Oligosaccharide composition of breast milk influences survival of uninfected children born to HIV-infected mothers in Lusaka, Zambia.

BACKGROUND: Human milk oligosaccharides (HMOs) have multiple immunomodulatory functions that influence child health. OBJECTIVE: In this study we investigated whether HMO composition influences survival to 2 y of age in HIV-infected and HIV-exposed, uninfected (HEU) children during and after breastfeeding. METHODS: In the context of an early weaning trial in 958 HIV-infected women in Lusaka, Zambia, we conducted a nested case-cohort analysis of mortality to 2 y of age among 103 HIV-infected and 143 HEU children. Breast-milk samples collected at 1 mo postpartum were analyzed for HMO content. Samples were selected to include mothers of all HIV-infected children detected by 6 wk of age, of whom 63 died at <2 y of age; mothers of all HEU children who died at <2 y of age (n = 66); and a random sample of 77 HEU survivors. Associations before and after weaning in HIV-infected and HEU infants separately were investigated by using Cox models. RESULTS: Among HEU children, higher maternal breast-milk concentrations of 2-linked fucosylated HMOs [2'-fucosyllactose and lacto-N-fucopentaose (LNFP) I] (HR: 0.33; 95% CI: 0.14, 0.74) as well as non-2-linked fucosylated HMOs (3-fucosyllactose and LNFP II/III; HR: 0.28; 95% CI: 0.13, 0.67) were significantly associated with reduced mortality during, but not after, breastfeeding after adjustment for confounders. Breastfeeding was protective against mortality only in HEU children with high concentrations of fucosylated HMOs. Among HIV-infected children, no consistent associations between HMOs and mortality were observed, but breastfeeding was protective against mortality. CONCLUSIONS: The oligosaccharide composition of breast milk may explain some of the benefits of breastfeeding in HEU children. HIV infection may modulate some of the consequences of HMOs on child survival.

Human milk oligosaccharide concentration and risk of postnatal transmission of HIV through breastfeeding.

BACKGROUND: The inefficiency of HIV breast-milk transmission may be caused by the presence of immunologically active factors, including human milk oligosaccharides (HMOs). OBJECTIVE: We investigated whether HMO concentrations are associated with a reduced risk of postnatal HIV transmission. DESIGN: A nested case-control study was conducted within a larger cohort study of HIV-infected women and their infants followed from birth to 24 mo in Lusaka, Zambia. Breast-milk samples collected at 1 mo from 81 HIV-infected women who transmitted via breastfeeding, a random sample of 86 HIV-infected women who did not transmit despite breastfeeding, and 36 uninfected breastfeeding women were selected. Total and specific HMO concentrations were measured by HPLC and compared between groups with adjustment for confounders by using logistic regression. RESULTS: HIV-infected women with total HMOs above the median (1.87 g/L) were less likely to transmit via breastfeeding (OR: 0.45; 95% CI: 0.21, 0.97; P = 0.04) after adjustment for CD4 count and breast-milk HIV RNA concentrations; a trend toward higher concentrations of lacto-N-neotetraose being associated with reduced transmission (OR: 0.49; 95% CI: 0.23, 1.04; P = 0.06) was also observed. The proportion of 3'-sialyllactose (3'-SL) per total HMOs was higher among transmitting than among nontransmitting women (P = 0.003) and correlated with higher plasma and breast-milk HIV RNA and lower CD4 counts. Neither Secretor nor Lewis status distinguished between transmitting and nontransmitting women. CONCLUSIONS: Higher concentrations of non-3'-SL HMOs were associated with protection against postnatal HIV transmission independent of other known risk factors. Further study of these novel, potentially anti-HIV components of breast milk is warranted.