LC-MS-Based Metabolomics for Dietary Biomarker Discovery in a Cohort of Pregnant and Lactating Women and Their Infants ^†

Abstract

Circulating food metabolites could improve dietary assessment by complementing more traditional, subjective methods. However, information is lacking on the accuracy of these objective markers during pregnancy and lactation. The objective of this paper was to measure a panel of candidate food intake biomarkers, representing different food groups, during pregnancy, delivery, and lactation and correlate their plasma levels with self-reported food intake. All data was collected within the Swedish birth cohort Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE). Plasma samples from the women (gestational week 29, N = 579; delivery, N = 532; and four months postpartum, N = 477) and their infants (delivery, N = 348; and four months, N = 193) were analyzed with untargeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics. Food intake was assessed during pregnancy (gestational week 34) and lactation (one and four months postpartum) using a semi-quantitative food frequency questionnaire. Spearman correlation analyses with plasma levels and reported food intake were adjusted for multiple testing. Acetylcarnitine, choline, indole-3-lactic acid, lutein, pipecolic acid, proline betaine, and 3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF) were identified in plasma. Self-reported intake of fruit juice correlated positively with proline betaine during pregnancy (rho = 0.38, p_adj < 0.001), delivery (rho = 0.23, p_adj < 0.001), and postpartum (rho = 0.41, p_adj < 0.001), and also with infant plasma levels at delivery (rho = 0.25, p_adj < 0.001). Lutein correlated with vegetables in general, both during pregnancy (rho=0.31, p_adj<0.001) and delivery (rho = 0.29, p_adj < 0.001). CMPF in plasma from mothers and infants at four months correlated with maternal intake of fatty fish (mother: rho = 0.30, p_adj < 0.001; breastfed infant: rho = 0.26, p_adj = 0.037). No clear associations were obtained for the remaining metabolites. Our study confirms the use of proline betaine as a citrus fruit intake biomarker, primarily in the form of juice, for pregnant and lactating women. Plasma lutein could be useful as a more general fruit and vegetable intake biomarker during pregnancy, and CMPF as a fish intake biomarker during lactation. ClinicalTrials.gov identifier: NCT05809479