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

JAMA. 2014 May;311(20):2074-82. doi: 10.1001/jama.2014.5217.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ascorbic Acid / therapeutic use*
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Newborn, Diseases / prevention & control
  • Lung / physiopathology*
  • Pregnancy
  • Prenatal Care
  • Prenatal Exposure Delayed Effects / prevention & control
  • Respiratory Function Tests
  • Respiratory Sounds* / etiology
  • Respiratory Sounds* / physiopathology
  • Respiratory Tract Diseases / prevention & control
  • Smoking / adverse effects*
  • Vitamins / therapeutic use*
  • Young Adult

Substances

  • Vitamins
  • Ascorbic Acid

Associated data

  • ClinicalTrials.gov/NCT00632476