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.

  • Article
  • Published:

Effect of fluctuation of oxygenation on the development of severe retinopathy of prematurity in extremely preterm infants

Journal of Perinatology volume 40, pages 515–521 (2020)Cite this article

Subjects

Abstract

Objective

To investigate factors associated with development of severe retinopathy of prematurity (ROP) in extremely preterm (EP) infants.

Study design

This retrospective cohort study included 213 EP infants (22 + 0 to 27 + 6 weeks gestation) who were admitted to the neonatal intensive care unit of Osaka Women’s and Children’s Hospital between 2009 and 2017. Multivariable logistic regression analysis was used to identify neonatal factors associated with severe ROP requiring treatment.

Result

After adjustments for gestational age (GA), birth weight, sex, red blood cell transfusion, average SpO2, and fluctuations of SpO2 from birth to 32 weeks postmenstrual age, fluctuations of SpO2 (odds ratio [OR]: 2.10, 95% confidence interval [CI]: 1.03–4.27), and low GA (OR: 0.95, 95% CI: 0.91–0.98) were significantly associated with severe ROP.

Conclusions

Fluctuations of SpO2 from birth to 32 weeks postmenstrual age and low GA were significantly associated with development of severe ROP requiring treatment in EP 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

Fig. 1

Similar content being viewed by others

References

  1. Kono Y, Mishina J, Yonemoto N, Kusuda S, Fujimura M. Neonatal correlates of adverse outcomes in very low-birthweight infants in the NICU Network. Pediatr Int. 2011;53:930–5.

    Article  PubMed  Google Scholar 

  2. Takeuchi A, Koeda T, Takayanagi T, Sato K, Sugino N, Bonno M, et al. Reading difficulty in school-aged very low birth weight infants in Japan. Brain Dev. 2016;38:800–6.

    Article  PubMed  Google Scholar 

  3. Molloy CS, Anderson PJ, Anderson VA, Doyle LW. The long-term outcome of extremely preterm (<28 weeks' gestational age) infants with and without severe retinopathy of prematurity. J Neuropsychol. 2016;10:276–94.

    Article  PubMed  Google Scholar 

  4. Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N. Engl J Med. 2012;367:2515–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chan-Ling T, C B, Stone J. The effect of oxygen on vasoformative cell division: evidence that ‘physiological hypoxia’ is the stimulus for normal retinal vasculogenesis. Investig Ophthalmol Vis Sci. 1995;36:1201–14.

    CAS  Google Scholar 

  6. Tin W, Milligan DW, Pennefather P, Hey E. Pulse oximetry, severe retinopathy, and outcome at one year in babies of less than 28 weeks gestation. Arch Dis Child Fetal Neonatal Ed. 2001;84:F106–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Noori S, Patel D, Friedlich P, Siassi B, Seri I, Ramanathan R. Effects of low oxygen saturation limits on the ductus arteriosus in extremely low birth weight infants. J Perinatol. 2009;29:553–7.

    Article  CAS  PubMed  Google Scholar 

  8. Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, et al. Target ranges of oxygen saturation in extremely preterm infants. N. Engl J Med. 2010;362:1959–69.

    Article  CAS  PubMed  Google Scholar 

  9. Tarnow-Mordi WO, Darlow B, Doyle L. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010;363:1285.

    Article  CAS  PubMed  Google Scholar 

  10. Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR, et al. Early CPAP versus surfactant in extremely preterm infants. N. Engl J Med. 2010;362:1970–9.

    Article  CAS  PubMed  Google Scholar 

  11. Stenson B, Brocklehurst P, Tarnow-Mordi W. Increased 36-week survival with high oxygen saturation target in extremely preterm infants. N Engl J Med. 2011;364:1680–2.

    Article  CAS  PubMed  Google Scholar 

  12. Penn JS, Henry MM, Tolman BL. Exposure to alternating hypoxia and hyperoxia causes severe proliferative retinopathy in the newborn rat. Pediatr Res. 1994;36:724–31.

    Article  CAS  PubMed  Google Scholar 

  13. Michaelson IC. The mode of development of the vascular system of the retina, with some observations on its significance for certain retinal diseases. Trans Ophthalmol Soc UK. 1948;68:137–80.

    Google Scholar 

  14. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–34.

    Article  CAS  PubMed  Google Scholar 

  15. International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123:991–9.

    Article  Google Scholar 

  16. Early Treatment For Retinopathy Of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol. 2003;121:1684–94.

    Article  Google Scholar 

  17. Kim SJ, Port AD, Swan R, Campbell JP, Chan RVP, Chiang MF. Retinopathy of prematurity: a review of risk factors and their clinical significance. Surv Ophthalmol. 2018;63:618–37.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Siswanto JE, Ronoatmodjo S, Adisasmita A, Soemantri A, Sitorus RS, Sauer PJJ. Risk factors for the development and progression of retinopathy of prematurity in preterm infants in Indonesia. J Neonatal Perinatal Med. 2019. https://doi.org/10.3233/NPM-190233.

  19. Anderson CG, Benitz WE, Madan A. Retinopathy of prematurity and pulse oximetry: a national survey of recent practices. J Perinatol. 2004;24:164–8.

    Article  PubMed  Google Scholar 

  20. Supplemental therapeutic oxygen for prethreshold retinopathy of 375 prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics. 2000;105:295–310.

  21. Patz AEA, Eastham A, Higginbotham DH, Kleh T. Oxygen studies in retrolental fibroplasia. Am J Ophthalmol. 1953;36:1511–22.

