Associations of maternal and infant metabolite profiles with foetal growth and the odds of adverse birth outcomes

Ellis Voerman; Vincent W.V. Jaddoe; Engy Shokry; George J.G. Ruijter; Janine F. Felix; Berthold Koletzko; Romy Gaillard

doi:10.1111/ijpo.12844

Associations of maternal and infant metabolite profiles with foetal growth and the odds of adverse birth outcomes

Ellis Voerman, Vincent W.V. Jaddoe, Engy Shokry, George J.G. Ruijter, Janine F. Felix, Berthold Koletzko, Romy Gaillard^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Adaptations in maternal and foetal metabolic pathways may predispose to altered foetal growth and adverse birth outcomes. Objective: To assess the associations of maternal early-pregnancy metabolite profiles and infant metabolite profiles at birth with foetal growth from first trimester onwards and the odds of adverse birth outcomes. Methods: In a prospective population-based cohort among 976 Dutch pregnant women and their children, serum concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL) and carnitines in maternal early-pregnancy blood and in cord blood were obtained by liquid-chromatography tandem mass spectrometry. Information on foetal growth was available from first trimester onwards. Results: After false discovery rate correction for multiple testing, higher infant total and individual NEFA concentrations were associated with a lower weight, length, and head circumference at birth. Higher infant total and individual acyl-lysophosphatidylcholine (lyso.PC.a) and alkyl-lysophosphatidylcholine concentrations were associated with higher weight and head circumference (lyso.PC.a only) at birth, higher odds of LGA and lower odds of SGA. Few individual maternal metabolites were associated with foetal growth measures in third trimester and at birth, but not with the odds of adverse birth outcomes. Conclusions: Our results suggest that infant metabolite profiles, particularly total and individual lyso.PC.a and NEFA concentrations, were strongly related to growth measures at birth and the odds of adverse birth outcomes. Few individual maternal early-pregnancy metabolites, but not total metabolite concentrations, are associated with foetal growth measures in third trimester and at birth.

Original language	English
Article number	e12844
Journal	Pediatric obesity
Volume	17
Issue number	2
Early online date	12 Aug 2021
DOIs	https://doi.org/10.1111/ijpo.12844
Publication status	Published - Feb 2022

Bibliographical note

Funding Information:
The Generation R Study is financially supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The research leading to these results received funding from the European Union Horizon 2020 Research and Innovation Programme under grant number 733206 (LifeCycle Project), as well as from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022). Vincent W. V. Jaddoe received a European Research Council Consolidator Grant (ERC‐2014‐CoG‐648916). Romy Gaillard received funding from the Dutch Heart Foundation (grant number 2017T013), the Dutch Diabetes Foundation (grant number 2017.81.002) and the Netherlands Organization for Health Research and Development (ZonMW, grant number 543003109). The metabolomic analyses were financially supported in part by the European Research Council Advanced Grant META‐GROWTH ERC‐2012‐AdG–no.322605, the European Joint Programming Initiative Project NutriPROGRAM, the German Ministry of Education and Research, Berlin (Grant Nr. 01 GI 0825), and the German Research Council (INST 409/224‐1 FUGG). The work of Berthold Koletzko is supported by an Else Kröner‐Seniorprofessorship co‐funded by the Else Kröner‐Fresenius Foundation and LMU University Hospitals. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of participating mothers, general practitioners, hospitals, midwives and pharmacies in Rotterdam. We thank Olaf Uhl and Linda Marchioro for their contributions to data acquisition and data processing, respectively.

Funding Information:
Diabetes Fonds, Grant/Award Number: 2017.81.002; Else Kröner‐Fresenius Foundation; Erasmus Medisch Centrum; Erasmus Universiteit Rotterdam; European Joint Programming Initiative; European Research Council, Grant/Award Numbers: ERC‐2012‐AdG‐no.322605, ERC‐2014‐CoG‐648916; European Research Council Horizon 2020, Grant/Award Number: 733206; German Research Council (INST 409/224‐1 FUGG); German Ministry of Education and Research, Grant/Award Number: 01 GI 0825; Hartstichting, Grant/Award Number: 2017T013; LMU University Hospitals; ZonMw, Grant/Award Numbers: 529051022, 543003109 Funding information

