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

Background Over 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic autopsies (CDAs)—the gold standard for cause of death determination—are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed. Methods and findings In this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI [0.56–0.99]). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI [0.18–0.63]). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction. Conclusions The MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented.
Clara Menendez and colleagues examine the validity of a minimally invasive autopsy to determine cause of death in stillborn babies and neonates compared with complete diagnostic autopsy in Mozambique.
Author summary Why was this study done? Over 5 million stillbirths and neonatal deaths occur annually. The vast majority of these deaths (99%) take place in low- and middle-income countries, where vital registration systems are inadequate or nonexistent and rarely medically certified. Verbal autopsies, the main source of information in these areas, are subject to a high degree of misclassification errors for conditions with poor clinical specificity such as most peri-neonatal deaths. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic autopsies—the gold standard for cause-of-death determination—are difficult to perform in most high-burden settings. We developed a simplified minimally invasive autopsy method, which would be feasible in middle- and low-income countries, and validated it against the complete autopsy, the gold standard, in a series of stillborn babies and neonates who died in Mozambique. What did the researchers do and find? The validity of a minimally invasive autopsy method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths. Concordance between the diagnosis obtained with the minimally invasive and the complete diagnostic autopsy was evaluated. The minimally invasive autopsy showed a substantial concordance with the complete autopsy in stillborn babies and a moderate concordance in neonates. The agreement was particularly high for infectious diseases. Moreover, the specific microorganisms causing death were accurately identified in the minimally invasive autopsy samples. What do these findings mean? The minimally invasive autopsy could be a useful tool for cause of death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented.