Improved Performance With the Micro-Hole Zone Intermittent Catheter: A Combined Analysis of 3 Randomized Controlled Studies Comparing the New Catheter Technology With a Conventional Eyelet Catheter.

PURPOSE: To assess the performance of a new urinary intermittent catheter (IC) prototype designed with a micro-hole drainage zone compared to a conventional eyelet catheter (CEC) in terms of flow-stop, bladder emptying, and hematuria. DESIGN: Randomized controlled crossover studies. SUBJECT AND SETTING: The sample comprised 15 male healthy volunteers (HV) and 15 IC users, along with 15 female HV and 15 IC users. The age range was lower for HV participants than for IC users (range: 20-57 years for HV vs 21-82 years for IC users). The study setting was the Department of Urology, located in Rigshospitalet, Copenhagen. METHODS: Number of flow-stop incidents, residual urine volume at first flow-stop (RV1), and dipstick hematuria were measured during and after catheterization by a health care professional (HV) and by self-catheterisation (IC-users). Results from the 3 studies were combined for HV and IC users on RV1 and number of flow-stop incidents but separated on sex. For incidents of hematuria, an effect of underlying condition was assumed, and a combined analysis on sex was performed, separating HV and IC users. RESULTS: When compared to the micro-hole drainage zone design, catheterizations with CEC resulted in a significantly higher mean RV1 (mean difference: 49 mL in males and 32 mL in females, both P < .001) and average number of flow-stop incidents (8 and 21 times more frequent for males and females, respectively, both P < .001). The likelihood for hematuria was 5.84 higher with CEC than with micro-hole drainage hole design, P = .053, during normal micturition in HV postcatheterization. No serious adverse events were reported. CONCLUSION: The micro-hole drainage zone catheter provides IC users fewer premature flow-stops. This design feature reduces modifiable urinary tract infection risk factors, such as residual urine and micro-trauma; additional research is needed to determine its effects on bladder health.

Risk factors for urinary tract infections associated with lower quality of life among intermittent catheter users.

BACKGROUND: Evidence shows that intermittent catheterisation (IC) for bladder emptying is linked to urinary tract infections (UTIs) and poor quality of life (QoL). AIM: To investigate the association between UTI risk factors and QoL and patient-reported UTIs respectively. METHODS: A survey was distributed to IC users from 13 countries. FINDINGS: Among 3464 respondents, a significantly poorer QoL was observed when experiencing blood in the urine, residual urine, bowel dysfunction, recurrent UTIs, being female, and applying withdrawal techniques. A lower UTI risk was found when blood was not apparent in urine (RR: 0.63; 95% CI: 0.55-0.71), the bladder was perceived empty (RR: 0.83; 95% CI: 0.72-0.96), not having bowel dysfunction (RR: 0.86; 95% CI: 0.76-0.98), and being male (RR: 0.70; 95% CI: 0.62-0.79). CONCLUSION: This study underlines the importance of risk factors and their link to QoL and UTIs, highlighting the need for addressing symptoms before UTIs become problematic.

Cow's milk allergy prevention and treatment by heat-treated whey-A study in Brown Norway rats.

BACKGROUND: Food processing, including heat-treatment, can affect protein structure and stability, and consequently affect protein immunogenicity and allergenicity. A few studies have shown that structural changes induced by heat-treatment impact the intestinal protein uptake and suggest this as a contributing factor for altered allergenicity. OBJECTIVE: To investigate the impact of heat-treatment of a whey-based protein product on allergenicity and tolerogenicity as well as on intestinal uptake in various animal models. METHODS: Immunogenicity and sensitizing capacity of the heat-treated whey product were compared to that of the unmodified product by intraperitoneal and oral exposure studies, while tolerogenic properties were assessed by oral primary prevention and desensitization studies in high-IgE responder Brown Norway rats. RESULTS: Heat-treatment of whey induced partial protein denaturation and aggregation, which reduced the intraperitoneal sensitizing capacity but not immunogenicity. In contrast, heat-treatment did not influence the oral sensitizing capacity, but the heat-treated whey showed a significantly reduced eliciting capacity compared to unmodified whey upon oral challenge. Heat-treatment did not reduce the tolerogenic properties of whey, as both products were equally good at preventing sensitization in naïve rats as well as desensitizing already sensitized rats. Results from inhibitory ELISA and immunoblots with sera from sensitized rats demonstrated that heat-treatment caused an altered protein and epitope reactivity. Protein uptake studies showed that heat-treatment changed the route of uptake with less whey being absorbed through the epithelium but more into the Peyer's patches. CONCLUSION AND CLINICAL RELEVANCE: These results support the notion that the physicochemical features of proteins affect their route of uptake and that the route of uptake may affect the protein allergenicity. Furthermore, the study highlights the potential for heat-treatment in the production of efficient and safe cow's milk protein-based products for prevention and treatment of cow's milk allergy.

Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow's Milk Allergy.

BACKGROUND: Infant formulas (IFs) based on hydrolysed cow's milk proteins are central in the management of cow's milk allergy (CMA) in infants and small children. New IF compositions with improved prevention and treatment properties are needed, along with appropriate preclinical animal models, to evaluate these properties before introduction into humans. OBJECTIVES: We aimed to develop preclinical models for the assessment of the primary preventive and desensitising capacity of cow's milk IF in allergy-prone, high-IgE responder Brown Norway rats. METHOD: Preventive capacity was assessed in cow's milk-naïve rats given a 2- or 4-week regimen of whey-based extensively hydrolysed IF (eHF), partially hydrolysed IF (pHF), or intact ß-lactoglobulin (BLG) ad libitum in drinking bottles, followed by intraperitoneal (i.p.) immunisation with BLG. Desensitising capacity was assessed in orally BLG-sensitised rats after a 3- or 6-week regimen of eHF, pHF, or intact BLG administration in drinking bottles, followed by i.p. challenge with BLG. Primary preventive and desensitising capacity were analysed by serum BLG-specific IgG1 and IgE. RESULTS: The preventive regimens did not induce detectable BLG-specific IgG1 or IgE in cow's milk-naïve rats. A preventive regimen consisting of pHF or BLG, but not eHF, induced complete tolerance to BLG, as demonstrated by the absence of BLG-specific IgE following i.p. immunisation. Desensitising regimens had a limited effect on BLG-specific IgG1 or IgE when comparing sensitised rats before and after treatment. Challenge with BLG (i.p.) increased BLG-specific IgE in all treatment regimens except for in the BLG group, suggesting a limited desensitising capacity of IF based on hydrolysates and a need for the presence of intact allergen for desensitisation. CONCLUSIONS: The presented models highlight that different mechanisms are at play in the induction of de novo tolerance to cow's milk proteins and the desensitisation of CMA. Different IF products may be needed for the primary prevention and treatment of CMA.

Osteopontin Levels in Human Milk Vary Across Countries and Within Lactation Period: Data From a Multicenter Study.

OBJECTIVES: Osteopontin (OPN) is a multifunctional protein expressed in many cell types, tissues and body fluids with the highest concentrations found in milk; significantly higher in human than in bovine milk. Intervention studies have indicated beneficial effects of supplementing infant formula with bovine OPN. In this multicenter study, we determined the OPN content in human milk samples from 629 Chinese, Danish, Japanese and Korean mothers. METHODS: At each study site, milk samples were collected and analyzed for OPN and protein concentration using ELISA and infrared spectroscopy, respectively. RESULTS: A total of 829 milk samples from 629 women were included. When delivering the first sample, mean maternal age was 31.4 years (SD 4.0), and median infant age was 13.4 weeks (interquartile range 4.6-17.9). The median OPN concentration varied across sites; from 99.7 mg/L in Danish, 185.0 mg/L in Japanese, 216.2 mg/L in Korean to 266.2 mg/L in Chinese mothers (P < 0.001), corresponding to 1.3%, 2.4%, 1.8% and 2.7% of the total protein content (OPN/protein%) (P < 0.05), respectively. Based on 75 Chinese and 33 Japanese mothers delivering more than 1 sample, multilevel (mixed model) linear regression analysis showed a decrease in OPN concentration with infant age (ß = (-11.3), 95% confidence interval (CI) = (-13.9) to (-8.8) and ß = (-2.1), 95% CI = (-3.2) to (-0.9), respectively). CONCLUSIONS: In this large multicenter study, we observed statistically significant differences in the OPN concentration and the OPN/protein% in human milk samples between countries. Based on mothers delivering more than 1 sample, a significant decrease within the lactation period was observed.

