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. 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.

The Role of Nicotine in the Effects of Maternal Smoking during Pregnancy on Lung Development and Childhood Respiratory Disease. Implications for Dangers of E-Cigarettes

“…At birth and before any significant exposure to postnatal smoke, infants born to smokers show decreased pulmonary function tests (PFTs), with decreased respiratory flows and respiratory compliance and altered tidal breathing patterns (31)(32)(33). These changes lead to increased wheezing, hospitalization for respiratory infections, and increased childhood asthma (34).…”

Prenatal Intake of Vitamins and Allergic Outcomes in the Offspring: A Systematic Review and Meta-Analysis

“…These included trials (including total of 2456 children) were represented by 217 five original papers [13][14][15][16][17] and four grouped as their companion papers [18][19][20][21] . 218 Table 1 shows the characteristics of the included trials, their companion 219 papers and study population.…”

“…The types of vitamin supplementations included 221 were as vitamins C+E 13 , vitamin D 14,[16][17] and crushed vitamin C 15 . The 222 duration of intervention and follow-up in the included studies varied from 3.5-4 223 to 7.5 months and 12 to 36 months respectively.…”

“…The studies were of unselected pregnant 377 women 16 , women with a history of atopy 17 , pregnant women at risk of 378 developing pre-eclampsia 13 , different ethnic/race groups 14 and smoking 379 pregnant women 15 . Two studies were judged to have a high risk of bias due to 380 their performance bias [13][14] or high rate of loss to follow-up 13 .…”

The Natural History of COPD: Beyond Fletcher and Peto

“…The studies of Barker et al, which related birth weight to health outcomes in later life, established that being born small had a measureable effect on lung function and increased COPD risk 19 , although the anatomic basis for this effect remains undetermined. Subsequent studies have also established a role for prematurity 20 , maternal smoking 21,22 , and maternal nutrition 15,23 as early life determinants of lung function that could contribute to COPD risk. These risk factors may explain the correlation between poverty and observed mortality rates from COPD and other lung diseases, including COPD in non-smokers 24 .…”