* I would like to thank Jennifer Degl for providing permission to use her photo for this post. She is the author of From Hope to Joy and does great work which can be found at: www.micropreemie.net
A publication this past week has been featured in multiple news stories across North America due to it’s impact on mortality and morbidity in the NICU. Shielding Parenteral Nutrition From Light Improves Survival Rate in Premature Infants: A Meta Analysis made the splash that it did because it’s premise is so simple yet has such an impact. In essence, protect TPN from light (including phototherapy) and you can cut mortality in the NICU in half!
A Canadian Research Story
The CBC has covered this as well with the following piece that also indicates that a survey of NICUs from 4 years ago indicated about half of hospitals did not employ such shielding. In fairness the meta-analysis has just been published which combined 4 studies and about 800 patients to yield these findings but the understanding that such practice could benefit newborns in NICU has been known for many years. What makes this story even more interesting to me is it’s Canadian origin in that Dr. Chessex performed much of the work in this field and his dedication to the area of oxidative stress in large part led to this finding.
In fact in 1999 he published the following paper Protecting solutions of parenteral nutrition from peroxidation which demonstrated that simply covering the bag of TPN was not enough to prevent oxidation from occurring. The whole set up including the bag, lines and during the preparation of TPN needed to be shielded or peroxide concentrations increased by 1.5 -2 times compared to when a clear set up was used. Furthermore phototherapy led to a further rise in the concentration of these oxidative harmful molecules. Ironically it is the necessary components of TPN including riboflavin and lipid that create the environment for light to create these oxidative products that can damage tissue.
You may ask yourself at this point why something that was known nearly 17 years ago did not lead to widespread adoption by NICUs across Canada and perhaps North America. For one, medicine is notoriously slow to change practice especially when there is an effort and cost that will need to be considered. Sourcing such materials is actually more difficult than it may seem as we learned locally two years ago when one of our hospitals began this change. Secondly, Neonatology is littered with bench research that while striking in its findings simply did not translate into a clinically relevant outcome. For example we know that phenobarbital increases the conjugation of bilirubin in the liver and therefore in theory should be a great adjunctive treatment to phototherapy for the usual newborn jaundice but that didn’t pan out in human trials. What is the story here though?
The Landmark Study Results That Made Headlines
The meta-analysis mentioned in the start of this piece and causing all this attention included four studies that examined possible reductions in mortality. In 2007 Chessex studied the effect of light protection (LP) on the incidence of BPD finding a 30% reduction in those infants in a randomized study of LP vs none. This finding alone should be enough to raise some eyebrows and it did as many centres were adopting LP around this time. The second study done in Egypt in 2009 demonstrated a similar finding in reduced BPD rates. The third study was by Chessex again in 2009 and once more demonstrated reductions in oxidant stress and BPD. Curiously the largest of the studies based out of France with 587 patients in 2014 randomized to LP or none found no difference in BPD or death but the latter was very close to meeting statistical significance. In all of these studies no difference in mortality was noted however when they were combined and examined as a group the following was identified. Herein lies the power so to speak of the meta-analysis. Small studies may not demonstrate a difference that reaches significance in the desired outcome of interest but if several studies that have very similar measurements are pooled together the power to find a difference may emerge. That would seem to be the case here in that not only is there a halving of mortality that reaches statistical significance but a specific disadvantage for males was uncovered in that they had a two fold risk compared to females of dying if their TPN was uncovered.
Are These Results Relevant to Modern Practice
The results of this study are profound in terms of the impact that they could have on both BPD and mortality in our NICUs. One caveat needs to be mentioned however and that is the utlilization of oxygen in the NICU now and during the time of these studies. Since the time periods that these studies were undertaken, the use of oxygen for many units including our own has become more tightly regulated. As per NRP guidelines we resuscitate our newborns with room air and use every effort at the bedside to avoid wide swings of FiO2 when addressing an episode of desaturation. Furthermore, antenatal steroids, surfactant, liberal use of CPAP have all led to marked reductions in need for FiO2 such that the days of infants being on 30% FiO2 by nasal prongs have been replaced by room air on CPAP for the most part (at least in our units). What would these results be now if these studies were repeated? My suspicion is not as dramatic but there is no question that for at least 17 years we have known about the risk of such oxidative stress.
Is there any logic behind waiting for more evidence in a modern cohort before implementing a strategy of protecting these solutions from light? I don’t think so and hope that the rest of our community agrees and does not wait many more years to implement such precautions. How many other conditions such as ROP could be affected by simply protecting these solutions from light? Quite frankly I don’t need to know. The time has come for change.
Thank you Dr. Chessex for your dedication in bringing this translational research from the bench to the bedside.