Oral Vitamin C (500 mg/d) to pregnant smokers improves infant airway function at 3 months (VCSIP) a randomized trial

Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the a5 nicotinic acetylcholine receptor. Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13–23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. Measurements and Main Results: The primary outcome was FEF₇₅ at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF₅₀ and FEF₂₅–₇₅ obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (n = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (n = 109) as measured by FEF₇₅ (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, 23.33 to 35.64; P = 0.10), FEF₅₀ (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10–61.30; P = 0.02), and FEF₂₅–₇₅ (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92–55.34; P = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the a5 nicotinic acetylcholine receptor (rs16969968). Conclusions: Although the primary outcome of FEF₇₅ was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF₅₀ and FEF₂₅–₇₅ were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF₅₀ and FEF₂₅–₇₅) at 3 months of age in infants after vitamin C supplementation to pregnant smokers.