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1.
Effect of omega-3 fatty acids supplementation during childhood in preventing allergic disease: a systematic review and Meta-Analysis.
Zhang, Y, Lin, J, Zhou, R, Zheng, X, Dai, J
The Journal of asthma : official journal of the Association for the Care of Asthma. 2021;(4):523-536
Abstract
BACKGROUND Early omega-3 fatty acids exposure can influence early immune development and potentially prevent allergic disease. OBJECTIVES To review the effects of omega-3 fatty acids during childhood on allergic disease outcomes. METHODS We conducted searches of the PubMed, EMBASE and Cochrane Central Register of Controlled Trials and international trial registers (ClinicalTrials.gov and ISRCTN Registry) to September 30, 2018. We included randomized controlled trials (RCTs) and prospective cohort studies regarding the effect of omega-3 fatty acids during childhood on allergic disease outcomes. A total of 8 publications from 2 prospective cohort studies and 6 reports representing 5 unique RCTs were included. RESULTS The results of meta-analysis showed that omega-3 fatty acids during childhood did not appear to significantly alter the risk of any atopy (≤3 years old: RR 0.70, 95% CI 0.47 to 1.04, p = 0.08; > 3 years old: RR 0.98, 95% CI 0.82 to 1.16, p = 0.77), wheeze (≤3 years old: RR 0.82, 95% CI 0.54 to 1.26, p = 0.375; > 3 years old: RR 1.03, 95% CI 0.53 to 2.00, p = 0.929) and eczema (≤3 years old: RR 0.86, 95% CI 0.68 to 1.08, p = 0.20; > 3 years old: RR 0.90, 95% CI 0.60 to 1.35, p = 0.60). CONCLUSIONS There is limited evidence to support omega-3 fatty acids during childhood could reduce the risk of allergic disease.
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Air pollution and IgE sensitization in 4 European birth cohorts-the MeDALL project.
Melén, E, Standl, M, Gehring, U, Altug, H, Antó, JM, Berdel, D, Bergström, A, Bousquet, J, Heinrich, J, Koppelman, GH, et al
The Journal of allergy and clinical immunology. 2021;(2):713-722
Abstract
BACKGROUND Whether long-term exposure air to pollution has effects on allergic sensitization is controversial. OBJECTIVE Our aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years. METHODS A total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 μm, less than 10 μm, and between 2.5 and 10 μm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021). RESULTS Air pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR] = 1.12 [95% CI = 1.01-1.25] per 10-μg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR = 3.33 [95% CI = 1.40-7.94] and OR = 4.98 [95% CI = 1.59-15.60], respectively, per 5-μg/m3 increase in exposure). CONCLUSION Air pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.
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3.
VDR Gene Polymorphisms and Allergic Diseases: Evidence from a Meta-analysis.
Zhang, L, Zhang, S, He, C, Wang, X
Immunological investigations. 2020;(1-2):166-177
Abstract
Associations between vitamin D receptor (VDR) gene polymorphisms and allergic diseases were already reported by many publications. The aim of this meta-analysis was to clarify associations between VDR gene polymorphisms and allergic diseases by combing the results of all relevant publications. Eligible publications were searched from Pubmed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies. Twenty-one studies were included in this study. Combined results proved that VDR rs1544410 BsmI (over-dominant comparison: p = .04, OR = 1.14, 95% CI 1.01-1.29; allele comparison: p = .03, OR = 1.11, 95% CI 1.01-1.22) and rs731236 TaqI (dominant comparison: p = .01, OR = 1.18, 95% CI 1.04-1.33) polymorphisms were both associated with allergic diseases. In subgroup analyses by type of disease, we confirmed positive results for rs1544410 BsmI polymorphism in both asthma and atopic dermatitis, and for rs731236 TaqI polymorphism in atopic dermatitis. Besides, in subgroup by ethnicity of participants, we observed significant associations with allergic diseases for rs7975232 ApaI polymorphism in Caucasians, for rs1544410 BsmI polymorphism in Asians and Caucasians, and for rs731236 TaqI polymorphism in Asians. We also investigated associations between VDR rs2228570 FokI polymorphism and allergic diseases, yet no any positive results were detected for this polymorphism. If we only focused on asthma, then positive findings were detected for rs1544410 BsmI polymorphism in Caucasians, and for rs731236 TaqI polymorphism in Asians. Collectively, this meta-analysis proved that VDR rs7975232 ApaI, rs1544410 BsmI and rs731236 TaqI gene polymorphisms may confer susceptibility to allergic diseases in certain populations.
