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.

As neonatal vitamin D status is determined by circulating maternal 25-hydroxyvitamin D [25(OH)D] concentrations, prevention of maternal vitamin D deficiency during pregnancy is essential for the avoidance of neonatal deficiency. However, a high prevalence of vitamin D deficiency has been extensively reported among gravidae and neonates from ethnic minorities and white populations resident at high latitude. Currently, regulatory authorities recommend vitamin D intakes for pregnant women that are similar to non-pregnant adults of the same age, at 10-15 µg/day (400-600 IU), to meet 25(OH)D thresholds of 25-50 nmol/liter. The lack of pregnancy-specific dietary recommendations is due to inadequate data indicating whether nutritional requirements for vitamin D during pregnancy differ from the non-pregnant state. In addition, there are few dose-response studies to determine the maternal 25(OH)D response to vitamin D intake throughout pregnancy at high latitude. These data are also required to determine vitamin D requirements during pregnancy for prevention of neonatal deficiency, an outcome which is likely to require a higher maternal 25(OH)D concentration than prevention of maternal deficiency only. With regard to the impact of vitamin D on perinatal health outcomes, which could guide pregnancy-specific 25(OH)D thresholds, dietary intervention studies to date have been inconsistent and recent systematic reviews have highlighted issues of low quality and a high risk of bias as drawbacks in the trial evidence to date. Many observational studies have been hampered by a reliance on retrospective data, unclear reporting, suboptimal clinical phenotyping and incomplete subject characterization. Current investigations of vitamin D metabolism during pregnancy have potentially exciting implications for clinical research. This paper provides an update of current dietary recommendations for vitamin D in pregnant women and a synopsis of the evidence relating vitamin D status with maternal and infant health.

Daily oral vitamin D supplementation (400 IU) is recommended for breastfeeding infants (≤1 y). Recent studies have examined alternative approaches to preventing vitamin D deficiency in this population. This systematic review and meta-analysis aimed to estimate the effects of maternal postpartum (M-PP) or infant intermittent (I-INT) vitamin D supplementation on infant 25-hydroxyvitamin D [25(OH)D] concentrations in comparison to routine direct infant daily (I-D) oral supplementation (400 IU). MEDLINE, MEDLINE In-Process, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to December 2018. Inclusion criteria consisted of published, peer-reviewed, vitamin D intervention trials involving lactating women and/or exclusively or partially breastfed term infants. Two reviewers independently extracted study characteristics (e.g., sample size, intervention dose, and duration and mode of administration) and related biochemical and clinical outcomes. Of 28 included trials, 5 randomized controlled trials were incorporated in meta-analyses examining infant 25(OH)D. Overall, M-PP supplementation resulted in modestly lower infant 25(OH)D compared with I-D supplementation (weighted mean difference = −8.1 nmol/L; 95% CI: −15.4, −0.9; I2 = 45%; P = 0.14; 3 trials), but the 2 most recent trials found M-PP to achieve similar infant 25(OH)D as I-D. Comparison of I-INT with I-D was confined to 2 trials with contradictory findings, and it was considered inappropriate for pooled analysis. Meta-analysis was therefore limited by a small number of eligible trials with variable quality of analytically derived 25(OH)D data and inconsistent reporting of safety outcomes, including effects on calcium homeostasis. Considering all 28 included trials, this systematic review highlights M-PP and I-INT regimens as plausible substitutes for routine daily infant vitamin D supplementation, but evidence remains too weak to support a policy update. Dose-ranging, adequately powered trials are required to establish the efficacy, safety, and feasibility of alternative strategies to prevent vitamin D deficiency in breastfeeding infants. This review was registered with PROSPERO as CRD42017069905.

Despite the inverse association between skin colour and efficiency of cutaneous vitamin D synthesis, in addition to the widely accepted racial disparity in vitamin D status, populations of ethnic minority are understudied in terms of setting target serum 25-hydroxyvitamin D concentrations and corresponding dietary requirements for vitamin D. In minority groups, prevention of vitamin D deficiency on a population basis is challenging due to the lack of clarity surrounding the metabolism and transport of vitamin D. Authoritative agencies have been unable to define pregnancy-specific dietary recommendations for vitamin D, owing to an absence of sufficient evidence to confirm whether nutritional requirements for vitamin D are altered during pregnancy. While the question of setting race- and pregnancy-specific dietary reference values for vitamin D has not been addressed to date, endemic vitamin D deficiency has been reported among gravidae worldwide, specifically among ethnic minorities and white women resident at high latitude. In light of the increased risk of nutritional rickets among infants of ethnic minority, coupled with growing evidence for potential non-skeletal roles of vitamin D in perinatal health, determination of the dietary vitamin D requirement that will prevent deficiency during pregnancy is a research priority. However, systematic approaches to establishing dietary requirements are limited by the quality of the available evidence and the under-representation of minority groups in clinical research. This review considers the evidence for racial differences in vitamin D status and response to vitamin D supplementation, with particular application to pregnancy-specific requirements among ethnic minorities resident at high latitudes.