Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Does Elevated Peak Bilirubin Protect from Retinopathy of Prematurity in Very Low Birthweight Infants

Journal of Perinatology volume 23, pages 208–211 (2003)Cite this article

Abstract

OBJECTIVE: Bilirubin is a potent in vitro antioxidant. Despite repeated study, its in vivo significance has yet to be defined. Bilirubin is universally elevated in very low birthweight (VLBW) infants. Retinopathy of prematurity (ROP) is a disease thought to be associated with exposure to oxygen free radicals in VLBW infants. The objective of this study was to determine whether there was an association between peak bilirubin levels and ROP.

METHODS: The risk for ROP, stages III and IV was measured as a function of increasing peak bilirubin levels in VLBW infants admitted to the neonatal ICU. A similar analysis was performed on a subgroup of VLBW infants with prolonged (≥28 days) oxygen requirement. The relation between peak bilirubin level and the duration of oxygen requirement was tested by logistic regression analysis. All analyses were conducted after controlling for birthweight and presence of intraventricular hemorrhage (IVH).

RESULTS: There was an increased risk for ROP, stages III and IV (OR 1.187; 95% CI 1.013 to 1.390; p=0.034) with elevated peak serum bilirubin levels in the entire population. Duration of oxygen requirement was not related to peak bilirubin (p>0.1). In the subgroup of infants with prolonged oxygen requirement (≥28 days), there was no association between peak serum bilirubin levels and ROP III and IV (p>0.1); however, there was an association with further increased duration of oxygen requirement (p=0.034).

CONCLUSION: Elevated peak bilirubin does not protect from and may be a risk for ROP in VLBW infants.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN . Bilirubin is an antioxidant of possible physiologic importance. Science 1987;71:233–238.

    Google Scholar 

  2. Kozaki N, Shimizu S, Chijiiwa K, et al. Bilirubin as an anti-oxidant for surgical stress: a preliminary report of bilirubin oxidative metabolites. HPB Surg 1999;11(4):241–248.

    Article  CAS  Google Scholar 

  3. Dennery PA, McDonagh AF, Spitz DR, Rodgers PA, Stevenson DK . Hyperbilirubinemia results in reduced injury in neonatal Gunn rats exposed to hyperoxia. Free Radical Biol and Med 1995;19:395–404.

    Article  CAS  Google Scholar 

  4. Hegyi T, Goldie E, Hiatt M . The protective role of bilirubin in oxygen-radical diseases of the preterm infant. J Perinatol 1994;XIV:296–300.

    Google Scholar 

  5. Yeo KL, Perlman M, Yong H, Mullaney P . Outcomes of extremely premature infants related to their peak serum bilirubin concentrations and exposure to phototherapy. Pediatrics 1998;102:1426–1431.

    Article  CAS  Google Scholar 

  6. Benaron DA, Bowen FW . Variation of initial serum bilirubin rise in newborn infants with type of illness. Lancet 1991;338:78–91.

    Article  CAS  Google Scholar 

  7. Heyman E, Ohlsson A, Girschek P . Retinopathy of prematurity and bilirubin. N Eng J Med 1989;320:256.

    CAS  Google Scholar 

  8. Fauchere JC, Meier-Gibbons FE, Koerner F, Bossi E . Retinopathy of pre maturity and bilirubin — no clinical evidence for a beneficial role of bilirubin as a physiological anti-oxidant. Eur J Pediatr 1994;153:358–362.

    Article  CAS  Google Scholar 

  9. Gaton DD, Gold J, Axer-Siegel R, Wielunsky E, Naor N, Nissenkorn I . Evaluation of bilirubin as possible protective factor in the prevention of retinopathy of prematurity. Br J Ophthalmol 1994;75:532–534.

    Article  Google Scholar 

  10. DeJonge MH, Khuntia A, Maisels MJ, Bandagi A . Bilirubin levels and severe retinopathy of prematurity in infants with estimated gestational ages of 23 to 26 weeks. J Pediatr 1999;135:102–104.

    Article  CAS  Google Scholar 

  11. Drury JA, Nycyk JA, Baines M, Cooke RW . Does total antioxidant status relate to outcome in very preterm infants? Clin Sci 1998;94(2):197–201.

    Article  CAS  Google Scholar 

  12. Romeo MG, Tina LG, Scuderi A, Di Pietro M, Caracciolo M, Distefano G . Variations of blood bilirubin levels in the newborn with and without retinopathy of prematurity (ROP). Pediatr Med Chir 1994;16:59–62.

    CAS  PubMed  Google Scholar 

  13. Teng RJ, Wu TJ, Yau KI . Retinopathy of prematurity in very-low-birthweight neonates: Epidemiology and risk factors. Chung-Hua Min Kuo Hsiao Erh Ko i Hsueh Hui Tsa Chih 1997;38(5):370–374.

    CAS  PubMed  Google Scholar 

  14. Epstein MF, Leviton A, Kuban KCK, et al. Bilirubin, intraventricular hemorrhage, and phenobarbital in very low birth weight babies. Pediatrics 1988;82:350–354.

    CAS  PubMed  Google Scholar 

  15. Kohelet D, Goldberg M, Arbel E . Factors affecting plasma bilirubin in preterm infants ventilated for respiratory distress syndrome. J Perinatol 2000;5:285–287.

    Article  Google Scholar 

  16. Dennery PA, Rodgers PA, Lum Melissa A, Jennings BC, Shokoohi V . Pediatr Res. 1996;40:815–821.

    Article  CAS  Google Scholar 

  17. Hommura S, Usuki Y, Takei K, et al. Ophthalmic care of very low birth weight infants, report 4: clinical studies of the influence of light on the incidence of ROP. Nippon Ganka Gakkai Zasshi. 1998;92:456.

    Google Scholar 

  18. Glass P, Avery GB, Subramanian KNS, Keys MP, Sostek AM, Friendly DS . Effects of bright light in the hospital nursery on the incidence of retinopathy of prematurity. N Engl J Med. 1985;313:401–404.

    Article  CAS  Google Scholar 

  19. Reynolds JD, Hardy RJ, Kennedy KA, Spencer R, van Heuven WAJ, Fielder AR . Lack of efficacy of light reduction in preventing retinopathy of prematurity. N Engl J Med. 1998;338:1572–1576.

    Article  CAS  Google Scholar 

  20. Ackerman B, Sherwonit E, Williams J . Reduced incidental light exposure: effect on the development of retinopathy of prematurity in low birth weight infants. Pediatrics 1989;83:958–962.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We express our deep appreciation to Cheng Shao, MD, MPH at the Children's Research Institution for her help with the statistical analysis.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Children's National Medical Center, Washington, DC, USA

    Joshua D Milner MD

  2. Department of Neonatology, Children's National Medical Center, Washington, DC, USA

    Hany Z Aly MD

  3. Department of Newborn Services, George Washington University Medical Center, Washington, DC, USA

    Hany Z Aly MD, Laura B Ward MD & Ayman El-Mohandes MD, MPH

Authors
  1. Joshua D Milner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hany Z Aly MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura B Ward MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ayman El-Mohandes MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Milner, J., Aly, H., Ward, L. et al. Does Elevated Peak Bilirubin Protect from Retinopathy of Prematurity in Very Low Birthweight Infants. J Perinatol 23, 208–211 (2003). https://doi.org/10.1038/sj.jp.7210887

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jp.7210887

This article is cited by

Search

Advanced search

Quick links