonatal genetic screening. This means that, from the moment of birth, it is possible to detect the risk of developing genetic diseases, thanks to the identification of variants in the DNA of the newborn associated with monogenic diseases.

What is newborn screening?

Newborn screening is an essential part of newborn medical care and represents an effective tool in the early detection and management of diseases.

Its main objective is to detect metabolic disorders or other diseases of genetic origin, especially those that are potentially serious and of early childhood onset, in order to initiate early interventions, provide appropriate treatments and offer genetic counseling to families.

It is estimated that about 10% of newborns may have genetic variants related to actionable diseases. In these cases, identifying genetic risk can be of great relevance to act quickly and personalize patient management in order to delay or prevent the onset of disease.

What types of neonatal testing are there?

In clinical practice neonatal screening is generally performed either through biochemical analysis or by using genetic testing.

Biochemical tests are mainly aimed at detecting metabolic disorders by analyzing metabolites in the newborn’s blood. These metabolites are often altered in certain genetic diseases, such as phenylketonuria or fatty acid oxidation disorders. This test is known as the “heel prick test”, is performed within 24 to 72 h after birth and, depending on local health authorities, includes between 5 and 20 diseases.

In the case of genetic testing, the DNA of the newborn is analyzed in order to detect genetic alterations that may cause disease. One advantage of genetic testing is that it allows a greater number of diseases to be analyzed simultaneously. For example, the myNewborn neonatal genomic screening test detects around 390 diseases that occur early in life. On the other hand, analyzing genetic information improves performance compared to biochemical tests, as we are identifying the molecular cause behind the pathology.

Genetic testing for neonatal screening can be performed from either a blood or saliva sample, since DNA can be extracted from both. The article “DNA extracted from blood and other sources: how is it used in genetics?” explains very simply how this extraction is performed. 

Due to the advantages of neonatal genetic testing, multiple initiatives are emerging to introduce neonatal genetic screening as part of the healthcare system. For example, in the United Kingdom, the “Newborn Genomes Programme” project is being carried out to sequence the genomes of 100,000 newborns as a pilot test for implementation in the national health system.

It should be noted that biochemical and genetic screening are complementary and the performance of both tests allows a complete evaluation of the health of the newborn. Biochemical tests are essential because of the rapidity of the results, necessary in certain metabolic diseases, while genetic tests are necessary for the confirmation of these diseases and because they greatly broaden the spectrum of diseases evaluated, complementing the heel prick test which is very limited in this respect.

What kind of diseases are detected by neonatal genetic screening?

There are different genetic tests for newborn genetic screening, generally aimed at detecting the following types of diseases:

• Actionable diseases of early onset during infancy

These are diseases that present in the first months or years of life and that if detected early allow the implementation of interventions or treatments to improve the prognosis.

For example, if phenylketonuria is diagnosed early, a diet can be implemented to prevent the accumulation of phenylalanine and thus minimize the brain damage or developmental delay characteristic of the disease. Another example would be glucose-6-phosphate dehydrogenase deficiency, this enzyme deficiency can cause hemolytic anemia when taking certain foods such as beans or drugs such as non-steroidal anti-inflammatory drugs, so that, if the presence of this disease is known, the symptoms can be avoided by eliminating the foods and drugs that trigger it from the diet. 

Other early onset actionable diseases that are often included in neonatal genetic screening are congenital hypothyroidism, cystic fibrosis or biotinidase deficiency.

• Diseases of adult onset but actionable during childhood

These are diseases that, although manifesting in adulthood, may benefit from early intervention in childhood. The benefits may involve improved symptom management, delayed disease progression or improved overall prognosis.

One example is Wilson’s disease, a disorder characterized by the accumulation of copper in the liver, brain and other organs. Although it can manifest at any age, early diagnosis allows for early intervention that helps prevent disease progression and complications.

More examples of actionable diseases during childhood are Marfan syndrome or familial hypercholesterolemia.

• Common diseases without effective treatment

Other diseases that can also be addressed in neonatal genetic screening are recessively inherited genetic diseases that are common in certain ethnic groups, but for which there is no effective treatment a priori. In this case, if a disease is detected and confirmed, early management can be initiated, even if it is not treatable. In addition, parents can receive reproductive genetic counseling, which is key for future pregnancies.

In this direction, for example, the myNewborn neonatal genomic screening test is designed to detect those recessive genetic diseases whose carrier frequency is greater than 1/100, i.e. when more than one in 100 people carry mutations responsible for the disease.

Rare diseases

Rare diseases are those that affect a small number of people, however, there are more than 7,000 rare diseases, and together, they affect a significant part of the population. One of the main difficulties associated with rare diseases is the time to diagnosis, which can be extremely long and complex. According to the Spanish Federation of Rare Diseases (Feder), in 20% of cases it takes 10 or more years to achieve a proper diagnosis, which is why neonatal genetic screening plays a crucial role in providing the opportunity for early diagnosis and improving the quality of life of those affected by these rare diseases.

Clinical applications of newborn genetic screening

There are multiple examples of how neonatal genetic screening can be beneficial for the health of the newborn, and even for other family members. Among the applications of this type of approach are the following:

• Prevention of disease development, by identifying genetic variants at risk before symptoms manifest, measures can be taken to prevent the development of signs and symptoms of the disease.
• Early detection of genetic diseases and hereditary disorders. Possibility of early medical interventions and personalized treatments.
• Information for clinical decision making and patient management.
• Genetic counseling for affected parents and families.

Considerations in neonatal genetic screening

Finally, although neonatal genetic screening offers multiple benefits, it must also be taken into account that it is a screening, so it is generally focused on those diseases with high penetrance, early onset or those that can benefit from early treatment. In other words, this type of testing is not designed for specific cases where a genetic disease is suspected. 

When a newborn presents signs or symptoms of a disease, the medical approach will be different. In these cases it is necessary to perform a genetic study directed to the clinical findings of the patient with the aim of finding a diagnosis that allows to start the management and treatment of the newborn. For this reason, it is always recommended to seek the advice and attention of professionals specialized in genetic diagnosis and laboratories with extensive experience in this type of studies.

Veritas provides medical professionals with the necessary tools to offer a complete perinatal service that includes prenatal and neonatal screening tests (myPrenatal and myNewborn), key for the detection and management of genetic diseases that may appear in the early stages of life. Our goal is to contribute to healthcare for newborns and their families by providing valuable information for medical decision-making and appropriate genetic counseling.

Sources:

Newborn Genomes Programme. https://www.genomicsengland.co.uk/initiatives/newborns

Newborn genetic screening (testing). https://www.genome.gov/es/genetics-glossary/Evaluacion-del-recien-nacido-o-examen-neonatal