Miller Michelle E, Allen Victoria M, Brock Jo-Ann K
Department of Obstetrics and Gynecology, Memorial University, St. John's, NL.
Department of Obstetrics and Gynaecology, Dalhousie University, Halifax, NS.
J Obstet Gynaecol Can. 2018 Jul;40(7):896-902. doi: 10.1016/j.jogc.2017.11.021. Epub 2018 Mar 2.
Fetal echogenic bowel (echogenic bowel) is associated with cystic fibrosis (CF), with a reported incidence ranging from 1% to 13%. Prenatal testing for CF in the setting of echogenic bowel can be done by screening parental or fetal samples for pathogenic CFTR variants. If only one pathogenic variant is identified, sequencing of the CFTR gene can be undertaken, to identify a second pathogenic variant not covered in the standard screening panel. Full gene sequencing, however, also introduces the potential to identify variants of uncertain significance (VUSs) that can create counselling challenges and cause parental anxiety. To provide accurate counselling for families in the study population, the incidence of CF associated with echogenic bowel and the carrier frequency of CFTR variants were investigated.
All pregnancies for which CF testing was undertaken for the indication of echogenic bowel (from Nova Scotia and Prince Edward Island) were identified (January 2007-July 2017). The CFTR screening and sequencing results were reviewed, and fetal outcomes related to CF were assessed.
A total of 463 pregnancies with echogenic bowel were tested. Four were confirmed to be affected with CF, giving an incidence of 0.9% in this cohort. The carrier frequency of CF among all parents in the cohort was 5.0% (1 in 20); however, when excluding parents of affected fetuses, the carrier frequency for the population was estimated at 4.1% (1 in 25). CFTR gene sequencing identified an additional VUS in two samples.
The incidence of CF in pregnancies with echogenic bowel in Nova Scotia and Prince Edward Island is 0.9%, with an estimated population carrier frequency of 4.1%. These results provide the basis for improved counselling to assess the risk of CF in the pregnancy, after parental carrier screening, using Bayesian probability. Counselling regarding VUSs should be undertaken before gene sequencing.
胎儿肠管回声增强（肠管回声增强）与囊性纤维化（CF）相关，据报道其发生率在1%至13%之间。在肠管回声增强的情况下，可通过筛查父母或胎儿样本中的致病性CFTR变异来进行CF的产前检测。如果仅鉴定出一个致病性变异，则可对CFTR基因进行测序，以鉴定标准筛查面板未涵盖的第二个致病性变异。然而，全基因测序也有可能鉴定出意义不明确的变异（VUS），这可能带来咨询方面的挑战并引起父母的焦虑。为了为研究人群中的家庭提供准确的咨询，对与肠管回声增强相关的CF发生率以及CFTR变异的携带者频率进行了调查。
确定所有因肠管回声增强指征而进行CF检测的妊娠（来自新斯科舍省和爱德华王子岛）（2007年1月至2017年7月）。回顾CFTR筛查和测序结果，并评估与CF相关的胎儿结局。
总共对463例肠管回声增强的妊娠进行了检测。4例被确诊患有CF，该队列中的发生率为0.9%。该队列中所有父母的CF携带者频率为5.0%（1/20）；然而，排除受影响胎儿的父母后，该人群的携带者频率估计为4.1%（1/25）。CFTR基因测序在两个样本中鉴定出另外的VUS。
新斯科舍省和爱德华王子岛肠管回声增强的妊娠中CF的发生率为0.9%，估计人群携带者频率为4.1%。这些结果为改进咨询提供了依据，以便在父母携带者筛查后，使用贝叶斯概率评估妊娠中CF的风险。应在基因测序前就VUS进行咨询。
