The impact of HIV on maternal mortality and more broadly on the health of women, remains poorly documented and understood. Two recent reports attempt to address the conceptual and methodological challenges that arise in estimating HIV-related maternal mortality and trends. This paper presents and compares the methods and discusses how they affect estimates at global and regional levels. Country examples of likely patterns of mortality among women of reproductive age are provided to illustrate the critical interactions between HIV and complications of pregnancy in high-HIV-burden countries. The implications for collaboration between HIV and reproductive health programmes are discussed, in support of accelerated action to reach the Millennium Development Goals and improve the health of women.
While recent reports indicate declining trends in maternal mortality [
The contribution of HIV to maternal mortality has been recognized for over a decade [
This paper aims to enhance the understanding of the methods used to estimate HIV-associated maternal deaths and how they affect global, regional, and country estimates. Country examples of likely patterns of mortality among women of reproductive age are provided to illustrate the critical interactions between HIV and maternal mortality in high-HIV-burden countries.
In the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, 1992 (ICD-10), WHO defines maternal death as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes [
Some of the deaths of pregnant women with HIV are incidental deaths due to an AIDS-defining condition, without any obvious association with pregnancy. These deaths are therefore classified as pregnancy-related deaths, but not maternal deaths. In practice, the distinction between incidental and indirect causes of death is difficult to make, especially in the case of HIV. The effect of pregnancy on HIV disease progression is uncertain [
Figure
The intersecting epidemics of HIV and maternal mortality.
In the real world, identifying maternal deaths and determining their causes, in order to differentiate deaths due to direct or indirect causes, or to incidental causes, poses many challenges. Most developing countries do not have civil registration systems to record the death of a woman of reproductive age, and identification of maternal deaths usually requires special methods of investigation, such as household surveys. In addition, there are well-documented problems with regard to the identification of cause of death in general and maternal death in particular, which are exacerbated in the context of HIV [
In the run-up to the 2015 deadline to achieve the Millennium Development Goals, increased efforts are being made to track progress in reducing maternal mortality. In 2010, two major reports provided estimates of maternal mortality trends at global, regional, and country levels [
Hogan and colleagues, at the Institute for Health Metrics and Evaluation (IHME) and other academic institutions, estimated levels and trends in maternal mortality for 181 countries between 1980 and 2008 and assessed the impact of HIV on these estimates. Details on the IHME methodological approach can be found in the published report [
The UN-affiliated Maternal Mortality Estimation Inter-Agency Group (MMEIG), together with academics from the University of California at Berkeley, developed estimates of indirect maternal deaths due to HIV as part of a larger effort to estimate country, regional, and global maternal mortality levels and trends between 1990 and 2008 [
The steps in this process were as follows (see also [
The interagency group estimated 21,000 HIV-associated maternal deaths (uncertainty interval 15,341–29,120), or 6% of the worldwide total of 358,000 maternal deaths in 2008. For the same year, the IHME calculated that 61,400 fewer maternal deaths (18%) would have occurred in the absence of HIV (uncertainty interval 58,200–66,400), of an estimated total of 342,900 maternal deaths. As noted above, the interagency model computed pregnancy-related HIV deaths and assumed that half of those were indirect maternal deaths. Direct maternal deaths in which HIV was present, and possibly a contributing factor, were not counted. The other model computed primarily pregnancy-related HIV deaths. Should the IHME model have used the interagency assumption about the proportion of pregnancy-related HIV deaths that are truly maternal, their estimated numbers of HIV-associated maternal death and total number of maternal deaths would have been reduced accordingly.
Both models show that the vast majority of HIV-associated maternal deaths occur in sub-Saharan Africa (86% in the interagency model and 92% in the IHME model) (Table
HIV-associated maternal deaths by region, 2008, by model.
MDG region | Number of HIV-associated maternal deaths | Proportion of all maternal deaths | ||
Interagency | IHME | Interagency | IHME | |
World total | 21,000 | 61,436 | 5.8% | 17.9% |
Developed regions | 90 | 45 | 5.6% | 3.4% |
CIS countries | 70 | 35 | 4.7% | 2.6% |
Developing regions | 21,000 | 61,356 | 5.8% | 18.0% |
Africa | 18,000 | 56,446 | 8.9% | 31.5% |
Northern Africa | 10 | 28 | 0.3% | 1.2% |
Sub-Saharan Africa | 18,000 | 56,418 | 9.0% | 31.9% |
Asia | 1,700 | 4,358 | 1.2% | 2.9% |
Eastern Asia | 80 | 42 | 1.0% | 0.5% |
South Asia | 1,300 | 3,632 | 1.2% | 3.0% |
South-Eastern Asia | 310 | 682 | 1.7% | 3.9% |
Western Asia | — | 2 | 0.0% | 0.0% |
Latin America and the Caribbean | 480 | 510 | 5.2% | 6.4% |
Oceania | 10 | 42 | 1.1% | 5.8% |
The ranking of countries with the highest number of HIV-related maternal deaths varies substantially by model (Table
10 Countries with the highest number of HIV-associated maternal deaths, 2008, by model.
Interagency | IHME | |||
Ranking | Country | #HIV-associated maternal deaths | Country | #HIV-associated maternal deaths |
1 | Nigeria | 2472 | Nigeria | 10422 |
2 | South Africa | 1920 | Malawi | 4689 |
3 | Zimbabwe | 1574 | Ethiopia | 3971 |
4 | Tanzania | 1552 | Tanzania | 3941 |
5 | Uganda | 1512 | India | 3531 |
6 | India | 1264 | Mozambique | 3448 |
7 | Mozambique | 1217 | Kenya | 3006 |
8 | Kenya | 1100 | Côte d'Ivoire | 2871 |
9 | Malawi | 961 | Uganda | 2611 |
10 | Ethiopia | 948 | Zambia | 2403 |
The countries with the highest fraction of HIV-related maternal deaths are shown in Table
