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Improved airway function appeared to mediate the association between vitamin C supplementation and wheeze in kids whose mothers smoked and received vitamin C during pregnancy, a secondary analysis of clinical trial data found.

Longitudinal analyses of forced expiratory flow between 25% and 75% expired volume (FEF_25%-75%) at ages 3, 12, and 60 months showed significantly higher values for children whose moms took vitamin C compared with kids of placebo-treated mothers (P<0.001), and a greater increase in FEF_25%-75% with increasing age despite no postnatal supplementation, reported Cindy McEvoy, MD, MCR, of Oregon Health & Science University in Portland, and co-authors.

Wheeze occurrence was significantly lower when children in the vitamin C group were between ages 4 and 6 years (OR 0.41, 95% CI 0.23-0.74, P=0.003). More than half of the vitamin C association with wheeze -- 54.2% -- was mediated through the vitamin C association with increased FEF_25%-75%, the researchers reported in .

"Our findings provide evidence for a direct association between maternal smoking during pregnancy and wheeze occurrence in the offspring," McEvoy and colleagues wrote.

Smoke exposure in utero is a later in life. In the U.S., the percentage of has declined over time, with the most recent CDC report indicating it was 4.6% in 2021.

McEvoy and colleagues assessed data from the Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function () trial, which randomized women who smoked during pregnancy to 500 mg/day of vitamin C or placebo. A follow-up study showed better airway flow and decreased wheeze for kids up to age 5 whose mothers took vitamin C during pregnancy.

In both the vitamin C and placebo cohorts, mothers smoked approximately eight cigarettes per day in the week before enrollment, then about 10 cigarettes per day by the time their offspring were 1 year old.

The researchers included spirometry FEF measurements taken when offspring were ages 3, 12, and 60 months in their analysis. Wheeze was assessed through quarterly standardized respiratory questionnaires.

A total of 243 offspring were delivered during the study, with 233 receiving an FEF measurement at least once. Most children (80%) who had data at 60 months also had data when they were ages 3 or 12 months.

The offspring population was 49.8% female and 50.2% male. Most (79.4%) were white; 12.4% were Black or African American, 6.4% were more than one race, 1.3% were American Indian or Alaska Native, and 0.4% were Native Hawaiian or other Pacific Islander.

At each age, no significant differences emerged for length, sex, race, or postnatal smoke exposure (assessed by reports and hair analysis).

The researchers acknowledged that wheeze in pediatric patients may be difficult to recognize, which may have influenced results.

"Since the vitamin C group had a greater increase in FEF_25%-75% from 3 months to 5 years of age, follow-up is required to determine whether FEF_25%-75% continues to increase beyond 5 years of age," they noted.

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