newborn screening for biliary atresia...xxx00.#####.ppt 7/17/2020 5:19:06 pm page 28 pilot results...
TRANSCRIPT
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Sanjiv Harpavat, MD [email protected]
Newborn Screening for Biliary Atresia
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Relevant Disclosure and Resolution• I am on the Data Monitoring Committee managed by Syneos Health, for a biliary atresia clinical trial sponsored by a Pharma company
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DSHS Acknowledgements• Patricia Hunt• Susan Tanksley • Amy Schlabach• Rachel Lee• Xinru Cao
• Charleta Guillory
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Outline• The Disease
• The Test
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Frankenburg (1974) Pediatrics 54:612-6.
I. Which diseases to screen?
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Frankenburg (1974) Pediatrics 54:612-6.
Disease is…
1. Important2. Relatively
prevalent3. Amenable to
early treatment
Which diseases to screen?
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UptoDate
Biliary Atresia (1:10-18,000)
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United Network for Organ Sharing.
#1 Reason for all transplants
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Moyer et al. (2010) Genome Medicine 2:33.
BA progresses rapidly
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UpToDate
The Kasai operation
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Nio et al. (2014) Surg Today, epub ahead of print.
An earlier Kasai may help
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Superina R et al. (2011) Annals of Surgery 254: 577-85.
National•Average age of Kasai = 64.6 days•Percent too late for Kasai = 9%
TCH (2007-2014)•Average age of Kasai = 61.6 days•Percent too late for Kasai = 20-25%
Early Kasai?
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http://www.ohmybaby.com.au/images/7088.jpg
BA starts insidiously
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Harpavat et al. (2018) JPGN 66: 850-6.
Transaminases normal initially
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The Disease – Summary • BA is the most common indication for pediatric
liver transplantation
• By intervening early, we can prevent liver transplant
“An ideal disease for newborn screening”
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Frankenburg (1974) Pediatrics 54:612-6.
Test is…
4. Acceptable5. Reliable6. Valid7. Reasonable cost
AND
Disease is…
1. Important2. Relatively
prevalent3. Amenable to
early treatment
II. The Test
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Stool Color
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Stool Color Card
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Stool Color Card
• Who answers the calls?
• Timetable: “Rolling”
• Subjective, categorical
• Sensitivity: 77% at 30 days 83% at 45 days 97% at 60 days
• “Asymptomatic”?
Hsiao et al. (2008) Hepatology 47:1233-40.Gu Y-H et al. (2015) J Peds 166: 897-902.
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When does bile back up?
UptoDate
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PhototherapyFetal red blood cells unconjugated bilirubin
conjugated bilirubin out
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Disease is present at birth
*
Harpavat et al. (2011) Pediatrics 128:e1428-33.
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DB/CB levels rise with time
Harpavat et al. (2011) Pediatrics 128:e1428-33.
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Prospective screen
NewbornTest
High Level
Normal Level
Repeat Test
High Level
Normal Level
2 weeks
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Newborn hospitals are diverse#1 #2 #3 #4
Type Pediatric,privateGeneral,
publicGeneral, private
General, private
Race/Ethnicity
White (71%) Black (21%)
Latino (80%)Black (12%)
White (78%) Other (14%)
Other (45%)White (30%)
Preterm 11.1% 11.9% 8.0% 2.0%Test Conjugated Direct Direct DirectRange 0.0-0.2 0.0-0.3 0.0-0.4 0.0-0.4
Similarities • Tests newborns routinely• Derives its own reference range• Refers cases to 2 centers
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Pilot Results
Newborn11,636
High 121
Normal 11,515
Repeat 114
High 11
Normal 103
2 weeks
Biliary atresia 2*A1AT (MZ) 1*Rh disease 1Resolved with labs 7
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Pilot Results
Harpavat et al. (2016) New England Journal of Medicine 375: 605-6.
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Ongoing testing
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Ongoing testing
Harpavat et al. (2020) JAMA 323: 1141-50.
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Ongoing testing
Harpavat et al. (2020) JAMA 323: 1141-50.
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Ongoing testing
Harpavat et al. (2020) JAMA 323: 1141-50.
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Important Considerations• Knowledge Issue
- What to do with a high value?
• Infrastructure Issues- Direct versus conjugated bilirubin and
reference intervals- Transcutaneous measurements- Nursery PCP communication
• Other‐ Acceptable, reliable, reasonable cost
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Summary• BA qualifies as a disease for which newborns
should be screened.
• A newborn screening test for BA has been developed in Texas.
• There is a special opportunity for Texas to guide the nation in newborn screening for BA.
Newborn Screening for Biliary AtresiaRelevant Disclosure and ResolutionDSHS AcknowledgementsOutlineI. Which diseases to screen?Which diseases to screen?Biliary Atresia (1:10-18,000)#1 Reason for all transplantsBA progresses rapidlyThe Kasai operationAn earlier Kasai may helpEarly Kasai?BA starts insidiouslyTransaminases normal initiallySlide Number 15The Disease – Summary II. The TestStool ColorStool Color CardStool Color CardWhen does bile back up?PhototherapyDisease is present at birthDB/CB levels rise with timeProspective screenSlide Number 26Newborn hospitals are diversePilot ResultsPilot ResultsOngoing testingOngoing testingOngoing testingOngoing testingImportant ConsiderationsSummary