Vitamin D supplementation during pregnancy and the risk of wheezing in offspring: a systematic review and dose-response meta-analysis

J Asthma. 2019 Dec;56(12):1266-1273. doi: 10.1080/02770903.2018.1536142. Epub 2018 Nov 5.


Background: In the past few years, growing evidence supports a preventive role of vitamin D supplementation during pregnancy for wheezing or asthma in offspring. However, the optimal dose of vitamin D intake is unclear. We conducted a meta-analysis to examine the linear and nonlinear dose-response pattern of vitamin D intake during pregnancy and asthma or wheezing in offspring. Questions/purposes: The purpose of this study was to answer the following question: Which dose of vitamin D is more effective in preventing wheezing in offspring? Method: We identified relevant studies by searching PubMed, EMBASE and CENTRAL up to December 2017 and by hand-searching reference lists. Meta-analysis and subgroup analysis were performed. Fixed or random effects model linear trends analyses were conducted based on the heterogeneity test. Then, if the data did not show linear trends, we considered a nonlinear trend analysis instead. Results: A total of 6068 participants were included in the study. Our analysis showed an inverse relationship between the intake of vitamin D during pregnancy and the occurrence of wheezing in offspring (pooled OR = 0.68, 95% CI = 0.55-0.83, I2 = 24%, Z statistic = 3.64, p < 0.01). We found a nonlinear U-shaped association between vitamin D supplementation during pregnancy and asthma or wheezing in offspring, with the lowest risk at approximately 800 IU/d. Publication bias was shown in a funnel plot without Egger's test. Conclusions: Vitamin D intake during pregnancy is inversely related to wheezing or asthma in offspring. Furthermore, the trend analysis indicates that offspring may benefit from approximately 800 IU/d vitamin D intake during pregnancy.

Keywords: Asthma; dose-response meta-analysis; pregnancy; vitamin D; wheezing.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Asthma / epidemiology
  • Asthma / prevention & control*
  • Child, Preschool
  • Cohort Studies
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Evidence-Based Medicine
  • Female
  • Humans
  • Infant
  • Linear Models
  • Pregnancy
  • Prenatal Care / methods
  • Primary Prevention / methods
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Reference Values
  • Respiratory Sounds / drug effects*
  • Vitamin D / administration & dosage*


  • Vitamin D