Longitudinal change of selected human milk oligosaccharides and association to infants' growth, an observatory, single center, longitudinal cohort study

Abstract

Background: Human milk is the recommended and sole nutrient source for newborns. One of the largest components of human milk is oligosaccharides (HMOs) with major constituents determined by the mother genotype for the fucosyltransferase 2 (FUT2, secretor) gene. HMO variation has been related with infant microbiota establishment, diarrhea incidence, morbidity and mortality, IgE associated eczema and body composition.

Objectives: We investigated the (i) dependence of several major representative HMOs on the FUT2 status assessed through breast milk 2'Fucosyllactose (2'FL) and (ii) the relation of the 2'FL status with infant growth up to 4 months of life.

Design: From an open observatory, single center, longitudinal cohort study with quantitative human milk collection at 30, 60, and 120 days postpartum from 50 mothers, who gave birth to 25 female and 25 male singleton infants, we collected a representative sample of human milk. We quantified the following 5 representative HMOs: 2'FL, Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL) and 6'Sialyllactose (6'SL). We grouped the milk samples and corresponding infants according to the measured milk 2'FL concentrations at 30 days of lactation, which clustered around low concentrations (95% CI of mean 12-42 mg/L) and high concentrations (95% CI of mean 1880-2460 mg/L) with the former likely representing Secretor negative mothers. Infant anthropometric measures were recorded at birth, 1, 2 and 4 months of age. Relations among the quantified HMOs and the relation of the high and low 2'FL HMOs groups with infant growth parameters were investigated via linear mixed models.

Results: The milk samples with low 2'FL concentration had higher LNT and lower LNnT concentrations compared to the samples with high 2'FL. The milk 3'- and 6'SL concentrations were independent of 2'FL. Over lactation time we observed a drop in the concentration of 2'FL, LNT, LNnT and 6'SL, especially from 1 to 2 months, while 3'SL remained at relatively constant concentration from 1 month onwards. Up to 4 months of age, we did not observe significant differences in body weight, body length, body mass index and head circumference of the infants who consumed breast milk with low or high FUT2 associated HMO concentrations and composition.

Conclusions: Our findings on HMO concentrations over time of lactation and clusters based on 2'FL concentrations confirm previous observations and suggest that LNnT and LNT are 'co-regulated' with the FUT2 dependent 2'FL concentration, with LNnT showing a positive and LNT a negative relation. Further, our findings also suggest that the relatively substantial variation in HMOs between the high and low 2'FL clusters do not impact infant growth of either sex up to 4 months of age. The study was registered in www.ClinicalTrial.gov (NCT01805011).

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: NS CADC PS and SKT are employees of Nestec S.A.; LYL received financial support from Nestle Nutrition to conduct the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Study flow chart of the observational cohort study.

Fig 2. Box plot of HMO concentrations over first 4 months of lactation separated by group with Low- and High 2’Fucosyllactose in milk.

(* indicates difference at a p

Fig 3. Body weight (in kg) and length (in cm) of infants over the first 4 months (120 days) from birth separated by gender and by those who were fed by mothers with Low 2’Fucosyllactose (Light red color; n = 16)) or High 2’Fucosyllactose (darker green color; n = 34) breast milk.

The light blue line indicates the mean of the WHO child growth standard curve with the 95% CI. Means with standard deviation are depicted.

Fig 4. Body mass index (BMI, in kg/m2) of infants over the first 4 months (120 days) from birth separated by gender and by those who were fed by mothers with Low 2’Fucosyllactose (Light red color; n = 16)) or High 2’Fucosyllactose (darker green color; n = 34) breast milk.

The light blue line indicates the mean of the WHO child growth standard curve with the 95% CI. Means with standard deviation are depicted.

Fig 5. Head circumference (in cm) of infants over the first 4 months (120 days) from birth separated by gender and by those who were fed by mothers with Low 2’Fucosyllactose (Light red color; n = 16)) or High 2’Fucosyllactose (darker green color; n = 34) breast milk.

The light blue line indicates the mean of the WHO child growth standard curve with the 95% CI. Means with standard deviation are depicted.