Investigating the association of villitis of unknown etiology with stillbirth and fetal growth restriction - A systematic review

Villitis of unknown etiology (VUE) is an inflammatory condition reported to occur in up to 15% of term placentas. It has been reported in association with fetal growth restriction and antepartum stillbirth. This study aimed to investigate the strength of these associations by completing a systematic review using established guidelines. 618 potentially relevant studies were identified. After exclusion of studies that were not relevant or of insufficient quality, a total of 24 case-control and cohort studies were included in the review. Studies were grouped according to whether their main focus was VUE, fetal growth restriction or stillbirth. A methodological quality assessment carried out for each group demonstrated significant heterogeneity in study design. VUE occurs more frequently in placentas of growth restricted infants. A significant link between VUE and stillbirth could not be reliably established because there were too few published studies. Further research into the pathological effects of VUE using robust protocols and reporting methods is required.