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Marsh and colleagues1 raise the spectre of a possible association between the use of sildenafil and the development of retinopathy of prematurity (ROP) in a baby of 26 weeks gestation with pulmonary hypertension. We are concerned that this report offers no real evidence for its claims and that a potentially lifesaving agent is being unfairly maligned.
The report describes the use of intravenous sildenafil of unspecified dose for 16 days in a 525 g preterm infant with a very difficult intensive care course. The management included a litany of recognised causes of ROP, including extreme prematurity, >6 weeks of mechanical ventilation with 80–100% oxygen, and bacterial and fungal infections.
Despite this, Marsh et al chose to incriminate sildenafil as the causal agent. The suggestion is even more perplexing as the baby had already received inhaled nitric oxide at high levels (40 ppm for 2–3 weeks) before the sildenafil; both are vasodilators and have the same mechanism of action.
The authors make the further statement that they observed a recent increase in treatable ROP in their unit, coinciding with the use of sildenafil. Where is their evidence?
As far as we are aware there is no evidence in the literature that sildenafil has any significant effect on either retinal or choroidal blood vessels. Pache et al reported2 that in adults, sildenafil induced a 5.8% dilatation of retinal vessels but this was not confirmed by Grunwald et al on either retinal or choroidal circulations.3,4 To date there are no data on the effect of sildenafil on the developing ocular circulations.
We entirely agree that vigilant monitoring and responsible reporting of side effects are mandatory for any new drug application. To our knowledge the only available intravenous sildenafil is being released on a named patient basis in a prospective study in neonates. How did the authors obtain and administer the drug in neonates? Sildenafil and inhaled nitric oxide are experimental therapies within the preterm population and as clinicians we have a responsibility to ensure that they are used as part of prospective randomised controlled trials with the appropriate short and long term follow up. Although being well intentioned, such unconvincing reports may impede the use of agents that might have an important future role in the management of primary pulmonary hypertension of the newborn.
Conflict of interest: The authors have acted in an independent consultant capacity (CMP, AJP, ARF) and are in receipt of financial support in the form of a research grant (CMP, AJP) from the manufacturers of sildenafil, Pfizer Ltd.