Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP): Rationale, design, and methods of a randomized, controlled trial of vitamin C supplementation in pregnancy for the primary prevention of effects of in utero tobacco smoke exposure on infant lung function and respiratory health

Abstract

Despite strong anti-smoking efforts, at least 12% of American women cannot quit smoking when pregnant resulting in more than 450,000 smoke-exposed infants born yearly. Smoking during pregnancy is the largest preventable cause of childhood respiratory illness including wheezing and asthma. Recent studies have shown a protective effect of vitamin C supplementation on the lung function of offspring exposed to in utero smoke in a non-human primate model and an initial human trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to evaluate pulmonary function at 3 months of age in infants delivered to pregnant smokers randomized to 500 mg/day of vitamin C versus placebo during pregnancy. Secondary aims evaluate the incidence of wheezing through 12 months and pulmonary function testing at 12 months of age. Women are randomized between 13–23 weeks gestation from clinical sites in Portland, Oregon at Oregon Health & Science University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from randomization to delivery. Monthly contact with participants and monitoring of medical records is performed to document medication adherence, changes in smoking and medical history, and adverse events. Pulmonary function testing of offspring occurs at 3 and 12 months of age and incidence of wheezing and respiratory illness through 12 months is captured via at least quarterly questionnaires. Ancillary studies are investigating the impact of vitamin C on placental blood flow and DNA methylation.

Long‐term pulmonary vascular consequences of perinatal insults

“…However, early success in modulating alveolar development through maternal vitamin C supplementation in infants exposed to in utero tobacco smoke was recently demonstrated (McEvoy et al . ), and suggests at least the future potential to favourably modulate vascular development.…”

Association between active tobacco use during pregnancy and infant respiratory health: a systematic review and meta-analysis

“…Our review highlights the importance of alleviating these harmful effects by promoting safe and effective tobacco use cessation interventions in pregnancy. Furthermore, the development of innovative interventions should be promoted in parallel, such as treatment of pregnant women who continue to smoke tobacco with high-dose vitamin C to reduce tobacco smoke-induced oxidative stress and improve infant lung function, 62 although this approach is yet to be explored for ST use.…”

The impact of tobacco chemicals and nicotine on placental development

“…In a multicenter, randomized, double-blind, placebocontrolled trial, daily Vitamin C supplementation or placebo was given to pregnant women who smoked tobacco cigarettes. 67 Vitamin C supplementation was found to be associated with improved pulmonary function in newborns within 72 hours of delivery as well as at 3 months of age, compared with those who received placebo. 68 There are many published reviews which prove a far more comprehensive overview on which epigenetic modifications are observed in the placenta, cord blood, and even among exposed offspring (buccal cells) following maternal tobacco smoke in utero.…”