Non‐visualization of fetal gallbladder (NVFGB) by ultrasound in second trimester of pregnancy: a systematic review of the literature on postnatal outcome

: 妊娠中期超声检测未显示胎儿胆囊:队列研究和产后预后文献的系统回顾 目标: 探讨我校三级附属医院随访中发现的胎儿胆囊未显影(NVFGB)的超声特点和预后，全面回顾NVFGB产前检查结果及预后的相关文献。 方法: NVFGB是指一周内进行的两次靶向超声检测中发现胆囊未显影。首先，回顾了我们中心在过去9年里负责管理的NVFGB病例的医疗记录。然后系统回顾了相关文献，鉴定NVFGB的相关研究。评估了分离和非分离的NVFGB胎儿的染色体异常、胆囊后期显影、胆囊发育不全、胆囊纤维化和胆道闭锁的发生率。还回顾了肝酶测定在NVFGB胎儿胆囊纤维化和胆道闭锁诊断中的作用。 结果: 我们中心随访了16例NVFGB病例，其中10例(62.5%)为孤立性发现。胆道闭锁发生率为12.5%，胆囊发育不全发生率为12.5%，无胆囊纤维化报道。妊娠晚期和产后胆囊显影率分别为43.8%和25.0%。包括我们的队列在内总共7项研究，共涉及280例NVFGB病例，符合系统回顾的纳入标准。总的来说，20.5%的胎儿发现相关的超声异常，该组中染色体异常发生率为20.4%。在孤立的NVFGB病例中，染色体异常发生率为1.9%。在核型正常的孤立性NVFGB胎儿中，70.4%的病例出现胆囊后期显影，而胆囊发育不全、胆囊纤维化和胆道闭锁的发生率分别为25.2%、3.1%和4.8%。在非孤立性NVFGB胎儿中，胆囊纤维化和胆道闭锁的发生率分别为23.1%和18.2%。妊娠22周前评估羊水酶水平对严重疾病(包括胆道闭锁或胆囊纤维化)的阴性预测值在94%至100%之间，22周后则降至88%。 结论: 对于持续性NVFGB病例，应该考虑产后罹患严重疾病的风险。应该进行仔细的超声检测，对父母进行胆囊纤维化基因突变检测。22周前的侵入性核型分析和肝酶浓度测定是一项合理的检查. 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.