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 daily vitamin C would have improved pulmonary function tests (PFTs) and decreased wheezing compared to those randomized to placebo. Design, Setting, Participants, Intervention Randomized, double-blind trial in three sites in the Pacific Northwest. Between March 2007 and January 2011, 206 pregnant smokers were recruited and 179 randomized to vitamin C (500 mg/day) versus placebo (89 to vitamin C and 90 to placebo). 159 newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through one year of age and PFTs were done at one year of age. Main Outcomes and Measures The primary outcome was measurements of newborn pulmonary function (specifically the 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 one year of age and PFTs at one year of age. A subgroup of pregnant smokers and nonsmokers had genotyping performed. Results Newborns of women randomized to vitamin C (n= 76) had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345; adjusted 95% confidence interval [CI] for difference 0.011, 0.062; p =0.006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg; 95% CI 0.02, 0.20; p =0.012) than those randomized to placebo (n=83). Offspring of women randomized to vitamin C had significantly decreased wheezing through 1 year of age (15/70 [21%] vs 31/77 [40%]; relative risk 0.56, 95% CI 0.33, 0.95; p =0.03). There were no significant differences in the one year PFTs between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the alpha 5 nicotinic receptor (rs16969968) (p value for interaction = 0.0006). Conclusion and Relevance Supplemental vitamin C to pregnant smokers improved newborn PFTs 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
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. OBJECTIVETo 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 MEASURESThe 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 H 2 O/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.
Higher maternal intake of vitamin E during pregnancy may result in increased metabolite concentrations in the fetal circulation, suggesting increased maternal or fetal liver metabolism of vitamin E. This trial was registered at clinicaltrials.gov as NCT00632476.
Objective To compare pulmonary function in extremely low birth weight (ELBW) infants with bronchopulmonary dysplasia (BPD) studied at 34-36 weeks postmenstrual age (PMA) with a reference group of "healthy" infants born at 34-36 weeks. We hypothesized that ELBW infants have decreased functional residual capacity (FRC) and respiratory compliance (Crs). Study design Pulmonary function testing was performed at 34-36 weeks PMA in infants with BPD and within 96 h of age in infants delivered at 34-36 weeks. Results Twenty BPD patients and 20 healthy infants were studied. FRC (18.9 versus 26.2 mL/kg; adjusted 95% CI 5.0, 10.9; P < 0.001) and Crs (0.80 versus 1.29-mL/cm H 2 O/kg; 95% CI 0.31, 0.71; P < 0.001) were decreased in BPD patients. Respiratory resistance was increased in BPD patients. Conclusions ELBW infants with BPD have decreased pulmonary function compared to healthy infants delivered at 34-36 weeks. This suggests that infants with BPD have smaller lung volumes.
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