title: The Vitamin D Antenatal Asthma Reduction Trial (VDAART): rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. Lack of a relation between serum 25-hydroxyvitamin D concentrations and asthma in adolescents. Maternal vitamin D status during pregnancy and child outcomes Effect of Vitamin D Supplementation on Moderate to Severe Bronchial Asthma Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial. Serum micronutrient concentrations and childhood asthma: the PIAMA birth cohort study.
abstract: There is intense interest in the role of vitamin D in the development of asthma and allergies . However , studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies . To address this uncertainty , the Vitamin D Antenatal Asthma Reduction Trial ( VDAART ) was developed . VDAART is a r and omized , double-blind , placebo-controlled trial of vitamin D supplementation  in pregnant women to determine whether prenatal supplementation can prevent the development of  asthma and allergies in women 's offspring . A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications , such as preeclampsia , preterm birth , and gestational diabetes .  Women were r and omized to the treatment arm of 4000IU/day of vitamin D3 plus a daily multivitamin that contained 400IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400IU daily of vitamin D3 . Women who were between the gestational ages of 10 and 18 weeks were r and omized from three clinical centers across the United States - Boston Medical Center , Washington University in St. Louis , and Kaiser Permanente Southern California Region ( San Diego , CA ) . Supplementation took place throughout pregnancy . Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events . Offspring are being evaluated quarterly through question naires and yearly during in-person visits until the 3rd birthday of the child . Ancillary studies will investigate neonatal T-regulatory cell function , maternal vaginal flora , and maternal and child intestinal flora BACKGROUND Asthma exacerbations , most often caused by respiratory tract infections , are the leading causes of asthma morbidity and comprise a significant proportion of asthma-related costs . Vitamin D status might play a role in preventing asthma exacerbations . OBJECTIVES We sought to assess the relationship between serum vitamin D levels and subsequent severe asthma exacerbations . METHODS We measured  25-hydroxyvitamin D levels in sera collected from 1024 children with mild-to-moderate persistent asthma at the time of enrollment in a multicenter clinical trial of children r and omized to receive budesonide , nedocromil , or placebo ( as-needed beta-agonists ) : the Childhood Asthma Management Program . Using multivariable modeling , we examined the relationship between baseline vitamin D levels and the odds of any hospitalization or emergency department visit over the 4 years of the trial . RESULTS Thirty-five percent of all subjects were  vitamin D insufficient , as defined by a level of 30 ng/mL or less 25-hydroxyvitamin D. Mean vitamin D levels were lowest in African American subjects and highest in white subjects . After adjusting for age , sex , body mass index , income , and treatment group , insufficient vitamin D status was associated with a higher odds of any hospitalization or emergency department visit ( odds ratio , 1.5 ; 95 % CI , 1.1 - 1.9 ; P = .01 ) . CONCLUSION Vitamin D insufficiency is common in this population of North American children with mild-to-moderate persistent asthma and is associated with higher odds of severe exacerbation over a 4-year period BACKGROUND Decreased 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with an increased prevalence and severity of asthma and a lower response to inhaled corticosteroids . OBJECTIVE The objective was to determine the association between serum 25(OH)D concentrations and asthma prevalence , severity , and response to asthma treatment . DESIGN Secondary analyses were conducted in 2 sample s of adolescents 12 - 20 y of age : 1 ) NHANES 2001 - 2006 ( n = 6487 ) , a cross-sectional nationally representative sample of the US population , and 2 ) a cohort of inner-city adolescents with asthma managed prospect ively for 46 wk with guidelines -based therapy in the Asthma Control Evaluation ( ACE ; n = 226 ) trial .  