Editor—We read with interest the recent annotation by Rennie and Bokhari1 on the subject of recent advances in neonatology. The piece was introduced by a foreword indicating that the article was aimed at the non-specialist. It seems particularly important therefore that the information contained should have been clear and well balanced; we feel that this was not the case with regard to inhaled nitric oxide (NO).

In relation to mature infants, a number of studies have shown that short term improvements in oxygenation can be achieved in some babies. What is more important, however, is to assess what this means in terms of more substantive clinical outcomes. One large trial conducted in North America did show that a significant number of infants with persistent pulmonary hypertension of the newborn can avoid extracorporeal membrane oxygenation if treated with NO, although no benefit in terms of preventing death was detected.2 Later outcome data for that study have recently been presented showing no significant difference between the groups at 18–24 months.3 The Bayley scores of the NO treated group were, however, some 8 points lower. This could have been due to chance, as the trial was not sized on this outcome. It is also plausible, however, that a poorer long term outcome may result from NO treatment as if there is no response referral for extracorporeal membrane oxygenation and the establishment of physiological stability is delayed.

The situation with regard to preterm babies is even less clear, and there is very little evidence either for or against NO use. Again short term improvements in oxygenation have been noted, but there are no studies reporting substantive longer term outcomes. It is in this group that concerns about intraventricular haemorrhage and toxicity are most acute. There are, as yet, no studies that adequately address the risks to the developing lung of NO exposure in terms of its ability to influence local inflammation and disrupt cell signalling pathways. The annotation simply refers to current recommendations on the environmental exposure of adults.

To state that NO “ . . .has already proved to be effective treatment” seems to distort the current picture. It is our view that sufficient uncertainty remains in relation to NO that its current use should remain part of a randomised trial such as INNOVO, funded by the MRC. New centres are still being recruited, and clinicians may choose to enter either term or preterm infants or both, depending on their position of equipoise. Currently, clinical uncertainty has mainly led to the recruitment of severely ill infants. In time, continued recruitment into INNOVO will allow more knowledgeable statements about the role of NO in this vulnerable population.