Factors influencing PCV13 specific antibody response in Danish children starting in day care.

This study examines different factors influencing the 13-valent pneumococcal conjugate vaccine (PCV13) specific antibody response in 8-13 months old Danish children starting in day care. We present secondary findings to the ProbiComp study, which included nose swabs, buccal swabs and blood samples from the children before entering day care (baseline) and again after 6 months. Pneumococci isolated from nose swabs were identified by latex agglutination kit and Quellung reaction. Luminex-based assay was used for antibody measurements against specific anti-pneumococcal capsular IgG. Buccal gene expression was analyzed by qPCR. Statistical analyses were performed in R and included Pearson's Chi-squared test, Welch two sample t-test and linear regression models. The PCV13 antibody response was unaffected by whether the children were carriers or non-carriers of any pneumococcal serotype. Having siblings increased the risk of carrying serotype 21 before day care (p = 0.020), and having siblings increased the PCV13 antibody response at the end of study (p = 0.0135). Hepatitis B-vaccination increased the PCV13 antibody response before day care attendance (p = 0.005). The expression of IL8 and IL1B was higher in children carrying any pneumococcal serotype at baseline compared to non-carriers (p = 0.0125 and p = 0.0268 respectively).

Effects of vitamin D supplementation on cardiometabolic outcomes in children and adolescents: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: In observational studies, higher S-25-hydroxyvitamin D [S-25(OH)D] has been associated with a more favorable cardiometabolic profile in childhood, but results may be confounded. We examined effects of vitamin D supplementation on cardiometabolic outcomes in children and adolescents. METHODS: We systematically searched relevant databases for randomized controlled trials (RCTs) examining effects of vitamin D supplementation compared to placebo or a lower dose of vitamin D on blood glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), glycated hemoglobin, cholesterol [total, high-density, and low-density lipoprotein (LDL-C)], triglycerides, or blood pressure. We conducted random-effects meta-analyses of weighted mean differences in all participants and in subgroups of overweight/obese versus normal weight participants with or without baseline S-25(OH)D < 50 nmol/L. We also explored associations between responses in S-25(OH)D and outcomes by meta-regression. RESULTS: Fourteen RCTs with a total of 1088 participants aged 4-19 years were included. In the meta-analysis, vitamin D supplementation increased S-25(OH)D by 27 nmol/L [95% CI 16; 37] (P < 0.0001) and increased LDL-C by 0.11 mmol/L [0.02; 0.20] (P = 0.02) without any subgroup differences and a generally low to moderate heterogeneity. Vitamin D supplementation had no other effects. However, in the meta-regression analysis, HOMA-IR decreased by 0.51 points [- 0.97; - 0.04] per 10 nmol/L increase in the endpoint S-25(OH)D among overweight/obese participants (P = 0.04). CONCLUSIONS: These results do not support the use of vitamin D supplementation for improving cardiometabolic health in childhood. Indicated beneficial effects on insulin resistance in those with obesity could be investigated further, while unfavorable effects on LDL-C may be a concern.

Human Milk Oligosaccharide Composition Is Associated With Excessive Weight Gain During Exclusive Breastfeeding-An Explorative Study.

Background: Some infants experience excessive weight gain during exclusive breastfeeding. The cause is unknown, but variation in human milk composition might play a role. Several human milk koligosaccharides (HMOs) have been associated with growth velocity in breastfed infants, and it has been suggested that the mechanism could be through an effect on infant gut microbiota composition. Objective: The purpose of this exploratory study was to evaluate if HMO composition was different in milk fed to infants with excessive weight gain compared to infants with normal weight gain. Furthermore, we aimed to examine if HMO composition was associated with growth velocity and change in body composition and if there were maternal determinants of HMO composition. Materials and Methods: We recruited 13 high weight-gain (HW) and 17 normal weight-gain (NW) breastfed infants, collected human milk and anthropometry data at 5 and 9 months, and analyzed HMO composition by high performance liquid chromatography. Results: In the HW group eight out of 11 infants received milk from secretor mothers and in the NW group 15 out of 17. Comparing milk from Secretor mothers only, four HMO's were significantly different between the HW and NW group at 5 months and two remained significant at 9 months. Total HMO concentrations as well as total HMO-bound fucose at 5 months were positively associated with both fat mass index (FMI) and weight velocity from 0 to 5 months (all p < 0.025). 2'-fucosyllactose (2'-FL) was positively associated with weight velocity from 0 to 5 months and FMI at 5 months. In contrast, lacto-N-neotetraose was lower in the HW group (p = 0.012) and negatively associated with height-for-age Z-scores (p = 0.008), weight velocity from 0 to 5 months (p = 0.009) and FMI (p = 0.033). Maternal BMI at 5 months was negatively associated with 6'-sialyllactose and sialyl-lacto-N-tetraose (LSTb) and positively with 2'-FL, total HMO and total HMO-bound fucose (all p ≤ 0.03). Conclusion: In a small cohort, we found significantly different HMO concentrations in milk to exclusively breastfed infants with excessive weight gain, suggesting that some HMOs, including 2'-FL, which is the most abundant HMO and currently added to some infant formula, could be part of the cause for the excessive weight gain.

