Project Summary/Abstract The beneficial infant outcomes of maternal vitamin C supplementation (500 mg/day) in pregnant smokers is supported by our robust pre-trial evidence in animal models and convincing human pilot data. This evidence served as the basis for our current multi-center double blind randomized trial ?Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function? (VCSIP; NCT01723696). Recruitment is completed as scheduled with 252 pregnant smokers randomized to vitamin C or placebo. VCSIP's primary and secondary outcomes, respectively, are pulmonary function testing (PFT) of infants at 3 months of age, and PFTs and the incidence of wheeze at 12 months of age. This application is a renewal for the VCSIP trial to continue following mothers and their offspring through 5 years of age. Time is critical, as the study population is predominantly under-resourced making rapport crucial to cohort retention, which requires personnel and time. The aim of this renewal proposal is to determine whether prenatal supplementation with vitamin C can improve pulmonary function and decrease recurrent wheeze through 5 years of age in the offspring of smokers. Our hypothesis is that supplemental vitamin C in pregnant smokers will significantly improve their children's pulmonary function and decrease recurrent wheeze. This is a logical continuation for the VCSIP trial as transient versus recurrent wheeze are not clinical distinguishable until 5 years of age. Following infants from the VCSIP until age 5 years: will differentiate patients with transient versus recurrent wheeze (a more likely predictor of asthma); will determine if early life protective effects of vitamin C are sustained to this older age; and will provide structure for continued biologic samples from the children for future mechanistic studies of vitamin C action. All investigators, clinical staff and participants will remain blinded to treatment allocation. We are currently completing the primary outcome, and based on the number of randomized smokers we will have a sufficient number of pulmonary function measurements at 3 months of age in the infants of randomized smokers to meet the predetermined sample size for this analysis. The first infants of VCSIP turned 1 year old in May 2014; therefore this proposal is being submitted now, prior to the analysis of the primary outcome of the VCSIP study, to minimize gaps in the follow-up of this valuable cohort. The children will be followed with quarterly respiratory questionnaires and yearly visits, collecting the following samples: maternal and child hair for nicotine; child buccal swabs; maternal exhaled carbon monoxide; pulmonary function tests at 3, 4,and 5 years of age. This competitive renewal will allow us to study the longer term outcome of our intervention with vitamin C with regards to childhood pulmonary function and the occurrence of recurrent wheeze through 5 years of age. It will also allow us to follow this unique, extensively phenotyped cohort of children born to pregnant smokers to 5 years of age to address important scientific questions related to maternal smoking and childhood respiratory health/wheeze/asthma.