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Is confirmatory genetic testing of all CF screen positives justified?
Abstracts
for an interview. We report cross-sectional analyses for Time-1, and longitudinal analyses for carrier testing uptake by Time-2. Results: We received completed surveys from 134 of 245 mothers (55%) at Time-1 and 96 of 214 (45%) at Time-2, and interviewed 66 mothers. 77 of 127 mothers (61%) reported one mutation in their infants (i.e., carrier-mothers); 30 (24%) reported no mutations and 20 (16%) were unsure (presumed non-carriers). Carrier testing uptake was 55% (n = 23/42) among carrier-mothers. 13 intended to have carrier testing at time-1 and of those 6 were tested by time-2. 91% of carrier-mothers told relatives they may be carriers (n = 70/77), as did 48% (n = 24/50) of non-carrier mothers. Results were expected to influence family planning for 35% of carrier-mothers (n = 26/74) and 24% of non-carrier mothers (n = 11/46). Interviewees valued carrier information whether or not they intended to share it with relevant relatives. Conclusion: While mothers describe reproductive value in carrier results, survey data are equivocal given moderate intended and actual CT uptake and limited influence on family planning. doi:10.1016/j.clinbiochem.2014.07.031
Is confirmatory genetic testing of all CF screen positives justified? Nita Chauhan, Erin Fleischer, Stephanie Ho, April K. Price Dept. of Paediatrics, Western University, London Health Sciences Centre, London, ON, Canada Objective: In April 2008, Newborn Screening Ontario (NSO) added cystic fibrosis (CF) to their screening panel. A two-tiered protocol is used, which includes immunoreactive trypsinogen (IRT) and genetic testing with a panel of 39 + 3 polymorphisms. The sweat chloride test is considered the gold standard to diagnose CF, and therefore is conducted on all screen positive infants. On these individuals, NSO recommends confirmatory genetic testing, which in our centre includes a larger panel of mutations (70 + 4 polymorphisms). Our objective is to elucidate the financial impact of conducting this extended panel for all positive screens. Methods: A retrospective descriptive analysis of our internal database identified individuals who were referred from NSO with a single mutation, and were found to have a second mutation with our extended panel. The cost to our centre to run each extended panel is $300. Results: 387 individuals were screen positive, of whom 22 (5.6%) had two mutations, 311 (80.1%) had one mutation, and 54 (13.9%) had no mutations. Our centre has expended $116,400 to identify 29 individuals with a second mutation. 19 of these infants had a negative sweat test, and 6 had a borderline sweat test. Conclusion: Confirmatory testing has cost our centre an average of $20,000 per annum. A total of 29 individuals were identified with a second mutation through our extended panel, of whom 19 had normal sweats. Further follow-up and research should be conducted to determine if identifying these individuals justifies the cost of confirmatory testing.
135
a
Institute of Health Policy Management Evaluation, University of Toronto, Ontario, Canada b Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada c Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada d Division of Paediatric Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada e Department of Pediatrics, Faculty of Medicine, University of Toronto, Ontario, Canada f Department of Family & Community Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada g Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada h Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada i Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada j Division of Health Care and Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada k Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada l Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada m Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada n The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada Objectives: Diagnostic uncertainty related to cystic fibrosis (CF) has long been challenging to understand and manage. Newborn screening (NBS) for CF extends these challenges to the early days of life. We explored the parental experience of diagnostic uncertainty arising from NBS. Methods: Drawing from a mixed methods of prospective cohort study of screen positive and screen negative control infants, we report on qualitative interviews with parents of children who received inconclusive results for CF after NBS and follow-up testing. Through the tertiary care center that manages the majority of screen positive care in Ontario, we recruited parents of children identified since the inception of CF NBS in Ontario (2008). We used qualitative description to analyze transcript data. Results: We conducted 19 interviews with 14 parents of infants with uncertain diagnoses, ranging from 3 months to 4 years in age. Five parents completed interviews at two time-points, separated by one year. We learned that parents gain support through research involvement, but struggle to understand the meaning of an uncertain diagnosis in the face of an apparently healthy newborn, worry about their infant's healthrelated vulnerability, and fear labeling and over-medicalization from continued medical surveillance. Time appears to mitigate concerns. Conclusion: The experience of diagnostic uncertainty is deeply challenging for some families, particularly in the early newborn period. These results should inform decisions by NBS programs and clinical teams about protocols for testing, clinical follow-up, and support for families of those who screen positive, but warrant triangulation with survey data and longitudinal follow-up.
