Cystic fibrosis carrier screening effects on birth prevalence and newborn screening

Abstract

Original research article INTRODUCTIONCystic fibrosis (CF), the most frequent life-shortening autosomal recessive disease in countries with a predominantly Caucasian population, is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. 1Because of the disease's severe clinical manifestations, the heavy burden of daily care, and the shortened life expectancy, carrier testing is routinely offered to relatives of CF patients. The CF carrier test may also be offered to individuals of reproductive age with no family history of CF. This carrier screening strategy has been recommended by the American College of Medical Genetics and Genomics 2 and by the American College of Obstetricians and Gynecologists, 3 whereas the European CF Society leaves the decision regarding its establishment up to individual countries. 4 Although no structured communitywide carrier screening has been implemented by any health jurisdiction, in the United States millions of carrier tests have been performed. 5 The CF carrier test is also offered to the general population in Israel 6 and in parts of Australia 7 and Italy. 8CF carrier screening has been found to be connected with a decrease in the annual birth prevalence of the disease in the United Kingdom, the United States, and Italy. 8-10Early diagnosis and management has been associated with better lung function and nutrition, as well as with reduced burden and cost of care. [11][12][13] To detect infants with CF soon after birth, newborn screening (NBS) has been implemented in most of Europe, North America, and Oceania, 14,15 and it is considered standard care.16,17 NBS-positive neonates undergo sweat chloride measurements to distinguish affected infants and healthy infants with false-positive results. In a subset of these infants, CF can be neither confirmed nor excluded. Several definitions have been suggested for this condition. In the United States it has been called "CFTR-related metabolic syndrome, " 18 and in Europe it is sometimes called "equivocal CF diagnosis" or "CF screening-positive inconclusive diagnosis. ". 19 In this article these situations are referred to as "uncertain CF. "The detection of false-positive results and of uncertain CF in infants is generally considered a secondary effect of the NBS system, and NBS programs are designed to minimize their number.15 It may be argued that the decrease in birth prevalence of CF associated with CF carrier screening 8 impairs the outcome of NBS by altering the proportions of CF, uncertain CF, and false-positive cases. 20This study was aimed at determining whether a negative correlation between carrier screening and birth prevalence of CF previously shown in northeastern Italy 8 is confirmed over a longer period, as well as whether it affects NBS practice. Purpose: We evaluated the effects of cystic fibrosis (CF) carrier screening on birth prevalence trends and newborn screening (NBS) efficiency by comparing two Italian regions; carrier screening was performed in one region (eastern region (ER)) and not in t...

The Role of Extended CFTR Gene Sequencing in Newborn Screening for Cystic Fibrosis

“…Preconception CF carrier screening has already been implemented in the US, Israël, and Northeast Italy [70]. Such a health public policy aims to detect most at-risk couples and this ineluctably impacts on the timing for a CF diagnosis and on the prevalence of CF births [71], which would then raise the question of the relevance of NBS. Reproductive attitudes would also inevitably change, as recently underlined [72].…”

International perspectives on the implementation of reproductive carrier screening

“…In the initial 20 years of CF carrier screening, the live‐birth prevalence decreased dramatically . However, since 2011, the number of carrier screening tests for CF has substantially decreased, likely a reflection of changes to local regulations for the test offer and reimbursement.…”

“…In the initial 20 years of CF carrier screening, the live-birth prevalence decreased dramatically. 35,36 However, since 2011, the number of carrier screening tests for CF has substantially decreased, likely a reflection of changes to local regulations for the test offer and reimbursement. There has been a concomitant increase in CF incidence, 37 confirming the inverse correlation between RCS and number of children born with CF.…”

Highlighting the impact of cascade carrier testing in cystic fibrosis families

“…Such programs are undertaken in some regions around the world, as in Australia, in the Veneto region in Italy or in the US [9][10][11].…”