This systematic review of the literature identified risk factors for stillbirth in developing countries and estimated the proportion of stillbirths that would be prevented if a particular risk factor is eliminated in a range of study settings.
Five risk factors (maternal syphilis, chorioamnionitis, maternal malnutrition, lack of antenatal care, and maternal socioeconomic disadvantage) were found to be significantly associated with stillbirth (with a PAF greater than 50%) in more than 1 study.
These findings can be categorized into 2 broad groups. The first group are context-dependent risk factors,27,28,43–47 such as maternal illiteracy, not receiving antenatal care, or socioeconomic disadvantage, i.e., risk factors for which a direct association to the outcome is not clear. The second group of risk factors relates to clinical conditions (maternal or fetal infections in particular) for which a causal pathway to the final outcome is already known or suspected,49 such as maternal syphilis16–20,28,34 or chorioamnionitis.35–37
It is possible that the contextual factors (the first group of risk factors) may not be the actual risk factors for stillbirth. However, they could be proxy factors for as yet unknown risks and could serve as useful indicators in specific populations. It is conceivable that providing accessible health-care services, especially to disadvantaged women, can lower stillbirth rates, irrespective of the actual cause, as is already seen in the case of infant mortality.50
For some of the specific clinical conditions identified as significant risk factors (second group of risk factors), on the other hand, cost-effective interventions to directly reduce the impact are already available. For example, antenatal syphilis screening with on-site testing and immediate treatment was shown to be cost-effective and reported to be beneficial in reducing not only the occurrence of stillbirth but also the burden of disease resulting from congenital syphilis.51 Routine incorporation of this intervention in antenatal care programs in developing countries could significantly reduce stillbirth rates in these settings. Indeed, the above-reported association of receipt of antenatal care with lower stillbirth rates might be partly due to provision of antenatal syphilis screening as part of antenatal care.
The PAF values calculated in this review for each risk factor varied widely in different settings. For example, for maternal syphilis the PAF ranged from 1.85% (95%CI 1.65–2.02) in a multicenter study in South America28 to 81.6% (95%CI 59.3–92.1) in the Russian Federation.16 One explanation for this large variation is that PAF depends not only on the rate ratio but also on the prevalence of exposure in a given context. Thus, it is quite plausible that elimination of syphilis (which in recent years has reemerged in former USSR countries),49 would have a larger impact in the Russian Federation than in countries where prevalence of syphilis is low. On the other hand, it is also possible that the variation is a reflection of the poor quality of studies such that inaccuracy in the estimation of the stillbirth rate is affecting the PAF calculation.2,52 In the case of certain studies it was not easy to use and interpret data, either because the data presented in tables were discordant with those presented in the text, or there were errors in data analysis25,37,38,44 (e.g., matched case–control studies analyzed as unmatched ones).
The reason for including studies found to be problematic was simply that data on this topic from developing countries are so scarce. Yet, it was to some extent reassuring that in relationship to maternal syphilis, chorioamnionitis, not receiving antenatal care, maternal malnutrition, and socioeconomic disadvantage there was a degree of concordance among the studies. Thus while the PAF values need to be interpreted with caution, they nonetheless can be considered as indicative of the actual risks.
Another consideration when interpreting PAF is that it indicates the proportion of stillbirths that could be avoided in case an intervention able to reduce immediately that particular exposure to zero could be implemented, while all other variables remain constant. For example, if PAF for stillbirth due to maternal syphilis is 80% in a given setting, by using the syphilis screening and treatment program in pregnant women53 the rate of maternal syphilis can be reduced to zero, and stillbirth rate could be reduced by 80% if other changes do not occur. This implies that resources to implement syphilis screening and treatment should not be diverted from other preventive programs (for example, immunization or delivery care) otherwise the amount of stillbirth reduction will diminish accordingly.
To our knowledge this is the first attempt to systematically review the literature providing data on this topic from developing countries settings, and to provide estimations of PAF. The review employed a comprehensive search strategy, that involved databases including studies from developing countries like LILACS and IMEMR irrespective of the language, thus increasing the chance of retrieving all relevant studies conducted in developing countries. The estimations of PAF, which measure the contribution of a particular exposure to the overall rate of disease in a given population, provide valuable messages to policy makers for priority setting in a specific country or region and therefore could significantly improve the health of women and children.
One limitation of this review is the considerable number of studies that could not be retrieved in full text (n = 24). Another limitation is the difficulty in interpreting PAF. As explained above, PAF estimates change in settings with different prevalence of exposure. Therefore, the results of a single study are not automatically applicable to different contexts. Second, the right interpretation of PAF depends on the quality of the study assessed; low-quality studies that provide invalid estimates of association will lead to invalid estimates of PAF.
Despite the lack of good-quality studies on stillbirths in developing countries, this review provides indications about important risk factors of stillbirths in those countries. Maternal syphilis, lack of appropriate antenatal care for all women, and socioeconomic disadvantage stand out as key risk factors in developing countries. Strengthening health services, including antenatal care services that comprise screening for syphilis, would help to alleviate the burden of ill health from stillbirths in developing countries.
Data on stillbirths from developing countries are scarce and often not reliable, and, as for many other public health conditions, the “inverse information and care law” is valid: “The communities with the most fetal deaths have the least information on these deaths and least access to cost-effective interventions to prevent them.”57 Better-quality research as well as more reliable estimates of stillbirths for each country is therefore needed. A greater amount of good-quality data translated into PAF would be valuable to guide the setting of priorities in public health programs in developing countries.
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