ART for mothers leading to decline in child deaths, KwaZulu Natal study finds

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A major decrease in the childhood mortality rate in children under the age of two (U2CMR), observed between 2001 and 2006 in northern rural KwaZulu Natal, South Africa, was associated with the rollout of antiretroviral therapy (ART) in that region, according to a presentation made at IAS 2009 in Cape Town this week.

Although some of the benefit may have been due to the introduction of programmes to prevent vertical (mother to child) transmission in 2001, researchers found that it was most strongly associated with maternal access to ART.

“Maternal survival is critical for the health of young children,” said Dr James Ndirangu of the Africa Centre for Health and Population Studies.

Background

Globally, the reduction of child mortality is a major public health priority (and one of the Millenium Development Goals). However, in areas with a high prevalence of HIV, child mortality rates have increased for a number of reasons. Quite obviously, children who are HIV-infected are at a much greater risk of death, but maternal HIV infection also contributes to mortality even in HIV-negative children — especially if their mothers die.

Glossary

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

exclusion criteria

Defines who cannot take part in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied.

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

Programmes to prevent mother to child transmission, and increasing access to ART, should hopefully have an impact on child mortality in these settings. In South Africa, PMTCT programmes, including infant feeding interventions, were first launched in 2001. The ART roll-out began in late 2004.

The investigators wished to establish the impact of programmes to prevent mother-to-child HIV transmission and HIV treatment for mothers on childhood mortality. They therefore examined mortality data for children aged under two years obtained between 2001 and 2006. These data were obtained from the Africa Centre Demographic Surveillance System, which was set up in 2000, in a largely rural area of northern Kwazulu-Natal, involving approximately 90,000 women. The Africa Centre began annual HIV surveillance in 2003.

The overall HIV prevalence in the cohort is 23% — 50% among women 24 to 29 years of age. Currently, there are over 9000 people on ART in the catchment area.

The fall in childhood mortality — and its causes

A total of 12,031 live births were included in the investigators’ analysis. Between 2001 and 2006, infant mortality declined from a peak of 86 per 1000 live births in 2001 to 37 per 1000 live births in 2006, a fall of 57%.

Post-neonatal mortality accounted for the largest decline, while neonatal mortality remained constant. Dr Ndirangu noted that after the rollout of ART, there was a statistically significant reduction in the cumulative risk of childhood mortality that becomes apparent after the first 100 days of life.

Dr Ndirangu showed an analysis of temporal changes in childhood mortality by clinic catchment areas within the region. This illustrated reductions in each district after PMTCT was implemented at the clinic, and then again, after the clinic began offering ART.

The researchers performed a multivariate analysis adjusting for maternal HIV, PMTCT availability and ART availability, that also adjusted for other factors that have been shown to be associated with child mortality, such as maternal age and education, child’s gender, multiple pregnancy, birth order, history of foetal and child death, delivery location, area of birth, household socio-economic factors (water and sanitation, electricity, household assets, distance to the health facility). In other words, the analysis excluded every other factor that the researchers could think of that may have contributed to the observed reduction in child mortality. For example, if there were improvements in the community’s socio-economic status, or health services, it would have helped reduce child mortality as well.

But it was clear that maternal HIV was a major risk factor for child mortality in this region.

“Children who are born to mothers known to be HIV-positive at the time of birth, were four times more likely to die compared to those born to HIV-negative mothers,” said Dr Ndirangu [with an adjusted hazard ratio [AHR] = 4.31, 95% confidence interval (CI) 3.09-6.01 p

According to the abstract, maternal death was associated with a modest increase in infant mortality, but this did not reach significance (AHR = 2.02, p = 0.076).

As to the impact of the availability of PMTCT and ART on mortality, the multivariate analysis indicated that children who were born when single-dose nevirapine (sdNVP) was available as PMTCT but before ART, were 15% less likely to die than those born at a time when there was no ART and no PMTCT, but this did not reach statistical significance.

However, among those who were born less than two years after the roll-out of ART began, there was a 34% decline in the risk of mortality [AHR = 0.66, 95% CI 0.55-0.79, p

“Overall, U2CMR substantially declined in our area from 2001 and this is despite a continued high HIV prevalence and incidence in the area,” said Dr Ndirangu. On the basis of the multivariate analysis, much of the effect was due to maternal access to ART.

He added that they further modelled the impact of the interventions using locally informed assumptions about transmission and the impact of the interventions and concluded that almost a third (31%) of the fall in infant mortality seen during the period of the study could be attributed to maternal antiretroviral treatment. A further 8% was likely explained by programmes to prevent mother to child transmission.

Further information

A webcast James Ndirangu's presentation is available on the IAS 2009 website.