Dynamics of human milk oligosaccharides in early lactation and relation with growth and appetitive traits of Filipino breastfed infants

Abstract

Human milk oligosaccharides play a key role in the maturation of the infant gut microbiome and immune system and are hypothesized to affect growth. This study examined the temporal changes of 24 HMOs and their associations to infant growth and appetitive traits in an exploratory, prospective, observational, study of 41 Filipino mother-infant dyads. Exclusively breastfed, healthy, term infants were enrolled at 21-26 days of age (≈ 0.75 mo) and followed for 6 months. Infant growth measures and appetitive traits were collected at visit 1 (V1) (≈ 0.75 mo), V2 (≈ 1.5 mo), V3 (2.5 mo), V4 (2.75 mo), V5 (4 mo), and V6 (6 mo), while HMOs were measured at V1, V2, V3 and V5. Overall exposure to each HMO was summarized as area under the curve from baseline to 4 months of age and examined in association with each measure of growth at 6 months using linear regression adjusted for maternal age at birth, infant sex, birth weight, and mode of delivery. We saw modest associations between several HMOs and infant growth parameters. Our results suggest that specific HMOs, partly as proxy for milk groups (defined by Secretor and Lewis status), may be associated with head circumference and length, increasing their relevance especially in populations at the lower end of the WHO growth curve. We did not identify the same HMOs associated with infant appetitive traits, indicating that at least in our cohort, changes in appetite were not driving the observed associations between HMOs and growth.Clinical trial registration: NCT03387124.

Figure 1

Study design and subject flow chart. *Only 1 enrolled subject had major protocol deviation (“Informed consent for breastmilk sample is signed but breastmilk sample is not collected”). This subject was not excluded from the per-protocol set for this deviation and thus the full analytic set and per protocol datasets both include 75 subjects.

Figure 2

Trajectories of HMO concentrations over the first 4 months of lactation by milk group with n = 25 for Se+/Le+, n = 5 for Se+/Le−, n = 10 for Se−/Le+ . Not shown is n = 1 for Se−/Le−. Full names of all HMOs are provided in the methods section.

Figure 3

Scatterplots for select HMO Area Under the Curve (AUC) until 4 months of lactation and head circumference and length at 6 months of age (a–c) and length- and weight gain, respectively (d,e) from birth to 6 months of age (N = 41). LDFT, lacto-difucosyltetraose; LNDFH-I, lacto-N-difucosylhexaose-I; LNnDFH, lacto-N-neodifucohexaose; 2’FL, 2’fucosyllactose; 6’GL, 6’galactosyllactose.

Figure 3

Scatterplots for select HMO Area Under the Curve (AUC) until 4 months of lactation and head circumference and length at 6 months of age (a–c) and length- and weight gain, respectively (d,e) from birth to 6 months of age (N = 41). LDFT, lacto-difucosyltetraose; LNDFH-I, lacto-N-difucosylhexaose-I; LNnDFH, lacto-N-neodifucohexaose; 2’FL, 2’fucosyllactose; 6’GL, 6’galactosyllactose.

Figure 4

Scatterplots for select HMO Area Under the Curve (AUC) until 4 months of lactation and length gain from birth to 6 months of age (a) and weight, length, head circumference and length gain at 6 months and length gain from birth to 6 months of age (b) (N = 41). 3FL, 3-fucosyllactose; MFLNH-III, monofucosyllacto-N-hexaose-III.