Newborn Screening Pilot Study Showed a High Incidence of Cystic Fibrosis in Republic of North Macedonia

Background: Cystic fibrosis (CF) is the most frequent, life limiting, genetic disease in Caucasians, caused by mutations in the CFTR gene. The incidence varies in different geographical areas and ethnic groups. The last two decades newborn screening (NBS) for CF has been implemented in the majority of countries where CF is common as a well-established public health strategy.

Objective: In May 2018, NBS for CF was introduced in R.N.Macedonia as a pilot study (in 13out of 30 maternities), included in National program for mothers and children’s care of the Ministry of Health.
Methods: Two steps IRT-IRT algorithm were performed, and then a sweat test for confirmation/exclusion of the CF diagnosis when IRT values were both over the cut off. In cases of positive or borderline sweat tests, mutation analysis of CFTR gene were performed (snapshot reaction for 11 most common regional CFTR mutations or extended gene analysis).

Results: During the period of 6 months 9332 newborns were screened for CF. For IRT1 the cut-off level of 70 ng/ml was established (99.5th percentile) and for IRT2 a fixed cut off was used at 40ng/ml. Out of 11 screening positive cases, diagnosis of CF was confirmed in 5 (sweat test results: 90. 102..101..106..102mmol/L). All diagnosed cases at the end of the first month of life, already had symptoms consistent with the diagnosis of CF. The patient`s genotypes were: F508del/F508del (3), F508del/G1349D and F508del/G542X. In the same period, two symptomatic cases were diagnosed (mean age of diagnosis 4.5 months), born in maternities where the pilot study was not conducted (genotypes: F508del/R1158X and F508del/CFTRdel2,3).

Conclusion: The pilot study showed a high incidence of CF in our region of 1:1860 live births. From 2019, NBS for CF will be implemented on the whole newborn population in the country, since early diagnosis of CF through NBS and the appropriate preventive and curative care management of affected children has a proven benefits with respect to clinical outcomes and health economics.