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.

Identification of clinical factors associated with timing and duration of spontaneous regression of retinopathy of prematurity not requiring treatment

Journal of Perinatology volume 43, pages 702–708 (2023)Cite this article

Subjects

Abstract

Objective

Identify clinical factors that delay or prolong spontaneous regression of retinopathy of prematurity (ROP).

Study design

Secondary analysis of three prospective studies with 76 infants with ROP not requiring treatment, born ≤30 weeks postmenstrual age (PMA) and ≤1500 grams. Outcomes were PMA at greatest severity of ROP (PMA MSROP), at which regression began, at time of complete vascularization (PMA CV), and regression duration. Pearson’s correlation coefficients, t-tests, or analyses of variance were calculated.

Results

Increased positive bacterial cultures, hyperglycemia, transfusion volume of platelets and red blood cells and severity of ROP were associated with later PMA MSROP. Positive bacterial cultures, maternal chorioamnionitis, and less iron deficiency were associated with later PMA CV and prolonged regression duration. Slower length gain was associated with later PMA CV. P < 0.05 for all.

Conclusions

Preterm infants with inflammatory exposures or linear growth impairment may require longer surveillance for ROP resolution and complete vascularization.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

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

Fig. 1: Research subject flow diagram.

Data availability

The dataset generated during this study is available from the corresponding author on reasonable request.

References

  1. Binenbaum G, Bell EF, Donohue P, Quinn G, Shaffer J, Tomlinson LA, et al. Development of modified screening criteria for retinopathy of prematurity: primary results from the postnatal growth and retinopathy of prematurity study. JAMA Ophthalmol. 2018;136:1034–40.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Khan SI, Ryu WY, Wood EH, Moshfeghi DM, Shah JK, Lambert SR. Retinopathy of prematurity treatment trends from 2003 to 2020 in the United States. Ophthalmology. 2022;129:1216–8.

    Article  PubMed  Google Scholar 

  3. Repka MX, Palmer EA, Tung B. Involution of retinopathy of prematurity. cryotherapy for retinopathy of prematurity cooperative group. Arch Ophthalmol. 2000;118:645–9.

    Article  CAS  PubMed  Google Scholar 

  4. Ni YQ, Huang X, Xue K, Yu J, Ruan L, Shan HD, et al. Natural involution of acute retinopathy of prematurity not requiring treatment: factors associated with the time course of involution. Invest Ophthalmol Vis Sci. 2014;55:3165–70.

    Article  PubMed  Google Scholar 

  5. Eliason KJ, Dane Osborn J, Amsel E, Richards SC. Incidence, progression, and duration of retinopathy of prematurity in Hispanic and white non-Hispanic infants. J AAPOS. 2007;11:447–51.

    Article  PubMed  Google Scholar 

  6. Ju RH, Zhang JQ, Ke XY, Lu XH, Liang LF, Wang WJ. Spontaneous regression of retinopathy of prematurity: incidence and predictive factors. Int J Ophthalmol. 2013;6:475–80.

    PubMed  PubMed Central  Google Scholar 

  7. Yum HR, Park SH. Clinical features of premature twin babies with intersibling asymmetry of retinopathy of prematurity severity. Can J Ophthalmol. 2022;57:337–43.

    Article  PubMed  Google Scholar 

  8. Wang L, Li M, Zhu J, Yan H, Wu L, Fan J, et al. Clinical features of spontaneous regression of retinopathy of prematurity in China: a 5-year retrospective case series. Front Med (Lausanne). 2021;8:731421.

    Article  PubMed  Google Scholar 

  9. Wu C, Löfqvist C, Smith LE, VanderVeen DK, Hellström A, Consortium W. Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants: a multicenter study analyzing weight velocity deviations for the prediction of retinopathy of prematurity. Arch Ophthalmol. 2012;130:992–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Belfort MB, Ramel SE, Martin CR, Fichorova R, Kuban KCK, Heeren T, et al. Systemic inflammation in the first 2 weeks after birth as a determinant of physical growth outcomes in hospitalized infants with extremely low gestational age. J Pediatr. 2022;240:37–43.e1.

    Article  CAS  PubMed  Google Scholar 

  11. Ramel SE, Demerath EW, Gray HL, Younge N, Boys C, Georgieff MK. The relationship of poor linear growth velocity with neonatal illness and two-year neurodevelopment in preterm infants. Neonatology. 2012;102:19–24.

    Article  PubMed  Google Scholar 

  12. Scheurer JM, Gray HL, Demerath EW, Rao R, Ramel SE. Diminished growth and lower adiposity in hyperglycemic very low birth weight neonates at 4 months corrected age. J Perinatol. 2016;36:145–50.

