Gestational autoimmune disease in newborns with an indeterminate cause of death following a complete autopsy

Gestational alloimmune liver disease (GALD) is the result of neonatal complement-mediated severe liver injury mediated by maternal alloantibodies, which is detected by immunohistochemistry staining for the complement C5b-9 complex. GALD leads to the neonatal hemochromatosis (NH) phenotype, which also shows extrahepatic siderosis, and can result in neonatal death. At autopsy, the histologic damage of the liver in GALD may be subtle and misinterpreted as non-specific post-mortem changes, resulting in the cause of death classified as indeterminate. We reviewed the pathologic diagnoses from autopsy material from 1996 to 2011 of infants 0-90 days of age from our institution. Liver samples were stained with H&E, trichrome and for C5b-9. 13 cases originally diagnosed as indeterminate cause of death were identified and divided in 3 groups: (1) No clinical or autopsy-derived diagnoses (n = 7), (2) Defined clinical diagnoses but no cause of death determined at autopsy (n = 2), and (3) Liver disease, but no clinical or autopsy diagnoses to establish the cause of the liver injury (n = 4). On reexamination, all group 1 and 3 cases were reclassified as GALD, based on a positive C5b-9 stain. Group 2 cases were not GALD, retaining the original, clinically-based cause of death. We conclude that, in cases of indeterminate cause of neonatal death, very careful examination for hepatocyte injury/necrosis, extrahepatic siderosis, liver fibrosis and/or C5b-9 stain should be considered.