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Vitamin D 3 deficiency and insufficiency are becoming a common global issue for us, especially in the most industrially developed countries. The only acknowledged activity of vitamin D 3 in vertebrates is to promote the absorption of calcium and, therefore, allow for the mineralization of bones. Accordingly, its deficiency is associated with diseases such as rickets. Other numerous vital functions associated with vitamin D 3 are yet to be considered, and the function of vitamin D 2 in plants is unknown. Thus, 100 years after its discovery, the importance of vitamin D still seems to be unacknowledged (except for rickets), with little attention given to its decrease throughout the world. In this review, I suggest that vitamin D deficiency and insufficiency may be linked to the westernized lifestyle in more developed countries. Furthermore, I suggest that, rather than the calcemic activity, the main function of vitamin D is, in general, that of strengthening living organisms. I conclude with the hypothesis that vitamin D deficiency may represent a marker for a greater risk of chronic inflammatory diseases and a shorter life expectancy.

Background: The role of maternal vitamin D supplementation in the prevention of infantile rickets is unknown, particularly in low- and middle-income countries without routine infant vitamin D supplementation. Through secondary analysis of a randomized, placebo-controlled trial in Bangladesh, we examined the dose-ranging effects of maternal vitamin D supplementation on the risk of biochemical rickets at 6 to 12 months of age., Methods: Pregnant women (n = 1300) were randomized into 5 groups: placebo, or vitamin D 4200 IU/week, 16 800 IU/week, or 28 000 IU/week from second trimester to delivery and placebo until 6 months postpartum; or 28 000 IU/week prenatally and until 6 months postpartum. Infants underwent biochemical rickets screening from 6 to 12 months of age (n = 790). Relative risks (RR) and 95% confidence intervals (95% CI) of biochemical rickets were estimated for each group versus placebo., Results: Overall, 39/790 (4.9%) infants had biochemical rickets. Prevalence was highest in the placebo group (7.8%), and the risk was significantly lower among infants whose mothers received combined prenatal and postpartum vitamin D at 28 000 IU/week (1.3%; RR, 0.16; 95% CI, 0.03-0.72). Risks among infants whose mothers received only prenatal supplementation (4200 IU, 16 800 IU, 28 000 IU weekly) were not significantly different from placebo: 3.8% (RR, 0.48; 95% CI, 0.19-1.22), 5.8% (RR, 0.74; 95% CI, 0.33-1.69), and 5.7% (RR, 0.73; 95% CI, 0.32-1.65), respectively., Conclusions: Maternal vitamin D supplementation (28 000 IU/week) during the third trimester of pregnancy until 6 months postpartum reduced the risk of infantile biochemical rickets. Further research is needed to define optimal postpartum supplementation dosing during lactation.

Background & objectives Globally, vitamin D deficiency has been incriminated in poor bone health and growth retardation in children, impaired adult musculoskeletal health (classically described), increased risk of cardiovascular events, immune dysfunction, neurologic disorders, insulin resistance and its multiple sequelae, polycystic ovary syndrome (PCOS) and certain cancers. This review intends to holistically highlight the burden of vitamin D deficiency among children in India, the public health importance, and potential therapeutic and preventive options, utilizing the concept of implementation research. Methods A systematic search was carried out on PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Cochrane database, clinicaltrials.gov, Google Scholar, and ctri.nic.in with the keywords or MeSH terms namely 'vitamin D', 'cholecalciferol', 'ergocalciferol', 'children', connected with appropriate boolean operators. Results Vitamin D deficiency/insufficiency prevalence varies from 70-90 per cent in Indian children. Rickets, stunting, impaired bone mineral health, and dental health are common problems in these children. Serum 25-hydroxy vitamin D (25(OH)D) should be maintained >20 ng/ml in children. Oral vitamin D supplementation has a high therapeutic window (1200-10,000 IU/d well tolerated). Fortification of grains, cereal, milk, bread, fruit juice, yogurt, and cheese with vitamin D has been tried in different countries across the globe. From Indian perspective, fortification of food items which is virtually used by everyone would be ideal like fortified milk or cooking oil. Fortification of "laddus" made from "Bengal gram" with vitamin D as a part of a mid-day meal programme for children can be an option. Interpretation & conclusions There is enough evidence from India to suggest the importance and utility of food fortification with vitamin D to address the epidemic of vitamin D deficiency/insufficiency in children.

