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Metabolism. 2017 Nov;76:11-22. doi: 10.1016/j.metabol.2017.07.001. Epub 2017 Jul 17.

Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva.

Author information

Department of Nutritional Sciences, Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA. Electronic address:
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Metabolon, Inc., Durham, NC, USA.
Department of Social Medicine, Faculty of Medicine University of Crete, Heraklion, Greece; Department of Preventive Medicine, Keck School of Medicine, University of South California, Los Angeles, CA, USA; Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.



Metabolomics has emerged as a powerful tool to characterize biomarkers and elucidate physiological processes underlying adverse health outcomes. Little is known of these relationships during gestation and infancy, which are critical period for development of metabolic disease risk.


To identify cord blood metabolite patterns associated with birth size; and to investigate relations of the birth size-associated metabolite patterns, and a branched chain amino acid (BCAA) metabolite pattern with a range of newborn and perinatal characteristics.


Using untargeted mass-spectrometry, we quantified metabolites in cord blood of 126 mother-child pairs. After excluding 103 xenobiotics, we used principal components analysis (PCA) to consolidate the remaining 606 metabolites into principal components ("factors"). Next, we identified factors associated with gestational age-and sex-standardized birthweight z-score (BW/GA) and examined associations of the BW/GA-associated pattern(s) and the BCAA pattern with cord blood insulin, leptin, adiponectin, insulin-like growth factor (IGF)-1, IGF-2, and IGF binding protein 3 (IGFBP-3) using multivariable linear regression. Finally, we examined associations of maternal/perinatal characteristics with the cord blood metabolite patterns.


Mean BW/GA z-score was 0.27±0.98 units. About half of the infants were male (52.4%) and white (57.1%). Of the 6 factors identified from PCA, one was associated with higher BW/GA: Factor 5, which comprised metabolites involved in energy production (malate, succinate, fumarate) and nucleotide turnover (inosine 5-monophosphate, adenosine 5-monophosphate, cytidine 5-monophosphate) pathways. In multivariable analysis, Factor 5 was related to higher cord blood leptin (1.64 [95% CI: 0.42, 2.87] ng/mL) and IGF-1 even after adjusting for IGFBP-3 (3.35 [0.25, 6.44] ng/mL). The BCAA pattern was associated with higher BW/GA (0.20 [0.03, 0.36] z-scores) and IGFBP-3 (106.5 [44.7, 168.2] ng/mL). No maternal characteristics were associated with either metabolite pattern; however, infants born via Cesarean delivery exhibited a higher score for Factor 5, and gestation length was inversely associated with the BCAA pattern.


Metabolites in energy production and DNA/RNA turnover pathways in cord blood are associated with larger size at birth, and higher leptin and IGF-1. Similarly, the BCAA pattern was associated with larger birth size and IGFBP-3.


Birth size; Branched-chain amino acids; Cord blood hormones; Metabolomics; Neonatal adiposity

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