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:

Cumulative illness severity and progression from moderate to severe retinopathy of prematurity

Journal of Perinatology volume 27, pages 502–509 (2007)Cite this article

Abstract

Objective:

To test cumulative neonatal illness severity (IS) and IS fluctuation as predictors of progression from moderate to severe retinopathy of prematurity (ROP).

Methods:

Data from research databases and medical record review were collected for infants from four neonatal intensive care unit (NICUs) admitted between 1995 and 2001 and diagnosed with prethreshold ROP. Cumulative neonatal IS measured using daily Scores for Neonatal Acute Physiology (SNAP) for the first 28 days of life, and IS fluctuation as assessed by summing changes between daily SNAP scores, were tested as predictors of progression to threshold ROP using logistic regression.

Results:

Infants progressing to threshold (n=79), compared to those not progressing to threshold (n=130), had significantly (P<0.05) lower gestational ages (25.2±1.1 versus 25.8±1.4 weeks), higher cumulative neonatal SNAP (255±77 versus 224±63 weeks) and had more severe hospitalizations as indicated by diagnoses and medical management. In regression analysis, gestational age, chronological age and presence of plus disease at first diagnosis of prethreshold were associated with development of threshold. After adjusting for these factors, cumulative neonatal SNAP was significantly associated with progression to threshold. However, addition of cumulative SNAP to the model only increased receiver-operating characteristic curve area from 0.77 to 0.78 (NS). Other factors, including SNAP fluctuation, were not associated with progression to threshold after adjustment using this model.

Conclusions:

Cumulative neonatal IS, as measured by cumulative SNAP, is an independent risk factor for progression from moderate to severe ROP. However, cumulative IS does not enhance assessment of risk for ROP progression after adjusting for simpler clinical factors.

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

Figure 1

Similar content being viewed by others

Article 16 February 2023

Evdokia Dimitriadis, Daniel L. Rolnik, … Ellen Menkhorst

References

  1. Good W, Hardy R, Dobson V, Palmer E, Phelps D, 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 

  2. Phelps DL . Retinopathy of prematurity. Pediatr Clin North Am 1993; 40: 705–714.

    Article  CAS  PubMed  Google Scholar 

  3. D'Ercole A . ROP-forme fruste. J Perinatol 2002; 22: 257–258.

    Article  Google Scholar 

  4. Manzoni P, Farina D, Leonessa M, Gomirato G, Arisio R . Risk factors for severe retinopathy of prematurity among very preterm infants: a unit-based or population-based approach? Pediatrics 2005; 116: 516–517.

    Article  PubMed  Google Scholar 

  5. Karna P, Muttineni J, Angell L, Karmaus W . Retinopathy of prematurity and risk factors: a prospective cohort study. BMC Pediatr 2005; 5: 18.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Termote J, Donders A, Schalij-Delfos N, Lenselink C, Derkzen van Angeren C, Lissone S et al. Can screening for retinopathy of prematurity be reduced? Biol Neonate 2005; 88: 92–97.

    Article  CAS  PubMed  Google Scholar 

  7. Karlowicz MG, Giannone PJ, Pestian J, Morrow AL, Shults J . Does candidemia predict threshold retinopathy of prematurity in extremely low birth weight (&lt;/=1000 g) neonates? Pediatrics 2000; 105: 1036–1040.

    Article  CAS  PubMed  Google Scholar 

  8. Brown DR, Biglan AW, Stretavsky MM . Retinopathy of prematurity: the relationship with intraventricular hemorrhage and bronchopulmonary dysplasia. J Pediatr Ophthalmol Strabismus 1990; 27: 268–271.

    CAS  PubMed  Google Scholar 

  9. Higgins RD, Mendelsohn AL, DeFeo MJ, Ucsel R, Hendricks-Munoz KD . Antenatal dexamethasone and decreased severity of retinopathy of prematurity. Arch Ophthalmol 1998; 116: 601–605.

    Article  CAS  PubMed  Google Scholar 

  10. York J, Landers S, Kirby R, Arbogast P, Penn J . Arterial oxygen fluctuation and retinopathy of prematurity in very low birth weight infants. J Perinatol 2004; 24: 82–87.

