Immunoreactive trypsinogen levels in newborn screened infants with an inconclusive diagnosis of cystic fibrosis.

Steven Kent, Tanja Gonska, Felix Ratjen, Peter R Durie, Janna Brusky, Peter Zuberbuhler, Melinda Solomon, Daniel Hughes, Dimas Mateos-Corral, April Price, Chee Y Ooi, Richard van Wylick, Mark A Chilvers, Candice Bjornson, Joe Reisman, Margaret Boland, Katherine Keenan, Carlo Castellani, Rosie Sutherland

Journal: BMC pediatrics 2020;19(1):369

PMID: 31640630

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Abstract

BACKGROUND

Newborn screening (NBS) for cystic fibrosis (CF) not only identifies infants with a diagnosis of CF, but also those with an uncertain diagnosis of cystic fibrosis (CF), i.e. CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID). These infants have an uncertain long-term outcome and it is currently unclear around time of diagnosis, which infants are at higher risk of later fulfilling a CF diagnosis. In this study, we hypothesised that immunoreactive trypsinogen (IRT) levels, used in NBS as a marker of pancreatic disease and function, may reflect the degree of CFTR dysfunction in each individual and therefore would help to identify those with CRMS/CSPID who are later at risk for meeting the criteria of CF.

METHODS

In this longitudinal, prospective study, infants with CRMS/CFSPID and CF were recruited and followed in 9 CF clinics (Canada and Italy). We compared NBS IRT levels between CF and CRMS/CFSPID, and between children with CRMS/CFSPID→CF and CRMS/CFSPID→CRMS/CFSPID during the period of June 2007 to April 2016.

RESULTS

Ninety eight CRMS/CFSPID and 120 CF subjects were enrolled. During the study period, 14 (14.3%) CRMS/CFSPID subjects fulfilled the diagnostic criteria for CF (CRMS/CFSPID→CF), while the diagnosis remained uncertain (CRMS/CFSPID→ CRMS/CFSPID) in 84 (85.7%) subjects. Significantly higher NBS IRT concentrations (ng/ml) were present in CF than CRMS/CFPSID (median (interquartile range): 143.8 (99.8-206.2) vs. 75.0 (61.0-105.9); P < 0.0001). Infants with CRMS/CFSPID→CF (n = 14) had significantly higher NBS IRT concentrations (ng/ml) than CRMS/CFSPID→ CRMS/CFSPID (n = 83) (median (interquartile range): 108.9 (72.3-126.8) vs. 73.7(60.0-96.0); P = 0.02).

CONCLUSIONS

Amongst infants who tested positive on NBS for CF, there is a gradation of elevated NBS IRT concentrations. Infants with CF have higher NBS IRT levels than CRMS/CFPSID, and higher NBS IRT concentrations were present in infants with CRMS/CFSPID→CF than CRMS/CFSPID→ CRMS/CFSPID. NBS IRT concentrations, in concert with other factors, may have the potential to predict the likelihood of CF amongst infants with CRMS/CFSPID.

Address: Discipline of Paediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia. [email protected].; miCF Research Centre and Department of Gastroenterology, Sydney Children's Hospital Randwick, High Street, Randwick NSW, Sydney, Australia. [email protected].; Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada. [email protected].; Discipline of Paediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.; Cystic Fibrosis Centre, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy.; Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Canada.; Department of Paediatrics, Division of Respirology, Children's Hospital of Eastern Ontario, Ottawa, Canada.; Department of Pediatrics, Section of Respiratory Medicine, University of Calgary, Alberta Children's Hospital, Calgary, Alberta, Canada.; Department of Pediatrics, Division of Pediatric Respiratory Medicine, BC Childrens Hospital, Vancouver, BC, Canada.; Department of Pediatrics, School of Medicine, Queen's University, Kingston, Ontario, Canada.; Victoria General Hospital, Victoria, BC, Canada.; Children's Hospital Of Western Ontario, London, Ontario, Canada.; IWK Health Centre, Halifax, Nova Scotia, Canada.; Department of Paediatrics, Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Canada.; Stollery Children's Hospital, Edmonton, Alberta, Canada.; Royal University Hospital, Saskatoon, Saskatchewan, Canada.; Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.

DOI: 10.1186/s12887-019-1756-4

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MeSH Terms: Cystic Fibrosis, Humans, Infant, Newborn, Longitudinal Studies, Neonatal Screening, Prospective Studies, Trypsinogen