doi:10.1016/j.clinbiochem.2014.07.032 doi:10.1016/j.clinbiochem.2014.07.033 Making sense of diagnostic uncertainty after newborn screening for cystic fibrosis Carolyn J. Barg a, Fiona A. Miller a, Robin Z. Hayeems a, b, Yvonne Bombard a, c, Peter Durie d, e, June C. Carroll f, Pranesh Chakraborty g, h, Beth K. Potter i, Jessica P. Bytautas j, Karen Tam k, Louise Taylor l, Elizabeth Kerr m, Christine Davies g, Jennifer Milburn g, Katherine Keenan d, Felix Ratjen d, e, l, Astrid Guttmann a, d, e, n
We are the 1%: Newborn screening for cystic fibrosis and true positive cases from category C screening Karen Tam a, Louise Taylor b, Tanja Gonska c, Melinda Solomon b, Felix Ratjen b a The Hospital for Sick Children, Division of Clinical and Metabolic Genetics, Toronto, Ontario, Canada
for an interview. We report cross-sectional analyses for Time-1, and longitudinal analyses for carrier testing uptake by Time-2. Results: We received completed surveys from 134 of 245 mothers (55%) at Time-1 and 96 of 214 (45%) at Time-2, and interviewed 66 mothers. 77 of 127 mothers (61%) reported one mutation in their infants (i.e., carrier-mothers); 30 (24%) reported no mutations and 20 (16%) were unsure (presumed non-carriers). Carrier testing uptake was 55% (n = 23/42) among carrier-mothers. 13 intended to have carrier testing at time-1 and of those 6 were tested by time-2. 91% of carrier-mothers told relatives they may be carriers (n = 70/77), as did 48% (n = 24/50) of non-carrier mothers. Results were expected to influence family planning for 35% of carrier-mothers (n = 26/74) and 24% of non-carrier mothers (n = 11/46). Interviewees valued carrier information whether or not they intended to share it with relevant relatives. Conclusion: While mothers describe reproductive value in carrier results, survey data are equivocal given moderate intended and actual CT uptake and limited influence on family planning. doi:10.1016/j.clinbiochem.2014.07.031
Is confirmatory genetic testing of all CF screen positives justified? Nita Chauhan, Erin Fleischer, Stephanie Ho, April K. Price Dept. of Paediatrics, Western University, London Health Sciences Centre, London, ON, Canada Objective: In April 2008, Newborn Screening Ontario (NSO) added cystic fibrosis (CF) to their screening panel. A two-tiered protocol is used, which includes immunoreactive trypsinogen (IRT) and genetic testing with a panel of 39 + 3 polymorphisms. The sweat chloride test is considered the gold standard to diagnose CF, and therefore is conducted on all screen positive infants. On these individuals, NSO recommends confirmatory genetic testing, which in our centre includes a larger panel of mutations (70 + 4 polymorphisms). Our objective is to elucidate the financial impact of conducting this extended panel for all positive screens. Methods: A retrospective descriptive analysis of our internal database identified individuals who were referred from NSO with a single mutation, and were found to have a second mutation with our extended panel. The cost to our centre to run each extended panel is $300. Results: 387 individuals were screen positive, of whom 22 (5.6%) had two mutations, 311 (80.1%) had one mutation, and 54 (13.9%) had no mutations. Our centre has expended $116,400 to identify 29 individuals with a second mutation. 19 of these infants had a negative sweat test, and 6 had a borderline sweat test. Conclusion: Confirmatory testing has cost our centre an average of $20,000 per annum. A total of 29 individuals were identified with a second mutation through our extended panel, of whom 19 had normal sweats. Further follow-up and research should be conducted to determine if identifying these individuals justifies the cost of confirmatory testing.
135
a
Institute of Health Policy Management Evaluation, University of Toronto, Ontario, Canada b Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada c Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada d Division of Paediatric Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada e Department of Pediatrics, Faculty of Medicine, University of Toronto, Ontario, Canada f Department of Family & Community Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada g Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada h Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada i Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada j Division of Health Care and Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada k Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada l Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada m Department of Psychology, The Hospital for Sick Children, Toronto, Ontario, Canada n The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada Objectives: Diagnostic uncertainty related to cystic fibrosis (CF) has long been challenging to understand and manage. Newborn screening (NBS) for CF extends these challenges to the early days of life. We explored the parental experience of diagnostic uncertainty arising from NBS. Methods: Drawing from a mixed methods of prospective cohort study of screen positive and screen negative control infants, we report on qualitative interviews with parents of children who received inconclusive results for CF after NBS and follow-up testing. Through the tertiary care center that manages the majority of screen positive care in Ontario, we recruited parents of children identified since the inception of CF NBS in Ontario (2008). We used qualitative description to analyze transcript data. Results: We conducted 19 interviews with 14 parents of infants with uncertain diagnoses, ranging from 3 months to 4 years in age. Five parents completed interviews at two time-points, separated by one year. We learned that parents gain support through research involvement, but struggle to understand the meaning of an uncertain diagnosis in the face of an apparently healthy newborn, worry about their infant's healthrelated vulnerability, and fear labeling and over-medicalization from continued medical surveillance. Time appears to mitigate concerns. Conclusion: The experience of diagnostic uncertainty is deeply challenging for some families, particularly in the early newborn period. These results should inform decisions by NBS programs and clinical teams about protocols for testing, clinical follow-up, and support for families of those who screen positive, but warrant triangulation with survey data and longitudinal follow-up.
doi:10.1016/j.clinbiochem.2014.07.032 doi:10.1016/j.clinbiochem.2014.07.033 Making sense of diagnostic uncertainty after newborn screening for cystic fibrosis Carolyn J. Barg a, Fiona A. Miller a, Robin Z. Hayeems a, b, Yvonne Bombard a, c, Peter Durie d, e, June C. Carroll f, Pranesh Chakraborty g, h, Beth K. Potter i, Jessica P. Bytautas j, Karen Tam k, Louise Taylor l, Elizabeth Kerr m, Christine Davies g, Jennifer Milburn g, Katherine Keenan d, Felix Ratjen d, e, l, Astrid Guttmann a, d, e, n
We are the 1%: Newborn screening for cystic fibrosis and true positive cases from category C screening Karen Tam a, Louise Taylor b, Tanja Gonska c, Melinda Solomon b, Felix Ratjen b a The Hospital for Sick Children, Division of Clinical and Metabolic Genetics, Toronto, Ontario, Canada