# Vitamin C to Decrease Effects of Smoking during Pregnancy on Offspring Airway Function, Airway Size, and Epigenetic Correlates: VCSIP cohort follow-up through 10 Years of Age

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $1,737,002

## Abstract

Project Summary/Abstract
 Maternal smoking during pregnancy leads to impaired fetal lung development, decreased airway function
(forced expiratory flows), and an increased risk for wheeze/asthma in the offspring. It is an important determinant
of lifelong lower airway function and greater respiratory morbidity. In our randomized controlled trial (“Vitamin C
to Decrease Effects of Smoking in Pregnancy on Infant Lung Function” [VCSIP]), we demonstrated that vitamin
C supplementation versus placebo to pregnant smokers resulted in better airway function in the offspring at 3
and 12 months, and at 5 years of age. These differences in airway function between the offspring of the
randomized groups also increased with age. We also demonstrated a significant decrease in the occurrence of
wheeze at 4 to 6 years of age. There was no difference in prenatal or postnatal smoke exposure between the
randomized groups. All clinical participants and investigators remain blinded to treatment allocations. Mediation
analysis indicates the effect of vitamin C on wheeze is primarily due to its effect on airway function. Interventions
early in life are important as longitudinal studies demonstrate that airway function trajectories are established
early, and children in the lower airway function percentiles tend to have persistently lower airway function into
adulthood and are likely at increased risk for adult pulmonary disease. Our studies are the first and only
studies to show that an in-utero intervention targeted for a known environmental toxin can produce a
persistent increase in airway function early in life. This finding is highly relevant to the aims of the NHLBI.
 The aims of this proposal are to continue to study the offspring from the unique VCSIP study to determine
whether prenatal supplementation with vitamin C to pregnant smokers produces an improved trajectory of airway
function and lower respiratory morbidity through 10 years of age (specific aim 1). In specific aims 2 and 3 we will
examine the structural and molecular mechanisms by which vitamin C may be acting to modify the effects of
maternal smoking during pregnancy on lung development. In specific aim 2, we will use low dose high-resolution
computed tomography (HRCT) scans done at 10 years of age to determine if increased airway size underlies
the improved airway function. In specific aim 3, evaluating DNA methylation changes in serial buccal and blood
samples, we will identify critical genes and pathways most affected by maternal smoking during pregnancy and
modified by vitamin C supplementation, as well as their association with respiratory outcomes of airway function,
respiratory morbidity, and airway size. The children will be studied with yearly airway function tests, buccal
swabs, hair for nicotine levels, blood at ages 7 and 10, and a low dose HRCT scan at 10 years of age. This
follow-up will determine whether the vitamin C supplementation in pregnant smokers improves airway function
and resp...

## Key facts

- **NIH application ID:** 10906255
- **Project number:** 5R01HL162951-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Cynthia T McEvoy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,737,002
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906255

## Citation

> US National Institutes of Health, RePORTER application 10906255, Vitamin C to Decrease Effects of Smoking during Pregnancy on Offspring Airway Function, Airway Size, and Epigenetic Correlates: VCSIP cohort follow-up through 10 Years of Age (5R01HL162951-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906255. Licensed CC0.

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