Low-Protein Infant Formula Enriched with Alpha-Lactalbumin during Early Infancy May Reduce Insulin Resistance at 12 Months: A Follow-Up of a Randomized Controlled Trial.

High protein intake during infancy results in accelerated early weight gain and potentially later obesity. The aim of this follow-up study at 12 months was to evaluate if modified low-protein formulas fed during early infancy have long-term effects on growth and metabolism. In a double-blinded RCT, the ALFoNS study, 245 healthy-term infants received low-protein formulas with either alpha-lactalbumin-enriched whey (α-lac-EW; 1.75 g protein/100 kcal), casein glycomacropeptide-reduced whey (CGMP-RW; 1.76 g protein/100 kcal), or standard infant formula (SF; 2.2 g protein/100 kcal) between 2 and 6 months of age. Breastfed (BF) infants served as a reference. At 12 months, anthropometrics and dietary intake were assessed, and serum was analyzed for insulin, C-peptide, and insulin-like growth factor 1 (IGF-1). Weight gain between 6 and 12 months and BMI at 12 months were higher in the SF than in the BF infants (p = 0.019; p < 0.001, respectively), but were not significantly different between the low-protein formula groups and the BF group. S-insulin and C-peptide were higher in the SF than in the BF group (p < 0.001; p = 0.003, respectively), but more alike in the low-protein formula groups and the BF group. Serum IGF-1 at 12 months was similar in all study groups. Conclusion: Feeding modified low-protein formula during early infancy seems to reduce insulin resistance, resulting in more similar growth, serum insulin, and C-peptide concentrations to BF infants at 6-months post intervention. Feeding modified low-protein formula during early infancy results in more similar growth, serum insulin, and C-peptide concentrations to BF infants 6-months post intervention, probably due to reduced insulin resistance in the low-protein groups.

Degree of hydrolysis is a poor predictor of the sensitizing capacity of whey- and casein-based hydrolysates in a Brown Norway rat model of cow's milk allergy.

The use of infant formulas (IFs) based on hydrolyzed cow's milk proteins to prevent cow's milk allergy (CMA) is highly debated. The risk of sensitization to milk proteins induced by IFs may be affected by the degree of hydrolysis (DH) as well as other physicochemical properties of the cow's milk-based protein hydrolysates within the IFs. The immunogenicity (specific IgG1 induction) and sensitizing capacity (specific IgE induction) of 30 whey- or casein-based hydrolysates with different physicochemical characteristics were compared using an intraperitoneal model of CMA in Brown Norway rats. In general, the whey-based hydrolysates demonstrated higher immunogenicity than casein-based hydrolysates, inducing higher levels of hydrolysate-specific and intact-specific IgG1. The immunogenicity of the hydrolysates was influenced by DH, peptide size distribution profile, peptide aggregation, nano-sized particle formation, and surface hydrophobicity. Yet, only the surface hydrophobicity was found to affect the sensitizing capacity of hydrolysates, as high hydrophobicity was associated with higher levels of specific IgE. The whey- and casein-based hydrolysates exhibited distinct immunological properties with highly diverse molecular composition and physicochemical properties which are not accounted for by measuring DH, which was a poor predictor of sensitizing capacity. Thus, future studies should consider and account for physicochemical characteristics when assessing the sensitizing capacity of cow's milk-based protein hydrolysates.

The Effect of Human and Bovine Milk Osteopontin on Intestinal Caco-2 Cells: A Transcriptome Comparison.

Osteopontin (OPN) is a multifunctional protein abundantly present in human milk, whereas the concentration is significantly lower in bovine milk. Human and bovine milk OPN are structurally similar and both proteins resist gastric digestion and reach the intestines in a bioactive form. Intervention studies have indicated the beneficial effects of supplementing infant formula with bovine milk OPN and several in vivo and in vitro studies have shown that bovine milk OPN positively influences intestinal development. To investigate the functional relationship, we compared the effect of simulated gastrointestinal digested human and bovine milk OPN on gene expression in Caco-2 cells. After incubation, total RNA was extracted and sequenced and transcripts were mapped to the human genome. Human and bovine milk OPN regulated the expression of 239 and 322 genes, respectively. A total of 131 genes were similarly regulated by the OPNs. As a control, a whey protein fraction with a high content of alpha-lactalbumin had a very limited transcriptional impact on the cells. Enrichment data analysis showed that biological processes related to the ubiquitin system, DNA binding, and genes associated with transcription and transcription control pathways were affected by the OPNs. Collectively, this study shows that human and bovine milk OPN have a significant and highly comparable effect on the intestinal transcriptome.