    Article  CAS  PubMed  Google Scholar 

  13. Ingolfsland EC, Haapala JL, Buckley LA, Demarath EW, Guiang SF, Ramel SE. Late growth and changes in body composition influence odds of developing retinopathy of prematurity among preterm infants. Nutrients. 2019;12:78.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Morris EE, Miller NC, Marka NA, Super JL, Nagel EM, Gonzalez JD, et al. Randomized trial of early enhanced parenteral nutrition and later neurodevelopment in preterm infants. Nutrients. 2022;14:3890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723–9.

    Article  CAS  PubMed  Google Scholar 

  16. Fierson WM, Ophthalmology AAOPSo, OPHTHALMOLOGY AAO, STRABISMUS AAFPOA, ORTHOPTISTS AAOC. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2018;142:e20183061.

    Article  PubMed  Google Scholar 

  17. Good WV, Hardy RJ, Dobson V, Palmer EA, Phelps DL, Quintos M, et al. The incidence and course of retinopathy of prematurity: findings from the early treatment for retinopathy of prematurity study. Pediatrics. 2005;116:15–23.

    Article  PubMed  Google Scholar 

  18. Good WV, Group ETfRoPC. Final results of the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial. Trans Am Ophthalmol Soc. 2004;102:233–48. discussion 48-50

    PubMed  PubMed Central  Google Scholar 

  19. Quinn GE, Ying GS, Bell EF, Donohue PK, Morrison D, Tomlinson LA, et al. Incidence and early course of retinopathy of prematurity: secondary analysis of the postnatal growth and retinopathy of prematurity (G-ROP) study. JAMA Ophthalmol. 2018;136:1383–9.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wang X, Tang K, Chen L, Cheng S, Xu H. Association between sepsis and retinopathy of prematurity: a systematic review and meta-analysis. BMJ Open. 2019;9:e025440.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Darlow BA, Hutchinson JL, Henderson-Smart DJ, Donoghue DA, Simpson JM, Evans NJ, et al. Prenatal risk factors for severe retinopathy of prematurity among very preterm infants of the Australian and New Zealand Neonatal Network. Pediatrics. 2005;115:990–6.

    Article  PubMed  Google Scholar 

  22. Brooks SE, Marcus DM, Gillis D, Pirie E, Johnson MH, Bhatia J. The effect of blood transfusion protocol on retinopathy of prematurity: a prospective, randomized study. Pediatrics. 1999;104:514–8.

    Article  CAS  PubMed  Google Scholar 

  23. Satrom KM, Ennis K, Sweis BM, Matveeva TM, Chen J, Hanson L, et al. Neonatal hyperglycemia induces CXCL10/CXCR3 signaling and microglial activation and impairs long-term synaptogenesis in the hippocampus and alters behavior in rats. J Neuroinflammation. 2018;15:82.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sun Q, Li J, Gao F. New insights into insulin: The anti-inflammatory effect and its clinical relevance. World J Diabetes. 2014;5:89–96.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Goldstein GP, Leonard SA, Kan P, Koo EB, Lee HC, Carmichael SL. Prenatal and postnatal inflammation-related risk factors for retinopathy of prematurity. J Perinatol. 2019;39:964–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jiang S, Yang Z, Shan R, Zhang Y, Yan W, Yang Y, et al. Neonatal outcomes following culture-negative late-onset sepsis among preterm infants. Pediatr Infect Dis J. 2020;39:232–8.

    Article  PubMed  Google Scholar 

  27. Kim CY, Jung E, Kim EN, Kim CJ, Lee JY, Hwang JH, et al. Chronic placental inflammation as a risk factor of severe retinopathy of prematurity. J Pathol Transl Med. 2018;52:290–7.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lynch AM, Berning AA, Thevarajah TS, Wagner BD, Post MD, McCourt EA, et al. The role of the maternal and fetal inflammatory response in retinopathy of prematurity. Am J Reprod Immunol. 2018;80:e12986.

    Article  PubMed  Google Scholar 

  29. Pfister KM, Ramel SE. Linear growth and neurodevelopmental outcomes. Clin Perinatol. 2014;41:309–21.

    Article  PubMed  Google Scholar 

  30. Belfort MB, Rifas-Shiman SL, Sullivan T, Collins CT, McPhee AJ, Ryan P, et al. Infant growth before and after term: effects on neurodevelopment in preterm infants. Pediatrics. 2011;128:e899–906.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Belfort MB, Rifas-Shiman SL, Kleinman KP, Guthrie LB, Bellinger DC, Taveras EM, et al. Infant feeding and childhood cognition at ages 3 and 7 years: Effects of breastfeeding duration and exclusivity. JAMA Pediatr. 2013;167:836–44.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Latal-Hajnal B, von Siebenthal K, Kovari H, Bucher HU, Largo RH. Postnatal growth in VLBW infants: significant association with neurodevelopmental outcome. J Pediatr. 2003;143:163–70.

