Background: With a neonatal mortality rate of 33 per 1000 livebirths in 2021, Ethiopia is working hard to attain the SDG target of 12 deaths per 1,000 livebirths by 2030. A better understanding of the major causes of neonatal mortality is needed to effectively design and implement interventions to achieve this goal. Minimally Invasive Tissue Sampling (MITS), an alternative to conventional autopsy, requires fewer resources and through task-shifting of sample collection from pathologists to nurses, has the potential to support the expansion of pathology-based post-mortem examination and improve mortality data. This study assesses the feasibility of MITS task-shifting by evaluating the accuracy and adequacy of MITS performed by nurses compared with pathologists.Methods: Nurses in a tertiary hospital and a district hospital in Ethiopia were trained using standardized protocols for MITS sample collection. The adequacy and accuracy of the samples collected by nurses were compared against standard pre-set criteria. Both pathologists and nurses conducted MITS in the tertiary hospital and only nurses did MITS in the district hospital. Proportions of MITS with adequate samples were compared to assess comparability and statistical significance.Findings: One hundred thirty-nine MITS were done:125 in hospitals and 14 inside homes within rural communities. The accuracy and adequacy of MITS samples collected by nurses was equal to that of pathologists in the tertiary hospital and in the district hospital except for brain samples from extremely preterm deaths.Interpretation: We showed that MITS could be done by nurses accurately and with comparable precision as pathologists in neonatal deaths in primary health facilities and home-based deaths. We recommend further research on a larger scale within the health system and within demographic and health surveillance systems.Funding Information: This study was funded by grants from the Bill & Melinda Gates Foundation (INV-004160) and RTI international project number 0216178 (Opp-1180554).Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study was approved by the research and publication committees of the Pediatrics and Child Health and the Pathology departments of Addis Ababa University College of Health Sciences. The proposal was approved by the Institutional review board of Addis Ababa university (IRB approval letter number AAUMF 03-008). Written consent was obtained from the parents or legal guardians. Consent was obtained in Amharic within 24 hours after death for both the hospital deaths as well as the home deaths.

Background Low- and middle-income countries (LMICs) face disproportionately high mortality rates, yet the causes of death in LMICs are not robustly understood, limiting the effectiveness of interventions to reduce mortality. Minimally invasive tissue sampling (MITS) is a standardized postmortem examination method that holds promise for use in LMICs, where other approaches for determining cause of death are too costly or unacceptable. This study documents the costs associated with implementing the MITS procedure in LMICs from the healthcare provider perspective and aims to inform resource allocation decisions by public health decisionmakers. Methods We surveyed 4 sites in LMICs across Sub-Saharan Africa and South Asia with experience conducting MITS. Using a bottom-up costing approach, we collected direct costs of resources (labor and materials) to conduct MITS and the pre-implementation costs required to initiate MITS. Results Initial investments range widely yet represent a substantial cost to implement MITS and are determined by the existing infrastructure and needs of a site. The costs to conduct a single case range between $609 and $1028 per case and are driven by labor, sample testing, and MITS supplies costs. Conclusions Variation in each site’s use of staff roles and testing protocols suggests sites conducting MITS may adapt use of resources based on available expertise, equipment, and surveillance objectives. This study is a first step toward necessary examinations of cost-effectiveness, which may provide insight into cost optimization and economic justification for the expansion of MITS.

Uncertainty about the causes of neonatal deaths impedes achieving global health targets to reduce mortality. Complete diagnostic autopsy (CDA) is the gold standard to determine cause of death. However, it is often difficult to perform in high-burden, low-income settings. Validations of more feasible methods to determine cause of death are needed. This prospective, multi-center study in Ethiopia assessed the validity of the minimally invasive tissue sampling (MITS) approach to contribute to causes of death in preterm neonates compared to CDA. The MITS and CDA of 105 cases were reviewed. The MITS sampling success for lungs and liver was 100% and 84%, respectively. The kidney and brain had sampling successes of 58% each. MITS showed good agreement with CDA for the diagnosis of hyaline membrane disease (kappa = 0.78), and moderate to substantial agreement for pneumonia and pulmonary hemorrhage (kappa = 0.59 and 0.68, respectively). Even though CDA is the gold standard in identifying the cause of death, we believe that the MITS method can be a useful alternative method in supporting determination of cause of death in low-resource settings.

BACKGROUND:Neonatal deaths now account for 47% of all deaths in children younger than 5 years globally. More than a third of newborn deaths are due to preterm birth complications, which is the leading cause of death. Understanding the causes and factors contributing to neonatal deaths is needed to identify interventions that will reduce mortality. We aimed to establish the major causes of preterm mortality in preterm infants in the first 28 days of life in Ethiopia. METHODS:We did a prospective, cross-sectional, observational study in five hospitals in Ethiopia. Study participants were preterm infants born in the study hospitals at younger than 37 gestational weeks. Infants whose gestational age could not be reliably estimated and those born as a result of induced abortion were excluded from the study. Data were collected on maternal and obstetric history, clinical maternal and neonatal conditions, and laboratory investigations. For neonates who died of those enrolled, consent was requested from parents for post-mortem examinations (both complete diagnostic autopsy and minimally invasive tissue sampling). An independent panel of experts established the primary and contributory causes of preterm mortality with available data. FINDINGS:Between July 1, 2016, to May 31, 2018, 4919 preterm infants were enrolled in the study and 3852 were admitted to neonatal intensive care units. By 28 days of post-natal age, 1109 (29%) of those admitted to the neonatal intensive care unit died. Complete diagnostic autopsy was done in 441 (40%) and minimally invasive tissue sampling in 126 (11%) of the neonatal intensive care unit deaths. The main primary causes of death in the 1109 infants were established as respiratory distress syndrome (502 [45%]); sepsis, pneumonia and meningitis (combined as neonatal infections; 331 [30%]), and asphyxia (151 [14%]). Hypothermia was the most common contributory cause of preterm mortality (770 [69%]). The highest mortality occurred in infants younger than 28 weeks of gestation (89 [86%] of 104), followed by infants aged 28-31 weeks (512 [54%] of 952), 32-34 weeks (349 [18%] of 1975), and 35-36 weeks (159 [8%] of 1888). INTERPRETATION:Three conditions accounted for 89% of all deaths among preterm infants in Ethiopia. Scale-up interventions are needed to prevent or treat these conditions. Further research is required to develop effective and affordable interventions to prevent and treat the major causes of preterm death. FUNDING:Bill & Melinda Gates Foundation.