The frequency and significance of alveolar haemosiderin-laden macrophages in sudden infant death

Abstract

Alveolar haemosiderin-laden macrophages (HLMs) in histological sections of the lung represent evidence of previous pulmonary haemorrhage and in infants may be associated with features of non-accidental injury (NAI). The aim of this study is to establish the frequency of alveolar HLMs detected at post-mortem in a large series of sudden unexpected infant deaths, and to determine their clinical significance with particular regard to a possible association with NAI. A search was performed of a database of 1516 anonymised paediatric autopsies to identify all infants (<1 year of age) that died suddenly and unexpectedly in whom HLMs were demonstrated on routine histological examination of lung sections using special iron (Perls') stains. Clinical details and other post-mortem findings were then reviewed. During the study period (1996-2005 inclusive), there were 601 sudden unexpected infant deaths. Of the 536 autopsies in whom histological data regarding HLMs were recorded and slides were available for review, 29 (5%) demonstrated alveolar HLMs in lung sections. In 9 (31%) infants there were additional features of NAI; in 11 (38%) infants, there were features in the clinical history and/or on pathological examination of natural disease sufficient to potentially explain the presence of HLMs, and 9 (31%) represented otherwise unexplained infant deaths with no significant clinical history or other abnormalities. HLMs were present in 9 of the 27 (33%) total infant deaths with other features indicative of NAI, compared to only 9 of the 242 (4%) unexplained infant deaths without any other features of NAI or other contributory pathology (difference 29.6%, 95% CI 14.6-48.6%, p<0.0001; positive likelihood ratio 9.0, 95% CI 3.9-19.8). This association remained even if cases with rib fractures were excluded. Alveolar HLMs may be identified in a significant minority of sudden infant deaths following routine histological examination of the lungs with special stains for iron pigment. In most, there will be features in the clinical history or findings at post-mortem to indicate underlying natural disease which may account for their presence. However, in the absence of such features, alveolar HLMs, whilst not diagnostic, are associated with a significantly increased risk for the detection of other features of NAI; the presence of otherwise unexplained alveolar HLMs at autopsy should therefore prompt a careful exclusion of inflicted injury.