Neonatal vitamin D status and asthma risk after age 5 years: A Danish population-based cohort study

BACKGROUND: Vitamin D may play a role in early lung development, yet epidemiologic evidence on its association with later asthma risk is mixed. We aimed to investigate the associations of neonatal 25-hydroxyvitamin D (25(OH)D) and vitamin D-binding protein (DBP) and their corresponding genetic predictors with asthma risk.

METHODS: We conducted a population-based cohort study of a random sample of individuals born in Denmark during 1991-2005 from the iPSYCH2012 study. Neonatal concentrations of 25(OH)D and DBP were measured via dried blood spots, and asthma cases were identified through diagnoses or asthma prescriptions after age 5 years. Cox regression was used to estimate hazard ratios (HRs) for asthma in relation to 25(OH)D, DBP, and polygenic scores (PGSs) for these traits and asthma to assess genetic liability to vitamin D status and asthma.

RESULTS: Of 14,005 individuals, 2308 (16.5%) developed asthma over a maximum follow-up of 25 years. We found no association between neonatal 25(OH)D (HR = 1.04, 95% CI: 0.99-1.09 per SD increase) or DBP (HR = 1.01, 95% CI: 0.97-1.05) and asthma risk. Analyses using tertiles to assess potential non-linear associations yielded similar null results. A higher asthma PGS was associated with increased asthma risk (HR = 1.42, 95% CI: 1.36-1.47 per SD increase), whereas PGSs for 25(OH)D (HR = 1.00, 95% CI: 0.96-1.05) and DBP (HR = 0.99, 95% CI: 0.95-1.04) were not.

CONCLUSIONS: Our study suggests that neonatal vitamin D status is not associated with asthma risk. Similarly, genetic liability related to vitamin D status, as reflected in PGSs for 25(OH)D and DBP, is not associated with an increased risk of asthma.