乌鸦传媒

SAN DIEGO -- Damage to the lungs of babies born to mothers who smoked through pregnancy may be mitigated with vitamin C supplementation during gestation, researchers reported here.

Newborns whose mothers smoked and took vitamin C had improved pulmonary function, as measured by the ratio of the time to peak tidal expiratory flow to expiratory time, compared with babies born to smokers on placebo (0.383 versus 0.345, P=0.006), said , of Oregon Health & Science University in Portland, and colleagues.

In the co-primary endpoint of passive respiratory compliance per kg within 72 hours of age, children whose mothers were on vitamin C also showed improved lung function (1.32 versus 1.20 mL/cm H₂O/kg, 95% CI 0.02-0.20, P=0.01), her group reported at the American Thoracic Society annual meeting and simultaneously online in the Journal of the American Medical Association.

In addition, offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year. Fifteen of the 70 children born to women who had supplementation were diagnosed with wheezing at year 1 compared with 31 of 77 children who were born to women who had not been receiving vitamin C supplements during pregnancy (P=0.03).

"Supplemental vitamin C taken by pregnant smokers improved newborn pulmonary function test results and decreased wheezing through 1 year in the offspring," McEvoy's group wrote. "Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities."

In her ATS presentation, McEvoy said that at least 12% of American women can't or won't quit smoking during pregnancy.

"The fetal lung is very sensitive to the effects of in-utero smoke, and maternal smoking during pregnancy adversely affects fetal lung development with lifelong decreased pulmonary function and increased asthma risk in the offspring," she explained. "Studies have shown that infants exposed to in-utero smoke have decreased pulmonary function at birth and before any exposure to passive smoke. These changes persist and are associated with increased morbidity in the offspring."

She said that studies in nonhuman primate models appeared to show that treatment with vitamin C could block some of those changes in the lungs.

McEvoy's team performed the randomized, double-blind, placebo-controlled study in 179 pregnant smokers (at least 15-years-old) between March 2007 and January 2011, with the last infant born in July 2011. The women had singleton gestation, were randomized at 22 weeks or less gestational age by last menstrual period, and had declined or failed smoking cessation.

They were given either 500 mg per day of vitamin C or placebo. The study medication consisting of crushed vitamin C or ground cornstarch (placebo) in gel capsules. The women were instructed to swallow one whole study capsule per day until delivery. They also were given a supply of standard prenatal vitamin that contained 60 mg of vitamin C.

A group of pregnant nonsmokers made up the control group and they were given the same standard prenatal vitamin.

The mean maternal age for women in both groups was similar (26.6 in the study arm and 25.5 in the control). More than 75% of the women were white in both groups. About 41% of the women in the supplementation group smoked at least 10 cigarettes a day; about 36% of the placebo group smoked more than 10 cigarettes a day. The differences between the groups were not statistically significant.

Medication adherence was calculated by dividing the number of capsules taken by the total number prescribed in a given period, and fasting plasma ascorbic acid levels were collected at 28 to 30 weeks of gestational age.

The authors also examined genetic polymorphisms linked to increased sensitivity to smoking and found that only one -- the maternal genotype for rs16969968 -- correlated with increased sensitivity of offspring to maternal smoking. The genotype is associated with increased risk of lung cancer, nicotine addiction, and chronic obstructive pulmonary disease.

The study had some limitations. First, 14.6% of the women in the study arm dropped out versus 7.7% loss in the placebo arm because of "social reasons," according to the authors, and this may have biased the outcomes. Also, the group did not measure a decrease in infant forced expiratory flows, which is a key effect of maternal smoking on infant pulmonary function tests.

Finally, they cautioned that "although supplemental vitamin C may improve respiratory outcomes, no evidence is presented for beneficial effects on prematurity, intrauterine growth restriction, or behavioral effects associated with maternal smoking during pregnancy."

"Although smoking cessation is the foremost goal, most pregnant smokers continue to smoke, supporting the need for a pharmacologic intervention," the group wrote. "We provided smoking cessation counseling throughout the study, and 10% of patients quit smoking. Birth cohort studies demonstrate that reduced pulmonary function in offspring of smokers continues into childhood and up to age 21 years. Individuals who begin life with decreased [pulmonary function test] measures may be at increased risk for chronic obstructive pulmonary disease."

In an accompanying editorial, , of the Telethon Kids Institute at University of Western Australia in West Perth, said the findings "offer an approach for potentially minimizing the harmful effects of maternal smoking during pregnancy on the respiratory health of infants."

"However, achieving smoking cessation should be the primary goal for women who smoke and who intend to or become pregnant," he said. "By preventing her developing fetus and newborn infant from becoming exposed to tobacco smoke, a pregnant woman can do more for the respiratory health and overall health of her child than any amount of vitamin C may be able to accomplish."

McEvoy's group is currently conducting a study of vitamin C versus placebo given to pregnant smokers that includes the measurement of infant forced expiratory flows at ages 3 and 12 months, as well as monthly respiratory questionnaires through age 12 months.

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