Funding Information:
The Generation R Study is financially supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The research leading to these results received funding from the European Union Horizon 2020 Research and Innovation Programme under grant number 733206 (LifeCycle Project), as well as from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022). Vincent W. V. Jaddoe received a European Research Council Consolidator Grant (ERC-2014-CoG-648916). Romy Gaillard received funding from the Dutch Heart Foundation (grant number 2017T013), the Dutch Diabetes Foundation (grant number 2017.81.002) and the Netherlands Organization for Health Research and Development (ZonMW, grant number 543003109). The metabolomic analyses were financially supported in part by the European Research Council Advanced Grant META-GROWTH ERC-2012-AdG–no.322605, the European Joint Programming Initiative Project NutriPROGRAM, the German Ministry of Education and Research, Berlin (Grant Nr. 01 GI 0825), and the German Research Council (INST 409/224-1 FUGG). The work of Berthold Koletzko is supported by an Else Kröner-Seniorprofessorship co-funded by the Else Kröner-Fresenius Foundation and LMU University Hospitals. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of participating mothers, general practitioners, hospitals, midwives and pharmacies in Rotterdam. We thank Olaf Uhl and Linda Marchioro for their contributions to data acquisition and data processing, respectively.

Publisher Copyright:
© 2021 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

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Associations of maternal and infant metabolite profiles with foetal growth and the odds of adverse birth outcomesFinal published version, 3.52 MBLicence: CC BY-NC-ND

Cite this

@article{ffd90a17cb80441d8ca9d2b10c46ed25,

title = "Associations of maternal and infant metabolite profiles with foetal growth and the odds of adverse birth outcomes",

abstract = "Background: Adaptations in maternal and foetal metabolic pathways may predispose to altered foetal growth and adverse birth outcomes. Objective: To assess the associations of maternal early-pregnancy metabolite profiles and infant metabolite profiles at birth with foetal growth from first trimester onwards and the odds of adverse birth outcomes. Methods: In a prospective population-based cohort among 976 Dutch pregnant women and their children, serum concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL) and carnitines in maternal early-pregnancy blood and in cord blood were obtained by liquid-chromatography tandem mass spectrometry. Information on foetal growth was available from first trimester onwards. Results: After false discovery rate correction for multiple testing, higher infant total and individual NEFA concentrations were associated with a lower weight, length, and head circumference at birth. Higher infant total and individual acyl-lysophosphatidylcholine (lyso.PC.a) and alkyl-lysophosphatidylcholine concentrations were associated with higher weight and head circumference (lyso.PC.a only) at birth, higher odds of LGA and lower odds of SGA. Few individual maternal metabolites were associated with foetal growth measures in third trimester and at birth, but not with the odds of adverse birth outcomes. Conclusions: Our results suggest that infant metabolite profiles, particularly total and individual lyso.PC.a and NEFA concentrations, were strongly related to growth measures at birth and the odds of adverse birth outcomes. Few individual maternal early-pregnancy metabolites, but not total metabolite concentrations, are associated with foetal growth measures in third trimester and at birth.",

author = "Ellis Voerman and Jaddoe, {Vincent W.V.} and Engy Shokry and Ruijter, {George J.G.} and Felix, {Janine F.} and Berthold Koletzko and Romy Gaillard",

