Cardiometabolic risk in childhood: Could bilirubin act as a circadian clock-related mediator via autonomic dysfunction?

bilirubin seems to increase after light therapy not only as a result of activation of photoreceptors but also impacted by circadian clock regulatory mechanisms. 4 Nonetheless, in their retrospective study, the authors of the aforementioned paper found that neonatal serum bilirubin levels were positively associated with childhood blood pressure/hypertension in preterm infants. This suggests that neurotoxicity of bilirubin and its plausible impact on autonomic pathways via sympathetic nerve fibers may be involved in the neonatal pathophysiological mechanisms leading to hypertension. Interestingly, in a prospective study in full-term newborn infants it was found that severe unconjugated hyperbilirubinemia may cause cardiac autonomic dysfunction, with parasympathetic predominance. 5 These findings can also raise the important question of whether newborn babies with kernicterus are predisposed to developing hypertension or cardiovascular morbidity. Despite the contradictory observations, the relationship of hyperbilirubinemia and autonomic function and their circadian variations is particularly important in preterm babies due to the immature nature of the brain-blood barrier and consequent higher risk of toxicity and encephalopathy leading to autonomic related cardiovascular and metabolic signs.