Prognostic Value of Amniotic Fluid Viral Load to Predict Adverse Outcome in Pregnancies Complicated by Congenital Cytomegalovirus Infection: A Multicenter Study

Abstract

Introduction: To report the prognostic value of Cytomegalovirus (CMV) viral load in the amniotic fluid (AF) in predicting the outcome of infected pregnancies. Methods: Multicenter retrospective study involving 11 Italian referral centers from 2012 to 2021. Inclusion criteria were fetuses with confirmed congenital CMV infection. The primary outcome was the prognostic value accuracy of CMV qPCR in AF in predicting the risk of additional anomalies detected either at follow-up ultrasound or fetal MRI. The secondary outcome was prediction of post-natal clinical symptoms related CMV infection. Multivariate logistic regression and area under the curve (AUC) analyses were used to analyze the data. Results: 104 fetuses were included. Associated anomalies detected at follow-up ultrasound or fetal MRI were detected in 14.4% of cases (15/104). Mean AF CMV viral load was significantly higher in fetuses with compared to those without additional anomalies at follow-up ultrasound or fetal MRI (3346634.27±402582.95 vs 761934±222513,2 p<0.001). At multivariate logistic regression analysis, CMV AF viral load was independently associated with the presence of additional anomalies at follow up ultrasound or MRI, with an OR of 1.07 (p= 0.010), while maternal age(p=0.24), trimester at maternal infection (p= 0.97), type of infection (primary vs non-primary) (p=0.12) were not. CMV AF viral load had AUC of 0.755 for the occurrence of anomalies due to CMV infection, with an optimal cut-off point of >1310520 copies/ml, a sensitivity of 66.7% and a specificity of 84.3% a positive likelihood ratio of 4.24. Once excluding fetuses with anomalies at ultrasound or MRI, the diagnostic performance of qPCR in identifying fetuses with symptomatic infection after birth was low, with an AUC of 0.586, Conclusion: CMV viral load at second trimester amniocentesis has a moderate accuracy for the occurrence of CMV related anomalies in fetuses with congenital infection and normal ultrasound at the initial diagnosis. Conversely, prediction of symptomatic infection is low.

Is a Higher Amniotic Fluid Viral Load Associated with a Greater Risk of Fetal Injury in Congenital Cytomegalovirus Infection—A Systematic Review and Meta-Analysis

“…Sixty-seven studies underwent full text review for assessment of eligibility and 59 of these were excluded for various reasons, as listed in Figure 1. Eight studies fulfilled inclusion criteria and were included in our meta-analysis [11,12,17,[19][20][21][22][23]. These studies were published between 2009 and 2023 and originated from Europe (six from Italy, one from France, and one from Belgium) and Asia (one from Israel).…”

Evaluation of Congenital Cytomegalovirus Infection in Pregnant Women Admitted to a University Hospital in Istanbul

“…It should be noted that almost all infants showing clinical signs of congenital CMV infection are born to mothers who contracted a primary CMV infection during their pregnancy, and congenital CMV infection occurs in 1% of infants globally [ 25 , 26 , 27 , 28 ]. After 20 weeks of pregnancy, an ultrasound can highlight potential indications of congenital CMV infection, but these must be confirmed using serological or PCR tests [ 29 ]. The diagnosis of congenital CMV is complex and should not rely on serological tests alone.…”

“…Research has shown that there is no direct correlation between the viral load in the amniotic fluid and symptoms of prenatal CMV infection [ 29 ]. Using amniocentesis to test the viral load yields a sensitivity and specificity of 66.7% and 84.3%, respectively.…”

“…Thus, the ability of this testing method to predict symptomatic infection is somewhat limited. Consequently, in prenatal CMV infections, the severity of the accompanying prenatal symptoms holds more weight than the CMV DNA viral load detected using amniocentesis [ 29 ].…”

Reply: Neurosonography and magnetic resonance imaging for cytomegalovirus infection – integration of imaging modalities is key

“…However, the performance of fetal neurosonography can be influenced by several factors, including fetal position, gestational age at assessment, maternal body mass index and type of CNS anomalies assessed, thus making published studies difficult to compare. Furthermore, we reported recently that high viral load in the amniotic fluid is an independent predictor of the occurrence of CMV‐related anomalies on follow‐up imaging or at birth 8,9 . In light of this, generalizing about the optimal imaging technique to assess fetuses with CMV might be difficult.…”