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Associations Between Human Milk Oligosaccharides at 1 Month and Infant Development Throughout the First Year of Life in a Brazilian Cohort

Ana Lorena L. Ferreira, Nadya H. Alves-Santos, Nathalia C. Freitas-Costa, Pedro P. T. Santos, Monica A. Batalha, Amanda C. C. Figueiredo, Chloe Yonemitsu, Nadia Manivong, Annalee Furst, Lars Bode, Gilberto Kac

JOURNAL OF NUTRITION(2021)

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Abstract
Background: Human milk oligosaccharides (HMOs) are unconjugated glycans associated with infant health and development. Objectives: To investigate the associations between HMO concentrations at 1 month and infant development throughout the first year of life. Methods: A prospective cohort of Brazilian women between 18-40 years of age and their infants was studied from baseline (between 28-35 gestational weeks) and followed at 1 (n = 73), 6 (n = 51), and 12 months (n = 45). A total of 19 HMOs were quantified by HPLC with fluorescence detection. Infant development was evaluated by the Brazilian Ages and Stages Questionnaire. A directed acyclic graph was used to define the minimally sufficient adjustment (gestational age at birth, gestational weight gain, prepregnancy BMI, maternal age, parity, and the mode of breastfeeding at 1 month). Cox regression models with HRs and Benjamini-Hochberg multiple corrections were performed to estimate associations of HMOs with the cumulative risk of inadequate development for 5 developmental domains or for >= 2 developmental domains in all women and in the subset of secretor women (defined as the presence or near absence of 2'-fucosyllactose and lacto-N-fucopentaose I). Results: The multivariate models with multiple corrections revealed an inverse association between lacto-N-tetrose (LNT) and the risk of inadequate development for personal-social skills (0.06; 95% CI: 0.01-0.76) and for >= 2 developmental domains (0.06; 95% CI: 0.01-0.59). The secretor mothers analysis also showed inverse associations with slightly different results for personal-social skills (0.09; 95% CI: 0.02-0.84) and >= 2 developmental domains (0.05; 95% CI: 0.01-0.70). Conclusions: Higher concentrations of LNT HMOs in Brazilian women are associated with their infants being less likely to be at risk of inadequate development for personal-social skills or for >= 2 developmental domains during the first year of life.
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Key words
human milk oligosaccharides,fucosylated,sialylated,child development,Cox regression,bioactive compound,lacto-N-tetrose
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