Asthma, In Utero Nicotine, Pulmonary Function, Wheezing
Conditions
Keywords
vitamin C, ascorbic acid, wheeze, nicotine, smoke exposure, long term follow up, pulmonary function testing, forced expiratory flows
Brief summary
In a randomized clinical trial (RCT) published in JAMA, the investigators have provided evidence that vitamin C supplementation (500 mg daily during pregnancy) ameliorates the effects of maternal smoking during pregnancy on offspring lung function and subsequent incidence of wheeze by 48% through 1 year of age. The investigators are currently completing a second RCT of vitamin C supplementation in pregnant smokers with more robust measures of pulmonary outcomes. The purpose of this ECHO application is to combine these 2 focused, interventional cohorts to allow critical longitudinal follow-up of respiratory outcomes in these children including the study of pulmonary function test (PFT) trajectories and incidence of recurrent wheeze/asthma from infancy through early adolescence in offspring of pregnant smokers randomized to vitamin C versus placebo.
Detailed description
In a randomized clinical trial (RCT) published in JAMA, the investigators have provided evidence that vitamin C supplementation (500 mg daily during pregnancy) ameliorates the effects of maternal smoking during pregnancy on offspring lung function and subsequent incidence of wheeze by 48% through 1 year of age. the investigators are currently completing a second RCT of vitamin C supplementation in pregnant smokers with more robust measures of pulmonary outcomes. The purpose of this ECHO application is to combine these 2 focused, interventional cohorts to allow critical longitudinal follow-up of respiratory outcomes in these children including the study of pulmonary function test (PFT) trajectories and incidence of recurrent wheeze/asthma from infancy through early adolescence in offspring of pregnant smokers randomized to vitamin C versus placebo. This will allow the investigators to study the duration of the protection vitamin C provides in the face of in-utero smoke, the relationship between PFTs and the development of recurrent wheeze and/or asthma. In addition we have preliminary data suggesting that, in parallel with the effects of vitamin C on the reduction of pulmonary harm, the supplementary vitamin C blocked the majority of significant changes in DNA methylation induced by maternal smoking in placentas, cord blood and offspring cheek cells. Thus this study will also study the association between the prevention of wheeze/asthma associated with maternal smoking during pregnancy and the prevention of epigenetic changes caused by maternal smoking during pregnancy. By linking the clinical outcomes of decreased wheeze/asthma and pulmonary function in offspring of smokers to epigenetic changes, this study has the potential to identify genes linked to the effects of maternal smoking on lung development and the protective effects of vitamin C.
Interventions
OTHERNo current intervention
This is a follow-up of two randomized trials. No active intervention is being given in the follow-up
Sponsors
Indiana University
National Institutes of Health (NIH)
Oregon Health and Science University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Months to 11 Years
Healthy volunteers
No
Inclusion criteria
* Women and their offspring randomized to vitamin C versus placebo during pregnancy in VCSIP1 or VCSIP2 as well as pregnant nonsmokers and their offspring enrolled as the reference group in VCSIP 1 or VCSIP2
Exclusion criteria
* Patients specifically withdrawing consent from VCSIP1 or VCSIP2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improved pulmonary function | through 15 years of age | The first primary aim of this study is to demonstrate improved pulmonary function trajectories as measured with forced expiratory flows through 15 years of age in the offspring of pregnant smokers randomized to vitamin C (500 mg/day) versus placebo. |
| Decreased recurrent wheeze/asthma | through 15 years of age | The second primary aim of this study is to demonstrate a decreased incidence of recurrent wheeze/ asthma through 15 years of age in the offspring of pregnant smokers randomized to vitamin C (500 mg/day) versus placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Decreased incidence of recurrent wheeze/asthma | through 15 years of age | A secondary aim of this study is to demonstrate a decreased incidence of recurrent wheeze/asthma through 15 years of age in offspring of pregnant smokers randomized to vitamin C (500 mg/day) versus placebo |
| Epigenetic changes | through 15 years of age | An additional secondary aim of the study is the analysis of epigenetic changes caused by maternal smoking and reversed by vitamin C at birth. DNA methylation will be measured in biologic samples and then followed longitudinally through ages 15. |
Countries
United States
Outcome results
None listed