Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial.
What this study found
Vitamin C improved newborn pulmonary function and reduced wheezing through age 1 year in infants of pregnant smokers. At birth, TPTEF:TE was higher with vitamin C than placebo (0.383 vs 0.345; adjusted 95% CI for difference, 0.011-0.062; P = .006), Crs/kg was higher (1.32 vs 1.20 mL/cm H2O/kg; 95% CI, 0.02-0.20; P = .01), and total Crs was higher (4.16 vs 3.92; adjusted mean difference 0.32, 0.02 to 0.62; P = .04). Wheezing through 1 year occurred in 15/70 (21%) vs 31/77 (40%) infants, with adjusted relative risk 0.56 (95% CI, 0.33-0.95; P = .03). No serious adverse events were related to…
- Study & population
- Randomized clinical trial in pregnant women who smoked during pregnancy at 3 clinical sites in the Portland, Oregon, and Vancouver, Washington areas.
- Intervention
- Pregnant smokers were assigned to oral vitamin C 500 mg/day, prepared as crushed ascorbic acid in a gel capsule, taken once daily from randomization until delivery.
- Key limitation
- The active arm was modest in size, and follow-up was incomplete for later infant assessments, with only 49 vitamin C-exposed infants contributing to 1-year pulmonary function testing.
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Open PDFOriginal 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.