Contribution of Fetal Blood Sampling to Determining the Prognosis of Congenital Cytomegalovirus Infections: A Case-Cohort Study in Switzerland.

Abstract

Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5-1% of live births in Europe. Congenital CMV infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish based on prenatal imaging alone. To identify predictors of moderate to severe symptomatic CMV infection among fetal blood parameters, and to propose an algorithm based on these parameters and on prenatal imaging that would provide the best positive and negative predictive values. Fetal blood sampling at 21-28 weeks' gestation was performed in fetuses with congenital CMV infection confirmed by amniocentesis after maternal infection in the first trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, gamma-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, β2-microglobulin, immunoglobulins G and M, and CMV DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, β2 microglobulin, IgM, and CMV viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cut-offs: thrombocytes < 120,000/mL, viremia ≥ 5 log10 /mL, and β2 microglobulin ≥ 12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. The combination of thrombocytes, β2-microglobulin, and CMV viral load in fetal blood can be used for prognosis determination, particularly in CMV-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir prior to fetal blood sampling.