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

Shabir A Madhi; Jayani Pathirana; Vicky Baillie; Alane Izu; Quique Bassat; Dianna M Blau; Robert F Breiman; Martin Hale; Azwifarwi Mathunjwa; Roosecelis B Martines; Firdose L Nakwa; Susan Nzenze; Jaume Ordi; Pratima L Raghunathan; Jana M Ritter; Fatima Solomon; Sithembiso Velaphi; Jeannette Wadula; Sherif R Zaki; Richard Chawana

doi:10.1093/cid/ciz574

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

Clin Infect Dis. 2019 Oct 9;69(Suppl 4):S351-S360. doi: 10.1093/cid/ciz574.

Authors

Shabir A Madhi^{1

2}, Jayani Pathirana^{1

2}, Vicky Baillie^{1

2}, Alane Izu^{1

2}, Quique Bassat^{3

4

5

6

7}, Dianna M Blau⁸, Robert F Breiman⁹, Martin Hale¹⁰, Azwifarwi Mathunjwa^{1

2}, Roosecelis B Martines¹¹, Firdose L Nakwa¹², Susan Nzenze^{1

2}, Jaume Ordi⁴, Pratima L Raghunathan⁸, Jana M Ritter¹¹, Fatima Solomon^{1

2}, Sithembiso Velaphi¹², Jeannette Wadula¹³, Sherif R Zaki¹¹, Richard Chawana^{1

2}

Affiliations

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

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.

Keywords: MITS; core biopsy; hospital acquired infection; immediate cause of death; underlying cause of death.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Autopsy / methods
Cause of Death
Female
Humans
Infant
Infant Mortality
Infant, Newborn
Male
Perinatal Death
Pilot Projects
Pregnancy
Prospective Studies
South Africa
Specimen Handling / methods*
Stillbirth