Health characteristics and outcomes of two randomized vitamin D supplementation trials during pregnancy: A combined analysis

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 4000111 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 2000111 group, and 193 in the 4000111 group. No differences between groups in baseline 25(OH)D were found; however, delivery and cord blood values were greater in the 4000111 group (p < 0.0001), an effect that persisted even after controlling for race and study. A greater percent were vitamin D replete in the 4000111 group (p < 0.0001). There was a trend where the 4000111 group had decreased rates of comorbidities of pregnancy. There was a strong association between COP and final maternal 25(OH)D; an effect that persisted even after controlling for race and study (p = 0.006). Conclusions: Supplementation with 4000 IU/day was associated with lower risk of hypovitaminosis D than Control and 2000111 groups. While not statistically significant, there was a trend toward lower rates of COP as supplementation dose increased. Maternal delivery 25(OH)D was inversely associated with any comorbidity of pregnancy, with fewer events as 25(OH)D increased. Future studies are needed to confirm these findings and determine the mechanisms of action of such effects. This article is part of a Special Issue entitled 'Vitamin D Workshop'. (c) 2013 Elsevier Ltd. All rights reserved.