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

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.

The evolution of minimally invasive tissue sampling in postmortem examination: a narrative review

“…Although two additional studies of MITS in adults in HICs were published in 2005 and 2009, beginning in 2010 there was a significant shift from HICs to LMICs [ 20 , 21 ]. In 2011 the number of publications documenting MITS in postmortem examination in LMICs began to increase, and between 2011 and 2019 articles from LMICs outnumbered those from HICs by a ratio of 3:1 [ 11 , 24 – 28 , 30 – 32 , 34 – 37 ].…”

“…The year 2019 saw a sharp rise in the quantity of MITS publications, including a study of children dying of respiratory illness in Kenya and a study of stillbirths and neonates in Ethiopia [34,35]. A large proportion of the 2019 increase in MITS publications is attributable to the October 2019 release of 13 articles describing MITS from the experience of the Child Health and Mortality Prevention Surveillance (CHAMPS) Network [2,15,33,36,37,[54][55][56][57][58][59][60][61][62]. With promising results from the relatively few validation studies completed, the CHAMPS Network rapidly endorsed the use of MITS and is poised to both build on earlier validation studies and also improve on a number of aspects of MITS such as reducing the time and expense associated with performing MITS.…”

“…Although two additional studies of MITS in adults in HICs were published in 2005 and 2009, beginning in 2010 there was a significant shift from HICs to LMICs [20,21]. In 2011 the number of publications documenting MITS in postmortem examination in LMICs began to increase, and between 2011 and 2019 articles from LMICs outnumbered those from HICs by a ratio of 3:1 [11,[24][25][26][27][28][30][31][32][34][35][36][37]. The number of qualitative studies aimed at understanding the facilitators and barriers to implementing MITS in a variety of cultures, religions, and populations, including health care providers, parents, families, and community leaders is relatively balanced in HICs versus LMICs.…”

“…Based on the sample sizes and ages identified in the 28 primary studies using MITS in postmortem examination there have been roughly 40% more MITS carried out in LMICs than in HICs. There have been nearly twice as many MITS in adults as in stillbirths, neonates, and children combined; however, in LMICs, the majority of MITS conducted have been in children, neonates, and stillbirths ( Figure 3) [10,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][35][36][37][38][39][40][41][42]64].…”

Epidemiology of Clinically Suspected and Laboratory-Confirmed Bloodstream Infections at A South African Neonatal Unit

“…17 In some African neonatal units, carbapenem-resistant Acinetobacter baumannii and Enterobacterales (CRE) are now leading causes of neonatal infectious deaths, especially in preterm infants. [18][19][20][21] In this paper we characterise the epidemiology of clinically suspected and laboratory-con rmed bloodstream infections at a large academic neonatal unit in South Africa, with analysis of factors associated with mortality in proven infections.…”