Establishing Correlates of Maternal-Fetal Cytomegalovirus Transmission-One Step Closer Through Predictive Modeling

J Infect Dis. 2024 Dec 16;230(6):e1274-e1286. doi: 10.1093/infdis/jiae281.

Abstract

Background: Determinants of maternal-fetal cytomegalovirus (CMV) transmission and factors influencing the severity of congenital CMV (cCMV) infection are not well understood.

Methods: We conducted a descriptive, multicenter study in pregnant women ≥18 years old with primary CMV infection and their newborns to explore maternal immune responses to CMV and determine potential immunologic/virologic correlates of cCMV following primary infection during pregnancy. We developed alternative approaches looking into univariate/multivariate factors associated with cCMV, including a participant clustering/stratification approach and an interpretable predictive model-based approach using trained decision trees for risk prediction (post hoc analyses).

Results: Pregnant women were grouped in 3 distinct clusters with similar baseline characteristics, particularly gestational age at diagnosis. We observed a trend for higher viral loads in urine and saliva samples from mothers of infants with cCMV versus without cCMV. When using a trained predictive-model approach that accounts for interaction effects between variables, anti-pentamer immunoglobulin G antibody concentration and viral load in saliva were identified as biomarkers jointly associated with the risk of maternal-fetal CMV transmission.

Conclusions: We identified biomarkers of CMV maternal-fetal transmission. After validation in larger studies, our findings will guide the management of primary infection during pregnancy and the development of vaccines against cCMV.

Clinical trials registration: NCT01251744.

Keywords: antibodies; congenital cytomegalovirus infection; correlate of risk; modeling; viral load.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Biomarkers
  • Cytomegalovirus Infections* / immunology
  • Cytomegalovirus Infections* / transmission
  • Cytomegalovirus* / immunology
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical*
  • Pregnancy
  • Pregnancy Complications, Infectious* / virology
  • Saliva* / virology
  • Viral Load*
  • Young Adult

Substances

  • Antibodies, Viral
  • Biomarkers
  • Immunoglobulin G

Associated data

  • ClinicalTrials.gov/NCT01251744