Effectiveness of neonatal screening for cystic fibrosis in the Russian Federation

Abstract

Mass neonatal screening (NS) for cystic fibrosis (CF) has been performed in the Russian Federation since 2006–2007. It includes measurement of serum immunoreactive trypsinogen (IRT) in the first week of life and repeated testing on day 21–28 in case of positive first test. The sweat test is used to confirm the diagnosis. Objective. To evaluate the effectiveness of neonatal screening for cystic fibrosis in the Russian Federation. Materials and methods. We collected information on key parameters of NS for cystic fibrosis for 2019 from regional specialists in medical genetics. Results. We collected information form 50 regions of the Russian Federation, where a total of 1,009,832 newborns had been examined. The number of newborns with elevated IRT was 9,138 (0.9%); 1388 (0.1%) newborns tested positive at reexamination. CF was diagnosed in 104 newborns. Two pathogenic variants in the CFTR gene were detected in 78 infants with CF (75%); one pathogenic variant, in 20 infants (19%); no pathogenic variants, in 3 infants (2.9%). The NS protocol was not completed in 395 patients (4.3%). False negative screening results were observed in 8 newborns (7.1%), including two with meconium ileus. The sensitivity of screening was approximately 93%. One hundred and four infants tested positive at reexamination had no final diagnosis. The mean age at examination by a CF specialist was 41 (±21) days. More than two-thirds of newborns (73%) were diagnosed in outpatient departments, while the remaining patients (27%) were diagnosed in hospitals. We obtained mean cut-off values for IRT. Conclusion. Dynamic analysis of NS performance is a promising approach for its optimization. Key words: cystic fibrosis, neonatal screening, immunoreactive trypsinogen, sweat test, false positive result