Vitamin C improves lung function in newborns of pregnant smoking women

05/22/12 Portland, Ore.

New research has potential to alter the fetal origins of respiratory disease by blocking some of the effects of smoking on lung development

Women who are unable to quit smoking during pregnancy can significantly improve the lung function of their newborns by taking Vitamin C daily, according to a new study at Oregon Health & Science University Doernbecher Children's Hospital.

"Smoking during pregnancy is known to adversely affect the lung development of the developing baby, causing lifelong decreased lung function and an increased risk of asthma," said Cindy McEvoy, M.D., M.C.R., neonatologist and associate professor of pediatrics at OHSU Doernbecher Children's Hospital. "We found that babies born to pregnant smoking women who took 500 milligrams of Vitamin C daily during their pregnancy had significantly improved pulmonary function tests measured at about 48 hours after delivery."

The results will be presented at the American Thoracic Society 2012 International Conference in San Francisco.

In this pilot study, McEvoy and colleagues randomly assigned 159 pregnant women who were unable to quit smoking to either daily Vitamin C or a placebo starting before 22 weeks gestation through delivery. A group of nonsmoking pregnant women also was studied as a reference group.

The researchers measured the pulmonary function in all newborns at approximately 48 hours of age and found the newborns of smoking women who received Vitamin C supplementation had significantly improved lung function compared with the newborns of smoking women who received a placebo, as measured by standard newborn pulmonary function testing (TPTeF:TE and Crs).

In addition, the scientists found that one particular genetic variant that has been shown to increase the risk of smokers developing cancer and is associated with both a reduced ability to quit smoking and a high likelihood of relapse also seemed to intensify the harmful effects of maternal smoking on babies' lungs.

"Getting women to quit smoking during pregnancy has to be priority one, but this study provides a way to potentially help the infants born to the 50 percent of women who cannot quit smoking when pregnant," said McEvoy. "Vitamin C supplementation may block some of the in-utero effects of smoking on fetal lung development."

"Our findings are important because improved lung function tests at birth are associated with less wheezing and asthma in childhood," McEvoy said. "Vitamin C is a simple, safe, and inexpensive treatment that may decrease the impact of smoking during pregnancy on the respiratory health of children."

The study was funded by the National Institutes of Health and supported by the Oregon Clinical Translational Research Institute.

# # #

ATS Abstract 25842

"Daily Vitamin C Improves Pulmonary Function In Newborns Of Pregnant Smoking Women: A Randomized Trial"

Type

Scientific Abstract

Authors

C. McEvoy¹, D. Schilling¹, N. Clay¹, M. Go¹, P. Spitale¹, C. Bunten², M. Leiva³, J. Hollister-Smith¹, M. Durand⁴, B. Frei⁵, A.S. Buist¹, D. Peters¹, C. Morris¹, E. Spindel¹; ¹Oregon Health & Science University - Portland, OR/US, ²Vancouver Clinic - Vancouver, WA/US, ³Providence Portland Medical Center - Portland, OR/US, ⁴University of Southern California - Los Angeles, CA/US, ⁵Oregon State University - Corvallis, OR/US

Abstract Body

RATIONALE: Maternal smoking during pregnancy adversely affects lung development with lifelong decreases in pulmonary function and increased risk of asthma. In a non-human primate model, supplemental vitamin C blocked the in-utero effects of nicotine on fetal lung development and offspring pulmonary function (Am J Respir Crit Care Med 2005; 171:1032-39). We hypothesized that newborns of smoking pregnant women randomized to daily vitamin C would have improved pulmonary function tests (PFTs) compared to those randomized to placebo.

