Objectives: This study was undertaken to investigate the incidence and associations of placental villitis of unknown origin or etiology (VUE).
Study design: Five hundred nine placentas from women delivered of small-for-gestational-age infants (SGAP) and 529 placentas from women delivering infants with birth weights appropriate for gestational age (AGAP) were examined prospectively for VUE as part of a population-based case control study of SGA infants at term.
Results: VUE was found in 17.3% of SGAP and 11.7% of AGAP and was an independent risk factor for SGA (adjusted odds ratio 2.35, 95% CI 1.55-3.56). Villitis in conjunction with maternal hypertension increased the risk of SGA substantially (adjusted odds ratio 17.7, 95%CI 3.6-86.9). A study of a wide range of pregnancy-related factors found no significant associations with VUE in AGAP. In contrast, VUE in SGAP had significant associations after multivariate analysis with maternal body mass index, multigravidity, ethnicity, and 1 index of maternal infection.
Conclusion: VUE is an independent risk factor for SGA at term. Maternal factors influence this association, possibly by modifying a systemic effect on fetal growth of villous inflammation at commonly occurring defects in the maternal-fetal immune barrier.