Our goal is to continue the Intermountain West Clinical Center for the Childhood Liver Disease Research Network (ChiLDReN) at the University of Utah and Primary Children's Hospital. During the previous funding cycle, we enrolled and retained a significant number of participants, achieved outstanding site performance, and participated in a highly collaborative manner in all Network activities. Additionally, during the previous funding cycle, we transferred, aligned, and processed DNA sequences in support of all Network genomics efforts, and provided the infrastructure to share these sequence data with Network investigators via web- based, password protected software tools.
In Aim 1, we will continue to enroll infants, children, and adolescents in current and future ChiLDReN protocols, continue to submit valuable biological specimens and accurate and timely data, and collaboratively participate in all Network activities.
In Aim 2, we propose to test the feasibility of a biliary atresia newborn screening program in a large integrated healthcare system covering ~30,000 deliveries per year. All newborns in this healthcare system already undergo total serum bilirubin screening as part of standard of care. We will embed a pilot study in Aim 2 to measure the impact on mothers of newborns with a false positive newborn screen using a case-control repeated measures study design.
In Aim 3, we will perform whole genome sequencing on 10 participants and their parents in whom exome sequencing failed to identify a molecular diagnosis. For this Aim, Network investigators will collaboratively select subjects for whole genome sequencing using University of Utah-developed web-based tools. These tools require no bioinformatic expertise and enable expert, Network-wide central genome review. Accomplishing the proposed aims as a highly collaborative Center for ChiLDReN will lead to new knowledge regarding the biochemistry, physiology, and mechanisms of childhood liver diseases, and improve the diagnostic and management options for children afflicted with them.

Public Health Relevance

/RELEVANCE TO PUBLIC HEALTH Liver diseases are a significant source of morbidity and mortality in infants and children. Because these diseases are rare, a multicenter collaborative network such as the Childhood Liver Disease Research Network is necessary to accrue sufficient number of children to understand the causes and natural histories of rare liver diseases and develop new therapies to treat them.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK103140-07
Application #
10019520
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Doo, Edward
Project Start
2014-08-20
Project End
2024-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Utah
Department
Pediatrics
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Ng, Vicky L; Sorensen, Lisa G; Alonso, Estella M et al. (2018) Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study. J Pediatr 196:139-147.e3
Alonso, Estella M; Ye, Wen; Hawthorne, Kieran et al. (2018) Impact of Steroid Therapy on Early Growth in Infants with Biliary Atresia: The Multicenter Steroids in Biliary Atresia Randomized Trial. J Pediatr 202:179-185.e4
Shneider, Benjamin L; Moore, Jeff; Kerkar, Nanda et al. (2017) Initial assessment of the infant with neonatal cholestasis-Is this biliary atresia? PLoS One 12:e0176275
Shneider, Benjamin L; Magee, John C; Karpen, Saul J et al. (2016) Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia. J Pediatr 170:211-7.e1-2
Russo, Pierre; Magee, John C; Anders, Robert A et al. (2016) Key Histopathologic Features of Liver Biopsies That Distinguish Biliary Atresia From Other Causes of Infantile Cholestasis and Their Correlation With Outcome: A Multicenter Study. Am J Surg Pathol 40:1601-1615