1.
Effect of season of birth on cord blood IgE and IgE at birth: A systematic review and meta-analysis.
Susanto, NH, Vicendese, D, Salim, A, Lowe, AJ, Dharmage, SC, Tham, R, Lodge, C, Garden, F, Allen, K, Svanes, C, et al
Environmental research. 2017;:198-205
Abstract
BACKGROUND Elevated cord blood IgE is important on the pathway to allergic disease. The association between season of birth and infant cord blood IgE is not well-established. Study findings differ on which birth season is associated with higher cord blood IgE risk and its magnitude. We conducted a systematic review and meta-analysis of studies on season of birth and cord blood IgE. METHODS We searched Medline, Web of Science, Scopus and ProQuest Health databases, and reviewed reference lists of articles that met the inclusion criteria. All included studies measured IgE as a binary variable using various cut-off values. We performed multivariate-random-effects meta-analysis to handle an exposure with multiple categories of Season of Birth. RESULTS Our search identified 275 records and 10 had sufficient data to be included in a meta-analysis. Relative to summer, winter birth had the greatest odds of high IgE (≥ 0.1IU/ml), meta-analysis OR = 1.24 (95%CI: 1.01-1.52). A similar OR, was found for IgE ≥ 0.5 IU/ml, OR = 1.30 (95%CI: 0.99-1.71). CONCLUSIONS A winter season of birth was associated with statistically significant higher odds of elevated cord blood IgE at cut-off ≥ 0.1IU/ml but borderline at cut-off ≥ 0.5IU/ml. This winter effect is likely to be a marker for a range of other environmental exposures during specific stages of pregnancy, such as aeroallergen exposures, maternal infections and vitamin D levels. Further research is required to support our finding and to identify the exact mechanisms that lead to the winter season of birth effect on circulating IgE levels, as this may have implications for allergic disease prevention.
2.
Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study.
Manousaki, D, Paternoster, L, Standl, M, Moffatt, MF, Farrall, M, Bouzigon, E, Strachan, DP, Demenais, F, Lathrop, M, Cookson, WOCM, et al
PLoS medicine. 2017;(5):e1002294
Abstract
BACKGROUND Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable. METHODS AND FINDINGS We aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval [CI] 0.90-1.19, p = 0.63) for asthma, 0.95 (95% CI 0.69-1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92-1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was -0.40 (95% CI -1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia. CONCLUSIONS In this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease.