Shadid ILC, Brustad N, Chawes BL, Moes DJAR, Weiss ST, Guchelaar HJ, Mirzakhani H. Biomed Pharmacother. 2025 Jan 27;183:117859. doi: 10.1016/j.biopha.2025.117859.
Highlights
• A PK model estimates prenatal 25(OH)D exposure after oral vitamin D supplementation.
• Higher prenatal 25(OH)D AUC links to reduced childhood asthma/wheezing at 3 and 6 years.
• Higher prenatal 25(OH)D relates to better lung function in children aged 6–8 years.
• AUC provides comprehensive measure of vitamin D status throughout pregnancy.
• AUC analysis reveals nuanced vitamin D-respiratory outcome relationships.
Abstract
Gestational 25-hydroxyvitamin D (25[OH]D) is important in fetal lung development and may influence offspring respiratory outcomes, making accurate exposure assessment essential to understand clinical associations. Therefore, we used the combined data from two large RCTs investigating prenatal vitamin D supplementation, which included early and late prenatal 25(OH)D measurements, to refine a population pharmacokinetic model of vitamin D-25(OH)D and estimate individual area under the curve (AUC) Z-scores. The primary outcome was physician-diagnosed offspring asthma/wheezing at ages 3 and 6 years, and lung function, as a secondary outcome, was evaluated by spirometry at the ages 6 and 8 years. In total, 1319 mother-child pairs were included. We found that clearance of 25(OH)D increased with gestational age and bodyweight, and decreased with higher baseline 25(OH)D levels. Prenatal 25(OH)D AUC Z-scores were negatively associated with asthma/wheezing at age 3 years (aOR = 0.75, 95 % CI = 0.64–0.88, p < 0.001) and 6 years (aOR = 0.83, 95 % CI = 0.72–0.95, p = 0.008). Longitudinal analysis of lung function from age 6–8 years showed that AUC Z-scores were positively associated with percent-predicted FEV1 (β = 1.21%, 95 % CI = 0.30–2.11; p = 0.009), FVC (β = 0.79 %, 95 % CI = 0.13–1.46; p = 0.021), FEV1/FVC ratio (β = 0.56 %, 95 % CI = 0.11–1.01; p = 0.015) and FEF25–75 % (β = 2.18 %, 95 % CI = 0.46–3.91; p = 0.009). These results together indicate an exposure-outcome relationship where higher gestational 25(OH)D exposure, estimated by AUC, is associated with reduced childhood asthma/recurrent wheeze and improved lung function.
