Evidence for infection, inflammation and shock in sudden infant death: parallels between a neonatal rat model of sudden death and infants who died of sudden infant death syndrome

Abstract

This study compared pathological findings from a neonatal rat model of sudden death with those from 40 sudden infant death syndrome (SIDS) infants collected at autopsy. In the rat model, influenza A virus was administered intranasally on postnatal day 10, and on day 12 a sublethal, intraperitoneal dose of Escherichia coli endotoxin; mortality was 80%. Tissue samples from the animals and infants were fixed in formaldehyde, embedded in paraffin, and sections stained with hematoxylin and eosin. Tissues from the SIDS specimens were additionally cultured for bacteria and viruses; post-mortem blood samples were evaluated for signs of inflammation. All sections were examined by a pediatric forensic pathologist familiar with SIDS pathology. Comparisons between the rat model and the human SIDS cases revealed that both exhibited gross and microscopic pathology related to organ shock, possibly associated with the presence of endotoxin. Uncompensated shock appeared to be a likely factor that caused death in both infants and rat pups. Response to a shock-inducing event might have played an important role in the events leading to death. The similarities between the neonatal rats and the human cases indicate that further research with the model might elucidate additional aspects of SIDS pathology.

Novel hypothesis for unexplained sudden unexpected death in infancy (SUDI)

“…There are three possible explanations for this finding of potential pathogens in usually sterile sites: (1) the bacteraemia is normally missed because of the small volumes of blood often available for testing; (2) bacterial presence might have previously been dismissed as post-mortem contamination; (3) because of the developmental stage of the infant, low antibody levels and/or inefficient innate immunity permit the organisms to spread rapidly into normally sterile tissues. This led to the hypothesis proposed in this article based on the pathologic4 5 and epidemiological evidence from unexplained SUDI. In reference to the literature, “SIDS” terminology is used, as was appropriate at the time of the original research publication.…”

Infectious causes of sudden infant death syndrome

“…Histopathological comparisons of respiratory flora showed gross and microscopic signs of tissue changes consistent with shock, potentially associated with the presence of endotoxin. This experiment suggested that uncompensated shock might be related to death from SIDS [22].…”

“…Blood-Siegfried and colleagues compared pathological findings from a neonatal rat model of sudden death with those from 40 SIDS infants collected at autopsy [22]. In a rat model, the investigators administered influenza A virus intranasally and E. coli endotoxin, intra-peritonealy on postnatal day 10 and 12, and 80% had a fatal outcome.…”

“…may increase inflammation either as super-antigens or via endotoxins in their cell wall. Several studies have shown that Escherichia coli (E. coli) is more likely to be found in post-mortem examination of SIDS infants compared with infants who died from proven non-infectious causes [22,23]. It is also thought that an irregular response to an infectious insult could act as a trigger for SIDS in some cases [24].…”

CD14 (C-260T) polymorphism is not associated with sudden infant death syndrome (SIDS) in a large South Australian cohort

“…1 Histological signs of shock, including fibrin thrombi in capillaries, megakaryocytes outside the lung, tubular cell necrosis and heart shock, have been found in 56.4% of SIDS cases. 2 Host factors, including genetic determinants, influence the outcome of interactions between toxin and host.…”