Effect of prenatal high-dose vitamin D on childhood atopic dermatitis is modified by maternal cotinine metabolome: A secondary analysis of a randomized clinical trial
Journal of the American Academy of Dermatology https://doi.org/10.1016/j.jaad.2025.08.044
Background
Tobacco exposure has been shown to modulate the effect of vitamin D on the risk of atopic diseases. However, randomized clinical trials investigating potential effect modification between tobacco exposure and vitamin D supplementation on atopic disease risk are lacking.
Objective
We sought to investigate the potential effect modification from maternal tobacco exposure on the effect of prenatal high-dose vitamin D supplementation on risk of child atopic dermatitis (AD), asthma and allergic rhinitis (AR).
Methods
A post hoc analysis in the double-blinded COPSAC2010 randomized clinical trial (RCT) (NCT00856947) including 581 mother-child pairs randomized to 2800 IU/day (high-dose) vs 400 IU/d (standard-dose) from pregnancy week 24. Maternal blood metabolomic profiling was performed at inclusion reflecting maternal tobacco exposure using a supervised sparse partial least square model.
Results
We found a significant effect modification from the maternal cotinine metabolome score (pinteraction<0.01) where high-dose vitamin D reduced AD until age 6 years in offspring from mothers with highest (4th quartile) cotinine metabolome score:
- crude; HR=0.46 (0.23-0.93), p=0.03, and
- adjusted for sex, birth season, socioeconomic circumstances, living environment, air pollution,
maternal diet, vitamin D levels and fish oil intervention; HR=0.36 (0.15-0.85), p=0.02.
Similarly, significant effect modification was demonstrated on risk of asthma (pinteraction=0.03) until age 6 years but not AR (pinteraction=0.08) at age 6 years.
Conclusions
This exploratory study of prespecified RCT outcomes demonstrates effect modifications of the maternal tobacco exposure metabolome on the primary preventive effect of prenatal high-dose vitamin D on offspring atopic disease risk suggesting a potential personalized prevention strategy targeting mothers exposed to tobacco smoking.
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