Novel method for predicting the severity of congenital cytomegalovirus infection in fetuses and newborns

Overview

Congenital cytomegalovirus (CMV) is the most common intrauterine infection, affecting in average 0.64 % of births and leading to infant brain damage. Approximately 25% of congenitally infected infants suffer from neurological and/or audiological disabilities, which can be apparent at birth or develop later during childhood.Following primary maternal infection during pregnancy, the risk of intrauterine transmission to the fetus is high (~30%). Pregnant women diagnosed with primary CMV infection are routinely referred for amniotic fluid PCR test for the diagnosis of fetal CMV infection. Once fetal infection is diagnosed, there have been (up until now) no established prenatal biomarkers of the severity of fetal disease. Women bearing infected fetuses are currently facing difficult moments of ambivalence and have no other choice but making harsh decisions on the fate of the fetus with potential termination of the pregnancy, based solely on general statistical data.

Our solution

 

Addressing this pressing clinical-diagnostic need, Prof. Dana Wolf and her team performed global proteome analysis of mid-gestation amniotic fluid samples (routinely obtained for the diagnosis of fetal CMV infection), comparing amniotic fluids of fetuses with severe congenital CMV infection with those of asymptomatic CMV-infected fetuses and newborns. The study resulted in the discovery of novel and accurate protein biomarkers, Chemerin and Galectin-3-binding protein (Gal-3BP), shown to be highly predictive (100-93.8% positive predictive value and 92.9-92.6% negative predictive value) of the severity of congenital CMV in the largest independent validation cohort examined to date.

Application

The groundbreaking discovery of biomarkers with unprecedented predictive accuracy will provide pregnant women, parents, and physicians with a long-awaited diagnostic tool, which could be employed to profoundly improve the prognostic assessment of CMV-infected fetuses and newborns and guide personalized decisions and treatment. The new biomarkers are likely to be integrated in clinical trials aimed to prevent congenital CMV infection and disease.

 

 

 

Market size

The groundbreaking discovery of biomarkers with unprecedented predictive accuracy will provide pregnant women, parents, and physicians with a long-awaited diagnostic tool, which could be employed to profoundly improve the prognostic assessment of CMV-infected fetuses and newborns and guide personalized decisions and treatment. The new biomarkers are likely to be integrated in clinical trials aimed to prevent congenital CMV infection and disease.

Development Status

• Expanded validation studies are currently ongoing.
• Prospected studies in neonates born with congenital CMV infection.

Intellectual Property

PCT Publication number: WO 2021/155860 A1

References:

Amniotic fluid biomarkers predict the severity of congenital cytomegalovirus infection Olesya Vorontsov, … , Amos Panet, Dana G. Wolf J Clin Invest. 2022;132(11):e157415. https://doi.org/10.1172/JCI157415