The US Food and Drug Administration recently approved nitric oxide (NO) inhalation therapy for newborn infants >34 wk of gestation with hypoxic respiratory failure associated with pulmonary hypertension. In clinical trials, this therapy has reduced the need for extracorporeal membrane oxygenation. It has not reduced mortality, however. A body of accumulating data indicates that NO may act as an antioxidant as well as a prooxidant, depending on a number of known and unknown factors, e.g. the concentration of NO itself and the concentration of other oxidants. In low doses, NO is an antioxidant and in high doses its prooxidant effects are more pronounced. In this issue of Acta Paediatrica, new information regarding this question has come to light. Turanlanthi et al. have found that NO in relatively high doses induces free radical mediated injury in the lungs of 10-wk-old Wistar rats, while in combination with hyperoxia it attenuates the oxidative stress of hyperoxia alone. Recently, it has also become clear that NO acts as a second messenger activating a number of cytokines and inducing apoptosis. There therefore seems to be a close relation between NO, oxidative stress, regulation of growth and inflammation. For these reasons, long-term follow-up studies of newborn infants treated with NO inhalation are needed. So far, NO therapy has not been successful in premature infants.
Conclusions: NO inhalation has a number of both short-term and long-term potential adverse effects, and is still at the experimental stage in premature infants. Consequently, there is a need for further clinical studies monitoring also the long-term consequences of this therapy.