Low-Protein Formulas with Alpha-Lactalbumin-Enriched or Glycomacropeptide-Reduced Whey: Effects on Growth, Nutrient Intake and Protein Metabolism during Early Infancy: A Randomized, Double-Blinded Controlled Trial.

Protein intake is higher in formula-fed than in breast-fed infants during infancy, which may lead to an increased risk of being overweight. Applying alpha-lactalbumin (α-lac)-enriched whey or casein glycomacropeptide (CGMP)-reduced whey to infant formula may enable further reduction of formula protein by improving the amino acid profile. Growth, nutrient intake, and protein metabolites were evaluated in a randomized, prospective, double-blinded intervention trial where term infants received standard formula (SF:2.2 g protein/100 kcal; n = 83) or low-protein formulas with α-lac-enriched whey (α-lac-EW;1.75 g protein/100 kcal; n = 82) or CGMP-reduced whey (CGMP-RW;1.76 g protein/100 kcal; n = 80) from 2 to 6 months. Breast-fed infants (BF; n = 83) served as reference. Except between 4 and 6 months, when weight gain did not differ between α-lac-EW and BF (p = 0.16), weight gain was higher in all formula groups compared to BF. Blood urea nitrogen did not differ between low-protein formula groups and BF during intervention, but was lower than in SF. Essential amino acids were similar or higher in α-lac-EW and CGMP-RW compared to BF. Conclusion: Low-protein formulas enriched with α-lac-enriched or CGMP-reduced whey supports adequate growth, with more similar weight gain in α-lac-enriched formula group and BF, and with metabolic profiles closer to that of BF infants.

New Intermittent Urinary Micro-Hole Zone Catheter Shows Enhanced Performance in Emptying the Bladder: A Randomised, Controlled Crossover Study.

Urinary tract infections (UTIs) are common and troublesome complications of clean intermittent catheterisation (CIC) in individuals suffering from incomplete bladder emptying, which may exacerbate the underlying disease and lead to hospitalisation. Aside from the design of the intermittent catheter and its handling, a recent review highlighted residual urine as one of several UTI risk factors. A new urinary intermittent catheter with multiple micro-holes has been developed for improved bladder emptying. In a controlled crossover study, adult male CIC users were randomised for a health care professional-led catheterisation with the new micro-hole zone catheter (MHZC) and a conventional eyelet catheter (CEC) in two individual test visits to compare the number of flow-stops and the residual urine at the first flow-stop as co-primary endpoints. In 42 male CIC users, the MHZC resulted in significantly fewer flow-stop episodes compared to the CEC (mean 0.17, 95% CI [0.06, 0.45] vs. mean 1.09, 95% CI [0.75, 1.6], respectively; p < 0.001) and significantly less residual urine at the first flow-stop (mean 5.10 mL, SE [1.14] vs. mean 39.40 mL, SE [9.65], respectively; p < 0.001). No adverse events were observed in this study. The results confirm the enhanced performance of the MHZC compared to a CEC, ensuring an uninterrupted free urine flow with no need to reposition the catheter until the bladder is thoroughly empty.

Naturally Occurring N-Terminal Fragments of Bovine Milk Osteopontin Are Transported across Models of the Intestinal Barrier.

Osteopontin (OPN) is a bioactive integrin-binding protein found in high concentrations in milk, where it is present both as a full-length protein and as several N-terminally derived fragments. OPN resists gastric digestion, and via interaction with receptors in the gut or by crossing the intestinal barrier into circulation, ingested milk OPN may influence physiological processes. The aim of this study was to investigate OPN interaction with intestinal cells and its transport across models of the intestinal barrier. Immunodetection of OPN incubated with Caco-2 cells at 4 °C and 37 °C showed that OPN binds to the intestinal cells, but it is not internalised. Transepithelial transport was studied using mono- and co-cultures of Caco-2 cells and mucus-producing HT29-MTX cells in transwell membranes. OPN was shown to cross the barrier models in a time-, temperature-, and energy-dependent process inhibited by wortmannin, indicating that the transport takes place via the transcytosis pathway. Analyses of the naturally occurring milk mixture of full-length and N-terminal fragments showed that the N-terminal fragments of OPN bound intestinal cells most effectively and that the fragments were transported across the intestinal membrane models. This suggests that proteolytic processing of OPN increases its biological activity after ingestion.

