Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal Smoking in Pregnancy

Rationale: Infants whose mothers smoked during pregnancy demonstrate lifelong decreases in pulmonary function. DNA methylation changes associated with maternal smoking during pregnancy have been described in placenta and cord blood at delivery, in fetal lung, and in buccal epithelium and blood during childhood. We demonstrated in a randomized clinical trial (ClinicalTrials.gov identifier, NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the impact of maternal smoking on offspring pulmonary function and decrease the incidence of wheeze at 1 year of age.Objectives: To determine whether vitamin C supplementation reduces changes in offspring methylation in response to maternal smoking and whether methylation at specific CpGs is also associated with respiratory outcomes.Methods: Targeted bisulfite sequencing was performed with a subset of placentas, cord blood samples, and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood d...