Interactive Effects of Maternal Vitamin D Status and Socio-Economic Status on the Risk of Spontaneous Abortion: Evidence from Henan Province, China.

BACKGROUND: Maternal vitamin D deficiency might generate adverse reproductive outcomes, and socio-economic inequalities in micronutrient-related diseases have often been found. This study aimed to explore the interactive effects of maternal vitamin D status and socio-economic status (SES) on risk of spontaneous abortion. METHODS: A population-based case-control study was conducted including 293 women with spontaneous abortion and 498 control women in December 2009 and January, 2010 in Henan Province, China. Information on pregnancy outcomes, maternal demographic, lifestyle and exposure factors and blood samples were collected at the same time. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. SES index was constructed with principal component analysis by aggregating women's and their husbands' education level and occupation, and household income and expenditure. Interactive effects were assessed on a multiplicative scale with ratio of the odds ratio (ROR). RESULTS: Compared to those with high SES and vitamin D sufficiency, women with vitamin D deficiency and low SES index had an increased risk of spontaneous abortion (aOR: 1.99; 95% CI: 1.23-3.23). The ROR was 2.06 (95% CI: 1.04-4.10), indicating a significant positive multiplicative interaction. CONCLUSIONS: Maternal low SES may strengthen the effect of vitamin D deficiency exposure on spontaneous abortion risk in this Chinese population.

The economic case for prevention of population vitamin D deficiency: a modelling study using data from England and Wales.

BACKGROUND: Vitamin D deficiency (VDD) affects the health and wellbeing of millions worldwide. In high latitude countries such as the United Kingdom (UK), severe complications disproportionally affect ethnic minority groups. OBJECTIVE: To develop a decision-analytic model to estimate the cost effectiveness of population strategies to prevent VDD. METHODS: An individual-level simulation model was used to compare: (I) wheat flour fortification; (II) supplementation of at-risk groups; and (III) combined flour fortification and supplementation; with (IV) a 'no additional intervention' scenario, reflecting the current Vitamin D policy in the UK. We simulated the whole population over 90 years. Data from national nutrition surveys were used to estimate the risk of deficiency under the alternative scenarios. Costs incurred by the health care sector, the government, local authorities, and the general public were considered. Results were expressed as total cost and effect of each strategy, and as the cost per 'prevented case of VDD' and the 'cost per Quality Adjusted Life Year (QALY)'. RESULTS: Wheat flour fortification was cost saving as its costs were more than offset by the cost savings from preventing VDD. The combination of supplementation and fortification was cost effective (£9.5 per QALY gained). The model estimated that wheat flour fortification alone would result in 25% fewer cases of VDD, while the combined strategy would reduce the number of cases by a further 8%. CONCLUSION: There is a strong economic case for fortifying wheat flour with Vitamin D, alone or in combination with targeted vitamin D3 supplementation.

Reducing waste: a guidelines-based approach to reducing inappropriate vitamin D and TSH testing in the inpatient rehabilitation setting.

Background: Laboratory overutilisation increases healthcare costs, and can lead to overdiagnosis, overtreatment and negative health outcomes. Discipline-specific guidelines do not support routine testing for Vitamin D and thyroid-stimulating hormone (TSH) in the inpatient rehabilitation setting, yet 94% of patients had Vitamin D and TSH tests on admission to inpatient rehabilitation at our institution. Our objective was to reduce Vitamin D and TSH testing by 25% on admission to inpatient Stroke, Spinal Cord Injury, Acquired Brain Injury and Amputee Rehabilitation units. Methods: A fishbone framework for root cause analysis revealed potential causes underlying overutilisation of Vitamin D and TSH testing. A series of Plan-Do-Study-Act (PDSA) cycles were introduced to target remediable factors, starting with an academic detailing intervention with key stakeholders that reviewed applicable clinical guidelines for each patient care discipline and the rationale for reducing admission testing. Simultaneously, computerised clinical decision support (CCDS) limited Vitamin D testing to specific criteria. Audit and feedback were used in a subsequent PDSA cycle. Frequency of Vitamin D and TSH testing on admission was the primary outcome measure. The number of electronic admission order caresets containing automatic Vitamin D and/or TSH orders before and after the interventions was the process measure. Rate of Vitamin D supplementation and changes in thyroid-related medication were the balancing measures. Results: After implementation, 2.9% of patients had admission Vitamin D testing (97% relative reduction) and 53% of patients had admission TSH testing (43% relative reduction). Admission order caresets with prepopulated Vitamin D and TSH orders decreased from 100% (n=6) to 0%. The interventions were successful; similar to previous literature, CCDS was more effective than education and audit and feedback interventions alone. The interventions represent >$9000 annualised savings.

