Comparison of two sweat test systems for the diagnosis of cystic fibrosis in newborns

Abstract

Objectives In the national newborn screening programme for CF in Switzerland, we compared the performance of two sweat test methods, by investigating the feasibility and diagnostic performance of the Macroduct® collection method (with chloride mesurement) and Nanoduct® test (measuring conductivity) for diagnosing CF. Study‐Design We included all newborns with a positive screening result between 2011 and 2015 who were referred to a CF‐centre for sweat testing. In the CF‐centre, a Macroduct and Nanoduct sweat test were performed simultaneously. If sweat test results were positive or borderline, a DNA analysis was performed. Final diagnosis was based on genetic mutations. Results Over 5 years, 445 children were screened positive and in 413 (114 with CF) at least one sweat test was performed (median age at first test, 22 days); both tests were performed in 371 children. A sweat test result was more often available with the Nanoduct compared to the Macroduct (79 vs 60%, P < 0.001). The Nanoduct was equally sensitive as the Macroduct in identifying newborns with CF (sensitivity 98 vs 99%) but less specific (specificity 79 vs 93%; P‐value comparing ROC curves = 0.033). Conclusions This national multicentre study revealed high failure rates for Macroduct and Nanoduct in newborns in real life practice. While this needs to be addressed, our results suggested that performing the Nanoduct in addition to the Macroduct might speed up the diagnostic process because it more often yields valid results with comparable diagnostic performance. The addition of the Nanoduct sweat test can therefore help to reduce the stressful time of uncertainty for parents and to start appropriate treatment earlier.

Processing Newborn Bloodspot Screening Results for CF

“…A sufficient amount of sweat is needed to determine the chloride concentration; the smaller the children are or the lighter they are, the more difficult it is to obtain sufficient sweat. A sweat test should not be performed in children <2 kg, and the rates of sweat collections with insufficient volume (called Quantity Not Sufficient, QNS) are below 10% if the child weighs ≥4 kg [15,16]. Collecting sweat from two sites (left and right arm), as is recommended in the US, can reduce the QNS rate.…”

“…Nanoduct™ is a newer sweat conductivity analysis system that was specially developed for newborns as it requires only 3–5 μL of sweat and measures conductivity in situ [ 28 ]. A few studies have assessed and confirmed its ability to discriminate between those affected by CF and healthy children [ 16 , 29 , 30 , 31 , 32 , 33 ]. According to current guidelines, conductivity measurement is an accepted method to rule out CF, but for a definite diagnosis, the determination of sweat chloride is required as it is better validated [ 9 , 14 , 24 ].…”

Sweat Testing and Recent Advances

“…It was developed especially for use with newborns, and only 3 μL of sweat is required. As soon as sweat enters the microconductivity cell, the ST result is shown on the display ( 35 ).…”

The Changing Face of Cystic Fibrosis and Its Implications for Screening

“…In 1959, Gibson and Cooke published a method for sweat induction by pilocarpine iontophoresis on a small body surface area [ 6 ], and it remains the diagnostic gold standard for CF even today. Measuring conductivity by Nanoduct ® can facilitate the diagnosis of screening-positive newborns, but is less specific than the sweat chloride measurement [ 7 ] and not recommended as a diagnostic measurement [ 8 ].…”