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High levels of omega-3 fatty acids in milk from omega-3 fatty acid-supplemented mothers are related to less immunoglobulin E-associated disease in infancy.
Warstedt, K, Furuhjelm, C, Fälth-Magnusson, K, Fagerås, M, Duchén, K
Acta paediatrica (Oslo, Norway : 1992). 2016;(11):1337-1347
Abstract
AIM: We previously reported a protective effect of maternal omega-3 fatty acid supplements on the development of immunoglobulin E (IgE)-associated disease in infancy. This study assessed omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in maternal milk in relation to omega-3 LCPUFA supplementation and the development of allergic disease in their infants. METHODS This study randomised 95 pregnant women at risk of having an allergic infant, to daily supplements of 2.6 g omega-3 LCPUFA or a placebo of 2.7 g soya bean oil from gestational week 25 until 3 months of lactation. Breast milk samples were collected as colostrum, at one and 3 months. Milk fatty acids were related to allergic outcome in the infants at 24 months. RESULTS Omega-3 milk fatty acids were higher in women who received omega-3 supplements than the placebo group (p < 0.01). Higher proportions of milk eicosapentaenoic acid and docosahexaenoic acid and a lower arachidonic/eicosapentaenoic acid ratio were associated with an absence of IgE-associated disease in the infants. None of the children developed IgE-associated atopic eczema above a level of 0.83 mol% eicosapentaenoic acid in colostrum. [Correction added on 7 July 2016, after online publication: In the preceding sentence, the correct word should be "above" instead of "below" and this has been amended in this current version.] CONCLUSION High omega-3 LCPUFA milk levels in mothers who received omega-3 LCPUFA supplements were related to fewer allergies in their children.
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Soluble CD14, α-and β-defensins in breast milk: association with the emergence of allergy in a high-risk population.
Savilahti, EM, Kukkonen, AK, Kuitunen, M, Savilahti, E
Innate immunity. 2015;(3):332-7
Abstract
As innate immunity factors in breast milk (BM) modulate infants' immune responses, we investigated whether soluble CD14 (sCD14) and defensin levels in BM are associated with the emergence of allergy in childhood. The randomly selected group of 260 mother-child pairs belonged to a randomized, double-blind placebo-controlled trial where 1223 mothers with fetuses at high risk for allergy received for the 4 last wk of pregnancy a mixture of probiotics, or placebo; after birth, the child received the treatment for 6 mo. Children were followed for the emergence of sensitization and allergic symptoms for 5 yr. IgE-mediated allergic disorder was diagnosed in 80 children by the age of 5 yr. Levels of sCD14, human neutrophil peptide (HNP) 1-3 and β-defensin 2 (HBD2) in colostrum and in BM 3 mo post-partum were measured with ELISA. BM sCD14 levels decreased from 0 to 3 mo. HNP1-3 and HBD2 were detected in colostrum, but not in BM 3 mo post-partum. High sCD14 levels in BM 3 mo post-partum were associated with children developing an IgE-mediated allergic disorder by the age of 5 yr. BM HNP1-3, HBD2 or sCD14 levels were not associated with probiotics treatment. Our results suggest that sCD14 in BM influences the emergence of allergy in children with atopic heredity.
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Bacillus Calmette-Guérin immunisation at birth and morbidity among Danish children: A prospective, randomised, clinical trial.
