Villitis of Unknown Etiology (VUE) is a poorly understood destructive placental lesion. In VUE, mononuclear cells infiltrate the chorionic villi, resulting in chronic inflammation, fibrosis and necrosis. VUE has been associated with adverse fetal outcomes including fetal growth restriction, preterm delivery and stillbirth. However, as VUE is reported to occur in up to 13.6% of all pregnancies (1), many of which are healthy, there is considerable uncertainty regarding its clinical relevance.
A recent prospective observational study was co-designed with the Australian Indigenous Butchulla to investigate disproportionally high rates of stillbirth occurring in the community. The study enrolled families expecting an Indigenous baby (n=83) between June 2022 and June 2023. Placentas were collected following live births and submitted for pathology (n=66). Analysis of pathology reports revealed a 25.5% incidence of VUE across the cohort, with 7.6% of cases considered high grade. As there is still no definitive pathogenesis for VUE, it is difficult to reconcile pathological findings with disease drivers.
A scoping review was subsequently undertaken to determine current practice in the diagnosis and emerging knowledge of VUE risk factors. The review was performed in accordance with the PRISMA international guidelines, with ProQuest, Scopus and PubMed databases searched for relevant MeSH terms (keywords). Results imported into Covidence, duplicates removed, and each source was independently screened according to pre-determined inclusion and exclusion criteria by two reviewers. Included sources were extracted for thematic analysis. Overall, our scoping review revealed inconsistencies in VUE diagnosis, grading, risk factors and rates. We discovered that despite the growing association of VUE with inflammatory mediators, the risk factors and molecular drivers of VUE remain poorly understood. The notable increase of VUE within our cohort of Australian Indigenous families requires further investigation to determine the relevance of both genetic and environmental factors in VUE risk and development.