Towards Prepared mums (TOP-mums) for a healthy start, a lifestyle intervention for women with overweight and a child wish: Study protocol for a randomised controlled trial in the Netherlands

Introduction Periconception obesity is associated with a higher risk for adverse perinatal outcomes such as gestational diabetes mellitus, preeclampsia, large for gestational age, operative delivery and preterm birth. Lifestyle interventions during pregnancy have resulted in insufficient effects on reducing these perinatal complications. A few reasons for this disappointing effect can be suggested: (1) the time period during pregnancy for improvement of developmental circumstances is too short; (2) the periconception period in which complications originate is not included; and (3) lifestyle interventions may not have been sufficiently multidisciplinary and customised. A preconception lifestyle intervention might be more effective to reduce perinatal complications. Therefore, the aim of the Towards Prepared mums study is to evaluate the effect of a lifestyle intervention starting prior to conception on lifestyle behaviour change. Methods and analysis This protocol outlines a non-blinded, randomised controlled trial. One hundred and twelve women (18-40 years of age) with overweight or obesity (body mass index≥25.0 kg/m 2) who plan to conceive within 1 year will be randomised to either the intervention or care as usual group. The intervention group will receive a multidisciplinary, customised lifestyle intervention stimulating physical activity, a healthy diet and smoking cessation, if applicable. The lifestyle intervention and monitoring will take place until 12 months postpartum. The primary outcome is difference in weight in kg from baseline to 6 weeks postpartum. Secondary outcomes are gestational weight gain, postpartum weight retention, smoking cessation, dietary and physical activity habits. Furthermore, exploratory outcomes include body composition, cardiometabolic alterations, time to pregnancy, need for assisted reproductive technologies, perinatal complications of mother and child, and lung function of the child. Vaginal and oral swabs, samples of faeces, breast milk, placenta and cord blood will be stored for evaluation of microbial flora, epigenetic markers and breast milk composition. Furthermore, a cost-effectiveness analysis will take place. Ethics and dissemination Ethical approval was obtained from the Medical Ethical Committee of Maastricht University Medical Centre+ (NL52452.068.15/METC152026). Knowledge derived from this study will be made available by publications in international peer-reviewed scientific journals and will be presented at (inter)national scientific conferences. A dissemination plan for regional and national implementation of the intervention is developed. Trial registration number ClinicalTrials.gov NCT02703753

Creatinine-based GFR-estimating equations in children with overweight and obesity

BACKGROUND: With the increasing prevalence of childhood obesity and related development of chronic kidney disease (CKD), there is a critical need to understand how best to assess kidney function in children with obesity. Since serum creatinine (SCr) is recommended as marker of first choice for GFR estimation, we evaluated and compared creatinine-based GFR equations in children with overweight and obesity. METHODS: Six hundred children with overweight and obesity (53.5% female; mean age 12.20 ± 3.28 years; mean BMI z-score 3.31 ± 0.75) were included from the Centre for Overweight Adolescent and Children’s Healthcare (COACH). RESULTS: Serum creatinine (SCr), normalized using Q-age polynomials obtained from reference values, results in median and mean SCr/Q value close to “1” for all age groups, and 96.5% of the children have a SCr/Q within the reference band [0.67–1.33], corresponding to the 2.5th and 97.5th percentile. eGFR CKiD (bedside Schwartz equation) and Schwartz-Lyon decreased with age, whereas eGFR EKFC and modified CKD-EPI40 showed no age-dependency, but the distribution of eGFR values was not symmetrical. eGFR CKiD under 25 (CKiDU25) demonstrated no age-dependency but major sex differences were observed. eGFR FAS age, FAS height, and adjusted-creatinine revised Lund-Malmö (LMR18) showed a relatively symmetrical distribution and no age-dependency. CONCLUSIONS: Serum creatinine (SCr) values of children with overweight and obesity are mostly within the reference range for children. Normalization of SCr using reference Q-age polynomials works very well in this cohort. After evaluation of the different equations, we suggest that FAS age, FAS height, and LMR18 are the preferred creatinine-based GFR-estimating equations in children with overweight and obesity. Clinical trial registration. ClinicalTrial.gov; Registration Number: NCT02091544. GRAPHICAL ABSTRACT: A higher resolution version of the Graphical abstract is available as Supplementary information [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-021-05396-y

Lipopolysaccharide-binding protein is vectorially secreted and transported by cultured intestinal epithelial cells and is present in the intestinal mucus of mice

Lipopolysaccharide-binding protein (LBP) is an important modulator of the host's response to endotoxin. In a previous study, we found evidence for the synthesis of LBP by intestinal epithelial cells, In this study, we explored the polarity of LBP secretion by these cells. Polarized monolayers of Caco-2 cells were used as intestinal mucosa model. Cells were stimulated apically or basally with cytokines, and LBP secretion was analyzed, Furthermore, the presence of LBP in intestinal mucus of healthy and endotoxemic mice was studied using a mucus-sampling technique. The constitutive unipolar LBP secretion from the apical cell surface was markedly enhanced when cells were exposed to cytokines at their apical surface. However, bioactive LBP was secreted from both cell surfaces after basolateral stimulation of cells. Cytokines also influenced the secretion of the acute phase proteins serum amyloid A, apoA-I, and apoB from both surfaces of Caco-2 cells. Furthermore, transport of exogenous LBP from the basolateral to the apical cell surface was demonstrated, In line with these in vitro data, the presence of LBP in intestinal mucus was strongly enhanced in mice after a challenge with endotoxin, The results indicate that LBP is present at the mucosal surface of the intestine, a phenomenon for which secretion and transport of LBP by intestinal epithelial cells may be responsible

