Human milk oligosaccharide profiles and child atopic dermatitis up to 2 years of age: The Ulm SPATZ Health Study.

BACKGROUND: Human milk oligosaccharides (HMOs) have several biological functions. Yet, very few studies have investigated the effect of HMOs on the development of allergies and even fewer on their specific associations with atopic dermatitis (AD) during early childhood. OBJECTIVE: This study investigated whether individual HMO concentrations, measured at two time points of lactation, were associated with reported diagnosis of AD in children up to two years of age. METHOD: Outcome data were available for HMOs measured in human milk samples collected at 6 weeks (n = 534) and 6 months (n = 356) of lactation. Associations of HMOs with AD, ascertained from parents and pediatricians at ages one and two years, were assessed in crude and adjusted logistic regression models. RESULTS: Few associations were statistically significant at the conventional level (p < .05), for example, 6-week Lacto-N-neotetraose with 2-year AD [OR 95%CI: 0.82 (0.66, 1.00)] and 6-month 3'-sialyllactose among non-secretor mothers with 1-year AD [2.59 (1.53, 6.81)]. Importantly, accounting for multiple testing, these and all further associations were not statistically significant (all p > .0031, which is the threshold for statistical significance after correction for multiple testing). CONCLUSION: Our findings suggest that the intake of different levels (or even absence) of the individual HMOs measured at 6 weeks and 6 months of lactation, in the current study, is not significantly associated with the development of AD in early childhood. Given the exploratory nature of our study and the limited sample size, these results should be interpreted with caution. The specific HMOs for which we show plausible associations at conventional level may warrant further research and investigation.

Associations of Human Milk Oligosaccharides With Otitis Media and Lower and Upper Respiratory Tract Infections up to 2 Years: The Ulm SPATZ Health Study.

Background: Human milk oligosaccharides (HMOs) support and concurrently shape the neonatal immune system through various mechanisms. Thereby, they may contribute to lower incidence of infections in infants. However, there is limited evidence on the role of individual HMOs in the risk of otitis media (OM), as well as lower and upper respiratory tract infections (LRTI and URTI, respectively) in children up to 2 years. Objective: To investigate whether individual HMO concentrations measured at 6 weeks of lactation were associated with risk of OM, LRTI or URTI up to 2 years in breastfed infants. Associations with OM, LRTI and URTI were determined for the most prominent human milk oligosaccharides including 13 neutral, partly isomeric structures (trioses up to hexaoses), two acidic trioses, and lactose. Design: HMO measurements and physician reported data on infections were available from human milk samples collected at 6 weeks postpartum (n = 667). Associations of HMOs with infections were assessed in crude and adjusted models using modified Poisson regression. Results: Absolute concentrations (median [min, max], in g/L) of 2'-fucosyllactose (2'-FL) tended (p = 0.04) to be lower, while lacto-N-tetraose (LNT) was higher in the milk for infants with OM in the 1st year of life (p = 0.0046). In the milk of secretor mothers, LNT was significantly higher in the milk for infants with OM (RR [95% CI]: 0.98 [0.15, 2.60]) compared to infants without OM (RR [95% CI]: 0.76 [0.14, 2.90]) at 1 year (p = 0.0019). No statistically significant milk group differences and associations were observed for OM, LRTI, and URTI (p > 0.0031). Conclusion: Our findings suggest that neither prominent neutral individual HMOs (ranging from 2'-FL to LNDFHs) nor acidic human milk sialyllactoses or lactose are significantly associated with a reduced or increased risk of infections in infants up to 2 years of age. Further research is needed to determine whether specific HMOs could potentially reduce the incidence or alleviate the course of distinct infections in early life.

Human Milk Oligosaccharide Profiles over 12 Months of Lactation: The Ulm SPATZ Health Study.

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.

Robust Bayesian Algorithm for Targeted Compound Screening in Forensic Toxicology.

As part of forensic toxicological investigation of cases involving unexpected death of an individual, targeted or untargeted xenobiotic screening of post-mortem samples is normally conducted. To this end, liquid chromatography (LC) coupled to high-resolution mass spectrometry (MS) is typically employed. For data analysis, almost all commonly applied algorithms are threshold-based (frequentist). These algorithms examine the value of a certain measurement (e.g., peak height) to decide whether a certain xenobiotic of interest (XOI) is present/absent, yielding a binary output. Frequentist methods pose a problem when several sources of information [e.g., shape of the chromatographic peak, isotopic distribution, estimated mass-to-charge ratio (m/z), adduct, etc.] need to be combined, requiring the approach to make arbitrary decisions at substep levels of data analysis. We hereby introduce a novel Bayesian probabilistic algorithm for toxicological screening. The method tackles the problem with a different strategy. It is not aimed at reaching a final conclusion regarding the presence of the XOI, but it estimates its probability. The algorithm effectively and efficiently combines all possible pieces of evidence from the chromatogram and calculates the posterior probability of the presence/absence of XOI features. This way, the model can accommodate more information by updating the probability if extra evidence is acquired. The final probabilistic result assists the end user to make a final decision with respect to the presence/absence of the xenobiotic. The Bayesian method was validated and found to perform better (in terms of false positives and false negatives) than the vendor-supplied software package.

Validation of transferability of DBA derivatization and LC-MS/MS determination method for isocyanates via an interlaboratory comparison.

An adapted method for the quantitative determination of isocyanates in air was implemented and validated in-house. The method was based on air sampling using an impinger flask containing di-n-butylamine (DBA) in toluene and a glass fibre filter in series. The DBA derivatives were determined using liquid chromatography and tandem mass spectrometry. Studied isocyanates were isophorone diisocyanate, isocyanic acid (ICA), methyl isocyanate, ethyl isocyanate, propyl isocyanate, hexamethylene diisocyanate (HDI), 2,6- and 2,4-toluene diisocyanate, 4,4'-methylene diphenyl diisocyanate (MDI), phenyl isocyanate (PhI), MDI oligomers and different HDI adducts. Monitoring of selected reactions resulted in quantifications with correlation coefficients >0.995, within-batch relative standard deviation (RSD) of repeatability was <13% for all analytes. Between-batch RSD (reproducibility) was determined for all the compounds with the exception of the adducts and oligomers and was also <13%. As an additional validation procedure, the method was evaluated by exchanging field (air) and standard samples between two laboratories. The RSDs observed by the two laboratories were comparable. The concentrations determined were between 80 and 120% of each other, depending on the analyte and the individual concentrations. The method was applied in a large field study on exposure of workers in car repair shops and industrial painters with >500 samples.