Outcome of non‐visualization of fetal gallbladder on second‐trimester ultrasound: cohort study and systematic review of literature

ABSTRACT Objectives To investigate the ultrasound characteristics and outcome of fetuses with non‐visualization of the fetal gallbladder (NVFGB) followed in our tertiary university hospital, and to provide a comprehensive review of the literature on prenatal findings and outcome of NVFGB. Methods NVFGB was defined as non‐visualization of the gallbladder on two targeted ultrasound examinations performed within a 1‐week period. First, we reviewed the medical records of NVFGB cases managed in our center over a 9‐year period. Then, we performed a systematic review of the literature to identify studies on NVFGB. The incidence of chromosomal anomalies, later visualization of the gallbladder, gallbladder agenesis, cystic fibrosis and biliary atresia was assessed in fetuses with isolated and non‐isolated NVFGB. The role of hepatic enzyme measurements in the diagnosis of cystic fibrosis and biliary atresia in fetuses with NVFGB was also reviewed. Results Sixteen cases of NVFGB were followed in our center, in 10 (62.5%) of which it was an isolated finding. The incidence of biliary atresia was 12.5% and that of gallbladder agenesis was 12.5%, while no case of cystic fibrosis was reported. The gallbladder was visualized later in pregnancy or postnatally in 43.8% and 25.0% of cases, respectively. A total of seven studies, including our cohort, involving a total of 280 NVFGB cases, met the inclusion criteria for the systematic review. Overall, 20.5% of fetuses had an associated ultrasound anomaly, and the incidence of chromosomal anomaly in this group was 20.4%. In cases with isolated NVFGB, the incidence of chromosomal anomaly was 1.9%. In fetuses with normal karyotype and isolated NVFGB, the gallbladder was later visualized in 70.4% of cases, while the incidence of gallbladder agenesis, cystic fibrosis and biliary atresia was 25.2%, 3.1% and 4.8%, respectively. In fetuses with non‐isolated NVFGB, the incidence of cystic fibrosis and biliary atresia was 23.1% and 18.2%, respectively. The negative predictive value of amniotic fluid enzyme levels for the prediction of severe disease (including biliary atresia or cystic fibrosis) ranged between 94% and 100% when evaluated before 22 weeks' gestation, and dropped to 88% after 22 weeks. Conclusions In cases with persistent NVFGB, the risk of a severe postnatal condition should be considered. A detailed ultrasound scan should be offered and parents tested for cystic fibrosis gene mutation. An invasive procedure for karyotyping and measurement of liver enzyme concentrations before 22 weeks constitutes a reasonable work‐up. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.