# Effects of Hyperbilirubinemia on Visuocortical Functioning in High-Risk Infants

> **NIH NIH R01** · SMITH-KETTLEWELL EYE RESEARCH INSTITUTE · 2020 · $671,311

## Abstract

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 ...

## Key facts

- **NIH application ID:** 10000102
- **Project number:** 5R01EY030537-02
- **Recipient organization:** SMITH-KETTLEWELL EYE RESEARCH INSTITUTE
- **Principal Investigator:** WILLIAM V GOOD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $671,311
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000102

## Citation

> US National Institutes of Health, RePORTER application 10000102, Effects of Hyperbilirubinemia on Visuocortical Functioning in High-Risk Infants (5R01EY030537-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000102. Licensed CC0.

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