Longitudinal Changes of One-Carbon Metabolites and Amino Acid Concentrations during Pregnancy in the Women First Maternal Nutrition Trial

Stephanie P Gilley, Nicholas E Weaver, Evan L Sticca, Purevsuren Jambal, Alexandra Palacios, Mattie E Kerns, Pratibha Anand, Jennifer F Kemp, Jamie E Westcott, Lester Figueroa, Ana Lucía Garcés, Sumera A Ali, Omrana Pasha, Sarah Saleem, K Michael Hambidge, Audrey E Hendricks, Nancy F Krebs, Sarah J Borengasser, Stephanie P Gilley, Nicholas E Weaver, Evan L Sticca, Purevsuren Jambal, Alexandra Palacios, Mattie E Kerns, Pratibha Anand, Jennifer F Kemp, Jamie E Westcott, Lester Figueroa, Ana Lucía Garcés, Sumera A Ali, Omrana Pasha, Sarah Saleem, K Michael Hambidge, Audrey E Hendricks, Nancy F Krebs, Sarah J Borengasser

Abstract

Background: Maternal dietary restriction and supplementation of one-carbon (1C) metabolites can impact offspring growth and DNA methylation. However, longitudinal research of 1C metabolite and amino acid (AA) concentrations over the reproductive cycle of human pregnancy is limited.

Objective: To investigate longitudinal 1C metabolite and AA concentrations prior to and during pregnancy and the effects of a small-quantity lipid-based nutrition supplement (LNS) containing >20 micronutrients and prepregnancy BMI (ppBMI).

Methods: This study was an ancillary study of the Women First Trial (NCT01883193, clinicaltrials.gov) focused on a subset of Guatemalan women (n = 134), 49% of whom entered pregnancy with a BMI ≥25 kg/m2. Ninety-five women received LNS during pregnancy (+LNS group), while the remainder did not (-LNS group). A subset of women from the Pakistan study site (n = 179) were used as a replication cohort, 124 of whom received LNS. Maternal blood was longitudinally collected on dried blood spot (DBS) cards at preconception, and at 12 and 34 wk gestation. A targeted metabolomics assay was performed on DBS samples at each time point using LC-MS/MS. Longitudinal analyses were performed using linear mixed modeling to investigate the influence of time, LNS, and ppBMI.

Results: Concentrations of 23 of 27 metabolites, including betaine, choline, and serine, changed from preconception across gestation after application of a Bonferroni multiple testing correction (P < 0.00185). Sixteen of those metabolites showed similar changes in the replication cohort. Asymmetric and symmetric dimethylarginine were decreased by LNS in the participants from Guatemala. Only tyrosine was statistically associated with ppBMI at both study sites.

Conclusions: Time influenced most 1C metabolite and AA concentrations with a high degree of similarity between the 2 diverse study populations. These patterns were not significantly altered by LNS consumption or ppBMI. Future investigations will focus on 1C metabolite changes associated with infant outcomes, including DNA methylation. This trial was registered at clinicaltrials.gov as NCT01883193.

Keywords: BMI; amino acids; malnutrition; obesity; one-carbon metabolism; preconception; pregnancy; supplementation; triple nutrition burden.

Copyright © The Author(s) 2019.

Figures

FIGURE 1
FIGURE 1
Study and analysis design schematic. At study enrollment women were randomized into 1 of 3 study arms. For the present analysis, blood draws that occurred when the subjects were not consuming LNS (represented by unfilled blood drops) were considered unsupplemented time points; blood draws that occurred when the subjects had taken LNS for at least 12 wk (represented by solid blood drops) were considered supplemented time points. Arms 1 and 2 were combined and represent the +LNS group, while Arm 3 comprised the −LNS group. LNS, small-quantity lipid-based nutrition supplement.

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