Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in Their Newborn Infants

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 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

Amelioration strategies fail to prevent tobacco smoke effects on neurodifferentiation: Nicotinic receptor blockade, antioxidants, methyl donors

“…In any case, though, our results for MDA and for antioxidant amelioration are surprising in light of the clear-cut oxidative stress experienced in vivo with maternal smoking (Aycicek and Ipek 2008; Fayol et al 2005; Orhon et al 2009; Rossner et al 2009), and the protection by antioxidants against fetal lung damage caused by maternal tobacco exposure (McEvoy et al 2014; Proskocil et al 2005). In that regard, TSE does not include volatile tobacco-smoke chemicals like HCN and CO that interfere with fetal oxygen delivery and utilization (Carmines and Rajendran 2008; Pettigrew et al 1977; Robkin 1997), nor does an in vitro model incorporate hypoxic stress resulting from uteroplacental vasoconstriction and reduced placental oxygen transfer, which are major contributors to fetal hypoxia in vivo (Albuquerque et al 2004; Bush et al 2000; Clark and Irion 1992).…”

“…This becomes crucial in attempting to offset the adverse effects of maternal smoking through interventions targeting putative mechanisms individually and without regard for heterogeneity of responses in different tissues. For example, recent studies have recommended maternal Vitamin C supplementation to protect lung development and respiratory function in offspring of smokers (McEvoy et al 2014; Proskocil et al 2005). However, this beneficial result is likely to be offset by adverse effects on brain development, both from augmentation of nicotine levels in the fetus (Slotkin et al 2005) and from interference with natural oxidative signals involved in neurodifferentiation, as seen here.…”

“…Smoking causes fetal oxidative stress (Aycicek and Ipek 2008; Fayol et al 2005; Gitto et al 2002; Orhon et al 2009) and consequently, attempts have been made to ameliorate the adverse effects through vitamin C supplementation. In vivo, Vitamin C prevents tobacco smoke-induced lung damage in the fetus and improves neonatal respiratory outcome (McEvoy et al 2014; Proskocil et al 2005). While Vitamin C also prevents oxidative damage to the developing brain (Slotkin et al 2011), it increases fetal nicotine levels, enhancing damage attributable to inappropriate nicotinic receptor stimulation (Slotkin et al 2005).…”

The association between environmental tobacco smoke exposure and childhood respiratory disease: a review

“…A randomized double-blind trial showed that supplemental vitamin C improved newborn pulmonary function and decreased wheezing in the first year of life in infants of mothers who smoked [117]. While prevention or avoidance of smoking should be the optimal strategy in pregnancy and postnatally, this intervention needs to be further studied in pregnant mothers who are unable to refrain from smoking in pregnancy.…”

Diet and asthma

“…In the only recent study of preventive effects of vitamin C against the development of asthma, vitamin C supplementation (500 mg/d) in 179 pregnant smokers led to improved pulmonary function and decreased risk of wheeze in their newborns, up to age 1 year (18). Given that most wheezing in early life is transient, it is unclear whether these findings are due to anti-viral effects or truly protective effects of vitamin C against asthma.…”