Oral Vitamin C (500 mg/d) to Pregnant Smokers Improves Infant Airway Function at 3 Months (VCSIP). A Randomized Trial

Abstract

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 FEF 75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF 50 and FEF 25-75 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 FEF 75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, 23.33 to 35.64; P = 0.10), FEF 50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF 25-75 (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 FEF 75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF 50 and FEF 25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF 50 and FEF 25-75 ) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT 01723696).

Pulmonary function in extremely low birth weight infants with bronchopulmonary dysplasia before hospital discharge

“…There are a number of longitudinal pulmonary function studies [ 17 – 19 ] demonstrating that individuals follow along a pulmonary function percentile that is established early in life, therefore emphasizing the importance of quantification of early life PFTs. There are several factors that can affect lung development and influence an individual’s placement on the PFT curve including in-utero factors such as in-utero smoke [ 20 , 21 ] or intrauterine growth restriction [ 22 ], but preterm delivery is the most common cause of altered lung development [ 22 , 23 ]. The application of PFTs has been important in quantifying the physiologic effects of several successful neonatal interventions such as antenatal steroids [ 24 ] and postnatal surfactant [ 25 ].…”

Recent advances in understanding and management of bronchopulmonary dysplasia

“…To date, among the many tried interventions, postnatal use of vitamin A 52 , 53 , caffeine 54 , and corticosteroids 55 are the only interventions that have led to a decrease in the rate of BPD. The use of vitamin C in pregnant smokers has been shown to improve pulmonary function tests in newborns at birth and 3 months of age with decreased wheezing up to 1 year of age 56 , 57 . Since smoking is a significant risk factor for BPD, use of vitamin C in this population may help to mitigate the effects of smoking on the developing lung; however, no clinical trials have evaluated this potential therapy as yet specifically to decrease BPD.…”

The impact of tobacco chemicals and nicotine on placental development

“…67 Vitamin C supplementation was found to be associated with improved pulmonary function in newborns within 72 hours of delivery as well as at 3 months of age, compared with those who received placebo. 68 There are many published reviews which prove a far more comprehensive overview on which epigenetic modifications are observed in the placenta, cord blood, and even among exposed offspring (buccal cells) following maternal tobacco smoke in utero. 48,55,72 A recent systematic review highlights 11 manuscripts reflecting changes in DNA methylation in the placenta with MTSE.…”