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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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 offspring of untreated mothers who smoked during pregnancy.
“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]
The Results report improved pulmonary function in newborns of smokers randomized to vitamin C and less wheezing through the first year compared with the placebo group. But the Secondary Outcomes section reports no significant difference in pulmonary function at one year, so the source does not establish better airflow throughout that year. (LLM, conf=0.86)
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“pregnant smokers RCT [67] Vitamin C 500 m”
BackgroundResultInfluentialThe impact of tobacco chemicals and nicotine on placental development
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“plementation was found to be associated with improved pulmonary function in newborns within 72 hours of delivery as well as at 3 months of age, compared with those who received placebo.(68,69)”
ResultRecent advances in antenatal factors predisposing to bronchopulmonary dysplasia
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Epigenetic regulation of immune function in asthma
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Reuniting overnutrition and undernutrition, macronutrients, and micronutrients
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Prenatal and Postnatal Household Air Pollution Exposures and Pneumonia Risk
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Self-citationSubgroup analysis and interaction tests: why they are important and how to avoid common mistakes
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The Role of Nutritional Factors in Asthma: Challenges and Opportunities for Epidemiological Research
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Acetaminophen and the Developing Lung: Could There Be Lifelong Consequences?
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“A recent randomised clinical trial suggested that vitamin C supplementation in pregnant, smoking females may reduce the deleterious effect of maternal smoking on infant pulmonary function [11].”
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Moving bronchopulmonary dysplasia research from the bedside to the bench
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“For example, a recent randomized controlled trial found that supplemental vitamin C taken by pregnant smokers was associated with improved pulmonary function in newborns as well as reduced incidence of wheezing respiratory illnesses up to age 1 year [44].”
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Self-citationNicotine replacement therapy and e-cigarettes in pregnancy and infant respiratory outcomes
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As You Eat It: Effects of Prenatal Nutrition on Asthma
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Time-Specific Factors Influencing the Development of Asthma in Children
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“[93] investigated the role of supplementation of vitamin C in smoking women during pregnancy, highlighting the capacity of this molecule to improve lung”
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“Exact pathophysiological mechanisms have not been ascertained, but it has been suggested that adverse early life risk factors such as maternal smoking, 37 poor maternal nutrition, 38 restricted intrauterine growth 39 and gestational age 40 could contribute to this.”
Duration of exclusive breastfeeding and wheezing in the first year of life: A longitudinal study
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Prenatal Diet and the Development of Childhood Allergic Diseases: Food for Thought
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Self-citationThe effects of maternal smoking on pregnancy outcome and placental histopathology lesions
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Respiratory Compliance in Late Preterm Infants (340/7-346/7 Weeks) after Antenatal Steroid Therapy
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Self-citationInfluence of iron deficiency anemia on glycated hemoglobin levels in non-diabetic Saudi women
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“In addition, the higher exposure to secondhand smoke reported by participants with moderate–severe anemia may have reduced their vitamin C levels, which could compromise iron absorption.(24) Furthermore, women in the moderate– severe anemia group reported a significantly higher consumption of caffeinated drinks and te…”
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“…RCTs have shown that treatment of women who smoked during pregnancy with high-dose vitamin C is associated with improved infant lung function indices at birth [157, 158], enhanced trajectory of pulmonary function parameters over the first 60 months of life, and reduced respiratory symptoms [159].”
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“Vitamin C has been extensively studied for its protective effects against oxidative stress induced by maternal smoking [106–108].”
Influence of Early-Life Environmental Exposures on Immune Function Across the Life Span
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- 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 › Physiology › 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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