Nutritional rickets is a global health problem reflecting both historical and contemporary health disparities arising from racial, ethnic, environmental, and geopolitical circumstances. It primarily affects marginalized populations and can contribute to long-term morbidity. Deficits in bone health in childhood may also contribute to osteomalacia/osteoporosis. Solutions require a global public health approach., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Vitamin D is one of the most important fat-soluble vitamins necessary for normal growth and development of the human body. According to a study done in Kabul shows that economic, racial, and social concerns are thought to be the main impediments to receiving appropriate amounts of this vitamin through dietary sources in countries like Afghanistan. Hypovitaminosis D, on the other hand, is now recognized as a pandemic in both industrialized and developing countries., Methods: To find out how common hypovitaminosis D is in children aged one month to eighteen years in afghan children Kabul, Afghanistan. Vitamin D deficiency and insufficiency are defined as serum levels of less than 20 ng/mL and 20 to 30 ng/mL, respectively. Children aged between 1 month to 18 years attending our hospital, AMC (Ariana Medical Complex) for health examination were checked for their 25-hydroxyvitamin D [25(OH)D]. Age, gender and address were recorded. 25(OH)D were determined using immunoassay auto analyzers. According to their serum 25(OH)D, the 25(OH)D were categorized into five categories: sufficiency: ≥ 30-100 ng/mL; insufficiency: ≥ 20-29 ng/mL; deficiency: < 20 ng/mL; severe deficiency: < 10 ng/mL; and intoxication: > 150 ng/mL. Participants who were intoxicated with vitamin D were excluded from the study., Results: A total of 4008 children aged 1 month to 18 years participated in this cross-sectional study. Hypovitaminosis D was found to be prevalent in 62.5 percent of the population. When compared to boys, female children were 1.2 times more likely to be vitamin D deficient. When compared to children of illiterate women, the odds of hypovitaminosis D were 1.4, 1.9, and 5.8 times lower in children with mothers educated up to primary school, graduation, and post-graduate. The average vitamin D level was 23 ng/mL, with a median of 15 ng/mL and maximum and minimum values of 135 ng/mL and 3 ng/mL, respectively. In all, 2500 (62.5%) of the children had low levels of vitamin D in their serum. Only 400 (16%) of the patients were sufficient, whereas 917 (36.7%) were severely deficient, 733 (29.3%) were deficient, and 450 (18%) were insufficient. With a female to male ratio of 1.2:1, the majority of those, 1335 (53.4%), were females and 1165 (46.6%) were males. Patients were 8.14 years old on average, with a median age of 7 years. The majority of the patients, 2152 (86.1%), were urban, while 348 (13.9%) were rural., Conclusion: The prevalence of hypovitaminosis D was very high in Afghan children. Female sex, higher socio economic status, higher educational status of the mother and living at urban areas were the factors with strong positive association with hypovitaminosis D., (© 2023. The Author(s).)

Background: Nutritional rickets (NR) is still a major problem and is exacerbated by an increasing influx of immigrants. In this study, Turkish and immigrant cases followed with the diagnosis of NR in our pediatric endocrinology clinic were retrospectively evaluated., Methods: Detailed data of cases diagnosed with NR between 2013 and 2020 and followed for at least six months were reviewed., Results: In the study period, 77 cases of NR were identified. Turkish children constituted 76.6% (n=59) while 18 (23.4%) were immigrant children. The mean age at diagnosis was 8.1±7.8 months, 32.5% (n=25) were female, and 67.5% (n=52) were male. The 25-hydroxyvitamin D3 was below normal in all patients, with a mean value of 4.3±2.6 ng/mL. Parathyroid hormone (PTH) was above normal in all and the mean value was 301.7±139.3 pg/ mL. While there were 3.9 cases of NR in 10,000 endocrine clinic patients in 2013, this rate increased more than four-fold to 15.7 patients in 2019., Conclusions: Despite the vitamin D prophylaxis program in Türkiye, NR is seen significantly more frequently in recent years, which may be associated with an increasing number of refugees. High PTH levels indicate the severity of NR cases admitted to our clinic. However, clinically significant NR is only the tip of the iceberg and the true burden of subclinical rickets is unknown. Increasing compliance with the vitamin D supplementation program in refugee and Turkish children is important for the prevention of nutritional rickets.

Background: Early childhood rickets increased in Alaska Native children after decreases in vitamin D-rich subsistence diet in childbearing-aged women. We evaluated the impact of routine prenatal vitamin D supplementation initiated in Alaska’s Yukon Kuskokwim Delta in Fall 2016. Methods: We queried electronic health records of prenatal women with 25(OH) vitamin D testing during the period 2015−2019. We evaluated 25(OH)D concentrations, vitamin D3 supplement refills, and decayed, missing, and filled teeth (dmft) scores and rickets in offspring. Results: Mean 25(OH)D concentrations increased 36.5% from pre- to post-supplementation; the percentage with deficient 25(OH)D decreased by 66.4%. Women with ≥ 60 vitamin D3 refill days had higher late pregnancy 25(OH)D concentrations than those with no refill days (p < 0.0001). Women with late pregnancy insufficient 25(OH)D concentrations had offspring with higher dmft scores than those with sufficient 25(OH)D (RR 1.3, p < 0.0001). Three children were diagnosed with nutritional rickets during the period 2001−2021, and none after 2017. Conclusions: These findings suggest that prenatal vitamin D supplementation can improve childhood outcomes in high-risk populations with high rates of rickets.

