Vitamin D status of pregnant women with obesity in the UK and its association with pregnancy outcomes: a secondary analysis of the UK Pregnancies Better Eating and Activity Trial (UPBEAT) study.

Prenatal vitamin D deficiency is widely reported and may affect perinatal outcomes. In this secondary analysis of the UK Pregnancies Better Eating and Activity Trial, we examined vitamin D status and its relationship with selected pregnancy outcomes in women with obesity (BMI ≥ 30 kg/m2) from multi-ethnic inner-city settings in the UK. Determinants of vitamin D status at a mean of 17 ± 1 weeks' gestation were assessed using multivariable linear regression and reported as percent differences in serum 25-hydroxyvitamin D (25(OH)D). Associations between 25(OH)D and clinical outcomes were examined using logistic regression. Among 1089 participants, 67 % had 25(OH)D < 50 nmol/l and 26 % had concentrations < 25 nmol/l. In fully adjusted models accounting for socio-demographic and anthropometric characteristics, 25(OH)D was lower among women of Black (% difference = -33; 95 % CI: -39, -27), Asian (% difference = -43; 95 % CI: -51, -35) and other non-White (% difference = -26; 95 % CI: -35, -14) ethnicity compared with women of White ethnicity (n 1086; P < 0·001 for all). In unadjusted analysis, risk of gestational diabetes was greater in women with 25(OH)D < 25 nmol/l compared with ≥ 50 nmol/l (OR = 1·58; 95 % CI: 1·09, 2·31), but the magnitude of effect estimates was attenuated in the multivariable model (OR = 1·33; 95 % CI: 0·88, 2·00). There were no associations between 25(OH)D and risk of preeclampsia, preterm birth or small for gestational age or large-for-gestational-age delivery. These findings demonstrate low 25(OH)D among pregnant women with obesity and highlight ethnic disparities in vitamin D status in the UK. However, evidence for a greater risk of adverse perinatal outcomes among women with vitamin D deficiency was limited.

Prenatal but not continued postpartum vitamin D supplementation reduces maternal bone resorption as measured by C-terminal telopeptide of type 1 collagen without effects on other biomarkers of bone metabolism.

Vitamin D is a key regulator of bone mineral homeostasis and may modulate maternal bone health during pregnancy and postpartum. Using previously-collected data from the Maternal Vitamin D for Infant Growth (MDIG) trial in Dhaka, Bangladesh, we aimed to investigate the effects of prenatal and postpartum vitamin D3 supplementation on circulating biomarkers of bone formation and resorption at delivery and 6 months postpartum. MDIG trial participants were randomized to receive a prenatal;postpartum regimen of placebo or vitamin D3 (IU/week) as either 0;0 (Group A), 4200;0 (B), 16,800;0 (C), 28,000;0 (D) or 28,000;28,000 (E) from 17 to 24 weeks' gestation to 6 months postpartum. As this sub-study was not pre-planned, the study sample included MDIG participants who had data for at least 1 biomarker of interest at delivery or 6 months postpartum, with a corresponding baseline measurement (n = 690; 53 % of 1300 enrolled trial participants). Biomarkers related to bone turnover were measured in maternal venous blood samples collected at enrolment, delivery, and 6 months postpartum: osteoprotegerin (OPG), osteocalcin (OC), receptor activator nuclear factor kappa-B ligand (RANKL), fibroblast growth factor 23 (FGF23), procollagen type 1 N-terminal propeptide, (P1NP) and carboxy terminal telopeptide of type 1 collagen (CTx). Supplementation effects were expressed as percent differences between each vitamin D group and placebo with 95 % confidence intervals (95 % CI). Of 690 participants, 64 % had 25-hydroxyvitamin D concentrations (25OHD) <30 nmol/L and 94 % had 25OHD < 50 nmol/L at trial enrolment. At delivery, mean CTx concentrations were 27 % lower in group E versus placebo (95 % CI: -38, -13; P < 0.001), adjusting for enrolment concentrations. However, at 6 months postpartum, CTx concentrations were not statistically different in group E versus placebo (14 %; 95 % CI: -5.3, 37; P = 0.168), adjusting for delivery CTx concentrations. Effects on other biomarkers at delivery or postpartum were not statistically significant. In conclusion, prenatal high-dose vitamin D supplementation reduced bone resorption during pregnancy, albeit by only one biomarker, and without evidence of a sustained effect in the postpartum period. However, further evidence is needed to substantiate potential maternal bone health benefits of vitamin D in the postpartum period.

Estimation of skeletal muscle mass in 4-year-old children using the D3-creatine dilution method.

