Padernal, Marilaine C.

BSN138

I. Clinical Question

In premature infants, is supplemental oxygen at pulse oximetry saturations of 96%

to 99% more effective than conventional oxygen at pulse oximetry saturations of
89% to 94% in reducing the progression from moderate (pre-threshold) to threshold
retinopathy of prematurity (ROP)?

II. Citation

Supplemental oxygen did not reduce progression of pre-threshold retinopathy of

prematurity in infants

III. Study Characteristics

1. Patients included

649 infants (mean gestational age 25 wks, 57% boys, 55% white) who were
born prematurely, had pre-threshold ROP in ≥1 eye, and had a median pulse
oximetry ≤94% oxygen saturation in room air. Infants were excluded if they had
lethal anomalies or congenital anomalies of the eye. Follow up was 92%.

2. Interventions Compared

After stratification by study centre and 2 levels of baseline ROP severity,

infants were randomised to receive supplemental oxygen therapy with pulse
oximetry targeted at 96% to 99% oxygen saturation (supplemental group, n=324)
or conventional oxygen therapy with pulse oximetry targeted at 89% to 94%
oxygen saturation (conventional group, n=325) for ≥2 weeks.

3. Outcomes Monitored

The main outcome measure was the rate of progression to threshold ROP in
≥1 eye. Secondary outcome measures were other ophthalmic and adverse events.
Infants had weekly eye examinations by an ophthalmologist.

IV. Methodology/Design

1. Design

Randomised (allocation concealed), blinded (outcome assessor), controlled

trial with 3 months of follow up.

2. Setting
 71 hospitals affiliated with 30 centres in the US.

3. Data Sources

(2000) Pediatrics 105, 295. The STOP-ROP Multicenter Study Group.. Supplemental
therapeutic oxygen for prethreshold retinopathy of prematurity (STOP-ROP), a
randomized, controlled trial. I: primary outcomes.. Feb;. :. –310
4. Has the original study been replicated?

The study conducted has not been replicated

5. What were the risks and benefits of the nursing

action/intervention tested in the study?

Premature babies which have the risk of retinal detachment mainly depends
on supplemental oxygen to temporarily delay the progress of the disease, this study
strongly suggest that giving supplemental oxygen is not enough and is not an
assurance that the progress of the disease will be delayed or stopped.

V. Results of the Study

Analysis was by intention to treat. Infants in the conventional and supplemental

groups did not differ for rates of progression to threshold ROP in ≥1 eye (48% v
41%) {p=0.06}*, retinal detachments or folds (4.4% v 4.1%), or macular ectopia
(3.9% v 3.9%). Compared with infants in the conventional group, more infants in the
supplemental group remained in hospital (7% v 13%, p=0.01), remained on oxygen
(37% v 47%, p=0.02), remained on diuretics (24% v 36%, p=0.002), and had ≥1
adverse pulmonary event defined as remaining in hospital or remaining on study
equipment, oxygen, steroids, methylxanthines, or diuretics (46% v 57%, p=0.005).

VI. Author’s Conclusions / Recommendations:

Supplemental therapeutic oxygen at pulse oximetry saturations of 96% to 99% did

not decrease the rate of progression from pre-threshold to threshold retin-opathy of
prematurity in infants but increased the risk of adverse pulmonary events.

VII. Applicability

1. Does the study provide a direct enough answer to your clinical question in terms
of type of patients, intervention and outcomes?

The study provides a direct and enough answer to the clinical question
raised.
2. Is it feasible to carry out the nursing action in the real world?

The nursing action in the study is feasible enough to be carried out in the real
world since the study was carefully done to have realistic results that can be carried
out in real setting.

VIII. Reviewer’s Conclusion/Commentary

Jacqueline M. McGrath, RN, NNP, CCNS, PhD

The aetiology and course of ROP has long been an issue of debate in neonatal
circles. Preterm infants who develop ROP appear to have lower birth weights, a
more complex medical course, and a longer duration of oxygen administration.1
Thus, the aetiology appears to be multifactorial, making cause and effect difficult to
establish. Supplemental oxygen to decrease hypoxic stimulus in the retina is a
biologically sound assumption. This multicentre, well controlled, randomised study,
however, did not support this premise.

Study strengths include use of many sites (30 US centres), randomisation to

supplemental or conventional group, a power level of 80% to detect differences
between groups (n=649), and 92% follow up. In the study, supplemental oxygen
was defined as oxygen needed to maintain saturations at 96% to 99% for most
infants. This was an approximate 10% increase in FIO2 over the control group, which
had saturations maintained at 89% to 94%. Infants who were in the supplemental
oxygen group were 1.8 times more likely to develop adverse pulmonary events
such as pneumonia or cardiovascular disease than those in the control group.

