Natural Diseases Causing Sudden Death in Infancy and Early Childhood

Abstract

Global childhood mortality rates in the under-5s were 44 per 1,000 live births in 2013, ranging from 2.3 in Singapore to 152.5 in Guinea-Bissau (Western sub-Saharan Africa), with rates of 4.9 per 1,000 live births in the United Kingdom (UK) (1). In England and Wales there are >5,000 deaths annually in children aged 0-19 years (2) from an estimated population of 12.9 million in this age group (3). Around 3,000 of these deaths are in infants (less than 1 year) with the majority having known serious medical conditions; such deaths are hence “expected”. Most are due to perinatal and immaturity-related conditions, which account for around 40% of cases, followed by congenital anomalies. Many of these deaths occur in the early (less than 7 days) or late neonatal (7 to 27 days) period (2). The next most commonly affected age group is adolescents, who account for around 1,000 deaths annually, with more than half being due to external, non-natural causes (2).Unexpected death occurring in an apparently healthy infant is termed “sudden unexpected death in infancy (SUDI)” and refers to such a presentation in an infant 7-365 days of age. According to most definitions, unexpected deaths in infants under 7 days of age are excluded from the SUDI category, and instead have been termed “sudden unexpected early neonatal death (SUEND)”. All cases of SUDI and SUEND require investigation to determine the cause of death. In England and Wales such cases are referred to Her Majesty’s Coroner (HMC), who will direct a post-mortem examination by a specialist pediatric pathologist. The primary rationale of the post-mortem examination, including its components and ancillary investigations, is to diagnose or exclude those natural (and non-natural) causes of death which are identifiable and to allow a specific cause of death to be provided (the specific details of the autopsy procedure are detailed in Chapter 24). Whilst many cases will subsequently be found to have died from previously unrecognized medical conditions, such as congenital anomalies or acquired natural diseases, a significant number will remain unexplained despite a complete autopsy including ancillary investigations (microbiology, virology, radiology, and metabolic studies). These cases are referred to as “unexplained SUDI”, “unascertained”, or “sudden infant death syndrome (SIDS)” according to the precise circumstances of the case and local practice, these terms by definition being diagnoses of exclusion.Excluding SIDS cases and neonatal deaths (0-27 days), for infants and children in England and Wales the most common acquired causes of natural deaths are neoplasms, diseases affecting the neurological, cardiovascular or respiratory systems, and infections (2) (Figure 25.1). It is likely that >50% of these cases may occur in infants and children with known life-limiting conditions. However, similar to in infancy, sudden unexpected death in childhood (SUDC; >1 year) also occurs, albeit less frequently than SUDI, with cases referred to the Coroner in the same manner. Following investigation, unexplained SUDC is less common than SIDS but remains a significant proportion of all childhood deaths; in England and Wales, for example, there were 212 registered SIDS cases compared to 27 unexplained SUDC cases in 2014 (4). However, globally, accurate figures regarding the proportions of explained and unexplained deaths following autopsy are difficult to establish. This is, in part, due to wide variability in the death certification process, making epidemiological evaluation unreliable (5), and a lack of large population-based studies, in particular those investigating SUDC. A recent review identified 24 published studies investigating 25 cohorts (17 in infants, 4 including both infants and children, and 4 children only) from 11 different countries; following full investigation the cause of death was found in 9-67% of SUDI and 22-86% of SUDC cases (6). In the same study, infection was reported as the commonest explanation for death overall in SUDI (52% of all the cases reported across studies) and variably reported in individual studies to account for between 15-86% of the explained cases. Of the studies in children >1 year, 36-68% of explained deaths were due to infectious causes (6).