Cost effectiveness of vitamin c supplementation for pregnant smokers to improve offspring lung function at birth and reduce childhood wheeze/asthma.
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ABSTRACT:
SUBMITTER: Yieh L
PROVIDER: S-EPMC6414472 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
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Cost effectiveness of vitamin c supplementation for pregnant smokers to improve offspring lung function at birth and reduce childhood wheeze/asthma.
Yieh Leah L McEvoy Cindy T CT Hoffman Scott W SW Caughey Aaron B AB MacDonald Kelvin D KD Dukhovny Dmitry D
Journal of perinatology : official journal of the California Perinatal Association 20180522 7
<h4>Objective</h4>To determine the implications of supplemental vitamin C for pregnant tobacco smokers and its effects on the prevalence of pediatric asthma, asthma-related mortality, and associated costs.<h4>Study design</h4>A decision-analytic model built via TreeAge compared the outcome of asthma in a theoretical annual cohort of 480,000 children born to pregnant smokers through 18 years of life. Vitamin C supplementation (500 mg/day) with a standard prenatal vitamin was compared to a prenata ...[more]
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Project description:BackgroundPrenatal vitamin D3 supplementation has been linked to reduced risk of early-life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional single nucleotide polymorphism rs12936231 of the child, which regulates the expression of ORMDL3 (ORM1-like 3) and for which the high-risk CC genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.MethodsWe determined the rs12936231 genotype of mother-child pairs from two randomised controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010, n=563), to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0-3 years between groups who received high-dose prenatal vitamin D3 supplementation versus placebo.ResultsOffspring of mothers with the low-risk GG or GC genotype who received high-dose vitamin D3 supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared with the placebo group (hazard ratio (HR) 0.54, 95% CI 0.37-0.77; p<0.001 for VDAART and HR 0.56, 95% CI 0.35-0.92; p=0.021 for COPSAC2010), whereas no difference was observed among the offspring of mothers with the high-risk CC genotype (HR 1.05, 95% CI 0.61-1.84; p=0.853 for VDAART and HR 1.11, 95% CI 0.54-2.28; p=0.785 for COPSAC2010).ConclusionMaternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.
| S-EPMC8410880 | biostudies-literature
Project description:Background: We recently published two independent randomized controlled trials of vitamin D supplementation during pregnancy, both indicating a >20% reduced risk of asthma/recurrent wheeze in the offspring by 3 years of age. However, neither reached statistical significance.Objective: To perform a combined analysis of the two trials and investigate whether maternal 25-hydroxy-vitamin D (25(OH)D) level at trial entry modified the intervention effect.Methods: VDAART (N = 806) and COPSAC2010. (N = 581) randomized pregnant women to daily high-dose vitamin D3 (4,000 IU/d and 2,400 IU/d, respectively) or placebo. All women also received a prenatal vitamin containing 400 IU/d vitamin D3. The primary outcome was asthma/recurrent wheeze from 0-3yrs. Secondary end-points were specific IgE, total IgE, eczema and lower respiratory tract infections (LRTI). We conducted random effects combined analyses of the treatment effect, individual patient data (IPD) meta-analyses, and analyses stratified by 25(OH)D level at study entry.Results: The analysis showed a 25% reduced risk of asthma/recurrent wheeze at 0-3yrs: adjusted odds ratio (aOR) = 0.74 (95% CI, 0.57-0.96), p = 0.02. The effect was strongest among women with 25(OH)D level ?30ng/ml at study entry: aOR = 0.54 (0.33-0.88), p = 0.01, whereas no significant effect was observed among women with 25(OH)D level <30ng/ml at study entry: aOR = 0.84 (0.62-1.15), p = 0.25. The IPD meta-analyses showed similar results. There was no effect on the secondary end-points.Conclusions: This combined analysis shows that vitamin D supplementation during pregnancy results in a significant reduced risk of asthma/recurrent wheeze in the offspring, especially among women with 25(OH)D level ? 30 ng/ml at randomization, where the risk was almost halved. Future studies should examine the possibility of raising 25(OH)D levels to at least 30 ng/ml early in pregnancy or using higher doses than used in our studies.Trial registration: COPSAC2010: ClinicalTrials.gov NCT00856947; VDAART: ClinicalTrials.gov NCT00920621.
