Objectives: The primary objective of this study was to evaluate early postnatal serum gut hormone concentrations in preterm infants as predictors of time to full enteral feedings. The secondary objective was to identify infant characteristics and nutritional factors that modulate serum gut hormone concentrations and time to full enteral feedings. Methods: Sixty-four preterm infants less than 30 weeks of gestation were included in this retrospective cohort study. Serum gut hormone concentrations at postnatal days 0 and 7 were measured using enzyme-linked immunosorbent assays. Linear regression and mediation analyses were performed. Results: Median (IQR) serum concentrations of glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) on postnatal day 7 were 31.3 pg/mL (18.2, 52.3) and 1181.7 pg/mL (859.0, 1650.2), respectively. GIP and PYY concentrations on day 7 were associated with days to full enteral feedings after adjustment for confounders (β = −1.1, p = 0.03; and β = −0.002, p = 0.02, respectively). Nutritional intake was correlated with serum concentrations of GIP and PYY on postnatal day 7 and time to full enteral feedings. Mediation analysis revealed that the effect of serum gut hormone concentrations on time to full enteral feedings was not fully explained by nutritional intake. Intrauterine growth restriction (IUGR), mechanical ventilation on postnatal day 7, and patent ductus arteriosus (PDA) treated with indomethacin were associated with longer time to full enteral feedings. Conclusions: Serum concentrations of GIP and PYY on postnatal 7 are independently associated with time to full enteral feedings. The link between serum gut hormone concentrations and time to full enteral feedings is not fully mediated by nutritional factors, suggesting an independent mechanism underlying the influence of gut hormones on feeding tolerance and time to full enteral feedings. Address correspondence and reprint requests to: Camilia R. Martin, MD, MS, Beth Israel Deaconess Medical Center, Department of Neonatology, 330 Brookline Avenue, Rose-318, Boston, MA 02215 (e-mail: cmartin1@bidmc.harvard.edu). Received 29 October, 2017 Accepted 16 March, 2018 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). Author Contributions: Kristen H. Shanahan: conception and design of the study, acquisition, analysis, and interpretation of the data, drafting and revision of manuscript, final approval of manuscript for submission Xinting Yu: analysis and interpretation of data, final approval of manuscript for submission Laura G. Miller: acquisition of data, final approval of manuscript for submission Steven D. Freedman: conception and design of the study, analysis and interpretation of the data, drafting and revision of manuscript, final approval of manuscript for submission Camilia R. Martin: conception and design of the study, analysis and interpretation of the data, drafting and revision of manuscript, final approval of manuscript for submission Conflicts of Interest and Sources of Funding: CRM receives research funding from Abbott Nutrition and Alcresta Therapeutics. The other authors have no conflicts of interest. KHS was supported by the Alpha Omega Alpha Honor Medical Society (Carolyn L. Kuckein Student Research Fellowship). CRM and SDF were supported by philanthropic contributions to the Charles and Judy Hood Family Infant Health Repository Program, Abbott Nutrition, and Alcresta Therapeutics. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
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