note = "Funding Information: The Generation R Study is financially supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The research leading to these results received funding from the European Union Horizon 2020 Research and Innovation Programme under grant number 733206 (LifeCycle Project), as well as from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022). Vincent W. V. Jaddoe received a European Research Council Consolidator Grant (ERC‐2014‐CoG‐648916). Romy Gaillard received funding from the Dutch Heart Foundation (grant number 2017T013), the Dutch Diabetes Foundation (grant number 2017.81.002) and the Netherlands Organization for Health Research and Development (ZonMW, grant number 543003109). The metabolomic analyses were financially supported in part by the European Research Council Advanced Grant META‐GROWTH ERC‐2012‐AdG–no.322605, the European Joint Programming Initiative Project NutriPROGRAM, the German Ministry of Education and Research, Berlin (Grant Nr. 01 GI 0825), and the German Research Council (INST 409/224‐1 FUGG). The work of Berthold Koletzko is supported by an Else Kr{\"o}ner‐Seniorprofessorship co‐funded by the Else Kr{\"o}ner‐Fresenius Foundation and LMU University Hospitals. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of participating mothers, general practitioners, hospitals, midwives and pharmacies in Rotterdam. We thank Olaf Uhl and Linda Marchioro for their contributions to data acquisition and data processing, respectively. Funding Information: Diabetes Fonds, Grant/Award Number: 2017.81.002; Else Kr{\"o}ner‐Fresenius Foundation; Erasmus Medisch Centrum; Erasmus Universiteit Rotterdam; European Joint Programming Initiative; European Research Council, Grant/Award Numbers: ERC‐2012‐AdG‐no.322605, ERC‐2014‐CoG‐648916; European Research Council Horizon 2020, Grant/Award Number: 733206; German Research Council (INST 409/224‐1 FUGG); German Ministry of Education and Research, Grant/Award Number: 01 GI 0825; Hartstichting, Grant/Award Number: 2017T013; LMU University Hospitals; ZonMw, Grant/Award Numbers: 529051022, 543003109 Funding information Funding Information: The Generation R Study is financially supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The research leading to these results received funding from the European Union Horizon 2020 Research and Innovation Programme under grant number 733206 (LifeCycle Project), as well as from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022). Vincent W. V. Jaddoe received a European Research Council Consolidator Grant (ERC-2014-CoG-648916). Romy Gaillard received funding from the Dutch Heart Foundation (grant number 2017T013), the Dutch Diabetes Foundation (grant number 2017.81.002) and the Netherlands Organization for Health Research and Development (ZonMW, grant number 543003109). The metabolomic analyses were financially supported in part by the European Research Council Advanced Grant META-GROWTH ERC-2012-AdG–no.322605, the European Joint Programming Initiative Project NutriPROGRAM, the German Ministry of Education and Research, Berlin (Grant Nr. 01 GI 0825), and the German Research Council (INST 409/224-1 FUGG). The work of Berthold Koletzko is supported by an Else Kr{\"o}ner-Seniorprofessorship co-funded by the Else Kr{\"o}ner-Fresenius Foundation and LMU University Hospitals. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of participating mothers, general practitioners, hospitals, midwives and pharmacies in Rotterdam. We thank Olaf Uhl and Linda Marchioro for their contributions to data acquisition and data processing, respectively. Publisher Copyright: {\textcopyright} 2021 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.",

year = "2022",

month = feb,

doi = "10.1111/ijpo.12844",

language = "English",

volume = "17",

journal = "Pediatric obesity",

issn = "2047-6302",

publisher = "Wiley-Blackwell for the International Association for the Study of Obesity",

number = "2",

}

TY - JOUR

T1 - Associations of maternal and infant metabolite profiles with foetal growth and the odds of adverse birth outcomes

AU - Voerman, Ellis

AU - Jaddoe, Vincent W.V.

AU - Shokry, Engy

AU - Ruijter, George J.G.

AU - Felix, Janine F.

AU - Koletzko, Berthold

AU - Gaillard, Romy

N1 - Funding Information: The Generation R Study is financially supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The research leading to these results received funding from the European Union Horizon 2020 Research and Innovation Programme under grant number 733206 (LifeCycle Project), as well as from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022). Vincent W. V. Jaddoe received a European Research Council Consolidator Grant (ERC‐2014‐CoG‐648916). Romy Gaillard received funding from the Dutch Heart Foundation (grant number 2017T013), the Dutch Diabetes Foundation (grant number 2017.81.002) and the Netherlands Organization for Health Research and Development (ZonMW, grant number 543003109). The metabolomic analyses were financially supported in part by the European Research Council Advanced Grant META‐GROWTH ERC‐2012‐AdG–no.322605, the European Joint Programming Initiative Project NutriPROGRAM, the German Ministry of Education and Research, Berlin (Grant Nr. 01 GI 0825), and the German Research Council (INST 409/224‐1 FUGG). The work of Berthold Koletzko is supported by an Else Kröner‐Seniorprofessorship co‐funded by the Else Kröner‐Fresenius Foundation and LMU University Hospitals. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of participating mothers, general practitioners, hospitals, midwives and pharmacies in Rotterdam. We thank Olaf Uhl and Linda Marchioro for their contributions to data acquisition and data processing, respectively. Funding Information: Diabetes Fonds, Grant/Award Number: 2017.81.002; Else Kröner‐Fresenius Foundation; Erasmus Medisch Centrum; Erasmus Universiteit Rotterdam; European Joint Programming Initiative; European Research Council, Grant/Award Numbers: ERC‐2012‐AdG‐no.322605, ERC‐2014‐CoG‐648916; European Research Council Horizon 2020, Grant/Award Number: 733206; German Research Council (INST 409/224‐1 FUGG); German Ministry of Education and Research, Grant/Award Number: 01 GI 0825; Hartstichting, Grant/Award Number: 2017T013; LMU University Hospitals; ZonMw, Grant/Award Numbers: 529051022, 543003109 Funding information Funding Information: The Generation R Study is financially supported by the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. The research leading to these results received funding from the European Union Horizon 2020 Research and Innovation Programme under grant number 733206 (LifeCycle Project), as well as from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022). Vincent W. V. Jaddoe received a European Research Council Consolidator Grant (ERC-2014-CoG-648916). Romy Gaillard received funding from the Dutch Heart Foundation (grant number 2017T013), the Dutch Diabetes Foundation (grant number 2017.81.002) and the Netherlands Organization for Health Research and Development (ZonMW, grant number 543003109). The metabolomic analyses were financially supported in part by the European Research Council Advanced Grant META-GROWTH ERC-2012-AdG–no.322605, the European Joint Programming Initiative Project NutriPROGRAM, the German Ministry of Education and Research, Berlin (Grant Nr. 01 GI 0825), and the German Research Council (INST 409/224-1 FUGG). The work of Berthold Koletzko is supported by an Else Kröner-Seniorprofessorship co-funded by the Else Kröner-Fresenius Foundation and LMU University Hospitals. The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of participating mothers, general practitioners, hospitals, midwives and pharmacies in Rotterdam. We thank Olaf Uhl and Linda Marchioro for their contributions to data acquisition and data processing, respectively. Publisher Copyright: © 2021 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

