EA 73-28, Université de Paris, Paris, France.
AP-HP, Department of Obstetrics and Fetal Medicine, Hopital Necker-E.M., Paris, France.
Ultrasound Obstet Gynecol. 2021 Apr;57(4):568-572. doi: 10.1002/uog.23608. Epub 2021 Mar 9.
To evaluate the feasibility of amplification of the viral genome by polymerase chain reaction (PCR) analysis of trophoblast samples obtained by chorionic villus sampling (CVS) in cases of maternal primary infection (MPI) with cytomegalovirus (CMV) in early pregnancy.
This was a prospective study carried out at the Department of Obstetrics and Fetal Medicine, Hopital Necker-E.M., between October 2019 and October 2020. Following CMV serology screening in early pregnancy, CVS was offered to women at 11-14 weeks' gestation after CMV-MPI ≤ 10 weeks. Array-comparative genomic hybridization and amplification of the viral genome by PCR were performed on the trophoblasts obtained by CVS. All cases also underwent amniocentesis from 17 weeks onwards and PCR was performed on the amniotic fluid. Secondary prevention with valacyclovir was initiated as soon as MPI was diagnosed, to decrease the risk of vertical transmission. We evaluated the diagnostic performance of CMV-PCR of trophoblast obtained by CVS, using as the reference standard PCR of amniotic fluid obtained by amniocentesis.
CVS was performed in 37 pregnancies, at a median (range) gestational age of 12.7 (11.3-14.4) weeks. CMV-PCR in chorionic villi was positive in three and negative in 34 cases. CMV-PCR following amniocentesis, performed at a median (range) gestational age of 17.6 (16.7-29.9) weeks, was positive for the three cases which were positive following CVS and, of the 34 patients with a negative finding following CVS, amniocentesis was negative in 31 and positive in three. The sensitivity of CMV-PCR analysis of trophoblast obtained by CVS for the diagnosis of CMV, using as the reference standard PCR analysis of amniotic fluid obtained by amniocentesis, was 50% (95% CI, 19-81%), specificity was 100% (95% CI, 89-100%), positive predictive value was 100% (95% CI, 44-100%) and negative predictive value was 91% (95% CI, 77-97%).
Diagnosis of placental infection following MPI in early pregnancy can be achieved by PCR amplification of the CMV genome in chorionic villi. We propose that negative CMV-PCR in the trophoblast after 12 weeks could be used to exclude CMV-related embryopathy leading to sequelae. However, this needs to be confirmed through long-term follow-up evaluation. These findings could help to establish CVS as the diagnostic test of choice following maternal serology screening in early pregnancy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
评估通过聚合酶链反应（PCR）分析在孕早期巨细胞病毒（CMV）母体原发感染（MPI）时通过绒毛膜绒毛取样（CVS）获得的滋养层样本中扩增病毒基因组的可行性。
这是 2019 年 10 月至 2020 年 10 月期间在 Necker-EM 医院妇产科进行的一项前瞻性研究。在孕早期进行 CMV 血清学筛查后，在 MPI≤10 周后，在 11-14 周妊娠时向孕妇提供 CVS。对 CVS 获得的滋养层进行比较基因组杂交微阵列和病毒基因组的 PCR 扩增。所有病例还在 17 周后进行羊膜穿刺术，并对羊水进行 PCR。一旦诊断出 MPI，立即开始使用伐昔洛韦进行二级预防，以降低垂直传播的风险。我们使用羊膜穿刺术获得的羊水 PCR 作为参考标准，评估通过 CVS 获得的滋养层 CMV-PCR 的诊断性能。
37 例妊娠进行了 CVS，中位（范围）妊娠龄为 12.7（11.3-14.4）周。CMV-PCR 在绒毛中为阳性的有 3 例，阴性的有 34 例。在中位（范围）妊娠龄为 17.6（16.7-29.9）周时进行的羊膜穿刺术，CMV-PCR 对 3 例 CVS 后阳性的病例呈阳性，而在 34 例 CVS 后阴性的病例中，31 例羊膜穿刺术阴性，3 例阳性。使用羊膜穿刺术获得的羊水 PCR 作为参考标准，通过 CVS 分析的滋养层中 CMV-PCR 对 CMV 的诊断灵敏度为 50%（95%CI，19-81%），特异性为 100%（95%CI，89-100%），阳性预测值为 100%（95%CI，44-100%），阴性预测值为 91%（95%CI，77-97%）。
孕早期 MPI 后胎盘感染的诊断可以通过 CMV 基因组在绒毛中的 PCR 扩增来实现。我们建议，12 周后滋养层中 CMV-PCR 阴性可排除导致后遗症的 CMV 相关胚胎病。然而，这需要通过长期的随访评估来证实。这些发现可以帮助建立 CVS 作为孕早期母体血清学筛查后的首选诊断试验。
