Background Breastfeeding modulates infant growth and protects against the development of obesity. However, whether or not maternal variation in human milk components, such as human milk oligosaccharides (HMOs), is associated with programming of child growth remains unknown. Objective Our objective was to determine the association between maternal HMO composition and child growth during the first 5 y of life. In addition, the association between maternal prepregnancy BMI and HMO composition was assessed. Methods Human milk samples from 802 mothers were obtained from a prospective population-based birth cohort study, Steps to healthy development of Children (STEPS), conducted in Turku, Finland. HMO composition in these milk samples was analyzed by HPLC. Child growth data from 3 mo to 5 y were collected from municipal well-baby clinics and linked to maternal HMO composition data to test for associations. Results Maternal HMO composition 3 mo after delivery was associated with height and weight during the first 5 y of life in children of secretor mothers. Specifically, HMO diversity and the concentration of lacto-N-neo-tetraose (LNnT) were inversely associated and that of 2′-fucosyllactose (2′FL) was directly associated with child height and weight z scores in a model adjusted for maternal prepregnancy BMI, mode of delivery, birthweight z score, sex, and time. Maternal prepregnancy BMI was associated with HMO composition. Conclusions The association between maternal HMO composition and childhood growth may imply a causal relation, which warrants additional testing in preclinical and clinical studies, especially since 2′FL and LNnT are among the HMOs now being added to infant formula. Furthermore, altered HMO composition may mediate the impact of maternal prepregnancy BMI on childhood obesity, which warrants further investigation to establish the cause-and-effect relation.

Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.

BackgroundChildhood obesity and overweight are among the greatest health challenges in the pediatric population. Obese individuals exhibit marked differences in the composition of the intestinal microbial community as compared to lean subjects. These changes in the gut microbiota precede the clinical manifestation of overweight. Convincing experimental data suggest a causal role for intestinal microbes in the development of obesity and associated metabolic disorders.DiscussionExposure to antibiotics exerts a devastating impact on the intestinal microbial community. Epidemiological studies have provided evidence indicating that early or repeated childhood exposure to antibiotics is associated with increased risk of overweight later in childhood but the causal role of this exposure in obesity development is not clear. However, data from studies conducted using experimental animal models indicate that antibiotic-induced changes in the gut microbiota influence host metabolism and lead to fat accumulation. The intestinal microbiota perturbation caused by antibiotic exposure in the perinatal period appears to program the host to an obesity-prone metabolic phenotype, which persists after the antibiotics have been discontinued and the gut microbiota has recovered. These observations may have serious implications in the clinical setting, since a substantial number of human infants are subjected to antibiotic treatment through the mother during delivery or directly in the immediate neonatal period. The clinical significance of these exposures remains unknown.SummaryPrudent use of antibiotics is paramount not only to reduce the propagation of antibiotic-resistant organisms but also to minimize the potentially detrimental long-term metabolic consequences of early antibiotic exposure. Improved means of reliably detecting neonates with bacterial infection would reduce the need for empirical antibiotic exposure initiated based on nonspecific symptoms and signs or risk factors. Finally, means to support healthy microbial contact in neonates and infants requiring antibiotic treatment are needed.