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4.
ω-3 LCPUFA supplementation during pregnancy and risk of allergic outcomes or sensitization in offspring: A systematic review and meta-analysis.
Vahdaninia, M, Mackenzie, H, Dean, T, Helps, S
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2019;(3):302-313.e2
Abstract
BACKGROUND Allergic diseases have increased worldwide in the last 2 decades, with children suffering the highest burden of the condition. The ω-3 long-chain poly-unsaturated fatty acid (LCPUFA) possesses anti-inflammatory properties that could lead to a reduction in inflammatory mediators in allergies. OBJECTIVE A systematic review and meta-analysis of the most recent follow-ups of randomized clinical trials (RCTs) was conducted to assess the effectiveness of ω-3 LCPUFA supplementation started during pregnancy on allergic outcomes in offspring. METHODS The RCTs with a minimum of 1-month follow-up post gestation were eligible for inclusion. The CENTRAL, MEDLINE, SCOPUS, WHO's International Clinical Trials Register, E-theses, and Web of Science databases were searched. Study quality was evaluated using the Cochrane Collaboration's risk of bias tool. RESULTS Ten RCTs (3,637 children), from 9 unique trials, examined the effectiveness of ω-3 LCPUFA supplementation started during pregnancy on the development of allergic outcomes in offspring. Heterogeneities were seen between the trials in terms of their sample, type, and duration of intervention and follow-up. Pooled estimates showed a significant reduction in childhood "sensitization to egg" (relative risk [RR] = 0.54, 95% confidence interval [CI] = 0.32-0.90), and "sensitization to peanut" (RR = 0.62, 95% CI = 0.40-0.96). No statistical differences were found for other allergic outcomes (eg, eczema, asthma/wheeze). CONCLUSION These results suggest that intake of ω-3 LCPUFA started during pregnancy can reduce the risk of sensitization to egg and peanut; however, the evidence is limited because of the small number of studies that contributed to the meta-analyses. The current evidence on the association between supplementation with ω-3 LCPUFA started during pregnancy and allergic outcomes is weak, because of the risk of bias and heterogeneities between studies.
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5.
Early-life antibiotic exposure increases the risk of developing allergic symptoms later in life: A meta-analysis.
Ahmadizar, F, Vijverberg, SJH, Arets, HGM, de Boer, A, Lang, JE, Garssen, J, Kraneveld, A, Maitland-van der Zee, AH
Allergy. 2018;(5):971-986
Abstract
This study systematically reviewed and quantified the relationship between exposure to antibiotics during the first 2 years of life and the risk of allergies/atopies including hay fever, eczema, food allergy, positive skin prick testing (SPT), or elevated allergen-specific serum/plasma immunoglobulin (Ig) E levels later in life. PubMed and Web of Science databases were searched for observational studies published from January 1966 through November 11, 2015. Overall pooled estimates of the odds ratios (ORs) were obtained using fixed or random-effects models. Early-life exposure to antibiotics appears to be related to an increased risk of allergic symptoms of hay fever, eczema, and food allergy later in life. The summary OR for the risk of hay fever (22 studies) was 1.23, 95% confidence interval (CI):1.13-1.34; I2 : 77.0%. The summary OR for the risk of eczema (22 studies) was 1.26, 95% CI: 1.15-1.37; I2 : 74.2%, and the summary OR for food allergy (3 studies) was 1.42, 95% CI: 1.08-1.87; I2 : 80.8%. However, no association was found for antibiotics exposure early in life and objective atopy measurements including positive SPT or elevated allergen-specific serum/plasma IgE levels.
