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Vitamin D supplementation during pregnancy, risk of asthma, wheezing in offspring

January 26, 2016

Two randomized trials in the January 26 issue of JAMA examine if vitamin D supplementation during pregnancy would reduce the risk of asthma or persistent wheezing in offspring.

Asthma often begins in early childhood and is the most common chronic childhood disorder. The incidence has increased during the last half-century in westernized societies. Vitamin D deficiency has also become a common health problem in westernized societies, possibly caused by a more sedentary indoor lifestyle and decreased intake of vitamin D containing foods. Vitamin D possesses a range of immune regulatory properties, and it has been speculated that vitamin D deficiency during pregnancy may affect fetal immune programming and contribute to the development of asthma.

In one study, Hans Bisgaard, M.D., D.M.Sc., of the University of Copenhagen, Denmark and colleagues randomly assigned 623 women daily vitamin D3 (2,400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D3 daily as part of usual pregnancy care. Follow-up of the children (n = 581) was completed when the youngest child reached age 3 years in March 2014.

Of these children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16 percent) in the vitamin D3 group and 57 children (20 percent) in the control group. Vitamin D3 supplementation was not associated with the risk of persistent wheeze. The authors note that a clinically important protective effect cannot be excluded, and that analyses showed a significant reduction in number of episodes of troublesome lung symptoms. However, the development of asthma, upper and lower respiratory tract infections, allergic sensitization, and eczema was unaffected by the vitamin D3 supplementation.

"Effective preventive strategies to alleviate the large burden of childhood wheezing and related disorders represent a major unmet clinical need. This randomized clinical trial of vitamin D3 supplementation during pregnancy did not show a statistically significant effect on the primary end point of persistent wheeze, although a clinically important protective effect cannot be excluded, and a protective effect is suggested by the observed effect on airway immunology and symptomatic episodes. Therefore, further studies with a larger sample size, higher dose, and potentially earlier intervention during pregnancy and postnatal supplementation should be performed to establish the potential benefits of vitamin D3 supplementation to pregnant women to reduce occurrence of wheezy disorders in the offspring," the researches write. (doi:10.1001/jama.2015.18318; Available pre-embargo to the media at http:/

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

In another study, Augusto A. Litonjua, M.D., M.P.H., of Brigham and Women's Hospital, Boston, and colleagues randomly assigned 881 pregnant women at 10 to 18 weeks' gestation and at high risk of having children with asthma to receive daily 4,000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D (n = 440), or a placebo plus a prenatal vitamin containing 400 IU vitamin D (n = 436). The researchers conducted the study to determine whether prenatal vitamin D (cholecalciferol) supplementation can prevent asthma or recurrent wheeze in early childhood.

Eight hundred ten infants were born during the study period, and 806 were included in the analyses for the 3-year outcomes. Two hundred eighteen children developed asthma or recurrent wheeze: 98 of 405 (24 percent) in the 4,400-IU group vs 120 of 401 (30 percent) in the 400-IU group. The absolute reduction (6 percent) was not statistically significant; the authors note that the study may have been underpowered.

"In addition, most of the secondary outcomes were not statistically significantly different between groups, and these analyses should be considered exploratory given the null primary outcome and the absence of adjustment for multiple comparisons. Therefore, whether supplementation of pregnant women with vitamin D will reduce asthma and recurrent wheeze in their offspring at age 3 years remains unclear," the authors write.

"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."

(doi:10.1001/jama.2015.18589; Available pre-embargo to the media at http:/
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

To contact Augusto A. Litonjua, M.D., M.P.H., call Johanna Younghans at 617- 525-6373 or email

Editorial: Inconclusive Results of Randomized Trials of Prenatal Vitamin D for Asthma Prevention in Offspring

It remains unclear whether the results of these studies indicate that vitamin D supplementation may have a role in asthma prevention, write Erika von Mutius, M.D., M.Sc., of Ludwig Maximilians University, Munich, Germany, and Fernando D. Martinez, M.D., of the University of Arizona, Tucson, in an accompanying editorial.

"The heterogeneous nature of wheezing illnesses during the first 3 years of life has been well established for 2 decades. Up to 60 percent of such episodes are transient and not associated with the subsequent development of asthma, and this is particularly true for incident episodes of wheezing occurring during the first 1 to 3 years of life. Therefore, it is too early to know if these findings indicate the potential for vitamin D supplementation to have any role in reducing the risk of asthma. For both trials, longer-term follow-up will be necessary to determine if maternal vitamin D supplementation in pregnancy might have any effect on risk of asthma during the early school years, if not beyond." (doi:10.1001/jama.2015.18963; Available pre-embargo to the media at http:/

Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

The JAMA Network Journals

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