Background The need, safety and effectiveness of vitamin D supplementation during pregnancy remain controversial. Design In this randomized controlled trial, women with a singleton pregnancy at 12–16 weeks’ gestation received 400, 2000 or 4000 IU vitamin D3/day until delivery. The primary outcome was maternal/neonatal circulating 25(OH)D at delivery, with secondary outcomes 25(OH)D ≥80 nmol/L achieved and 25(OH)D concentration required to achieve maximal 1,25(OH)2D production. Results Of the 494 women enrolled, 350 women continued until delivery: Mean 25(OH)D by group at delivery and 1-month before delivery were significantly different (p<0.0001), and percent who achieved sufficiency was significantly different by group, greatest in 4000 IU group (p<0.0001). The relative risk (RR) for achieving ≥80 nmol/L within one month of delivery was significantly different between 2000 vs. 400 IU (RR 1.52 [CI 1.24–1.86]); 4000 vs. 400 (RR 1.60 [CI 1.32–1.95]), but not between 4000 vs. 2000 (RR 1.06 [CI 0.93–1.19]). Circulating 25(OH)D had a direct influence on circulating 1,25(OH)2D concentrations throughout pregnancy (p<0.0001) with maximal production of 1,25(OH)2D in all strata in the 4000 IU group. There were no differences between groups on any safety measure. Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels. Conclusions Vitamin D supplementation of 4,000 IU/day for pregnant women was safe and most effective in achieving sufficiency in all women and their neonates regardless of race while the current estimated average requirement was comparatively ineffective at achieving adequate circulating 25(OH)D, especially in African Americans.

OBJECTIVE Vitamin D deficiency has been linked to adverse pregnancy outcomes. The purpose of this investigation was to assess total 25-hydroxyvitamin D (25-OH-D) levels at diagnosis of early-onset severe preeclampsia (EOSPE). STUDY DESIGN Following IRB approval, subjects with EOSPE (< 34 weeks gestation with severe preeclampsia) were enrolled in this case-control investigation in a 1:2 ratio with gestation matched, contemporaneous controls. Demographic and outcome information was collected for each subject. Plasma total 25-OH-D levels were determined by radioimmunoassay and reported in ng/mL. Results were analyzed by Mann-Whitney U and multivariable regression. RESULTS Subjects with EOSPE (n=50) were noted to have decreased total 25-OH-D levels relative to healthy controls (n=100; p<0.001). This difference in total 25-OH-D remained significant after controlling for potential confounders. CONCLUSION Total 25-OH-D is decreased at diagnosis of EOSPE. Further study is needed to understand the impact of vitamin D deficiency on pregnancy outcomes.

The objective was to determine the incidence of vitamin D deficiency, insufficiency, and sufficiency in African-American, Hispanic, and Caucasian pregnant women. Blood samples were taken from 154 African-American, 194 Hispanic, and 146 Caucasian women at <14 weeks of gestation; 25 hydroxyvitamin D levels (25(OH)D) levels were measured by radioimmunoassay. The mean 25(OH)D levels in African-American, Hispanic, and Caucasian pregnant women were 15.5 ± 7.2 (standard deviation), 24.1 ± 8.7, 29.0 ± 8.5 ng/mL, respectively. Ninety-seven percent of African-Americans, 81% of Hispanics, and 67% of Caucasians were deficient (25(OH)D levels <20 ng/mL or <50 nmol/L) or insufficient (25(OH)D levels ≥ 20 ng/mL or <32 ng/mL or ≥ 50 nmol/L or <80 nmol/L). Of these pregnant women, 82% had vitamin D levels <32 ng/mL (<80 ng/mL). In logistic regression models, race was the most important risk factor for vitamin D deficiency or insufficiency. African-American women and Hispanic women were more likely to have vitamin D insufficiency and deficiency than Caucasian women. Furthermore, primigravid women were more at risk for vitamin D insufficiency. This study demonstrates widespread vitamin D deficiency and insufficiency in pregnant females living at a southern latitude. African-Americans are at greatest risk.

Despite its discovery a hundred years ago, vitamin D has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to vitamin D’s indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of vitamin D supplementation during pregnancy. An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered.

Objective-To assess the safety and health effects of vitamin D supplementation during pregnancy.Methods and Design-Datasets from two randomized clinical trials were first analyzed separately then combined for this analysis using a common data dictionary. In the NICHD trial, women were randomized to 400, 2000, or 4000 IU vitamin D 3 /day, stratified by race. In the Thrasher Research Fund trial, participants were randomized to 2000 or 4000 IU vitamin D 3 /day. Study drugs were from the same manufacturing lot for both trials. Identical questionnaires were given for comparable sociodemographics & clinical characteristics. Outcome measures were: (1) maternal and neonatal 25(OH)D achieved, and (2) maternal comorbidities of pregnancy (COP). SAS 9.3 was used for all analyses.Results-In the combined cohort, there were 110 controls, 201 in the 2000 IU group, and 193 in the 4000 IU group. No differences between groups in baseline 25(OH)D were found; however, delivery and cord blood values were greater in the 4000 IU group (p<0.0001), an effect that persisted even after controlling for race and study. A greater percent were vitamin D replete in the 4000 IU group (p<0.0001). There was a trend where the 4000 IU group had decreased rates of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access