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

Oliver Robinson*, Pekka Keski-Rahkonen, Leda Chatzi, Manolis Kogevinas, Tim Nawrot, Costanza Pizzi, Michelle Plusquin, Lorenzo Richiardi, Nivonirina Robinot, Jordi Sunyer, Roel Vermeulen, Martine Vrijheid, Paolo Vineis, Augustin Scalbert, Marc Chadeau-Hyam

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Pages (from-to)1235-1247
Number of pages13
JournalJournal of Proteome Research
Volume17
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • metabolomics
  • birth weight
  • fetal growth
  • cord blood
  • metabolism
  • pathway perturbation
  • AMBIENT AIR-POLLUTION
  • VITAMIN-A
  • EARLY-PREGNANCY
  • TRYPTOPHAN-METABOLISM
  • FETAL-GROWTH
  • COHORT
  • RISK
  • INMA
  • PROGESTERONE
  • OUTCOMES
  • MOTHER
  • BREAST-CANCER
  • GROWTH
  • ASSOCIATION

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