Clinical trial NCT03206710: Vitamin C Supplementation to Pregnant Smokers: Follow-up of 2 Randomized Trials Plus Changes in DNA Methylation
Official title: Maternal Vitamin C Supplementation to Decrease Effects of Smoking During Pregnancy on Infant Lung Function and Health: Follow-up of 2 Randomized Trials and Association With Changes in DNA Methylation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Wheezing
In Utero Nicotine
Pulmonary Function
Keywords: vitamin C
ascorbic acid
wheeze
nicotine
smoke exposure
long term follow up
pulmonary function testing
forced expiratory flows
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Indiana University
name: National Institutes of Health (NIH)
First posted: 2017-07-02
Enrollment: 395
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study is a follow-up of women and their offspring who previously participated in NCT00632476 and/or NCT01723696.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Improved pulmonary function
timeFrame: through 15 years of age
measure: Decreased recurrent wheeze/asthma
timeFrame: through 15 years of age
Secondary outcomes:
measure: Decreased incidence of recurrent wheeze/asthma
timeFrame: through 15 years of age
measure: Epigenetic changes
timeFrame: through 15 years of age
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
Study officials:
References:
citation: McEvoy CT, Schilling D, Clay N, Jackson K, Go MD, Spitale P, Bunten C, Leiva M, Gonzales D, Hollister-Smith J, Durand M, Frei B, Buist AS, Peters D, Morris CD, Spindel ER. Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial. JAMA. 2014 May;311(20):2074-82. doi: 10.1001/jama.2014.5217.