Validity of a minimally invasive autopsy tool for cause of death determination in pediatric deaths in Mozambique: An observational study

Abstract

Background

In recent decades, the world has witnessed unprecedented progress in child survival. However, our knowledge of what is killing nearly 6 million children annually in low- and middle-income countries remains poor, partly because of the inadequacy and reduced precision of the methods currently utilized in these settings to investigate causes of death (CoDs). The study objective was to validate the use of a minimally invasive autopsy (MIA) approach as an adequate and more acceptable substitute for the complete diagnostic autopsy (CDA) for pediatric CoD investigation in a poor setting.

Methods and findings

In this observational study, the validity of the MIA approach in determining the CoD was assessed in 54 post-neonatal pediatric deaths (age range: ≥1 mo to 15 y) in a referral hospital of Mozambique by comparing the results of the MIA with those of the CDA. Concordance in the category of disease obtained by the two methods was evaluated by the Kappa statistic, and the sensitivity, specificity, and positive and negative predictive values of the MIA diagnoses were calculated.

A CoD was identified in all cases in the CDA and in 52/54 (96%) of the cases in the MIA, with infections and malignant tumors accounting for the majority of diagnoses. The MIA categorization of disease showed a substantial concordance with the CDA categorization (Kappa = 0.70, 95% CI 0.49–0.92), and sensitivity, specificity, and overall accuracy were high. The ICD-10 diagnoses were coincident in up to 75% (36/48) of the cases. The MIA allowed the identification of the specific pathogen deemed responsible for the death in two-thirds (21/32; 66%) of all deaths of infectious origin. Discrepancies between the MIA and the CDA in individual diagnoses could be minimized with the addition of some basic clinical information such as those ascertainable through a verbal autopsy or clinical record. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation.

Conclusions

The MIA showed substantial concordance with CDA for CoD identification in this series of pediatric deaths in Mozambique. This minimally invasive approach, simpler and more readily acceptable than the more invasive CDA, could provide robust data for CoD surveillance, especially in resource-limited settings, which could be helpful for guiding child survival strategies in the future.

Abstract

Quique Bassat and colleagues examine the validity of a standardized minimally invasive autopsy approach by comparison with that of the complete diagnostic autopsy in a series of children who died at Maputo Central Hospital in Mozambique.

Author summary

Why was this study done?

• Child mortality has been steadily decreasing globally in the last 25 years, but nearly 6 million child deaths still occur every year, predominantly in low- and middle-income countries.

• In these settings, current knowledge on the specific causes of child death is jeopardized by the scarcity of good-quality mortality data.

• Complete diagnostic autopsies, indisputably considered the reference method for cause of death investigation, are seldom conducted in poor settings, both on account of their limited acceptability and because of a generalized scarcity of the required pathological technical expertise.

• We aimed to validate a simpler and potentially much more acceptable minimally invasive autopsy (MIA) approach, by comparing its performance against the complete diagnostic autopsy for cause of death investigation in pediatric deaths.

What did the researchers do and find?

• In this study, 54 deaths in Mozambican children <15 years of age were independently studied using both the MIA method and the full autopsy.

• A comparison of the results of both methods was conducted, and concordance assessed.

• The MIA approach produced good-quality tissues and bodily fluids for histopathological and microbiological investigations.

• The MIA categorization of disease showed substantial concordance with the complete diagnostic autopsy, and the diagnostic accuracy of the MIA method was also high.

• Coincidence (matching) of the precise ICD-10 diagnosis between the MIA and the full autopsy was moderate, almost perfect, or perfect in 36/48 of the cases (75%) in which both methods were concordant for general categorization of disease.

• The MIA approach was particularly accurate in the diagnosis of infectious and oncological causes of death, but failed to identify congenital conditions.

• Additionally, the specific microorganisms associated with mortality were readily identified in the majority of MIA-obtained samples.

What do these findings mean?

• The MIA can identify with significant precision and accuracy the ultimate cause of a child’s death and even other underlying conditions.

• Due to its less invasive nature, such a method could be more easily utilized in resource-constrained settings for cause of death investigation and mortality surveillance.

• Reliable estimates of the causes of child mortality can help policy makers design and implement better and more evidence-based preventive strategies to improve child survival in high-burden low-income settings.