There is a general consensus that maternal mortality is a major health problem worldwide as well as a fundamental public health indicator [1]. The problem of maternal mortality is concentrated in low-income countries, particularly in sub-Saharan Africa, where one in 16 women die of pregnancy-related complications [2,3]. Reduction of this intolerable burden is one of the Millennium Development Goals set up by the United Nations in 2000 [2].

The main source of information on the causes of maternal deaths in developing countries, clinical records and verbal autopsies (VA) [4–13], have serious limitations due to the frequent discrepancies between the clinically presumed and the actual cause of death [14]. It has recently been claimed that there is an urgent need for studies focused on providing an accurate knowledge of the causes of maternal death in developing countries [15]. Autopsy studies may thus improve the knowledge of the causes of maternal death by increasing the accuracy of cause-of-death reports [16].

Postmortem examination is also an essential tool to improve overall clinical diagnostic performance, since clinicians can only diagnose diseases for which they have been looking. Thus, the analysis of false positive and false negative diagnoses is essential to evaluate and improve the diagnostic process [17,18]. Unfortunately, very little information exists on discrepancies between clinical and necropsy data in maternal mortality causes in developing countries [19]. As a consequence, very little data is available on the impact of medical errors on maternal mortality.

In order to evaluate clinical practice and diagnostic performance, which could help to reduce the problem of maternal deaths in developing countries, we conducted a retrospective study on the discrepancies between clinical and postmortem diagnosis in maternal deaths at the Maputo Central Hospital (MCH) in Mozambique.

During the study period, there were 179 maternal deaths. In 139 women (77.6%) a complete autopsy with adequate histological sampling as well as clinical information was available.

A major diagnostic discrepancy was detected in 56 (40.3%) maternal deaths; 47 (83.9%) of them were classified as class I, and nine (16.1%) as class II. A minor diagnostic discrepancy (class III or IV) was identified in 30 maternal deaths (21.6%). An additional minor discrepancy was identified in 24 maternal deaths with a major error. Thus, an overall number of 54 minor discrepancies (38.8%) were identified. In 45 maternal deaths (32.4%), there was complete agreement between the clinical and the autopsy diagnoses (class V). In eight maternal deaths (5.7%), no diagnosis was reached in the autopsy and the deaths were thus considered as not suitable for evaluation (class VI). Macroscopic examination alone detected 24/56 (42.9%) clinical major errors, while the remaining 32 errors were detected only in the histological study. Table 1 shows the causes of death detected in the autopsies, the number of clinically suspected diagnoses for each final autopsy diagnosis, and the number and percentage of major diagnostic errors.

Both evaluations of diagnostic discrepancy were coincident in 117 cases. A discordant evaluation was observed in 19 cases (13.7%), thus requiring a consensus. Sixteen of these disagreements were qualified as minor (eight class I versus class II; eight class III versus class IV). Three cases were qualified as major disagreements and required consultation with a senior pathologist.

Seven diagnoses (obstetric hemorrhage, eclampsia, puerperal sepsis, HIV/AIDS-related conditions, pyogenic bronchopneumonia, malaria, and pyogenic meningitis), each responsible for ten or more maternal deaths, were further analyzed. Figure 1 shows the percentage of major errors (class I and II) in each of these diagnostic categories, and Table 2 the sensitivity, specificity, PPV, NPV, and accuracy of the clinical diagnosis for these seven categories.

Disseminated tuberculosis was diagnosed in 12 women, of whom ten were HIV positive (and thus, included as HIV/AIDS-related condition). The diagnosis of tuberculosis had an overall sensitivity of 25.0% (95% confidence interval [CI]: 0.5%–49.5%), a specificity of 98.3% (95% CI: 96.0%–100%), a PPV of 60.0% (95% CI: 32.3%–87.7%), an NPV of 92.9% (95% CI: 88.3%–97.5%), and an accuracy of 91.6% (95% CI: 86.8%–96.4%).

