Trial Outcomes & Findings for Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function (NCT NCT01723696)

Last Updated: 2019-04-17

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

252 participants

Primary outcome timeframe

3 months of age

Results posted on

2019-04-17

Participant Flow

Study staff screened women at prenatal clinics between December, 2012 and June, 2015 in the catchment area of the three clinical sites to identify eligible women who continued to smoke cigarettes.

To exclude highly non-compliant subjects, consented patients entered a medication compliance trial of 14 ± 7 days. Placebo tablets were given to participants and they were excluded if they failed to return for a post compliance visit within 14 ± 7 days of the screening visit or if they took \< 75% of the required tablets.

Participant milestones

Participant milestones
Measure	Placebo Tablet+Prenatal Vitamin Participants in this arm were to take a daily placebo tablet+prenatal vitamin. Placebo tablets contained microcrystalline cellulose and 100 mg of citric acid to mimic the taste of Vitamin C.	Vitamin C +Prenatal Vitamin Vitamin C +prenatal vitamin: Pregnant smoking women will be randomized to daily vitamin C (500 mg) versus daily placebo
Overall Study STARTED	126	126
Overall Study COMPLETED	109	113
Overall Study NOT COMPLETED	17	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Tablet+Prenatal Vitamin n=126 Participants A daily placebo tablet Placebo tablet+prenatal vitamin	Vitamin C +Prenatal Vitamin n=125 Participants Vitamin C +prenatal vitamin: Pregnant smoking women will be randomized to daily vitamin C (500 mg) versus daily placebo	Total n=251 Participants Total of all reporting groups
Age, Categorical <=18 years	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	116 Participants n=5 Participants	119 Participants n=7 Participants	235 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	26.4 years STANDARD_DEVIATION 5.9 • n=5 Participants	26.6 years STANDARD_DEVIATION 5.2 • n=7 Participants	26.5 years STANDARD_DEVIATION 5.6 • n=5 Participants
Sex: Female, Male Female	126 Participants n=5 Participants	125 Participants n=7 Participants	251 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	119 Participants n=5 Participants	122 Participants n=7 Participants	241 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	20 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) White	100 Participants n=5 Participants	97 Participants n=7 Participants	197 Participants n=5 Participants
Race (NIH/OMB) More than one race	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	126 participants n=5 Participants	125 participants n=7 Participants	251 participants n=5 Participants
Marital Status Married	31 Participants n=5 Participants	22 Participants n=7 Participants	53 Participants n=5 Participants
Marital Status Single	49 Participants n=5 Participants	39 Participants n=7 Participants	88 Participants n=5 Participants
Marital Status Divorced	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Marital Status Significant Other	39 Participants n=5 Participants	56 Participants n=7 Participants	95 Participants n=5 Participants
Highest Education Level Attained Less than High School	31 Participants n=5 Participants	20 Participants n=7 Participants	51 Participants n=5 Participants
Highest Education Level Attained High School or GED	40 Participants n=5 Participants	59 Participants n=7 Participants	99 Participants n=5 Participants
Highest Education Level Attained Some College	49 Participants n=5 Participants	43 Participants n=7 Participants	92 Participants n=5 Participants
Highest Education Level Attained Bachelor's Degree	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Highest Education Level Attained Graduate School	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Health Insurance Type Government Assistance	106 Participants n=5 Participants	112 Participants n=7 Participants	218 Participants n=5 Participants
Health Insurance Type Private Insurance	18 Participants n=5 Participants	13 Participants n=7 Participants	31 Participants n=5 Participants
Health Insurance Type None or Self Pay	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Gestational Age at Enrollment	16.4 weeks STANDARD_DEVIATION 2.9 • n=5 Participants	16.7 weeks STANDARD_DEVIATION 3.1 • n=7 Participants	16.5 weeks STANDARD_DEVIATION 3.0 • n=5 Participants
Gestational Age at Randomization	18.2 weeks STANDARD_DEVIATION 2.8 • n=5 Participants	18.4 weeks STANDARD_DEVIATION 3.0 • n=7 Participants	18.3 weeks STANDARD_DEVIATION 2.9 • n=5 Participants
BMI at Enrollment	30.0 kg/m^2 STANDARD_DEVIATION 7.3 • n=5 Participants	28.6 kg/m^2 STANDARD_DEVIATION 6.5 • n=7 Participants	29.3 kg/m^2 STANDARD_DEVIATION 6.9 • n=5 Participants
Gravida	3.5 pregnancies STANDARD_DEVIATION 2.4 • n=5 Participants	3.3 pregnancies STANDARD_DEVIATION 2 • n=7 Participants	3.4 pregnancies STANDARD_DEVIATION 2.2 • n=5 Participants
Cigarette Smoking at Enrollment	7.8 cigarettes per day STANDARD_DEVIATION 4.9 • n=5 Participants	8.0 cigarettes per day STANDARD_DEVIATION 5.0 • n=7 Participants	7.9 cigarettes per day STANDARD_DEVIATION 4.9 • n=5 Participants
Cigarette Smoking 3 months prior to Pregnancy	17.7 cigarettes per day STANDARD_DEVIATION 10.8 • n=5 Participants	15.9 cigarettes per day STANDARD_DEVIATION 7.7 • n=7 Participants	16.8 cigarettes per day STANDARD_DEVIATION 9.4 • n=5 Participants
Maternal History of Asthma Yes	38 Participants n=5 Participants	44 Participants n=7 Participants	82 Participants n=5 Participants
Maternal History of Asthma No	88 Participants n=5 Participants	81 Participants n=7 Participants	169 Participants n=5 Participants
Maternal History of Substance Abuse Yes	16 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants
Maternal History of Substance Abuse No	110 Participants n=5 Participants	105 Participants n=7 Participants	215 Participants n=5 Participants
Maternal History of Alcohol Abuse Yes	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Maternal History of Alcohol Abuse No	126 Participants n=5 Participants	121 Participants n=7 Participants	247 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months of age

