Effects of hyperbilirubunemia on visuocortical functioning in high-risk infants Abstract Bilirubin in its unconjugated version can cross the blood-brain barrier (BBB), where it is a potent neurotoxin in neonates. Levels of this substance are therefore closely monitored to ensure the neonate is not subject to bilirubin encephalopathy, a potentially devastating event. Recently, effects on an infant's neurological system that fall short of full-blown bilirubin encephalopathy have been described (syndromes of bilirubin-induced neurologic dysfunction [BIND]). In a study from our laboratory, we showed that relatively low levels of total serum/plasma bilirubin (TB) will produce undesired effects on visuocortical functioning. Since bilirubin is usually cleared in infants within week of age, our findings of deleterious effects at 6 months and repeated at 12 months are potentially alarming. The cohort for this study was low-risk infants; i.e., those who were full-term, healthy, and had no known hemolytic disease. Most of the children in this cohort did not qualify for therapy for their elevated TB (phototherapy or exchange transfusion). In a subsequent preliminary study of jaundiced preterm infants, we found that the effect on visuocortical functioning is much more pronounced than that seen in full term infants. Two types of neonates are at particularly high-risk for BIND, and could show more significant effects from bilirubin exposure: preterm infants, who have a more immature BBB (32?38 wks gestational age at birth); and infants who have hemolytic disease will release larger quantities of bilirubin into circulation. We will use the sweep visual evoked potential (sVEP) to measure 3 types of vision in these infants at 6 months of age. Vernier acuity refers to the ability to see fine offsets of lines. Since the offsets are smaller than the resolution afforded by the spacing of cone cells in the retina, the perception of these offsets requires considerable cortical input. Contrast sensitivity and grating acuity are also important aspects of vision. All 3 are subserved by different cortical mechanisms. We will measure acuity thresholds, conduction time, suprathreshold changes, and other components of vision processing and compare these to bilirubin values measured in the hospital and in the Stanford laboratory. This is a potentially highly significant study and could affect the manner in which bilirubin is treated in certain neonates. The majority of premature infants have some degree of hyperbilirubinemia, so the stakes are especially high. Since we don't know the level at which bilirubin should be treated in a given infant, tests at Stanford, to include bilirubin binding capacity, TB, and unbound bilirubin could pave the way to a more individualized approach to hyperbilirubinemia management. End-tidal carbon monoxide levels will be measured for all infants in the study at the hospital and compared to sVEP findings. This novel approach could pave the way to a noninvasive measure of bilirubin neurotoxicity.
80% of born prematurely infants, develop some degree of jaundice. Jaundice is caused by bilirubin, a known neurotoxin, but we don't know when or whether to treat this problem in preterm infants. This study will demonstrate any negative effects of bilirubin on the developing nervous system, and will help us learn who, amongst the millions of infants with this problem, should be treated.
