Effects of Immediate Telephone Follow-Up with Providers on Sweat Chloride Test Timing after Cystic Fibrosis Newborn Screening Identifies a Single Mutation

Abstract

Objectives To assess whether reporting “possible cystic fibrosis (CF)” newborn screening (NBS) results via fax plus simultaneous telephone contact with primary care providers (PCPs), versus fax alone, influenced three outcomes: getting a sweat chloride test, age at sweat chloride test, and sweat-testing before 8 weeks old. Study Design Retrospective cohort comparison of infants born in Wisconsin whose PCPs received telephone intervention (n=301), versus recent historical controls whose PCP did not (n=355). Intervention data were collected during a longitudinal research and quality improvement effort; de-identified comparison data were constructed from auxiliary NBS tracking information. Parametric and nonparametric statistical analyses tested for group differences. Results Most infants (92%) with “possible CF” NBS results whose PCPs lacked telephone intervention ultimately underwent sweat-testing, underlining efficacy for fax-only reporting. Telephone intervention was significantly associated with improvements in infants undergoing sweat-testing at both ≤6 and <8 weeks and a slight, but non-significant, 3.5-day reduction in infants’ age at sweat-testing. The effect of telephone intervention was greater for PCPs whose patients underwent sweat-testing at community-affiliated medical centers versus academic medical centers (p=0.008). Conclusion Reporting “possible CF” NBS results via fax plus simultaneous telephone follow-up with PCPs increases the number of infants who have sweat chloride tests before 8 weeks of age, when affected infants are more likely to receive full benefits of early diagnosis and treatment.

Improving newborn screening for cystic fibrosis using next-generation sequencing technology: a technical feasibility study

“…When two CF-causing mutations are detected, the confirmation of a CF diagnosis by sweat testing can be routinely achieved within two weeks. 9 …”

“…6 Moreover, ~90% of infants with one mutation have normal sweat test results and are therefore CF heterozygote carrier infants who are categorized as screening false positive. 7 These CF NBS false-positive results can cause parental anxiety, 8–10 add considerable expense to NBS, 11 and may delay the diagnosis of CF when one mutation is detected 9 or insufficient quantities of sweat are obtained. 6 Therefore, the challenges associated with false positives based on carrier detection in the common IRT/DNA protocol are significant and magnified by the disproportionately large number of carriers in the population with high IRT levels.…”

“…6 Therefore, the challenges associated with false positives based on carrier detection in the common IRT/DNA protocol are significant and magnified by the disproportionately large number of carriers in the population with high IRT levels. 9,10 Although restricting the number of CFTR mutations in CFTR panels can reduce carrier detection and potentially improve the positive predictive value (PPV), the NBS goals of equity and the highest possible sensitivity become more difficult to achieve. Finally, NBS via the IRT/DNA algorithm has identified a new and unexpected challenge:identifying infants who do not meet the criteria for a diagnosis of CF but are labeled as having CFTR -related metabolic syndrome (CRMS) in the United States since 2009.…”

Parental Preferences about Policy Options Regarding Disclosure of Incidental Genetic Findings in Newborn Screening: Using Videos and the Internet to Educate and Obtain Input

“…In fact, at least one country (Norway) by law does not reveal CFTR carrier status discovered through NBS [ 4 ]. In the USA, many IF results are returned to the primary care provider who may lack sufficient time, knowledge or counseling skill [ 19 , 20 ], and may not even know the family because of inaccurate or insufficient labeling of dried blood spot specimens [ 21 , 22 ]. Therefore, parents can become anxious or confused about the implications of the results, as has been noted after NBS and other community screening programs [ 23 , 24 ].…”

Newborn Screening Quality Assurance Program for CFTR Mutation Detection and Gene Sequencing to Identify Cystic Fibrosis

“…13 False CF-positive results, while unavoidable in newborn screening, cause parental anxiety, unnecessary clinical testing, and downstream genetic counseling. [14][15][16][17] Thus, there are ongoing efforts to redefine a positive newborn screening test such that it requires the identification of 2 CF-causing CFTR mutations 18 similar to what is being done in California. 13 Since there are >2000 mutations or variants in the CFTR gene with more still being discovered, 19,20 the requirement of identifying 2 CFcausing mutations would likely necessitate either gene sequencing or a greatly expanded genotyping panel of CFTR mutations.…”