Population-Based Newborn Screening for Genetic Disorders When Multiple Mutation DNA Testing Is Incorporated: A Cystic Fibrosis Newborn Screening Model Demonstrating Increased Sensitivity but More Carrier Detections

Comeau, Anne Marie; Parad, Richard B.; Dorkin, Henry L.; Dovey, Mark; Gerstle, Robert; Haver, Kenan; Lapey, Allen; O’Sullivan, Brian; Waltz, David A.; Zwerdling, Robert G.; Eaton, Roger B.

doi:10.1542/peds.113.6.1573

Cited by 141 publications

(123 citation statements)

References 14 publications

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“…Because cases of meconium ileus are identified in the absence of screening, removing these infants from the calculation produces a detection rate of 95%. Reports from other programs typically range from 92% to 98% (Table 7) [25][26][27][28][29] ; however, these rates are likely overestimated due to shorter follow-up periods and/or less rigorous identification of missed cases than the present study.…”

Section: Resultsmentioning

confidence: 64%

Newborn Screening for Cystic Fibrosis in California

et al. 2015

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, on behalf of the California Cystic Fibrosis Newborn Screening Consortium abstract OBJECTIVES: This article describes the methods used and the program performance results for the first 5 years of newborn screening for cystic fibrosis (CF) in California.METHODS: From July 16, 2007, to June 30, 2012, a total of 2 573 293 newborns were screened for CF by using a 3-step model: (1) measuring immunoreactive trypsinogen in all dried blood spot specimens; (2) testing 28 to 40 selected cystic fibrosis transmembrane conductance regulator (CFTR) mutations in specimens with immunoreactive trypsinogen values $62 ng/mL (top 1.6%); and (3) performing DNA sequencing on specimens found to have only 1 mutation in step 2. Infants with $2 mutations/variants were referred to CF care centers for diagnostic evaluation and follow-up. Infants with 1 mutation were considered carriers and their parents offered telephone genetic counseling.RESULTS: Overall, 345 CF cases, 533 CFTR-related metabolic syndrome cases, and 1617 carriers were detected; 28 cases of CF were missed. Of the 345 CF cases, 20 (5.8%) infants were initially assessed as having CFTR-related metabolic syndrome, and their CF diagnosis occurred after age 6 months (median follow-up: 4.5 years). Program sensitivity was 92%, and the positive predictive value was 34%. CF prevalence was 1 in 6899 births. A total of 303 CFTR mutations were identified, including 78 novel variants. The median age at referral to a CF care center was 34 days (18 and 37 days for step 2 and 3 screening test-positive infants, respectively). CONCLUSIONS:The 3-step model had high detection and low false-positive levels in this diverse population. WHAT'S KNOWN ON THIS SUBJECT:Several newborn screening models for cystic fibrosis (CF) exist, including DNA-based models that use mutation panels. There is limited experience with models (such as used in California) that include comprehensive DNA sequence testing methods as part of newborn screening.WHAT THIS STUDY ADDS: California' s 3-step newborn screening model for CF showed high efficiency, sensitivity, and positive predictive value. More than 300 mutations were found, reflecting the state' s diverse population. Some CF transmembrane conductance regulator-related metabolic syndrome cases converted to CF over time.

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Section: Resultsmentioning

confidence: 64%

Newborn Screening for Cystic Fibrosis in California

et al. 2015

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“…Newborn screening (NBS) for CF has been largely implemented in Australia and in many countries in Europe and, more recently, in most of the states in the U.S. (Comeau et al 2004). Improvement in outcome for CF patients diagnosed by newborn screening (as opposed to diagnosis based on symptoms) is not as clearly beneficial as for other conditions, such as phenylketonuria.…”

Section: Newborn Screening For Cfmentioning

confidence: 99%

Assessing the Disease-Liability of Mutations in CFTR

Férec

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2012

Cold Spring Harbor Perspectives in Medicine

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“…Proper education of the primary care community is helpful in accomplishing the objectives of the CF NBS program and diminishing misunderstanding about the abilities and limits of the screen. Although state-of-the-art screening will identify 96% to 99% of CF-affected infants, [36][37][38] false-negative results could cause a significantly delayed diagnosis because of complacency of the PCP, who may ignore clinical signs of the disease. 25 Regardless of CF NBS results, diagnostic evaluation including sweat testing should be performed on any infant who evokes clinical concern, including all infants with meconium ileus (MI), and any infant whose parents are both carriers.…”

Section: Prescreen Educationmentioning

confidence: 99%

Guidelines for Implementation of Cystic Fibrosis Newborn Screening Programs: Cystic Fibrosis Foundation Workshop Report

et al. 2007

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Newborn screening for cystic fibrosis offers the opportunity for early intervention and improved outcomes. This summary, resulting from a workshop sponsored by the Cystic Fibrosis Foundation to facilitate implementation of widespread high quality cystic fibrosis newborn screening, outlines the steps necessary for success based on the experience of existing programs. Planning should begin with a workgroup composed of those who will be responsible for the success of the local program, typically including the state newborn screening program director and cystic fibrosis care center directors. The workgroup must develop a screening algorithm based on program resources and goals including mechanisms available for sample collection, regional demographics, the spectrum of cystic fibrosis disease to be detected, and acceptable failure rates of the screen. The workgroup must also ensure that all necessary guidelines and resources for screening, diagnosis, and care be in place prior to cystic fibrosis newborn screening implementation. These include educational materials for parents and primary care providers; systems for screening and for providing diagnostic testing and counseling for screen-positive infants and their families; and protocols for care of this unique population. This summary explores the benefits and risks of various screening algorithms, including complex situations that can occur involving unclear diagnostic results, and provides guidelines and sample materials for state newborn screening programs to develop and implement high quality screening for cystic fibrosis.

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Population-Based Newborn Screening for Genetic Disorders When Multiple Mutation DNA Testing Is Incorporated: A Cystic Fibrosis Newborn Screening Model Demonstrating Increased Sensitivity but More Carrier Detections

Abstract: Use of multiple-CFTR-mutation testing improved sensitivity and postscreening prediction of CF at the cost of increased referrals and carrier identification.

Cited by 141 publications

References 14 publications

Newborn Screening for Cystic Fibrosis in California

Newborn Screening for Cystic Fibrosis in California

Assessing the Disease-Liability of Mutations in CFTR

Guidelines for Implementation of Cystic Fibrosis Newborn Screening Programs: Cystic Fibrosis Foundation Workshop Report

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