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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

O'Callaghan, Karen M, Hennessy, Áine, Hull, George L J, Healy, Karina, Ritz, Christian, Kenny, Louise C, Cashman, Kevin D, Kiely, Mairead E
TheAmerican journal of clinical nutrition 2018 v.108 no.1 pp. 77-91
Dietary Reference Intakes, adults, blood serum, cholecalciferol, diet, dose response, latitude, liquid chromatography, metabolites, neonates, nutrition risk assessment, placebos, pregnancy, pregnant women, regression analysis, rickets, tandem mass spectrometry, umbilical cord, Ireland
In the absence of dose-response data, Dietary Reference Values for vitamin D in nonpregnant adults are extended to pregnancy. 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. 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. 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. 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 as NCT02506439.