Objective: To determine the pancreatic phenotype of infants with cystic fibrosis (CF) diagnosed in the first week of life by a combined immunoreactive trypsin/mutation screening program.
Design: A prospective evaluation of pancreatic function in CF infants at the time of neonatal diagnosis and up to the first 12 years of life.
Setting: Two different centres, Verona (VCFC), Italy and Westmead (CHW), Australia to enable comparison of results between a region where <60% of CF patients have ¡Ý a single DF508 mutation and another with ¡Ý90% having ¡Ý one DF508 mutation.
Patients: A total of 315 CF children, 149 at VCFC and 166 at CHW.
Interventions: Fat balance studies over 3-5 days and pancreatic stimulation tests with main outcome measures being faecal fat or pancreatic colipase secretion.
Results: At VCFC 34 (23%) and at CHW 46 (28%) were pancreatic sufficient with normal absorption at diagnosis within the first month of life. Of those with two Class I, II or III ¡°severe¡± mutations 15% and with Class IV or V mutations 26/28 (93%) were PS at this early age. Of the total 80 with PS 18 have developed PI up to 5 years of age. All 18 had two ¡°severe¡± mutations.
Conclusion: Neonatal mutational screening programs for CF are less likely to detect PS patients with non-DF508 mutations. Of those PS patients who are detected, those with two severe Class I, II or III mutations are particularly at high risk of becoming PI during early childhood.
- cystic fibrosis
- genetic analysis
- neonatal screening
- pancreatic phenotype