Prenatal Diagnosis of Biliary Atresia Ori Shen MD Shaare 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?

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

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

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 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

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

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

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 malformation BCM

Approximately 10% of all cases of BA

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

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

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

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