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Introduction: We sought to compare risk of death among children aged under-2 years born to HIV positive mother (HIV-exposed) and to HIV negative mother (HIV non-exposed), and identify determinants of under-2 mortality among the two groups in Rwanda. Methods: In a stratified, two-stage cluster sampling design, we selected mother-child pairs using national Antenatal Care (ANC) registers. Household interview with each mother was conducted to capture socio-demographic data and information related to pregnancy, delivery and post-partum. Data were censored at the date of child death. Using Cox proportional hazard model, we compared the hazard of death among HIV-exposed children and HIV nonexposed children. Results: Of 1,455 HIV-exposed children, 29 (2.0%; 95% CI: 1.3%-2.7%) died by 6 months compared to 18 children of the 1,565 HIV non-exposed children (1.2%; 95% CI: 0.6%-1.7%). By 9 months, cumulative risks of death were 3.0% (95%; CI: 2.2%-3.9%) and 1.3% (96%; CI: 0.7%-1.8%) among HIV-exposed and HIV non-exposed children, respectively. By 2 years, the hazard of death among HIVexposed children was more than 3 times higher (aHR:3.5; 95% CI: 1.8-6.9) among HIV-exposed versus non-exposed children. Risk of death by 9- 24 months 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 assets (aHR: 0.7, 95% CI: 0.5-1.0). Conclusion: Infant mortality was independent of perinatal HIV exposure among children by 6 months of age. However, HIV-exposed children were 3.5 times more likely to die by 2 years. Fewer antenatal visits, lower household assets and maternal HIV seropositive status were associated with increased mortality by 9-24 months. © Placidie Mugwaneza et al.
This retrospective cohort study is based on a cross-sectional survey of HIV-positive and HIV-negative mothers and their children. The participants included both mothers and children. Mother participants were HIV-positive or HIV-negative and expecting a child (or children) between March 2007 and June 2008; these only included mothers for whom at least one ANC visit was recorded. Maternal HIV status was determined by HIV rapid test and the national algorithm used at the time of the study, which included three tests: Determine, Unigold and Capillus. Child participants included the mothers’ children who were born during the aforementioned dates. Health facilities that were not providing PMTCT services, in addition to those who had not been providing PMTCT services for fewer than 36 months, were excluded from the study. Mothers who had not had at least one ANC visit and/or who were not expecting a child between the provided dates were excluded from participation. Children whose mothers were not participants in the study were excluded from the study. A stratified two-stage cluster sampling method was used to select participants. First, health centers that had offered PMTCT services for at least 36 months prior to the survey were stratified dichotomously into urban and rural groups. Second, a random sample of health centers was selected from each stratum. Mothers were divided into three groups: HIV-positive mothers who had completed at least 4 ANC visits, HIV-positive mothers who did not complete 4 ANC visits; and HIV-negative mothers. As the recruitment was based on data from ANC registries, it was assumed that women with 4 ANC visits were more likely to comply with other PMTCT program activities than women who had not completed 4 ANC visits. Third, the mother-child pairs were randomly selected from each group and then tracked back to their homes for interviews. A transmission rate of 35% without intervention was assumed according to UNAIDS estimates [26], and a 10% reduction in transmission was assumed with intervention (25% transmission) given that estimates in Rwanda were not available at the time of the study. The 25% and 35% respective transmission rates allowed for a robust sample size calculation that met requirements for a 5% significance level, an 80% statistical power, an assumed 10% non-response rate, and a design effect of 2. Accordingly, a sample size of 3,420 mother-child pairs was required. The methodology was approved by the National Institute of Statistics of Rwanda. At the household level, data were collected using two instruments: a questionnaire for mothers and a child health assessment card. The questionnaire was developed and the outcome and predictor variables were selected based on a literature review. The questionnaire was further refined in close collaboration with PMTCT professionals in Rwanda. Methods were pretested and revised accordingly. The questionnaire was administered in Kinyarwanda, the only local language in Rwanda. Interviews were conducted over the period of 45 minutes on average. This questionnaire was used to capture information about the knowledge of mothers about HIV (with a particular focus on PMTCT), the use of PMTCT services by HIV-positive women, and the use of reproductive health services. Several variables including number of ANC visits, ARVs taken by mother and child, place of delivery, and feeding options were measured using this questionnaire. The child health assessment card was used to record child basic demographics such as age and sex, overall health, as well as weight, height and HIV status. The data presented in this article derive from a larger study on child health and HIV/AIDS in Rwanda. Blood samples were collected at the household level from child participants who were alive at the time of data collection. However, for the purposes of the present findings, and given that not all child participants were alive at the time of data collection, the child’s HIV status was not included for the analysis in this article. Further, the cut-off of 9-24 months was chosen as part of the larger study on child health and HIV/AIDS in Rwanda wherein the child’s HIV status between the ages 9-24 months was required for analysis. In Rwanda, the national PMTCT guidelines mandate the first HIV test for children born to HIV-infected mothers and HIV-discordant couples be administered at 6 weeks using the Polymerase Chain Reaction (PCR). The second and third tests are administered at 9 and 18 months, respectively, using the HIV rapid test. At the time of data collection, the test at 6 weeks had not been implemented in all health facilities that had been offering PMTCT services for the past 36 months. As such, the cut-off of 9 months was chosen to enable the HIV rapid test data to be used. The cut-off of 24 months was used according to PMTCT guidelines in Rwanda as a month wherein HIV-exposed children attend follow-up visits at the health facility. Completed questionnaires were periodically brought in from the field to the School of Public Health of the National University of Rwanda for data entry. Data were entered using CSPro 4.0. A quality control program was used to detect errors in data collection and data entry. This information was shared with field teams during supervisory visits and weekly meetings were held to improve data quality. In addition, 10% of the questionnaires were double-entered for data quality control at entry. Data was exported to STATA 10.1 for data analysis. We used descriptive statistics to describe essential demographic, social, and economic characteristics of participants. The primary study endpoint was the cumulative risk of death among children 9-24 months old according to maternal HIV status. Secondary endpoints included social, and economic and behavioral factors that were associated with child mortality. The potential predictor variables included socio-demographic characteristics of the mother; indices for decision-making power about health and nutrition as well as decision-making power about short and long term investment strategies, housing material, household assets; in addition to household size, access to clean water, location of household, and ANC utilization. The risk of death among children born to HIV-infected mothers was compared to the risk of death among children of the same age born to HIV-negative mothers. As stated above, the purpose of this comparison was to determine if children born to HIV-infected mothers might be at higher risk of death than the rest of the children of the same age. All confidence intervals (CI) were at the 95% level of significance, and P-values of 0.05 and below were considered statistically significant. Kaplan-Meier survival analysis and log rank test were used to assess the difference in survival between children born to HIV-positive mothers and those born to HIV-negative mothers (Figure 2). We modeled the risk of dying by 9-24 months among children born to HIV-infected mothers using a Cox proportional hazard regression model. Categorical independent variables were coded as dummy variables in the regression model. Stepwise selection with a probability of 0.05 for a variable to enter the model and a probability of 0.15 to be removed from the model were used to test the model of the determinants of hazard of death among children. The final model included three variables: mother’s HIV serostatus, the number of ANC visits, and ownership of assets index (Table 3). Kaplan –Meier survival curve of children born to HIV-negative and HIV-positive mothers Background Characteristics of HIV-positive and HIV-negative mothers expecting a child between March 2007 and June 2008, Rwanda, 2009 Appropriate measures were taken to ensure survey participant protection, signed and informed consent, voluntary participation and confidentiality. In addition, formal review and approval of the instruments were obtained from the Rwandan National Ethics Committee.
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