BACKGROUND: Given limited experience in applying the creatine-(methyl-D3) (D3Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh. METHODS: Following D3Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2-4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D3Cr and D3-creatinine enrichment were analyzed by liquid chromatography-tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer. RESULTS: SMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: -0.031, 0.038; n = 91). CONCLUSIONS: The D3Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach. IMPACT: The D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants. SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength. High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings.

Maternal prenatal, with or without postpartum, vitamin D3 supplementation does not improve maternal iron status at delivery or infant iron status at 6 months of age: secondary analysis of a randomised controlled trial.

Background: Vitamin D may modify iron status through regulation of hepcidin and inflammatory pathways. This study aimed to investigate effects of maternal vitamin D supplementation on iron status in pregnancy and early infancy. Methods: In a trial in Dhaka, Bangladesh, women (n=1300) were randomised to one of five vitamin D3 regimens from 17 to 24 weeks' gestation until 26 weeks postpartum (prenatal; postpartum doses): 0;0, 4200;0, 16 800;0, 28 000;0 or 28 000;28 000 IU/week. All participants received standard iron-folic acid supplementation. In this secondary analysis (n=998), we examined effects of prenatal;postpartum vitamin D on serum ferritin and other biomarkers of maternal iron status (transferrin saturation, total iron binding capacity, soluble transferrin receptor and hepcidin) at delivery, and infant ferritin and haemoglobin at 6 months of age. Using linear regression, we estimated per cent mean differences between each intervention group and placebo with 95% CIs, with and without adjustment for baseline ferritin or inflammatory biomarkers (C reactive protein and α-1-acid glycoprotein (AGP)). Results: At delivery, ferritin concentrations were similar between each intervention group and placebo in unadjusted (n=998) and baseline ferritin-adjusted analyses (n=992; p>0.05). Compared with placebo, AGP was lower in each intervention group (per cent difference (95% CI) = -11% (-21 to -1.0), -14% (-23 to -3.5) and -11% (-19 to -2.0) in the 4200 IU/week, 16 800 IU/week and 28 000 IU/week groups, respectively; n=779). In the subgroup of women with baseline 25-hydroxyvitamin D < 30 nmol/L, ferritin was lower in each intervention group versus placebo (-23% (-37 to -5.0), -20% (-35 to -1.9) and -20% (-33 to -4.1) in the 4200 IU/week, 16 800 IU/week and 28 000 IU/week groups, respectively; n=645); effects were slightly attenuated after adjustment for inflammation (n=510). There were no effects of vitamin D on other iron biomarkers among women at delivery or infants aged 6 months. Conclusion: These findings do not support improvement of iron status by vitamin D. The effect of prenatal vitamin D supplementation on ferritin may reflect an anti-inflammatory mechanism.

Fecal Iron Measurement in Studies of the Human Intestinal Microbiome.

Iron is an essential micronutrient for humans and their intestinal microbiota. Host intestinal cells and iron-dependent bacteria compete for intraluminal iron, so the composition and functions of the gut microbiota may influence iron availability. Studies of the effects of the microbiota or probiotic interventions on host iron absorption may be particularly relevant to settings with high burdens of iron deficiency and gastrointestinal infections, since inflammation reduces iron bioavailability and unabsorbed intraluminal iron may modify the composition of the microbiota. The quantification of stool iron content may serve as an indicator of the amount of intraluminal iron to which the intestinal microbiota is exposed, which is particularly relevant for studies of the effect of iron on the intestinal microbiome, where fecal samples collected for purposes of microbiome characterization can be leveraged for stool iron analysis. However, few studies are available to guide researchers in the selection and implementation of stool iron assays, particularly because cross-comparison of available methods is limited in literature. This review aims to describe the available stool iron quantification methods and highlight their potential application in studies of iron-microbiome relationships, with a focus on pediatric research. MS-based methods offer high sensitivity and precision, but the need for expensive equipment and the high per-sample and maintenance costs may limit their widespread use. Conversely, colorimetric assays offer lower cost, ease of use, and rapid turnaround times but have thus far been optimized primarily for blood-derived matrices rather than stool. Further research efforts are needed to validate and standardize methods for stool iron assessment and to determine if the incorporation of such analyses in human microbiome studies 1) yields insights into the interactions between intestinal microbiota and iron and 2) contributes to the development of interventions that mitigate iron deficiency and promote a healthy microbiome.

Effect of maternal prenatal and postpartum vitamin D supplementation on offspring bone mass and muscle strength in early childhood: follow-up of a randomized controlled trial.

