Sudden Intrauterine Unexplained Death (SIUD) «Gray Zone» or borderline

The author reports the histopathological findings of 9 fetuses (3 females and 6 males, ranging in age from 34 to 41 gestational weeks) that died suddenly and unexpectedly in utero. They presented brainstem and cardiac conduction system lesions together with abnormalities of the fetal adnexa. A complete autopsy was performed, including detained investigation of the brainstem and cardiac conduction system on serial sections, as well as of the fetal adnexa, according to our guidelines. Histological examination of the fetal adnexa disclosed the presence of chorioamnionitis (7 cases), an abnormally short umbilical cord (1 case), and placental infection by parvovirus (1 case). These lesions were associated with brainstem lesions, i.e., hypoplasia of the arcuate nucleus (6 cases), inflammatory infiltrates in the brainstem (2 cases), hypoplasia of the raphe obscurus nucleus (2 cases), hypoplasia of the parabrachial Kölliker-Fuse complex (1 case), hypoplasia of the pre-Bötzinger complex (1 case), agenesis of the facial/parafacial complex (1 case), as well as conduction system lesions, i.e., dispersion or septation of the atrio-ventricular junction (9 cases), islands of the conduction system inside the central fibrous body (5 cases) resorptive degeneration (4 cases), cartilaginous meta-hyperplasia (2 cases), Mahaim fibers (1 case). Each SIUD victim presented at least one of these brainstem and/or cardiac conduction abnormalities, more than one change being present in the same fetus. The SIUD «gray zone», or borderline cases, are hereby described as those cases in which the lesions of the fetal adnexa alone might not have accounted for the sudden deaths, had it not been for the concomitant presence of brainstem and cardiac conduction lesions representing the morphological substrates for SIUD, as well as for SIDS. Our 9 cases are consistent with the triple-risk model, a hypothesis introduced for SIDS postulating an underlying biological vulnerability to exogenous stressors or triggering factors in a critical developmental period. In conclusion, we are convinced that there is a continuum between SIUD and SIDS and the triple-risk model is herein considered for the first time also for SIUD “gray zone” victims.