RESULTS Mean ( ±SD ) serum 25(OH)D concentrations in the NHANES and ACE sample s were lower in African Americans than in non-African Americans ( NHANES : 14.9 ± 6.5 compared with 23.0 ± 8.4 ng/mL , P < 0.0001 ; ACE : 11.2 ± 6.9 compared with 15.8 ± 7.1 ng/mL , P < 0.0001 ) . In the NHANES sample , mean concentrations did not differ between participants without and with asthma ( African Americans : 14.9 ± 6.4 compared with 15.0 ± 6.6 ng/mL , respectively , P = 0.87 ; non-African Americans : 23.0 ± 8.5 compared with 23.6 ± 8.2 ng/mL , respectively , P = 0.16 ) . In the ACE models that used either a predefined cutoff ( < 20 ng/mL ) or linear regression , 25(OH)D concentrations showed either no relation or minor contradictory correlations with indicators of asthma severity , treatment requirements , spirometry , or atopy/inflammation . CONCLUSION In 2 sample s of adolescents , overall serum 25(OH)D concentrations were low and were not consistently associated with the presence of asthma , multiple asthma characteristics , asthma morbidity , or response to treatment . The ACE trial was registered at clinical trials.gov as NCT0011441 Objective : To investigate whether exposure to high maternal concentrations of 25(OH)-vitamin D in pregnancy poses any risk to the child . Design : Prospect i ve study . Setting : Princess Anne Maternity Hospital , Southampton , UK.Subjects : A group of 596 pregnant women were recruited . A total of 466 ( 78 % ) children were examined at birth , 440 ( 74 % ) at age 9 months and 178 ( 30 % ) at age 9 years . Methods :  Maternal 25 (OH)-vitamin D concentrations  were measured in late pregnancy . Anthropometry of the child was recorded at birth , 9 months and 9 years . At 9 months , atopic eczema was assessed . At 9 years , children had an echocardiogram and a dual energy x-ray absorptiometry scan , blood pressure , arterial compliance and carotid intima-media thickness were measured and intelligence and psychological function assessed . Results : There were no associations between maternal 25(OH)-vitamin D concentrations and the child 's body size or measures of the child 's intelligence , psychological health or cardiovascular system . Children whose mothers had a 25(OH)-vitamin D concentration in pregnancy > 75 nmol/l had an increased risk of eczema on examination at 9 months ( OR 3.26 , 95 % CI 1.15–9.29 , P=0.025 ) and asthma at age 9 years ( OR 5.40 , 95 % CI , 1.09–26.65 , P=0.038 ) compared to children whose mothers had a concentration of < 30 nmol/l . Conclusion : Exposure to maternal concentrations of 25(OH)-vitamin D in pregnancy in excess of 75 nmol/l does not appear to influence the child 's intelligence , psychological health or cardiovascular system ; there could be an increased risk of atopic disorders , but this needs confirmation in other studies .Sponsorship : The study was supported by the Medical Research Council and WellChild ( previously known as Children Nationwide ) Objective To define the therapeutic role of vitamin D in children with moderate to severe bronchial asthma as an adjunct to st and ard treatment . Methods Hundred asthmatic children of either sex , attending the respiratory and asthma clinic were enroled in the study . Diagnosis was made on the basis of history and clinical examination . R and omization was done using sealed opaque envelop method . In addition to the treatment as per GINA guidelines , one group received oral vitamin D3 ( Cholecalciferol ) 60,000 IU per month for 6 mo and the other group received placebo powder in the form of glucose sachet with a double blinded design . Monthly follow up of every patient was done and during every visit change in severity , level of control , Peak expiratory flow rate ( PEFR ) , steroid dosage , number of exacerbations and number of emergency visits were assessed . Results Monthly doses of 60,000 IU vitamin D significantly reduced the number of exacerbations as compared to placebo ( p = 0.011 ) . PEFR significantly increased in the treatment group ( p = 0.000 ) . Monthly doses of vitamin D significantly reduced the requirement of steroids ( p = 0.013 ) and emergency visits ( p = 0.015 ) . Control of asthma was achieved earlier in patients who received monthly vitamin D. Vitamin D significantly reduced the level of severity of asthma patients over 6 mo of treatment ( p = 0.016 ) . Conclusions Vitamin D has a definite role in the management of moderate to severe persistent bronchial asthma as an adjunct to st and ard treatment