Public health newborn screening (NBS) programs continuously evolve, taking advantage of international shared learning. NBS for severe combined immunodeficiency (SCID) has recently been introduced in many countries. However, comparison of screening outcomes has been hampered by use of disparate terminology and imprecise or variable case definitions for non-SCID conditions with T-cell lymphopenia.
Standardized screening terminology could overcome a Babylonian confusion, while improved case definitions would promote international exchange of knowledge.
A systematic literature review highlighted the diverse terminology in SCID NBS programs internationally. While, as expected, individual screening strategies and tests were tailored to each program, we found uniform terminology to be lacking in definitions of disease targets, sensitivity and specificity required for comparisons across programs.
Our recommendations reflect current evidence from literature and existing guidelines coupled with opinion of experts in public health screening and immunology. Terminologies were aligned. The distinction between actionable and non-actionable T-cell lymphopenia among non-SCID cases was clarified, the former being infants with T-cell lymphopenia who could benefit from interventions such as protection from infections, antibiotic prophylaxis, and live-attenuated vaccine avoidance.
By bringing together the previously unconnected public health screening community and clinical immunology community, our SCID NBS deliberations bridged the gaps in language and perspective between these disciplines. We propose that international specialists in each disorder for which NBS is performed join forces to hone their definitions and recommend uniform registration of outcomes of NBS. Standardization of terminology will promote international exchange of knowledge and optimize each phase of NBS and follow-up care, advancing health outcomes for children worldwide.
Our recommendations reflect currently available evidence coupled with expert opinion for uniform registration of screening test outcomes and case definitions after diagnostic follow-up in newborn screening for severe combined immunodeficiency.