10 Countries with the highest fraction of HIV-associated maternal deaths, 2008, by model.
Interagency | IHME | |||
Ranking | Country | Fraction of HIV-associated maternal deaths | Country | Fraction of HIV-associated maternal deaths |
1 | Botswana | 78% | Botswana | 84% |
2 | Swaziland | 75% | Swaziland | 84% |
3 | Lesotho | 59% | Lesotho | 83% |
4 | Zimbabwe | 53% | Zimbabwe | 82% |
5 | Namibia | 50% | South Africa | 78% |
6 | South Africa | 43% | Zambia | 73% |
7 | Zambia | 37% | Namibia | 73% |
8 | Belize | 35% | Malawi | 69% |
9 | Malawi | 32% | Mozambique | 66% |
10 | Trinidad and Tobago | 28% | Uganda | 51% |
Figure
Intersection of HIV and maternal mortality in Zambia, 2008. Source:
Figure
Intersection of HIV and maternal mortality in DRC, 2008. Source:
Intersection of HIV and maternal mortality in Zimbabwe, 2008. Source:
We examined some of the challenges in defining and counting HIV-associated maternal deaths and reviewed two recent methodological approaches for their estimation. (This paper does not attempt to explain why the interagency and IHME estimates for maternal deaths might differ. For further discussion, see Section 3.6 of [
There are major differences in the way each model identifies pregnancy-related HIV deaths and examines the association of HIV with maternal deaths. The IHME model produces somewhat higher results, with the number of HIV-associated maternal deaths (61,400) about three times higher than the interagency estimates. In part because the IHME model has a lower overall number of maternal deaths, the fraction of maternal deaths associated with HIV is substantially higher when compared to the interagency model. Regional estimates of both numbers and affected fraction follow a similar pattern between models. At the country level, the models produce similar rankings in terms of the most affected countries, although the estimated numbers and affected fractions vary.
These comparisons should be made with caution, partly because of the different model approaches and in how the results are presented. The interagency estimate distinguishes between incidental pregnancy-related HIV deaths and indirect HIV-related maternal deaths, to keep strictly to the ICD-10 definition of maternal death, without being able to fully delineate the differences between the two. The IHME model notes that the evidence to identify the proportion of pregnancy-related deaths that are incidental is scant, and its estimates are based on total numbers of pregnancy-related deaths in which HIV was present, while recognizing that this strategy biases the estimates upwards.
Despite these differences, estimates using the different methods clearly reinforce that the HIV epidemic is having a profound influence on maternal mortality and, more broadly, pregnancy-related mortality. Worldwide estimates of the fraction of maternal deaths due to HIV range between 6 and 18%, with the majority of HIV-associated maternal deaths in the sub-Saharan region, where the affected fraction is between 9–32%. Country rankings between models are similar and provide a general but not precise estimate of the HIV epidemic’s contribution to maternal mortality.
More detailed examination at country level of the impact of HIV on maternal and pregnancy-related deaths shows diverse patterns. National estimates are usually based on few data points and are subject to all the caveats mentioned earlier about the identification of pregnancy-related deaths and the classification of cause of death. Nonetheless, they give an idea of the severe adverse effect of the HIV epidemic on women's health in high-burden countries.
Despite methodological challenges, assessments of trends in maternal mortality clearly indicate that HIV has become a leading cause of death during pregnancy and the postpartum period in countries with high HIV prevalence and that the HIV epidemic has slowed down progress in improving maternal health.
Improved knowledge of the contribution of HIV to maternal and pregnancy-related mortality should help to direct scarce resources to appropriate policy and programmatic responses and spur better collaboration between HIV and reproductive health services [
It would be useful to distinguish between maternal HIV-associated death due to direct obstetric causes or indirect HIV-related causes and incidental pregnancy-related HIV deaths. The new ICD-10 amendment introducing a new code for an “indirect maternal death” is a step forward. However, this is likely to continue to remain a source of misclassification, given the ongoing clinical uncertainty around the relationship between HIV and other causes of maternal death. Further discussion among experts in ICD-compliant death certification and coding is needed to help clarify how best such interrelated causes of deaths should be classified. Adoption of a common terminology among researchers and health service providers would be a further benefit.
There is also an urgent need to carry out systematic reviews of existing studies on the key parameters that underpin the estimates. These include studies on the relative risk of maternal death in HIV-infected versus uninfected pregnant women and the relative risk of dying from HIV disease of a pregnant versus a nonpregnant woman. More studies are also needed to elucidate the mechanisms by which HIV can contribute to direct or indirect maternal deaths.
Nonetheless, given the close, almost inextricable interactions between HIV and other causes of death during and around pregnancy and inadequate systems for civil registration in most countries, it will remain difficult to quantify the precise impact of HIV on maternal mortality in the foreseeable future. This should not serve as an excuse for inaction. Urgent measures are required to provide the many girls and young women who face the dual risks of HIV infection and pregnancy with the services that they need. In settings with a high HIV burden and continuing high maternal mortality ratios, especially in sub-Saharan Africa, this means scaling up comprehensive and integrated programmes that include
The authors thank Carla Abou-Zahr, Eleanor Gouws, Peter Ghys, and Lale Say for their careful review and helpful advice and Terhi Aaltonen for her thorough editorial support.