MedicalResearch.com Interview with:
Hans Bisgaard, MD, DMSc
Professor of Pediatrics
The Faculty of Health Sciences
University of Copenhagen
Head of the Copenhagen Prospective Studies on Asthma in Childhood
University of Copenhagen and Naestved Hospital
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Bisgaard: Vitamin D deficiency has 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 asthma pathogenesis. Asthma often begins in early childhood and is the most common chronic childhood disorder. Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. In our double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort we supplemented 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d in the control group. Although the maternal supplementation did not result in a statistically significant reduction of risk of persistent wheeze in the offspring through age 3 years, the interpretation of the study is limited by a wide confidence interval that includes a clinically important protective effect.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Bisgaard: Of the 581 children we followed-up, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D3 group and 57 children (20%) in the control group. Vitamin D3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated. There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D3 group vs 23 neonates (8%) in the control group.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Bisgaard: The primary strength of the study is the single-center design with standardized diagnoses performed solely by the experienced research pediatricians. However, the study is limited by a reduced statistical power to detect an effect on the primary endpoint of persistent wheeze. In addition, the vitamin D3 supplementation dose may have been too low, as suggested by the significant decreased risk of persistent wheeze per increase in maternal serum vitamin D level at cessation of the trial. Also, we may have begun supplementation too late, as only 81% of the women had serum vitamin D3 above 30 ng/mL after the intervention. Therefore, further studies with a larger sample size, higher dose, and potentially earlier intervention during pregnancy as well as postnatal supplementation should be performed to establish the likely benefits of vitamin D3 supplementation to pregnant women to reduce occurrence of wheezy disorders in the offspring.
MedicalResearch: Is there anything else you would like to add?
Dr. Bisgaard: Effective preventive strategies to alleviate the large burden of childhood wheezing and related disorders represent a major unmet clinical need. This randomized controlled 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.