No abstract

Human milk oligosaccharides (HMOs) have specific dose-dependent effects on child health outcomes. The HMO profile differs across mothers and is largely dependent on gene expression of specific transferase enzymes in the lactocytes. This study investigated the trajectories of absolute HMO concentrations at three time points during lactation, using a more accurate, robust, and extensively validated method for HMO quantification. We analyzed human milk sampled at 6 weeks (n = 682), 6 months (n = 448), and 12 months (n = 73) of lactation in a birth cohort study conducted in south Germany, using label-free targeted liquid chromatography mass spectrometry (LC-MS2). We assessed trajectories of HMO concentrations over time and used linear mixed models to explore the effect of secretor status and milk group on these trajectories. Generalized linear model-based analysis was used to examine associations between HMOs measured at 6 weeks of lactation and maternal characteristics. Results: Overall, 74%, 18%, 7%, and 1% of human milk samples were attributed to milk groups I, II, III, and IV, respectively. Most HMO concentrations declined over lactation, but some increased. Cross-sectionally, HMOs presented high variations within milk groups and secretor groups. The trajectories of HMO concentrations during lactation were largely attributed to the milk group and secretor status. None of the other maternal characteristics were associated with the HMO concentrations. The observed changes in the HMO concentrations at different time points during lactation and variations of HMOs between milk groups warrant further investigation of their potential impact on child health outcomes. These results will aid in the evaluation and determination of adequate nutrient intakes, as well as further (or future) investigation of the dose-dependent impact of these biological components on infant and child health outcomes.

The objective of the study was to investigate the potential association of human milk leptin concentrations with child body mass index (BMI) and BMI trajectory patterns up to two years of age among children in the Ulm SPATZ Health Study. Leptin concentration was measured in skimmed human milk by ELISA (R&D System). Child BMI was determined at two to three days, three to four weeks, four to five months, one year, and two years of age. In SPATZ, leptin concentration at six weeks was inversely associated with child BMI at four to five weeks [beta –0.13, 95%CI –0.21;–0.05)] and at three to four months –0.12 –0.21;–0.03)]. Among infants of average BMI shortly after delivery, six week leptin was positively associated with greater increase in BMI from four to five weeks up to two years of age [0.16 (0.04;0.27)]. No associations were observed for six month leptin. Direction of association was the same in the Ulm Birth Cohort Study (UBCS), but statistically insignificant as the point estimate included the null effect value. Our results from SPATZ suggest human milk leptin may play a role in early infant growth. However, it is plausible that the lack of associations in UBCS suggest that these differences of human milk leptin composition between populations could have an impact in infant growth and development in a given population.

The lipid fraction of human milk provides the infant with the fatty acids that are necessary for optimal growth and development. The aim of this study was to investigate the fatty acid composition of human milk at three time points during lactation and its change over time using appropriate statistical methods. Human milk samples from breastfeeding mothers at 6 weeks (n = 706), 6 months (n = 483), and 12 months (n = 81 with all three time points) were analyzed. Centered log-ratio (clr) transformation was applied to the fatty acid data. Principal component analysis (PCA) and generalized linear model-based repeated measure analysis were used to assess changes over time. The total lipid content was significantly higher at 6 months (β = 0.199, p < 0.029) and 12 months of lactation (β = 0.421, p < 0.001). The constituents of C20:3n-6 and C20:3n-3 were lower at 6 months (p < 0.001). Four distinct sub-compositional fatty acid groups were only identified at 12 months of lactation. The inclusion of small fatty acids of small constituent size in the analysis resulted in a shift in the balance between fatty acid constituents. Human milk fatty acid composition during prolonged lactation is different from that of human milk during a short duration of lactation. Our findings support the hypothesis that a combination of multiple fatty acids is important in fatty acid profiling beyond the presentation of individual fatty acids. Furthermore, the high variability of small fatty acids warrants attention because a compositional analysis may show more pronounced changes.

ObjectivesTo review available health and nutrition claims for infant formula products in multiple countries and to evaluate the validity of the evidence used for substantiation of claims.DesignInternational cross sectional survey.SettingPublic facing and healthcare professional facing company owned or company managed formula industry websites providing information about products marketed for healthy infants delivered at full term in 15 countries: Australia, Canada, Germany, India, Italy, Japan, Nigeria, Norway, Pakistan, Russia, Saudi Arabia, South Africa, Spain, the United Kingdom, and the United States in 2020-22.Main outcome measuresNumber and type of claims made for each product and ingredient. References cited were reviewed and risk of bias was assessed for registered clinical trials using the Cochrane risk of bias tool, and for systematic reviews using the Risk Of Bias in Systematic reviews tool.Results757 infant formula products were identified, each with a median of two claims (range from 1 (Australia) to 4 (US)), and 31 types of claims across all products. Of 608 products with ≥1 claims, the most common claim types were “helps/supports development of brain and/or eyes and/or nervous system” (323 (53%) products, 13 ingredients), “strengthens/supports a healthy immune system” (239 (39%) products, 12 ingredients), and “helps/supports growth and development” (224 (37%) products, 20 ingredients). 41 groups of ingredients were associated with ≥1claims, but many claims were made without reference to a specific ingredient (307 (50%) products). The most common groups of ingredients cited in claims were long chain polyunsaturated fatty acids (278 (46%) products, 9 different claims); prebiotics, probiotics, or synbiotics (225 (37%) products, 19 claims); and hydrolysed protein (120 (20%) products, 9 claims). 161/608 (26%) products with ≥1 claims provided a scientific reference to support the claim—266 unique references were cited for 24 different claim types for 161 products. The reference types most frequently cited were clinical trials (50%, 134/266) and reviews (20%, 52/266). 28% (38/134) of referenced clinical trials were registered, 14% (19/134) prospectively. 58 claims referred to 32 registered clinical trials, of which 51 claims (27 trials) related to a randomised comparison. 46 of 51 claims (90%) referenced registered clinical trial outcomes at high risk of bias, and all cited systematic reviews and pooled analyses, carried a high risk of bias.ConclusionsMost infant formula products had at least one health and nutrition claim. Multiple ingredients were claimed to achieve similar health or nutrition effects, multiple claims were made for the same ingredient type, most products did not provide scientific references to support claims, and referenced claims were not supported by robust clinical trial evidence.