    Article  PubMed  Google Scholar 

  33. Silveira RC, Fortes Filho JB, Procianoy RS. Assessment of the contribution of cytokine plasma levels to detect retinopathy of prematurity in very low birth weight infants. Invest Ophthalmol Vis Sci. 2011;52:1297–301.

    Article  CAS  PubMed  Google Scholar 

  34. Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ. Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem. 1996;271:736–41.

    Article  CAS  PubMed  Google Scholar 

  35. Lee J, Dammann O. Perinatal infection, inflammation, and retinopathy of prematurity. Semin Fetal Neonatal Med. 2012;17:26–9.

    Article  PubMed  Google Scholar 

  36. Rao R, Georgieff MK. Perinatal aspects of iron metabolism. Acta Paediatr Suppl. 2002;91:124–9.

    Article  CAS  PubMed  Google Scholar 

  37. Fortes Filho JB, Bonomo PP, Maia M, Procianoy RS. Weight gain measured at 6 weeks after birth as a predictor for severe retinopathy of prematurity: study with 317 very low birth weight preterm babies. Graefes Arch Clin Exp Ophthalmol. 2009;247:831–6.

    Article  PubMed  Google Scholar 

  38. Lundgren P, Stoltz Sjöström E, Domellöf M, Källen K, Holmström G, Hård AL, et al. WINROP identifies severe retinopathy of prematurity at an early stage in a nation-based cohort of extremely preterm infants. PLoS One. 2013;8:e73256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Arthur CM, Nalbant D, Feldman HA, Saeedi BJ, Matthews J, Robinson BS, et al. Anemia induces gut inflammation and injury in an animal model of preterm infants. Transfusion. 2019;59:1233–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Singh G, Wallin DJ, Abrahante Lloréns JE, Tran PV, Feldman HA, Georgieff MK, et al. Dose- and sex-dependent effects of phlebotomy-induced anemia on the neonatal mouse hippocampal transcriptome. Pediatr Res. 2022;92:712–20.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Cao JH, Wagner BD, McCourt EA, Cerda A, Sillau S, Palestine A, et al. The Colorado-retinopathy of prematurity model (CO-ROP): postnatal weight gain screening algorithm. J AAPOS. 2016;20:19–24.

    Article  PubMed  Google Scholar 

  42. Nagurney JT, Brown DF, Sane S, Weiner JB, Wang AC, Chang Y. The accuracy and completeness of data collected by prospective and retrospective methods. Acad Emerg Med. 2005;12:884–95.

    Article  PubMed  Google Scholar 

Download references

Funding

The Clinical and Translational Science Institute2 at the University of MN is supported by the National Institutes of Health’s National Center for Advancing Translational Sciences, grant UL1TR002494 (author SL).

Author information

Author notes

  1. These authors contributed equally: Jamee Schoephoerster, Sydney Roston.

Authors and Affiliations

  1. University of Minnesota Medical School, Minneapolis, MN, USA

    Jamee Schoephoerster & Sydney Roston

  2. Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN, USA

    Scott Lunos

  3. Department of Pediatrics, Division of Neonatology, University of Minnesota, Minneapolis, MN, USA

    Sara E. Ramel, Michael K. Georgieff & Ellen C. Ingolfsland

  4. Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA

    Jill Anderson

Authors
  1. Jamee Schoephoerster
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sydney Roston
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott Lunos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sara E. Ramel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jill Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael K. Georgieff
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ellen C. Ingolfsland
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JS and SR performed the investigation, contributed to the data analysis, and wrote the initial draft. SL designed the methodology, performed the formal data analysis, and edited the final manuscript. SR conceptualized the study, performed the investigation, provided resources and supervision, and edited the final manuscript. MG conceptualized the study, provided supervision, and edited the final manuscript. JA conceptualized the study and defined the methodology, provided supervision, and wrote and edited the manuscript. EI conceptualized the study, developed the methodology, curated the data, provided supervision, and drafted and edited the manuscript.

Corresponding author

Correspondence to Ellen C. Ingolfsland.

Ethics declarations

Competing interests

This sponsor had no role in the study design, data collection, analysis, or interpretation, writing of the report, or decision to submit for publication. There are no other competing financial interests in relation to the work described.

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

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schoephoerster, J., Roston, S., Lunos, S. et al. Identification of clinical factors associated with timing and duration of spontaneous regression of retinopathy of prematurity not requiring treatment. J Perinatol 43, 702–708 (2023). https://doi.org/10.1038/s41372-023-01649-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-023-01649-w

Search

Advanced search

Quick links