The Vitamin D Antenatal Asthma Reduction Trial (VDAART): Rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children

Abstract

There is intense interest in the role of vitamin D in the development of asthma and allergies. However, studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies. To address this uncertainty, the Vitamin D Antenatal Asthma Reduction Trial (VDAART) was developed. VDAART is a randomized, double-blind, placebo-controlled trial of vitamin D supplementation in pregnant women to determine whether prenatal supplementation can prevent the development of asthma and allergies in the women’s offspring. A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications, such as preeclampsia, preterm birth, and gestational diabetes. Women were randomized to the treatment arm of 4,000 IU/day of vitamin D3 plus a daily multivitamin that contained 400 IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400 IU daily of vitamin D3. Women who were between the gestational ages of 10–18 weeks were randomized from three clinical centers across the United States – Boston Medical Center, Washington University in St. Louis, and Kaiser Permanente Southern California Region (San Diego, CA). Supplementation took place throughout pregnancy. Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events. Offspring are being evaluated quarterly through questionnaires and yearly during in-person visits until the 3rd birthday of the child. Ancillary studies will investigate neonatal T-regulatory cell function, maternal vaginal flora, and maternal and child intestinal flora.

Revisiting the hygiene hypothesis for allergy and asthma

“…70 There are potentially effective and safe options on the horizon, 16 microbiome research is exploding, and inspiration can be gleaned from recent clinical trials demonstrating effective and safe immunomodulatory prevention of peanut allergy with intervention in infancy 71 and an asthma prevention trial with prenatal maternal vitamin D supplementation that is nearing conclusion. 72 Controversial and paradoxical, hygiene theory doubters are unlikely to become believers until microbe-based preventive interventions are developed and demonstrated to be effective and safe, which is the end goal for current believers.…”

Prenatal Intake of Vitamins and Allergic Outcomes in the Offspring: A Systematic Review and Meta-Analysis

“…These included trials (including total of 2456 children) were represented by 217 five original papers [13][14][15][16][17] and four grouped as their companion papers [18][19][20][21] . 218 Table 1 shows the characteristics of the included trials, their companion 219 papers and study population.…”

Vitamin E and D regulation of allergic asthma immunopathogenesis

“…Based on these clinical observations as well as laboratory evidence that vitamin D deficiency may skew immune responses towards Th2 responses, these researchers have raised the hypothesis that vitamin D supplementation during pregnancy or early infant life may be protective against development of asthma 93 . As a result, interventional double-blinded, placebo-controlled, randomized clinical (DBPCRT) trials are now under way to examine this hypothesis 94 . However, a recent study raised concerns about this strategy.…”