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Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in Their Newborn Infants: A Randomized Clinical Trial
Open accessAbstract
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.
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“A recent randomized placebo-controlled study found that the offspring of smoking mothers who received vitamin C during in utero life had better airflow and less wheezing through the first year of life compared with those of untreated mothers who smoked during pregnancy.43”
From Impact of Tobacco Smoke and Nicotine Exposure on Lung Development (2016) · cites this paper as [43]
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Citations
Cites
Nicotine Chemistry, Metabolism, Kinetics and Biomarkers
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Meta-analysis and imputation refines the association of 15q25 with smoking quantity
The Wellcome Trust Case Control Consortium, Liu, J. Z., Tozzi, F., Waterworth, D. M., Pillai, S. G., Muglia, P., Middleton, L., Berrettini, W., Knouff, C. W., Yuan, X., et al. (2010) · Nature Genetics · doi:10.1038/ng.572 · Cited by 614
Cord-Blood 25-Hydroxyvitamin D Levels and Risk of Respiratory Infection, Wheezing, and Asthma
Camargo, C. A., Ingham, T. R., Wickens, K. L., Thadhani, R., Silvers, K. M., Epton, M., Town, G. I., Pattemore, P., Espinola, J. A., Crane, J., et al. (2010) · PEDIATRICS · doi:10.1542/peds.2010-0442 · Cited by 522
Schleicher, R. L., Carroll, M. D., Ford, E. S., & Lacher, D. A. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.27016 · Cited by 504
A new recommended dietary allowance of vitamin C for healthy young women
Levine, M., Wang, Y., Padayatty, S. J., & Morrow, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171318198 · Cited by 496
Vitamins C and E to Prevent Complications of Pregnancy-Associated Hypertension
Roberts, J. M., Myatt, L., Spong, C. Y., Thom, E. A., Hauth, J. C., Leveno, K. J., Pearson, G. D., Wapner, R. J., Varner, M. W., Thorp, J. M., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0908056 · Cited by 402
Research works printed but not linked: 1
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“Vitamin C supplementation administered to pregnant women can reduce wheezing at 1 year of age in newborns whose mothers were smokers.(31) Maternal smoking was also identified as a postdischarge factor that was independently associated with later respiratory morbidity in the first year of life.”
BackgroundRisk factors for asthma: is prevention possible?
Beasley, R. W., Semprini, A. C., & Mitchell, E. A. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00156-7 · Cited by 534
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Agustí, A. G. N., & Faner, R. (2019) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(18)30529-0 · Cited by 371
Agustí, A. G. N., Melén, E., DeMeo, D. L., Breyer‐Kohansal, R., & Faner, R. (2022) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(21)00555-5 · Cited by 346
McEvoy, C. T., & Spindel, E. R. (2016) · Paediatric Respiratory Reviews · doi:10.1016/j.prrv.2016.08.005 · Cited by 285
Self-citation
Metadata
- Authors
- McEvoy, C. T., Schilling, D., Clay, N., Jackson, K., Go, M. D., Spitale, P., Bunten, C., Leiva, M., Gonzales, D., Hollister-Smith, J., Durand, M., Frei, B., Buist, A. S., Peters, D., Morris, C. D., & Spindel, E. R.
- Affiliations
- Oregon Health & Science University (US)
- Southwest Washington Medical Center (US)
- Vancouver Clinic (US)
- Providence Maternal Care Clinic, Portland, Oregon
- Oregon National Primate Research Center, Beaverton
- University of Southern California (US)
- Oregon State University (US)
- Oregon National Primate Research Center (US)
- Corresponding author
- McEvoy, Cindy T.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2014-05-28
- Volume
- 311
- Issue
- 20
- Pages
- 2074
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC4296045
- OpenAlex
- W1976336434
- Cited by
- 217
- References
- 41
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 21 · 2023: 11 · 2022: 24 · 2021: 18 · 2020: 24 · 2019: 10 · 2018: 27 · 2017: 24 · 2016: 18 · 2015: 13 · 2014: 5
- FWCI
- 13.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- JAMA (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000128, P51OD011092)
- National Heart, Lung, and Blood Institute (HL105447, HL087710, R01HL087710, K23HL080231, R01HL105447)
- National Center for Research Resources (UL1RR024140)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- vitamin C supplementation, smoking during pregnancy, prenatal nicotine exposure, wheezing, respiratory compliance, lung development, asthma risk, infant lung function, birth weight, gestational age, infant feeding practices, infant motor development
- MeSH terms
- Adult, Ascorbic Acid, Double-Blind Method, Female, Humans, Infant, Infant, Newborn, Infant, Newborn, Diseases, Lung, Pregnancy, Prenatal Care, Prenatal Exposure Delayed Effects, Respiratory Function Tests, Respiratory Sounds, Respiratory Tract Diseases, Smoking, Vitamins, Dietary Supplements, Young Adult
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