Comparative performance of CMV IgM and IgG avidity assays for diagnosing a recent primary infection in the first trimester of pregnancy.

UNLABELLED: First-trimester (T1) cytomegalovirus (CMV) screening relies on IgG, IgM, and IgG avidity testing, but assay performance may vary according to the infection timing. To evaluate the ability of two IgM and three IgG avidity assays to detect maternal primary CMV infection (MPI) occurring in T1 or the periconceptional period. We analyzed 176 serum samples from 94 pregnant women with precisely dated MPI based on seroconversion. Samples were tested using two IgM assays (LIAISON CMV IgM II, Alinity i CMV IgM) and three IgG avidity assays (VIDAS CMV IgG Avidity II, LIAISON CMV IgG Avidity II, Alinity i CMV IgG avidity). For detection of MPI within 4 months, the IgM sensitivity was 99% (122/123) with LIAISON and 92% (94/102) with Alinity i. IgG avidity sensitivity for excluding MPI <4 months was 99% (124/125) with LIAISON, 98% (121/123) with VIDAS, and 92% (111/120) with Alinity i. The positive predictive value of low avidity was highest with VIDAS, followed by LIAISON and Alinity i. Retesting intermediate-avidity results with a second assay improved the estimation of MPI timing. All three avidity assays reliably excluded T1 MPI. Alinity i showed reduced sensitivity for ruling out periconceptional infection, supporting confirmatory testing in equivocal cases.

IMPORTANCE

In the context of universal first-trimester cytomegalovirus (CMV) screening and the demonstrated efficacy of valacyclovir to prevent vertical transmission, reliable identification of recent maternal primary infection has become crucial. In this study, we compared the performance of two CMV IgM kits (LIAISON CMV IgM II [DiaSorin]; Alinity i CMV IgM [Abbott Diagnostics]) and three CMV IgG avidity kits (LIAISON CMV IgG Avidity II [DiaSorin]; VIDAS CMV IgG Avidity II [Biomérieux]; Alinity i CMV IgG avidity [Abbott Diagnostics]). Our study assesses the performance of commonly used CMV IgM and IgG avidity assays in a large cohort of pregnant women with precisely dated primary infections, a setting rarely available for assay validation. We provide gestational age-specific performance data and highlight the limited positive predictive value of intermediate-IgG avidity results. Based on these findings, we propose a pragmatic diagnostic algorithm aimed at reducing misclassification and inappropriate clinical management.