BACKGROUND: Maternal vitamin D status during pregnancy and lactation is a modifiable factor that may influence offspring musculoskeletal outcomes. However, few randomized trials have tested the effects of prenatal or postpartum vitamin D supplementation on offspring bone and muscle development. OBJECTIVES: The aim was to examine hypothesized effects of improvements in early-life vitamin D status on childhood musculoskeletal health in Dhaka, Bangladesh. METHODS: In a previously completed, double-blind, dose-ranging trial, healthy pregnant women (n = 1300) were recruited at 17-24 weeks' gestation and randomly assigned to a prenatal/postpartum regimen of 0/0, 4200/0, 16,800/0, 28,000/0, or 28,000/28,000 IU cholecalciferol (vitamin D3)/wk until 26 wk postpartum. In this new report, we describe additional follow-up at 4 y of age (n = 642) for longer-term outcomes. Bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by DXA. Grip strength was tested using a hand-held dynamometer. The primary comparison was children of women assigned to 28,000 IU/wk prenatally compared with placebo. Differences are expressed as means and 95% CIs. RESULTS: Total-body-less-head (TBLH) BMC, TBLH aBMD, and grip strength were similar in the combined high-dose prenatal (28,000/0 and 28,000/28,000 IU/wk) compared with placebo groups (mean difference [95% CI] = 0.61 g [-10.90, 12.13], 0.0004 g/cm2 [-0.0089, 0.0097], and 0.02 kg [-0.26, 0.31], respectively). In dose-ranging analyses, TBLH BMC and aBMD, whole-body BMC and aBMD, and grip strength in each of the prenatal vitamin D groups were not significantly different from placebo (P > 0.05 for all comparisons). Only head aBMD was greater in children of women assigned to the 28,000/28,000-IU regimen compared with placebo (mean difference [95% CI] = 0.024 g/cm2 [0.0009, 0.047], P = 0.042); the effect was attenuated upon adjustment for child height, weight, and sex (P = 0.11). CONCLUSIONS: Maternal prenatal, with or without postpartum, vitamin D supplementation does not improve child BMC, aBMD, or grip strength at 4 y of age. The MDIG trial and present follow-up study were registered prospectively at www.clinicaltrials.gov as NCT01924013 and NCT03537443, respectively.

Basal Vitamin D Status and Supplement Dose Are Primary Contributors to Maternal 25-Hydroxyvitamin D Response to Prenatal and Postpartum Cholecalciferol Supplementation.

BACKGROUND: Variability in the 25-hydroxyvitamin D [25(OH)D] response to prenatal and postpartum vitamin D supplementation is an important consideration for establishing vitamin D deficiency prevention regimens. OBJECTIVES: We aimed to examine interindividual variation in maternal and infant 25(OH)D following maternal vitamin D supplementation. METHODS: In a randomized trial of maternal vitamin D supplementation (Maternal Vitamin D for Infant Growth Trial), healthy pregnant women (n = 1300) received a prenatal cholecalciferol (vitamin D-3) dose of 0, 4200, 16,800, or 28,000 IU/wk from 17 to 24 wk of gestation followed by placebo to 6 mo postpartum. A fifth group received 28,000 IU cholecalciferol/wk both prenatally and postpartum. In a subset of participants, associations of 25(OH)D with hypothesized explanatory factors were estimated in women at delivery (n = 655) and 6 mo postpartum (n = 566), and in their infants at birth (n = 502) and 6 mo of age (n = 215). Base models included initial 25(OH)D and supplemental vitamin D dose. Multivariable models were extended to include other individual characteristics and specimen-related factors. The model coefficient of determination (R2) was used to express the percentage of total variance explained. RESULTS: Supplemental vitamin D intake and initial 25(OH)D accounted for the majority of variance in maternal 25(OH)D at delivery and postpartum (R2 = 70% and 79%, respectively). Additional characteristics, including BMI, contributed negligibly to remaining variance (<5% increase in R2). Variance in neonatal 25(OH)D was explained mostly by maternal delivery 25(OH)D and prenatal vitamin D intake (R2 = 82%). Variance in 25(OH)D in later infancy could only partly be explained by numerous biological, sociodemographic, and laboratory-related characteristics, including feeding practices (R2 = 43%). CONCLUSIONS: Presupplementation 25(OH)D and vitamin D supplemental dose are the major determinants of the response to maternal prenatal vitamin D intake. Vitamin D dosing regimens to prevent maternal and infant vitamin D deficiency should take into consideration the mean 25(OH)D concentration of the target population.

Vitamin D in Breastfed Infants: Systematic Review of Alternatives to Daily Supplementation.

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.

Interactions between Vitamin D Status, Calcium Intake and Parathyroid Hormone Concentrations in Healthy White-Skinned Pregnant Women at Northern Latitude.

