Abstract
Fetal and neonatal inflammation is associated with several morbidities of prematurity. Its relationship to retinopathy of prematurity (ROP) has not been investigated. Our objective was to determine the relationship between cytokine levels and ROP in the first 3 postnatal wks. Data for this study were derived from the NICHD Cytokine Study. Dried blood spots (DBS) were obtained from infants <1000 g on days 0–1, 3 ± 1, 7 ± 2, 14 ± 3, and 21 ± 3. Infants were classified into three groups—no, mild, and severe ROP. Multiplex Luminex assay was used to quantify 20 cytokines. Temporal profiles of cytokines were evaluated using mixed-effects models after controlling for covariates. Of 1074 infants enrolled, 890 were examined for ROP and 877 included in the analysis. ROP was associated with several clinical characteristics on unadjusted analyses. Eight cytokines remained significantly different across ROP groups in adjusted analyses. IL-6 and IL-17 showed significant effects in early time periods (D0–3); TGF-β, brain-derived neurotrophic factor (BDNF), and regulated on activation, normal T cell expressed and secreted (RANTES) in later time periods (D7–21) and IL-18, C-reactive protein (CRP), and neurotrophin-4 (NT-4) in both early and later time periods. We conclude that perinatal inflammation may be involved in the pathogenesis of ROP.
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Abbreviations
- BDNF:
-
brain-derived neurotrophic factor
- CRP:
-
C-reactive protein
- FIRS:
-
fetal inflammatory response syndrome
- GM-CSF:
-
granulocyte-macrophage colony-stimulating factor
- IVH:
-
intraventricular hemorrhage
- MCP-1:
-
monocyte chemoattractant protein-1
- MIP-1α:
-
macrophage inflammatory protein-1α
- MMP-9:
-
matrix metalloproteinase-9
- NEC:
-
necrotizing enterocolitis
- NT-4:
-
neurotrophin-4
- PVL:
-
periventricular leukomalacia
- RANTES:
-
regulated upon activation, normal T cell expressed and secreted
- ROP:
-
retinopathy of prematurity
- sIL-6R:
-
soluble IL-6 receptor
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Supported by The National Institutes of Health (General Clinical Research Center grants M01 RR30, M01 RR32, M01 RR39, M01 RR70, M01 RR80, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01 RR7122, M01 RR8084, and M01 RR16587), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grants U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34216, U10 HD40461, U10 HD40492, U10 HD40498, and U10 HD40689), and the Centers for Disease Control and Prevention (Interagency Agreement Y1-HD-5000-01) provided grant support for recruitment for 1999–2001 and data analysis for the Neonatal Research Network's Cytokines Study. The funding agencies provided overall oversight for study conduct, but all data analyses and interpretation were independent of the funding agencies.
Presented, in part, at the Pediatric Academic Societies' Annual Meeting on May 4, 2008 at Honolulu, Hawaii.
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.
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Sood, B., Madan, A., Saha, S. et al. Perinatal Systemic Inflammatory Response Syndrome and Retinopathy of Prematurity. Pediatr Res 67, 394–400 (2010). https://doi.org/10.1203/PDR.0b013e3181d01a36
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DOI: https://doi.org/10.1203/PDR.0b013e3181d01a36
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