Vitamin D deficiency in children: a challenging diagnosis!

The concern about the assessment of vitamin D status is growing. Numerous publications warn about the high prevalence of vitamin D deficiency, as well as the potential role of vitamin D in non-bone health outcomes. The status of vitamin D is usually assessed by measuring serum total 25-hydroxyvitamin D (25OHD) concentration. This is the major circulating form of vitamin D and keeps an inverse correlation with serum parathyroid hormone (PTH) concentration. A value of 25OHD of 20 ng/ml is generally assumed as threshold of vitamin D sufficiency in epidemiologic studies because serum PTH tends to increase when the 25OHD concentration stands below this value. In pediatric population, very few studies have analyzed this issue and the negative relationship between serum 25OHD and serum PTH is not clear, which is the suitable circulating concentration of 25OHD and the threshold of deficiency being matters of controversy. The majority of 25OHD circulates in serum tightly bound to a globulin (DBP). According to the free hormone hypothesis, protein-bound hormones are not biologically available and it is the free form that exerts or facilitates the physiologic actions. If this is true, factors that affect DBP may alter the interpretation of total serum 25OHD measurements.

Screening for hypovitaminosis D: cost-effective or not?

Few topics have elicited more emotion than the issue of screening for vitamin D status and the discussion on the need for global supplementation with vitamin D metabolites. The importance of the problem is highlighted by the USPSTF posted draft research plan with the aim of making an update recommendations statement, possibly next year. Here, we discuss two different viewpoints on screening for vitamin D status: for and against. In the literature there are scientifically sound opinions supporting pro and cons positions. However, we believe that the best way to definitively elucidate this issue is the implementation of a randomized controlled trial evaluating clinical outcomes or harms in persons screened versus those not screened for vitamin D deficiency. The feasibility of such a trial is probably questionable owing to uncertainties still present concerning threshold for vitamin D sufficiency and end points (that is, for example, improved bone mineral density, reduced risk of falls and so on) to be reached.

Vitamin D status of tuberculosis patients with diabetes mellitus in different economic areas and associated factors in China.

BACKGROUND: Vitamin D could be a mediator in the association between tuberculosis (TB) and diabetes mellitus (DM). A large scale multi-center study confirmed that TB patients with DM had significantly lower serum vitamin D level compared with those without DM and reported that DM was a strong independent risk factor for vitamin D deficiency. OBJECTIVES: This study was undertaken to determine amongst patients with both TB and DM living in different economically defined areas in China: i) their baseline characteristics, ii) their vitamin D status and iii) whether certain baseline characteristics were associated with vitamin D deficiency. METHODS: In DM-TB patients consecutively attending seven clinics or hospitals, we measured 25 hydroxycholecalciferol at the time of registration using electrochemiluminescence in a COBASE 601 Roche analyser by chemiluminescence immunoassay. Data analysis was performed using chi square test and multivariate logistic regression. RESULTS: There were 178 DM-TB patients that included 50 from economically well-developed areas, 103 from better-off areas and 25 from a poverty area. Median vitamin D levels in well-developed, better-off and poverty areas were 11.5ng/ml, 12.2ng/ml and 11.5ng/ml respectively. Amongst all patients, 149 (84%) had vitamin D deficiency-91 (51%) with vitamin D deficiency (10-19.9 ng/ml) and 58 (33%) with severe deficiency (< 10 ng/ml). There was a significantly higher proportion with vitamin D deficiency in the poverty area. The adjusted odds of vitamin D deficiency (25-(OH)D3 <20 ng/ml) were significantly higher in those with longer history of DM (P = 0.038) and with HbA1c≥10% (P = 0.003). CONCLUSION: Over 80% of TB patients with DM in China were vitamin D deficient, with risk factors being residence in a poverty area, a long duration of DM and uncontrolled DM. TB programme managers and clinicians need to pay more attention to the vitamin D status of their patients.

Vitamin D and health care costs: Results from two independent population-based cohort studies.