PY - 2022/2

Y1 - 2022/2

N2 - Background: Adaptations in maternal and foetal metabolic pathways may predispose to altered foetal growth and adverse birth outcomes. Objective: To assess the associations of maternal early-pregnancy metabolite profiles and infant metabolite profiles at birth with foetal growth from first trimester onwards and the odds of adverse birth outcomes. Methods: In a prospective population-based cohort among 976 Dutch pregnant women and their children, serum concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL) and carnitines in maternal early-pregnancy blood and in cord blood were obtained by liquid-chromatography tandem mass spectrometry. Information on foetal growth was available from first trimester onwards. Results: After false discovery rate correction for multiple testing, higher infant total and individual NEFA concentrations were associated with a lower weight, length, and head circumference at birth. Higher infant total and individual acyl-lysophosphatidylcholine (lyso.PC.a) and alkyl-lysophosphatidylcholine concentrations were associated with higher weight and head circumference (lyso.PC.a only) at birth, higher odds of LGA and lower odds of SGA. Few individual maternal metabolites were associated with foetal growth measures in third trimester and at birth, but not with the odds of adverse birth outcomes. Conclusions: Our results suggest that infant metabolite profiles, particularly total and individual lyso.PC.a and NEFA concentrations, were strongly related to growth measures at birth and the odds of adverse birth outcomes. Few individual maternal early-pregnancy metabolites, but not total metabolite concentrations, are associated with foetal growth measures in third trimester and at birth.

AB - Background: Adaptations in maternal and foetal metabolic pathways may predispose to altered foetal growth and adverse birth outcomes. Objective: To assess the associations of maternal early-pregnancy metabolite profiles and infant metabolite profiles at birth with foetal growth from first trimester onwards and the odds of adverse birth outcomes. Methods: In a prospective population-based cohort among 976 Dutch pregnant women and their children, serum concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL) and carnitines in maternal early-pregnancy blood and in cord blood were obtained by liquid-chromatography tandem mass spectrometry. Information on foetal growth was available from first trimester onwards. Results: After false discovery rate correction for multiple testing, higher infant total and individual NEFA concentrations were associated with a lower weight, length, and head circumference at birth. Higher infant total and individual acyl-lysophosphatidylcholine (lyso.PC.a) and alkyl-lysophosphatidylcholine concentrations were associated with higher weight and head circumference (lyso.PC.a only) at birth, higher odds of LGA and lower odds of SGA. Few individual maternal metabolites were associated with foetal growth measures in third trimester and at birth, but not with the odds of adverse birth outcomes. Conclusions: Our results suggest that infant metabolite profiles, particularly total and individual lyso.PC.a and NEFA concentrations, were strongly related to growth measures at birth and the odds of adverse birth outcomes. Few individual maternal early-pregnancy metabolites, but not total metabolite concentrations, are associated with foetal growth measures in third trimester and at birth.

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U2 - 10.1111/ijpo.12844

DO - 10.1111/ijpo.12844

M3 - Article

C2 - 34384140

AN - SCOPUS:85112338183

SN - 2047-6302

VL - 17

JO - Pediatric obesity

JF - Pediatric obesity

IS - 2

M1 - e12844

ER -

Associations of maternal and infant metabolite profiles with foetal growth and the odds of adverse birth outcomes

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