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


METHODS
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.


METHODS
Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90).


METHODS
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
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00632476.
Oregon Health & Science University, Portland.
Cindy T
CT
McEvoy
Oregon Health & Science University, Portland.
Diane
D
Schilling
Oregon Health & Science University, Portland.
Nakia
N
Clay
PeaceHealth Southwest Medical Center, Vancouver, Washington.
Keith
K
Jackson
Oregon Health & Science University, Portland.
Mitzi D
MD
Go
PeaceHealth Southwest Medical Center, Vancouver, Washington.
Patricia
P
Spitale
Vancouver Clinic, Vancouver, Washington.
Carol
C
Bunten
Providence Maternal Care Clinic, Portland, Oregon.
Maria
M
Leiva
Oregon Health & Science University, Portland.
David
D
Gonzales
Oregon National Primate Research Center, Beaverton.
Julie
J
Hollister-Smith
University of Southern California, Keck School of Medicine, LAC-USC Medical Center, Los Angeles, California.
Manuel
M
Durand
Linus Pauling Institute, Oregon State University, Corvallis.
Balz
B
Frei
Oregon Health & Science University, Portland.
A Sonia
AS
Buist
Oregon Health & Science University, Portland.
Dawn
D
Peters
Oregon Health & Science University, Portland.
Cynthia D
CD
Morris
Oregon National Primate Research Center, Beaverton.
Eliot R
ER
Spindel
D000328:Adult; D001205:Ascorbic Acid / Q000627:therapeutic use*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000517:prevention & control; D008168:Lung / Q000503:physiopathology*; D011247:Pregnancy; D011295:Prenatal Care; D011297:Prenatal Exposure Delayed Effects / Q000517:prevention & control; D012129:Respiratory Function Tests; D012135:Respiratory Sounds / Q000209:etiology / Q000503:physiopathology; D012140:Respiratory Tract Diseases / Q000517:prevention & control; D012907:Smoking / Q000009:adverse effects*; D014815:Vitamins / Q000627:therapeutic use*; D055815:Young Adult
D014815:Vitamins; D001205:Ascorbic Acid