Estimation of the maternal vitamin D intake that maintains circulating 25-hydroxyvitamin D in late gestation at a concentration sufficient to keep umbilical cord sera ≥25-30 nmol/L: a dose-response, double-blind, randomized placebo-controlled trial in pregnant women at northern latitude

Background: In the absence of dose-response data, Dietary Reference Values for vitamin D in nonpregnant adults are extended to pregnancy. Objective: The aim was to estimate vitamin D intake needed to maintain maternal 25-hydroxyvitamin D [25(OH)D] in late gestation at a concentration sufficient to prevent newborn 25(OH)D <25-30 nmol/L, a threshold indicative of increased risk of nutritional rickets. Design: We conducted a 3-arm, dose-response, double-blind, randomized placebo-controlled trial in Cork, Ireland (51.9 degrees N). A total of 144 white-skinned pregnant women were assigned to receive 0, 10 (400 IU), or 20 (800 IU) mu g vitamin D-3/d from <= 18 wk of gestation. Vitamin D metabolites at 14, 24, and 36 wk of gestation and in cord sera, including 25(OH)D-3, 3-epi-25(OH)D-3, 24,25(OH)(2)D-3, and 25(OH)D-2 were quantified by liquid chromatography-tandem mass spectrometry. A curvilinear regression model predicted the total vitamin D intake (from diet and antenatal supplements plus treatment dose) that maintained maternal 25(OH)D in late gestation at a concentration sufficient to maintain cord 25(OH)D at >= 25-30 nmol/L. Results: Mean +/- SD baseline 25(OH)D was 54.9 +/- 10.7 nmol/L. Total vitamin D intakes at the study endpoint (36 wk of gestation) were 12.1 +/- 8.0, 21.9 +/- 5.3, and 33.7 +/- 5.1 mu g/d in the placebo and 10-mu g and 20-mu g vitamin D-3 groups, respectively; and 25(OH)D was 24.3 +/- 5.8 and 29.2 +/- 5.6 nmol/L higher in the 10- and 20-mu g groups, respectively, compared with placebo (P < 0.001). For maternal 25(OH)D concentrations >= 50 nmol/L, 95% of cord sera were >= 30 nmol/L and 99% were > 25 nmol/L. The estimated vitamin D intake required to maintain serum 25(OH)D at >= 50 nmol/L in 97.5% of women was 28.9 mu g/d. Conclusions: Thirty micrograms of vitamin D per day safely maintained serum 25(OH)D concentrations at >= 50 nmol/L in almost all white-skinned women during pregnancy at a northern latitude, which kept 25(OH)D at > 25 nmol/L in 99% and >= 30 nmol/L in 95% of umbilical cord sera.