Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns

Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina" s HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring

Consequences of chronic obstructive pulmonary disease and chronic heart failure: The relationship between objective and subjective health

This study investigates whether the relationship between objective health parameters and general health perceptions was mediated by symptoms of dyspnoea and physical functioning in patients with chronic obstructive pulmonary disease (COPD) and patients with chronic heart failure (CHF). The different health parameters were organised according to Wilson and Cleary's conceptual model of patient outcomes (Wilson & Cleary (1995). Journal of the American Medical Association, 273, 59-65). Second, we investigated whether perceptions of personal control were related to the health parameters in the model. Consecutive patients with COPD and CHF were included from the outpatient clinics of a university hospital and a general hospital, and from a rehabilitation centre, all in the Netherlands. Ninety-five COPD patients (aged 65.0+/-9.3; forced expiratory volume in 1s (FEV(1))<70%) were included and compared with 90 CHF patients (aged 59.6+/-10.0; left ventricular ejection fraction (LVEF)<45%). The relationship between objective health parameters (FEV(1) or LVEF) and subjective health (self-reported physical functioning) was not mediated by symptoms of dyspnoea. FEV(1) or LVEF and symptoms of dyspnoea were independently related to self-reported physical functioning, which was directly related to general health perceptions. Perceived health competence was related to symptoms of dyspnoea and general health perceptions in patients with either COPD or CHF. Although patients with COPD reported lower levels in all self-reported health parameters in the model than the patients with CHF, this study showed that the relations between the health parameters in the model were comparable for COPD and CHF patients

Estimating Infarct Severity from the ECG using a Realistic Heart Model

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Internet-based self-management compared with usual care in adolescents with asthma: a randomized controlled trial

Asthma control often is poor in adolescents and this causes considerable morbidity. Internet-based self-management (IBSM) improves asthma-related quality of life in adults. We hypothesized that IBSM improves asthma-related quality of life in adolescents. Adolescents (12-18 years) with persistent and not well-controlled asthma participated in a randomized controlled trial with 1 year follow-up and were allocated to IBSM (n = 46) or usual care (UC, n = 44). IBSM consisted of weekly asthma control monitoring with treatment advice by a web-based algorithm. Outcomes included asthma-related quality of life (Pediatric Asthma Quality of Life Questionnaire, PAQLQ) and asthma control (Asthma Control Questionnaire, ACQ) and were analyzed by a linear mixed-effects model. At 3 months, PAQLQ improved with 0.40 points (95% CI: 0.17-0.62, P < 0.01), by IBSM compared to 0.0 points for UC (P = 0.02 for the difference). At 12 months the between-group difference was -0.05 (95% CI: -0.50 to 0.41, P = 0.85). At 3 months ACQ improved more in IBSM than in UC (difference: -0.32 points; 95% CI: -0.56 to -0.079, P < 0.01). At 12 months the difference was -0.05 (95% CI: -0.35 to 0.25, P = 0.75). IBSM improved asthma-related quality of life and asthma control in adolescents with not well-controlled asthma after 3 months, but not after 12 month

The impact of Helicobacter pylori on atopic disorders in childhood

Background: The prevalence of Helicobacter pylori in Western populations has steadily decreased. This has been suggested as one of the factors involved in the recent increase of asthma and allergy. Some studies have reported a negative association between H. pylori and asthma and allergy, but data are inconsistent and there are a few studies in children. Aim: We investigated whether the prevalence of H. pylori was associated with asthma symptoms, allergic rhinitis, and atopic dermatitis in childhood. Methods: We determined IgG anti-H. pylori and CagA antibodies in serum of Dutch children, who took part in the PIAMA birth cohort study. Serum was collected from 545 children, aged 7-9years (Dutch ethnicity 91.5%). Symptoms of asthma and atopy were assessed by yearly questionnaires. Chi-square tests and logistic regression were used. Results: We found 9%H. pylori and 0.9% CagA seropositivity. Twelve (5.9%) children with reported wheezing ever were H. pylori positive, compared to 37 (10.9%) of the non-wheezers (p=.05). No significant differences in H. pylori prevalence were found between children with or without allergic rhinitis (8.5% vs 9.5%), atopic dermatitis (8.7% vs 9.2%), and physician-diagnosed asthma (7.1% vs 9.4%). Multivariate analysis showed no significant associations between H. pylori seropositivity and wheezing (OR 0.52; 95% CI 0.25-1.06), allergic rhinitis (OR 0.96; 95% CI 0.51-1.81), atopic dermatitis (OR 1.05; 95% CI 0.56-1.98) or physician-diagnosed asthma (OR 0.87; 95% CI 0.37-2.08). Conclusion: We found a borderline significantly lower H. pylori seropositivity in children with wheezing compared to non-wheezers, but no association between H. pylori serum-antibody status and allergic rhinitis, atopic dermatitis, or asthma

Helicobacter pylori in children with asthmatic conditions at school age, and their mothers

Background Helicobacter pylori prevalence in Western countries has been declining simultaneously with increases in childhood asthma and allergic diseases; prior studies have linked these phenomena. Aims To examine the association between H. pylori colonisation in children and risk of asthma and related conditions at school age. We secondly examined additional effects of maternal H. pylori status by pairing with children's status. Methods This study was embedded in a multi-ethnic population-based cohort in Rotterdam, The Netherlands. We measured anti-H. pylori and anti-CagA antibodies in serum of children obtained at age 6 years, and of their mothers obtained during midpregnancy. Asthma or related conditions were reported for children at age 6 years. We used multivariate logistic regression analyses among 3797 subjects. Results In children, the H. pylori positivity rate was 8.7%, and 29.2% of these were CagA-positive. A child's colonisation with a CagA-negative-H. pylori strain was associated with an increased risk of asthma (Odds ratio 2.11; 95% CI 1.23-3.60), but this differed for European (3.64; 1.97-6.73) and non-European (0.52; 0.14-1.89) children. When taking into account maternal H. pylori status, only H. pylori-positive children with an H. pylori-negative mother had increased risk of asthma (2.42; 1.11-5.27), accounting for 3.4% of the asthma risk. Conclusions Colonisation of a European child with a CagA-negative-H. pylori strain at age 6 was associated with an increased prevalence of asthma, but there was no association for non-European children. The underlying mechanisms for the observed risk differences require further research