The new face of cystic fibrosis in the era of population genetic carrier screening.

Antenatal screening Cystic fibrosis Population carrier screening Pre-implantation genetic diagnosis

Journal

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966

Informations de publication

Date de publication:
16 Nov 2023
Historique:
received: 03 08 2023
revised: 02 11 2023
accepted: 06 11 2023
medline: 19 11 2023
pubmed: 19 11 2023
entrez: 18 11 2023
Statut: aheadofprint

Résumé

Population genetic carrier screening (PGCS) for cystic fibrosis (CF) has been offered to couples in Israel since 1999 and was included in a fully subsidized national program in 2008. We evaluated the impact of PGCS on CF incidence, genetic and clinical features. This was a retrospective national study. Demographic and clinical characteristics of children with CF born in Israel between 2008 and 2018 were obtained from the national CF registry and from patients' medical records. Data on CF births, preimplantation genetic testing (PGT), pregnancy termination and de-identified data from the PGCS program were collected. CF births per 100,000 live births decreased from 8.29 in 2008 to 0.54 in 2018 (IRR = 0.84, p < 0.001). The CF pregnancy termination rate did not change (IRR = 1, p=  0.9) while the CF-related PGT rate increased markedly (IRR = 1.33, p < 0.001). One hundred and two children were born with CF between 2008 and 2018 with a median age at diagnosis of 4.8 months, range 0-111 months. Unlike the generally high uptake nationally, 65/102 had not performed PGCS. Even if all had utilized PGCS, only 51 would have been detected by the existing genetic screening panel. Clinically, 34 % of children were pancreatic sufficient compared to 23 % before 2008 (p = 0.04). Since institution of a nationwide PGCS program, the birth of children with CF decreased markedly. Residual function variants and pancreatic sufficiency were more common. A broader genetic screening panel and increased PGCS utilization may further decrease the birth of children with CF.

Sections du résumé

BACKGROUND BACKGROUND
Population genetic carrier screening (PGCS) for cystic fibrosis (CF) has been offered to couples in Israel since 1999 and was included in a fully subsidized national program in 2008. We evaluated the impact of PGCS on CF incidence, genetic and clinical features.
METHODS METHODS
This was a retrospective national study. Demographic and clinical characteristics of children with CF born in Israel between 2008 and 2018 were obtained from the national CF registry and from patients' medical records. Data on CF births, preimplantation genetic testing (PGT), pregnancy termination and de-identified data from the PGCS program were collected.
RESULTS RESULTS
CF births per 100,000 live births decreased from 8.29 in 2008 to 0.54 in 2018 (IRR = 0.84, p < 0.001). The CF pregnancy termination rate did not change (IRR = 1, p=  0.9) while the CF-related PGT rate increased markedly (IRR = 1.33, p < 0.001). One hundred and two children were born with CF between 2008 and 2018 with a median age at diagnosis of 4.8 months, range 0-111 months. Unlike the generally high uptake nationally, 65/102 had not performed PGCS. Even if all had utilized PGCS, only 51 would have been detected by the existing genetic screening panel. Clinically, 34 % of children were pancreatic sufficient compared to 23 % before 2008 (p = 0.04).
CONCLUSIONS CONCLUSIONS
Since institution of a nationwide PGCS program, the birth of children with CF decreased markedly. Residual function variants and pancreatic sufficiency were more common. A broader genetic screening panel and increased PGCS utilization may further decrease the birth of children with CF.

Identifiants

DOI: 10.1016/j.jcf.2023.11.003 PMID: 37980178
pubmed: 37980178
pii: S1569-1993(23)01674-0
doi: 10.1016/j.jcf.2023.11.003
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose.

Auteurs

Miri Dotan (M)

Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Hannah Blau (H)

Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Amihood Singer (A)

Public Health Services, Ministry of Health, Jerusalem, Israel.

Patrick Stafler (P)

Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Dario Prais (D)

Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Malena Cohen-Cymberknoh (M)

Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel.

Joel Reiter (J)

Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel.

Ori Efrati (O)

Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

Adi Dagan (A)

Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel.

Lea Bentur (L)

Pediatric Pulmonary Institute and CF Center, Rambam Health Care Campus, Rappaport Children's Hospital, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Michal Gur (M)

Pediatric Pulmonary Institute and CF Center, Rambam Health Care Campus, Rappaport Children's Hospital, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Galit Livnat (G)

Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Pediatric Pulmonology Unit and CF center, Carmel Medical Center, Haifa, Israel.

Karin Yaacoby-Bianu (K)

Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Pediatric Pulmonology Unit and CF center, Carmel Medical Center, Haifa, Israel.

Micha Aviram (M)

Soroka University Medical Center, Pediatric Pulmonary Unit, Ben Gurion University, Beer Sheva, Israel.

Inbal Golan Tripto (I)

Soroka University Medical Center, Pediatric Pulmonary Unit, Ben Gurion University, Beer Sheva, Israel.

Ophir Bar-On (O)

Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Reut Matar (R)

Raphael Recanati Genetic Institute, Rabin Medical Center, Petach Tikva, Israel.

Shani Hagit (S)

Danek Gertner Institute of Human Genetics, Sheba Medical Center, Ramat-Gan, Israel.

Mira Malcov (M)

Wolfe PGD-Stem Cell Laboratory, Racine IVF Unit, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.

Gheona Altarescu (G)

Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel.

Hanna Segev (H)

Medical Genetics Institute, Rambam Health Care Campus, Haifa, Israel.

Baruch Feldman (B)

PGD Program and Laboratory, Assuta Medical Center, Tel Aviv, Israel.

Eitan Kerem (E)

Pediatric Pulmonary Unit and Cystic fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel.

Meir Mei-Zahav (M)

Kathy and Lee Graub Cystic Fibrosis Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: meir_zahav@clalit.org.il.

Classifications MeSH