Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function

Phase 2

Completed

• Conditions: Pulmonary Function; Newborn, Abnormal; Infant Wheeze; In-utero Nicotine; Second Hand Smoke
• Interventions: Dietary Supplement: Vitamin C +prenatal vitamin; Dietary Supplement: Placebo tablet+prenatal vitamin

• Registration Number: NCT01723696
• Lead Sponsor: Oregon Health and Science University

Brief Summary

Vitamin C supplementation (500 mg per day) given to pregnant women who can not quit smoking will improve the pulmonary function tests in their offspring measured at 3 months of age.

Detailed Description

Smoking during pregnancy remains a major public health problem as at least 12% of pregnant women cannot quit smoking during pregnancy. This addiction is the largest preventable cause of childhood respiratory illness, including asthma, and children whose mothers smoked during pregnancy show lifetime decreases in pulmonary function. Smoking is a unique morbidity in that it is addictive, heavily advertised and recent genome studies show there are genotypes that significantly increase the likelihood of being unable to quit. Teen pregnancy, low income, low education, and living with another smoker are important factors increasing the odds of smoking during pregnancy. Pulmonary function tests done shortly after birth in babies born to mothers who smoked during pregnancy show decreased pulmonary function as measured by decreased respiratory flows and respiratory compliance and altered tidal breathing patterns. These changes can still be measured even after the infants have reached adulthood. Multiple epidemiologic studies show that these decreases in pulmonary function lead to increased respiratory disease and costs of hundreds of millions of dollars per year.

The primary aim of this double-blind, placebo controlled, randomized, multi-site study is to demonstrate improved pulmonary function testing at 3 months of age, in infants delivered to smoking mothers who are randomized to 500 mg/day of supplemental vitamin C versus placebo at less than or equal to 22 weeks of pregnancy. We will recruit 278 smoking pregnant women into the study. Patients will meet with research personnel at each prenatal visit and smoking cessation will be actively encouraged. Patients will be monitored with a set of serial biomarkers to assess smoking and medication compliance, including urine cotinine levels, smoking questionnaires, pill counts and fasting plasma ascorbic acid levels. Pulmonary function tests will be done at 3 months of age and will measure forced expiratory flows. The infants will also be followed through one year of age with monthly validated respiratory questionnaires and a follow-up pulmonary function test at 12 months of age. Success of this study is supported by strong pilot data showing statistically significant improvements at about 48 hours of age in pulmonary function tests in infants born to smoking mothers who received vitamin C versus placebo, and preliminary data showing a lower incidence of wheezing at 12 months of age in these infants. Key genetic polymorphisms shown to increase sensitivity to in-utero smoke exposure will also be measured. The success of this study is also supported by animal models showing the effectiveness of vitamin C to preserve pulmonary function and genetic and epidemiologic studies linking the effects of smoking during pregnancy to oxidant mechanisms. The secondary aims of the study include: 1) to demonstrate a decreased incidence of wheezing through 12 months of age in infants delivered to smoking mothers who are randomized to 500mg/day of supplemental vitamin C versus placebo during pregnancy; 2) to demonstrate improved pulmonary function tests at 12 months of age in these infants.

Study Timeline

• Study First Submitted: 2012-11-06
• Study First Submitted QC: 2012-11-07
• Study First Posted: 2012-11-08
• Study Start: 2012-12
• Primary Completion: 2016-04
• Study Completion: 2017-12
• Results First Submitted: 2018-10-15
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-28
• Last Update Submitted: 2019-03-28
• Results First Posted: 2019-04-17
• Last Update Posted: 2019-04-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 252

Inclusion Criteria

At randomization:

• Singleton gestation
• ≥ 15 years old
• Gestational age between 13 and 22 weeks
• Receiving prenatal care
• Current smoker
• English speaking

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Exclusion Criteria

• Gestational age ≥ 23 and 0/7 weeks
• Multiple gestation
• Major fetal congenital anomalies
• Current use of illicit drugs
• Current alcohol abuse
• Use of vitamin C (≥ 500 mg/day)>3 days per week since last menstrual period
• Refusal to abstain from vitamin or supplements containing significant vitamin C other than those provided through or approved by study staff
• History of kidney stone in patient
• Insulin dependent diabetes
• Complex maternal medical conditions
• Participation in other conflicting research projects
• Unable to demonstrate stable method of communication
• Pregnancy by in-vitro fertilization
• Plan to terminate pregnancy
• Failure of medication compliance trial
• Failure to return in designated period during placebo run-in
• Body mass index > 50 at screening

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vitamin C +prenatal vitamin	Vitamin C +prenatal vitamin	500 mg vitamin C /day
placebo tablet+prenatal vitamin	Placebo tablet+prenatal vitamin	A daily placebo tablet

Primary Outcome Measures

Name	Time	Method
Forced Expiratory Flow at 75% of Expired Volume (FEF75)	3 months of age	The primary outcome was the comparison of infant FEFs at 3 months of age obtained using the raised volume rapid thoracic compression (RVRTC) technique in offspring of pregnant smokers randomized to vitamin C versus placebo. The specific primary outcome parameter was the measurement of FEF at 75% of the expired volume (FEF75)

Secondary Outcome Measures

Name	Time	Method
Forced Expiratory Flow at 75% of Expired Volume (FEF75)	12 months of age	The measurement of forced expiratory flows and specifically FEF75 will be done at 12 months of age in infants born to pregnant smoking women randomized to vitamin C versus placebo during pregnancy. FEF75 will be measured with the raised volume rapid thoracic compression technique.
Incidence of Wheezing Through 12 Months of Age	12 months of age	The incidence of wheezing through 12 months of age will be compared in the infants delivered to smoking pregnant women who were randomized to vitamin C (500 mg) versus placebo during pregnancy.

Trial Locations

Locations (2)

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States