Unexplained fetal death has a biological signature of maternal anti‐fetal rejection: chronic chorioamnionitis and alloimmune anti‐human leucocyte antigen antibodies

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Abstract
Lee J, Romero R, Dong Z, Xu Y, Qureshi F, Jacques S, Yoo W, Chaiworapongsa T, Mittal P, Hassan S S & Kim C J (2011) Histopathology 59, 928–938Unexplained fetal death has a biological signature of maternal anti‐fetal rejection: chronic chorioamnionitis and alloimmune anti‐human leucocyte antigen antibodiesAims:  Chronic chorioamnionitis is a histological manifestation of maternal anti‐fetal cellular rejection. As failure of graft survival is the most catastrophic event in organ transplantation, we hypothesized that fetal death could be a consequence of maternal rejection. The aim of this study was to assess whether there is evidence of cellular and antibody‐mediated rejection in fetal death.Methods and results:  Placental histology was reviewed for the presence of chronic chorioamnionitis in unexplained preterm fetal death (n = 30) and preterm live birth (n = 103). Amniotic fluid CXCL10 concentrations were measured with a specific immunoassay. Chronic chorioamnionitis was more frequent in fetal death than in live birth (60.0% versus 37.9%; P < 0.05) and fetal death had a higher median amniotic fluid CXCL10 concentration than live birth (2.0 versus 1.8 ng/ml, P < 0.05), after adjusting for gestational age at amniocentesis. Maternal anti‐human leucocyte antigen class II panel‐reactive seropositivity determined by flow cytometry was higher in fetal death compared to live birth (35.7% versus 10.9%; P < 0.05).Conclusions:  Chronic chorioamnionitis is a common pathologic feature in unexplained preterm fetal death. This novel finding suggests that cellular and antibody‐mediated anti‐fetal rejection of the mother is associated with fetal death (graft failure) in human pregnancy.