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Effects of Hyperbilirubinemia on Visuocortical Functioning in High-Risk Infants

Award Number: R01EY030537
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2024

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2022	THE SMITH-KETTLEWELL EYE RESEARCH INSTITUTE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	000	4	2/25/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $608,379 )
2022	2022	SMITH-KETTLEWELL EYE RESEARCH INSTITUTE, THE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	000	4	8/19/2022	NON-COMPETING CONTINUATION	$608,379
														Subtotal = $608,379

Issue Date FY: 2021 ( Subtotal = $651,171 )
2021	2021	SMITH-KETTLEWELL EYE RESEARCH INSTITUTE, THE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	000	3	8/12/2021	NON-COMPETING CONTINUATION	$651,171
														Subtotal = $651,171

Issue Date FY: 2020 ( Subtotal = $671,311 )
2020	2020	SMITH-KETTLEWELL EYE RESEARCH INSTITUTE, THE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	003	2	8/3/2020	NON-COMPETING CONTINUATION	$671,311
2020	2019	SMITH-KETTLEWELL EYE RESEARCH INSTITUTE, THE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	001	1	4/6/2020	NEW	$0
2020	2019	SMITH-KETTLEWELL EYE RESEARCH INSTITUTE, THE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	000	1	11/20/2019	NEW	$0
2020	2019	SMITH-KETTLEWELL EYE RESEARCH INSTITUTE, THE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	002	1	6/5/2020	NEW	$0
														Subtotal = $671,311

Issue Date FY: 2019 ( Subtotal = $704,311 )
2019	2019	SMITH-KETTLEWELL EYE RESEARCH INSTITUTE, THE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	000	1	8/21/2019	NEW	$704,311
														Subtotal = $704,311

Grand Total All Awards = $2,635,172

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Effects of Hyperbilirubinemia on Visuocortical Functioning in High-Risk Infants

Award Number: R01EY030537

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2024

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