Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network

• Type of Material: Article
• Authors: Robert Breiman, Emory University; Dianna M Blau, Centers for Disease Control and Prevention, Atlanta; Portia Mutevedzi, University of Witwatersrand; Victor Akelo, US Centers for Disease Control and Prevention-Kenya; Inacio Mandomando, Centro de Investigação em Saúde de Manhiça [CISM], Manhica, Mozambique; Ikechukwu Ogbuanu, Emory University; Samba O Sow, Ministère de la Santé, Bamako, Mali; Lola Madrid, London School of Hygiene & Tropical Medicine; Shams El Arifeen, International Center for Diarrhoeal Diseases Research (icddr, b); Mischka Garel, Emory University; Nana Bukiwe Thwala, University of Witwatersrand; Dickens Onyango, Kisumu County, Kenya Department of Health; Antonio Sitoe, Centro de Investigação em Saúde de Manhiça [CISM]; Ima-Abasi Bassey, Columbia University; Adama Mamby Keita, Ministère de la Santé; Addisu Alemu, Haramaya University; Muntasir Alam, International Center for Diarrhoeal Diseases Research (icddr, b); Sana Mahtab, University of Witwatersrand; Dickson Gethi, Kenya Medical Research Institute (KEMRI); Rosauro Varo, Centro de Investigação em Saúde de Manhiça [CISM]; Julius Ojulong, Columbia University; Solomon Samura, World Hope International; Ashka Mehta, Univ Maryland; Alexander M Ibrahim, Haramaya University; Afruna Rahman, International Center for Diarrhoeal Diseases Research (icddr, b); Pio Vitorino, Centro de Investigação em Saúde de Manhiça [CISM]; Vicky L Baillie, University of Witwatersrand; Janet Agaya, Kenya Medical Research Institute (KEMRI) Center for Global Health Research; Milagritos D Tapia, University of Maryland; Nega Assefa, Haramaya University; Atique Iqbal Chowdhury, International Center for Diarrhoeal Diseases Research (icddr, b); Anthony JG Scott, London School of Hygiene & Tropical Medicine; Emily S Gurley, International Center for Diarrhoeal Diseases Research (icddr, b); Karen L Kotloff, University of Maryland; Amara Jambai, Ministry of Health and Sanitation; Quique Bassat, Centro de Investigação em Saúde de Manhiça [CISM]; Beth A Tippett-Barr, US Centers for Disease Control and Prevention-Kenya; Shabir A Madhi, University of Witwatersrand; Cynthia Whitney, Emory University
• Language: English
• Date: 2021-09-01
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © The Royal Society of Chemistry 2018
• License: Creative Commons Universal : Public Domain Dedication
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pmed.1003814
• Title of Journal or Parent Work: PLOS MEDICINE
• Volume: 18
• Issue: 9
• Start Page: e1003814
• End Page: e1003814
• Grant/Funding Information: This work was funded by the Bill and Melinda Gates Foundation (Grant number: OPP1126780) to RFB and CGW. https://www.gatesfoundation.org The funder participated in discussions of study design and data collection. They did not participate in analysis or conclusions of this work and did not play a role in decision to publish and preparation of this manuscript.
• Keywords: PATHOLOGY; Medicine, General & Internal; General & Internal Medicine; AUTOPSY; Life Sciences & Biomedicine; Science & Technology

Abstract

Background The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. Methods and findings We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings. Conclusions Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.