title: Oligosaccharide composition of breast milk influences survival of uninfected children born to HIV-infected mothers in Lusaka, Zambia.
abstract: 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.
authors.affiliation: Gertrude H Sergievsky Center and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY;
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
authors.affiliation: Gertrude H Sergievsky Center and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY;
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Division of Neonatal Medicine and Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of California, San Diego, San Diego, CA;
authors.forename: Lauren
authors.initials: L
authors.lastname: Hsiao
authors.affiliation: Division of Neonatal Medicine and Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of California, San Diego, San Diego, CA;
authors.forename: Caroline
authors.initials: C
authors.lastname: Nissan
authors.affiliation: University Teaching Hospital, University of Zambia, Lusaka, Zambia;
authors.forename: Chipepo
authors.initials: C
authors.lastname: Kankasa
authors.affiliation: University Teaching Hospital, University of Zambia, Lusaka, Zambia;
authors.forename: Mwiya
authors.initials: M
authors.lastname: Mwiya
authors.affiliation: Center for International Health and Development, Boston University School of Public Health, Boston, MA; and.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Thea
authors.affiliation: Department of Pediatrics, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA.
authors.forename: Grace M
authors.initials: GM
authors.lastname: Aldrovandi
authors.affiliation: Division of Neonatal Medicine and Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of California, San Diego, San Diego, CA; lbode@ucsd.edu.
authors.forename: Lars
authors.initials: L
authors.lastname: Bode
mesh_terms: D000328:Adult; D000818:Animals; D001942:Breast Feeding; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000401:mortality* / Q000517:prevention & control / Q000635:transmission*; D006801:Humans; D007155:Immunologic Factors; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008892:Milk; D008895:Milk, Human / Q000737:chemistry*; D009844:Oligosaccharides / Q000032:analysis*; D056692:Prebiotics / Q000032:analysis; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D014312:Trisaccharides / Q000032:analysis; D015024:Zambia
chemical_list: D007155:Immunologic Factors; D009844:Oligosaccharides; D056692:Prebiotics; D014312:Trisaccharides; C041762:lacto-N-fucopentaose II; C035714:3'-fucosyllactose; C045442:lacto-N-fucopentaose I; C031420:2'-fucosyllactose
keywords: HIV-exposed uninfected; breastfeeding; child survival; human milk oligosaccharides; mother-to-child HIV transmission