In a randomized clinical trial (RCT) published in JAMA, the investigators have providedvidence that vitamin C supplementation (500 mg daily during pregnancy) ameliorates theking during pregnancy on offspring lung function and subsequentdence of wheeze by 48% through 1 year of age. the investigators are currently completingd RCT of vitamin C supplementation in pregnant smokers with more robust measures ofulmonary outcomes. The purpose of this ECHO application is to combine these 2 focused,ventional cohorts to allow critical longitudinal follow-up of respiratory outcomes inhese children including the study of pulmonary function test (PFT) trajectories anddence of recurrent wheeze/asthma from infancy through early adolescence in offspring ofgnant smokers randomized to vitamin C versus placebo.

This will allow the investigators to study the duration of the protection vitamin C provideshe 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 withhe 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 ind blood and offspring cheek cells. Thus this study will also study thebetween the prevention of wheeze/asthma associated with maternal smoking duringgnancy and the prevention of epigenetic changes caused by maternal smoking duringgnancy. By linking the clinical outcomes of decreased wheeze/asthma and pulmonary functiong of smokers to epigenetic changes, this study has the potential to identify genesked to the effects of maternal smoking on lung development and the protective effects of vitamin C.