Outcome of fetuses with congenital cytomegalovirus infection: a systematic review and meta-analysis

Objective: To report the outcome of fetuses with congenital Cytomegalovirus (CMV) infection and normal ultrasound at the time of diagnosis. Methods: Medline, Embase, Cinahl and Cochrane databases were explored. Inclusion criteria were fetuses with confirmed CMV infection and normal ultrasound assessment at the time of initial evaluation. The outcomes observed were anomalies detected at follow-up ultrasound scan, at prenatal magnetic resonance imaging (MRI) and at postnatal assessment, perinatal mortality, symptomatic infections at birth, neurodevelopmental outcomes, hearing and visual deficits. Random-effect meta-analysis of proportions were used to analyze the data. Results: 26 studies (2603 fetuses) were included. The overall rate of central nervous system (CNS) associated anomalies detected exclusively at follow-up ultrasound was 4.4% (95% CI 1.4-8.8; 32/523; 15 studies), while those detected exclusively by MRI or postnatally were 5.8% (95% CI 1.9-11.5; 19/357; 11 studies) and 3.2% (95% CI 0.3-9.0; 50/660; 17 studies), respectively. The rate of extra-CNS associated anomalies detected exclusively at follow-up ultrasound was 2.9% (95% CI 0.8-6.3; 19/523; 15 studies), while those detected exclusively by MRI or postnatally were 0% (95% CI 0.0-1.7; 0/357; 11 studies) and 0.9% (95% CI 0.3-1.8; 4/660; 17 studies), respectively. Both intrauterine death and perinatal death occurred in 0.7% of cases (95% CI 0.3-14.0; 2/824; 23 studies). A symptomatic infection was shown in 1.5% (95% CI 0.7-2.7; 6/548; 19 studies) of cases and the rate of overall neurodevelopmental anomalies was 3.1% (95% CI 1.6-5.1; 16/550; 19 studies), with hearing problems affecting 6.5% of children (95% CI 3.8-10.0; 36/550; 19 studies). Sub-analyses according to the trimester at infection were affected by the very small number of included cases and lack of comparison of the observed outcomes in the original studies. Fetuses infected in the first trimester had a relatively higher risk of having additional anomalies at follow-up ultrasound and MRI, symptomatic infection, abnormal neurodevelopmental outcome and hearing problems. Conclusions: In fetuses with congenital CMV infection showing no anomalies on both US and MRI, the risk of adverse postnatal outcome is lower compared to what reported from previously published literature not considering the role of antenatal imaging assessment. The findings from this study can enhance prenatal counselling of pregnancies with congenital CMV infection with normal prenatal imaging.