Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. Methods: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. Results: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. Conclusion: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium. (J Allergy Clin Immunol 2019;143:2062-74.)

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni < 1.06 x 10 −7 ). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Purpose Validated measures of asthma and eczema at the population level remain a challenge. Our aim was to ascertain if register‐based information on asthma/eczema medication can function as a proxy for an asthma/eczema diagnosis and to validate register‐based asthma diagnoses. Methods Information was requested on all 0–45‐year‐old individuals with reported asthma/eczema medication and/or diagnoses in the Swedish Prescribed Drug Register and National Patient Register, between July 2005 and December 2009 (N = 250 691). Medical records for 1952 randomly selected individuals were reviewed to estimate the proportion of individuals with the following: (1) asthma/eczema medication that fulfilled predefined criteria of asthma/eczema (positive predictive value (PPV)) and (2) a register‐based asthma diagnosis verified as asthma by predefined criteria. Results Positive predictive value for asthma by predefined criteria ranged between 0.75 (95%CI: 0.70–0.78) to 0.94 (95%CI: 0.91–0.96), depending on age group. In pre‐school children, PPV for asthma in combination with obstructive bronchitis was 0.87 (95%CI: 0.83–0.90), and PPV for eczema was estimated to 0.45 (95%CI: 0.38–0.51). Eighty percent of children 0–4.5 years and 99% of children >4.5–17 years with a register‐based diagnosis of asthma were verified as asthmatics. Conclusion Asthma medication is a suitable proxy for asthma in older children and adults; the same approach is insufficient for eczema. This validation study of two Swedish registers opens for future large nation‐wide register‐based studies on asthma. Copyright © 2013 John Wiley & Sons, Ltd.

Objective To investigate the association between exposure to antibiotics in fetal and early life and asthma in childhood, with adjustment for confounding factors.Design Nationwide prospective population based cohort study, including sibling control design.Setting Swedish population identified from national demographic and health registers.Participants 493 785 children born 2006-10; 180 894 of these were eligible for sibling analyses.Main outcome measure Asthma defined as having both an asthma diagnosis and dispensed asthma drugs. The association between antibiotic exposure and asthma was investigated in the whole cohort with Cox proportional hazard regression. A stratified proportional hazards model conditional on sibling group was used to adjust for shared factors within families. Confounding by respiratory infections was assessed by investigating whether specific groups of antibiotics were associated with asthma.Results Antibiotic exposure in fetal life was associated with an increased risk of asthma in cohort analyses (hazard ratio 1.28, 95% confidence interval 1.25 to 1.32), but not in sibling analyses (0.99, 0.92 to 1.07). In cohort analyses, antibiotics used to treat respiratory infections in childhood were associated with a more pronounced increased risk of asthma (4.12, 3.78 to 4.50) than antibiotics used for urinary tract and skin infections (1.54, 1.24 to 1.92). In sibling analyses, the excess risks after exposure to antibiotics for respiratory infections decreased (2.36, 1.78 to 3.13) and disappeared for antibiotics for urinary tract and skin (0.85, 0.47 to 1.55).Conclusions Previous positive associations between exposure to antibiotics in fetal and early life and subsequent childhood asthma could have been caused by confounding by shared familial factors, in addition to confounding by respiratory infections.

IMPORTANCE Data about the safety of vaccines against SARS-CoV-2 during pregnancy are limited.OBJECTIVE To examine the risk of adverse pregnancy outcomes after vaccination against SARS-CoV-2 during pregnancy.

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IMPORTANCEThe association between early exposure to animals and childhood asthma is not clear, and previous studies have yielded contradictory results. OBJECTIVE To determine whether exposure to dogs and farm animals confers a risk of asthma.

There is an association between fetal growth and childhood asthma that is independent of GA and shared (familial) environment and genetic factors, which indicates that fetal growth restriction affects lung development, supporting additional studies on the early metabolic and physiologic mechanisms of childhood asthma.