The Evidence Mounts Against Use of Pure Oxygen in Newborn Resuscitation

Abstract

In this issue of The Journal, the analysis of Spector et al1 of the venerable data of the National Collaborative Perinatal Project (NCPP) describes a slightly higher risk of cancer in children exposed to >3 minutes of oxygen in the delivery room than in children without oxygen exposure. From the perspective of the individual, the excess risk is quite small. The NCPP data suggest that a population of 10,000 unexposed children will have about 6 cancers by the age of 5, whereas 10,000 children exposed to >3 minutes of O2 in the delivery room might experience 17 or 18 cases. The overwhelming majority of exposed children will not have cancer, which is the usual scenario when common exposures are implicated in disease, and the reason for popular skepticism. Everyone knows someone who is exposed to the risk, and it is overwhelmingly likely that the person you know will not have the disease in question. For example, 90% to 95% of smokers are never diagnosed with lung cancer. From a public health perspective, of course, the numbers look different. Of the 48 cancers in the study, I calculated that 7, or nearly 15% of the total, might have been prevented if oxygen had not been used in resuscitation. To my knowledge, we have no other means available to remove about 1 in 7 cancers from the childhood population. By now readers should be saying. “Stop! How do we know that this purported relationship between oxygen and cancer isn't spurious?” The short answer is, of course, that we don't. Absolute assurance is never available from relationships that emerge from observational research, but at the same time we cannot afford to ignore statistically significant observations made in large studies. The proper path between skepticism and faith in research is paved with careful scrutiny of the observation and its context. Applying that scrutiny in the discussion that follows, I use the term oxygen to indicate exposure to 3 or more minutes of oxygen, the exposure level where a cancer risk is indicated by the data, and follow some of the criteria that epidemiologists use in weighing observational evidence. The study is one of the largest prospective studies of child health ever mounted, and the data on events in the delivery room were carefully collected and recorded years before most cancer diagnoses were established. Cancer in children is unlikely to be either missed or misclassified. Unfortunately, we cannot know exactly what concentration of oxygen these children were exposed to in the late 1950s and 1960s. A range of variables were examined, and none seemed capable of explaining the association by confounding. Low Apgar score at 1 minute (but oddly, not at 5 minutes) was also associated with cancer risk, but less convincingly than oxygen. It is not unreasonable to suppose that if oxygen is a cancer risk, a low Apgar score would appear to be also, because the 2 phenomena necessarily cluster together, but the article does not tell us if controlling for oxygen eliminates the low Apgar association. But on the grounds of both biologic plausibility and strength of association, oxygen seems a more likely determinant of cancer