Prenatal Diagnosis of Biliary Atresia
Ori Shen MDShaare Zedek Medical Center
Biliary Atresia
• 15% syndromatic• 85% “perinatal”, “acquired” • Etiology of acquired type multifactorial, possibly
viral• Onset of symptoms at several days or weeks• Postnatal diagnosis by liver biopsy or at surgery
• It is unlikely BA can be diagnosed at 20 weeks gestation
Prenatal Nonvisualization of Fetal Gallbladder (PNVGB)
• Incidence 1:875
• DD of isolated PNVGB– Transient ~ 50-75%– Isolated Gallbladder Agenesis ~ 20-45%– Cystic Fibrosis ~5%– BA?– Aneuploidy?
Case series with PNVGB
• 34 cases (Blazer, Radiology 2002)
– 14 associated anomalies (triploidy, CF, Potter …)
– 20 isolated
–0 cases with BA
100% normal outcome
Case series with PNVGB
• 96/101 normal outcome (Hertzberg, Radiology 1996)
– 4 minor problems– 1 trisomy 21
–0 cases with BA
Case series with PNVGB
• 17 cases, all isolated (Ochshorn, Prenatal Diagnosis 2007)
– 14 normal– 3 abnormal (triple X, thyroid aplasia, CF)
–0 cases with BA
20 cases with PNVGBShaare Zedek +Hadassah
– 3 with aneuploidy• 2 trisomy 18• 1 triploidy
– 1 with heterotaxy, cardiac anomaly– 1 with minor anomaly (interrupted IVC)– 15 isolated
• 1 TOP due to CF• 14 good outcome
– 7 transient– 7 isolated gallbladder agenesis/dysgenesis
–0 cases with BA
Summary of case series
• 172 cases of PNVGB
•0 cases BA
It is unlikely PNVGB is associated with BA at 20 weeks
• What of studies on PNVGB with BA from Japan?
• None Exist• What of pathology reports from fetal autopsies with
BA?
• None Exist
It is unlikely PNVGB is associated with BA at 20 weeks
What of retrospective studies of BA infants?
– 3/89 infants with BA had prenatal biliary cystic malformations
– 3/13 cases with BCM and biliary disease had BA
–0 cases of PNVGB
It is unlikely PNVGB is associated with BA at 20 weeks
When is the diagnosis considered?
Biliary cystic malformationBCM
Approximately 10% of all cases of BA
Case reports linking abnormal amniotic fluid enzymes and BA: 20 years of research
Single case linking isolated PNVGB, low enzymes and BA
Ref US Aminopep M
AP GGTP Intestinal AP
N
LetterLancet 1991
Echogenic mass, none
Normal Normal <1 st% Normal 2 Muller
BJOG 2001
BCM <10th% Normal <10th% Normal 1 Burc
Prenatal Diagnosis
2002
PNVGB 0.12 MOM
0.4 MOM 5th%
0.08 MOM 1 Ben Ami Muller
Prenatal Diagnosis
2008
PNVGB GGTP and LAP low at 27 weeksILEAL NECROSIS
1 Bhouganim Muller
Japanese have not picked it up despite presence of a rat model
No retrospective studies linking abnormal enzymes and BA
Questions concerning amniotic fluid microvillar enzyme analysis
• What are its sensitivity and specificity for BA?
• Which enzymes(s) to use and/or in what combination?
Amniotic fluid digestive enzymes are of unproven diagnostic value for
confirming or ruling out BA
Association of PNVGB and aneuploidy
Isolated PNVGB• Trisomy 21 – 1 case. Isolated (Hertzberg)• Triple X – 1 case. Isolated (Ochshorn)
Not Isolated PNVGB• Trisomy XYY- 1 case. Not isolated (Bronshtein)• Trisomy 18-2 cases. Not isolated (Shen)• Triploidy – 5 cases. Not isolated (Bronshtein, Shen)
Conclusions 1
• PNVGB is not associated with BA• There is no theoretical basis linking non
syndromic, non cystic BA with PNVGB or low amniotic GGTP
• Amniotic fluid digestive enzymes are of unproven diagnostic value for confirming or ruling out BA
•Amniotic fluid digestive enzyme analysis should only be considered in the framework of a research protocol •Amniocentesis is not a routine part of PNVGB workup
Conclusions 2