The study findings are important for healthcare providers working with preterm
infants with ROP because of the worry about adequate saturation levels to support
the retina. However, given the potential increased risks of chronic lung disease,
respiratory related needs should be a focus of concern in these medically complex
infants. Using supplemental oxygen does not appear to be advantageous for these
infants. This study, however, examined oxygen supplementation after diagnosis of
pre-threshold ROP and therefore cannot be used to make assumptions about
oxygen supplementation before this time. Lastly, a subgroup analysis found that
infants with pre-threshold ROP without plus disease (dilated and tortuous vessels in
≥2 quadrants of the posterior pole) who received supplemental oxygen appeared to
benefit from the treatment. More research is needed to confirm these results.
ARTICLE:
Supplemental Therapeutic Oxygen for Prethreshold
Retinopathy of Prematurity (STOP-ROP), A
Randomized, Controlled Trial. I: Primary Outcomes
Received Oct 13, 1999; accepted Nov 2, 1999.

The STOP-ROP Multicenter Study Group

From the STOP-ROP Multicenter Study Group.

Objective. To determine the efficacy and safety of supplemental therapeutic oxygen for infants with
prethreshold retinopathy of prematurity (ROP) to reduce the probability of progression to threshold ROP
and the need for peripheral retinal ablation.

Methods. Premature infants with confirmed prethreshold ROP in at least 1 eye and median pulse
oximetry <94% saturation were randomized to a conventional oxygen arm with pulse oximetry targeted at
89% to 94% saturation or a supplemental arm with pulse oximetry targeted at 96% to 99% saturation, for
at least 2 weeks, and until both eyes were at study endpoints. Certified examiners masked to treatment
assignment conducted weekly eye examinations until each study eye reached ophthalmic endpoint. An
adverse ophthalmic endpoint for an infant was defined as reaching threshold criteria for laser or
cryotherapy in at least 1 study eye. A favorable ophthalmic endpoint was regression of the ROP into zone
III for at least 2 consecutive weekly examinations or full retinal vascularization. At 3 months after the due
date of the infant, ophthalmic findings, pulmonary status, growth, and interim illnesses were again
recorded.

Results. Six hundred forty-nine infants (325 conventional and 324 supplemental) were enrolled from
30 centers over 5 years. Five hundred ninety-seven (92.0%) infants attained known ophthalmic endpoints,
and 600 (92%) completed the ophthalmic 3-month assessment. The rate of progression to threshold in at
least 1 eye was 48% in the conventional arm and 41% in the supplemental arm. After adjustment for
baseline ROP severity stratum, plus disease, race, and gestational age, the odds ratio (supplemental vs
conventional) for progression was .72 (95% confidence interval: .52, 1.01). Final structural status of all
study eyes at 3 months of corrected age showed similar rates of severe sequelae in both treatment arms:
retinal detachments or folds (4.4% conventional vs 4.1% supplemental), and macular ectopia (3.9%
conventional vs 3.9% supplemental). Within the prespecified ROP severity strata, ROP progression rates
were lower with supplemental oxygen than with conventional oxygen, but the differences were not
statistically significant. A post hoc subgroup analysis of plus disease (dilated and tortuous vessels in at
least 2 quadrants of the posterior pole) suggested that infants without plus disease may be more
responsive to supplemental therapy (46% progression in the conventional arm vs 32% in the
supplemental arm) than infants with plus disease (52% progression in conventional vs 57% in
supplemental). Pneumonia and/or exacerbations of chronic lung disease occurred in more infants in the
supplemental arm (8.5% conventional vs 13.2% supplemental). Also, at 50 weeks of postmenstrual age,
fewer conventional than supplemental infants remained hospitalized (6.8% vs 12.7%), on oxygen (37.0%
vs 46.8%), and on diuretics (24.4% vs 35.8%). Growth and developmental milestones did not differ
between the 2 arms.

Conclusions. Use of supplemental oxygen at pulse oximetry saturations of 96% to 99% did not cause
additional progression of prethreshold ROP but also did not significantly reduce the number of infants
requiring peripheral ablative surgery. A subgroup analysis suggested a benefit of supplemental oxygen
among infants who have prethreshold ROP without plus disease, but this finding requires additional study.
Supplemental oxygen increased the risk of adverse pulmonary events including pneumonia and/or
exacerbations of chronic lung disease and the need for oxygen, diuretics, and hospitalization at 3 months
of corrected age. Although the relative risk/benefit of supplemental oxygen for each infant must be
individually considered, clinicians need no longer be concerned that supplemental oxygen, as used in this
study, will exacerbate active prethreshold ROP. Key words: retinopathy of prematurity, oxygen therapy,
visual loss, oxygen toxicity, prematurity, neonatal outcomes, bronchopulmonary dysplasia.