Thøstesen, LM, Nissen, TN, Kjærgaard, J, Pihl, GT, Birk, NM, Benn, CS, Greisen, G, Kofoed, PE, Pryds, O, Ravn, H, et al
Contemporary clinical trials. 2015;:213-8
Abstract
BACKGROUND Studies from low-income countries report positive non-specific effects of early Bacillus Calmette-Guérin (BCG) immunisation on childhood health and survival. Neonatal immunisation with BCG may prime the immune system and offer partial protection against other infectious and possibly allergic diseases. The potential clinical value of these non-specific effects has not yet been examined in a large randomised trial in high-income countries. METHODS The Danish Calmette Study is a multicentre randomised clinical trial conducted between October 2012 and November 2015. Within the first 7 days of life, infants were randomly assigned to intra-dermal vaccination with BCG or no intervention. At 3 and 13 months of age structured telephone interviews and clinical examinations of the children were conducted. In a subgroup of children blood samples were drawn and stool samples collected at age 4 days, 3 and 13 months. Thymus index was assessed by ultrasound in a subgroup at randomisation and at 3 months. The primary study outcome is hospitalisation within the first 15 months of life as assessed in Danish health registers. Secondary outcomes include infectious disease hospitalisations, wheezing, eczema, use of prescribed medication, growth, development, thymus index, T- and B-cell subpopulations assessed by flow cytometry, in vitro cytokine responses and specific antibody responses to other vaccines. Adverse reactions were registered. DISCUSSION With participation of 4184 families and more than 93% adherence to clinical follow-up at 3 and 13 months, this randomised clinical trial has the potential to create evidence regarding non-specific effects of BCG vaccination in a high-income setting.
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The Vitamin D Antenatal Asthma Reduction Trial (VDAART): rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children.
Litonjua, AA, Lange, NE, Carey, VJ, Brown, S, Laranjo, N, Harshfield, BJ, O'Connor, GT, Sandel, M, Strunk, RC, Bacharier, LB, et al
Contemporary clinical trials. 2014;(1):37-50
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Abstract
There is intense interest in the role of vitamin D in the development of asthma and allergies. However, studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies. To address this uncertainty, the Vitamin D Antenatal Asthma Reduction Trial (VDAART) was developed. VDAART is a randomized, double-blind, placebo-controlled trial of vitamin D supplementation in pregnant women to determine whether prenatal supplementation can prevent the development of asthma and allergies in women's offspring. A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications, such as preeclampsia, preterm birth, and gestational diabetes. Women were randomized to the treatment arm of 4000IU/day of vitamin D3 plus a daily multivitamin that contained 400IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400IU daily of vitamin D3. Women who were between the gestational ages of 10 and 18 weeks were randomized from three clinical centers across the United States - Boston Medical Center, Washington University in St. Louis, and Kaiser Permanente Southern California Region (San Diego, CA). Supplementation took place throughout pregnancy. Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events. Offspring are being evaluated quarterly through questionnaires and yearly during in-person visits until the 3rd birthday of the child. Ancillary studies will investigate neonatal T-regulatory cell function, maternal vaginal flora, and maternal and child intestinal flora.
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Metal release and metal allergy after total hip replacement with resurfacing versus conventional hybrid prosthesis.
Gustafson, K, Jakobsen, SS, Lorenzen, ND, Thyssen, JP, Johansen, JD, Bonefeld, CM, Stilling, M, Baad-Hansen, T, Søballe, K
Acta orthopaedica. 2014;(4):348-54
Abstract
BACKGROUND Metal-on-metal (MOM) total hip arthroplasties were reintroduced because of the problems with osteolysis and aseptic loosening related to polyethylene wear of early metal-on-polyethylene (MOP) arthroplasties. The volumetric wear rate has been greatly reduced with MOM arthroplasties; however, because of nano-size wear particles, the absolute number has been greatly increased. Thus, a source of metal ion exposure with the potential to sensitize patients is present. We hypothesized that higher amounts of wear particles result in increased release of metal ions and ultimately lead to an increased incidence of metal allergy. METHODS 52 hips in 52 patients (median age 60 (51-64) years, 30 women) were randomized to either a MOM hip resurfacing system (ReCap) or a standard MOP total hip arthoplasty (Mallory Head/Exeter). Spot urine samples were collected preoperatively, postoperatively, after 3 months, and after 1, 2, and 5 years and tested with inductively coupled plasma-sector field mass spectrometry. After 5 years, hypersensitivity to metals was evaluated by patch testing and lymphocyte transformation assay. In addition, the patients answered a questionnaire about hypersensitivity. RESULTS A statistically significant 10- to 20-fold increase in urinary levels of cobalt and chromium was observed throughout the entire follow-up in the MOM group. The prevalence of metal allergy was similar between groups. INTERPRETATION While we observed significantly increased levels of metal ions in the urine during the entire follow-up period, no difference in prevalence of metal allergy was observed in the MOM group. However, the effect of long-term metal exposure remains uncertain.