| S-EPMC5659607 | biostudies-literature
Project description:The in utero environment during pregnancy has important implications for the developing health of the child. We aim to examine the potential impact of maternal metabolome at two different timepoints in pregnancy on offspring respiratory health in early life. In 685 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial, we assessed the prospective associations between maternal metabolites at both baseline (10-18 weeks gestation) and third trimester (32-38 weeks gestation) and the risk of child asthma or recurrent wheeze by age three using logistic regression models accounting for confounding factors. Subgroup analyses were performed by child sex. Among 632 metabolites, 19 (3.0%) and 62 (9.8%) from baseline and third trimester, respectively, were associated with the outcome (p-value < 0.05). Coffee-related metabolites in the maternal metabolome appeared to be of particular importance. Caffeine, theophylline, trigonelline, quinate, and 3-hydroxypyridine sulfate were inversely associated with asthma risk at a minimum of one timepoint. Additional observations also highlight the roles of steroid and sphingolipid metabolites. Overall, there was a stronger relationship between the metabolome in later pregnancy and offspring asthma risk. Our results suggest that alterations in prenatal metabolites may act as drivers of the development of offspring asthma.
| S-EPMC7910853 | biostudies-literature
Project description:ImportanceThere is growing evidence that vitamin D plays a role in the pathogenesis of asthma but it is unclear whether supplementation during childhood may improve asthma outcomes.ObjectivesThe objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of vitamin D supplementation as a treatment or adjunct treatment for asthma.Data sourcesWe searched MEDLINE, Embase, CENTRAL, and CINAHL through July 2014.Study selectionWe included RCTs that evaluated vitamin D supplementation in children versus active control or placebo for asthma.Data extraction and synthesisOne reviewer extracted data and one reviewer verified data accuracy. We qualitatively summarized the main results of efficacy and safety and meta-analyzed data on comparable outcomes across studies. We used GRADE for strength of evidence.Main outcome measuresMain planned outcomes measures were ED visits and hospitalizations. As secondary outcomes, we examined measures of asthma control, including frequency of asthma exacerbations, asthma symptom scores, measures of lung function, β2-agonist use and daily steroid use, adverse events and 25-hydroxyvitamin D levels.ResultsEight RCTs (one parallel, one crossover design) comprising 573 children aged 3 to 18 years were included. One study (moderate-quality, n = 100) reported significantly less ED visits for children treated with vitamin D. No other studies examined the primary outcome (ED visits and hospitalizations). There was a reduced risk of asthma exacerbations in children receiving vitamin D (low-quality; RR 0.41, 95% CI 0.27 to 0.63, 3 studies, n = 378). There was no significant effect for asthma symptom scores and lung function. The serum 25(OH)D level was higher in the vitamin D group at the end of the intervention (low-quality; MD 19.66 nmol/L, 95% CI 5.96 nmol/L to 33.37 nmol/L, 5 studies, n = 167).LimitationsWe identified a high degree of clinical diversity (interventions and outcomes) and methodological heterogeneity (sample size and risk of bias) in included trials.Conclusions and relevanceRandomized controlled trials provide some low-quality evidence to support vitamin D supplementation for the reduction of asthma exacerbations. Evidence on the benefits of vitamin D supplementation for other asthma-related outcomes in children is either limited or inconclusive. We recommend that future trials focus on patient-relevant outcomes that are comparable across studies, including standardized definitions of asthma exacerbations.
| S-EPMC4556456 | biostudies-literature
Project description:Background: Maternal vitamin D status during pregnancy may influence lung development and risk of childhood wheeze and asthma. We investigated the relationship between prenatal vitamin D and child asthma in a racially diverse cohort with a high burden of vitamin D insufficiency and child asthma.Materials and methods: We included mother-child dyads in the prenatal Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort (2006-2011, Shelby County, Tennessee). Maternal plasma vitamin D [25(OH)D] was measured from second trimester (n = 1091) and delivery specimens (n = 907). At age 4-6 years, we obtained parent report of current child wheeze (symptoms within the past 12 months) and asthma (physician diagnosis and/or medication or symptoms within the past 12 months). We used multivariable logistic regression to assess associations of 25(OH)D and child wheeze/asthma, including an interaction term for maternal race.Results: Median second trimester 25(OH)D levels were 25.1 and 19.1 ng/ml in White (n = 366) and Black women (N = 725), respectively. We detected significant interactions by maternal race for second-trimester plasma 25(OH)D and child current wheeze (p = .014) and asthma (p = .011). Odds of current wheeze and asthma decreased with increasing 25(OH)D in dyads with White mothers and increased in dyads with Black mothers, e.g. adjusted odds ratio (95% confidence interval) for asthma: 0.63 (0.36-1.09) and 1.41 (1.01-1.97) per interquartile range (15-27 ng/ml 25[OH]D) increase, respectively. At delivery, protective associations in White dyads were attenuated.Conclusion: We detected effect modification by maternal race in associations between prenatal 25(OH)D and child wheeze/asthma. Further research in racially diverse populations is needed.
