Emerging Prognostic and Predictive Biomarkers for Human Cytomegalovirus Infection During Pregnancy: Unmet Needs and Future Perspectives

Abstract

Human cytomegalovirus (HCMV) infection during pregnancy is a leading cause of congenital infections worldwide, posing significant risks to fetal health. Despite advances in prenatal care, managing HCMV infection remains challenging. Early detection, accurate risk assessment, and timely intervention are critical to mitigating the adverse outcomes associated with congenital HCMV (cHCMV), such as neurodevelopmental delays and hearing loss. However, the current landscape of biomarkers for HCMV infection in pregnancy is marked by several unmet needs. These gaps in biomarker development and application limit our ability to predict fetal transmission, assess the risk of fetal damage, and prognosticate long-term outcomes. Addressing these challenges through the identification and validation of novel biomarkers could revolutionize the management of HCMV in pregnancy, leading to improved outcomes for both mothers and their children. This review examines the critical unmet needs regarding HCMV biomarkers during pregnancy, emphasizing the priority areas for further research and innovation.

Keywords: DNAemia; HCMV; NIPT; T-cell response; biomarkers; exosomes; serology.

Figure 1

Rates of vertical transmission (green) and fetal disease (blue) for primary human cytomegalovirus infection in pregnancy.

Figure 2

Biomarkers for human cytomegalovirus (HCMV) infection in pregnancy. Overview of potential biomarkers used for diagnosing, monitoring, and predicting the outcomes of HCMV infection during pregnancy. These include traditional serological and molecular markers (HCMV DNA, IgG, and IgG avidity), immune response markers (T-cell responses), and emerging non-invasive biomarkers such as non-invasive prenatal testing (NIPT) for cell-free DNA (cfDNA-HCMV) and placental exosomes.