Newborn Screening for CF across the Globe—Where Is It Worthwhile?

Abstract

Newborn screening (NBS) for cystic fibrosis (CF) has been performed in many countries for as long as four decades and has transformed the routine method for diagnosing this genetic disease and improved the quality and quantity of life for people with this potentially fatal disorder. Each region has typically undertaken CF NBS after analysis of the advantages, costs, and challenges, particularly regarding the relationship of benefits to risks. The very fact that all regions that began screening for CF have continued their programs implies that public health and clinical leaders consider early diagnosis through screening to be worthwhile. Currently, many regions where CF NBS has not yet been introduced are considering options and in some situations negotiating with healthcare authorities as policy and economic factors are being debated. To consider the assigned question (where is it worthwhile?), we have completed a worldwide analysis of data and factors that should be considered when CF NBS is being contemplated. This article describes the lessons learned from the journey toward universal screening wherever CF is prevalent and an analytical framework for application in those undecided regions. In fact, the lessons learned provide insights about what is necessary to make CF NBS worthwhile.

The Impact of the CFTR Gene Discovery on Cystic Fibrosis Diagnosis, Counseling, and Preventive Therapy

“…Consequently, the Wisconsin RCT incorporated IRT/DNA as the screening test in 1991, and the project was expanded to a comprehensive epidemiologic study of childhood CF [23]. By 1991, IRT/DNA was also successfully implemented for routine screening in South Australia by Ranieri et al [24] and soon thereafter in other regions [1], such as Brittany, where the molecular genetics expertise of Claude Férec's laboratory was readily applied to two-tier CF NBS [25]. In retrospect, the discovery that about 90% of Europeans and Europe-derived CF populations have at least one p.Phe508del variant greatly facilitated widespread implementation of the world's first DNA-based population screening test-the IRT/DNA(p.Phe508del) method.…”

“…Every physician's first duty is to diagnose-accurately and promptly-because diagnosis is the first step of treatment. In the case of cystic fibrosis (CF), accurate and prompt diagnosis was impossible before the newborn screening (NBS) era for the majority of patients [1]. In fact, children with CF typically experienced a diagnostic odyssey [2] and suffered irreversible malnutrition [3] and/or lung disease [4] before they had their diagnoses established through sweat chloride tests.…”

“…Others, perhaps 5%-10% and certainly at least 1% [5], died undiagnosed; those unfortunate patients would have had fatal hyponatremic/hypochloremic dehydration, protein-energy malnutrition, or catastrophic lung disease [3,4]. It is likely that these tragic fatalities continue in some regions of the world where CF NBS has not yet been implemented [1]. The advantages of early diagnosis are not only intuitive but were identified in clinical research as early as 1970, when Shwachman et al [6] reported a classic study showing that survival was much better when diagnosis occurred before three months of age.…”

“…Consequently, it became clear that more research was needed on all aspects of CF NBS and that the IRT method of screening needed to be improved. In fact, a decade after the report from New Zealand, there was still worldwide debate among health policy decision-makers whether or not CF NBS was worthwhile [1] and even doubt among organizations like the US Cystic Fibrosis Foundation (CFF)-expressed emphatically when it sponsored a negative but influential commentary [11]. Consequently, CF NBS implementation was slow in North America and Europe, and one country (France) even discontinued their national IRT-based program [1].…”

“…In fact, a decade after the report from New Zealand, there was still worldwide debate among health policy decision-makers whether or not CF NBS was worthwhile [1] and even doubt among organizations like the US Cystic Fibrosis Foundation (CFF)-expressed emphatically when it sponsored a negative but influential commentary [11]. Consequently, CF NBS implementation was slow in North America and Europe, and one country (France) even discontinued their national IRT-based program [1]. Suddenly, however, the situation changed dramatically, when the CFTR discovery was reported in September 1989 [14].…”