Vitamins C and E during pregnancy may reduce risk of wheezing in children

Australian scientists from the University of Newcastle have published the first comprehensive systematic review and meta-analysis of the effects of maternal intake of vitamins A, C and E on the risk of respiratory symptoms in children under five years of age in the Journal of Human Nutrition and Dietetics. The analysis included data from 12 observational studies (58,769 mother-child pairs) and six randomised controlled trials (RCTs) on vitamin C and E supplements.

Prerequisites

Acute and chronic respiratory disease in children (wheezing, asthma, respiratory distress syndrome) causes a significant burden on families and the health care system. Antioxidants - vitamins C and E - could protect the fetal lungs from oxidative stress, especially if the mother smokes or has an inadequate diet.

Study design

• Observational cohorts assessed usual dietary intakes ranging from low to high vitamin intakes using food frequency questionnaires and food diaries among pregnant women.
• The RCTs included smoking mothers who were given 500 mg of vitamin C daily or placebo from the second trimester until delivery. Two trials followed children up to 1 year (n=206) and one followed children up to 5 years (n=213).
• Outcomes: primary outcome – presence of wheezing in the child; secondary outcome – development of respiratory distress syndrome (RDS) in newborns.

Key Results

1. Vitamin C in Smoking Mothers

   • RCTs showed a statistically significant reduction in the risk of wheezing in children:

     • By 12 months – by 30% (RR≈0.70; p<0.05).

     • By 5 years – by 35% (RR≈0.65; p<0.05).

   • Observational data on non-prayers strongly supported the trend, but the effect did not reach statistical significance (aOR 0.85; 95% CI 0.63–1.16).

2. Vitamin E from Food and Supplements

   • In two independent observational cohorts, mothers in the top quartile of vitamin E intake had a 36% lower risk of wheezing in their child at 2 years (aOR 0.64; 95% CI 0.47–0.87).

   • There were no RCTs for vitamin E, increasing the uncertainty of the evidence.

3. Combination C + E and Vitamin A

   • Two RCTs comparing the vitamin C+E combination with placebo found no effect on the risk of RDS in neonates (OR 1.15; 95% CI 0.80–1.64).

   • Vitamin A has not shown significant effects in either observational studies or clinical trials.

Quality of evidence and limitations

• Moderate (for RCTs on C and RDS) and very low (for observational data) evidence according to GRADE.
• Heterogeneity of studies by methods of assessing vitamin intake and by age of observation of children.
• Lack of RCTs for vitamin E and complete lack of large trials for vitamin A.

Clinical and practical implications

• 500 mg of vitamin C daily during the second and third trimesters is recommended for smoking pregnant women to reduce the risk of wheezing in children in the first years of life.
• High vitamin E intake (≥ 15 mg/day) may confer additional protection but requires confirmation in an RCT.
• Combination therapy of C+E and vitamin A has not been shown to be beneficial in preventing RDS or infantile wheezing.

Prospects

The authors call for large randomized trials:

• for vitamin E during pregnancy with long-term (≥ 5 years) follow-up of respiratory outcomes in children;
• for vitamin C among different maternal groups (not just smokers) to assess the breadth of the effect;
• for vitamin A in case of deficiency in the diet.

If confirmed, these data may form the basis for updated recommendations for prenatal dietary support, particularly for high-risk groups for childhood respiratory disease.