Outcome of fetuses with congenital cytomegalovirus infection and normal ultrasound at diagnosis: 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, and to evaluate the rate of an additional anomaly detected only on magnetic resonance imaging (MRI). Methods: Medline, EMBASE, CINAHL and Cochrane databases were searched for studies reporting on the outcome of fetuses with congenital CMV infection. Inclusion criteria were fetuses with confirmed CMV infection and normal ultrasound assessment at the time of the initial evaluation. The outcomes observed were an anomaly detected on a follow-up ultrasound scan, an anomaly detected on prenatal MRI but missed on ultrasound, an anomaly detected on postnatal assessment but missed prenatally, perinatal mortality, symptomatic infection at birth, neurodevelopmental outcome and hearing and visual deficits. Neurodevelopmental outcome was assessed only in cases of isolated CMV infection confirmed at birth. Subgroup analysis was performed according to the trimester in which maternal infection occurred. Random-effects meta-analysis of proportions was used to analyze the data. Results: Twenty-six studies were included, comprising 2603 fetuses with congenital CMV infection, of which 1178 (45.3%) had normal ultrasound at the time of diagnosis and were included in the analysis. The overall rate of an associated central nervous system (CNS) anomaly detected on a follow-up ultrasound scan was 4.4% (95% CI, 1.4–8.8%) (32/523; 15 studies), while the rates of those detected exclusively on prenatal MRI or on postnatal imaging 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 an associated extra-CNS anomaly detected on a follow-up ultrasound scan was 2.9% (95% CI, 0.8–6.3%) (19/523; 15 studies), while the rates of those detected exclusively on MRI or on postnatal imaging 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. Intrauterine death and perinatal death each occurred in 0.7% (95% CI, 0.3–1.4%) (2/824; 23 studies) of cases. In cases without an associated anomaly detected pre- or postnatally, symptomatic infection was found in 1.5% (95% CI, 0.7–2.7%) (6/548; 19 studies) of infants, the overall rate of a neurodevelopmental anomaly was 3.1% (95% CI, 1.6–5.1%) (16/550; 19 studies), and hearing problems affected 6.5% (95% CI, 3.8–10.0%) (36/550; 19 studies) of children. Subanalyses according to the trimester in which maternal infection occurred were affected by the very small number of included cases and lack of comparison of the observed outcomes in the original studies. Compared with fetuses infected in the second or third trimester, those infected in the first trimester had a relatively higher risk of having an additional anomaly detected on follow-up ultrasound or MRI, abnormal neurodevelopmental outcome and hearing problems. Conclusions: In fetuses with congenital CMV infection in which no anomalies are detected on prenatal ultrasound or MRI, the risk of adverse postnatal outcome is lower than that reported previously in the published literature when not considering the role of antenatal imaging assessment. The results from this review also highlight the potential role of MRI, even in fetuses with no anomalies detected on ultrasound, as an anomaly can be detected exclusively on MRI in about 6% of cases. The findings from this study could enhance prenatal counseling of pregnancies with congenital CMV infection with normal prenatal imaging. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.