Vitamin D prenatal programming of childhood metabolomics profiles at age 3 y

Am J Clin Nutr. 2017 Oct;106(4):1092-1099. doi: 10.3945/ajcn.117.158220. Epub 2017 Aug 23.


Background: Vitamin D deficiency is implicated in a range of common complex diseases that may be prevented by gestational vitamin D repletion. Understanding the metabolic mechanisms related to in utero vitamin D exposure may therefore shed light on complex disease susceptibility.Objective: The goal was to analyze the programming role of in utero vitamin D exposure on children's metabolomics profiles.Design: First, unsupervised clustering was done with plasma metabolomics profiles from a case-control subset of 245 children aged 3 y with and without asthma from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), in which pregnant women were randomly assigned to vitamin D supplementation or placebo. Thereafter, we analyzed the influence of maternal pre- and postsupplement vitamin D concentrations on cluster membership. Finally, we used the metabolites driving the clustering of children to identify the dominant metabolic pathways that were influential in each cluster.Results: We identified 3 clusters of children characterized by 1) high concentrations of fatty acids and amines and low maternal postsupplement vitamin D (mean ± SD; 27.5 ± 11.0 ng/mL), 2) high concentrations of amines, moderate concentrations of fatty acids, and normal maternal postsupplement vitamin D (34.0 ± 14.1 ng/mL), and 3) low concentrations of fatty acids, amines, and normal maternal postsupplement vitamin D (35.2 ± 15.9 ng/mL). Adjusting for sample storage time, maternal age and education, and both child asthma and vitamin D concentration at age 3 y did not modify the association between maternal postsupplement vitamin D and cluster membership (P = 0.0014). Maternal presupplement vitamin D did not influence cluster membership, whereas the combination of pre- and postsupplement concentrations did (P = 0.03).Conclusions: Young children can be clustered into distinct biologically meaningful groups by their metabolomics profiles. The clusters differed in concentrations of inflammatory mediators, and cluster membership was influenced by in utero vitamin D exposure, suggesting a prenatal programming role of vitamin D on the child's metabolome. This trial was registered at as NCT00920621.

Keywords: airway inflammation; metabolomics; polyunsaturated fatty acids; prenatal programming; vitamin D.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amines / blood
  • Asthma
  • Child Health*
  • Child, Preschool
  • Dietary Supplements*
  • Disease Susceptibility
  • Fatty Acids / blood
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation Mediators / blood
  • Male
  • Metabolic Networks and Pathways
  • Metabolome / drug effects*
  • Metabolomics
  • Pregnancy
  • Pregnancy Complications* / blood
  • Pregnancy Complications* / drug therapy
  • Prenatal Exposure Delayed Effects*
  • Vitamin D / blood
  • Vitamin D / pharmacology*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / drug therapy
  • Vitamin D Deficiency / metabolism*
  • Vitamins / blood
  • Vitamins / pharmacology
  • Young Adult


  • Amines
  • Fatty Acids
  • Inflammation Mediators
  • Vitamins
  • Vitamin D

Associated data