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

Author:

Madhi Shabir A12,Pathirana Jayani12,Baillie Vicky12,Izu Alane12,Bassat Quique34567,Blau Dianna M8,Breiman Robert F9,Hale Martin10,Mathunjwa Azwifarwi12,Martines Roosecelis B11,Nakwa Firdose L12,Nzenze Susan12,Ordi Jaume4,Raghunathan Pratima L8,Ritter Jana M11,Solomon Fatima12,Velaphi Sithembiso12,Wadula Jeannette13,Zaki Sherif R11,Chawana Richard12

Affiliation:

1. Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Faculty of Health Science, Johannesburg, South Africa

2. Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa

3. ISGlobal, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain

4. Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique

5. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain

6. Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital de Sant Joan de Deu, University of Barcelona, Barcelona, Spain

7. Consorcio de Investigacion Biomedica en Red de Epidemiologia y Salud, Madrid, Spain

8. Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

9. Emory Global Health Institute, Emory University, Atlanta, Georgia, USA

10. National Health Laboratory Service, Department of Anatomical Pathology, School of Pathology, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa

11. Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

12. Department of Paediatrics, Chris Hani Baragwanath Academic Hospital, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

13. National Health Laboratory Service, Department of Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Abstract

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.

Funder

Bill and Melinda Gates Foundation

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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