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Am J Perinatol 2017; 34(03): 240-247
DOI: 10.1055/s-0036-1585419
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants

Authors

  • Lee A. Denson

    1   Department of Pediatrics, Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio

  • Scott A. McDonald

    2   Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina

  • Abhik Das

    2   Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina

  • Diana E. Schendel

    3   National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia

  • Kristin Skogstrand

    4   Department of Clinical Biochemistry and Immunology, Section of Neonatal Screening and Hormones, Statens Serum Institut, Copenhagen, Denmark

  • David M. Hougaard

    4   Department of Clinical Biochemistry and Immunology, Section of Neonatal Screening and Hormones, Statens Serum Institut, Copenhagen, Denmark

  • Seetha Shankaran

    5   Department of Pediatrics, Neonatal-Perinatal Medicine, Wayne State University, Detroit, Michigan

  • Rosemary D. Higgins

    6   Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland

  • Waldemar A. Carlo

    7   Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama

  • Richard A. Ehrenkranz

    8   Division of Perinatal Medicine, Department of Pediatrics, Yale-New Haven Children's Hospital and the Yale University School of Medicine, New Haven, Connecticut
    • for the Cytokines Study Subcommittee of the NICHD Neonatal Research Network
Further Information

Publication History

15 March 2016

09 June 2016

Publication Date:
25 July 2016 (online)

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Abstract

Objective To determine whether reduced growth velocity (GV) in extremely low birth weight infants is preceded by elevated inflammatory cytokines.

Study Design GV was determined at 36 weeks' postmenstrual age (PMA) in 768 infants 401 to 1,000 g birth weight (BW). Association between blood cytokines measured through day of life 21 and GV was explored using linear regression models that adjusted for late-onset sepsis (LOS), BW, small for gestational age (SGA), gender, race, energy intake, and center.

Results Serum interleukin-6 (IL-6) was increased at days 14 and 21 in LOS infants. LOS was associated with reduced energy intake and GV for weight (weight-GV) at 36 weeks' PMA. Linear regression analysis controlling for LOS and energy intake showed significant relationships between increased IL-6 at days 14 and 21 with reduced weight-GV at 36 weeks' PMA (p < 0.0001). The relationship between day 21 IL-6 and weight-GV was not associated with LOS (p = 0.12) when controlling for BW and energy intake. Both BW (p = 0.02) and energy intake (p = 0.003) influenced the relationship between day 14 IL-6 and weight-GV.

Conclusion IL-6 elevation during the first month of life is associated with lower weight-GV at 36 weeks' PMA and may have a direct effect upon energy balance and postnatal growth.

Keywords

cytokines - growth retardation - growth velocity - preterm infant - sepsis

Funding

The authors have no financial arrangement(s) with a company whose product figures prominently in the submitted manuscript or with a company making a competing product.


The study was supported by United States Public Health Service grants to the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network and NIH grant R01 DK058259 to Dr. Denson.


The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Centers for Disease Control and Prevention provided grant support for recruitment for 1999–2001 and data analysis for the Neonatal Research Network's Cytokines Study. In addition, Dr. Denson received support from National Institutes of Health through grant R01 DK058259. The funding agencies provided overall oversight for study conduct, but all data analyses and interpretation were independent of the funding agencies. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study.


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