IMPORTANCE In asthma and other diseases , vitamin D insufficiency is associated with adverse outcomes . It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency . OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS The VIDA ( Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma ) r and omized , double-blind , parallel , placebo-controlled trial study ing adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart , Lung , and Blood Institute 's AsthmaNet network , with enrollment starting in April 2011 and follow-up complete by January 2014 . After a run-in period that included treatment with an inhaled corticosteroid , 408 patients were r and omized . INTERVENTIONS Oral vitamin D3 ( 100,000 IU once , then 4000 IU/d for 28 weeks ; n = 201 ) or placebo ( n = 207 ) was added to inhaled ciclesonide ( 320 µg/d ) . If asthma control was achieved after 12 weeks , ciclesonide was tapered to 160 µg/d for 8 weeks , then to 80 µg/d for 8 weeks if asthma control was maintained . MAIN OUTCOMES AND MEASURES The primary outcome was time to first asthma treatment failure ( a composite outcome of decline in lung function and increases in use of β-agonists , systemic corticosteroids , and health care ) . RESULTS Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks ( 28 % [ 95 % CI , 21%-34 % ] with vitamin D3 vs 29 % [ 95 % CI , 23%-35 % ] with placebo ; adjusted hazard ratio , 0.9 [ 95 % CI , 0.6 - 1.3 ] ) . Of 14 prespecified secondary outcomes , 9 were analyzed , including asthma exacerbation ; of those 9 , the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control ( 111.3 µg/d [ 95 % CI , 102.2 - 120.4 µg/d ] in the vitamin D3 group vs 126.2 µg/d [ 95 % CI , 117.2 - 135.3 µg/d ] in the placebo group ; difference of 14.9 µg/d [ 95 % CI , 2.1 - 27.7 µg/d ] ) . CONCLUSIONS AND RELEVANCE Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency . These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01248065 BACKGROUND Research suggests an influence of micronutrients on  childhood asthma .  So far , evidence mainly originates from cross-sectional studies using nutrient intake data , which is not an accurate measure of nutrient status . This study aim ed to investigate the cross-sectional and prospect i ve associations between serum concentrations of magnesium , vitamin D , selenium , and zinc and prevalence of ( severe ) asthma , atopy , and bronchial hyperresponsiveness ( BHR ) in childhood . METHODS In the Prevention and Incidence of Asthma and Mite Allergy birth cohort study , serum nutrient concentrations were available for a 4-yr-old subgroup ( n = 372 ) and for a different 8-yr-old subgroup ( n = 328 ) . Yearly question naires inquired about asthma prevalence until 8 yr of age . Allergic sensitization was measured at 4 and 8 yr of age ; BHR was measured at 8 yr of age . Data were analyzed with logistic regression and generalized estimating equations models . RESULTS There was a consistent ( non-significant ) inverse association between serum magnesium concentrations and asthma prevalence . Serum vitamin D concentrations measured at age 4 were inversely associated with asthma at ages 4 - 8 [ e.g. , cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma : odds ratio ( OR ) : 0.49 , 95 % confidence interval ( CI ) : 0.25 - 0.95 ] , whereas vitamin D measured at age 8 was positively associated with asthma at age 8 ( e.g. , cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma : OR : 2.14 , 95 % CI : 0.67 - 6.82 ) . CONCLUSIONS Our study contributes to the evidence that children with higher serum magnesium concentrations are less likely to have asthma . The associations between serum vitamin D concentrations and asthma were age-dependent
target: Collectively , the evidence suggests that higher serum levels of 25(OH)D are associated with a reduced risk of asthma exacerbations , but there was little evidence to suggest an association with asthma incidence , prevalence or severity .
background: Asthma is a major public health issue .
  The co-occurrence of the high prevalence of asthma and vitamin D deficiency documented globally in recent decades has prompted several investigations into a possible association between the two conditions .
  The objective of this paper was to synthesize the evidence from studies that have measured the association between serum vitamin D  and asthma incidence , prevalence , severity and exacerbations .