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6.
Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids (LCPUFA) supplementation for preventing allergies in early childhood.
Gunaratne, AW, Makrides, M, Collins, CT
The Cochrane database of systematic reviews. 2015;(7):CD010085
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Abstract
BACKGROUND Allergies have become more prevalent globally over the last 20 years. Dietary consumption of n-3 (or omega 3) long chain polyunsaturated fatty acids (LCPUFA) has declined over the same period of time. This, together with the known role of n-3 LCPUFA in inhibiting inflammation, has resulted in speculation that n-3 LCPUFA may prevent allergy development. Dietary n-3 fatty acids supplements may change the developing immune system of the newborn before allergic responses are established, particularly for those with a genetic predisposition to the production of the immunoglobulin E (IgE) antibody. Individuals with IgE-mediated allergies have both the signs and symptoms of the allergic disease and a positive skin prick test (SPT) to the allergen. OBJECTIVES To assess the effect of n-3 LCPUFA supplementation in pregnant and/or breastfeeding women on allergy outcomes (food allergy, atopic dermatitis (eczema), allergic rhinitis (hay fever) and asthma/wheeze) in their children. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 August 2014), PubMed (1966 to 01 August 2014), CINAHL via EBSCOhost (1984 to 01 August 2014), Scopus (1995 to 01 August 2014), Web of Knowledge (1864 to 01 August 2014) and ClinicalTrials.gov (01 August 2014) and reference lists of retrieved studies. SELECTION CRITERIA We included randomised controlled trials (RCTs) evaluating the effect of n-3 LCPUFA supplementation of pregnant and/or lactating women (compared with placebo or no treatment) on allergy outcomes of the infants or children. Trials using a cross-over design and trials examining biochemical outcomes only were not eligible for inclusion. DATA COLLECTION AND ANALYSIS Two review authors independently assessed eligibility and trial quality and performed data extraction. Where the review authors were also investigators on trials selected, an independent reviewer assessed trial quality and performed data extraction. MAIN RESULTS Eight trials involving 3366 women and their 3175 children were included in the review. In these trials, women were supplemented with n-3 LCPUFA during pregnancy (five trials), lactation (two trials) or both pregnancy and lactation (one trial). All trials randomly allocated women to either a n-3 LCPUFA supplement or a control group. The risk of bias varied across the eight included trials in this review with only two trials with a low risk of selection, performance and attrition bias.N-3 LCPUFA supplementation showed a clear reduction in the primary outcome of any allergy (medically diagnosed IgE mediated) in children aged 12 to 36 months (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.98; two RCTs; 823 children), but not beyond 36 months (RR 0.86, 95% CI 0.61 to 1.20; one RCT, 706 children). For any allergy (medically diagnosed IgE mediated and/or parental report), no clear differences were seen in children either at 12 to 36 months (RR 0.89, 95% CI 0.71 to 1.11; two RCTs, 823 children) or beyond 36 months of age (RR 0.96, 95% CI 0.84 to 1.09; three RCTs, 1765 children).For the secondary outcomes of specific allergies there were no clear differences for food allergies at 12 to 36 months and beyond 36 months, but a clear reduction was seen for children in their first 12 months with n-3 LCPUFA (both for medically diagnosed IgE mediated and medically diagnosed IgE mediated and/or parental report). There was a clear reduction in medically diagnosed IgE-mediated eczema with n-3 LCPUFA for children 12 to 36 months of age, but not at any other time point for both medically diagnosed IgE mediated and medically diagnosed IgE mediated and/or parental report. No clear differences for allergic rhinitis or asthma/wheeze were seen at any time point for both medically diagnosed IgE mediated, and medically diagnosed IgE mediated and/or parental report.There was a clear reduction in children's sensitisation to egg and sensitisation to any allergen between 12 to 36 months of age when mothers were supplemented with n-3 LCPUFA.In terms of safety for the mother and child, n-3 LCPUFA supplementation during pregnancy did not show increased risk of postpartum haemorrhage or early childhood infections. AUTHORS' CONCLUSIONS Overall, there is limited evidence to support maternal n-3 LCPUFA supplementation during pregnancy and/or lactation for reducing allergic disease in children. Few differences in childhood allergic disease were seen between women who were supplemented with n-3 LCPUFA and those who were not.
