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


OBJECTIVE
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.


METHODS
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).
Nestlé Research Center, Nestec Ltd., Vers-chez-les-Blanc, Switzerland.
Norbert
http://orcid.org/0000-0003-4880-2750
N
Sprenger
Consultant Neonatologist, Department of Neonatology, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, Singapore.|Assistant Professor, Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Le Ye
LY
Lee
Nestlé Research Center, Nestec Ltd., Vers-chez-les-Blanc, Switzerland.
Carlos Antonio
CA
De Castro
Nestlé Nutrition, Vevey, Switzerland.
Philippe
P
Steenhout
Nestlé Research Center, Nestec Ltd., Vers-chez-les-Blanc, Switzerland.
Sagar K
SK
Thakkar
D000328:Adult; D001942:Breast Feeding; D002657:Child Development / Q000502:physiology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007774:Lactation / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008895:Milk, Human / Q000737:chemistry* / Q000378:metabolism; D009035:Mothers; D009844:Oligosaccharides / Q000032:analysis* / Q000378:metabolism; D055815:Young Adult
D009844:Oligosaccharides