Nesfatin-1 in Human Milk and Its Association with Infant Anthropometry.

Breastfed infants have different growth patterns to formula-fed infants and are less likely to develop obesity later in life. Nesfatin-1 is an anorexigenic adipokine that was discovered in human milk more than a decade ago, and its role in infant appetite regulation is not clear. Our aim was to describe nesfatin-1 levels in human milk collected 3-4 months postpartum, associations with infant anthropometry, and factors (maternal pre-pregnancy body mass index (mBMI), high weight gain during pregnancy, milk fat, and energy content) possibly influencing nesfatin-1 levels. We hypothesized that nesfatin-1 levels in mother's milk would differ for infants that were large (high weight-for-age Z-score (WAZ)) or small (low WAZ) at the time of milk sample collection. We used enzyme-linked immunosorbent assay to detect the nesfatin-1 concentration in milk samples from mothers to high WAZ (n = 50) and low WAZ (n = 50) infants. We investigated associations between nesfatin-1 levels and infant anthropometry at 3-4 months of age and growth since birth, using linear regression adjusted for mBMI, birth weight, infant sex, and exclusivity of breastfeeding. We found no difference in nesfatin-1 levels between the two groups and no association with infant anthropometry, even after adjusting for potential confounders. However, high nesfatin-1 levels were correlated with low mBMI. Future research should investigate serum nesfatin-1 level in both mothers, infants and associations with growth in breastfed children.

Partially Hydrolysed Whey Has Superior Allergy Preventive Capacity Compared to Intact Whey Regardless of Amoxicillin Administration in Brown Norway Rats.

Background: It remains largely unknown how physicochemical properties of hydrolysed infant formulas influence their allergy preventive capacity, and results from clinical and animal studies comparing the preventive capacity of hydrolysed infant formula with conventional infant formula are inconclusive. Thus, the use of hydrolysed infant formula for allergy prevention in atopy-prone infants is highly debated. Furthermore, knowledge on how gut microbiota influences allergy prevention remains scarce. Objective: To gain knowledge on (1) how physicochemical properties of hydrolysed whey products influence the allergy preventive capacity, (2) whether host microbiota disturbance influences allergy prevention, and (3) to what extent hydrolysed whey products influence gut microbiota composition. Methods: The preventive capacity of four different ad libitum administered whey products was investigated in Brown Norway rats with either a conventional or an amoxicillin-disturbed gut microbiota. The preventive capacity of products was evaluated as the capacity to reduce whey-specific sensitisation and allergic reactions to intact whey after intraperitoneal post-immunisations with intact whey. Additionally, the direct effect of the whey products on the growth of gut bacteria derived from healthy human infant donors was evaluated by in vitro incubation. Results: Two partially hydrolysed whey products with different physicochemical characteristics were found to be superior in preventing whey-specific sensitisation compared to intact and extensively hydrolysed whey products. Daily oral amoxicillin administration, initiated one week prior to intervention with whey products, disturbed the gut microbiota but did not impair the prevention of whey-specific sensitisation. The in vitro incubation of infant faecal samples with whey products indicated that partially hydrolysed whey products might confer a selective advantage to enterococci. Conclusions: Our results support the use of partially hydrolysed whey products for prevention of cow's milk allergy in atopy-predisposed infants regardless of their microbiota status. However, possible direct effects of partially hydrolysed whey products on gut microbiota composition warrants further investigation.

Seeking Windows of Opportunity to Shape Lifelong Immune Health: A Network-Based Strategy to Predict and Prioritize Markers of Early Life Immune Modulation.

