Vitamin D Status Affects Serum Metabolomic Profiles in Pregnant Adolescents

Abstract

Vitamin D is linked to a number of adverse pregnancy outcomes through largely unknown mechanisms. This study was conducted to examine the role of vitamin D status in metabolomic profiles in a group of 30 pregnant, African American adolescents (17.1 ± 1.1 years) at midgestation (26.8 ± 2.8 weeks), in 15 adolescents with 25-hydroxy vitamin D (25(OH)D) ≥20 ng/mL, and in 15 teens with 25(OH)D <20 ng/mL. Serum metabolomic profiles were examined using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. A novel hierarchical mixture model was used to evaluate differences in metabolite profiles between low and high groups. A total of 326 compounds were identified and included in subsequent statistical analyses. Eleven metabolites had significantly different means between the 2 vitamin D groups, after correcting for multiple hypothesis testing: pyridoxate, bilirubin, xylose, and cholate were higher, and leukotrienes, 1,2-propanediol, azelate, undecanedioate, sebacate, inflammation associated complement component 3 peptide (HWESASXX), and piperine were lower in serum from adolescents with 25(OH)D ≥20 ng/mL. Lower maternal vitamin D status at midgestation impacted serum metabolic profiles in pregnant adolescents.

Keywords: adolescent; biomarker; metabolomics; pregnancy; vitamin D.

Figure 1.

This figure depicts the mean and variance of the metabolites in the raw data (prior to transformation and median equalization). The mean and the variance are highly correlated (Panel A). There is a clear trend—that is, the variance increases exponentially with the mean—which necessitates data transformation. Panel B displays the Harvest plot: the difference between the means, between high and low 25(OH)D groups, is plotted along the horizontal axis, and the ratio between the variances is plotted along the vertical axis.

Figure 2.

This figure depicts the mean and variance of metabolites after applying a variance stabilizing transformation to the data (by taking the logarithm) and equalizing the medians of all 30 profiles. The mean and the variance are no longer correlated (Panel A). The Harvest plot is presented in Panel B: the difference between the means (between high and low serum vitamin D groups) is plotted along the horizontal axis, and the logarithm of the ratio between the variances is plotted along the vertical axis. The 11 metabolites with significantly different means are depicted as dark red squares.

Figure 3.

The panels present a heat map of serum metabolic profiles by vitamin D status and pathway. Significant differences between vitamin D groups are highlighted in green (elevated) and red (decreased) and indicate differences in the 11 metabolites linked to inflammation, oxidase enzymes, fatty acid β-oxidation, and gut microbiome metabolism. (The color version of this article is available at http://rs.sagepub.com.)