The Relationship Between Vitamin D Intake and Serum 25-hydroxyvitamin D in Young Children: A Meta-Regression to Inform WHO/FAO Vitamin D Intake Recommendations

Background: This work was commissioned by the World Health Organization and Food and Agriculture Organization to inform their update on the vitamin D requirements for children aged <4 y. Objectives: The objective of this work was to undertake multilevel and multivariable dose-response modeling of serum 25-hydroxyvitamin D (25OHD) to total vitamin D intake in children aged <4 y with the goal of deriving updated vitamin D requirements for young children. Methods: Systematically identified randomized controlled trials among healthy children from 2 wk up to 3.9 y of age provided with daily vitamin D supplements or vitamin D-fortified foods were included. Linear and nonlinear random effects multilevel meta-regression models with and without covariates were fitted and compared. Interindividual variability was included by simulating the individual serum 25OHD responses. The percentage of individuals reaching set minimal and maximal serum 25OHD thresholds was calculated and used to derive vitamin D requirements. Results: A total of 31 trials with 186 data points from North America, Europe, Asia, and Australasia/Oceania, with latitudes ranging from 61 degrees N to 38 degrees S, and with participants of likely mostly light or medium skin pigmentation, were included. In 29 studies the children received vitamin D supplements and in 2 studies the children received vitamin D-fortified milk with or without supplements. The dose-response relationship between vitamin D intake and serum 25OHD was best fitted with the unadjusted quadratic model. Adding additional covariates, such as age, did not significantly improve the model. At a vitamin D intake of 10 mu g/d, 97.3% of the individuals were predicted to achieve a minimal serum 25OHD threshold of 28 nmol/L. At a vitamin D intake of 35 mu g/d, 1.4% of the individuals predicted to reach a maximal serum 25OHD threshold of 200 nmol/L. Conclusions: In conclusion, this paper details the methodological steps taken to derive vitamin D requirements in children aged <4 y, including the addition of an interindividual variability component.