High-Dose Vitamin D in Pregnancy May Reduce Atopic Dermatitis Risk in Children of Smoking Mothers: Study

Atopic diseases such as atopic dermatitis, asthma, and allergic rhinitis are major public health concerns in pediatric populations and are increasing in prevalence worldwide. Vitamin D has been identified as a significant immunomodulatory nutrient and has the potential to affect immune tolerance and inflammatory responses.

The analysis was carried out based on the COPSAC2010 randomized clinical trial (NCT00856947), which is a double-blinded study designed for the evaluation of prenatal interventions for the prevention of childhood diseases. A total of 581 mother-child pairs were included in the study and were randomly assigned to receive either high-dose vitamin D supplementation at a dose of 2800 IU/d or standard-dose supplementation at a dose of 400 IU/d from week 24 of pregnancy.

To more accurately measure maternal tobacco exposure, maternal blood metabolomic analysis was carried out at the time of inclusion in the study. A supervised sparse partial least squares model was applied for the generation of a cotinine metabolome score based on biochemical markers for tobacco exposure. Cotinine is a well-established metabolite of nicotine and a reliable biomarker for tobacco exposure.

Key findings:

• In a post hoc analysis of the COPSAC2010 RCT, 581 mother-child pairs received vitamin D supplement at a dose of 2800 IU/day (high-dose) or 400 IU/day (standard-dose) from gestational week 24.

• Maternal tobacco exposure was measured by blood metabolome profiling and cotinine metabolome scoring.

• In the analysis, a significant interaction between tobacco exposure and vitamin D supplementation on atopic dermatitis risk was observed (Pinteraction <0.01).

• High-dose vitamin D supplements reduced atopic dermatitis risk among children of mothers in the highest quartile of cotinine metabolome scoring with a crude hazard ratio of 0.46 (95% CI 0.23-0.93; P = 0.03) and adjusted hazard ratio of 0.36 (95% CI 0.15-0.85; P = 0.02).

• In addition, a significant effect modification of vitamin D supplements on asthma risk up to 6 years of age was observed (Pinteraction = 0.03), whereas no significant modification of vitamin D supplements on allergic rhinitis at 6 years of age was observed (Pinteraction = 0.08).

Prenatal high-dose vitamin D supplementation has shown promise in the prevention of atopic dermatitis and has shown potential in the prevention of childhood asthma in the offspring of women with higher tobacco exposure. This has shown a significant interaction between the maternal tobacco metabolomic profiles and the effect of prenatal high-dose vitamin D supplementation. This has shown promise in the development of personalized prevention strategies for the prevention of atopic diseases in the offspring of women who are exposed to tobacco during pregnancy.

Reference:

Brustad, N., Wang, T., Chen, L., Kaiser, H., Gomes, B., Klein, A., Vahman, N., Skov, L., Stokholm, J., Schoos, A. M., Bønnelykke, K., & Chawes, B. (2026). 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, 94(1), 88–95. https://doi.org/10.1016/j.jaad.2025.08.044