Human milk oligosaccharides and their association with late-onset neonatal sepsis in Peruvian very-low-birth-weight infants

Abstract

Background: Oligosaccharides are the third most abundant component in human milk. They are a potential protective agent against neonatal sepsis.

Objectives: We aimed to explore the association between human milk oligosaccharides (HMOs) and late-onset sepsis in very-low-birth-weight infants, and to describe the composition and characteristics of HMOs in Peruvian mothers of these infants.

Methods: This is a secondary data analysis of a randomized clinical trial. We conducted a retrospective cohort study of mothers and their very-low-birth-weight (<1500 g) infants with ≥1 milk sample and follow-up data for >30 d. HMOs were measured by high performance liquid chromatography (HPLC). We used factor analysis and the Mantel-Cox test to explore the association between HMOs and late-onset neonatal sepsis.

Results: We included 153 mother-infant pairs and 208 milk samples. Overall, the frequency of the secretor phenotype was 93%. Secretors and nonsecretors were defined by the presence and near-absence of α1-2-fucosylated HMOs, respectively. The most abundant oligosaccharides were 2'-fucosyllactose, lacto-N-fucopentaose (LNFP) I, and difucosyllacto-N-tetraose in secretors and lacto-N-tetraose and LNFP II in nonsecretors. Secretors had higher amounts of total oligosaccharides than nonsecretors (11.45 g/L; IQR: 0.773 g/L compared with 8.04 g/L; IQR: 0.449 g/L). Mature milk samples were more diverse in terms of HMOs than colostrum (Simpson's Reciprocal Diversity Index). We found an association of factor 3 in colostrum with a reduced risk of late-onset sepsis (HR: 0.63; 95% CI: 0.41, 0.97). Fucosyl-disialyllacto-N-hexose (FDSLNH) was the only oligosaccharide correlated to factor 3.

Conclusions: These findings suggest that concentrations of different HMOs vary from one individual to another according to their lactation period and secretor status. We also found that FDSLNH might protect infants with very low birth weight from late-onset neonatal sepsis. Confirming this association could prove 1 more mechanism by which human milk protects infants against infections and open the door to clinical applications of HMOs.This trial was registered at clinicaltrials.gov as NCT01525316.

Keywords: breast milk; breastfeeding; human milk oligosaccharides; intensive care unit; neonatal sepsis; very-low-birth-weight infants.

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

Figures

FIGURE 1

Flow diagram of newborns and milk samples through the study. For factor analysis, we excluded infants who did not consume breast milk on any day within the first 7 d of life from the colostrum cohort and those who did not consume breast milk on any day within the entire neonatal period from the mature milk cohort. HPLC-FL, high-performance liquid chromatography with fluorescence detection.

FIGURE 2

Concentrations of FDSLNH (μg/mL) in colostrum of mothers of infants with and without late-onset neonatal sepsis. Data are displayed in a box plot where the median is represented by a horizontal line within the box and the upper and lower borders of the box correspond to quartiles 3 and 1, respectively. FDSLNH, fucosyl-disialyllacto-N-hexose.

FIGURE 3

Kaplan–Meier survival graph of infants developing late-onset neonatal sepsis within the neonatal period (3–30 d). Having an FDSLNH concentration in colostrum above the median was considered high FDSLNH (n = 50). Having an FDSLNH concentration in colostrum below the median was considered low FDSLNH (n = 49). FDSLNH, fucosyl-disialyllacto-N-hexose.