Rickets is one of the most prevalent non-communicable diseases in children in the developing world. It is often found in cultures in which children follow strict vegetarian diets and are not exposed to vitamin D-enhanced foods. While a rare occurrence, X-linked hypophosphatemic rickets may be the most frequent type of the disease seen outside the Third World today. However, there is not much credible information on the extent of the development of rickets. Therefore, pediatric nurses must be able to recognize children at risk and provide best practice care for the prevention and treatment of rickets. When caring for children in hospitals, communities or classrooms, nurses play a vital role in identifying children at risk for hypovitaminosis D and advising families to, if possible, follow safe diets and take supplements in order to avoid health complications associated with low levels of vitamin D. This study examines the prevalence and variables contributing to rickets, including hypovitaminosis vitamin D, the consequent orthopedic problems and the role of nurses in preventing and managing the pathogenesis of rickets and ultimately avoiding extreme deficits that result in bone deformities and the need for corrective surgery.

BACKGROUND Rickets is the deficiency in mineralization of the bone associated with lack of sunlight exposure and inadequate dietary calcium and/or vitamin D in children. Important efforts to eradicate rickets include appropriate sunlight exposure advice and fortification of food and milk with vitamin D. However, there is a growing concern that the current Coronavirus Disease 2019 (COVID-19) pandemic will increase the incidence of rickets due to inadequate sunlight exposure resulting from movement restriction measures imposed by governments across the world. CASE REPORT A 22-month-old girl presented to our primary care clinic in Selangor, Malaysia with abnormal gait and bowing of the legs during the COVID-19 pandemic. She had a history of inadequate sun exposure as she lived in an apartment and there was a Movement Control Order in place because of the pandemic. Calcium intake was also poor as she could not tolerate formula milk and did not consume any other dairy products. Investigations revealed severe hypocalcemia and low vitamin D level. She was diagnosed with nutritional rickets and was referred for admission to correct the hypocalcemia. She was subsequently discharged with oral calcium and vitamin D supplementation. Her calcium and vitamin D levels improved and at her 6-month review, her bilateral bowed legs had improved significantly. CONCLUSIONS This case highlights the importance of having a high degree of suspicion for vitamin D deficiency and rickets in young children growing up during the COVID-19 pandemic. Public health messages on preventing the spread of COVID-19 should also be interlaced with messages addressing the possible effects of our new norms such as inadequate sunlight exposure.

Objectives: Nutritional rickets (NR) is still an important problem and one which increasing influxes of immigrants are further exacerbating. This study evaluated cases of mostly immigrant children followed up with diagnoses of NR in our pediatric endocrinology clinic., Methods: Details of 20 cases diagnosed with NR between 2017 and 2020 were retrieved from file records., Results: Twenty (11 male) cases were included in the study. Three (15%) were Turkish nationals and the others (85%) were immigrants. Hypocalcemia and hypophosphatemia were detected in 17 and 13, respectively. Alkaline phosphatase (ALP) values were normal in two cases, while ALP and parathyroid hormone (PTH) values were elevated in all other cases, and PTH levels were very high (473.64 ± 197.05 pg/mL). 25-hydroxyvitamin D levels were below 20 ng/mL in all cases. Patients with NR received high-dose long-term vitamin D or stoss therapy. Six patients failed to attend long-term follow-up, while PTH and ALP levels and clinical findings improved at long-term follow-up in the other 14 cases., Conclusions: The elevated PTH levels suggest only the most severe cases of NR presented to our clinic. Clinically evident NR is therefore only the tip of the iceberg, and the true burden of subclinical rickets and osteomalacia remains unidentified. Public health policies should therefore focus on universal vitamin D supplementation and adequate dietary calcium provision, their integration into child surveillance programs, adequate advice and support to ensure normal nutrition, exposure to sunlight, and informing families of the increased risk not only for resident populations but also for refugee and immigrant children., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Severe prolonged vitamin D deficiency can cause rickets or osteomalacia. Both can be prevented by sunshine exposure or vitamin D supplementation. Although New Zealand guidance does not recommend vitamin D supplementation for the general population, it can be considered for individuals at risk of vitamin D deficiency. Routine measurement of 25-hydroxyvitamin D (25OHD) is also considered unnecessary., Methods: We investigated the rates of vitamin D supplementation, rickets and osteomalacia in New Zealand, and of 25OHD results in Auckland, over the last two decades., Results: Vitamin D prescriptions increased 14-fold, from 86,295/year to 1,215,507/year, between 2003 and 2019, with medication costs alone in 2019 being >$1 million. Despite these changes, the annual prevalence of hospital admissions for rickets, osteomalacia and unspecified vitamin D deficiency remained low and stable (10-20/year). 25OHD concentrations increased between 2002 and 2003 and between 2009 and 2019, and in the later time-period, 25OHD tests mainly identified individuals without vitamin D deficiency (40-50% >75nmol/L, 65-70% >50nmol/L and only 7-12.5% <25nmol/L)., Conclusions: Osteomalacia and rickets persist at low rates despite widespread, increasingly costly vitamin D supplementation and testing, which largely identifies individuals without vitamin D deficiency. These results suggest that vitamin D guidance and practice in New Zealand should change., Competing Interests: None of the authors have any financial conflicts of interest, but all authors have co-authored randomised controlled trials and systematic reviews of the efficacy of vitamin D supplements and co-authored articles concluding that there is no role for routine vitamin D supplementation in community dwelling individuals.

