A recent randomized controlled trial found that vitamin D supplementation during pregnancy did not reduce children’s development of asthma and recurrent wheezing at age 3.
Asthma is the most common chronic disease during childhood. Lung development begins during the 4th fetal week; thus, maternal nutritional status at this time may play a large role for optimal lung development. In addition, asthma and allergies develop early in life, leading researchers to believe prevention methods may need to begin prenatally.
Research has found that vitamin D has many effects on the developing lung and immune system during the fetal and infancy periods. Therefore, multiple longitudinal cohorts have sought to understand whether vitamin D status is related to the development of asthma and allergies. However, these studies have produced mixed results.
In an effort to clarify the role of vitamin D in the prevention of asthma and allergies, researchers recently conducted a randomized controlled trail (RCT) of 806 pregnant women. All women were 10 to 18 weeks into their pregnancy. They were randomized into two groups: the vitamin D group, which received 4,400 IU daily of vitamin D3, or the placebo group, which received 400 IU daily. The treatment period lasted for the remaining duration of the woman’s pregnancy, ranging from 22 to 30 weeks and stopped at birth. The authors did not say what percentage of the newborns took vitamin D.
The women were given questionnaires at baseline and monthly during their pregnancy, inquiring about maternal health, new disease diagnoses and medications. Once they gave birth, the women received quarterly questionnaires via the phone up until the child turned three. These questionnaires inquired about vitamin D supplementation and the health of the child, specifically the occurrence of wheezing, asthma and allergies. After one year, the researchers did not continue gathering data on childhood vitamin D supplementation. Clinical visits occurred yearly, in which the researchers obtained various data, including vitamin D status and anthropometric measurements.
The researchers were most interested in learning how vitamin D supplementation was related to the diagnosis of asthma, recurrent wheezing and allergic sensitization.
Here is what the researchers found:
- 74.9% of the vitamin D group achieved vitamin D levels 30 ng/ml or higher at birth; whereas, only 34.0% in the placebo group achieved this (p < 0.001).
- The average maternal vitamin D status in the third trimester was 39.2 ng/ml and 26.8 ng/ml in the vitamin D group and placebo group, respectively (p < 0.001).
- The average cord blood vitamin D status was 28.0 ng/ml and 19.2 ng/ml for infants in the vitamin D group and the placebo group, respectively.
- A total of 218 children developed asthma or recurrent wheeze.
- 24.3% of children from the vitamin D group developed asthma or recurrent wheeze compared to 30.4% in the placebo group (p = 0.051).
The researchers also evaluated the effects of vitamin D supplementation on secondary outcomes, including eczema, lower respiratory tract infections and immunoglobulin E (IgE) levels. IgE levels are used as markers for allergies. When a person has an allergy, the immune system overreacts to an allergen by producing antibodies called IgE. There were no significant differences in the development of eczema, lower respiratory tract infections and total IgE levels. However, children in the vitamin D group had fewer positive specific IgE tests than children in the placebo group (p = 0.02).
The researchers summarized their main findings,
“The incidence of asthma and recurrent wheezing in their children at age 3 years was lower by 6.1%, but this did not meet statistical significance; however, the study may have been underpowered.”
Before jumping to the conclusion that prenatal vitamin D supplementation does not reduce the incidence of asthma and recurrent wheezing in children, it’s important to acknowledge the study’s limitations.
First, as the researchers noted, the study may have been underpowered. Statistical power depends on several factors: the statistical significance criteria, the magnitude of the effect of interest in the population and the sample size used to detect the effect.
In this study, the magnitude of the effect was limited with only 27% of the children developing recurrent wheezing and asthma. This may explain why the incidence of wheezing and asthma did not quite reach statistical significance between the two groups. Instead, the statistical significance reached a p-value of 0.051, meaning that there was a 5.1% probability that the results were due to chance. For a study to reach statistical significance, the p-value must be less than or equal to 0.05, depicting that there is a 5% probability that the results were due to chance. If this study had merely 0.1% less probability that the results were due to chance, the media would be telling the public a drastically different story.
The researchers pointed out several other limitations. Vitamin D supplementation did not begin until about the 14th week of pregnancy; though, lung development begins in the 4th week. In addition, after birth the children apparently did not supplement with vitamin D. While the vitamin D levels of the cord blood were significantly different between the 2 groups, this difference disappeared by the first year. Since lung development continues throughout childhood, it’s plausible that vitamin D continues to exert its benefits on the respiratory and immune system in the post-natal period.
Also, the placebo group (400 IU/day) had a relatively high level of 25(OH)D of around 27 ng/ml in the third trimester, which may have masked a treatment effect. Also, they did not report if there was a difference in wheezing at 3 years of age between the highest and lowest 25(OH)D quartile. Both of these things could have easily been done.
The researchers concluded,
“Larger studies and longer follow-up of the children in this study will be needed to answer the question. If additional studies identify a significant effect, given the high prevalence of low vitamin D levels in pregnant women, the effect of this inexpensive intervention on child health could be substantial.”
Tovey, A. & Cannell, JJ. RCT finds prenatal vitamin D supplementation may not reduce incidence of asthma and recurrent wheezing in children. Vitamin D Council Blog & Newsletter. January, 2016.