The primary outcome of this longitudinal follow-up study is the comparison of airway function tests (specifically the forced expiratory flow between 25%and 75% of expired volume \[FEF25-75\]) measured yearly through 10 years of age by forced expiratory maneuvers with spirometry between the children of the pregnant smokers randomized to vitamin C (500 mg/day) versus placebo during pregnancy. The occurrence of wheeze obtained with quarterly standardized respiratory questionnaires will also be compared between the two groups of children. This is a follow-up of the original "Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function" (VCSIP) trial.
The secondary outcomes are:
1. A single low dose high-resolution computed tomography (HRCT) image of the lungs (acquired during inspiration) will be done at 10 years of age in offspring of pregnant smokers who were randomized to vitamin C (500 mg/day) versus placebo during pregnancy. Image analysis will be performed by Dr. Miranda Kirby's Quantitative Image Analysis in Medicine laboratory at Ryerson University in Toronto, ON using certified pulmonary image analysis software. The airway lumen cross sectional areas to at least the fifth generation of airways will be compared between the two groups of children. The number of airways and the lumen, wall, and total cross sectional areas and the segment lengths will also be quantified.
2. A secondary aim is to quantify the differences in DNA methylation between the two groups and measure the correlation between the differences in DNA methylation and respiratory outcomes.