Objective: This study explores whether data relating to rickets from the French medico-historical literature (FMHL) and bioarchaeological grey literature are useful in evaluating its epidemiology during the industrialisation of France. Unlike other European countries such as England, industrialisation in France was a slow and continuous process with two phases: the first in 1830-1870 and the second in 1870-1914., Materials and Methods: A bibliographical analysis of 2800 FMHL sources from the 18th to the early 20th centuries and 50 archaeological excavation reports from the last 21 years was undertaken., Results: The FMHL data is very heterogeneous and predominantly dates to the second phase of industrialisation. The bioarchaeological data is very incomplete and predominantly relates to the period before industrialisation. At the same time, knowledge improvement and institutional changes to protect children could explain more systematic registration of cases of rickets., Conclusions: No solid conclusions can be made regarding the prevalence of rickets at present, however these data hold great potential., Significance: In comparison to England, no systematic investigation of rickets prevalence during the period of industrialisation in France has been undertaken to date., Limitations: The lack of archaeological excavations from this period and the limited paleopathological analysis of the sites excavated have contributed to our current lack of understanding regarding the impact of industrialization on the prevalence of rickets on the French population., Suggestions for Further Work: The FMHL data needs to be homogenized and osteoarchaeological collections need to be restudied with a common protocol focusing on signs of vitamin D deficiency., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cholecalciferol (vitamin D 3 ) is essentially known for its role in the phosphocalcic metabolism and its associated pathologies, such as rickets. In Switzerland, 35 to 50% of children are vitamin D deficient. Due to skin colour, poor nutrition, living conditions and cultural practices, migrant population is particularly at risk. Our aim is to attest the prevalence of hypovitaminosis D in children arriving in Switzerland. We retrospectively assessed 528 children's vitamin D status and parathyroid hormone, phosphate and calcium levels between 2015 and 2018 by electrochemiluminescence and spectrophotometry. Cholecalciferol was considered insufficient under 50 nmol/L and severely deficient below 25 nmol/L. Seventy-three percent of children showed hypovitaminosis D and 28% had a severe deficiency. Highest prevalence of deficiency was found in children from Eastern Mediterranean (80%) and African regions (75%). Severe deficiency was more prevalent in the South East Asian (39%) and Eastern Mediterranean regions (33%) and more frequent in females. Deficiency was more frequent and more severe in winter. Hypovitaminosis D increased with age. Two children presented with all three biological manifestations associated to severe hypovitaminosis D (hyperparathyroidism, hypocalcaemia and hypophosphatemia).Conclusion: A majority of migrant children presented with hypovitaminosis D. They should be supplemented to prevent complications. A strategy could be to supplement all children at arrival and during wintertime without regular vitamin D level checks. What is Known: Hypovitaminosis D is frequent in children and can lead to bone-related complications. Migrant children are particularly at risk of deficiency. What is New: Three-quarters of migrant children evaluated at our migrant clinic in Geneva's children hospital are deficient in vitamin D, one third severely. A strategy to correct the deficiency would be to supplement all migrant children at arrival and in winter., (© 2021. The Author(s).)

Suboptimal vitamin D status is a global health issue that affects children and adults worldwide. The prevalence of vitamin D deficiency and insufficiency has been well documented in the pediatric population in the United States. Although vitamin D deficiency is common, radiographic findings are uncommon and can be subtle. Additionally, because of the high prevalence of pediatric vitamin D insufficiency, it is commonly identified in young children with fractures. However, the majority of pediatric fractures are caused by trauma to healthy bones. Some, especially in infants and toddlers, are caused by non-accidental trauma. A small percentage is related to medical disease, including those associated with disorders of collagen, disorders of mineralization, and non-fracture mimics. Despite the scientific evidence, among disorders of mineralization, non-rachitic disorders of vitamin D have become a popular non-scientific theory to explain the fractures identified in abused children. Although infants and young children with rickets can fracture bones, the vast majority of fractures identified in abused infants are not caused by bone disease. Here we present a review of the literature on bone disease in the setting of accidental and non-accidental trauma. This context can help physicians remain vigilant about identifying vulnerable young children whose injuries are caused by non-accidental trauma.

During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.