| S-EPMC6824925 | biostudies-literature
Project description:The Asthma Predictive Index (API) and persistent wheezing phenotypes are associated with childhood asthma, but previous studies have not assessed their ability to predict objectively confirmed asthma.To determine whether the University of Cincinnati API Index (ucAPI) and/or persistent wheezing at age 3 can accurately predict objectively confirmed asthma at age 7.Data from the Cincinnati Childhood Allergy and Air Pollution Study, a high-risk prospective birth cohort, was used. Asthma was defined as parent-reported or physician-diagnosed asthma objectively confirmed by a change in FEV1 of ?12% after bronchodilator or a positive methacholine challenge (PC20 ? 4 mg/mL); or as prior treatment with daily asthma controller medication(s). Multivariate logistic regression was used to investigate the relationship between confirmed asthma at age 7 and a positive ucAPI (adapted and modified from prior published API definitions) and persistent wheezing at age 3.At age 7, 103 of 589 children (17.5%) satisfied the criteria for asthma. Confirmed asthma at age 7 was significantly associated with a positive ucAPI (adjusted odds ratio [aOR] 13.3 [95% CI, 7.0-25.2]; P < .01) and the persistent wheezing phenotype (aOR 9.8 [95% CI, 4.9-19.5]; P < .01) at age 3. Allergic persistent wheezing was associated with a significantly higher risk of asthma (aOR 10.4 [95% CI, 4.1-26.0]; P < .01) than nonallergic persistent wheezing (aOR 5.4 [95% CI, 2.04-14.06]; P < .01).Both a positive ucAPI and persistent wheeze at age 3 were associated with objectively confirmed asthma at age 7; however, the highest risk was associated with ucAPI. These results demonstrate the ucAPI as a clinically useful tool for predicting future asthma in school-age children.
| S-EPMC4254628 | biostudies-literature
Project description:Evidence suggests vitamin D has preventive potential in asthma; however, not all children benefit from this intervention. This study aimed to investigate whether variation in the functional 17q21 single nucleotide polymorphism rs12936231 affects the preventive potential of vitamin D against asthma.A combined secondary analysis of two randomised controlled trials of prenatal vitamin D supplementation for the prevention of asthma in offspring (Vitamin D Antenatal Asthma Reduction Trial (VDAART) and Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010)) was performed, stratifying by genotype and integrating metabolite data to explore underlying mechanisms.The protective effect of vitamin D on asthma/wheeze was evident among children with the low-risk rs12936231 GG genotype (hazard ratio (HR) 0.49, 95% CI 0.26-0.94, p=0.032) but not the high-risk CC genotype (HR 1.08, 95% CI 0.69-1.69, p=0.751). In VDAART, in the GG genotype vitamin D supplementation was associated with increased plasma levels of sphingolipids, including sphingosine-1-phosphate (? 0.022, 95% CI 0.001-0.044, p=0.038), but this was not evident with the CC genotype, known to be associated with increased expression of ORMDL3 in bronchial epithelial cells. Sphingolipid levels were associated with decreased risk of asthma/wheeze, and there was evidence of interactions between sphingolipid levels, vitamin D and genotype (p-interactionvitaminD*genotype*sphingosine-1-phosphate=0.035). In a cellular model, there was a significant difference in the induction of sphingosine-1-phosphate by vitamin D between a control human bronchial epithelial cell line and a cell line overexpressing ORMDL3 (p=0.002).Results suggest prenatal vitamin D supplementation may reduce the risk of early childhood asthma/wheeze via alterations of sphingolipid metabolism dependent on the 17q21 genotype.
