1. Prenatal Diagnosis of Biliary Atresia
Ori Shen MD
Shaare Zedek Medical Center

3. 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

4. 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?

5. 0 cases with BA Case series with PNVGB 100% normal outcome
34 cases (Blazer, Radiology 2002)
14 associated anomalies (triploidy, CF, Potter …)
20 isolated
0 cases with BA
100% normal outcome

6. 0 cases with BA Case series with PNVGB
96/101 normal outcome (Hertzberg, Radiology 1996)
4 minor problems
1 trisomy 21
0 cases with BA

7. 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

8. 20 cases with PNVGB Shaare 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

9. It is unlikely PNVGB is associated with BA at 20 weeks
Summary of case series
172 cases of PNVGB
0 cases BA
It is unlikely PNVGB is associated with BA at 20 weeks

10. 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?
It is unlikely PNVGB is associated with BA at 20 weeks

11. 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

12. When is the diagnosis considered?
Biliary cystic malformation
BCM

13. Approximately 10% of all cases of BA

14. Single case linking isolated PNVGB, low enzymes and BA
Case reports linking abnormal amniotic fluid enzymes and BA: 20 years of research
Ref US
Aminopep M AP
GGTP
Intestinal AP N
Letter
Lancet 1991
Echogenic mass, none
Normal
<1 st % 2
Muller
BJOG 2001
BCM
<10th % 1
Burc
Prenatal Diagnosis
2002
PNVGB
0.12 MOM
0.4 MOM 5th %
0.08 MOM
Ben Ami Muller
Prenatal Diagnosis 2008
GGTP and LAP low at 27 weeks
ILEAL NECROSIS
Bhouganim Muller
Single case linking isolated PNVGB, low enzymes and BA

15. Japanese have not picked it up despite presence of a rat model
No retrospective studies linking abnormal enzymes and BA
Japanese have not picked it up despite presence of a rat model

16. 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

17. 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)

19. 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

20. Conclusions 2
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