Third-Trimester Stillbirths: Correlative Neuropathology and Placental Pathology

Abstract

Although in recent years placental pathology has been the subject of a wealth of detailed descriptions and diagnostic categorization, systematic correlation of these conditions with the pathology of stillbirth has not been attempted. We examine the relationship between specific inflammatory, maternal, and fetal vascular pathologies and the central nervous system pathology and histological indicators of fetal compromise. Our design was a retrospective case series of 37 3rd-trimester intrauterine fetal deaths. In general, mixed placental pathologies were the rule, with three quarters of the placentas demonstrating combinations of maternal vascular pathology, fetal vascular pathologies, umbilical cord abnormalities, or inflammatory lesions. The range of brain pathology was limited to acute, severe congestion, white matter edema, and neuronal karyorrhexis (pontosubicular necrosis with or without neuronal karyorrhexis at other sites). Established periventricular leukomalacia was present in only 2 cases. The presence of neuronal karyorrhexis or white matter gliosis was correlated with the presence of a high-grade inflammatory lesion and with fetal thymic involution. Neuronal karyorrhexis, but not white matter gliosis, correlated as well with histologically established fetal vascular lesions in the placenta, even once the effect of inflammation was accounted for. Gliosis also correlated with inflammation, meconium staining, and thymic involution. Central nervous system injury may be the end result of complex placental pathologies, and neuronal injury may be a consequence of the fetal inflammatory response. The correspondence between the time courses of histological features of chorioamnionitis, neuronal karyorrhexis, and thymic involution points to irreversible central nervous system injury being common 12-48 hours prior to in utero demise.

Does aetiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy influence the outcome of treatment?

“…32,33 However, the nature of the placental abnormality differs in several ways, supporting the aetiological diversity of these clinical syndromes. As there appears to be an important role for the placenta in the illnesses underlying the majority of neonatal encephalopathy, current animal models of asphyxial HIE may be inadequate for studying neonatal encephalopathy in human infants.…”

The neuropathology of stillbirth — Correlation with apolipoprotein genotype in a Scottish population based study

“…The dearth of brain damage in this group is perhaps surprising in view of other studies that have linked the two pathologies [9,16,60] but the number of intrapartum deaths is relatively small in this cohort. In all groups in the present study there was a trend for placental inflammation to be linked to preterm stillbirth, as in other studies [61], but it should be noted that chorioamnionitis was generally mild in most cases.…”

“…βAPP positive axons have been linked to traumatic injury [49] but any insult that interferes with axonal transport can lead to accumulation of axonal proteins [50,52]. Chang et al [16] investigated βAPP expression in 37 stillbirths but did not report the percentage of cases that displayed axonal positivity.…”

“…The neuropathology of perinatal death has been described both in classic and recent studies [1][2][3][4][5][6][7][8][9][10], but most of these do not clearly separate live born from stillborn infants and relatively few are devoted solely to stillbirths [9,[11][12][13][14][15][16][17]. However, there is sufficient evidence in the literature to show that most if not all of the lesions seen in neonates may also be found in the brains of stillborn foetuses [3,7,9,12].…”

“…The important role of the placenta in relation to foetal brain injury has been stressed in a number of studies of stillbirths [8,10,13,16] and examination of the placenta is included in the present study. In addition, genetic and environmental factors are increasingly recognised as likely contributors to the risk of stillbirth and of foetal brain injury [26].…”