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Prenatal vitamin d supplementation and child respiratory health: a randomised controlled trial.
Goldring, ST, Griffiths, CJ, Martineau, AR, Robinson, S, Yu, C, Poulton, S, Kirkby, JC, Stocks, J, Hooper, R, Shaheen, SO, et al
PloS one. 2013;(6):e66627
Abstract
BACKGROUND Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing. We examined the effect of prenatal vitamin D on childhood wheezing in an interventional study. METHODS We randomised 180 pregnant women at 27 weeks gestation to either no vitamin D, 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol, in an ethnically stratified, randomised controlled trial. Supplementation improved but did not optimise vitamin D status. Researchers blind to allocation assessed offspring at 3 years. Primary outcome was any history of wheeze assessed by validated questionnaire. Secondary outcomes included atopy, respiratory infection, impulse oscillometry and exhaled nitric oxide. Primary analyses used logistic and linear regression. RESULTS We evaluated 158 of 180 (88%) offspring at age 3 years for the primary outcome. Atopy was assessed by skin test for 95 children (53%), serum IgE for 86 (48%), exhaled nitric oxide for 62 (34%) and impulse oscillometry of acceptable quality for 51 (28%). We found no difference between supplemented and control groups in risk of wheeze [no vitamin D: 14/50 (28%); any vitamin D: 26/108 (24%) (risk ratio 0.86; 95% confidence interval 0.49, 1.50; P = 0.69)]. There was no significant difference in atopy, eczema risk, lung function or exhaled nitric oxide between supplemented groups and controls. CONCLUSION Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level, was not associated with decreased wheezing in offspring at age three years. TRIAL REGISTRATION Controlled-Trials.com ISRCTN68645785.
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Th1 and Th2 chemokines, vaccine-induced immunity, and allergic disease in infants after maternal ω-3 fatty acid supplementation during pregnancy and lactation.
Furuhjelm, C, Jenmalm, MC, Fälth-Magnusson, K, Duchén, K
Pediatric research. 2011;(3):259-64
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Abstract
We investigated whether the previously reported preventive effect of maternal ω-3 fatty acid supplementation on IgE-associated allergic disease in infancy may be mediated by facilitating a balanced circulating Th2/Th1 chemokine profile in the infant. Vaccine-induced immune responses at 2 y of age were also evaluated. Pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo from the 25th gestational week through 3.5 mo of breastfeeding. Infant plasma was analyzed for chemokines (cord blood, 3, 12, 24 mo) and anti-tetanus and anti-diphtheria IgG (24 mo). High Th2-associated CC-chemokine ligand 17 (CCL17) levels were associated with infant allergic disease (p < 0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CCL17/CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p < 0.05). Furthermore, in nonallergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p < 0.05), as well as increased IgG titers to diphtheria (p = 0.01) and tetanus (p = 0.05) toxins. Thus, the prospect of balancing the infant immune system toward a less Th2-dominated response, by maternal ω-3 fatty acid supplementation, seems to be influenced by allergic status.
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Demonstrating the safety of manuka honey UMF 20+in a human clinical trial with healthy individuals.
