Cord Blood Plasma Metabolome-wide Associations With Height From Birth to Adolescence

Tingyi Cao, Jiaxuan Zhao, Xiumei Hong, Guoying Wang, Colleen Pearson, William G. Adams, Frank B. Hu, Xiaobin Wang, Liming Liang

Research output: Contribution to journalArticlepeer-review


Although the maternal intrauterine metabolic environment has been recognized to have a profound impact on fetal growth and development with lifelong health implications, to our knowledge, there have been few large-scale birth cohort studies linking the cord metabolome (reflecting both the maternal and fetal metabolic state) with postnatal height measurements across the pediatric age range. Using data from the Boston Birth Cohort, an ongoing prospective birth cohort, this study investigated the association of cord plasma metabolites with children's height from birth to adolescence. Height was analyzed as attained height and longitudinal trajectories. Distinctive cord metabolite types were associated with attained height at different developmental windows: triacylglycerols [TAGs], diacylglycerols [DAGs], cholesterol ester [CEs], phospholipids, amino acids [AAs], acylcarnitines [ACs], and nucleotides in early (age 0–4 years) and middle (age 6–12 years) childhood; various metabolite types other than TAGs in later childhood (after age 14 years). Functional principal component analysis on children's repeated height measurements summarized two typical height trajectory components: loadings on first eigenfunction [FPC1] representing overall height by age, and loadings on second eigenfunction [FPC2] representing speed of pubertal height growth. Although only one cord metabolite was correlated with FPC1 after accounting for multiple testing, the study found 27 metabolites with significant overall effect on FPC2 among females and 18 among males. These metabolites were mostly phospholipids (including phosphatidylethanolamines [PEs], phosphatidylethanolamine plasmalogens [PE_Ps], phosphatidylcholines [PCs], lysophosphatidylethanolamines [LPEs], and lysophosphatidylcholines [LPCs]), AAs, and nucleotides. Their associations with height differed between overweight/obesity (OWO) and non-OWO children, especially among females. In this prospective study of US understudied urban, low-income, racially diverse children, we demonstrated that cord plasma metabolites were significantly associated with postnatal attained height at different age windows as well as height trajectories from birth to adolescence. We also revealed how these associations differed by children's sex and OWO status. Our findings help elucidate metabolic pathways underlying fetal origins of height growth across developmental stages.

Original languageEnglish (US)
Pages (from-to)707-718
Number of pages12
JournalJournal of Bone and Mineral Research
Issue number5
StatePublished - May 2023



ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine


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