TY - JOUR
T1 - Early detection of active Human CytomegaloVirus (hCMV) infection in pregnant women using data generated for noninvasive fetal aneuploidy testing
AU - Faas, Brigitte H.W.
AU - Astuti, Galuh
AU - Melchers, Willem J.G.
AU - Reuss, Annette
AU - Gilissen, Christian
AU - Macville, Merryn V.E.
AU - Ghesquiere, Stijn A.I.
AU - Houben, Leonieke M.H.
AU - Srebniak, Malgorzata Ilona
AU - Geeven, Geert
AU - Rahamat-Langendoen, Janette C.
AU - Sistermans, Erik A.
AU - Linthorst, Jasper
N1 - Funding Information:
This work was partly funded by the Prenatal Screening Foundation Nijmegen, the Netherlands.We thank Prof. Em Dr. B. Frank Vandenbussche for his helpful initiating discussions. Paul Daemen and Bart van den Bosch from the Department of Medical Microbiology, Radboud university medical center Nijmegen, The Netherlands, are kindly acknowledged for their expert technical assistance with the validation and interpretation studies.
Publisher Copyright:
© 2024 The Author(s)
PY - 2024/2/1
Y1 - 2024/2/1
N2 - Background: Prenatal hCMV infections can lead to severe embryopathy and neurological sequelae in neonates. Screening during pregnancy is not recommended by global societies, as there is no effective therapy. Recently, several groups showed that maternal–fetal hCMV transmission can be strongly reduced by administering anti-viral agents early in pregnancy. This calls for a screening method to identify at risk pregnancies at an appropriate gestational age, with the possibility for large-scale enrolment. Non-Invasive Prenatal Testing (NIPT) for fetal aneuploidy screening early in pregnancy is already implemented in many countries and performed on a large-scale basis. We investigated the use of whole genome cell-free DNA (cfDNA) sequencing data, generated for the purpose of NIPT, as (pre-)screening tool to identify women with active hCMV-infections, eligible for therapy. Methods: Coded raw sequencing NIPT data from 204,818 pregnant women from three testing laboratories were analyzed for the presence of hCMV-cfDNA. Samples were stratified by cfDNA-hCMV load. For validation and interpretation, diagnostic hCMV-qPCR and serology testing were performed on a subset of cfDNA-hCMV-positive (n = 112) and -negative (n = 127) samples. Findings: In 1930 samples (0.94%) hCMV fragments were detected. Validation by hCMV-qPCR showed that samples with high cfDNA-hCMV load tested positive and cfDNA-hCMV-negative samples tested negative. In 32/112 cfDNA-hCMV-positive samples (28.6%) the serological profile suggested a recent primary infection: this was more likely in samples with high cfDNA-hCMV load (78.6%) than in samples with low cfDNA-hCMV load (11.0%). In none of the cfDNA-hCMV-negative samples serology was indicative of a recent primary infection. Interpretation: Our study shows that large-scale (pre-)screening for both genetic fetal aberrations and active maternal hCMV infections during pregnancy can be combined in one cfDNA sequencing test, performed on a single blood sample, drawn in the first trimester of pregnancy. Funding: This work was partly funded by the Prenatal Screening Foundation Nijmegen, the Netherlands.
AB - Background: Prenatal hCMV infections can lead to severe embryopathy and neurological sequelae in neonates. Screening during pregnancy is not recommended by global societies, as there is no effective therapy. Recently, several groups showed that maternal–fetal hCMV transmission can be strongly reduced by administering anti-viral agents early in pregnancy. This calls for a screening method to identify at risk pregnancies at an appropriate gestational age, with the possibility for large-scale enrolment. Non-Invasive Prenatal Testing (NIPT) for fetal aneuploidy screening early in pregnancy is already implemented in many countries and performed on a large-scale basis. We investigated the use of whole genome cell-free DNA (cfDNA) sequencing data, generated for the purpose of NIPT, as (pre-)screening tool to identify women with active hCMV-infections, eligible for therapy. Methods: Coded raw sequencing NIPT data from 204,818 pregnant women from three testing laboratories were analyzed for the presence of hCMV-cfDNA. Samples were stratified by cfDNA-hCMV load. For validation and interpretation, diagnostic hCMV-qPCR and serology testing were performed on a subset of cfDNA-hCMV-positive (n = 112) and -negative (n = 127) samples. Findings: In 1930 samples (0.94%) hCMV fragments were detected. Validation by hCMV-qPCR showed that samples with high cfDNA-hCMV load tested positive and cfDNA-hCMV-negative samples tested negative. In 32/112 cfDNA-hCMV-positive samples (28.6%) the serological profile suggested a recent primary infection: this was more likely in samples with high cfDNA-hCMV load (78.6%) than in samples with low cfDNA-hCMV load (11.0%). In none of the cfDNA-hCMV-negative samples serology was indicative of a recent primary infection. Interpretation: Our study shows that large-scale (pre-)screening for both genetic fetal aberrations and active maternal hCMV infections during pregnancy can be combined in one cfDNA sequencing test, performed on a single blood sample, drawn in the first trimester of pregnancy. Funding: This work was partly funded by the Prenatal Screening Foundation Nijmegen, the Netherlands.
KW - Cell-free DNA
KW - Human cytomegalovirus
KW - Noninvasive prenatal testing
KW - Screening
KW - hCMV
U2 - 10.1016/j.ebiom.2024.104983
DO - 10.1016/j.ebiom.2024.104983
M3 - Article
SN - 2352-3964
VL - 100
JO - EBioMedicine
JF - EBioMedicine
M1 - 104983
ER -