    Article  PubMed  Google Scholar 

  11. Hussain N, Clive J, Bhandari V . Current incidence of retinopathy of prematurity, 1989–1997. Pediatrics 1999; 104: e26.

    Article  CAS  PubMed  Google Scholar 

  12. Dani C, Reali M, Bertini G, Martelli E, Pezzati M, Rubaltelli F . The role of blood transfusions and iron intake on retinopathy of prematurity. Early Hum Dev 2001; 62: 57–63.

    Article  CAS  PubMed  Google Scholar 

  13. Englert J, Sounders R, Purohit D, Hulsey T, Ebeling M . The effect of anemia on retinopathy of prematurity in extremely low birth weight infants. J Perinatol 2001; 21: 21–26.

    Article  CAS  PubMed  Google Scholar 

  14. Cuculich PS, DeLozier KA, Mellen BG, Shenai JP . Postnatal dexamethasone treatment and retinopathy of prematurity in very-low-birth-weight neonates. Biol Neonate 2001; 79: 9–14.

    Article  CAS  PubMed  Google Scholar 

  15. Richardson D, Tarnow-Mordi WO, Lee SK . Risk adjustment for quality improvement. Pediatrics 1999; 103: 255–265.

    CAS  PubMed  Google Scholar 

  16. Richardson D, Gray J, McCormick M, Workman K, Goldmann D . Score for neonatal acute physiology: a physiologic severity index for neonatal intensive care. Pediatrics 1993; 91: 617–623.

    CAS  PubMed  Google Scholar 

  17. Anderson C, Richardson D, Stewart J, Leviton A . Predicting retinopathy of prematurity from NICU admission data. Pediatr Res 1994; 35: 263A.

    Article  Google Scholar 

  18. Cole C, Hagadorn J, Rand W, Richardson D, Stewart J . Prediction of retinopathy of prematurity progression to threshold. Pediatr Res 2001; 49: 390A.

    Google Scholar 

  19. Mattia F, deRegnier R . Chronic physiologic instability is associated with neurodevelopmental morbidity at one and two years in extremely premature infants. Pediatrics 1998; 102: E35.

    Article  CAS  PubMed  Google Scholar 

  20. Merchant J, Mattia F, deRegnier R . Gestational age and prolonged physiological instability are correlated with preschool cognitive function in premature infants ⩽32 weeks gestation. Pediatr Res 1999; 45: 251A.

    Article  Google Scholar 

  21. The STOP-ROP Multicenter Study Group. Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics 2000; 105: 295–310.

    Article  Google Scholar 

  22. Committee for the Classification of Retinopathy of Prematurity. An international classification of retinopathy of prematurity. Arch Ophthalmol 1984; 102: 1130–1134.

    Article  Google Scholar 

  23. The International Neonatal Network. The CRIB (clinical risk index for babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. Lancet 1993; 342: 193–198.

    Article  Google Scholar 

  24. Hardy R, Palmer E, Dobson V, Summers C, Phelps D, Quinn G et al. Risk analysis of prethreshold retinopathy of prematurity. Arch Ophthalmol 2003; 121: 1697–1701.

    Article  PubMed  Google Scholar 

  25. Hardy R, Palmer E, Schaffer D, Phelps D, Davis B, Cooper C . Outcome-based management of retinopathy of prematurity. J AAPOS 1997; 1: 46–54.

    Article  CAS  PubMed  Google Scholar 

  26. Harrell Jr FE, Lee KL, Mark DB . Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 1996; 15: 361–387.

    Article  CAS  Google Scholar 

  27. Hanley J . Receiver operating characteristic (ROC) methodology: the state of the art. Crit Rev Diagn Imaging 1989; 29: 307–335.

    CAS  PubMed  Google Scholar 

  28. Hanley J, NcNeil B . A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 1983; 148: 839–843.

    Article  CAS  PubMed  Google Scholar 

  29. McColm J, Cunningham S, Wade J, Sedowofia K, Gellen B, Sharma T et al. Hypoxic oxygen fluctuations produce less severe retinopathy than hyperoxic fluctuations in a rat model of retinopathy of prematurity. Pediatr Res 2004; 55: 107–113.

