Antenatal imaging and clinical outcome in congenital CMV infection: A field-wide systematic review and meta-analysis

Objectives: Postnatal outcome in fetuses with congenital cytomegalovirus infection (cCMV) varies from asymptomatic infection to severe neurodevelopmental impairment. Αntenatal biomarkers of long-term clinical outcome, have yet to be established. Α systematic review and meta-analysis was performed to examine whether prenatal cerebral ultrasonography (US) and magnetic resonance imaging (MRI) findings in cCMV fetuses may predict clinical outcome.

Methods: PubMed and the Web of Science were systematically searched to identify studies reporting on any prenatal US and/or MRI imaging of fetuses with cCMV as well as their postnatal clinical outcome. All reported associations between imaging and postnatal clinical outcome were systematically extracted. Where appropriate, the reported associations were quantitatively synthesized within Bayesian random-effects meta-analyses.

Results: A total of 1336 studies were screened to identify 26 eligible observational studies. Overall, 4181 fetuses were studied, of which 1518 had been diagnosed with cCMV. All studies performed fetal US while in 14 (54%) MRI was also performed. Studies substantially varied in timing of fetal imaging, reporting of abnormalities, definition of poor outcome and statistical analysis. Among studies reporting on statistical significance, 6/6 for US and 3/4 for MRI identified significant associations between imaging findings and outcome. In our meta-analyses, within isolated abnormalities, only microcephaly had greater than 95% probability of being associated with poor outcome (OR 26.7; 95% CI, 1.44-1464.5; I², 19%). Effect sizes for US were higher than those for MRI findings.

Conclusions: Although studies displayed significant heterogeneity in both methodology and analytical decisions, it became evident that when both prenatal cerebral US and MRI are normal the negative predictive value of poor outcome is high. This is important for clinicians when consulting pregnant women. Need to standardize practices and definitions become evident.

Funding: There was no source of funding.