Key takeaways:

• Vitamin C supplementation during pregnancy may reduce wheeze in children of smoking mothers, researchers found.
• The effects expanded as children aged, a new analysis of trial data showed.

A new analysis of randomized clinical trial data showed that vitamin C supplementation during pregnancy may reduce wheeze in the offspring of mothers who smoke, researchers reported in JAMA Pediatrics.

The analysis identified a lower occurrence of wheeze among offspring of smoking mothers who received vitamin C supplementation during pregnancy compared with those born to smoking mothers who did not — a result of vitamin C’s ability to improve airway function, according to Cindy T. McEvoy, MD, MCR, professor of pediatrics and director of child health research at the Oregon Health & Science University School of Medicine, and colleagues.

The findings “provide evidence for a direct association between maternal smoking during pregnancy and wheeze occurrence in the offspring,” they wrote.

McEvoy and colleagues conducted a new longitudinal analysis of forced expiratory flows (FEFs) obtained from children enrolled in a randomized clinical trial that previously found that vitamin C supplementation, in conjunction with smoking cessation counseling, significantly increased airway function through 12 months of age among the offspring of pregnant smokers.

The double-blind randomized trial was conducted at three clinical sites, with McEvoy and colleagues randomly assigning women who were pregnant and could not quit smoking cigarettes to receive either a daily 500 mg vitamin C supplement or placebo. They measured FEFs in the offspring at age 3 and 12 months and 5 years.

“We collected quarterly respiratory questionnaires on the offspring through 5 years of age that documented their clinical respiratory outcomes,” McEvoy told Healio. “We also collected yearly DNA samples from cheek swabs on the offspring so we could explore the role of epigenetics in making the protective effects of vitamin C long lasting and also carefully measured secondhand tobacco exposure to make sure it was equal between groups.”

Among 243 offspring, longitudinal FEF analyses at age 5 years demonstrated significantly higher values for the offspring of the vitamin C group (P < .001) and a greater increase in FEF with increasing age, with wheeze occurrence significantly lower (OR = 0.41; 95% CI, 0.23-0.74) in the vitamin C group.

A new mediation analysis conducted by McEvoy and colleagues found that “most of the vitamin C association with wheeze” — total proportion, 54% — “was mediated through the vitamin C association with increased FEF,” they wrote.

“I think we were all very surprised that the effect just seems to be getting bigger over time. If anything, we might have suspected that the protective effect might decrease over time, but it’s been the opposite,” McEvoy said. “It is quite remarkable, and we are cautiously optimistic that we are improving the lifelong respiratory outcomes of these children.”

McEvoy said she is interested in conducting a “simpler, larger study” to confirm the findings under typical prenatal practice conditions.

“While our data certainly strongly support the use of vitamin C by pregnant smokers, a definitive, real-world study in which everything is not as tightly controlled as it has been in our studies has not yet been performed,” McEvoy said. “We always like to mention that, because our and others’ data suggest nicotine is the ingredient in tobacco that harms the lung. Vaping during pregnancy will probably harm the fetal lung as much as tobacco does.”