Sweat conductivity for diagnosing cystic fibrosis after positive newborn screening: prospective, diagnostic test accuracy study

Abstract

Objective: To assess the accuracy of sweat conductivity among newborns and very young infants.

Design: Prospective, population-based, diagnostic test accuracy study.

Setting: Public Statewide Newborn Screening Programme where the incidence rate of cystic fibrosis (CF) is ≈1:11 000.

Patients: Newborns and very young infants with positive two-tiered immunoreactive trypsinogen.

Interventions: Sweat conductivity and sweat chloride were performed simultaneously, on the same day and facility by independent technicians, with the cut-off values of 80 mmol/L and 60 mmol/L, respectively.

Main outcome measures: Sensitivity, specificity, positive and negative predictive values (PPV and NPV), overall accuracy, positive and negative likelihood ratios (+LR, -LR) and post (sweat conductivity (SC)) test probability were calculated to assess SC performance.

Results: 1193 participants were included, 68 with and 1108 without CF, and 17 with intermediate values. The mean (SD) age was 48 (19.2) days, ranging from 15 to 90 days. SC yielded sensitivity of 98.5% (95% CI 95.7 to 100), specificity of 99.9% (95% CI 99.7 to 100), PPV of 98.5% (95% CI 95.7 to 100) and NPV of 99.9% (95% CI 99.7 to 100), overall accuracy of 99.8% (95% CI 99.6 to 100), +LR of 1091.7 (95% CI 153.8 to 7744.9) and -LR of 0.01 (95% CI 0.00 to 0.10). After a positive and negative sweat conductivity result, the patient's probability of CF increases around 350 times and drops to virtually zero, respectively.

Conclusion: Sweat conductivity had excellent accuracy in ruling in or ruling out CF after positive two-tiered immunoreactive trypsinogen among newborns and very young infants.

Keywords: child health services; cystic fibrosis.