Cystic Fibrosis in the Age of Population Carrier Screening

מירי דותן ^1,2 Hannah Blau ^1,2 Patrick Stafler ^1,2 Malena Cohen-Symbercnoh ³ Ori Efrati ⁴ Lea Bentur ^5,7 Michal Gur ^5,7 Galit Livnat ^6,7 Micha Aviram ⁸ Inbal Golan Tripto ⁸ Dario Prais ^1,2 Amihood Singer ⁹ Reut Matar ¹⁰ Hanna Segev ¹⁴ Shani Hagit ¹¹ Mira Malcov ¹² Gheona Altarescu ¹³ Meir Mei-Zahav ^1,2

¹Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children’s Medical Center of Israel, ישראל
²Sackler Faculty of Medicine, Tel Aviv University, ישראל
³Cystic Fibrosis Center, Hadassah Medical Center, ישראל
⁴Safra Children’s Hospital, Sheba Medical Center, ישראל
⁵Pediatric Pulmonary Institute and CF Center, Rappaport Children’s Hospital, Rambam Health Care Campus, ישראל
⁶Pediatric pulmonology, Carmel Medical Center, ישראל
⁷Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, ישראל
⁸Soroka Medical Center, Division of Pediatrics, ישראל
⁹Public Health Services, Ministry of Health, ישראל
¹⁰Raphael Recanati Genetic Institute, Rabin Medical Center, ישראל
¹¹Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat-Gan, ישראל
¹²Wolfe PGD-Stem Cell Laboratory, Racine IVF Unit, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Centerl, ישראל
¹³Medical Genetics Institute, Shaare Zedek Medical Center, ישראל
¹⁴Medical Genetics Institute, Rambam Health Care Campus, ישראל

Background: Cystic fibrosis (CF) is the most common life-limiting genetic disorder among Caucasians. Population carrier screening (PCS) commenced in Israel in 1999 and has been universally subsidized since 2008. Previous work showed that PCS markedly reduced CF birth rates with a shift towards milder mutations. As the nationwide PCS program has been available for more than a decade, it is vital to re-evaluate its impact on CF diagnosis and severity.

Methods: This is a multicenter study that examined data between 2008-2018. Demographic and clinical characteristics of CF patients were collected from the six Israeli CF centers. De-identified data from the PCS program were collected from the Israeli Ministry of Health.

Results: CF rate per 100,000 live births has decreased from 8.29 in 2008 to 0.54 in 2018. During this time, PGD rates rose, and the pregnancy termination rate did not change significantly. Of the 104 children born with CF between 2008-2018, only 52 had two mutations that were found on the national PCS panel, 34% of the patients were pancreatic sufficient. Different populations utilized PCS at different rates, and there was an over-representation of the Arab and the Orthodox Jewish populations in the CF cohort.

Conclusions: There has been a further decrease in CF rate since the nationwide PCS program became subsidized in 2008. The current PCS panel could not have identified half of the CF patients born in the past decade. We need to evaluate the need for a broader mutation panel and perhaps implement newborn screening for CF.