Corrigendum: Human Milk Oligosaccharide Composition Is Associated With Excessive Weight Gain During Exclusive Breastfeeding-An Explorative Study.

[This corrects the article DOI: 10.3389/fped.2019.00297.].

Probiotics and carriage of Streptococcus pneumoniae serotypes in Danish children, a double-blind randomized controlled trial.

This study examined the carriage of Streptococcus pneumoniae in healthy Danish children aged 8-19 months and assessed the effect of the probiotics Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis on the pneumococcal carriage during daycare enrolment. Potential risk factors of pneumococcal carriage were analysed and the carriage study was compared with registered invasive pneumococcal disease (IPD) data. This study is a part of the ProbiComp study, which was a double-blind, randomized controlled trial, including 290 children allocated to probiotics or placebo for 6 months and recruited during two autumn seasons (2014/2015). Pneumococci were identified by optochin sensitivity, bile solubility, α-hemolysis and/or capsular reaction. Serotyping was performed by latex agglutination kit and Quellung reaction. The carriage rate of S. pneumoniae was 26.0% at baseline and 67.4% at the end of intervention. No significant difference was observed between the placebo group and the probiotics group (p = 0.508). Children aged 8-19 months were carriers of non-pneumococcal vaccine serotypes causing IPD in children aged 0-4 years. However, serotypes causing most IPD cases in Danish elderly were either not found or found with low prevalence suggesting that children are not the main reservoir of those serotypes and other age groups need to be considered as carriers.

Probiotics for respiratory tract infections in children attending day care centers-a systematic review.

Probiotics have been suggested to have a preventive effect on respiratory tract infections (RTIs), but limited evidence exist on strain-specific effects. The main aim of this systematic review and meta-analysis was to evaluate strain-specific probiotic effects on RTIs in children attending day care. We included 15 RCTs with 5121 children in day care settings (aged 3 months to 7 years), but due to high diversity in reported outcomes, different number of RCTs were available for evaluated outcomes. Twelve RCTs (n = 4527) reported results which could be compared in at least one outcome of the meta-analysis. Compared to placebo, Lactobacillus rhamnosus GG (LGG) significantly reduced duration of RTIs (three RCTs, n = 1295, mean difference - 0.78 days, 95% confidence interval (CI) - 1.46; - 0.09), whereas no effect was found on other evaluated outcomes. Based on the results from two studies (n = 343), Bifidobacterium animalis subsp. lactis BB-12 showed no effect on duration of RTIs or on absence from day care. Meta-analyses on other strains or their combination were not possible due to limited data and different outcome measures.Conclusion: LGG is modestly effective in decreasing the duration of RTIs. More RCTs investigating specific probiotic strains or their combinations in prevention of RTIs are needed. What is known: • Previously published systematic reviews have suggested that probiotics may have a preventive effect on respiratory infections, but limited data exist on strain specific effects. What is new: • This systematic review showed that use of Lactobacillus rhamnosus GG modestly reduces the duration of respiratory tract infections.

Risks for upper respiratory infections in infants during their first months in day care included environmental and child-related factors.

AIM: We examined the frequency and potential risk factors for respiratory infections, diarrhoea and absences in infants during their first months in day care. METHODS: This prospective cohort study comprised 269 Danish infants aged eight months to 14 months and was part of a study that examined how probiotics affected absences from day care due to respiratory and gastrointestinal infections. The risk factors examined were the household, child characteristics and type of day care facility. Parents registered upper respiratory tract infections (URTIs), lower respiratory tract infections (LRTIs), diarrhoea and day care absences on web-based questionnaires. RESULTS: Over a mean of 5.6 months in day care, 36% and 20% of the infants had at least one URTI or LRTI, and 60% had diarrhoeal episodes. The risk of at least one URTI was increased by previous respiratory infections, with an odds ratio (OR) of 2.65, but was inversely associated with having a pet (OR: 0.43), being cared for by registered child minders compared to day care centres (OR: 0.36), birthweight (OR 0.40) and age at day care enrolment (OR: 0.64). No significant risk factors for LRTIs and diarrhoea were found. CONCLUSION: Infection risks were associated with environmental factors and factors related to the child.

Faecalibacterium Gut Colonization Is Accelerated by Presence of Older Siblings.

