Global network for women's and children's health research: probable Causes of stillbirth in low- and middle-income countries using a prospectively Defined classification system

Abstract

Globally, stillbirth rates remain high in resource-limited settings with few global estimates of cause of stillbirth pub- lished. 1–3 Knowing the medical causes of stillbirth is impor- tant for development of strategies to reduce stillbirths. 4–6 To date, over 50 stillbirth classification systems have been developed, 7–22 most requiring extensive diagnostics and most relevant in high-income countries (HIC). Addition- ally, systems vary in definitions of primary and secondary causes, associated causes, contributing causes, underlying cause and preventable causes. Few systems have been devel- oped for low/middle-income countries (LMIC) where diag- nostic tools such as autopsy or placental histology are usually unavailable. Examples of systems include Frøen et al.’s Cause of Death and Associated Conditions (CODAC) system, which focuses on perinatal death and includes 10 categories 19,20 and Neonatal and Intrauterine deaths Classification according to Etiology (NICE), includ- ing 13 causes for perinatal death. 22 However, to date, these systems have only been used in small studies in LMIC and generally do not distinguish between stillbirth and neonatal deaths to characterise aetiology. 20–24 Determining cause of stillbirth has historically been chal- lenging, as the fetus is not directly observed when death occurs and the pathway to death is often unclear. 5 Thus, cause has often been defined by maternal or obstetric con- ditions that may be associated directly or indirectly with the fetal death. 25–27 In LMIC, common clinical conditions associated with stillbirth include prolonged and obstructed labour, pre-eclampsia/eclampsia, multiple births, and abnormal presentations. Most stillbirths associated with these conditions are caused by diminished placental or fetal blood flow and fetal asphyxia is the final common pathway leading to death 25,28 Stillbirths are also classified as macer- ated or non-macerated stillbirths, with the former generally occurring more than 24 hours before delivery. 29 Non- maceration suggests that the death likely occurred during labour. Recognising these limitations, the World Health Organization (WHO) has established an international clas- sification of diseases (ICD) perinatal mortality system, which examines the timing of the perinatal death, associ- ated maternal conditions, and cause of perinatal death. 30,31 However, the factors used to determine cause of death vary. To improve upon existing systems to determine cause of stillbirth in LMIC, we developed a hierarchal classification system, the Global Network Classification System, 32 which relies exclusively on readily available clinical data. Our objective for this analysis was to determine cause of still- birth across sites in six LMICs and to compare these results with current evidence