Elevations in mortality associated with weaning persist into the second year of life among uninfected children born to HIV-infected mothers

Abstract

Background: Early weaning has been recommended to reduce postnatal human immunodeficiency virus (HIV) transmission. We evaluated the safety of stopping breast-feeding at different ages for mortality of uninfected children born to HIV-infected mothers.

Methods: During a trial of early weaning, 958 HIV-infected mothers and their infants were recruited and followed up from birth to 24 months postpartum in Lusaka, Zambia. One-half of the cohort was randomized to wean abruptly at 4 months, and the other half of the cohort was randomized to continue breast-feeding. We examined associations between uninfected child mortality and actual breast-feeding duration and investigated possible confounding and effect modification.

Results: The mortality rate among 749 uninfected children was 9.4% by 12 months of age and 13.6% by 24 months of age. Weaning during the interval encouraged by the protocol (4-5 months of age) was associated with a 2.03-fold increased risk of mortality (95% confidence interval [CI], 1.13-3.65), weaning at 6-11 months of age was associated with a 3.54-fold increase (95% CI, 1.68-7.46), and weaning at 12-18 months of age was associated with a 4.22-fold increase (95% CI, 1.59-11.24). Significant effect modification was detected, such that risks associated with weaning were stronger among infants born to mothers with higher CD4(+) cell counts (>350 cells/microL).

Conclusion: Shortening the normal duration of breast-feeding for uninfected children born to HIV-infected mothers living in low-resource settings is associated with significant increases in mortality extending into the second year of life. Intensive nutritional and counseling interventions reduce but do not eliminate this excess mortality.

Figure 1

Survival function estimates calculated from a Cox Proportional Hazards model utilizing breastfeeding cessation as a time-dependent covariate for uninfected children born to HIV-infected mothers if weaned at 5 months of age (dashed line) or if weaned at 18 months of age (solid line).

Figure 2

Survival function estimates calculated from a Cox Proportional Hazards model using breastfeeding cessation as a time-dependent covariate for uninfected children born to HIV-infected mothers if weaned at 5 months of age (dashed line) or if weaned at 18 months of age (solid line) stratified by maternal CD4 count < 350 cells/ml (thin) or maternal CD4 count ≥ 350 cells/ml (thick) at enrollment.