Faecalibacterium prausnitzii is a highly abundant human gut microbe in healthy individuals, but it is present at reduced levels in individuals with gastrointestinal inflammatory diseases. It has therefore been suggested to constitute a marker of a healthy gut and is associated with anti-inflammatory properties. However, factors affecting the colonization of F. prausnitzii in the human gut during early life are very poorly understood. By analysis of 16S rRNA amplicon sequencing data from three separate infant study populations, we determined the colonization dynamics of Faecalibacterium and factors affecting its establishment in the gut. We found that in particular, the presence of older siblings was consistently associated with Faecalibacterium gut colonization during late infancy and conclude that acquisition of Faecalibacterium is very likely to be accelerated through transfer between siblings. IMPORTANCEFaecalibacterium prausnitzii has been suggested to constitute a key marker of a healthy gut, yet the factors shaping the colonization of this highly oxygen-sensitive, non-spore-forming species in the intestinal environment remain poorly understood. Here, we provide evidence from three separate infant study populations that F. prausnitzii colonization in the gut happens during late infancy and is affected by the number of older siblings in the family. We conclude that Faecalibacterium acquisition is highly likely to be accelerated by contact between siblings. Bearing in mind the immunoregulatory properties of F. prausnitzii and the well-established protective effects against allergic disorders related to the presence of older siblings, early colonization of this species may have profound consequences for child health.

Administration of two probiotic strains during early childhood does not affect the endogenous gut microbiota composition despite probiotic proliferation.

BACKGROUND: Probiotics are increasingly applied to prevent and treat a range of infectious, immune related and gastrointestinal diseases. Despite this, the mechanisms behind the putative effects of probiotics are poorly understood. One of the suggested modes of probiotic action is modulation of the endogenous gut microbiota, however probiotic intervention studies in adults have failed to show significant effects on gut microbiota composition. The gut microbiota of young children is known to be unstable and more responsive to external factors than that of adults. Therefore, potential effects of probiotic intervention on gut microbiota may be easier detectable in early life. We thus investigated the effects of a 6 month placebo-controlled probiotic intervention with Bifidobacterium animalis subsp. lactis (BB-12®) and Lactobacillus rhamnosus (LGG®) on gut microbiota composition and diversity in more than 200 Danish infants (N = 290 enrolled; N = 201 all samples analyzed), as assessed by 16S rRNA amplicon sequencing. Further, we evaluated probiotic presence and proliferation by use of specific quantitative polymerase chain reaction (qPCR). RESULTS: Probiotic administration did not significantly alter gut microbiota community structure or diversity as compared to placebo. The probiotic strains were detected in 91.3% of the fecal samples from children receiving probiotics and in 1% of the placebo treated children. Baseline gut microbiota was not found to predict the ability of probiotics to establish in the gut after the 6 month intervention. Within the probiotics group, proliferation of the strains LGG® and BB-12® in the gut was detected in 44.7% and 83.5% of the participants, respectively. A sub-analysis of the gut microbiota including only individuals with detected growth of the probiotics LGG® or BB-12® and comparing these to placebo revealed no differences in community structure or diversity. CONCLUSION: Six months of probiotic administration during early life did not change gut microbiota community structure or diversity, despite active proliferation of the administered probiotic strains. Therefore, alteration of the healthy infant gut microbiota is not likely to be a prominent mechanism by which these specific probiotics works to exert beneficial effects on host health. TRIAL REGISTRATION: NCT02180581 . Registered 30 June 2014.

Probiotics and Child Care Absence Due to Infections: A Randomized Controlled Trial.

OBJECTIVES: The risk of infections is higher in children attending child care compared with children cared for at home. This study examined the effect of a combination of probiotics on absence from child care because of respiratory and gastrointestinal infections in healthy infants aged 8 to 14 months at the time of enrollment in child care. METHODS: The ProbiComp study was a randomized, double-blind, placebo-controlled study. A total of 290 infants were randomly allocated to receive a placebo or a combination of Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus in a dose of 109 colony-forming units of each daily for a 6-month intervention period. Absence from child care, occurrence of infant symptoms of illness, and doctor visits were registered by the parents using daily and weekly Web-based questionnaires. RESULTS: Median absence from child care was 11 days (interquartile range: 6-16). Intention-to-treat analysis showed no difference between the probiotics and placebo groups (P = .19). Additionally, there was no difference in any of the secondary outcomes between groups; the number of children with doctor-diagnosed upper or lower respiratory tract infections, the number of doctor visits, antibiotic treatments, occurrence and duration of diarrhea, and days with common cold symptoms, fever, vomiting, or caregivers' absence from work. CONCLUSIONS: A daily administration of a combination of B animalis subsp lactis and L rhamnosus for 6 months did not reduce the number of days absent from child care in healthy infants at the time of enrollment in child care.