A physiologic reduced oxygen protocol decreases the incidence of threshold retinopathy of prematurity

Trans Am Ophthalmol Soc. 2006;104:78-84.


Purpose: To report the incidence of threshold retinopathy of prematurity (ROP) in very low birth weight premature infants from three neonatal intensive care units (NICUs) before and after implementation of a physiologic reduced oxygen protocol (PROP).

Methods: PROSPECTIVE, OBSERVATIONAL STUDY OF DATA FROM THREE NICUS: Cedars-Sinai Medical Center (CSMC), Los Angeles; Good Samaritan Hospital (GSH), Los Angeles; and National University Hospital (NUH), Singapore. PROP was implemented to keep oxygen saturation values by pulse oximeter (SpO2) between 83% and 93% (as described in Pediatrics 2003;111:339-345). The incidence of threshold ROP in the year before and the year after implementation of PROP was compared. Data from the transition year were not included in the analysis.

Results: THE INCIDENCE OF THRESHOLD ROP DECREASED IN EACH CENTER: CSMC, 3.3% to 0.0% (3/92 to 0/88); GSH, 14.8% to 4.9% (8/54 to 2/41); and NUH, 6.7% to 0.0% (3/45 to 0/30). Overall, the incidence of threshold ROP decreased from 7.3% to 1.3%. (P <.05). The 95% confidence interval was 4.3% to 12% for the pre-PROP group and 0.05% to 4.76% for the post-PROP group.

Conclusions: Physiologic hypoxia is the normal fetal state. Exposure of newborn premature infants to hyperoxia down-regulates retinal vascular endothelial growth factor. This arrests the normal retinal vascular migration and causes vaso-obliteration, the first phase of ROP. The hypothesis is that maintaining SpO2 values between 83% and 93% in the immediate postgestation life, combined with strict control of oxygen fluctuations, prevents the early vaso-obliterative phase and subsequent development of severe ROP. Significant reduction of threshold disease after implementation of PROP in all three centers supports the hypothesis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Protocols
  • Gestational Age
  • Humans
  • Incidence
  • Infant, Newborn
  • Infant, Very Low Birth Weight
  • Intensive Care Units, Neonatal / trends
  • Oximetry
  • Oxygen / administration & dosage*
  • Oxygen Consumption*
  • Oxygen Inhalation Therapy / methods*
  • Prospective Studies
  • Retinopathy of Prematurity / epidemiology*
  • Retinopathy of Prematurity / prevention & control
  • Retinopathy of Prematurity / surgery


  • Oxygen