Neonatal screening in the diagnosis of cystic fibrosis

There is a new French collaborative study about the neonatal diagnosis of cystic fibrosis. Cystic fibrosis (CF) is the most frequent life-limiting autosomal recessive disorder in the white. It is caused by mutations in 2 alleles of the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, which acts mainly as a cyclic AMP (cAMP)-activated chloride channel. The product of this gene helps to create sweat, digestive juices, and mucus.

Newborn screening programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT is elevated by testing for a panel of CF-causing mutations. But the following factors make this method problematic:

  • Some children may have persistent hypertrypsinogenemia
  • only one or no identified CFTR gene mutation
  • and sweat chloride concentrations close to normal values.

There is an other solution:

Measurements of transepithelial nasal potential differences (NPD) in adults accurately characterize CFTR-related ion transport. The aim of the present study is to establish reference values for NPD measurements for healthy children and those with CF aged 3 months to 3 years, the age range of most difficult-to-diagnose patients with suspected CF. The ultimate goal of our study is to validate NPD testing as a diagnostic tool for children with borderline results in neonatal screening.

So in this new screening protocoll, they have adapted the standard NPD protocol for young children, designed a special catheter for them, used a slower perfusion rate, and shortened the protocol to include only measurement of basal PD, transepithelial sodium (Na+) transport in response to the Na+ channel inhibitor amiloride, and CFTR-mediated chloride (Cl) secretion in response to isoproterenol, a β-agonist in a Clfree solution.

Pediatric catheter device.
Source:The CF-CIRC study

Why can it be useful?

This study will provide the basis for interpreting findings from a new and rapid diagnostic tool in patients with suspected CF after neonatal screening. This should help clinicians to alleviate parental distress and provide earlier therapeutic interventions and genetic counselling.


  1. The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening
  2. Wikipedia article
  3. Corey M, McLaughlin FJ, Williams M, Levison H. A comparison of survival, growth, and pulmonary function in patients with cystic fibrosis in Boston and Toronto. J Clin Epidemiol. 1988;41:583–591. doi: 10.1016/0895-4356(88)90063-7. [PubMed]
  4. Doughty IM, Ward I, Schwarz M, David TJ. Delayed diagnosis of cystic fibrosis due to normal sweat electrolytes. J R Soc Med. 1995;88:417P–418P. [PubMed]