{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:49:53Z","timestamp":1790315393623,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pmed.1003814","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000}}],"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1126780"],"award-info":[{"award-number":["OPP1126780"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The current burden of &gt;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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>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 &lt;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 (<jats:italic>n<\/jats:italic> = 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 \u22651 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 \u22651 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had \u22651 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1003814","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T19:49:53Z","timestamp":1633031393000},"page":"e1003814","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":54,"title":["Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7099-2936","authenticated-orcid":true,"given":"Robert F.","family":"Breiman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianna M.","family":"Blau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Portia","family":"Mutevedzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7518-2855","authenticated-orcid":true,"given":"Victor","family":"Akelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-2187","authenticated-orcid":true,"given":"Inacio","family":"Mandomando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0670-6026","authenticated-orcid":true,"given":"Ikechukwu U.","family":"Ogbuanu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samba O.","family":"Sow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lola","family":"Madrid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5372-5932","authenticated-orcid":true,"given":"Shams","family":"El Arifeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mischka","family":"Garel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3948-3121","authenticated-orcid":true,"given":"Nana Bukiwe","family":"Thwala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1634-0531","authenticated-orcid":true,"given":"Dickens","family":"Onyango","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Sitoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8914-3638","authenticated-orcid":true,"given":"Ima-Abasi","family":"Bassey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adama Mamby","family":"Keita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8219-6259","authenticated-orcid":true,"given":"Addisu","family":"Alemu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muntasir","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Mahtab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dickson","family":"Gethi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4282-5572","authenticated-orcid":true,"given":"Rosauro","family":"Varo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2200-8954","authenticated-orcid":true,"given":"Julius","family":"Ojulong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon","family":"Samura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashka","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4774-5416","authenticated-orcid":true,"given":"Alexander M.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7693-2491","authenticated-orcid":true,"given":"Afruna","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pio","family":"Vitorino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1327-9090","authenticated-orcid":true,"given":"Vicky L.","family":"Baillie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1251-6621","authenticated-orcid":true,"given":"Janet","family":"Agaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milagritos D.","family":"Tapia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0341-2329","authenticated-orcid":true,"given":"Nega","family":"Assefa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-5983","authenticated-orcid":true,"given":"Atique Iqbal","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7533-5006","authenticated-orcid":true,"given":"J. Anthony G.