A healthy immune status is strongly conditioned during early life stages. Insights into the molecular drivers of early life immune development and function are prerequisite to identify strategies to enhance immune health. Even though several starting points for targeted immune modulation have been identified and are being developed into prophylactic or therapeutic approaches, there is no regulatory guidance on how to assess the risk and benefit balance of such interventions. Six early life immune causal networks, each compromising a different time period in early life (the 1st, 2nd, 3rd trimester of gestations, birth, newborn, and infant period), were generated. Thereto information was extracted and structured from early life literature using the automated text mining and machine learning tool: Integrated Network and Dynamical Reasoning Assembler (INDRA). The tool identified relevant entities (e.g., genes/proteins/metabolites/processes/diseases), extracted causal relationships among these entities, and assembled them into early life-immune causal networks. These causal early life immune networks were denoised using GeneMania, enriched with data from the gene-disease association database DisGeNET and Gene Ontology resource tools (GO/GO-SLIM), inferred missing relationships and added expert knowledge to generate information-dense early life immune networks. Analysis of the six early life immune networks by PageRank, not only confirmed the central role of the "commonly used immune markers" (e.g., chemokines, interleukins, IFN, TNF, TGFB, and other immune activation regulators (e.g., CD55, FOXP3, GATA3, CD79A, C4BPA), but also identified less obvious candidates (e.g., CYP1A2, FOXK2, NELFCD, RENBP). Comparison of the different early life periods resulted in the prediction of 11 key early life genes overlapping all early life periods (TNF, IL6, IL10, CD4, FOXP3, IL4, NELFCD, CD79A, IL5, RENBP, and IFNG), and also genes that were only described in certain early life period(s). Concluding, here we describe a network-based approach that provides a science-based and systematical method to explore the functional development of the early life immune system through time. This systems approach aids the generation of a testing strategy for the safety and efficacy of early life immune modulation by predicting the key candidate markers during different phases of early life immune development.

The Impact of Immune Interventions: A Systems Biology Strategy for Predicting Adverse and Beneficial Immune Effects.

Despite scientific advances it remains difficult to predict the risk and benefit balance of immune interventions. Since a few years, network models have been built based on comprehensive datasets at multiple molecular/cellular levels (genes, gene products, metabolic intermediates, macromolecules, cells) to illuminate functional and structural relationships. Here we used a systems biology approach to identify key immune pathways involved in immune health endpoints and rank crucial candidate biomarkers to predict adverse and beneficial effects of nutritional immune interventions. First, a literature search was performed to select the molecular and cellular dynamics involved in hypersensitivity, autoimmunity and resistance to infection and cancer. Thereafter, molecular interaction between molecules and immune health endpoints was defined by connecting their relations by using database information. MeSH terms related to the immune health endpoints were selected resulting in the following selection: hypersensitivity (D006967: 184 genes), autoimmunity (D001327: 564 genes), infection (parasitic, bacterial, fungal and viral: 357 genes), and cancer (D009369: 3173 genes). In addition, a sequence of key processes was determined using Gene Ontology which drives the development of immune health disturbances resulting in the following selection: hypersensitivity (164 processes), autoimmunity (203 processes), infection (187 processes), and cancer (309 processes). Finally, an evaluation of the genes for each of the immune health endpoints was performed, which indicated that many genes played a role in multiple immune health endpoints, but also unique genes were observed for each immune health endpoint. This approach helps to build a screening/prediction tool which indicates the interaction of chemicals or food substances with immune health endpoint-related genes and suggests candidate biomarkers to evaluate risks and benefits. Several anti-cancer drugs and omega 3 fatty acids were evaluated as in silico test cases. To conclude, here we provide a systems biology approach to identify genes/molecules and their interaction with immune related disorders. Our examples illustrate that the prediction with our systems biology approach is promising and can be used to find both negatively and positively correlated interactions. This enables identification of candidate biomarkers to monitor safety and efficacy of therapeutic immune interventions.

Content of n-3 LC-PUFA in Breast Milk Four Months Postpartum is Associated with Infancy Blood Pressure in Boys and Infancy Blood Lipid Profile in Girls.

