Associations of cord blood metabolites with perinatal characteristics,newborn anthropometry,and cord blood hormones in project viva |
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| Affiliation: | 1. Department of Nutritional Sciences, Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA;2. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, Boston, MA, USA;3. Metabolon, Inc., Durham, NC, USA;4. Department of Social Medicine, Faculty of Medicine University of Crete, Heraklion, Greece;5. Department of Preventive Medicine, Keck School of Medicine, University of South California, Los Angeles, CA, USA;6. Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands;7. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;8. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA;1. School of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia;2. Division of Obstetrics & Gynaecology, School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia;3. Department of Maternal Fetal Medicine, King Edward Memorial Hospital, 374 Bagot Rd, Subiaco, WA 6008, Australia;1. Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada;2. Centre de recherche de l''Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, Canada;3. Department of Medicine, Division of Endocrinology, Centre de recherche du Centre hospitalier universitaire de Sherbrooke, Université de Sherbrooke, Québec, Canada;4. Department of Surgery, Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Université Laval, Québec, Canada;1. Pharmacy Practice, MCPHS University, 179 Longwood Avenue, Boston, MA 02115, United States;2. VA Boston Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130, United States;3. Global Regulatory Sciences at Biogen, Cambridge, MA, United States;4. Global Medical Writing MCPHS University, Boston, MA, United States;5. Division of Endocrinology, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA 02215, United States;1. Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;2. Key Laboratory of Rare Metabolic Diseases, Nanjing Medical University, Nanjing 211166, China;3. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 210023, China;4. Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, China;1. Liver Center, Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States;2. Department of Biostatistics, University of Washington, Seattle, WA, United States;3. Department of Cardiology, Mount Sinai St. Luke''s Roosevelt Hospital (Bronx-Lebanon Hospital Center), United States;4. Children''s Nutrition Research Center, Baylor College of Medicine, Houston, TX, United States;5. Los Angeles Biomedical Research Institute, Division of Cardiology, Harbor-UCLA Medical Center, Los Angeles, CA, United States |
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| Abstract: | ContextMetabolomics 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.ObjectivesTo 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.MethodsUsing 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.ResultsMean 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.ConclusionsMetabolites 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. |
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