BACKGROUND & AIMS: Vitamin D deficiency is associated with higher morbidity. However, there is few data regarding the effect of vitamin D deficiency on health care costs. This study examined the cross-sectional and longitudinal associations between the serum 25-hydroxy vitamin D concentration (25OHD) and direct health care costs and hospitalization in two independent samples of the general population in North-Eastern Germany. METHODS: We studied 7217 healthy individuals from the 'Study of Health in Pomerania' (SHIP n = 3203) and the 'Study of Health in Pomerania-Trend' (SHIP-Trend n = 4014) who had valid 25OHD measurements and provided data on annual total costs, outpatient costs, hospital stays, and inpatient costs. The associations between 25OHD concentrations (modelled continuously using factional polynomials) and health care costs were examined using a generalized linear model with gamma distribution and a log link. Poisson regression models were used to estimate relative risks of hospitalization. RESULTS: In cross-sectional analysis of SHIP-Trend, non-linear associations between the 25OHD concentration and inpatient costs and hospitalization were detected: participants with 25OHD concentrations of 5, 10 and 15 ng/ml had 226.1%, 51.5% and 14.1%, respectively, higher inpatient costs than those with 25OHD concentrations of 20 ng/ml (overall p-value = 0.001) in multivariable models. CONCLUSIONS: We found a relation between lower 25OHD concentrations and increased inpatient health care costs and hospitalization. Our results thus indicate an influence of vitamin D deficiency on health care costs in the general population.

Costs of vitamin D testing and prescribing among children in primary care.

Vitamin D has attracted considerable interest in recent years, with a marked increase in diagnosis of vitamin D deficiency seen among children in clinical practice in the UK. The economic implications of this change in diagnostic behaviour have not been explored. We performed a cohort study to examine longitudinal trends in healthcare expenditure arising from vitamin D testing and prescribing for children in primary care in England, using the electronic healthcare records of 722,525 children aged 0-17 years held in The Health Improvement Network database. Combined costs of vitamin D tests and prescriptions increased from £1647 per 100,000 person-years in 2008 (95% CI, £934 to £3007) to £28,913 per 100,000 person-years in 2014 (95% CI, £26,361 to £31,739). The total cost of vitamin D prescriptions and tests for children in primary care at the national level in England in 2014 was estimated to be £4.31 million (95% CI, £2.96-£6.48 million). CONCLUSION: There has been a marked increase in healthcare expenditure on vitamin D tests and prescriptions for children in primary care over the past decade. Future research should explore the drivers for this change in diagnostic behaviour and the reasons prompting investigation of vitamin D status in clinical practice. What is Known: • Vitamin D deficiency has attracted considerable interest in recent years, with a marked increase in diagnosis seen in children. • The economic implications of this change in diagnostic behaviour have not been explored. What is New: • There has been a large increase in healthcare expenditure on vitamin D tests and prescriptions for children in primary care in England over the past decade (> 15 fold between 2008 and 2013). • Screening of vitamin D status in children without specific risk factors or clinical features of deficiency may represent avoidable healthcare expenditure.

Preventing vitamin D deficiency (VDD): a systematic review of economic evaluations.

Background: Vitamin D deficiency (VDD) is a public health concern worldwide. If untreated, it can lead to reduced quality of life and escalated costs brought about by ill-health. Preventive programmes to improve population vitamin D status exist but little is known about their cost-effectiveness. This information is vital so that decision-makers adopt efficient strategies and optimise use of public resources. Aims: Systematically review and critically appraise economic evaluations of population strategies to prevent VDD. Methods: The databases reviewed were MEDLINE, EMBASE, Econlit, NHS EED, CEA, and RepEc. All full economic evaluations of VDD prevention strategies were included. Interventions considered were food fortification, supplementation and public health campaigns. Data extracted included type of evaluation, population, setting, measure of benefit and main results. Results: Of the 2492 records screened, 14 studies were included. The majority of studies focused on supplementation within at-risk groups with the primary objective of either preventing fractures or falls in older adults. There was insufficient economic evidence to draw conclusions about the cost-effectiveness of population strategies. No study was identified that offered a direct comparison of the two main alternative population strategies: food fortification vs. supplementation. Conclusions: Whilst there is a growing body of evidence on the cost-effectiveness of micro nutrient programmes, there is a paucity of data on vitamin D fortification and how fortification programmes compare to population supplementation programmes. We highlight research gaps, and offer suggestions of what is required to undertake population-based cost-effectiveness analysis.

An estimate of the economic burden of vitamin D deficiency in pregnant women in the United Kingdom.

Pregnancy is associated with an increased risk of vitamin D deficiency beyond that of the general population. The aim of the current analysis was to synthesize the current evidence on the dose-outcome relationship of vitamin D/serum 25 hydroxyvitamin D (25-OHD) and complications during pregnancy. An additional aim was to estimate the economic burden attributable to inadequate levels of serum 25-OHD. Published literature on the effects of vitamin D supplementation/serum 25-OHD on pregnancy complications, including randomized control trials and non-interventional studies, was searched in bibliographic databases including Pubmed, Google Scholar, Scopus and EMBASE. A positive and significant treatment effect was obtained for pre-eclampsia (OR = 0.75 95% CI 0.662-0.843), but not for preterm birth (OR = 0.783, 95% CI 0.49-1.251) or small for gestational age (OR = 0.76 95% CI 0.38-1.28). Inadequate vitamin D accounted for 14.04% of risk for pre-eclampsia. It is estimated that addressing vitamin D inadequacy in pregnant women in England and Wales would reduce the number of cases of pre-eclampsia by 4126; and would result in a net saving of £18.6 million for the NHS in England and Wales. The current results suggest that based on current evidence a public health policy preventing vitamin D inadequacy in pregnant women is likely to have a positive impact on the NHS budget in England and Wales. This is contingent upon further evidence regarding the vitamin D dose-pregnancy outcome relationship becoming available.

