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