Table 3 shows the reported clinical diagnoses in maternal deaths of obstetric hemorrhage, puerperal septicemia, eclampsia, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis with false negative diagnoses in the autopsy. The HIV positive status had been confirmed before death in eight out of 18 (44.4%) women with HIV/AIDS-related diseases, but only in six of them (33.3%) had the opportunistic infection directly causing the death been correctly diagnosed. Table 4 shows the false negative clinical diagnoses in maternal deaths with final diagnosis of HIV/AIDS-related diseases.

False positive diagnoses were particularly frequent for eclampsia with 12 maternal deaths (Table 1). The autopsy diagnoses in maternal deaths with false positive clinical diagnosis of eclampsia were: pyogenic meningitis (four maternal deaths), meningioma (two maternal deaths), puerperal sepsis (two maternal deaths), pyogenic bronchopneumonia (two maternal deaths), tuberculosis (one maternal death), and postpartum hemorrhage (one maternal death). No pathological lesions related to eclampsia were detected in any of these women.

This is, to our knowledge, the first study focused on the evaluation of diagnostic discrepancies in maternal mortality in sub-Saharan Africa and even in developing countries, based on complete autopsies and including a histological study. This study has shown a high frequency of major clinico-pathological discrepancies (40.3%) in maternal deaths in a tertiary-referral hospital in sub-Saharan Africa. In most cases a change in clinical management could have significantly modified the prognosis. The proportion of discrepancies observed in this study is higher than that currently reported in studies based on nonselected hospital patients [17,27]. Remarkably, this study, unlike most previous studies, was based only on maternal deaths. These are extremely infrequent in developed countries [2,28], and tend to show lower discrepancy rates between clinical and autopsy diagnoses [16,21].

A sole description of the correlation between clinical and autopsy diagnosis was done retrospectively in Nigeria including data from 1989 to 1998 [19]. The prevalence of major diagnostic errors in that study was 10.4%, a figure much lower than that reported here. This fact may be explained mainly by methodological differences, since neither histological study nor HIV testing were used in the Nigerian study. Interestingly, in our study only 17.3% clinical major discrepancies were detected in the macroscopic study, whereas 57.1% of the discrepancies were found only in the histological study, as it has been shown in other studies [29,30].

The evaluation of sensitivity, specificity, PPVs, and NPVs may provide some insight into the possible factors behind major diagnostic errors. A high rate of false negative diagnoses was observed for infectious diseases, both obstetrical (puerperal septicemia) and nonobstetric. Other studies have shown that infectious diseases tend to show higher rates of diagnostic errors [21,31]. Interestingly, three frequent nonobstetric infectious categories (HIV/AIDS-related conditions, pyogenic bronchopneumonia, and pyogenic meningitis, as well as tuberculosis) had sensitivities below 40%. This number is very relevant since it indicates that significant reductions in maternal mortality could be reached by decreasing the false negative clinical diagnoses of some frequent infectious diseases, through improvements in their diagnosis. Although false negative diagnoses may occur either by omission, or lack of sensitivity of available diagnostic tests or inadequate synthesis in the diagnostic process [14,32,33], underestimation of prevalence plays an important role in this type of error [14,32,33]. It has been shown that increasing clinical awareness and the correct estimation of the prevalence of infectious diseases may lead to a reduction in the number of diagnostic errors [14,34]. Limited access to necessary diagnostic tests and particularly to microbiological cultures in developing countries, especially in sub-Saharan Africa, represents a major handicap for the diagnosis of many infectious diseases and significantly slows down the provision of drug therapy [35,36].

