First‐trimester diagnosis of congenital cytomegalovirus infection after maternal primary infection in early pregnancy: feasibility study of viral genome amplification by PCR on chorionic villi obtained by CVS

ABSTRACT Objective 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. Methods 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. Results 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%). Conclusions 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 Obstet