Maternite "Les Bluets", Paris, France

This is a 30 year-old primigravida with unremarkable medical history. The first trimester scan was normal. At 18 weeks an amniocentesis was performed because of an abnormal triple test . The karyotype was normal. The second trimester scan was normal, except for the fetal gallbladder that could not be seen and the bowel appeared to be slightly hyperechoic. The serology test for cytomegalovirus was negative.

A week later, the non-visualization of the fetal gallbladder was confirmed by two different sonographers. Hyperechoic bowel associated with non visualization of the gallbladder and normal karyotype lead to the suspicion of cystic fibrosis. The asymptomatic mother and the father were tested for cystic fibrosis and the result was positive for the DF508 mutation of the CFTR protein. A sample of the amniotic fluid (stored by the genetic laboratory after karyotyping) was then sent for cystic fibrosis testing. The cystic fibrosis screen was positive and the fetus was found homozygote for the DF508 CFTR mutation.

After discussion and genetic counseling, the parents decided for interruption of the pregnancy. No gallbladder was found at autopsy.

Discussion

The gallbladder (with the stomach and the course of the umbilical vein) is one of the main landmarks of the fetal abdominal anatomical structures. Color Doppler is useful to differentiate from non vascular structures. The gallbladder is normally visible in the beginning of the second trimester and sometimes less visible in the end of the pregnancy. Non-visualization of the fetal gallbladder is rare (about 1:1000), but associated in 40% with other severe fetal anomalies. In case of non-visualization, the scan should be repeated after one week.

What to look for, when the gallbladder is not visible?

1. Cystic fibrosis (mucoviscidosis)
   Cystic fibrosis is the most common lethal genetic disorder today. It affects approximately 1:3,000 live births. It is an autosomal recessive disorder of abnormal mucous secretion, with a carrier rate of 4%. Most of the newly diagnosed patients, do not have an affected relative and therefore are not known to be at risk. Several hundreds mutations in the cystic fibrosis gene have been identified. The major cystic fibrosis mutation is the DF508 which accounts for 70% in Caucasians. Prenatal diagnosis is possible in case of familial history. Several ultrasound findings have been described including hyperechoic bowel, digestive dilatation, meconium peritonitis, ascites, absent gallbladder.
   
2. Aneuploidies: trisomy 21, triploidy, trisomy 18, XYY, and others. In some cases,  the finding may be an enlarged cystic gallbladder instead.
   
3. Viral infections: cytomegalovirus, meconium peritonitis.
   
4. Associated structural malformations: Potter syndrome, abnormal kidneys, hydrops, diaphragmatic hernia-right sided, and others
   
5. Biliary atresia: Uncommon, severe prognosis. A rare case of extra-hepatic biliary atresia was diagnosed by a combination of prenatal ultrasound and measurements of fetal digestive enzymes in amniotic fluid. Ultrasound at 15 and 18 weeks failed to detect the gallbladder and amniotic fluid digestive enzyme values were below the fifth percentile. A "triangular cord sign" has been described in these cases. In the left isomerism,  extra-hepatic biliary atresia with the absence of the gallbladder is the most severe complex extra-cardiac malformation.  Two important findings can be expected in left isomerism : interruption of the inferior vena cava in its intrahepatic part and presence of persistent arrhythmia. Antenatal diagnosis of biliary atresia remains exceptional. Types I and II can be suspected on ultrasound examination when a cystic structure is detected in the liver hilum.
   
6. Anatomical variant: the gallbladder is also not detectable in one or the other symptom-free parent
   
7. Normal healthy newborn: the gallbladder is detected later in pregnancy or even after birth

Conclusion

The fetal gallbladder is normally detected in the second trimester of pregnancy. Constant non-visualization of the fetal gallbladder should prompt specific investigations since severe fetal anomalies may be associated in these cases. 

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