| S-EPMC7181456 | biostudies-literature
Project description:Asthma heritability has only been partially explained by genetic variants and is known to be sensitive to environmental factors, implicating epigenetic modifications such as DNA methylation in its pathogenesis.Using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC), we assessed associations of asthma and wheeze with DNA methylation at 7.5 and 16.5 years, at over 450,000 CpG sites in DNA from the peripheral blood of approx. 1000 participants. We used Mendelian randomization (MR), a method of causal inference that uses genetic variants as instrumental variables, to infer the direction of association between DNA methylation and asthma.We identified 302 CpGs associated with current asthma status (FDR-adjusted P value <?0.05) and 445 with current wheeze status at 7.5 years, with substantial overlap between the two. Genes annotated to the 302 associated CpGs were enriched for pathways related to movement of cellular/subcellular components, locomotion, interleukin-4 production and eosinophil migration. All associations attenuated when adjusted for eosinophil and neutrophil cell count estimates. At 16.5 years, two sites were associated with current asthma after adjustment for cell counts. The CpGs mapped to the AP2A2 and IL5RA genes, with a -?2.32 [95% CI -?1.47, -?3.18] and -?2.49 [95% CI -?1.56, -?3.43] difference in percentage methylation in asthma cases respectively. Two-sample bi-directional MR indicated a causal effect of asthma on DNA methylation at several CpG sites at 7.5 years. However, associations did not persist after adjustment for multiple testing. There was no evidence of a causal effect of asthma on DNA methylation at either of the two CpG sites at 16.5 years.The majority of observed associations are driven by higher eosinophil cell counts in asthma cases, acting as an intermediate phenotype, with important implications for future studies of DNA methylation in atopic diseases.
| S-EPMC5640901 | biostudies-other
Project description:This study was prepared to identify and characterize potential factors associated with childhood asthma and wheeze in Chinese preschool-aged children. A comprehensive questionnaire was designed for children aged 3-6 years and their parents or guardians in Beijing and Tangshan from September to December 2020. The least absolute shrinkage and selection operator (LASSO) model was used to identify factors in a significant association with childhood asthma and wheeze, respectively. The LASSO model was internally validated using bootstrap resampling with 100 replications. A total of 9,529 questionnaires were certified as eligible for inclusion after stringent quality control. The prevalence of doctor-diagnosed childhood asthma and parent-reported wheeze was 2.8 and 6.2%, respectively. Factors simultaneously associated with childhood asthma and wheeze were children with a history of allergic rhinitis, hay fever, eczema, initial age of using antibiotics, body mass index category, and family history of asthma. Specifically, children's vitamin D supplement duration was significantly associated with childhood asthma, whereas the association with childhood wheeze was significant for intake frequency of night meals for children and their screen time. Modeling of significant factors in nomograms had decent prediction accuracies, with C-index reaching 0.728 and 0.707 for asthma and wheeze, respectively. In addition, internal validation was good, with bootstrap C-statistic of being 0.736 for asthma and 0.708 for wheeze. Taken together, our findings indicated that the development of asthma and wheeze among preschool-aged children was probably determined by the joint contribution of multiple factors including inherited, nutritional, unhealthy lifestyles, and history of allergic disease. Further validation in other groups is necessary.
| S-EPMC8599959 | biostudies-literature
Project description:BackgroundWheeze and allergic sensitization are the strongest early-life predictors of childhood asthma development; the molecular origins of these early-life phenotypes are poorly understood.ObjectivesWe sought to identify metabolites associated with early-life wheeze, allergic sensitization, and childhood asthma.MethodsWe conducted a nested case-control study using Environmental influences on Child Health Outcomes Program cohorts for discovery and independent replication. Wheeze and allergic sensitization were defined by number of wheeze episodes and positive specific IgE at age 1 year, respectively. Asthma was defined as physician diagnosis of asthma at age 5 or 6 years. We used untargeted metabolomics, controlling for observed and latent confounding factors, to assess associations between the plasma metabolome and early-life wheeze, allergy, and childhood asthma.ResultsEighteen plasma metabolites were associated with first-year wheeze in the discovery cohort (n = 338). Z,Z unconjugated bilirubin (UCB) and its related metabolites exhibited a dose-response relationship with wheeze frequency; UCB levels were 13% (β = 0.87; 95% CI, 0.74-1.02) and 22% (β = 0.78; 95% CI, 0.68-0.91) lower in children with 1 to 3 and 4+ wheeze episodes compared with those who never wheezed, respectively. UCB levels were also associated with childhood asthma (β = 0.82; 95% CI, 0.68-0.98). Similar trends were observed in 2 independent cohorts. UCB was significantly negatively correlated with eicosanoid- and oxidative stress-related metabolites. There were no significant associations between metabolites and allergic sensitization.ConclusionsWe identified a novel inverse, dose-dependent association between UCB and recurrent wheeze and childhood asthma. Inflammatory lipid mediators and oxidative stress byproducts inversely correlated with UCB, suggesting that UCB modulates pathways critical to the development of early-life recurrent wheeze and childhood asthma.
| S-EPMC8271087 | biostudies-literature