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
What this study found
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%…
- Study & population
- Double-blind, randomized, placebo-controlled dose-response trial in healthy, white-skinned pregnant women living in Cork, Ireland.
- Intervention
- 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.
- Key limitation
- 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.
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Open PDFOriginal abstract
ABSTRACT 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 (51.9oN). A total of 144 white-skinned pregnant women were assigned to receive 0, 10 (400 IU), or 20 (800 IU) µg vitamin D3/d from ≤18 wk of gestation. Vitamin D metabolites at 14, 24, and 36 wk of gestation and in cord sera, including 25(OH)D3, 3-epi-25(OH)D3, 24,25(OH)2D3, and 25(OH)D2 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 µg/d in the placebo and 10-µg and 20-µg vitamin D3 groups, respectively; and 25(OH)D was 24.3 ± 5.8 and 29.2 ± 5.6 nmol/L higher in the 10- and 20-µg 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 µg/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. This trial was registered at www.clinicaltrials.gov as NCT02506439.