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7.
Prebiotics in infants for prevention of allergy.
Osborn, DA, Sinn, JK
The Cochrane database of systematic reviews. 2013;(3):CD006474
Abstract
BACKGROUND Prebiotics (commonly oligosaccharides) added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens. OBJECTIVES To determine the effect of prebiotic given to infants for the prevention of allergy. SEARCH METHODS We performed an updated search in August 2012 of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 8), MEDLINE, EMBASE, conference proceedings, citations, expert informants and clinical trials registries. SELECTION CRITERIA Randomised and quasi-randomised controlled trials that compared the use of a prebiotic to no prebiotic, or a specific prebiotic compared to a different prebiotic in infants for prevention of allergy. DATA COLLECTION AND ANALYSIS Assessment of trial quality, data extraction and synthesis of data were performed using the standard methods of The Cochrane Collaboration. MAIN RESULTS The 2012 update identified 13 studies classified as ongoing or awaiting classification (yet to report allergy outcomes). Forty-three studies were excluded, primarily as no allergy data were reported, although none of these enrolled infants were at high risk of allergy. Four studies enrolling 1428 infants were eligible for inclusion. All studies were at high risk of attrition bias. Allergy outcomes were reported from four months to two years of age.Meta-analysis of two studies (226 infants) found no significant difference in infant asthma although significant heterogeneity was found between studies. Meta-analysis of four studies found a significant reduction in eczema (1218 infants, typical risk ratio 0.68, 95% CI 0.48 to 0.97; typical risk difference -0.04, 95% CI -0.07 to -0.00; number needed to treat to benefit (NNTB) 25, 95% CI 14 to > 100; P = 0.03). No statistically significant heterogeneity was found between studies. One study reported no significant difference in urticaria.No statistically significant subgroup differences were found according to infant risk of allergy or type of infant feed. However, individual studies reported a significant reduction in asthma and eczema from supplementation with a mixture of galacto- and fructo-oligosaccharide (GOS/FOS 9:1 ratio) (8 g/L) in infants at high risk of allergy; and in eczema from supplementation with GOS/FOS (9:1) (6.8 g/L) and acidic oligosacccharide (1.2 g/L) in infants not selected for allergy risk. AUTHORS' CONCLUSIONS Further research is needed before routine use of prebiotics can be recommended for prevention of allergy in formula fed infants. There is some evidence that a prebiotic supplement added to infant feeds may prevent eczema. It is unclear whether the use of prebiotic should be restricted to infants at high risk of allergy or may have an effect in low risk populations; or whether it may have an effect on other allergic diseases including asthma.
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Meta-analysis of the evidence for a partially hydrolyzed 100% whey formula for the prevention of allergic diseases.
