Role of breastfeeding cessation in mediating the relationship between maternal HIV disease stage and increased child mortality among HIV-exposed uninfected children

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Abstract
Background Maternal CD4 count predicts child mortality in HIV-uninfected children born to HIV-infected women. Methods To explore the mediating role of breastfeeding cessation in this relationship, we compared marginal structural models of maternal CD4 count on child death with and without adjustment for breastfeeding. Results In crude analyses, children of mothers with CD4 < 200 during pregnancy were 3.2 times more likely to die by 18 months (CI 1.3–8.1) as children whose mothers had CD4 > 500. Earlier breastfeeding cessation was also associated with low CD4 (HR 1.8; CI 1.2–2.7). After adjusting for breastfeeding and low birth weight using a marginal structural model, the low CD4 count-child mortality association through 18 months was reduced 17%. The change was overestimated using a traditional Cox proportional hazards model (35% reduction in HR from 3.4 to 2.5). Conclusions Our analysis suggests that only a small part of the effect of low vs high CD4 count on child mortality through 18 months is mediated through breastfeeding cessation. Our results must be taken into account when deciding whether or not to recommend breastfeeding for infants of HIV-infected mothers.