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Original Article

Open Access Gateway

Cord Blood Metabolome Is Highly Associated with Birth Weight, but Less Predictive for Later Weight Development

Hellmuth C.a · Uhl O.a · Standl M.b · Demmelmair H.a · Heinrich J.b, c · Koletzko B.a · Thiering E.a, b

Author affiliations

aDivision of Metabolic and Nutritional Medicine, Dr. von Hauner Childrenʼs Hospital, University of Munich Medical Center, Ludwig-Maximilians-Universität München, Munich, Germany; bInstitute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; cInstitute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University of Munich Medical Center, Ludwig-Maximilians-Universität München, Munich, Germany

Corresponding Author

Prof. Dr. Berthold Koletzko

Division of Metabolic and Nutritional Medicine, Dr. von Hauner Childrenʼs Hospital

University of Munich Medical Center, Ludwig-Maximilians-Universität München

Lindwurmstraße 4, 80337 Munich, Germany

office.koletzko@med.lmu.de

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Abstract

Background/Aims: Fetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence. Methods: Over 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA), polar lipids, non-esterified fatty acids (NEFA), and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables. Results: Cord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing. Conclusion: Potential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome.

© 2017 The Author(s) Published by S. Karger GmbH, Freiburg


References

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Article / Publication Details

First-Page Preview
Abstract of Original Article

Received: July 06, 2016
Accepted: October 27, 2016
Published online: April 05, 2017
Issue release date: April 2017

Number of Print Pages: 16
Number of Figures: 4
Number of Tables: 3

ISSN: 1662-4025 (Print)
eISSN: 1662-4033 (Online)

