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.

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

Objective: Determine prevalence of vitamin D deficiency (VDD) in a diverse group of women presenting for obstetrical care at two community health centers in South Carolina at latitude 32°N. Methods and Design: Any pregnant woman presenting for care at 2 community health centers was eligible to participate. Sociodemographic and clinical history were recorded. A single blood sample was taken to measure circulating 25(OH)D as indicator of vitamin D status [25(OH)D < 20 ng/mL (50 nmol/L deficiency; <32 ng/mL (80 nmol/L) insufficiency]. Total serum calcium, phosphorus, creatinine, and intact parathyroid hormone also were measured. Results: 559 women, [mean age 25.0 ± 5.4 (range 14–43) years] participated: African American (48%), Hispanic (38%), Caucasian/Other (14%). Mean gestational age was 18.5 ± 8.4 (median 14.6, range 6.4–39.6) weeks' gestation. 48% were VDD; an additional 37% insufficient. Greatest degree was in the African American women (68% deficient; 94% insufficient). In multivariable regression, 25(OH)D retained a significant negative association with PTH (P < .001). Conclusions: VDD was high in a diverse group of women, greatest in those of darker pigmentation. The negative correlation between 25(OH)D and PTH confirms their corroborative use as biomarkers of VDD. These findings raise the issue of adequacy of current vitamin D recommendations for pregnant women.

There have been observational reports that maternal vitamin D status at baseline and not closest to delivery is a better predictor of pregnancy outcomes, suggesting that a cascade of events is set into motion that is not modifiable by vitamin D supplementation during later pregnancy. To address this issue, in this exploratory post-hoc analysis using correlation and logistic regression, we sought to measure the strength of the association between serum 25(OH)D concentrations at 3 timepoints during pregnancy: baseline, 1st trimester (<16 wks); 2nd trimester (16-26 wks); and 3rd trimester (≥27 wks) and preterm birth. It was hypothesized that the 25(OH)D value closest to delivery would be most significantly associated with preterm birth. To accomplish this objective, the datasets from NICHD (n=333) and Thrasher Research Fund (n=154) vitamin D supplementation pregnancy studies were combined. The results of this analysis were that 25(OH)D values closer to delivery were more strongly correlated with gestational age at delivery than earlier values: 1st trimester: r=0.11 (p=0.02); 2nd trimester: r=0.08 (p=0.09); and 3rd trimester: r=0.15 (p=0.001). When logistic regression was performed with preterm birth (<37 weeks) as the outcome and 25(OH)D quartiles as the predictor variable, adjusting for study and participant race/ethnicity, as with the correlation analysis, the measurements closer to delivery were more significantly associated and had a higher magnitude of effect. That is, at baseline, those who had serum concentrations <50 nmol/L (20 ng/mL) had 3.3 times of odds of a preterm birth compared to those with serum concentrations ≥100 nmol/L (40 ng/mL; p=0.27). At 2nd trimester, the odds were 2.0 fold (p=0.21) and at the end of pregnancy, the odds were 3.8 fold (p=0.01). The major findings from this exploratory analysis were: (1) maternal vitamin D status closest to delivery date was more significantly associated with preterm birth, suggesting that later intervention as a rescue treatment may positively impact the risk of preterm delivery, and (2) a serum concentration of 100 nmol/L (40 ng/mL) in the 3rd trimester was associated with a 47% reduction in preterm births.

Background Two vitamin D pregnancy supplementation trials were recently undertaken in South Carolina: The NICHD (n=346) and Thrasher Research Fund (TRF, n=163) studies. The findings suggest increased dosages of supplemental vitamin D were associated with improved health outcomes of both mother and newborn, including risk of preterm birth (<37 weeks gestation). How that risk was associated with 25(OH)D serum concentration, a better indicator of vitamin D status than dosage, by race/ethnic group and the potential impact in the community was not previously explored. While a recent IOM report suggested a concentration of 20 ng/mL should be targeted, more recent work suggests optimal conversion of 25(OH)D to 1,25(OH)2D takes place at 40 ng/mL in pregnant women. Objective Post-hoc analysis of the relationship between 25(OH)D concentration and preterm birth rates in the NICHD and TRF studies with comparison to Charleston County, South Carolina March of Dimes (CC-MOD) published rates of preterm birth to assess potential risk reduction in the community. Methods Using the combined cohort datasets (n=509), preterm birth rates both for the overall population and for the subpopulations achieving 25(OH)D concentrations of ≤20 ng/mL, >20 to <40 ng/mL, and ≥40 ng/mL were calculated; subpopulations broken down by race/ethnicity were also examined. Log-binomial regression was used to test if an association between 25(OH)D serum concentration and preterm birth was present when adjusted for covariates; locally weighted regression (LOESS) was used to explore the relationship between 25(OH)D concentration and gestational age (weeks) at delivery in more detail. These rates were compared with 2009-2011 CC-MOD data to assess potential risk reductions in preterm birth. Results Women with serum 25(OH)D concentrations ≥40 ng/mL (n=233) had a 57% lower risk of preterm birth compared to those with concentrations ≤20 ng/mL [n=82; RR=0.43, 95% confidence interval (CI)=0.22,0.83]; this lower risk was essentially unchanged after adjusting for covariates (RR=0.41, 95% CI=0.20,0.86). The fitted LOESS curve shows gestation week at birth initially rising steadily with increasing 25(OH)D and then plateauing at ~40 ng/mL. Broken down by race/ethnicity, there was a 79% lower risk of preterm birth among Hispanic women with 25(OH)D concentrations ≥40 ng/mL (n=92) compared to those with 25(OH)D concentrations ≤20 ng/mL (n=29; RR=0.21, 95% CI=0.06,0.69) and a 45% lower risk among Black women (n=52 and n=50; RR=0.55, 95% CI=0.17,1.76). There were too few white women with low 25(OH)D concentrations for assessment (n=3). Differences by race/ethnicity were not statistically significant with 25(OH)D included as a covariate. Compared to the CC-MOD reference group, women with serum concentrations ≥40 ng/mL in the combined cohort had a 46% lower rate of preterm birth overall (n=233, p=0.004) with a 66% lower rate among Hispanic women (n=92, p=0.01) and a 58% lower rate among black women (n=52, p=0.04). Conclusions In this post-hoc analysis, achieving a 25...