Neonatal Jaundice

In 1956 Rolf Zetterström & Lars Ernster published their seminal observations demonstrating that bilirubin uncoupled oxidative phosphorylation in isolated mitochondria (1). On the other side of the Atlantic, Richard Day had found that bilirubin inhibited the uptake of oxygen by slices or homogenates of rat brain (2). These novel discoveries appeared to lead the way to understanding the unique toxicity of bilirubin in the newborn. The decades which followed the publication of these papers have seen thousands of additional publications concerning bilirubin and neonatal jaundice, but we do not seem that much closer to a convincing demonstration of the basis for kernicterus nor lesser forms of bilirubin toxicity (3). The neurotoxicity of bilirubin was recently reviewed here by Hansen & Bratlid (4); their article provides an excellent, balanced summary of the field. In contrast, this article offers a particular perspective of evolving work on the toxicity of bilirubin.