Eclampsia was the main source of false positive diagnoses (n = 12, 57.1%). It cannot be completely excluded that preeclampsia–eclampsia was a true diagnosis in some of these patients, and lack of an appropriate management of the condition a contributor to maternal death. However, a different cause of death was found in all these women. Moreover, no pathological lesions related to eclampsia were detected in any of them. False-positive diagnoses may occur due to premature closure of the diagnostic process and low specificity of diagnostic tests, but overestimation of prevalence also plays a major role in this type of error [14,32,33]. Generally, eclampsia is more likely to be diagnosed too frequently rather than overlooked. On the other hand, epilepsy, infections or space-occupying lesions of the central nervous system, cerebrovascular accidents, hypertensive diseases, metabolic disorders, and thrombotic thrombocytopenic purpura may all simulate eclampsia, but they are less frequent [37–39]. On the basis of clinical reports and VAs [4–12], eclampsia is widely accepted as one of the major causes of maternal death in sub-Saharan Africa [4,8,12]. The current study suggests that eclampsia remains a significant cause of maternal death in that setting, but its prevalence is probably overestimated.

The main limitation of our study is that it was conducted in a large university hospital located in the capital of Mozambique, which could limit the extrapolation of these findings to other hospitals and health facilities. It has been shown that the frequency of discrepancies between clinical and autopsy diagnoses is lower in larger hospitals [21], and this might suggest that the number of diagnostic errors in other health facilities would be underestimated. On the other hand, complicated or high risk pregnancies are often referred to these larger hospitals resulting in a high number of cases of increased diagnostic difficulty.

Four necessary conditions have been proposed for necropsy to be a valid monitor of clinical diagnosis performance: a high necropsy rate, specified and stable conditions of autopsy procedure (extent of organ assessment and sampling, availability of clinical information), calculation of sensitivity and specificity rather than accuracy, and estimate of the errors in postmortem diagnosis [40]. Our study met three of these conditions, but did not assess the error of autopsy diagnosis itself. The classification into the discrepancy classes was not clear-cut in all cases. A disagreement rate of 13.7% in class assignment was detected in our study, a figure that is similar to the disagreement rate reported in other studies [14]. This result could be seen as a limitation of the discrepancy classification.

The significant reduction of diagnostic errors reported in developed countries during the second half of the 20th century has been mainly attributed to the improvement of clinical skills and to the impact of new diagnostic procedures [14]. Necropsy has had in this regard the dual role of a method to detect diagnostic errors and a source of knowledge to be applied to future cases. This dual role has not only influenced learning but has also added relevant data on local epidemiology of diseases. The scientific, public health, and educational benefits of the autopsy remain difficult to evaluate, but are generally acknowledged [41]. The almost complete absence of studies based on necropsy data and focused on diagnostic error is a severe handicap for medical practice in sub-Saharan Africa. Thus, autopsy could help to reduce maternal mortality by providing information critical to improve diagnostic accuracy and therefore clinical management. In this regard, this study suggests that correct awareness of the prevalence of infectious diseases and the implementation of a few inexpensive diagnostic tools and a thorough evaluation of cases clinically thought to be eclampsia may lead to a significant reduction in the number of diagnostic errors [42]. The implementation of morbidity and mortality conferences may also have an important effect on maternal mortality in sub-Saharan Africa [43]. Additional studies are needed to assess whether analysis of how and when diagnostic errors occur might improve epidemiological data in maternal mortality cases and clinical diagnostic performance.

In addition to their intrinsic clinical relevance, missed diagnoses detected at autopsy may have important implications for research. The main source of information on the causes of maternal deaths in developing countries is VA, an established method of ascertaining the likely causes of death by interpretation of interviews with relatives or carers of the deceased. VAs are not based on clinical or laboratory measures and have been questioned because they are subject to a relatively high degree of misclassification error [44,45]. Our data indicate that not only VAs but also medical records may contain substantial inaccuracies regarding the main diagnoses causing or contributing to death. It is noteworthy that studies based on these methodologies tend to underreport infectious diseases [2,46]. Since diagnoses and causes of death are determined without autopsy in the vast majority of cases, especially in sub-Saharan-Africa, vital statistics, clinical registries, and even randomized trials, may capture incorrect causes of death. These inaccuracies have important policy implications, as major funding and policy decisions are derived in part from vital statistics and other registries of disease burden.