Abstract
Background
Childhood obesity is associated with elevated blood concentrations of inflammation markers. It is not known to what extent inflammation precedes the development of obesity.
Methods
In a cohort of 882 infants born before 28 weeks of gestation, we examined relationships between concentrations of 25 inflammation-related proteins in blood obtained during the first two postnatal weeks and body mass index at 2 years of age.
Results
Among children delivered for spontaneous indications (n=734), obesity was associated with elevated concentrations of four proteins (IL-1β, IL-6, TNF-R1, and MCP-1) on the first postnatal day; one protein (IL-6) on postnatal day 7; and two proteins (ICAM-3 and VEGF-R1) on postnatal day 14. Among children delivered for maternal or fetal indications (n=148), obesity was associated with elevated concentrations of seven proteins on the 14th postnatal day. In multivariable models in the spontaneous indications subsample, elevated IL-6 on day 1 predicted obesity (odds ratio: 2.9; 95% confidence limits: 1.2, 6.8), whereas elevated VCAM-1 on day 14 predicted overweight at 2 years of age (odds ratio: 2.3; 95% confidence limits: 1.2, 4.3).
Conclusions
In this cohort, neonatal systemic inflammation preceded the onset of obesity, suggesting that inflammation might contribute to the development of obesity.
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Acknowledgements
Participating institutions and ELGAN Study collaborators who made this report possible: Children’s Hospital, Boston, MA: Kathleen Lee, Anne McGovern, Jill Gambardella, Susan Ursprung, Ruth Blomquist Kristen Ecklund, Haim Bassan, Samantha Butler, Adré Duplessis, Cecil Hahn, Catherine Limperopoulos, Omar Khwaja, and Janet S. Soul. Baystate Medical Center, Springfield, MA: Bhavesh Shah, Karen Christianson, Frederick Hampf, Herbert Gilmore, and Susan McQuiston. Beth Israel Deaconess Medical Center, Boston, MA: Camilia R. Martin, Colleen Hallisey, Caitlin Hurley, Miren Creixell, and Jane Share. Brigham and Women’s Hospital, Boston, MA: Linda J. Van Marter, Sara Durfee. Massachusetts General Hospital, Boston, MA: Robert M. Insoft, Jennifer G. Wilson, Maureen Pimental, Sjirk J. Westra, and Kalpathy Krishnamoorthy. Floating Hospital for Children at Tufts Medical Center, Boston, MA: Cynthia Cole, John M. Fiascone, Janet Madden, Ellen Nylen, Anne Furey Roy McCauley, Paige T. Church, Cecelia Keller, and Karen J. Miller. U Mass Memorial Health Care, Worcester, MA: Francis Bednarek (deceased), Mary Naples, Beth Powers, Jacqueline Wellman, Robin Adair, Richard Bream, Alice Miller, Albert Scheiner, and Christy Stine. Yale University School of Medicine, New Haven, CT: Richard Ehrenkranz, Joanne Williams, Elaine Romano, Cindy Miller, Nancy Close, Elaine Romano, and Joanne Williams. Wake Forest Baptist Medical Center and Forsyth Medical Center, Winston-Salem, NC: T. Michael O’Shea, Debbie Gordon, Teresa Harold, Barbara Specter, Deborah Allred, Robert Dillard, Don Goldstein, Deborah Hiatt (deceased), Gail Hounshell, Ellen Waldrep, Lisa Washburn, and Cherrie D. Welch. University Health Systems of Eastern Carolina, Greenville, NC: Stephen C. Engelke, Sherry Moseley, Linda Pare, Donna Smart, Joan Wilson, Ira Adler, Sharon Buckwald, Rebecca Helms, Kathyrn Kerkering, Scott S. MacGilvray, and Peter Resnik. North Carolina Children’s Hospital, Chapel Hill, NC: Carl Bose, Gennie Bose, Lynn A. Fordham, Lisa Bostic, Diane Marshall, Kristi Milowic, and Janice Wereszczak. Helen DeVos Children’s Hospital, Grand Rapids, MI: Mariel Poortenga, Dinah Sutton, Bradford W. Betz, Steven L. Bezinque, Joseph Junewick, Wendy Burdo-Hartman, Lynn Fagerman, Kim Lohr, Steve Pastyrnak, and Dinah Sutton. Sparrow Hospital, Lansing, MI: Carolyn Solomon, Ellen Cavenagh, Victoria J. Caine, Nicholas Olomu, and Joan Price. Michigan State University, East Lansing, MI: Nigel Paneth, Padmani Karna, and Madeleine Lenski. University of Chicago Medical Center, Chicago, IL: Michael D. Schreiber, Grace Yoon, Kate Feinstein, Leslie Caldarelli, Sunila E. O’Connor, Michael Msall, and Susan Plesha-Troyke. William Beaumont Hospital, Royal Oak, MI: Daniel Batton, Beth Kring, Karen Brooklier, Beth Kring, Melisa J. Oca, and Katherine M. Solomon.
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STATEMENT OF FINANCIAL SUPPORT
This study was supported by The National Institute of Neurological Disorders and Stroke (5U01NS040069-05; 2R01NS040069-06A2), the National Institute of Child Health and Human Development (5P30HD018655-28), and the Office of the Director, National Institutes of Health (1UG3OD023348-01).
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Perrin, E., O'Shea, T., Skinner, A. et al. Elevations of inflammatory proteins in neonatal blood are associated with obesity and overweight among 2-year-old children born extremely premature. Pediatr Res 83, 1110–1119 (2018). https://doi.org/10.1038/pr.2017.313
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DOI: https://doi.org/10.1038/pr.2017.313
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