Vitamin D status and monitoring in female veterans.

An increasing number of women are serving in the military. We initiated a retrospective study to evaluate vitamin D status and monitoring in female veterans, and to examine the potential link between vitamin D status, age, race, post-traumatic stress disorder (PTSD), health care costs, and utilization. Approximately 44 percent of the 3,608 female veterans evaluated between 2001 and 2010 were vitamin D deficient (25(OH)D < 20 ng/ml), a rate substantially higher than that of the general population. While younger (<55 years) and older (55+ years) women did not differ significantly in initial vitamin D status, older women had significantly more vitamin D monitoring and follow-up testing than younger women. Approximately 44 percent of vitamin D deficient women did not receive follow-up vitamin D testing. Minority female veterans were most likely to be vitamin D deficient. Female veterans with PTSD did not differ from others regarding their initial vitamin D status; those that were initially deficient were significantly more likely to receive follow-up testing and were more likely to achieve a replete state. Vitamin D deficiency in female veterans was also associated with increased health-care costs. Appropriate monitoring and replacement of vitamin D should be offered to all female veterans.

Comparison of cost-effectiveness of vitamin D screening with that of universal supplementation in preventing falls in community-dwelling older adults.

OBJECTIVES: To compare the cost-effectiveness of population screening for vitamin D insufficiency with that of universal vitamin D supplementation in community-dwelling older adults. DESIGN: A Markov decision model simulating follow-up over a 36-month period. Published data were used to estimate values for the model, including costs (measured in 2011 U.S. dollars), utilities (measured in quality-adjusted life years (QALYs)), and probabilities. SETTING: Decision analysis simulation from a societal perspective. PARTICIPANTS: Hypothetical cohort of community-dwelling women and men aged 65 to 80. MEASUREMENTS: Net monetary benefit (NMB) was calculated by subtracting the incremental cost of the strategy from the product of incremental QALYs and willingness-to-pay threshold. A higher NMB indicates greater cost-effectiveness. RESULTS: In women aged 65 to 80, population screening was slightly more cost-effective than universal supplementation, with an incremental NMB of $224 compared with $189 (P < .001). Population screening in men was also more cost-effective than universal supplementation (incremental NMB $298 vs $260, P < .001). Results differed according to age group. In those aged 65, population screening had cost-effectiveness similar to that of universal supplementation in women ($59 vs $71) and men ($114 vs $120), whereas in those aged 80, population screening was substantially more cost-effective than universal supplementation in women ($563 vs $428) and men ($703 vs $571). CONCLUSION: Population screening and universal supplementation for vitamin D insufficiency are cost-effective strategies in community-dwelling older women and men. In the oldest old, population screening may be more cost-effective than universal supplementation.

Should measurement of vitamin D and treatment of vitamin D insufficiency be routine in New Zealand?

Epidemiological studies have reported associations between lower vitamin D levels and a great variety of diseases, prompting calls for widespread treatment of individuals with low vitamin D levels. Most of New Zealand's population have vitamin D levels for at least part of the year that are considered insufficient (25-hydroxyvitamin D <50-80 nmol/L). However, evidence for benefits of vitamin D supplementation in such populations is controversial and there is some evidence of harmful effects. Until adequately powered, randomised, controlled trials of vitamin D supplementation demonstrate safe improvements in health, clinicians should not focus on detecting/treating individuals with vitamin D insufficiency, instead treating those at high risk of vitamin D deficiency (25-hydroxyvitamin D <25 nmol/L), such as the frail elderly, and those with specific clinical indications. Treatment for such individuals does not require vitamin D measurements. Requests for vitamin D measurements in Auckland have nearly quadrupled in the past decade, from 8500 in the year 2000 to 32,800 in 2010, with substantial increases in cost. Vitamin D measurement is often inaccurate and imprecise, and the vast majority of tests performed currently do not reveal vitamin D deficiency. Therefore, a move away from routine vitamin D measurements seems sensible, though they are still indicated when investigating suspected metabolic bone disease or hypocalcaemia.