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-9403","authenticated-orcid":true,"given":"Emily S.","family":"Gurley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Kotloff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amara","family":"Jambai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0875-7596","authenticated-orcid":true,"given":"Quique","family":"Bassat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5877-2968","authenticated-orcid":true,"given":"Beth A.","family":"Tippett-Barr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-0636","authenticated-orcid":true,"given":"Shabir A.","family":"Madhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia G.","family":"Whitney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CHAMPS Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"pmed.1003814.ref001","unstructured":"United Nations Inter-agency Group for Child Mortality Estimation (UN IGME). Levels & Trends in Child Mortality. Report 2019. Estimates developed by the UN Inter-agency Group for Child Mortality Estimation. New York; 2019 [cited 11 Jan 2020]. Available from: https:\/\/childmortality.org\/reports."},{"issue":"10010","key":"pmed.1003814.ref002","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1016\/S0140-6736(15)00120-8","article-title":"Global, regional, and national levels and trends in under-5 mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Inter-agency Group for Child Mortality Estimation","volume":"386","author":"D You","year":"2015","journal-title":"Lancet"},{"key":"pmed.1003814.ref003","unstructured":"UNICEF. Committing to child survival: a promised renewed. New York: Progress Report; 2015."},{"key":"pmed.1003814.ref004","doi-asserted-by":"crossref","first-page":"k373","DOI":"10.1136\/bmj.k373","article-title":"How many lives are at stake? Assessing 2030 sustainable development goal trajectories for maternal and child health","volume":"360","author":"JW McArthur","year":"2018","journal-title":"BMJ"},{"issue":"9061","key":"pmed.1003814.ref005","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/S0140-6736(96)07493-4","article-title":"Mortality by cause for eight regions of the world: Global Burden of Disease Study","volume":"349","author":"CJL Murray","year":"1997","journal-title":"Lancet"},{"issue":"3","key":"pmed.1003814.ref006","doi-asserted-by":"crossref","first-page":"e125","DOI":"10.1016\/S2214-109X(13)70037-8","article-title":"Development of a post-mortem procedure to reduce the uncertainty regarding causes of death in developing countries","volume":"1","author":"Q Bassat","year":"2013","journal-title":"Lancet Glob Health"},{"issue":"4","key":"pmed.1003814.ref007","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/pd.4077","article-title":"Acceptability of a minimally invasive perinatal\/paediatric autopsy: healthcare professionals\u2019 views and implications for practice","volume":"33","author":"K Ben-Sasi","year":"2013","journal-title":"Prenat Diagn"},{"issue":"11","key":"pmed.1003814.ref008","doi-asserted-by":"crossref","first-page":"e1002173","DOI":"10.1371\/journal.pmed.1002173","article-title":"Minimally Invasive Autopsy: A New Paradigm for Understanding Global Health?","volume":"13","author":"P Byass","year":"2016","journal-title":"PLoS Med"},{"issue":"3","key":"pmed.1003814.ref009","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2471\/BLT.05.027003","article-title":"Verbal autopsy: current practices and challenges","volume":"84","author":"N Soleman","year":"2006","journal-title":"Bull World Health Organ"},{"issue":"6","key":"pmed.1003814.ref010","doi-asserted-by":"crossref","first-page":"e1002317","DOI":"10.1371\/journal.pmed.1002317","article-title":"Validity of a minimally invasive autopsy tool for cause of death determination in pediatric deaths in Mozambique: An observational study","volume":"14","author":"Q Bassat","year":"2017","journal-title":"PLoS Med"},{"issue":"5","key":"pmed.1003814.ref011","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s00428-019-02602-z","article-title":"Performance of the minimally invasive autopsy tool for cause of death determination in adult deaths from the Brazilian Amazon: an observational study","volume":"475","author":"AEM Palhares","year":"2019","journal-title":"Virchows Arch"},{"issue":"6","key":"pmed.1003814.ref012","doi-asserted-by":"crossref","first-page":"e1002318","DOI":"10.1371\/journal.pmed.1002318","article-title":"Validity of a minimally invasive autopsy for cause of death determination in stillborn babies and neonates in Mozambique: an observational study","volume":"14","author":"C Menendez","year":"2017","journal-title":"PLoS Med"},{"key":"pmed.1003814.ref013","doi-asserted-by":"crossref","first-page":"S262","DOI":"10.1093\/cid\/ciz599","article-title":"Mortality Surveillance Methods to Identify and Characterize Deaths in Child Health and Mortality Prevention Surveillance Network Sites","volume":"69","author":"NT Salzberg","year":"2019","journal-title":"Clin Infect Dis"},{"key":"pmed.1003814.ref014","doi-asserted-by":"crossref","first-page":"S333","DOI":"10.1093\/cid\/ciz572","article-title":"Overview and Development of the Child Health and Mortality Prevention Surveillance