Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years: Follow-up of a Randomized Clinical Trial

Cindy T. McEvoy, Lyndsey E. Shorey-Kendrick, Kristin Milner, Julia Harris, Brittany Vuylsteke, Michelle Cunningham, Christina Tiller, Jaclene Stewart, Diane Schilling, Julie Brownsberger, Hope Titus, Kelvin D. Macdonald, David Gonzales, Annette Vu, Byung S. Park, Eliot R. Spindel, Cynthia D. Morris, Robert S. Tepper

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Importance: Vitamin C supplementation (500 mg/d) for pregnant smokers has been reported to increase offspring airway function as measured by forced expiratory flow (FEF) through age 12 months; however, its effects on airway function at age 5 years remain to be assessed. Objective: To assess whether vitamin C supplementation in pregnant smokers is associated with increased and/or improved airway function in their offspring at age 5 years and whether vitamin C decreases the occurrence of wheeze. Design, Setting, and Participants: This study followed up the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) double-blind, placebo-controlled randomized clinical trial conducted at 3 centers in the US (in Oregon, Washington, and Indiana) between 2012 and 2016. Investigators and participants remain unaware of the treatment assignments. Forced expiratory flow measurements at age 5 years were completed from 2018 to 2021. Interventions: Pregnant smokers were randomized to vitamin C (500 mg/d) or placebo treatment. Main Outcomes and Measures: The primary outcome was the prespecified measurement of FEF between 25% and 75% expired volume (FEF25-75) by spirometry at age 5 years. Secondary outcomes included FEF measurements at 50% and 75% of expiration (FEF50and FEF75), forced expiratory volume in 1 second (FEV1), and occurrence of wheeze. Results: Of the 251 pregnant smokers included in this study, 125 (49.8%) were randomized to vitamin C and 126 (50.2%) were randomized to placebo. Of 213 children from the VCSIP trial who were reconsented into this follow-up study, 192 (90.1%) had successful FEF measurements at age 5 years; 212 (99.5%) were included in the analysis of wheeze. Analysis of covariance demonstrated that offspring of pregnant smokers allocated to vitamin C compared with placebo had 17.2% significantly higher mean (SE) measurements of FEF25-75at age 5 years (1.45 [0.04] vs 1.24 [0.04] L/s; adjusted mean difference, 0.21 [95% CI, 0.13-0.30]; P <.001). Mean (SE) measurements were also significantly increased by 14.1% for FEF50(1.59 [0.04] vs 1.39 [0.04] L/s; adjusted mean difference, 0.20 [95% CI, 0.11-0.30]; P <.001), 25.9% for FEF75(0.79 [0.02] vs 0.63 [0.02] L/s; 0.16 [95% CI, 0.11-0.22]; P <.001), and 4.4% for FEV1(1.13 [0.02] vs 1.09 [0.02] L; 0.05 [95% CI, 0.01-0.09]; P =.02). In addition, offspring of pregnant smokers randomized to vitamin C had significantly decreased wheeze (28.3% vs 47.2%; estimated odds ratio, 0.41 [95% CI, 0.23-0.74]; P =.003). Conclusions and Relevance: In this follow-up study of offspring of pregnant smokers randomized to vitamin C vs placebo, vitamin C supplementation during pregnancy resulted in significantly increased airway function of offspring at age 5 years and significantly decreased the occurrence of wheeze. These findings suggest that vitamin C supplementation for pregnant smokers may decrease the effects of smoking in pregnancy on childhood airway function and respiratory health. Trial Registration: ClinicalTrials.gov Identifier: NCT03203603.

Original languageEnglish (US)
Pages (from-to)16-24
Number of pages9
JournalJAMA Pediatrics
Issue number1
StatePublished - Jan 3 2023

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


Dive into the research topics of 'Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years: Follow-up of a Randomized Clinical Trial'. Together they form a unique fingerprint.

Cite this