A randomized trial of vitamin D supplementation in 2 community health center networks in South Carolina

Abstract

Objective-To determine whether 4000 IU vitamin D 3 /day (vs. 2000 IU/day) during pregnancy is safe and improves maternal/neonatal 25(OH)D in a dose-dependent manner.Study Design-257 pregnant women 12-16 weeks' gestation were enrolled. Randomization to 2000-vs. 4000 IU/day followed one-month run-in at 2000 IU/day. Participants were monitored for hypercalciuria, hypercalcemia and 25(OH)D status.Results-Maternal 25(OH)D (n=161) increased from 22.7(SD 9.7) at baseline to 36.2(SD 15) and 37.9(SD 13.5) in the 2000-and 4000 IU groups, respectively. While maternal 25(OH)D change from baseline did not differ between groups, 25(OH)D monthly increase differed between groups (p<0.01). No supplementation-related adverse events occurred. Mean cord blood 25(OH)D (ng/mL) was 22.1±10.3 in 2000-and 27.0±13.3 in 4000 IU group (p=0.024). After controlling for race and study site, preterm birth and labor were inversely associated with pre-delivery-and mean 25(OH)D, but not baseline 25(OH)D,.Conclusions-Maternal supplementation with 2000 and 4000 IU vitamin D/day during pregnancy improved maternal/neonatal vitamin D status. Evidence of risk reduction in infection, preterm labor and preterm birth was suggestive, requiring additional studies powered for these endpoints.

Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial

“…These findings are in marked contrast to the results of a recent report involving several thousand subjects consuming up to 10 000 IU vitamin D per day for 1.5 years that demonstrated no relationship with renal stones. 44 In our studies, we have never observed an event of hypercalciuria associated with vitamin D intake or circulating levels of 25(OH)D. 7,8,40,41 Concern remains about vitamin D toxicity as it relates to mortality. 45 A recent metaanalysis by Garland et al on the subject, however, clearly demonstrated increased all-cause mortality at low circulating levels with no such relationship at higher levels.…”

“…39 An Investigational New Drug application to the US Food and Drug Administration was mandated to conduct both the current study and our pregnancy vitamin D supplementation trials. 40,41 Since that time, the IOM has increased the upper limit to 4000 IU per day, 1 and the Endocrine Society set the upper limit at 10 000 IU/day. 42 During the past decade several studies, including our own, were performed using our original Food and Drug Administration Investigational New Drug application involving several thousand patients.…”

Prevalence and predictors of vitamin D deficiency based on maternal mid-gestation and neonatal cord bloods: The Generation R Study

“…Randomized controlled trials of vitamin D supplementation during pregnancy have clarified issues related to optimal dosing and safety (Wagner et al, 2013b, Wagner et al, 2013a but larger trials will be needed in order to focus on the range of adverse health outcomes associated with gestational vitamin D deficiency.…”

Association between vitamin D levels and early onset sepsis in infants: a prospective observational study

“…[3][4][5] Recently, two new randomized controlled studies showed that a daily intake of higher (4000 IU per day) vitamin D resulted with higher circulating 25-OHD levels in pregnant women compared with low doses (200 IU per day and 2000 IU per day). 6,7 Therefore, it was suggested that higher vitamin D supplementation might be required for prevention of hypovitaminosis D and achievement of normal circulating 25-OHD levels (40 to 60 ng ml -1 ) during pregnancy, which would also decrease the incidence of co-morbidities of pregnancy. 8,9 A more recent study showed that lower maternal 25-OHD levels were associated with increased risk of dental caries in infants.…”