Neuroprotective Core Measure 6: Protecting Skin - Neuroprotective Care in the Newborn: Does Skin Protect the Immature Brain From Hyperbilirubinemia?

Hyperbilirubinemia continues to pose a significant and common problem in the newborn period. Exposure of the brain to high levels of unconjugated bilirubin leads to acute bilirubin encephalopathy and kernicterus, especially in preterm infants. Given the shared embryological origin of the skin (epidermis) and brain, we hypothesized that cutaneous binding of unconjugated bilirubin to skin (i.e., jaundice) might protect the immature brain. Support for this hypothesis requires direct quantification of binding of unconjugated bilirubin to cutaneous structures. Bilirubin binding was tested using a series of in vitro experiments wherein newborn skin and vernix caseosa were exposed to physiologically-relevant solutions of bilirubin. Tissue binding was assessed spectrophotometrically and via bilirubin autofluorescence. Study findings indicate the following: (1) unconjugated bilirubin binds quickly and avidly to thin films of vernix caseosa; (2) bilirubin binds to human epidermis in vitro via a mechanism involving dermal diffusion; (3) unconjugated bilirubin localizes to the dermis and epidermis as shown by autofluorescence; and (4) topical application of vernix caseosa to the epidermis augments bilirubin binding; i.e., increases jaundice. These findings are consistent with a physiological neuroprotective role for the skin in shielding the immature brain from high levels of unconjugated bilirubin. New therapies based on these results are envisioned with the goal of increasing cutaneous bilirubin binding (jaundice) thereby protecting the developing brain and facilitating bilirubin excretion with phototherapy.