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

Abstract

BackgroundDespite global health efforts to reduce maternal mortality, rates continue to be unacceptably high in large parts of the world. Feasible, acceptable, and accurate postmortem sampling methods could provide the necessary evidence to improve the understanding of the real causes of maternal mortality, guiding the design of interventions to reduce this burden.Methods and findingsThe validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in an observational study in 57 maternal deaths by comparing the results of the MIA with those of the gold standard (complete diagnostic autopsy [CDA], which includes any available clinical information). Concordance between the MIA and the gold standard diagnostic categories was assessed by the kappa statistic, and the sensitivity, specificity, positive and negative predictive values and their 95% confidence intervals (95% CI) to identify the categories of diagnoses were estimated. The main limitation of the study is that both the MIA and the CDA include some degree of subjective interpretation in the attribution of cause of death.A cause of death was identified in the CDA in 98% (56/57) of cases, with indirect obstetric conditions accounting for 32 (56%) deaths and direct obstetric complications for 24 (42%) deaths. Nonobstetric infectious diseases (22/32, 69%) and obstetric hemorrhage (13/24, 54%) were the most common causes of death among indirect and direct obstetric conditions, respectively. Thirty-six (63%) women were HIV positive, and HIV-related conditions accounted for 16 (28%) of all deaths. Cerebral malaria caused 4 (7%) deaths. The MIA identified a cause of death in 86% of women. The overall concordance of the MIA with the CDA was moderate (kappa = 0.48, 95% CI: 0.31–0.66). Both methods agreed in 68% of the diagnostic categories and the agreement was higher for indirect (91%) than for direct obstetric causes (38%). All HIV infections and cerebral malaria cases were identified in the MIA. The main limitation of the technique is its relatively low performance for identifying obstetric causes of death in the absence of clinical information.ConclusionsThe MIA procedure could be a valuable tool to determine the causes of maternal death, especially for indirect obstetric conditions, most of which are infectious diseases.The information provided by the MIA could help to prioritize interventions to reduce maternal mortality and to monitor progress towards achieving global health targets.

Postmortem Interval and Diagnostic Performance of the Autopsy Methods

“…Detailed MIA pathological and microbiological methods have been reported elsewhere 1 , 3 – 6 . In brief, the procedure included an initial disinfection of the surface of the body followed by the collection of blood and cerebrospinal fluid (CSF), aiming to collect ~10–15 mL of each fluid, and puncture of solid organs (liver, lungs, and central nervous system [CNS]) using biopsy needles (14G-16G), for microbiological and pathological analysis.…”

“…The histological evaluation included staining with hematoxylin and eosin in all samples and additional histochemical and/or immunohistochemical staining whenever needed to reach a diagnosis 1 , 3 – 6 . All microbiological methods, that included both culture and molecular tests, have been reported in detail elsewhere 15 , 19 .…”

“…Two scales ranging from 0 to 4 were developed to grade the strength of the evidence of the findings; one based on the severity of the pathological findings and the other on the pathogenicity of each individual microorganism, the number of organs (one or more organs) and the type of techniques (classic cultures, molecular tests or both) in which the microorganism was identified 3 – 6 . Microorganisms were categorized as causing true infection or as contaminants based on criteria previously reported by our group, which varied slightly for adults, children, neonates and stillborn babies 3 – 6 . Briefly, these criteria comprised the type of microorganism, the number of organs involved, the presence or absence of pathologic findings associated with the infection, and the clinical data (for the CDA).…”

“…Moreover, the use of needles without manipulation of the organs allows collecting samples for microbiology analysis with lower risk of contamination compared with CDA. The procedure has recently been validated in Mozambique in all age groups, including stillbirths, neonates, children, adults and maternal deaths 3 – 6 . In this validation analysis, the concordance with the CDA, the gold standard for cause of death determination, was moderate to good, and the MIA reliably recognized most infectious diseases and cancers causing death.…”

Socio-anthropological methods to study the feasibility and acceptability of the minimally invasive autopsy from the perspective of local communities: lessons learnt from a large multi-centre study

“…The MIA is a protocolized and systematic post-mortem methodology targeting key organs (brain, lungs, heart, liver, spleen, kidneys, bone marrow, uterus) and bodily fluids (blood and cerebrospinal fluid), and aiming to provide sufficiently good quality samples for pathological and microbiological investigations so as to substitute the complete pathological autopsy. The MIA has been validated for CoD investigation in all age groups [11][12][13][14] and has been used in different settings [15,16]. CoD results derived from the use of the MIA tool could also contribute in the future to modify and improve current analytical approaches utilized for VA data interpretation.…”