Primary Immunodeficiencies (PIDs) are still underdiagnosed, and there is a significant delay in diagnosis even in developed countries resulting in significant implications for morbidity and mortality. Early diagnosis is a key factor in enabling early therapeutic intervention before infections occur and may save the lives of some PAs, especially Severe Mixed – Sever Combined ImmunoDefficiencies (SCID). The establishment of newborn screening programs (NewBorn Screening-NBS) for the early detection and management of these PAs becomes imperative.

SCID is an absolute pediatric emergency. Without early diagnosis and treatment these infants may not survive, succumbing to severe infection, usually within the first year of life. Children born with SCID are partially protected from infection during the first weeks of life due to the presence of maternal antibodies, and those who are breastfed will continue to receive some antibodies through breast milk (although it can also lead to CMV infection ). Once maternal antibodies disappear from the body, infants become susceptible to serious, life-threatening infections.

Newborn screening is the only way to universally detect SCID before infection occurs (in cases without a positive family history of SCID). Systematic screening at birth for SCID allows for early detection and intervention with therapeutic Haematopoietic Stem Cell Transplantation (HSCT) or gene therapy when possible, as this is still an innovative and experimental treatment that is only possible in certain forms SCID and in some centers.

Infants diagnosed with SCID and treated before the age of 3.5 months without active infection at the time of treatment (HSCT and/or gene therapy) may have a chance of survival greater than 96%. A delay in the diagnosis of SCID reduces the success of a treatment option and compromises survival or the quality of immune reconstitution and quality of life due to subsequent complications. Screening for SCID soon after birth is feasible and can be performed on dried blood spot samples that are currently collected in a standardized manner from all newborns almost worldwide.

The SCID screening test is based on an assay that measures T-cell receptor excision circles (TRECs). Some may also include analyzes of kappa-deleting recombination excision circles (KRECs). These tests allow the identification of infants with severe forms of PA characterized by T- and/or B-cell lymphopenia, who will require appropriate management in immunological reference centers.

The cost-effectiveness of SCID case finding is likely to be economically balanced relative to the costs of medical care for this group of disorders as a whole. One of the most important and determining factors is the detection of SCID at birth, as it allows a child to receive treatment before complications occur that often require prolonged and expensive intensive care management that significantly increases healthcare costs. Rapid access to treatment also negates the societal burden, enormous degradation in quality of life, and incalculable societal cost associated with an undiagnosed SCID.

Currently, there are no published prospective studies providing evidence on the cost-effectiveness of neonatal screening for SCID, however favorable theoretical calculations have been made. Given that the benefits of a neonatal screening program should outweigh the harm, the lifesaving nature of an NBS program for children with SCID is arguably privileged.

The development of an effective, reasonably competitive and validated method for population-based SCID screening of newborns during recent years has changed the outlook of survival towards a normal life for patients with this severe Primary Immunodeficiency.

Despite the favorable evaluation of a newborn screening program for SCID, its implementation at the national level is pending in most countries that have a long tradition of NBS programs. However, the example of SCID will advance future research on preventive medicine for other severe primary immunodeficiencies, including, but not limited to, hereditary agammaglobulinemias and hemophagocytic syndromes.

In conclusion

Newborn Screening for SCID saves lives. Without early diagnosis and treatment, children born with SCID usually do not survive beyond their first year of life. It is well established that active infection and older age at the time of transplantation decrease the survival chances of affected children. With the possibility of treatment and cost-effective newborn screening tests, it is imperative to implement NBS newborn screening for Severe Mixed Immunodeficiencies – SCID in our country as well.