Determination of Cause of Death (DeCoDe) Process and DeCoDe Diagnosis Standards","volume":"69","author":"DM Blau","year":"2019","journal-title":"Clin Infect Dis"},{"issue":"7","key":"pmed.1003814.ref015","doi-asserted-by":"crossref","first-page":"e909","DOI":"10.1016\/S2214-109X(20)30205-9","article-title":"Initial findings from a novel population-based child mortality surveillance approach: a descriptive study","volume":"8","author":"AW Taylor","year":"2020","journal-title":"Lancet Glob Health"},{"issue":"suppl 4","key":"pmed.1003814.ref016","doi-asserted-by":"crossref","first-page":"S302","DOI":"10.1093\/cid\/ciz565","article-title":"Standardization of minimally invasive tissue sampling specimen collection and pathology training for the Child Health and Mortality Prevention Surveillance Network","volume":"69","author":"N Rakislova","year":"2019","journal-title":"Clin Infect Dis"},{"issue":"suppl 4","key":"pmed.1003814.ref017","doi-asserted-by":"crossref","first-page":"S311","DOI":"10.1093\/cid\/ciz571","article-title":"Development and implementation of multiplex TaqMan array cards for specimen testing at Child Health and Mortality Prevention Surveillance site laboratories","volume":"69","author":"MH Diaz","year":"2019","journal-title":"Clin Infect Dis"},{"issue":"suppl 4","key":"pmed.1003814.ref018","doi-asserted-by":"crossref","first-page":"S322","DOI":"10.1093\/cid\/ciz579","article-title":"Pathology and telepathology methods in the Child Health and Mortality Prevention Surveillance Network","volume":"69","author":"RB Martines","year":"2019","journal-title":"Clin Infect Dis"},{"key":"pmed.1003814.ref019","unstructured":"WHO. Verbal autopsy standards: the 2016 WHO verbal autopsy instrument. Geneva: World Health Organization; 2016."},{"key":"pmed.1003814.ref020","unstructured":"WHO. ICD-10: international statistical classification of diseases and related health problems, tenth revision. 2nd ed. Geneva: World Health Organization; 2004."},{"key":"pmed.1003814.ref021","unstructured":"WHO. The WHO application of ICD-10 to deaths during the perinatal period: ICD-PM. Geneva: World Health Organization; 2016."},{"key":"pmed.1003814.ref022","unstructured":"Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2019 (GBD 2019) Cause List Mapped to ICD Codes. Seattle, United States of America: Institute for Health Metrics and Evaluation (IHME); 2020. doi: 10.6069\/GHCW-8955"},{"key":"pmed.1003814.ref023","unstructured":"UN Inter-agency Group for Child Mortality Estimation (IGME). Levels and trends in child mortality: report 2015. New York: UNICEF; 2015. Available from: http:\/\/www.childmortality.org"},{"key":"pmed.1003814.ref024","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1186\/s13104-019-4668-3","article-title":"Factors affecting neonatal mortality in the general population: evidence from the 2016 Ethiopian Demographic and Health Survey (EDHS)\u2014multilevel analysis","volume":"12","author":"HF Wolde","year":"2019","journal-title":"BMC Res Notes"},{"issue":"6491","key":"pmed.1003814.ref025","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1126\/science.aaz9447","article-title":"Vaccination strategies to enhance immunity in neonates","volume":"368","author":"TR Kollmann","year":"2020","journal-title":"Science"},{"issue":"4","key":"pmed.1003814.ref026","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3390\/antibiotics9040155","article-title":"Monoclonal Antibodies as an Antibacterial Approach Against Bacterial Pathogens","volume":"9","author":"DV Zurawski","year":"2020","journal-title":"Antibiotics (Basel)"},{"key":"pmed.1003814.ref027","doi-asserted-by":"crossref","first-page":"18655","DOI":"10.1073\/pnas.1907833116","article-title":"A promising bioconjugate vaccine against hypervirulent Klebsiella pneumoniae","volume":"116","author":"MF Feldman","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pmed.1003814.ref028","first-page":"403","article-title":"Social Autopsy Working Group","volume":"90","author":"P Waiswa","year":"2012","journal-title":"Bull World Health Organ"}],"updated-by":[{"DOI":"10.1371\/journal.pmed.1003814","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000}}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003814","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T21:09:59Z","timestamp":1634245799000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003814"}},"subtitle":[],"editor":[{"given":"Marie-Louise","family":"Newell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,9,30]]},"references-count":28,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1003814","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pmed.1003814","asserted-by":"object"}]},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,30]]}}}