Wallace, A, Eady, S, Miles, M, Martin, H, McLachlan, A, Rodier, M, Willis, J, Scott, R, Sutherland, J
The British journal of nutrition. 2010;(7):1023-8
Abstract
Honey is an established traditional medicine with a variety of putative nutritional and health effects, including antibacterial, antioxidant, anti-inflammatory and prebiotic. The aim of the present study was to investigate the safety of consuming manuka honey, UMF 20+, on healthy individuals by establishing whether UMF 20+caused an allergic response (as measured by IgE levels), changed major commensal and beneficial microbial groups in the gut and/or affected levels of one of the most common advanced glycation endpoints, N-(carboxymethyl)-lysine (CML). The study had a randomised, double-blind cross-over design. A total of twenty healthy individuals aged 42-64 years were recruited. We tested two different honeys- a multiflora honey and UMF 20+, both produced by Comvita New Zealand Ltd (Te Puke, New Zealand). Multiflora honey or UMF 20+(20 g) was consumed daily for 4 weeks, with a 2-week 'washout' period in between. Blood samples were collected every week for each intervention period and used to measure total IgE levels in serum and advanced glycation endproducts - a consequence of methyglyoxal accumulation. Faecal samples were collected at the beginning and end of each 4-week period. DNA was extracted from faecal samples and the levels of a number of microbial groups in the gut, both beneficial and commensal, were analysed. Neither product changed the levels of IgE or CML or altered gut microbial profiles during the trial, confirming that UMF 20+is safe for healthy individuals to consume. Despite anecdotal evidence suggesting that manuka honey is good for digestive health, we observed no beneficial effects on lower gut bacterial levels with either honey in this healthy population.
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"Breast is best": The evidence.
Kramer, MS
Early human development. 2010;(11):729-32
Abstract
Although the benefits of breastfeeding in reducing morbidity and mortality from gastrointestinal and respiratory infections, sudden infant death syndrome, and (in preterm infants) necrotizing enterocolitis are well-established, long-term health effects are more controversial. The evidence is conflicting concerning the "programming" effect of breastfeeding in protecting against child obesity, hyperlipidemia, hypertension, type 2 diabetes, and atopic disease. Accelerated neurocognitive development has been associated with breastfeeding in many studies, although doubts remain about the potential for residual confounding due to cognitive and behavioural differences between mothers who breastfeed (or those who breastfeed for a longer duration or more exclusively) and those who do not. Most of this paper will summarize the methods and results of a large, cluster-randomized trial of a breastfeeding promotion intervention in the Republic of Belarus. Its experimental design and intention-to-treat analysis have yielded important findings bearing on several of these longer-term health and developmental outcomes.
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Efficacy of probiotic Lactobacillus GG on allergic sensitization and asthma in infants at risk.
Rose, MA, Stieglitz, F, Köksal, A, Schubert, R, Schulze, J, Zielen, S
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2010;(9):1398-405
Abstract
BACKGROUND Probiotics are perceived to exert beneficial effects in the prevention and treatment of allergic diseases. OBJECTIVE There are conflicting data from studies as to an impact on allergic sensitization and asthma. METHODS Our prospective double-blind study randomly assigned 131 children (6-24 months old) with at least two wheezing episodes and a first-degree family history of atopic disease to 6 months of Lactobacillus rhamnosus (LGG, 10(10) colony forming units) or placebo. Atopic dermatitis and asthma-related events (e.g. need of inhalation, symptom-free days) were documented throughout the intervention and 6-month follow-up. We determined IgE, a representative panel of specific IgE, eosinophils, eosinophilic cationic protein, and TGF-beta before, at the end of intervention, and after 6 months of follow-up. RESULTS There were no significant differences as to atopic dermatitis or asthma-related events. In a subgroup with antecedent allergic sensitizations, asthmatic complaints were even slightly worse. We found fewer sensitizations towards aeroallergens after 6 months of LGG (P=0.027) and after 6 months of follow-up (P=0.03). Supplementation was well-tolerated and no severe adverse events occurred. CONCLUSIONS In young children with recurrent wheeze and an atopic family history, oral LGG had no clinical effect on atopic dermatitis or asthma-related events, and only mild effects on allergic sensitization. This effect persisted 6 months after the cessation of the supplementation.