High-dose vitamin D in pregnancy likely cuts childhood wheeze risk, but infant supplements fall short

New evidence suggests giving pregnant women higher doses of vitamin D may help protect their babies from wheezing, but benefits don’t extend to supplements given after birth.

Review: Vitamin D supplementation in pregnant or breastfeeding women or young children for preventing asthma. Image Credit: Tekkol / ShutterstockReview: Vitamin D supplementation in pregnant or breastfeeding women or young children for preventing asthma. Image Credit: Tekkol / Shutterstock

In a recent review published in the journal Cochrane Database of Systematic Reviews, researchers conducted a comprehensive review comprising several scientific repositories, 18 randomized controlled trials, and more than 10,000 cumulative participants to investigate relationships between vitamin D supplementation during pregnancy or infancy and childhood asthma.

Review findings revealed that high-dose vitamin D supplementation during pregnancy likely reduces the risk of childhood wheeze, a key precursor to asthma. However, the evidence for a direct effect on a formal asthma diagnosis remains uncertain, with moderate-certainty evidence suggesting no statistically significant difference.

Parents, caregivers, and public health officials are advised that, for supplementation in infants and young children, the current data as of October 2023 is of low to very low certainty and insufficient to draw firm conclusions.

One small trial also suggested a possible reduction in childhood asthma with any dose of vitamin D in pregnancy, but this was based on low-certainty evidence.

Background

Childhood asthma is a leading cause of chronic disease that may persist well into adulthood. It causes long-term and sometimes irreparable lung damage, resulting in recurrent episodes of wheezing, coughing, and breathlessness. Previous research suggests a complex interplay of genetic and early-life environmental factors drives its development.

Vitamin D is an essential nutrient with established roles in immune system development and has long been an intervention candidate in asthma prevention research. Vitamin D deficiencies have been linked to higher risks of allergic diseases, leading researchers to hypothesize that supplementing during the crucial developmental windows of pregnancy and infancy could help prevent asthma from taking hold, improving long-term physiological outcomes.

Previous systematic reviews have yielded inconclusive results, often limited by the number of available studies. A concrete understanding of the role of vitamin D supplementation in early lung development would help guide future recommendations for parents and public health practitioners on how to ensure the healthy development of the next generation.

About the review

The present Cochrane systematic review represents the gold standard in evidence-based medicine. It aims to address this knowledge gap by comprehensively synthesizing all available scientific information on the efficacy of vitamin D supplementation during pregnancy, breastfeeding, or early childhood for the primary prevention of asthma.

Review data collection comprised an exhaustive search of multiple (n = 7) medical databases, including CENTRAL, MEDLINE, and Embase, up to October 2023, for relevant systematic reviews or meta-analyses on the topic of interest. Original study authors were contacted for additional details/study data when required.

Studies compared various vitamin D supplementation strategies:

  • Any dose of vitamin D versus a placebo or no treatment in pregnant or breastfeeding women,
  • Any dose of vitamin D versus a placebo or no treatment in infants or young children,
  • A high dose of vitamin D versus a low/standard dose (≤ 400 IU/day) in pregnant or breastfeeding women, and
  • A high dose of vitamin D versus a low/standard dose in infants or young children.

The review’s primary outcomes of interest were the incidence of childhood asthma and wheeze (a whistling sound during breathing strongly associated with the later development of asthma). The certainty of each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.

Study findings

Title, abstract, and full-text screening identified 18 studies, totalling 10,611 individuals for inclusion in the systematic review, 16 of which were also included in the meta-analysis.

The review’s main findings were multifaceted and nuanced, but they revealed promising results for high-dose supplementation during pregnancy. Supplementation during pregnancy analyses found that high-dose vitamin D (commonly 2800 to 4400 IU/day) supplementation reduced the risk of childhood wheeze by 21% (Risk Ratio [RR] 0.79, 95% Confidence Interval [CI] 0.64 to 0.98) compared to the standard prenatal dose (400 IU/day). While vitamin D’s effect on a formal asthma diagnosis trended in the same protective direction, moderate-certainty evidence indicated the results were not statistically significant (RR 0.81, 95% CI 0.63 to 1.04).

In contrast, evidence for supplementing infants or young children with vitamin D was far less clear. When comparing any dose of vitamin D to a placebo, the analysis of three studies (588 participants) showed no statistically significant effect on the risk of developing asthma (RR 0.69, 95% CI 0.47 to 1.03), with the evidence rated as very low certainty.

Similarly, comparing high-dose to low-dose vitamin D in infants suggested a potential reduction in wheeze, but the evidence was very uncertain. However, a pooled analysis of six studies (2,385 participants) did suggest that high-dose vitamin D in early childhood may slightly reduce the risk of airway infections (RR 0.94, 95% CI 0.90 to 0.98), though the evidence was of low certainty.

Conclusions

The current Cochrane review demonstrates that high-dose vitamin D supplementation during pregnancy likely helps prevent childhood wheeze. While the effect on a definitive asthma diagnosis is not yet statistically proven, the consistent trend is promising and warrants further investigation.

Unfortunately, the current evidence is too uncertain for supplementation given directly to infants to support a clear benefit for asthma or wheeze prevention.

Journal reference:
  • Patchen, B. K., Best, C. M., Boiteau, J., Solvik, B. S., Vonderschmidt, A., Xu, J., Cohen, R. T., & Cassano, P. A. (2025). Vitamin D supplementation in pregnant or breastfeeding women or young children for preventing asthma. Cochrane Database of Systematic Reviews. DOI – 10.1002/14651858.CD013396.pub2. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013396.pub2/full
Hugo Francisco de Souza

Written by

Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.

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