Objective: By applying a joint medico-historical and paleopathological perspective, this paper aims to improve our understanding of factors influencing past vitamin D deficiency in ten Dutch 17th to 19th-century communities of varying socioeconomic status and settlement type., Materials: Vitamin D deficiency is evaluated in 733 individuals of both sexes and all age groups: Silvolde (n = 16), Rotterdam (n = 23), Rhenen (n = 24), Noordwijkerhout (n = 27), Gouda1and 2 (n = 40; n = 59), Roosendaal (n = 51), Den Haag (n = 93), Hattem (n = 113), and Beemster (n = 287)., Methods: Rickets and residual rickets are macroscopically assessed using established criteria. Hypotheses formulated based on medico-historical texts are investigated via multivariate statistical analysis of vitamin D deficiency prevalence., Results: Vitamin D deficiency prevalence ranges from 13.7 % (7/51) in Roosendaal to 48.1 % (13/27) in Noordwijkerhout, with an onset of < 4 years, and higher rates in cities, conforming to medico-historical texts. Patterns of child labor are likely key. In contrast, socioeconomic status did not statistically significantly influence vitamin D deficiency prevalence rates., Conclusion: Systematically collected paleopathological data enabled evaluation of medico-historical texts and provided insights into the role that socioeconomic status and settlement type played on the prevalence of vitamin D deficiency., Significance: Combining medico-historical texts and large-scale paleopathological data enables disease patterning to be embedded in a comprehensive biocultural perspective., Limitations: Comparisons may be limited by the small sample size of high socioeconomic status nonadults and some of the collections., Suggestions for Future Research: Analysis of more individuals and sites would improve our understanding of disease patterns., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Objectives: Vitamin D is essential for healthy development of bones, but little is known about the effects of supplementation in young stunted children. Our objective was to assess the effect of vitamin D supplementation on risk of rickets and linear growth among Afghan children., Methods: In this double-blind, placebo-controlled trial, 3046 children ages 1 to 11 months from inner-city Kabul were randomly assigned to receive oral vitamin D 3 (100 000 IU) or placebo every 3 months for 18 months. Rickets Severity Score was calculated by using wrist and knee radiographs for 631 randomly selected infants at 18 months, and rickets was defined as a score >1.5. Weight and length were measured at baseline and 18 months by using standard techniques, and z scores were calculated., Results: Mean (95% confidence interval [CI]) serum 25-hydroxyvitamin D (seasonally corrected) and dietary calcium intake were insufficient at 37 (35-39) nmol/L and 372 (327-418) mg/day, respectively. Prevalence of rickets was 5.5% (placebo) and 5.3% (vitamin D): odds ratio 0.96 (95% CI: 0.48 to 1.92); P = .9. The mean difference in height-for-age z score was 0.05 (95% CI: -0.05 to 0.15), P = .3, although the effect of vitamin D was greater for those consuming >300 mg/day of dietary calcium (0.14 [95% CI: 0 to 0.29]; P = .05). There were no between-group differences in weight-for-age or weight-for-height z scores., Conclusions: Except in those with higher calcium intake, vitamin D supplementation had no effect on rickets or growth., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Competing Interests: CM and PS are members of the advisory board for Kyowa Kirin and have received speaker fees. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Literature on the cost of management of rickets and cost-effectiveness of vitamin D supplementation in preventing rickets is lacking. Methods: This study considered the cost-effectiveness of providing free vitamin D supplementation to pregnant women and children <4 years of age with varying degrees of skin pigmentation to prevent rickets in children. Estimates for the prevalence of rickets were calculated using all cases of rickets diagnosed in Central Manchester, UK and census data from the region. Cost of management of rickets were calculated using National Health Service, UK tariffs. The efficacy of vitamin D supplementation was based on a similar programme implemented in Birmingham. Quality of life was assessed using utility estimates derived from a systematic literature review. In this analysis the intervention was considered cost-effective if the incremental cost-effectiveness ratio (ICER) is below the National Institute for Health and Care Excellence, UK cost-effectiveness threshold of £20,000 per Quality-adjusted life year (QALY). Results: Fifty-seven patients (26 dark, 29 medium and 2 light skin tones) were managed for rickets and associated complications over 4-years. Rickets has an estimated annual incidence of 29·75 per 100,000 children <4 years of age. In the dark skin tone population vitamin D supplementation proved to be cost saving. In a medium skin tone population and light skin tone populations the ICER was £19,295 per QALY and £404,047 per QALY, respectively. Conclusion: Our study demonstrates that a vitamin D supplementation to prevent rickets is cost effective in dark and medium skin tone populations., (Copyright © 2020 Floreskul, Juma, Daniel, Zamir, Rawdin, Stevenson, Mughal and Padidela.)

