Reply

Abstract

Hoehn et al contribute a summary of stimulating concepts regarding the known effects of nitric oxide (NO) on the neonatal central nervous system. We also appreciate their discussion regarding the associations between exogenous NO on platelet aggregation, intraventricular hemorrhage, neurodevelopmental outcome, and cerebral autoregulation. In our clinical commentary1Gressens P Rogido M Paindaveine B Sola A. The impact of neonatal intensive care practices on the developing brain.J Pediatr. 2002; 140: 646-653Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar we attempted to summarize more than 20 years of experience, while focusing on the effects of many neonatal intensive clinical care practices on the developing brain. We initially submitted a manuscript that was much more lengthy, inclusive, and had double the number of references than what the published article has. Because of space limitations and editorial reviews, we had to make choices to significantly shorten the manuscript. Specifically, among the topics we decided to make much briefer were the ambiguous and potential role of exogenous NO on the developing brain. Admittedly, our statement regarding the hypoxic-ischemic neonatal rat pups model and the association of specific NO synthase isoforms with neuroprotective or neurodamaging effects is oversimplified. In addition, one of the many references that was deleted for the revised version was the one from Gidday2Gidday JM Shah AR Maceren RG Wang Q Pelligrino DA Holtzman DM et al.Nitric oxide mediates cerebral ischemic tolerance in a neonatal rat model of hypoxic preconditioning.J Cereb Blood Flow Metab. 1999; 19: 331-340Crossref PubMed Scopus (205) Google Scholar et al. We are thankful for the letter by Hoehn et al, which helps expand those concepts and the related bibliography. However, we would like to emphasize that in no way was it our intention to make an association between what occurs in a hypoxic-ischemic model with endogenous NO and the potential (if any) mechanisms of injury for exogenous NO in preterm infants. Our intention was to remind practicing clinicians that NO and its associated synthase isoforms are present in the central nervous system, and to increase their awareness that exogenous NO could conceivably have an effect on the neonatal brain. Clearly, there remains much research to be done before we can tease out the precise effects and mechanisms of action of NO in hypoxic-ischemic or any other form of neonatal brain injury. We hope that our manuscript will continue to foster thinking, discussion, and concern over the impact of neonatal practices on the developing brain. New research in the actual and possible neurologic effects of endogenous and exogenous NO and of frequent neonatal intensive care practices, used alone or in combination, we hope will provide us with more clear answers in the future. In the meantime, we should remind ourselves of our own ignorance and remain extremely vigilant to recognize that combinations of practices and therapies, and the adoption of practices without knowing their risks, may prove to be more deleterious than beneficial for the preterm infant. YMPD75