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

TY - JOUR

T1 - Vitamin D prenatal programming of childhood metabolomics profiles at age 3 y

AU - Blighe, Kevin

AU - Chawes, Bo L

AU - Kelly, Rachel S

AU - Mirzakhani, Hooman

AU - McGeachie, Michael

AU - Litonjua, Augusto A

AU - Weiss, Scott T

AU - Lasky-Su, Jessica A

N1 - © 2017 American Society for Nutrition.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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 6 SD; 27.5 6 11.0 ng/mL), 2) high concentrations of amines, moderate concentrations of fatty acids, and normal maternal postsupplement vitamin D (34.0 6 14.1 ng/mL), and 3) low concentrations of fatty acids, amines, and normal maternal postsupplement vitamin D (35.2 6 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 clinicaltrials.gov as NCT00920621.

AB - 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 6 SD; 27.5 6 11.0 ng/mL), 2) high concentrations of amines, moderate concentrations of fatty acids, and normal maternal postsupplement vitamin D (34.0 6 14.1 ng/mL), and 3) low concentrations of fatty acids, amines, and normal maternal postsupplement vitamin D (35.2 6 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 clinicaltrials.gov as NCT00920621.

KW - Adult

KW - Amines/blood

KW - Asthma

KW - Child Health

KW - Child, Preschool

KW - Dietary Supplements

KW - Disease Susceptibility

KW - Fatty Acids/blood

KW - Female

KW - Humans

KW - Inflammation/blood

KW - Inflammation Mediators/blood

KW - Male

KW - Metabolic Networks and Pathways

KW - Metabolome/drug effects

KW - Metabolomics

KW - Pregnancy

KW - Pregnancy Complications/blood

KW - Prenatal Exposure Delayed Effects

KW - Vitamin D/blood

KW - Vitamin D Deficiency/blood

KW - Vitamins/blood

KW - Young Adult

U2 - 10.3945/ajcn.117.158220

DO - 10.3945/ajcn.117.158220

M3 - Journal article

C2 - 28835366

SN - 0002-9165

VL - 106

SP - 1092

EP - 1099

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 4

ER -