Unraveling Specific Causes of Neonatal Mortality Using Minimally Invasive Tissue Sampling: An Observational Study

• Type of Material: Article
• Authors: Shabir A Madhi, University of Witwatersrand; Jayani Pathirana, University of Witwatersrand; Vicky Baillie, University of Witwatersrand; Alane Izu, University of Witwatersrand; Quique Bassat, University of Barcelona; Dianna M Blau, Centers for Disease Control and Prevention; Robert F Breiman, Emory University; Martin Hale, University of Witwatersrand; Azwifarwi Mathunjwa, University of Witwatersrand; Roosecelis B Martines, Centers for Disease Control and Prevention; Firdose L Nakwa, University of Witwatersrand; Susan Nzenze, University of Witwatersrand; Jaume Ordi, Centro de Investigação em Saúde de Manhiça; Pratima L Raghunathan, Centers for Disease Control and Prevention; Jana M Ritter, Centers for Disease Control and Prevention; Fatima Solomon, University of Witwatersrand; Sithembiso Velaphi, University of Witwatersrand; Jeannette Wadula, University of Witwatersrand; Sherif R Zaki, Centers for Disease Control and Prevention; Richard Chawana, University of Witwatersrand
• Language: English
• Date: 2019-10-15
• Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option C
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/cid/ciz574
• Title of Journal or Parent Work: Clinical Infectious Diseases
• ISSN: 1058-4838
• Volume: 69
• Issue: 4
• Start Page: S351
• End Page: S360
• Grant/Funding Information: This work was supported by the Bill & Melinda Gates Foundation [OPP1101764].; This supplement is sponsored by the Emory Global Health Institute and the Bill & Melinda Gates Foundation.
• Keywords: SEPSIS; RESISTANCE; hospital acquired infection; RISK; Infectious Diseases; Immunology; MITS; underlying cause of death; DEATH; Microbiology; Life Sciences & Biomedicine; Science & Technology; immediate cause of death; core biopsy
• Research Categories: Health Sciences, Public Health

Abstract

BACKGROUND: Postmortem minimally invasive tissue sampling (MITS) is a potential alternative to the gold standard complete diagnostic autopsy for identifying specific causes of childhood deaths. We investigated the utility of MITS, interpreted with available clinical data, for attributing underlying and immediate causes of neonatal deaths. METHODS: This prospective, observational pilot study enrolled neonatal deaths at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. The MITS included needle core-biopsy sampling for histopathology of brain, lung, and liver tissue. Microbiological culture and/or molecular tests were performed on lung, liver, blood, cerebrospinal fluid, and stool samples. The "underlying" and "immediate" causes of death (CoD) were determined for each case by an international panel of 12-15 medical specialists. RESULTS: We enrolled 153 neonatal deaths, 106 aged 3-28 days. Leading underlying CoD included "complications of prematurity" (52.9%), "complications of intrapartum events" (15.0%), "congenital malformations" (13.1%), and "infection related" (9.8%). Overall, infections were the immediate or underlying CoD in 57.5% (n = 88) of all neonatal deaths, including the immediate CoD in 70.4% (58/81) of neonates with "complications of prematurity" as the underlying cause. Overall, 74.4% of 90 infection-related deaths were hospital acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%). Streptococcus agalactiae was the most common pathogen (5/15 [33.3%]) among deaths with "infections" as the underlying cause. CONCLUSIONS: MITS has potential to address the knowledge gap on specific causes of neonatal mortality. In our setting, this included the hitherto underrecognized dominant role of hospital-acquired multidrug-resistant bacterial infections as the leading immediate cause of neonatal deaths.