The present study is the first to report and compare mortality among HIV-exposed and HIV non-exposed children up to 2 years of age in a national PMTCT program in resource limited settings. The cumulative risk of death was 2.0% (95% CI: 1.3%-2.7%) by 6 months among HIV-exposed children and comparable to 1.2% (95% CI: 0.6%-1.7%) among HIV non-exposed children. By 9 months, the cumulative risk of death increased notably to 3.0% (95% CI: 2.2%-3.9%) among HIV-exposed children compared to 1.3% (96% CI: 0.7%-1.8%) among HIV non-exposed children. By 2 years, the cumulative risk of death reached 4.2% (95% CI: 2.2%-3.9%) among HIV-exposed children compared to 1.5% (96% CI: 0.7%-1.8%) among HIV non-exposed children. By 2 years, the hazard of death among HIV-exposed children was more than 3 times higher (aHR: 3.5, 95% CI: 1.8-6.9) compared to HIV non-exposed children. Risk of children death by 2 years of age was 50% lower among mothers who attended 4 or more antenatal care (ANC) visits (aHR: 0.5, 95% CI: 0.3-0.9), and 26% lower among families who had more household assets (aHR: 0.7, 95% CI: 0.5-1.0).
The mortality rate among HIV-exposed children in Rwanda is less than half of the rate reported from a pooled analysis of 3,468 HIV-exposed children in Africa showing an 11% mortality rate [2
]. Although two years cumulative risk of death among HIV-exposed children is nearly three times higher than among HIV non-exposed children, it remains lower than the baseline infant mortality (6.2%) and under-five mortality rates (10.3%) in Rwanda [29
In our study, maternal HIV status was associated with an increased risk of death (3.5 times) among under-two year children. Our findings are consistent with previous reports showing higher mortality (2.2-6.3 times) among children born to HIV-positive mothers compared to children born to HIV-negative mothers [2
]. But no published studies reported mortality by 2 years, but mainly by 6 months. During the first 6 months of life, our study evidenced that mortality was low and independent from maternal HIV status. The low 6-month mortality (2.0%; 95% CI: 1.3%-2.7%) among HIV-exposed children from our study could be attributed in our context to the scaling up of various interventions including the PMTCT programs (roll-out of more efficacious ARV regimens including HAART for eligible pregnant women), promotion of exclusive breastfeeding for the first 4-6months, as well as increased access to cotrimoxazole [34
] and ARV prophylaxis or treatment for HIV-exposed or infected children [35
However, mortality significantly increased after 6 months among HIV-exposed children – a finding similar to those in other sub-Saharan African countries. These reports demonstrate early weaning at 4–6 months of age to be the most important and modifiable risk factor for infant mortality among HIV-exposed children after 6 months of age [36
]. The infant feeding guidelines in Rwanda were aligned with the WHO guidelines of 2003 which recommended exclusive breastfeeding with rapid weaning at 4-6 months for HIV-exposed children when all the criteria to formula feed from birth were not met [21
In a trial on the effect of early weaning on child health outcomes in Zambia, authors reported that children who died by 24 months were more likely to have mothers with low CD4 counts and high viral loads, and were more likely to have had mothers who died, as compared to children who did not die by 24 months [40
]. This study demonstrated the important role maternal health plays as determinant of child survival. Without antiretroviral treatment, half of all HIV-infected children would die within the first 2 years of life [41
]. Our study did not measure access to treatment for eligible women during pregnancy, nor did we assess early infection in children (6 weeks old) or children's HIV status at the time of death. However, we hypothesize that maternal health and treatment for HIV-infected children did not play a significant role on the increased child mortality after 6 months in our study. Shorter breast-feeding (or no breast-feeding) may increase mortality from common childhood illnesses [36
] and could be more detrimental for HIV-exposed but uninfected children. Mortality rates among HIV-exposed but uninfected children have been reported to exceed rates among HIV non-exposed children, even when feeding patterns are similar; intensive nutritional and counseling interventions reduce but do not eliminate this excess mortality [30
From a public health standpoint, our findings support the recent revision of the PMTCT and infant feeding guidelines in Rwanda which promote improved maternal health, and extended breastfeeding with antiretroviral prophylaxis during 18 months [42
]. Exclusive breastfeeding of HIV-exposed children is recommended for the first six months with the introduction of healthy, balanced, and appropriate complementary food at six months and continuation of breastfeeding without exceeding the maximum recommended duration of 18 months. Weaning should be done gradually over a period of one month in conjunction with advice and nutritional support.
In our study, higher frequency of ANC visits is associated with lower risk of death in children. Similarly, in a study conducted in Ghana, children born to mothers who did not receive antenatal care were 1.7 times more likely to die before reaching their first birthday than children of mothers who did receive antenatal care [15
]. Receiving prenatal care was also found to be associated with lower risk of infant mortality in Bangladesh [43
Another significant factor in child mortality evidenced in our study and in the current literature concerns household assets. The present research found that more assets owned by a household are associated with lower risk of death in children. Similarly, a study conducted in Cambodia revealed that children born in the poorest 40% of households were more than twice as likely to die during infancy as those born in the richest 20% of households [44
]. During a clinical trial on child health outcomes in Zambia, authors reported that children who died were more likely to have lived in households reporting food insecurity and with more than one child under 5 years of age [40
]. A number of studies found an association with maternal health care seeking behavior and household wealth. In a study conducted in Bangladesh among rural women, 22% of those in the lowest wealth quintile and 69% in the highest quintile reported having sought antenatal care from a medically trained provider [45
]. Another study in Bangladesh found that low household asset status was a major determinant of health-seeking behavior [46
Our analysis was based on data collected from a household survey of mothers selected from ANC registers in PMTCT sites. Even those women who had had only one ANC visit were included in the study sample. According to the 2007-08 Rwanda Interim Demographic and Health Survey, 94% of women who had live births in the past five years received ANC [24
] from trained health personnel at least once. Thus, our sample was drawn from 94% of pregnant women in Rwanda. Given that 73% of women attending ANC visit were offered HIV testing in Rwanda [47
], we were able to identify our sample from 68% of the all mothers who delivered a live birth infant from March 2007 to June 2008.
Our study is representative of all women who had attended at least one ANC visit in PMTCT program sites, and we used a robust two-stage cluster sampling approach. Yet we excluded some health facilities that had been offered PMTCT services for less than 36 months. Mothers who did not consult ANC services were also excluded from the study, and thus did not represent all expecting women during this timeframe. As part of the larger study from which these data on mortality derived, HIV tests were administered at the household level to those children who were still alive at the time of the study. However, given the retrospective nature of the study, many child participants had died at the time of the data collection. Therefore, it was not possible to link the child's death to his or her HIV status. It is uncertain as to whether mothers completely stopped breastfeeding at 9 months, which could confound the data analysis on weaning and survival. Although most mothers responded to all questions, the absence of responses from some participating mothers is an additional limitation. Finally, recall bias concerning PMTCT service use may have influenced study findings.
Further studies should be conducted to fill current gaps in the literature. A longitudinal study on a cohort of children born to HIV-positive and HIV-negative mothers who come for infant immunization at 6 weeks, and HIV tests and follow-up visits until 24 months, would be beneficial. This would diminish recall bias and fit into the regular health visits of a family. In addition, a multivariate analysis comparing ANC utilization to maternal characteristics would be a valuable addition to current scientific literature on child mortality.