LAUSR

Routine newborn screening for cystic fibrosis (CF) uses serum immunoreactive trypsin (IRT). If this is raised, newborns are sent for a sweat test and analysis for gene mutations. If IRT is raised, but sweat test is normal, and no CF genes are detected, the parents are told the child does not have CF. Researchers contacted the general practitioners of babies with a negative sweat test performed in one of four London CF centres to determine outcome. Of 511 newborns with raised serum IRT, 95 (19%) had a normal sweat test. Five (5%) had CF diagnosed genetically. Eleven (12%) were deemed inconclusive, of whom one was eventually diagnosed genetically with CF. Seventy-nine (83%) children were deemed ‘false-positive’ cases. The researchers found follow-up data on 51 of 79 (65%), of whom 32 (63%) had been healthy and 19 (37%) had multiple other significant non-CF pathologies, none suggestive of CF, including congenital heart disease (4), problems related to prematurity (3), global developmental delay (3) and malignancy (1). While the results are reassuring in that false-positives did not present with CF symptoms, the findings are limited by having lost 35% to follow-up. The high rate of non-CF morbidity may relate to other causes of high IRT at birth and suggests that sweat testnegative newborns should be followed up. Children who develop CF symptoms should have extended genome sequencing for rarer CF genes.