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Background: Retinopathy 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., Objectives: To 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 Strategy: Searches 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 Criteria: Randomized 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 Analysis: Data 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 Results: Two 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 Conclusions: D-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.

Background: This section is under preparation and will be included in the next issue., Objectives: To 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 Strategy: Searches were made of multiple electronic databases, previous reviews including cross references, abstracts, conference/symposia proceedings, and expert informants., Selection Criteria: Randomized 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 Analysis: Data 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 Results: Two 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 Conclusions: D-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.

A prospective controlled trial has recently been reported to show the effectiveness of D-penicillamine (DPA) in the prevention of retinopathy of prematurity (ROP) among infants less than 2000 g birth-weight. The present paper is a comprehensive overview of a cohort of 204 prematures enrolled in the above study, with respect to mortality and outcome. Survival rate in the DPA treated group was the same as of those receiving conventional therapy. When the outcome of the DPA treated and the control infants was compared in terms of both major and minor impairments, the frequency of disabled and handicapped infants was higher in the control group. The same was observed with respect to the number of repeated hospital treatments, which was significantly higher among the control babies. The results suggest that DPA effectively prevents ROP among very-low-birth-weight infants, and also that the drug has no adverse effect on either mortality or late development.

204 infants with birthweights between 751 and 2000 g and 26-35 weeks gestational age (100 treated and 104 control subjects) were enrolled in a prospective controlled trial of the effectiveness of D-penicillamine (DPA) in the prevention of retinopathy of prematurity (ROP). The two groups did not differ significantly in gestational age, birth weight, Apgar scores, the time of exposure to oxygen and in the incidence of PDA or in the number of exchange transfusions and RBTs. Of the treated infants 29, and of the control infants 34 died before the tenth week of life. These cases were not included in further analysis. Patients were subsequently examined and assessed by two ophthalmologists independently, who did not know which babies were receiving DPA. Six of the 70 surviving control infants and none of the 71 surviving treated infants had ROP stage II or graver. The results suggested that ROP may effectively be prevented with DPA in very low-birth-weight-infants, and that the drug has no serious adverse effects during the neonatal period.

Superoxide dismutase activity of alveolar macrophages, lung, liver, retina and choroid has been studied in rats and rabbits exposed to oxygen at high concentration by itself and in combination with D-penicillamine. Prolonged hyperoxia caused an increase in superoxide dismutase activity while D-penicillamine was found to inhibit the inductive effect of oxygen. It is assumed that the antioxidative effect of D-penicillamine makes it unnecessary to augment the production of superoxide dismutase.