METHODS: Pregnant women unable to quit smoking were randomized to daily vitamin C (500 mg) versus placebo prior to 22 weeks gestation through delivery. Urine cotinine and fasting plasma ascorbic acid were measured. A group of non smoking pregnant women was also studied (reference group). The primary outcome was the measurement of PFTs in the newborns at about 48 hours of age. Flow volume characteristics including the time to peak tidal expiratory flow to expiratory time (TPTEF:TE) and passive respiratory mechanics (respiratory compliance [Crs]) were measured (Viassys Jaeger BabyBody). Analysis of the primary outcomes was done on intention-to-treat using linear regression and adjusting for stratification for randomization (<16 versus ≥ 16 weeks' gestation).

RESULTS: 159 newborns of randomized smoking women and 76 of non smoking women were studied. There were no significant differences between randomized groups with regards to maternal age, insurance coverage, cotinine levels, women smoking ≥ 10 cigarettes daily, medication adherence, or history of asthma. The smoking women randomized to placebo had significantly lower levels of ascorbic acid than non-smokers, but vitamin C returned levels to that of non-smokers (Table). There was no significant difference between randomized groups in gestational age at randomization, delivery mode, and gestational age at birth, birth weight, race or gender. Newborns of smoking women randomized to placebo had decreased TPTEF:TE and Crs compared to non-smokers, but vitamin C supplementation significantly increased TPTEF:TE and Crs, returning them nearly to levels of non-smokers.

Table. Clinical Characteristics and PFTs of Newborns
	Newborns of placebo-treated smokers (n=83)	Newborns of vitamin C treated smokers (n=76)	Newborns of non smokers (n=76)
Birth weight (g)	3311 ± 475	3163 ± 694	3303 ± 596
Gestational age (wks)	38.9 ± 1.6	38.5 ± 2.1	38.7 ± 2.1
Mid gestation Ascorbic Acid level (μmol/L)	39.8 ± 20.5	58.9 ± 26.8*	57.8 ± 22.8
Respiratory rate (bpm)	57 ± 12	57 ± 12	53 ± 12
TPTEF:TE	0.345±0.078	0.383±0.084*	0.399±0.077
Crs/kg (mL/cmH2O/kg)	1.20 ± 0.24	1.32 ± 0.30*	1.36 ± 0.30

Values are Mean±SD; *p<0.01 for vitamin C versus placebo treated.

CONCLUSION

Newborns delivered to smoking women randomized to vitamin C had significantly improved PFTs (increased TPTEF:TE and Crs) compared to those randomized to placebo. Assessment of clinical outcomes through one year of age is ongoing. We speculate that vitamin C supplementation in pregnant women who cannot quit smoking has great public health significance to potentially alter the fetal origins of respiratory disease by blocking some of the effects of in-utero smoke on lung development.

About OHSU Doernbecher Children's Hospital

OHSU Doernbecher Children's Hospital ranks among the top children's hospitals in the United States in eight clinical specialties.* It ranks 36th nationally for NIH-awarded pediatric research funding among children's hospitals affiliated with an academic medical center**, and is one of only 22 NIH-designated Child Health Research Centers in the country.

OHSU Doernbecher cares for tens of thousands of children each year from Oregon, southwest Washington and around the nation, resulting in more than 175,000 discharges, surgeries, transports and outpatient visits annually.

Nationally recognized OHSU Doernbecher physicians and nurses provide a full range of pediatric care in the most patient- and family-centered environment. These highly trained clinicians also travel throughout Oregon and southwest Washington, providing specialty care to more than 3,000 children at more than 150 outreach clinics in 15 locations. In addition, OHSU Doernbecher delivers neonatal and pediatric critical care consultation to community hospitals statewide through its state-of-the-art telemedicine network.

* U.S. News Best Children's Hospitals 2011-12
** National Association of Children's Hospitals and Related Institutions

About OHSU

Oregon Health & Science University is the state's only academic health and research university. As Portland's largest employer with nearly 14,000 employees, OHSU's size contributes to its ability to provide many services and community support not found anywhere else in the state. OHSU serves patients from every corner of Oregon and is a conduit for learning for more than 4,300 students and trainees. OHSU is the source of more than 200 community outreach programs that bring health and education services to each county in the state.