Objectives: A high prevalence of rickets of unknown aetiology has been reported in Chakaria, Bangladesh. Classically, rickets is caused by vitamin D deficiency but increasing evidence from Africa and Asia points towards other nutritional deficiencies or excessive exposure to some metals. The aim of this study was to investigate the aetiology of rickets in rural Bangladeshi children., Methods: 64 cases with rickets-like deformities were recruited at first presentation together with age-sex-village matched controls. Data and sample acquisition included anthropometry, radiographs, fasted plasma and urinary samples, 24 h weighed dietary intake together with a 24 h urine collection, and 13 C-breath tests to detect Helicobacter (H.) pylori infection., Results: One child had active rickets and frank hypovitaminosis D (F, n = 1) and one had deformities with radiological features of Blount disease (M, n = 1). The remaining cases were grouped into those with active rickets, defined as a radiographic Thacher score ≥1.5 (Group A, n = 24, 12M, 12F) and rickets-like bone deformities but not active rickets (Group B, n = 38, 28M, 10F). All children had a low dietary calcium intake, but this was lower in Group A than their controls (mean (SD): 156 (80) versus 323 (249) mg/day, p = 0.005). Plasma 25-hydroxyvitamin D (25OHD) was lower in Group A compared to controls; 63% of Group A and 8% of controls had a concentration <25 nmol/L (p ≤ 0.0001). There was, however, no evidence of differences in skin sunshine exposure. Group A had lower plasma calcium and phosphate and higher 1,25-dihydroxyvitamin D (1,25(OH) 2 D) and parathyroid hormone (PTH). 88% of Group A and 0% of controls had undetectable plasma intact fibroblast growth factor (iFGF23), with c-terminal FGF23 (cFGF23) concentrations in the normal range. Urinary phosphate and daily outputs of environmental metals relative to creatinine were higher and tubular maximal phosphate reabsorption per unit glomerular filtration rate (TmP/GFR) was lower in Group A compared to controls. Although less pronounced than Group A, Group B had higher alkaline phosphatase, 1,25(OH) 2 D and PTH concentrations than controls but similar calcium intake, TmP/GFR, iFGF23 and cFGF23 concentrations. Mean 25OHD concentrations were also similar to controls and there was no significant difference in the percentage <25 nmol/L (Group B: 13%, controls: 5%, p = 0.2) No group differences were seen in prevalence of anaemia, iron deficiency or H. pylori infection., Conclusion: Nutritional rickets in this region is likely to be predominantly due to low calcium intake in the context of poor vitamin D status and exposure to environmental metals, but not H. pylori infection, anaemia or iron deficiency., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The UK national incidence of nutritional rickets is unknown. We aimed to describe the incidence, presentation and clinical management of children under 16 years with nutritional rickets in the UK presenting to secondary care., Methods: Prospective data were collected monthly between March 2015 and March 2017 from 3500 consultant paediatricians using British Paediatric Surveillance Unit methodology. Clinicians completed online clinical questionnaires for cases fitting the surveillance case definition., Results: 125 cases met the case definition, an annual incidence of 0.48 (95% CI 0.37 to 0.62) per 100 000 children under 16 years. 116 children were under 5 years (annual incidence of 1.39 (95% CI 1.05 to 1.81) per 100 000. Boys (70%) were significantly more affected than girls (30%) (OR 2.17, 95% CI 1.25 to 3.78). The majority were of Black (43%) or South Asian (38%) ethnicity. 77.6% of children were not taking vitamin D supplements despite being eligible. Complications included delayed gross motor development (26.4%), fractures (9.6%), hypocalcaemic seizures (8%) and dilated cardiomyopathy (3%). Two children died (1.6%). In eight cases, rickets was confirmed radiologically and biochemically [raised serum alkaline phosphatase (ALP) and parathyroid hormone (PTH) levels ] but were excluded from the incidence analysis for not meeting the case definition of 25-hydroxyvitamin D of <25 nmol/L., Conclusion: The incidence of nutritional rickets in the UK is lower than expected. Serious complications and unexpected deaths, particularly in Black and South Asian children under 5 years, occurred. Both vitamin D deficiency and dietary calcium deficiency are role players in pathogenesis. Uptake of vitamin D supplementation remains low., Competing Interests: Competing interests: MB receives funding from the National Institute for Health Research under the Collaborations for Leadership in Applied Health Research and Care programme for North West London. ZM has received honoraria from Internis Pharmaceuticals Ltd., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the extent to which micronutrient deficiencies (MND) affect children's health-related quality of life (HRQoL), using vitamin D deficiency (VDD) as a case study., Design: Proxy valuation study to estimate the impact of VDD on the HRQoL of younger (0-4 years) and older (>4 years) children. We used the Child Health Utility 9 Dimension (CHU9D) questionnaire to estimate HRQoL for children within six VDD-related health states: 'hypocalcaemic cardiomyopathy', 'hypocalcaemic seizures', 'active rickets', 'bone deformities', 'pain and muscle weakness' and 'subclinical VDD'., Setting: Sampling was not restricted to any particular setting and worldwide experts were recruited., Participants: Respondents were paediatric bone experts recruited through network sampling., Results: Thirty-eight experts completed the survey. The health state with the largest detrimental impact (mean score (se)) on children's HRQoL was hypocalcaemic cardiomyopathy (0·47 (0·02)), followed by hypocalcaemic seizures (0·50 (0·02)) and active rickets (0·62 (0·02) in young children; 0·57 (0·02) in older children). Asymptomatic VDD had a modest but noticeable negative impact on HRQoL, attributed mostly to tiredness in both age groups and pain in the older paediatric population., Conclusions: Elicitation of HRQoL from clinical experts suggests a negative impact of VDD on HRQoL, even if there is no recognizable clinical manifestation. HRQoL data from populations of patients with MND will inform public health policy decisions. In some settings, routine collection of HRQoL data alongside national nutrition surveys may help capture the full burden of MND and prioritize resources towards effective prevention.

Fortification of food products with vitamin D was central to the eradication of rickets in the early parts of the 20th century in the United States. In the subsequent almost 100 years since, accumulating evidence has linked vitamin D deficiency to a variety of outcomes, and this has paralleled greater public interest and awareness of the health benefits of vitamin D. Supplements containing vitamin D are now widely available in both industrialized and developing countries, and many are in the form of unregulated formulations sold to the public with little guidance for safe administration. Together, this has contributed to a transition whereby a dramatic global increase in cases of vitamin D toxicity has been reported. Clinicians are now faced with the challenge of managing this condition that can present on a spectrum from asymptomatic to acute life-threatening complications. This article considers contemporary data on vitamin D toxicity, and diagnostic and management strategies relevant to clinical practice.

