Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial.

JAMA

May 2014

DOI: 10.1001/jama.2014.5217

Citations:188

Influential Citations:6

Interventional (Human) Studies

Enhanced Details

Methods

Design: randomized, double-blind, placebo-controlled trial at three sites in the Pacific Northwest. Participants: pregnant smokers aged ≥15 years with singleton gestation, smoking ≥1 cigarette/day, randomized at ≤22 weeks gestation; a reference group of pregnant nonsmokers was enrolled. 179 women were randomized to vitamin C (n=89) or placebo (n=90); newborn PFTs were performed in 159 infants (76 vitamin C; 83 placebo). Wheezing and PFTs through 1 year were assessed.

Intervention

Vitamin C 500 mg/day, orally as a daily capsule, from randomization until delivery.

Results

Newborns of mothers randomized to vitamin C showed improved pulmonary function at birth (TPTEF:TE 0.383 vs 0.345; Crs/kg 1.32 vs 1.20 mL/cm H2O/kg; p=0.006 and p=0.012 respectively) and a lower incidence of wheezing through 1 year (21% vs 40%; RR 0.56; p=0.03). No significant differences in 1-year PFTs. The vitamin C effect interacted with maternal rs16969968 genotype; homozygous risk allele carriers had the largest TPTEF:TE decrease, which was not present with vitamin C; among carriers, wheezing through 1 year was reduced with vitamin C (14% vs 48%; p=0.02). Adverse events were not related to the intervention. Conclusion: Supplemental vitamin C during pregnancy for smokers improved newborn PFTs and reduced wheezing through age 1, suggesting it may be a simple, inexpensive approach to lessen smoking-related respiratory effects in offspring; further study is warranted.

Limitations

Differential loss to follow-up (7.7% in placebo vs 14.6% in vitamin C) may bias results; not all infants completed 1-year PFTs due to the need for sedation (only a subset were tested at 1 year); genotype interaction analyses relied on small subgroups; generalizability may be limited to populations similar to the study sample.

Abstract

IMPORTANCE Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00632476. show less