Celiac Disease and the Gluten Free Diet during the COVID-19 Pandemic: Experiences of Children and Parents

The COVID-19 pandemic perturbed the everyday life of children and those with chronic illnesses, along with the lives of their families. Patients with celiac disease (CD) follow a strict gluten-free diet (GFD), and gluten ingestion is associated with negative health outcomes. The aim of this study was to investigate the experiences of children with CD and their families concerning their GFD, symptoms and CD management during the first period of the COVID-19 pandemic. A cross-sectional questionnaire-based study was performed including 37 Dutch pediatric patients with CD, along with their parents. The majority reported good compliance to the GFD and stated that the diet was easier to follow during the pandemic, mainly due to eating more meals in the home. Some discovered a greater variety of GF products by utilizing online shopping, potentially increasing the financial burden of the GFD. Concerning general dietary habits, 21.6% reported a healthier eating pattern, in contrast to 37.8% and 10.8% who consumed more unhealthy snacks and fewer fruits and vegetables, respectively, than normal during the pandemic. The natural experiment of the COVID-19 pandemic provides valuable information regarding the management of pediatric CD. Education on healthy dietary patterns is important, especially for children with restrictive diets, and the findings of this study show that there is room for improvement in this respect, regardless of the current pandemic

Lipopolysaccharide binding protein and serum amyloid A secretion by human intestinal epithelial cells during the acute phase response.

Department of General Surgery, Maastricht University, The Netherlands. [email protected] The acute phase proteins LPS binding protein (LBP) and serum amyloid A (SAA) are produced by the liver and are present in the circulation. Both proteins have been shown to participate in the immune response to endotoxins. The intestinal mucosa forms a large surface that is continuously exposed to these microbial products. By secretion of antimicrobial and immunomodulating agents, the intestinal epithelium contributes to the defense against bacteria and their products. The aim of this study was to explore the influence of the inflammatory mediators TNF-alpha, IL-6, and IL-1beta on the release of LBP and SAA by intestinal epithelial cells (IEC). In addition, the induction of LBP and SAA release by cell lines of intestinal epithelial cells and hepatic cells was compared. The data obtained show that in addition to liver cells, IEC also expressed LBP mRNA and released bioactive LBP and SAA upon stimulation. Regulation of LBP and SAA release by IEC and hepatocytes was typical for class 1 acute phase proteins, although differences in regulation between the cell types were observed. Endotoxin did not induce LBP and SAA release. Glucocorticoids were demonstrated to strongly enhance the cytokine-induced release of LBP and SAA by IEC, corresponding to hepatocytes. The data from this study, which imply that human IEC can produce LBP and SAA, suggest a role for these proteins in the local defense mechanism of the gut to endotoxin. Furthermore, the results demonstrate that tissues other than the liver are involved in the acute phase response

Lipopolysaccharide (LPS)-binding protein mediates LPS detoxification by chylomicrons

Lipopolysaccharide (LPS)-binding protein mediates LPS detoxification by chylomicrons. Vreugdenhil AC, Rousseau CH, Hartung T, Greve JW, van 't Veer C, Buurman WA. Nutrition and Toxicology Research Institute Maastricht, Department of General Surgery, Maastricht University, Maastricht, The Netherlands. Chylomicrons have been shown to protect against endotoxin-induced lethality. LPS-binding protein (LBP) is involved in the inactivation of bacterial toxin by lipoproteins. The current study examined the interaction among LBP, chylomicrons, and bacterial toxin. LBP was demonstrated to associate with chylomicrons and enhance the amount of LPS binding to chylomicrons in a dose-dependent fashion. In addition, LBP accelerated LPS binding to chylomicrons. This LBP-induced interaction of LPS with chylomicrons prevented endotoxin toxicity, as demonstrated by reduced cytokine secretion by PBMC. When postprandial circulating concentrations of chylomicrons were compared with circulating levels of low density lipoprotein, very low density lipoprotein, and high density lipoprotein, chylomicrons exceeded the other lipoproteins in LPS-inactivating capacity. Furthermore, highly purified lipoteichoic acid, an immunostimulatory component of Gram-positive bacteria, was detoxified by incubation with LBP and chylomicrons. In conclusion, our results indicate that LBP associates with chylomicrons and enables chylomicrons to rapidly bind bacterial toxin, thereby preventing cell activation. Besides a role in the detoxification of bacterial toxin present in the circulation, we believe that LBP-chylomicron complexes may be part of a local defense mechanism of the intestine against translocated bacterial toxi