• D L Phelps, L Lakatos, and J L Watts.
• Pediatrics and Ophthalmology, University of Rochester, Box 651, Pediatrics, 601 Elmwood Ave, Rochester, New York, USA, 14642. dale phelps@urmc.rochester.edu
• Cochrane Db Syst Rev. 2001 Jan 1 (1): CD001073.

BackgroundRetinopathy of prematurity remains a common problem. A low rate of this disorder was unexpectedly observed among infants treated with intravenous d-penicillamine to prevent hyperbilirubinemia. This observation led to the investigation of its use to prevent retinopathy of prematurity.ObjectivesTo answer the question: Among very low birth weight infants, what is the effect of prophylactic administration of d-penicillamine on the incidence of acute ROP or severe ROP, and side effects including death?Search StrategySearches were made of multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants. The search was updated to November 2000.Selection CriteriaRandomized or quasi-randomized controlled trials that administered d-penicillamine to infants less than 2000g birth weight within the day following birth were considered relevant to this review. Additional case series were examined for potential side effects.Data Collection And AnalysisData on clinical outcomes were excerpted by 3 reviewers independently, and consensus reached. Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group.Main ResultsTwo randomized trials on the effects on ROP were identified. When combined, they showed a significantly lower incidence of acute ROP in the treated infants, relative risk of 0.09, 95% CI [0.01,0.71]. Severe stages of ROP could not be analyzed. There was no effect on death rates, relative risk 0.99 95% CI [0.70,1.39]. No side effects were reported, and follow up at one year revealed no significant differences in spasticity or developmental delay, although there were more rehospitalizations among the controls. In other reports of using d-penicillamine in over 140 infants for hyperbilirubinemia, skin rashes were reported in 2 infants and one had vomiting that may have been related.Reviewer's ConclusionsD-penicillamine is unlikely to affect survival, and may reduce the incidence of acute ROP among survivors. Studies to date justify further investigation of this drug in a broader population; careful attention to possible side effects is needed.

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