    Article  CAS  PubMed  Google Scholar 

  22. Ashton NWB, Serpell G. Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasia. Br J ophthalmol. 1954;38:397–432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Saito Y, Omoto T, Cho Y, Hatsukawa Y, Fujimura M, Takeuchi T. The progression of retinopathy of prematurity and fluctuation in blood gas tension. Graefes Arch Clin Exp Ophthalmol. 1993;231:151–6.

    Article  CAS  PubMed  Google Scholar 

  24. York JR, Landers S, Kirby RS, Arbogast PG, Penn JS. Arterial oxygen fluctuation and retinopathy of prematurity in very-low-birth-weight infants. J Perinatol. 2004;24:82–87.

    Article  PubMed  Google Scholar 

  25. Biglan AW, Brown DR, Reynolds JD, Milley JR. Risk factors associated with retrolental fibroplasia. Ophthalmology. 1984;91:1504–11.

    Article  CAS  PubMed  Google Scholar 

  26. Katzman G, Satish M, Krishnan V. Hypoxemia and retinopathy of prematurity. Pediatrics. 1987;80:972.

    CAS  PubMed  Google Scholar 

  27. Cunningham S, Fleck BW, Elton RA, McIntosh N. Transcutaneous oxygen levels in retinopathy of prematurity. Lancet. 1995;346:1464–5.

    Article  CAS  PubMed  Google Scholar 

  28. Das A, Mhanna M, Sears J, Houdek JW, Kumar N, Gunzler D, et al. Effect of fluctuation of oxygenation and time spent in the target range on retinopathy of prematurity in extremely low birth weight infants. J Neonatal Perinat Med. 2018;11:257–63.

    Article  CAS  Google Scholar 

  29. Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu VK, et al. A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr. 2010;157:69–73.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gunn TR, Easdown J, Outerbridge EW, Aranda JV. Risk factors in retrolental fibroplasia. Pediatrics. 1980;65:1096–1100.

    CAS  PubMed  Google Scholar 

  31. Pillekamp F, Hermann C, Keller T, von Gontard A, Kribs A, Roth B. Factors influencing apnea and bradycardia of prematurity - implications for neurodevelopment. Neonatology. 2007;91:155–61.

    Article  CAS  PubMed  Google Scholar 

  32. Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, et al. Association between intermittent hypoxemia or bradycardia and late death or disability in extremely preterm infants. Jama. 2015;314:595–603.

    Article  CAS  PubMed  Google Scholar 

  33. Di Fiore JM, Martin RJ, Li H, Morris N, Carlo WA, Finer N, et al. Patterns of oxygenation, mortality, and growth status in the surfactant positive pressure and oxygen trial cohort. J Pediatr. 2017. https://doi.org/10.1016/j.jpeds.2017.01.057.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Raffay TM, Dylag AM, Sattar A, Abu Jawdeh EG, Cao S, Pax BM, et al. Neonatal intermittent hypoxemia events are associated with diagnosis of bronchopulmonary dysplasia at 36 weeks postmenstrual age. Pediatr Res. 2019;85:318–23.

    Article  PubMed  Google Scholar 

  35. Di Fiore JM, Dylag AM, Honomichl RD, Hibbs AM, Martin RJ, Tatsuoka C, et al. Early inspired oxygen and intermittent hypoxemic events in extremely premature infants are associated with asthma medication use at 2 years of age. J Perinatol. 2019;39:203–11.

    Article  PubMed  Google Scholar 

  36. McGregor ML, Bremer DL, Cole C, McClead RE, Phelps DL, Fellows RR, et al. Retinopathy of prematurity outcome in infants with prethreshold retinopathy of prematurity and oxygen saturation >94% in room air: the high oxygen percentage in retinopathy of prematurity study. Pediatrics. 2002;110:540–4.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Drs Masashi Hotta, Yasuka Kimoto, Eriko Iwasaki, Makoto Tamura, Kazue Morikawa, Natsuko Yamamichi, and the medical staff working in the neonatal intensive care unit at Osaka Women’s and Children’s Hospital for their support during this study. We thank Ryan Chastain-Gross, Ph.D., from Edanz Group (https://en-author-services.edanzgroup.com) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Neonatal Medicine, Osaka Women’s and Children’s Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan

    Yousuke Imanishi, Katsuya Hirata, Masatoshi Nozaki, Narutaka Mochizuki, Shinya Hirano & Kazuko Wada

  2. Department of Ophthalmology, Osaka Women’s and Children’s Hospital, Izumi, Osaka, Japan

    Yoko Fukushima & Yoshikazu Hatsukawa

Authors
  1. Yousuke Imanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katsuya Hirata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masatoshi Nozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Narutaka Mochizuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shinya Hirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoko Fukushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoshikazu Hatsukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazuko Wada
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YI and KH conceptualized and designed the study, contributed to data analysis, and drafted the manuscript. MN, NM, SH, YF, YH, and KW reviewed results and gave conceptual suggestions. All authors reviewed the draft manuscript and approved the final manuscript.

Corresponding author

Correspondence to Katsuya Hirata.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Imanishi, Y., Hirata, K., Nozaki, M. et al. Effect of fluctuation of oxygenation on the development of severe retinopathy of prematurity in extremely preterm infants. J Perinatol 40, 515–521 (2020). https://doi.org/10.1038/s41372-019-0571-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-019-0571-y

This article is cited by

Search

Advanced search

Quick links