Szajewska, H, Horvath, A
Current medical research and opinion. 2010;(2):423-37
Abstract
OBJECTIVE Infants with a documented hereditary risk of atopy (i.e., an affected parent and/or sibling) who cannot be breastfed exclusively are recommended to receive a formula with confirmed reduced allergenicity, i.e., a partially or extensively hydrolyzed formula (pHF and eHF, respectively), as a means of preventing allergic reactions. The efficacy of each hydrolyzed formula for the prevention of allergic diseases should be established separately, as factors such as the protein source, hydrolysis method and degree of hydrolysis that often depend on the manufacturer contribute to differences among hydrolysates. The aim was to systematically review data on the efficacy of a partially hydrolyzed 100% whey formula (pHF) in reducing the risk of allergy in healthy infants at high risk for allergy. METHODS The Cochrane Library, MEDLINE, EMBASE, and CINAHL databases were searched in September 2009 (from inception to September 2009) for randomized and quasi-randomized controlled trials (RCTs); additional references were obtained from reviewed articles. The company that manufactures the pHF used was contacted for unpublished data. RESULTS The search yielded 84 citations. Fifteen RCTs were included, some of which had potential methodological limitations such as unclear or inadequate allocation concealment, no intention-to-treat analysis, and no true blinding. For primary outcomes, i.e., all allergic diseases and atopic eczema/atopic dermatitis, use of the pHF compared with standard formula (SF) was associated with reduced risks (incidence, cumulative incidence, period prevalence) that were statistically significant for most, albeit not all, time points. Comparison of groups who received the pHF versus extensively hydrolyzed (eH) whey formula revealed no significant differences in outcomes except for reductions in the cumulative incidences of all allergic diseases at 0 to 36 months of age. Comparison of groups who received the pHF versus eH casein formula revealed no significant difference in outcomes between groups. CONCLUSIONS The use of the pHF compared to SF is effective in allergy prevention in children at high risk for allergy at most time points. These results should be interpreted with caution due to a lack of methodological rigor in many trials. Reassuringly, the strongest evidence comes from a well-designed and conducted, independently funded RCT.
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9.
Probiotics in infants for prevention of allergic disease and food hypersensitivity.
Osborn, DA, Sinn, JK
The Cochrane database of systematic reviews. 2007;(4):CD006475
Abstract
BACKGROUND The composition of the intestinal microflora may be different in individuals with atopic eczema from those without this condition, and such differences may precede the development of eczema. Probiotics are live bacteria that colonize the gastrointestinal tract and provide a health benefit to the host. Probiotics added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens. OBJECTIVES To determine the effect of probiotics given to infants for the prevention of allergic disease or food hypersensitivity. SEARCH STRATEGY This included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (1966 - February 2007), EMBASE, PREMEDLINE, abstracts of conference proceedings and citations of published articles, and expert informants. SELECTION CRITERIA Randomised and quasi-randomised controlled trials that compare the use of a probiotic to no probiotic; or the use a specific probiotic compared to a different probiotic; or a probiotic with added prebiotic to control. DATA COLLECTION AND ANALYSIS Assessment of trial quality, data extraction and synthesis of data were performed using standard methods of the Cochrane Neonatal Review Group. MAIN RESULTS Twelve studies were eligible for inclusion. Allergic disease and / or food hypersensitivity outcomes were assessed by 6 studies enrolling 2080 infants, but outcomes for only 1549 infants were reported. Studies generally had adequate randomisation, allocation concealment and blinding of treatment. However, the findings of this review should be treated with caution due to excess losses in patient follow-up (17% to 61%). Meta-analysis of five studies reporting the outcomes of 1477 infants found a significant reduction in infant eczema (typical RR 0.82, 95% CI 0.70, 0.95). However, there was significant and substantial heterogeneity between studies. One study reported that the difference in eczema between groups persisted to 4 years age. When the analysis was restricted to studies reporting atopic eczema (confirmed by skin prick test or specific IgE), the findings were no longer significant (typical RR 0.80, 95% CI 0.62, 1.02). All studies reporting significant benefits used probiotic supplements containing L. rhamnosus and enrolled infants at high risk of allergy. No other benefits were reported for any other allergic disease or food hypersensitivity outcome. AUTHORS' CONCLUSIONS There is insufficient evidence to recommend the addition of probiotics to infant feeds for prevention of allergic disease or food hypersensitivity. Although there was a reduction in clinical eczema in infants, this effect was not consistent between studies and caution is advised in view of methodological concerns regarding included studies. Further studies are required to determine whether the findings are reproducible.