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

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.

Variation in plasma 25-hydroxyvitamin D2 and D3 in normal pregnancy with gestational age, sampling season, and complications: A longitudinal cohort study

“…At that time, two-thirds of women reported using supplements, although two-thirds took less than 10 μg/day [22]. The present results indicate, in accordance with those of other studies, that 10 μg of vitamin D3 daily is not sufficient to maintain 25(OH)D concentrations above 50 nmol/L in pregnancy, especially during winter and spring [23,24]. Some of the variations in recommendations might be due to…”

The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data

“…Some aspects of vitamin D metabolism are of physiologic relevance in pregnancy [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Compared to non-pregnant women, there is a significant increase in 1,25(OH)2D concentrations, with a 2-fold increase in in the first trimester of pregnancy and a further rise to a 2- to 3-fold increase during the course of pregnancy and a rapid decline after delivery [ 35 ].…”

“…While 25(OH)D crosses the placenta, 1,25(OH)2D does not but is produced by the fetal kidneys [ 41 ]. In general, cord blood 25(OH)D concentrations are about 50 to 80% of serum 25(OH)D concentrations of the mother [ 39 ]. This underscores the importance of adequate vitamin D supply to pregnant women.…”

“…We did not restrict our search to cover specific outcomes but rather aimed to include all available outcomes regarding fertility as well as pregnancy and lactation because the purpose of this review is to provide an up to date overview of all clinical data on these issues. We refer the reader to other publications regarding physiologic mechanisms underlying the proposed effects of vitamin D on fertility, pregnancy and lactation [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

Mineral Homeostasis in Murine Fetuses Is Sensitive to Maternal Calcitriol but Not to Absence of Fetal Calcitriol

“…(5) Compared with adult values, cord blood normally shows low calcitriol, 25OHD concentrations about 75% to 100% of maternal values, proportionately higher concentrations of 24-hydroxylated and C-3-epimerized vitamin D metabolites compared with 25OHD and calcitriol, increased serum calcium and phosphorus, low PTH, and low to normal intact FGF23. (5,29,30) Severely vitamin D-deficient babies have shown normal calcium, phosphorus, and PTH, whereas skeletal morphology and mineral content have generally been normal. (5) Intestinal calcium absorption is largely passive at birth (especially so in premature babies) but becomes calcitriol-dependent gradually after birth.…”