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J Proteome Res. 2018 Mar 2;17(3):1235-1247. doi: 10.1021/acs.jproteome.7b00846. Epub 2018 Feb 9.

Cord Blood Metabolic Signatures of Birth Weight: A Population-Based Study.

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MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London , St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
International Agency for Research on Cancer (IARC) , 150 Cours Albert Thomas, 69372 Lyon, France.
Department of Social Medicine, Faculty of Medicine, University of Crete , Voutes University Campus, Heraklion, Crete, GR-70013, Greece.
Department of Preventive Medicine, Keck School of Medicine, University of South California , Soto Street Building 2001 N Soto Street, Suite 201-D, Los Angeles, California 90032-3628, United States.
Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University , Universiteitssingel 40, 6229 Maastricht, The Netherlands.
ISGlobal, Centre for Research in Environmental Epidemiology (CREAL) , PRBB, C/ Doctor Aiguader, 88, 08003, Barcelona Spain.
Universitat Pompeu Fabra (UPF) , Plaça de la Mercè, 10, Barcelona 08002, Spain.
CIBER Epidemiología y Salud Pública (CIBERESP) , PRBB, C/ Doctor Aiguader, 88, E-08003 Barcelona, Spain.
Centre for Environmental Sciences, Hasselt University , Campus Diepenbeek, Agoralaan building D, BE3590 Diepenbeek, Belgium.
Department of Public Health & Primary Care, Leuven University , Oude Markt 13, B-3000 Leuven, Belgium.
Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO-Piemonte , C.So, Dogliotti, 14, 10126 Turin, Italy.
Institute for Risk Assessment Sciences, Environmental Epidemiology Division, Utrecht University , POB 80178, Utrecht NL-3508, The Netherlands.


Birth weight is an important indicator of maternal and fetal health and a predictor of health in later life. However, the determinants of variance in birth weight are still poorly understood. We aimed to identify the biological pathways, which may be perturbed by environmental exposures, that are important in determining birth weight. We applied untargeted mass-spectrometry-based metabolomics to 481 cord blood samples collected at delivery in four birth cohorts from across Europe: ENVIRONAGE (Belgium), INMA (Spain), Piccolipiu (Italy), and Rhea (Greece). We performed a metabolome-wide association scan for birth weight on over 4000 metabolic features, controlling the false discovery rate at 5%. Annotation of compounds was conducted through reference to authentic standards. We identified 68 metabolites significantly associated with birth weight, including vitamin A, progesterone, docosahexaenoic acid, indolelactic acid, and multiple acylcarnitines and phosphatidylcholines. We observed enrichment (p < 0.05) of the tryptophan metabolism, prostaglandin formation, C21-steroid hormone signaling, carnitine shuttle, and glycerophospholipid metabolism pathways. Vitamin A was associated with both maternal smoking and birth weight, suggesting a mediation pathway. Our findings shed new light on the pathways central to fetal growth and will have implications for antenatal and perinatal care and potentially for health in later life.


birth weight; cord blood; fetal growth; metabolism; metabolomics; pathway perturbation

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