Population: Population included in analysis were infants who were able to complete technically acceptable PFT/FEF measurements at 3 months of age.

Outcome measures

Outcome measures
Measure	Placebo Tablet+Prenatal Vitamin n=109 Participants A daily placebo tablet Placebo tablet+prenatal vitamin	Vitamin C +Prenatal Vitamin n=113 Participants Vitamin C +prenatal vitamin: Pregnant smoking women will be randomized to daily vitamin C (500 mg) versus daily placebo
Forced Expiratory Flow at 75% of Expired Volume (FEF75)	188.7 ml/s Standard Deviation 66.4	200.7 ml/s Standard Deviation 71.1

SECONDARY outcome

Timeframe: 12 months of age

Population: These measurements were performed at the 12 month visit.

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.

Outcome measures

Outcome measures
Measure	Placebo Tablet+Prenatal Vitamin n=101 Participants A daily placebo tablet Placebo tablet+prenatal vitamin	Vitamin C +Prenatal Vitamin n=101 Participants Vitamin C +prenatal vitamin: Pregnant smoking women will be randomized to daily vitamin C (500 mg) versus daily placebo
Forced Expiratory Flow at 75% of Expired Volume (FEF75)	324 mL/s Standard Deviation 84.1	351.6 mL/s Standard Deviation 71.1

SECONDARY outcome

Timeframe: 12 months of age

Population: Population is infants who have reached 12 months of age, and whose parent/caregiver has completed at least 1 respiratory questionnaire past 122 days after birth.

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.

Outcome measures

Outcome measures
Measure	Placebo Tablet+Prenatal Vitamin n=119 Participants A daily placebo tablet Placebo tablet+prenatal vitamin	Vitamin C +Prenatal Vitamin n=118 Participants Vitamin C +prenatal vitamin: Pregnant smoking women will be randomized to daily vitamin C (500 mg) versus daily placebo
Incidence of Wheezing Through 12 Months of Age	63 Participants	51 Participants

Adverse Events

Maternal/Fetal (Placebo)

Serious events: 30 serious events

Other events: 54 other events

Deaths: 1 deaths

Maternal/Fetal (Vitamin C)

Serious events: 20 serious events

Other events: 59 other events

Deaths: 1 deaths

Infant (Placebo)

Serious events: 31 serious events

Other events: 0 other events

Deaths: 1 deaths

Infant (Vitamin C)

Serious events: 33 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Maternal/Fetal (Placebo) n=126 participants at risk A daily placebo tablet Placebo tablet+prenatal vitamin	Maternal/Fetal (Vitamin C) n=125 participants at risk Vitamin C +prenatal vitamin: Pregnant smoking women will be randomized to daily vitamin C (500 mg) versus daily placebo	Infant (Placebo) n=123 participants at risk Infants of mothers in the Placebo group, who took a daily placebo + prenatal vitamin.	Infant (Vitamin C) n=120 participants at risk Infants of mothers in the Vitamin C group, who took daily vitamin C (500 mg) and a prenatal vitamin
Blood and lymphatic system disorders Anaemia	7.1% 9/126 • Number of events 9 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	7.2% 9/125 • Number of events 9 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/123 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/120 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery
Pregnancy, puerperium and perinatal conditions Gestational diabetes	12.7% 16/126 • Number of events 17 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	7.2% 9/125 • Number of events 11 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/123 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/120 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	11.9% 15/126 • Number of events 15 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	15.2% 19/125 • Number of events 21 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/123 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/120 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery
Pregnancy, puerperium and perinatal conditions Foetal hypokinesia	4.8% 6/126 • Number of events 6 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	5.6% 7/125 • Number of events 7 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/123 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/120 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery
Infections and infestations Urinary tract infection	6.3% 8/126 • Number of events 8 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	12.8% 16/125 • Number of events 16 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/123 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/120 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery
Reproductive system and breast disorders Vulvovaginal mycotic infection	6.3% 8/126 • Number of events 8 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	9.6% 12/125 • Number of events 12 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/123 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/120 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery
Reproductive system and breast disorders Vaginitis bacterial	7.1% 9/126 • Number of events 9 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	8.0% 10/125 • Number of events 10 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/123 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery	0.00% 0/120 • Adverse events were monitored and collect from time of enrollment until 12 months post delivery. Population at risk for infants are different than population at risk for mother/fetus because we had some dropout from time of randomization to delivery

Additional Information

Cindy McEvoy, MD

OHSU

Phone: 503-494-0223

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place