Christian Hellmuth1, Karen L Lindsay2,3, Olaf Uhl1, Claudia Buss2,4,3, Pathik D Wadhwa2,5,3, Berthold Koletzko1, Sonja Entringer4,3. 1. Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Ludwig-Maximilian-Universität München, 80337, München, Germany. 2. Department of Pediatrics, University of California, Irvine, CA, 92697, USA. 3. UC Irvine Development, Health and Disease Research Program, University of California, Irvine, CA, 92697, USA. 4. Institute of Medical Psychology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany. 5. Department of Psychiatry and Human Behavior and Department of Obstetrics and Gynecology, University of California, Irvine, CA, 92697, USA.
Abstract
SCOPE: The fetal programming paradigm posits that the origins of obesity can be traced, in part, to the intrauterine period of life. However, the mechanisms underlying fetal programming are not well understood, and few studies have measured offspring adiposity in the neonatal period. The aim of this study is to identify maternal metabolites, and their determinants, that are associated with neonatal adiposity. METHODS AND RESULTS: A targeted metabolomics approach is applied to analyze plasma samples collected across gestation from a well-characterized cohort of 253 pregnant women participating in a prospective study at the University of California, Irvine. Whole-body dual X-ray absorptiometry (DXA) imaging of body composition is obtained in N = 121 newborns. Statistical models are adjusted for potential confounders and multiple testing. The authors identify six alkyl-linked phosphatidylcholines (PCae), containing fatty acid 20:4, that are significantly and negatively associated with neonatal body fat percentage. Factors indicating higher socioeconomic status, non-Hispanic ethnicity, and higher nonesterified fatty acid percentages are positively associated with these PCae. CONCLUSIONS: The polyunsaturated fatty acid 20:4 contained in PCae may exert a beneficial effect with respect to future propensity for obesity development. Prepregnancy and early pregnancy factors are determinants of these PCae, highlighting the importance of addressing preconceptional conditions for fetal programming of newborn adiposity.
SCOPE: The fetal programming paradigm posits that the origins of obesity can be traced, in part, to the intrauterine period of life. However, the mechanisms underlying fetal programming are not well understood, and few studies have measured offspring adiposity in the neonatal period. The aim of this study is to identify maternal metabolites, and their determinants, that are associated with neonatal adiposity. METHODS AND RESULTS: A targeted metabolomics approach is applied to analyze plasma samples collected across gestation from a well-characterized cohort of 253 pregnant women participating in a prospective study at the University of California, Irvine. Whole-body dual X-ray absorptiometry (DXA) imaging of body composition is obtained in N = 121 newborns. Statistical models are adjusted for potential confounders and multiple testing. The authors identify six alkyl-linked phosphatidylcholines (PCae), containing fatty acid 20:4, that are significantly and negatively associated with neonatal body fat percentage. Factors indicating higher socioeconomic status, non-Hispanic ethnicity, and higher nonesterified fatty acid percentages are positively associated with these PCae. CONCLUSIONS: The polyunsaturated fatty acid 20:4 contained in PCae may exert a beneficial effect with respect to future propensity for obesity development. Prepregnancy and early pregnancy factors are determinants of these PCae, highlighting the importance of addressing preconceptional conditions for fetal programming of newborn adiposity.
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