Blood pressure (BP) and blood lipid profile (BLP) have been shown to track from childhood into adulthood, and n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) in breast milk have been suggested as mediators of the beneficial long-term effect of breastfeeding on BP and BLP. We aimed to investigate associations between n-3 LC-PUFA content in breast milk at 4 months postpartum and offspring BP and BLP in early life. BP and BLP were measured at 4, 18, and 36 months. Statistical analyses were sex-stratified and adjusted for gestational age, maternal pre-pregnancy body mass index (BMI), and maternal educational level. Based on 336 mother-child dyads, high n-3 LC-PUFA in breast milk was inversely associated with systolic and diastolic BP in boys at 4 months (ß = -20.0 (95% CI = -33.4, -6.7), p = 0.004 and ß = -10.2 (95% CI = -19.8, -0.5), p = 0.039, respectively); inversely associated with HDL cholesterol, and directly associated with triglyceride in girls at 4 months (ß = -0.7 (95% CI = -1.1, -0.3), p = 0.001 and ß = 3.1 (95% CI = 1.0, 5.2), p = 0.005, respectively). Associations observed at the later time points were non-significant. Furthermore, we observed sex-specific changes over time in both size and direction of the associations. Our results indicate that early intake of n-3 LC-PUFA can affect early development in cardiometabolic factors such as BP and BLP in a sex-specific manner. Follow-up and further investigation in later childhood is planned.

Satiety Factors Oleoylethanolamide, Stearoylethanolamide, and Palmitoylethanolamide in Mother's Milk Are Strongly Associated with Infant Weight at Four Months of Age-Data from the Odense Child Cohort.

Regulation of appetite and food intake is partly regulated by N-acylethanolamine lipids oleoylethanolamide (OEA), stearoylethanolamide (SEA), and palmitoylethanolamide (PEA), which induce satiety through endogenous formation in the small intestine upon feeding, but also when orally or systemic administered. OEA, SEA, and PEA are present in human milk, and we hypothesized that the content of OEA, SEA, and PEA in mother's milk differed for infants being heavy (high weight-for-age Z-score (WAZ)) or light (low WAZ) at time of milk sample collection. Ultra-high performance liquid chromatography-mass spectrometry was used to determine the concentration of OEA, SEA, and PEA in milk samples collected four months postpartum from mothers to high (n = 50) or low (n = 50) WAZ infants. Associations between OEA, SEA, and PEA concentration and infant anthropometry at four months of age as well as growth from birth were investigated using linear and logistic regression analyses, adjusted for birth weight, early infant formula supplementation, and maternal pre-pregnancy body mass index. Mean OEA, SEA, and PEA concentrations were lower in the high compared to the low WAZ group (all p < 0.02), and a higher concentration of SEA was associated with lower anthropometric measures, e.g., triceps skinfold thickness (mm) (ß = -2.235, 95% CI = -4.04, -0.43, p = 0.016), and weight gain per day since birth (g) (ß = -8.169, 95% CI = -15.26, -1.08, p = 0.024). This raises the possibility, that the content of satiety factors OEA, SEA, and PEA in human milk may affect infant growth.

Breastfeeding, Infant Formula, and Introduction to Complementary Foods-Comparing Data Obtained by Questionnaires and Health Visitors' Reports to Weekly Short Message Service Text Messages.

BACKGROUND: Studies on prevalence and effects of breastfeeding call for reliable and precise data collection to optimize infant nutrition, growth, and health. Data on breastfeeding and infant nutrition are at risk of, for example, recall bias or social desirability bias. OBJECTIVE: The aim of the present analysis was to compare data on infant nutrition, that is, breastfeeding, use of infant formula, and introduction to complementary foods, obtained by four different methods. We assumed that weekly short message service (SMS) questions were the most reliable method, to which the other methods were compared. DESIGN: The study population was part of the Odense Child Cohort. The four methods used were: (a) self-administered questionnaire 3 months postpartum, (b) self-administered questionnaire 18 months postpartum, (c) registrations from health visitors visiting the families several times within the first year of life, and (d) weekly SMS questions introduced shortly after birth. RESULTS: In total, 639 singleton mothers with data from all four methods were included. The proportion of mothers initiating breastfeeding varied from 86% to 97%, the mean duration of exclusive breastfeeding from 12 to 19 weeks, and the mean age when introduced to complementary foods from 19 to 21 weeks. The mean duration of any breastfeeding was 33 weeks across methods. CONCLUSIONS: Compared with the weekly SMS questions, the self-administered questionnaires and the health visitors' reports resulted in a greater proportion of mothers with an unknown breastfeeding status, a longer duration of exclusive breastfeeding and later introduction to complementary foods, while the duration of any breastfeeding did not differ.