One-in-four pregnancy-related deaths is due to HIV in countries with a high HIV prevalence, a meta-analysis of 23 studies shows.
HIV-infected women have eight times the risk of a
pregnancy-related death compared to uninfected women (pooled relative risk [RR]: 7.75, 95% CI: 5.37-11.16), according to results from the meta-analysis published in the
advance online edition of AIDS.
Researchers from the London School of Hygiene and Tropical
Medicine found that, at the population level, a very high proportion of pregnancy-related deaths can be
attributed to HIV. This means the considerable
proportion of excess deaths due to HIV (mostly in the absence of ART) among
HIV-infected pregnant and postpartum women (pooled attributable risk [AR]: 994
per 100,000 pregnant women, 95%, CI: 677-1310) has a significant impact on all
causes of pregnancy-related deaths even in areas where HIV prevalence is low.
“In areas where HIV prevalence among pregnant women is as
low as 2%, 12% of all pregnancy-related
deaths may be attributable to HIV. This figure rises to 50% in areas with an
HIV prevalence of 15%”, the authors write.
Based on 2011 UNAIDS’ estimated HIV prevalence rates among
adults of reproductive age, an estimated 5% of all pregnancy-related deaths
worldwide, and one in four (25%) in sub-Saharan Africa, are attributable to HIV.
These findings, they note, highlight the importance of
integrating HIV and reproductive health services and monitoring trends in
While HIV is the leading cause of death among women of
reproductive age worldwide, women in sub-Saharan Africa
also experience the highest rates of maternal death.
The effect of HIV on pregnancy and vice versa is poorly
understood. Evidence is lacking to support the argument that pregnancy
increases HIV progression and conversely that the risk of obstetric
complications among HIV-infected women is increased.
While much is known, the authors write, about the
contribution of HIV to adult mortality, little is known about how HIV
contributes to mortality during pregnancy and the postpartum period.
The authors cite two approaches used to estimate the
proportion of maternal deaths attributable to HIV. The first, a systematic
review of the causes of maternal deaths, based on only eight studies and 'verbal
autopsies' (a research method that helps determine probable causes of death in cases where
there is no medical record, relying on reports from family members or others) with no defined criteria for classifying a maternal death as
HIV/AIDS-related, attributed 6.2% of maternal deaths to HIV in 2006 in Africa.
The second approach uses mathematical models in the absence of empirical data. Two
models dominate, offering vastly different estimates for 2008, the latest year
both models provided estimates. While the Institute for Health Metrics and Evaluation
estimated 17.9% of maternal deaths worldwide were attributable to HIV, the Maternal Mortality Estimation
Inter-agency Group model
gave an estimate of only 5.9%.
The main difference between the models, the authors note, is
in the assumptions made about the number of deaths among HIV-infected pregnant
and postpartum women attributed to pregnancy and so classified as maternal
deaths. In the former, all are classified as maternal, while in the latter only
The authors proposed an alternative approach.
Basing calculations on empirical data from a systematic review of studies
comparing death during pregnancy and the postpartum period in HIV-positive and
negative women, they reported on the risk ratio and prevalence of HIV.
Eligible studies included those comparing death during
pregnancy, delivery and/or up to 365 days postpartum between HIV-positive and
negative women using a cohort, census or case-control study design. Death
could be defined as “pregnancy-related” (including all deaths) or “maternal”
(excluding deaths which were accidental or incidental to the pregnancy). Only
studies where HIV status was determined by HIV testing and which had a sample size of at
least 30 women in each study group were included.
Summary estimates of relative (RR) and attributable risks
(AR) for the link between HIV and death during pregnancy and the postpartum
period were calculated through meta-analyses.
The authors predicted the effect of HIV on pregnancy-related
death at the population level by calculating population-attributable fractions
for each study individually and in scenarios with varying HIV prevalence using
the pooled RR from the meta-analysis.
Of the 18,949 potentially relevant articles identified,
17,640 were excluded through abstract and title screening. Twenty-three studies out of
1291 full texts had data on the risk of pregnancy-related death in HIV-positive and
Study populations were from South
the Republic of Congo (Congo-Brazzaville), the Democratic Republic of Congo, Malawi,
Zimbabwe, Rwanda, Uganda,
Kenya, India, Spain,
USA and Mexico.
Excess mortality due to HIV among HIV-infected pregnant and
postpartum women, the authors note, is not surprising. Most women were not on
ART, and many would be at an advanced stage of illness resulting inan increased
risk of death. However, the extent of the excess is higher than expected.
The authors believe their approach has two main advantages
over previous studies. First, their findings are based on empirical, not modelled,
data. Their summary estimate is based on 23 studies from across the world.
However, heterogeneity between the studies suggest the results be interpreted
with caution. So the summary estimate should be considered “an average RR about
which the true study RRs actually vary”.
Second, estimation of the contribution of HIV to
pregnancy-related death, not maternal death, means no assumptions need be made
about HIV being indirectly related or coincidental to pregnancy.
Most pregnancy-related deaths are among HIV-infected women
in sub-Saharan Africa where verbal autopsy is
routinely used to report cause of death.
The authors cite a recent WHO document suggesting deaths in
HIV-infected pregnant and postpartum women be categorised into direct obstetric
deaths, “AIDS-related indirect maternal deaths” (those who die because of effect
of pregnancy on HIV), and “HIV-related deaths” (who die of a fatal complication
of HIV or AIDS that is coincidental to the pregnancy). Distinguishing
AIDS-related indirect deaths from HIV-related coincidental deaths is limited
and no guidance is given.
Severe anaemia and tuberculosis, note the authors, can be
considered as both causes of indirect maternal deaths and HIV-related deaths.
They suggest reporting pregnancy-related – and not maternal – death will resolve
the issue and allow for more reliable monitoring of causes.
These findings, conclude the authors, have important
implications for integrated service delivery.
Future research, they add, “should focus on how to identify
HIV-related deaths using verbal autopsies, so that pregnancy-related mortality
can be monitored including and excluding HIV-related deaths”.