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

Double-blind, randomized, placebo-controlled dose-response trial in healthy, white-skinned pregnant women living in Cork, Ireland. Participants were adults aged 18 years or older and enrolled at 14 ± 2 weeks gestation, with supplementation started by 18 weeks gestation or earlier.

Vitamin D3 was given orally once daily at 10 µg/d (400 IU/d) or 20 µg/d (800 IU/d) from 18 weeks gestation or earlier through 36 weeks gestation. Tablets were identical in appearance in this double-blind, placebo-controlled dose-response trial.

Overall, higher vitamin D3 intake produced a clear dose-response improvement in maternal and cord 25(OH)D status, and the authors concluded that a total vitamin D intake of 30 µg/d safely maintains late-pregnancy maternal 25(OH)D and keeps newborn cord 25(OH)D above the threshold for nutritional rickets. At 36 weeks, maternal 25(OH)D was 24.3 ± 5.8 nmol/L higher than placebo in the 10 µg/d group and 29.2 ± 5.6 nmol/L higher in the 20 µg/d group (P < 0.001). Umbilical cord 25(OH)D was 11.3 ± 3.83 nmol/L higher with 20 µg/d than placebo (P = 0.011), and cord 25(OH)D <30 nmol/L occurred in 31% of placebo versus 3% of the 20 µg/d group (P = 0.008). No hypercalcemia or other safety signal was observed, and adverse events did not differ by group.

The intervention arms were small (N=48 each), and the population was limited to healthy, white-skinned pregnant women in Cork, Ireland, which restricts generalizability. Follow-up was limited to late gestation and delivery, so longer-term maternal or infant clinical outcomes were not assessed.