Key takeaways:
- Secondary analysis of the VCISP trial showed that offspring of pregnant smokers who received vitamin C supplementation had significantly higher forced expiratory flows (FEF25-75) through 5 years of age compared to those who received a placebo.
- The vitamin C group also exhibited a lower occurrence of wheeze at 4 to 6 years of age compared to the placebo group.
- Mediation analysis suggested that most of the association between vitamin C and reduced wheeze occurrence was mediated through the improvement in FEF25-75.
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 FEF25-75 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 FEF25-75 and a significantly lower wheeze occurrence.1
To assess the association of FEF25-75 with wheeze occurrence at 4 to 6 years of age, the study authors performed a new longitudinal analysis of the FEF25-75 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 FEF25-75 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 FEF25-75 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 FEF25-75 (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 FEF25-75 trajectory in their offspring, through 5 years of age. Difference in FEF25-75 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