Aim: To describe the demographic characteristics, risk factors, and presenting features of children with symptomatic nutritional rickets in France., Methods: This is a retrospective study of 38 children diagnosed with nutritional rickets from 1998 to 2019., Results: We observed a higher frequency of rickets in males (74 vs. 26%), in young children (median age at diagnosis: 23 months; 82% were younger than 5 years), and in children with a non-Caucasian ethnic background (89%). Most children were exclusively breastfed (78%) without adequate vitamin D supplementation (89%). The most common presentations were bowed legs (63%), hypocalcemic seizures (21%), and growth retardation (11%). Approximately half (62%) of the children were hypocalcemic. The children presenting with hypocalcemic seizures were significantly younger (0.8 vs. 2.2 years; p = 0.041) and had lower total serum calcium levels (1.44 vs. 2.17 mmol/L; p < 0.0001), higher phosphatemia (1.43 vs. 1.23 mmol/L; p = 0.020), and lower 25-hydroxy vitamin D levels (3 vs. 7 ng/mL; p = 0.020) but similar parathyroid hormone levels (357 vs. 289 ng/mL; p = 0.940) compared to rickets cases who did not experience hypocalcemic seizures. A dilated cardiomyopathy was detected in 14% of the children who had undergone echocardiography., Conclusion: Nutritional rickets remains endemic in the pediatric population and its most severe forms can have life-threatening sequelae. Health practitioners need to be cognizant of these facts to raise awareness and screen high-risk populations., (© 2020 S. Karger AG, Basel.)

Aim: This population-based study assessed the incidence of rickets in infants up to age of one born in Sweden from 1997 to 2014. We also examined maternal and perinatal factors and co-morbidity., Methods: We used Swedish National Board of Health and Welfare registers and data from Statistics Sweden. The outcome measure was an International Classification of Diseases, Tenth Revision, code for rickets., Results: There were 273 cases of rickets, with an incidence of 14.7 per 100 000 and a 10-fold incidence increase between 1997 and 2014. The majority (78.4%) were born preterm, half were small-for-gestational age (SGA) (birthweight <10th percentile), 4.8% were born to Asian-born mothers and 3.5% to African-born mothers. The adjusted odds ratios by birth week were 182 (95% CI: 121-272) before 32 weeks and 10.8 (95% CI: 6.72-17.4) by 32-36 weeks. Preterm infants with necrotising enterocolitis had very high odds for rickets and so did SGA term-born infants and those born to African-born mothers. The odds for rickets among preterm infants increased considerably during the later years., Conclusion: Rickets increased 10-fold in Sweden from 1997 to 2014 and was mainly associated with prematurity, SGA and foreign-born mothers. Possible reasons may include increased preterm survival rates and improved clinical detection and registration., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: The aim was to clarify whether children born preterm with a history of necrotizing enterocolitis (NEC) had an increased risk of rickets, fractures, and/or vitamin D deficiency during childhood and adolescence compared to controls without NEC, matched for gestational age., Methods: All infants born in Sweden between 1987 and 2009 with a gestational age <32 + 0 weeks and a diagnosis of NEC were identified. Totally, 465 children with a history of NEC and 2127 controls were included. International Classification of Diseases codes for all categories of fractures, rickets, vitamin D deficiency, and malnutrition were analyzed., Results: In total, 94 of the 465 children with NEC died within 28 days. Of the 2127 controls, 288 died within 28 days. Among the remaining 371 NEC cases, 39 fracture occasions were identified. The 1839 controls had 204 fracture occasions. There was no significant difference in fractures. Rickets was diagnosed in 11 (3%) of the children with a history of NEC compared to 21 (1%) of the controls (odds ratio 2.65, 95% CI 1.26-5.53, p = 0.007)., Conclusions: This study showed an increased risk of rickets but not fractures during childhood and adolescence in children born preterm and with a history of NEC, compared to matched controls.

Understanding the role of vitamin D is an important component of the proper care of the pediatric orthopedic patient. Vitamin D is an essential component of bone metabolism in the growth and development of the pediatric skeleton, which can be acutely affected by changes to the body's vitamin D, calcium, and phosphate levels, resulting in pathologic conditions such as rickets or fractures. This article reviews the main areas in which vitamin D relates to pediatric orthopedics and highlights some of the areas where future research is being directed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Preptin is a 34-residue pancreatic hormone that stimulates osteoblast proliferation and reduces osteoblast apoptosis., Research Aims: To measure levels of serum Preptin in rachitic children and in breastmilk of their mothers and to compare with levels in healthy non-rachitic children., Methods: Thirty children with rickets and another 30 non-rachitic age and sex matched controls were subjected to detailed history, physical examination including anthropometric measurements, assessment of signs of rickets and laboratory measurement of serum vitamin D, calcium, phosphorus, alkaline phosphatase and Preptin. Mothers' breast milk Preptin were also measured., Results: Significantly lower serum Preptin (p < 0.001) in rachitic children with a significant negative correlation between serum Preptin and alkaline phosphatase (P < 0.0001). Lower breastmilk Preptin levels in mothers of rachitic children (P < 0.001) with a negative correlation between breastmilk Preptin and both maternal weight and BMI(P < 0.01&P < 0.02). Mothers' milk Preptin is positively correlated with serum Preptin and calcium in non-rachitic children(P < 0.001&0.04), but negatively correlated with their mothers' age (P < 0.01)., Conclusion: Preptin may play a role in the etiology of rickets in children. Further studies are recommended to evaluate Preptin role in treatment of rickets in children.

