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.
Maternal smoking during pregnancy is the largest preventable cause of childhood respiratory illness, and children whose mothers smoked during pregnancy show lifetime decreases in pulmonary function and increased respiratory illnesses and asthma. Sadly, more than 50% of smokers who become pregnant continue to smoke and approximately 20% of expenditures for childhood respiratory illness are caused by maternal smoking amounting to over $1 billion annually in current health care dollars. The findings from this project will support the addition of daily vitamin C supplementation to pregnant smokers, a simple, safe, and inexpensive adjunct to current smoking cessation counseling that would significantly decrease the impact of smoking during pregnancy on child respiratory health both in the United States and world-wide.
| McEvoy, Cindy T; Milner, Kristin F; Scherman, Ashley J et al. (2017) 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 Contemp Clin Trials 58:66-77 |
