Intrauterine Fetal Demise, Spontaneous Abortion and Congenital Cytomegalovirus: A Systematic Review of the Incidence and Histopathologic Features

The objective was to review the existing literature reporting on spontaneous abortion (SA) and intrauterine fetal demise (IUFD) associated with cytomegalovirus (CMV) infection. A review using standardized terminology such as ‘intrauterine fetal death’, ‘congenital cytomegalovirus’ and ‘CMV’ was performed using PubMed and Embase (Medline) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Twenty-one studies met inclusion criteria. CMV was identified as a potential or likely factor in a median of 7.1% of SA or IUFD in study cohorts. Of the studies, 11 used fetal remains, 18 used placenta, 6 used serum, and 1 used post-mortem dried blood spot as specimens for testing for CMV. Features commonly observed were fetal thrombotic vasculopathy, hydrops fetalis and chronic villitis. CMV is frequently noted in studies evaluating viral etiologies of SA or IUFD. Large population-based studies are needed to estimate the incidence of CMV-associated SA or IUFD. CMV and congenital CMV should be included on the differential diagnosis in all cases of SA or IUFD of unknown etiology.