    Article  CAS  PubMed  Google Scholar 

  30. Smith L . IGF-1 and retinopathy of prematurity in the preterm infant. Biol Neonate 2005; 88: 237–244.

    Article  CAS  PubMed  Google Scholar 

  31. Verhaeghe J, Van Herck E, Billen J, Moerman P, Van Assche F, Giudice L . Regulation of insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in preterm fetuses. Am J Obstet Gynecol 2003; 188: 485–491.

    Article  CAS  PubMed  Google Scholar 

  32. 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: 1684–1694.

    Article  Google Scholar 

  33. Palmer E, Flynn J, Hardy R, Phelps D, Phillips C, Schaffer D et al. Incidence and early course of retinopathy of prematurity. Ophthalmology 1991; 98: 1628–1640.

    Article  CAS  PubMed  Google Scholar 

  34. Tadesse M, Dhanireddy R, Mittal M, Higgins RD . Race, Candida sepsis, and retinopathy of prematurity. Biol Neonate 2002; 81: 86–90.

    Article  PubMed  Google Scholar 

  35. Schaffer D, Palmer E, Plotsky D, Metz H, Flynn J, Tung B . Prognostic factors in the natural course of retinopathy of prematurity. Ophthalmology 1993; 100: 230–236.

    Article  CAS  PubMed  Google Scholar 

  36. Yang M . Ethnic variation in the incidence and severity of retinopathy of prematurity: possible explanations, including racial differences in illness severity. Int Ophthalmol Clin 2003; 43: 91–103.

    Article  PubMed  Google Scholar 

  37. Berman S, Richardson D, Cohen A, Pursley D, Lieberman E . Relationship of race and severity of neonatal illness. Am J Obstet Gynecol 2001; 184: 668–672.

    Article  CAS  PubMed  Google Scholar 

  38. Manzoni P, Maestri A, Leonessa M, Mostert M, Farina D, Gomirato G . Fungal and bacterial sepsis and threshold ROP in preterm very low birth weight neonates. J Perinatol 2006; 26: 23–30.

    Article  CAS  PubMed  Google Scholar 

  39. Parupia M, Dhanireddy R . Association of postnatal dexamethasone use and fungal sepsis in the development of severe retinopathy of prematurity and progression to laser therapy in extremely low-birth-weight infants. J Perinatol 2001; 21: 242–247.

    Article  Google Scholar 

  40. Noyola D, Bohra L, Paysse E, Fernandez M, Coats D . Association of candidemia and retinopathy of prematurity in very low birthweight infants. Ophthalmology 2002; 109: 80–84.

    Article  PubMed  Google Scholar 

  41. Mittal M, Dhanireddy R, Higgins R . Candida sepsis and association with retinopathy of prematurity. Pediatrics 1998; 101: 654–657.

    Article  CAS  PubMed  Google Scholar 

  42. Bell M, Ternberg J, Feigin R, Keating J, Marshall R, Barton L et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187: 1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the efforts of Ralph Beltran, Jennifer Cho, Brian Costner, Julia Deanehan, Julie Hayner, Sarah Little, Kathleen O'Connell, Christina Patoine, Sonja Payne, Alaka Ray, Erika Vargas, Tamra Carter and Lisa Valente. This study was funded by NEI K23 EY/HD00420, the Society for Pediatric Research Student Research Program, and the Tufts University School of Medicine Minority Student Research Program.

Author information

Author notes

  1. D K Richardson: Deceased

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Connecticut Children's Medical Center, University of Connecticut School of Medicine, Hartford, CT, USA

    J I Hagadorn

  2. Department of Neonatology, Beth Israel-Deaconess Medical Center, Harvard University School of Medicine, Boston, MA, USA

    D K Richardson & C H Cole

  3. Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA, USA

    C H Schmid

Authors
  1. J I Hagadorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D K Richardson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C H Schmid
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C H Cole
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J I Hagadorn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hagadorn, J., Richardson, D., Schmid, C. et al. Cumulative illness severity and progression from moderate to severe retinopathy of prematurity. J Perinatol 27, 502–509 (2007). https://doi.org/10.1038/sj.jp.7211780

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jp.7211780

Keywords

This article is cited by

Search

Advanced search

Quick links