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, padj < 0.001), delivery (rho = 0.23, padj < 0.001), and postpartum (rho = 0.41, padj < 0.001), and also with infant plasma levels at delivery (rho = 0.25, padj < 0.001). Lutein correlated with vegetables in general, both during pregnancy (rho=0.31, padj<0.001) and delivery (rho = 0.29, padj < 0.001). CMPF in plasma from mothers and infants at four months correlated with maternal intake of fatty fish (mother: rho = 0.30, padj < 0.001; breastfed infant: rho = 0.26, padj = 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
Author Contributions
Conceptualization, M.B., A.S., A.E.W. and A.-S.S.; Data curation, M.S., O.H. and S.N.; Formal analysis, M.S.; Funding acquisition, M.S., A.S., A.E.W. and A.-S.S.; Investigation, M.S., O.H. and A.S.; Methodology, M.B. and A.-S.S.; Project administration, M.B., A.S. and A.-S.S.; Supervision, M.B. and A.-S.S.; Visualization, M.S.; Writing—original draft, M.S.; Writing—review & editing, O.H., S.N., M.B., A.S., A.E.W. and A.-S.S. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by Swedish Research Council (VR) [521-2013-3154 and 2019-01317]; Swedish Research Council for Health, Working Life and Welfare (FORTE) [2014-0923, 2016-00700, 2018-00485]; Västra Götaland Region (RUN) [612-0618-15]; Research and Innovation Unit at Region Norrbotten; Jane och Dan Olssons stiftelse [2020-23]; FORMAS [2019-02201] under the umbrella of the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) and of the ERA-NET Cofund HDHL-INesTInal MICrobiome (INTIMIC) (GA no. 727565 of the EU Horizon 2020 Research and Innovation Programme). The APC was funded by Adlerbert Research Foundation.
Institutional Review Board Statement
The study was conducted in accordance with the Helsinki Declaration and approved by the Regional Ethical Review Board in Umeå, Sweden (2013/18–31M, 2015–71–32).
Informed Consent Statement
Written informed consent was obtained from all expecting parents concerning themselves and their expected child.
Data Availability Statement
The R-code for conducting the statistical analyses can be obtained from: https://gitlab.com/miastravik/dietary-biomarkers. The in-house developed R-based OCEAN Shiny app used for metabolite identification can be obtained from: https://gitlab.com/parasitetwin/autoannotshiny. Data described in the manuscript will not be made available because it relates to information that could compromise research participant privacy or consent. The food frequency questionnaires are not publicly available due to proprietary rights.
Conflicts of Interest
The authors declare no conflict of interest.
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