Does vitamin C among pregnant smokers improve airway function trajectory in offspring?

Investigators of a recent research letter published in JAMA Pediatrics highlighted a secondary analysis of randomized clinical trial to better understand how vitamin C supplementation among pregnant smokers impacts airway function trajectory in the offspring.¹

In the original study, the Vitamin C to Decrease Effects of Smoking in Pregnancy on Infant Lung Function (VCISP) trial, vitamin C supplementation among women who smoked during pregnancy "significantly" increased the offspring's forced expiratory flows (FEFs) at 3 and 12 months of age.¹

The trial was randomized, double-blinded, placebo-controlled, and was conducted across 3 centers that featured 251 pregnant smokers, who were randomized at 13-23 weeks of gestation. Of these participants, 125 were randomized to vitamin C (500 mg / d) and 126 to placebo.^2,3

The primary outcome was FEF₇₅ (measurement of FEF at 75% of the expired volume) at 3 months. This outcome was not met, however, secondary outcomes of FEF₅₀ and FEF_25-75 were significantly improved at ages 3 months and 12 months.^2,3

The investigators demonstrated, via a 60-month longitudinal follow-up study, that the offspring continued to have significantly higher FEF_25-75 and a significantly lower wheeze occurrence.¹

To assess the association of FEF_25-75 with wheeze occurrence at 4 to 6 years of age, the study authors performed a new longitudinal analysis of the FEF_25-75 obtained at 3, 12, and 60 months of age in the offspring of the women who smoked during pregnancy in the VCSIP trial and new mediation analyses.¹

FEFs were measured using spirometry at 3, 12, and 60 months of age and wheeze by quarterly standardized respiratory questionnaires. Longitudinal treatment differences in FEF_25-75 were evaluated by general linear mixed-model, repeated-measures of covariance.¹

According to results, 243 offspring were delivered and 233 had an FEF measurement performed at 1 of 3 times, while 80% with data at 60 months had data at 3 or 12 months of age.¹

Longitudinal FEF_25-75 analysis demonstrated "significantly higher values for the offspring of the vitamin C group (P < .001) and a greater increase in FEF25%-75% with increasing age," stated the investigators.¹ In the vitamin C group, wheeze occurrence was significantly lower (30 vs 50 [28.3% vs 47.2%], odds ratio: 0.41, 95% CI, 0.23-0.74 [P = .003]).¹

In addition, mediation analysis revealed that most of the vitamin C association with wheeze was mediated through the vitamin C association with increased FEF_25-75 (total proportion, 54.2% [P = .03]).¹

The secondary analysis revealed vitamin C supplementation to women who smoked during their pregnancies resulted in an increase in FEF_25-75 trajectory in their offspring, through 5 years of age. Difference in FEF_25-75 between treated groups increased with age despite no postnatal supplementation, wrote the investigators.¹

Further, the vitamin C group had a lower wheeze occurrence at 4 to 6 years of age.

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

References:

1. McEvoy CT, Shorey-Kendrick LE, MacDonald KD, et al. Vitamin C Supplementation Among Pregnant Smokers and Airway Function Trajectory in Offspring: A Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. Published online April 08, 2024. doi:10.1001/jamapediatrics.2024.0430

2. McEvoy CT, Shorey-Kendrick LE, Milner K, et al. Oral Vitamin C (500 mg/d) to Pregnant Smokers Improves Infant Airway Function at 3 Months (VCSIP). A Randomized Trial. Am J Respir Crit Care Med. 2019;199(9):1139-1147. doi:10.1164/rccm.201805-1011OC

3. McEvoy CT, Shorey-Kendrick LE, Milner K, et al. Vitamin C to pregnant smokers persistently improves infant airway function to 12 months of age: a randomized trial. European Respiratory Journal. Dec 2020, 56 (6) 1902208; DOI: 10.1183/13993003.02208-2019