For additional information: https://www.karger.com/OFA

References

  1. Barker DJ, Osmond C: Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1986;1:1077-1081.
  2. Koletzko B, Brands B, Chourdakis M, Cramer S, Grote V, Hellmuth C, Kirchberg F, Prell C, Rzehak P, Uhl O, Weber M: The power of programming and the earlynutrition project: opportunities for health promotion by nutrition during the first thousand days of life and beyond. Ann Nutr Metab 2014;64:187-196.
  3. Sookoian S, Gianotti TF, Burgueno AL, Pirola CJ: Fetal metabolic programming and epigenetic modifications: a systems biology approach. Pediatr Res 2013;73:531-542.
  4. Hales CN, Barker DJ: The thrifty phenotype hypothesis. Br Med Bull 2001;60:5-20.
  5. Okada T, Takahashi S, Nagano N, Yoshikawa K, Usukura Y, Hosono S: Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat. Pediatr Res 2015;77:136-142.
  6. Ong KK, Emmett PM, Noble S, Ness A, Dunger DB, Team AS: Dietary energy intake at the age of 4 months predicts postnatal weight gain and childhood body mass index. Pediatrics 2006;117:e503-508.
  7. Singhal A, Lucas A: Early origins of cardiovascular disease: is there a unifying hypothesis? Lancet 2004;363:1642-1645.
  8. Huxley R, Owen CG, Whincup PH, Cook DG, Rich-Edwards J, Smith GD, Collins R: Is birth weight a risk factor for ischemic heart disease in later life? Am J Clin Nutr 2007;85:1244-1250.
    External Resources
  9. Harder T, Rodekamp E, Schellong K, Dudenhausen JW, Plagemann A: Birth weight and subsequent risk of type 2 diabetes: a meta-analysis. Am J Epidemiol 2007;165:849-857.
  10. Coughlin SS: Toward a road map for global -omics: a primer on -omic technologies. Am J Epidemiol 2014;180:1188-1195.
  11. Rauschert S, Uhl O, Koletzko B, Hellmuth C: Metabolomic biomarkers for obesity in humans: a short review. Ann Nutr Metab 2014;64:314-324.
  12. Ivorra C, Garcia-Vicent C, Chaves FJ, Monleon D, Morales JM, Lurbe E: Metabolomic profiling in blood from umbilical cords of low birth weight newborns. J Transl Med 2012;10:142.
  13. Alexandre-Gouabau MC, Courant F, Moyon T, Kuster A, Le Gall G, Tea I, Antignac JP, Darmaun D: Maternal and cord blood LC-HRMS metabolomics reveal alterations in energy and polyamine metabolism, and oxidative stress in very-low birth weight infants. J Proteome Res 2013;12:2764-2778.
  14. Favretto D, Cosmi E, Ragazzi E, Visentin S, Tucci M, Fais P, Cecchetto G, Zanardo V, Viel G, Ferrara SD: Cord blood metabolomic profiling in intrauterine growth restriction. Anal Bioanal Chem 2012;402:1109-1121.
  15. Isganaitis E, Rifas-Shiman SL, Oken E, Dreyfuss JM, Gall W, Gillman MW, Patti ME: Associations of cord blood metabolites with early childhood obesity risk. Int J Obes (Lond) 2015;39:1041-1048.
  16. Gibbons H, O'Gorman A, Brennan L: Metabolomics as a tool in nutritional research. Curr Opin Lipidol 2015;26:30-34.
  17. Heinrich J, Bolte G, Holscher B, Douwes J, Lehmann I, Fahlbusch B, Bischof W, Weiss M, Borte M, Wichmann HE, Group LS: Allergens and endotoxin on mothers' mattresses and total immunoglobulin E in cord blood of neonates. Eur Respir J 2002;20:617-623.
  18. Glaser C, Demmelmair H, Koletzko B: High-throughput analysis of total plasma fatty acid composition with direct in situ transesterification. PLoS One 20109;5:e12045.
  19. Rauschert S, Uhl O, Koletzko B, Kirchberg F, Mori TA, Huang RC, Beilin LJ, Hellmuth C, Oddy WH: Lipidomics reveals associations of phospholipids with obesity and insulin resistance in young adults. J Clin Endocrinol Metab 2016;101:871-879.
  20. Harder U, Koletzko B, Peissner W: Quantification of 22 plasma amino acids combining derivatization and ion-pair LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 2011;879:495-504.
  21. Hellmuth C, Weber M, Koletzko B, Peissner W: Nonesterified fatty acid determination for functional lipidomics: comprehensive ultrahigh performance liquid chromatography-tandem mass spectrometry quantitation, qualification, and parameter prediction. Anal Chem 2012;84:1483-1490.
  22. Paton CM, Ntambi JM: Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab 2009;297:E28-37.
  23. de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J: Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ 2007;85:660-667.
  24. Koletzko B, Chourdakis M, Grote V, Hellmuth C, Prell C, Rzehak P, Uhl O, Weber M: Regulation of early human growth: impact on long-term health. Ann Nutr Metab 2014;65:101-109.
  25. Kabaran S, Besler H: Do fatty acids affect fetal programming? JJ Health Popul Nutr 2015;33:14.
  26. Pantham P, Rosario FJ, Nijland M, Cheung A, Nathanielsz PW, Powell TL, Galan HL, Li C, Jansson T: Reduced placental amino acid transport in response to maternal nutrient restriction in the baboon. Am J Physiol Regul Integr Comp Physiol 2015;309:R740-746.
  27. Tounian P: Programming towards childhood obesity. Ann Nutr Metab 2011;58(suppl 2):30-41.
  28. Rzehak P, Sausenthaler S, Koletzko S, Bauer CP, Schaaf B, von Berg A, Berdel D, Borte M, Herbarth O, Kramer U, Fenske N, Wichmann HE, Heinrich J: Period-specific growth, overweight and modification by breastfeeding in the GINI and LISA birth cohorts up to age 6 years. Eur J Epidemiol 2009;24:449-467.
  29. Haggarty P: Fatty acid supply to the human fetus. Annu Rev Nutr 2010;30:237-255.
  30. Sevastou I, Kaffe E, Mouratis MA, Aidinis V: Lysoglycerophospholipids in chronic inflammatory disorders: The PLA(2)/LPC and ATX/LPA axes. Biochim Biophys Acta 2013;1831:42-60.
  31. Jonas A: Lecithin cholesterol acyltransferase. Biochim Biophys Acta 2000;1529:245-256.
  32. Prieto-Sanchez MT, Ruiz-Palacios M, Blanco-Carnero JE, Pagan A, Hellmuth C, Uhl O, Peissner W, Ruiz-Alcaraz AJ, Parrilla JJ, Koletzko B, Larque E: Placental MFSD2A transporter is related to decreased DHA in cord blood of women with treated gestational diabetes. Clin Nutr 2016;36:513-521.
  33. Graessler J, Schwudke D, Schwarz PE, Herzog R, Shevchenko A, Bornstein SR: Top-down lipidomics reveals ether lipid deficiency in blood plasma of hypertensive patients. PLoS One 2009;4:e6261.
  34. Pietilainen KH, Sysi-Aho M, Rissanen A, Seppanen-Laakso T, Yki-Jarvinen H, Kaprio J, Oresic M: Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects - a monozygotic twin study. PLoS One 2007;2:e218.
  35. Barber MN, Risis S, Yang C, Meikle PJ, Staples M, Febbraio MA, Bruce CR: Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes. PLoS One 2012;7:e41456.
  36. Heimerl S, Fischer M, Baessler A, Liebisch G, Sigruener A, Wallner S, Schmitz G: Alterations of plasma lysophosphatidylcholine species in obesity and weight loss. PLoS One 2014;9:e111348.
  37. Wahl S, Yu Z, Kleber M, Singmann P, Holzapfel C, He Y, Mittelstrass K, Polonikov A, Prehn C, Romisch-Margl W, Adamski J, Suhre K, Grallert H, Illig T, Wang-Sattler R, Reinehr T: Childhood obesity is associated with changes in the serum metabolite profile. Obes Facts 2012;5:660-670.
  38. Reinehr T, Wolters B, Knop C, Lass N, Hellmuth C, Harder U, Peissner W, Wahl S, Grallert H, Adamski J, Illig T, Prehn C, Yu Z, Wang-Sattler R, Koletzko B: Changes in the serum metabolite profile in obese children with weight loss. Eur J Nutr 2015;54:173-181.
  39. Kim JY, Park JY, Kim OY, Ham BM, Kim HJ, Kwon DY, Jang Y, Lee JH: Metabolic profiling of plasma in overweight/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS). J Proteome Res 2010;9:4368-4375.
  40. Brett D, Howling D, Morris LJ, James AT: Specificity of the fatty acid desaturases. The conversion of saturated to monoenoic acids. Arch Biochem Biophys 1971;143:535-547.
  41. Hulver MW, Berggren JR, Carper MJ, Miyazaki M, Ntambi JM, Hoffman EP, Thyfault JP, Stevens R, Dohm GL, Houmard JA, Muoio DM: Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab 2005;2:251-261.
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