Abstract
Background:
The goal was to identify cytokines associated with necrotizing enterocolitis (NEC). Based on our earlier reports of decreased tissue expression of transforming growth factor (TGF)-β, we hypothesized that infants with NEC also have low blood TGF-β levels. We further hypothesized that because fetal inflammation increases the risk of NEC, infants who develop NEC have elevated blood cytokine levels in early neonatal period.
Methods:
Data on 104 extremely-low-birth-weight infants with NEC and 893 without NEC from 17 centers were analyzed. Clinical information was correlated with blood cytokine levels on postnatal day 1 (D1), D3, D7, D14, and D21.
Results:
Male gender, non-Caucasian/non–African American ethnicity, sepsis, lower blood TGF-β and interleukin (IL)-2 levels, and higher IL-8 levels were associated with NEC. The NEC group had lower TGF-β levels than controls since D1. The diagnosis of NEC was associated with elevated IL-1β, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1/CC-motif ligand-2, macrophage inflammatory protein-1β/CC-motif ligand-3, and C-reactive protein.
Conclusion:
Clinical characteristics, such as gender and ethnicity, and low blood TGF-β levels are associated with higher risk of NEC. Infants who developed NEC did not start with high blood levels of inflammatory cytokines, but these rose mainly after the onset of NEC.
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Acknowledgements
A.M., R.L.S., R.A.D., and W.A.C. conceptualized and designed the study and wrote the manuscript. B.M.-H., A.D., and S.A.M. maintained the database and performed statistical analysis. P.T., K.S., and D.M.H. provided critical expertise on methodological issues. R.D.H. provided critical expertise in study design and execution. All the authors reviewed and approved the manuscript. The following investigators participated in this study: Alan Jobe, University of Cincinnati; William Oh, Abbot R. Laptook, Lewis P. Rubin, Angelita M. Hensman, Brown University; Avroy A. Fanaroff, Michele C. Walsh, Nancy S. Newman, Bonnie S. Siner, Case Western Reserve University; Diana E. Schendel, Centers for Disease Control and Prevention; Edward F. Donovan, Vivek Narendran, Barbara Alexander, Cathy Grisby, Marcia Worley Mersmann, Holly L. Mincey, Jody Hessling, Cincinnati Children’s Hospital Medical Center; Ronald N. Goldberg, C. Michael Cotten, Kathy J. Auten, Duke University; Barbara J. Stoll, Ira Adams-Chapman, Ellen C. Hale, Emory University; Linda L. Wright, Rosemary D. Higgins, Sumner J. Yaffe, Elizabeth M. McClure, Eunice Kennedy Shriver National Institute of Child Health and Human Development; James A. Lemons, Brenda B. Poindexter, Diana D. Appel, Dianne E. Herron, Leslie D. Wilson, Indiana University; W. Kenneth Poole, Abhik Das, Scott A. McDonald, Betty Hastings, Kristin Zaterka-Baxter, Jeanette O’Donnell Auman, RTI International; David K. Stevenson, Krisa P. Van Meurs, M. Bethany Ball, Stanford University; Kristin Skogstrand, David M. Hougaard, Statens Serum Institut; Poul Thorsen, University of Aarhus, Denmark; Namasivayam Ambalavanan, Monica V. Collins, Shirley S. Cosby, University of Alabama at Birmingham; Neil N. Finer, Maynard R. Rasmussen, David Kaegi, Kathy Arnell, Clarence Demetrio, Wade Rich, University of California, San Diego; Charles R. Bauer, Shahnaz Duara, Ruth Everett-Thomas, University of Miami; Lu-Ann Papile, Conra Backstrom Lacy, University of New Mexico; Sheldon B. Korones, Henrietta S. Bada, Tina Hudson, University of Tennessee; Abbot R. Laptook, Walid A. Salhab, R. Sue Broyles, Susie Madison, Jackie F. Hickman, Sally S. Adams, Linda A. Madden, Elizabeth Heyne, Cristin Dooley, University of Texas Southwestern Medical Center at Dallas; Jon E. Tyson, Kathleen Kennedy, Brenda H. Morris, Esther G. Akpa, Patty A. Cluff, Claudia Y. Franco, Anna E. Lis, Georgia E. McDavid, Patti L. Tate, University of Texas Health Science Center at Houston; T. Michael O’Shea, Robert G. Dillard, Lisa K. Washburn, Barbara G. Jackson, Nancy J. Peters, Wake Forest University; G. Ganesh Konduri, Geraldine Muran, Rebecca Bara, Wayne State University; Richard A. Ehrenkranz, Patricia Gettner, Monica Konstantino, Elaine Romano, Yale University. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC), Atlanta, GA.
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Maheshwari, A., Schelonka, R., Dimmitt, R. et al. Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants. Pediatr Res 76, 100–108 (2014). https://doi.org/10.1038/pr.2014.48
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DOI: https://doi.org/10.1038/pr.2014.48
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