Adverse effects of low vitamin D status and calcium intakes in pregnancy may be mediated through functional effects on the calcium metabolic system. Little explored in pregnancy, we aimed to examine the relative importance of serum 25-hydroxyvitamin D (25(OH)D) and calcium intake on parathyroid hormone (PTH) concentrations in healthy white-skinned pregnant women. This cross-sectional analysis included 142 participants (14 ± 2 weeks' gestation) at baseline of a vitamin D intervention trial at 51.9 °N. Serum 25(OH)D, PTH, and albumin-corrected calcium were quantified biochemically. Total vitamin D and calcium intakes (diet and supplements) were estimated using a validated food frequency questionnaire. The mean ± SD vitamin D intake was 10.7 ± 5.2 µg/day. With a mean ± SD serum 25(OH)D of 54.9 ± 22.6 nmol/L, 44% of women were <50 nmol/L and 13% <30 nmol/L. Calcium intakes (mean ± SD) were 1182 ± 488 mg/day and 23% of participants consumed <800 mg/day. The mean ± SD serum albumin-adjusted calcium was 2.2 ± 0.1 mmol/L and geometric mean (95% CI) PTH was 9.2 (8.4, 10.2) pg/mL. PTH was inversely correlated with serum 25(OH)D (r = -0.311, p < 0.001), but not with calcium intake or serum calcium (r = -0.087 and 0.057, respectively, both p > 0.05). Analysis of variance showed that while serum 25(OH)D (dichotomised at 50 nmol/L) had a significant effect on PTH (p = 0.025), calcium intake (<800, 800⁻1000, ≥1000 mg/day) had no effect (p = 0.822). There was no 25(OH)D-calcium intake interaction effect on PTH (p = 0.941). In this group of white-skinned women with largely sufficient calcium intakes, serum 25(OH)D was important for maintaining normal PTH concentration.

Central haemodynamics in normal pregnancy: a prospective longitudinal study.

OBJECTIVE: To conduct a longitudinal evaluation of the central haemodynamic adaptations of normal pregnancy. METHODS: This was a prospective longitudinal study involving healthy, normotensive women who were having an uncomplicated, singleton pregnancy. Brachial and central SBP, DBP, mean arterial pressure (MAP), brachial and central pulse pressure (PP), aorta-to-brachial pulse pressure amplification (AMPA-B), heart rate (HR), augmentation index adjusted for HR (AIx75), carotid-femoral pulse wave velocity (cfPWV) and cardiac output (CO) were measured at a mean gestational age of 14, 24 and 36 weeks. RESULTS: One hundred women were followed prospectively throughout pregnancy. Brachial and central SBP, DBP and MAP decreased slightly in early gestation, followed by a significant increase in late gestation (P < 0.05). Brachial PP was lowest in the final trimester (P = 0.011) whereas central PP remained unchanged, resulting in a significant decrease in AMPA-B (P < 0.001). HR and AIx75 rose continuously throughout pregnancy (P < 0.001). A significant fall in cfPWV was observed mid-pregnancy, which remained significant after adjustment for MAP and HR (P < 0.05). CO rose mid-pregnancy, before returning to baseline values by week 36 of gestation (P < 0.05). CONCLUSION: To our knowledge, this is the largest prospective study to evaluate several central haemodynamic parameters in normotensive pregnancies, including adjusted-AIx and the gold-standard cfPWV. These data are a necessary foundation for the establishment of pregnancy-specific reference values and provide reference data for future trial design.

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.

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.

Systematic Review of Vitamin D and Hypertensive Disorders of Pregnancy.

This narrative systematic review evaluates growing evidence of an association between low maternal vitamin D status and increased risk of hypertensive disorders. The inclusion of interventional, observational, and dietary studies on vitamin D and all hypertensive disorders of pregnancy is a novel aspect of this review, providing a unique contribution to an intensively-researched area that still lacks a definitive conclusion. To date, trial evidence supports a protective effect of combined vitamin D and calcium supplementation against preeclampsia. Conflicting data for an association of vitamin D with gestational hypertensive disorders in observational studies arises from a number of sources, including large heterogeneity between study designs, lack of adherence to standardized perinatal outcome definitions, variable quality of analytical data for 25-hydroxyvitamin D (25(OH)D), and inconsistent data reporting of vitamin D status. While evidence does appear to lean towards an increased risk of gestational hypertensive disorders at 25(OH)D concentrations <50 nmol/L, caution should be exercised with dosing in trials, given the lack of data on long-term safety. The possibility that a fairly narrow target range for circulating 25(OH)D for achievement of clinically-relevant improvements requires further exploration. As hypertension alone, and not preeclampsia specifically, limits intrauterine growth, evaluation of the relationship between vitamin D status and all terms of hypertension in pregnancy is a clinically relevant area for research and should be prioritised in future randomised trials.

Ethnic disparities in the dietary requirement for vitamin D during pregnancy: considerations for nutrition policy and research.

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.

Vitamin D in pregnancy: current perspectives and future directions.

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.