Vitamin C Supplementation to Pregnant Smokers: Follow-up of 2 Randomized Trials Plus Changes in DNA Methylation

Completed

• Conditions: Pulmonary Function; Asthma; Wheezing; In Utero Nicotine
• Interventions: Other: No current intervention

• Registration Number: NCT03206710
• Lead Sponsor: Oregon Health and Science University

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.

Study Timeline

• Study Start: 2017-06-01
• Study First Submitted: 2017-06-27
• Study First Submitted QC: 2017-06-30
• Study First Posted: 2017-07-02
• Primary Completion: 2023-12-01
• Study Completion: 2024-12-31
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-20
• Last Update Posted: 2025-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 395

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
smokers who received Vitamin C	No current intervention	-
smokers who received placebo	No current intervention	-
control group non-smokers	No current intervention	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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

Trial Locations

Locations (2)

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States