Placental C4d as a common feature of chromosomally normal and abnormal miscarriages

Placental C4d deposition is a feature of classical complement pathway activation and has been documented in various obstetrical settings. However, it is unknown whether placental C4d deposition is present in miscarriages and its frequency is different between chromosomally normal and abnormal miscarriages. This study was conducted to assess villous C4d deposition in miscarriages and to determine whether its frequency is different between chromosomally normal and abnormal miscarriages. Tissue samples (N = 58) of elective abortions (n = 20), miscarriages with normal chromosomes (n = 15), trisomy 16 (n = 13), and trisomy 22 (n = 10) were analyzed. Immunohistochemical staining for C4d and CD138 was done. Placental C4d deposition was defined as linear C4d immunoreactivity along the syncytiotrophoblast. Placental C4d immunoreactivity was detected in 73.3 % (11/15) and 56.5 % (13/23) of miscarriages with normal chromosomes and trisomy cases, respectively, while it was found in 5 % (1/20) of elective abortions (p < 0.05). Placental C4d deposition was more frequent in recurrent miscarriages (previous spontaneous abortion ≥2) than in sporadic miscarriages (76.5 vs. 30.0 %; p = 0.001). Chronic deciduitis was observed in 20.0 % (3/15) and 30.4 % (7/23) of miscarriages with normal chromosomes and trisomy cases, respectively, but not in elective abortions (p = 0.07 and 0.01, for each). The frequencies of C4d deposition (46.2 vs. 70.0 %) and chronic deciduitis (38.5 vs. 20.0 %) were not also different between trisomy 16 and trisomy 22 cases. Placental C4d deposition is a prominent feature of miscarriages regardless of their chromosomal status. The overall findings suggest that complement-mediated placental injury is a common pathology of miscarriage with diagnostic values in routine pathology practice.