Long-term effects of birth order and age at diagnosis in cystic fibrosis: a sibling cohort study

Abstract

Background: Siblings with cystic fibrosis (CF) share many genetic and environmental factors but may present different phenotypes. Younger sibs are mostly earlier diagnosed with CF than their older sibs, but might be at risk for an earlier colonization with Pseudomonas aeruginosa (PA) than their older counterparts due to cross-infection within families.

Aims: To analyze the effects of birth order and age at diagnosis on lung function, PA colonization, nutritional status, and survival during the first two decades of life in siblings with CF.

Methods: A retrospective cohort study of 52 sibling pairs was performed in two Dutch CF centers. Data were analyzed both cross-sectionally and longitudinally using Kaplan-Meier curves and modified log-rank tests.

Results: Median age at diagnosis was significantly higher in the older sib compared with the younger sib (3.0 and 0.2 years, respectively, P < 0.0001). At the age of 5, 10, and 15 years no difference in lung function was found. However, at the age of 20 years, forced expiratory volume in 1 sec (FEV(1)) in older sibs was 19.4% (95% CI: 5.9-32.9%, P = 0.007) lower than in younger sibs. In the younger sibs group, FEV(1) at age 20 years was significantly better in those who had a diagnosis before the age of 6 months (difference 22.9%, 95% CI: 0.1-45.8%, P < 0.05). In the first 10 years of life the younger sibs tended to be earlier colonized with PA than their older counterparts. No differences in nutritional status and survival were observed.

Conclusion: In this sibling cohort study, an early diagnosis of CF was associated with better lung function after two decades of life. Although younger siblings tended to be colonized with PA at an earlier age, they showed better lung function outcomes. This underscores the importance of early diagnosis with newborn screening and early referral to a specialized center in the prevention of long-term deleterious effects on lung function.