Ensuring that the entire Australian population is Vitamin D sufficient is challenging, given the wide range of latitudes spanned by the country, its multicultural population and highly urbanised lifestyle of the majority of its population. Specific issues related to the unique aspects of vitamin D metabolism during pregnancy and infancy further complicate how best to develop a universally safe and effective public health policy to ensure vitamin D adequacy for all. Furthermore, as Australia is considered a "sunny country", it does not yet have a national vitamin D food supplementation policy. Rickets remains very uncommon in Australian infants and children, however it has been recognised for decades that infants of newly arrived immigrants remain particularly at risk. Yet vitamin D deficiency rickets is entirely preventable, with the caveat that when rickets occurs in the absence of preexisting risk factors and/or is poorly responsive to adequate treatment, consideration needs to be given to genetic forms of rickets.

China has serious lead pollution and a high incidence of childhood rickets. High lead levels have been reported in childhood rickets, but the results were inconsistent.To evaluate the association between body lead levels and childhood rickets.After a systematic literature search, we identified 15 studies determining body lead levels between rickets children and healthy controls, and 4 studies focusing on the cases of different disease severity. Standard mean differences (SMD) and the corresponding 95% confidence intervals (CI) were pooled to compare the lead levels between different groups.Sixteen case-control studies were included with a total of 5082 cases and 6054 controls. Compared with healthy controls, the body lead levels in rickets children were significantly higher (SMD (95%CI): 0.67 (0.41-0.93)), and subgroup analyses showed consistent results. The cases with moderate-to-severe disease activity also had a significantly higher lead level than mild-to-moderate cases (SMD (95%CI): 0.64 (0.31-0.97)).This meta-analysis suggested an association between body lead levels and childhood rickets, and lead exposure might be a risk factor for rickets.

Objective: Maternal vitamin D deficiency is an important risk factor that causes infantile rickets in the neonatal and infantile period. The aim of this study was to review the prevalence, clinical characteristics, and treatment of vitamin D deficiency and the follow-ups with infants and their mothers by the neonatal intensive care unit of Afiyet Hospital in Turkey., Methods: Calcium (Ca), phosphorus (P) and 25 (OH) vitamin D were studied and prospectively recorded in infants and their mothers detected to have hypocalcemia during routine biochemistry tests performed on the third postnatal day of the patients follow up and treated with different diagnoses., Results: A total of 2,460 infants were admitted into the neonatal intensive care unit between August 2014 and January 2018. Of the infants included in the study, 324 (66.1%) were male and 166 (33.8%) were female, and 366 (74.6%) of them had been delivered by cesarean section (C/S), 124 (25.3%) of them had been delivered by Normal Spontaneous Delivery (NSD). Hypocalcemia was detected in 490 (19.9%) of the infants. In a total of 190 (38.7%) infants and 86 mothers (17.5%), the levels of 25 (OH) vitamin D were found to be below the laboratory detection limit of <3 ng/ml. When vitamin D deficiency + insufficiency is assessed by season, 151 of them were found to be in summer (30.99%), 118 in spring (24.18%), 117 in the winter season(23.87%), and 93 in autumn(18.97%), respectively. There was a statistically significant positive correlation of 78.7% between the vitamins D values of the mothers and the infants (p: 0.000, p<0.05)., Conclusion: This study conducted that a positive correlation of between the vitamin D values of the mothers and the infants. In order to prevent maternal vitamin D deficiency, the appropriate dose of prophylaxis providing optimal levels of vitamin D and should be given by according to the levels of 25 (OH) D vitamin during pregnancy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In spite of the availability of guidelines for the management of severe acute malnutrition (SAM) in Ethiopia, high comorbidity and poor treatment outcomes are still observed in therapeutic feeding centers among under -five children with SAM. The aim of this study was to assess comorbidity, treatment outcomes and factors affecting the recovery rate of children aged 1-59 months with SAM admitted into Therapeutic Feeding Centers (TFCs)., Methods: A total of 413 records of children with SAM admitted in three selected hospitals from July 2013 to July 2015 G.C were retrospectively reviewed. Descriptive analysis was used to compare performance indicator values with SPHERE project reference standards (the minimum standard to be attained during nutritional therapy). Cox-proportional hazard regression analysis was performed to estimate the predictors of recovery rate at p-value < 0.05., Result: The mean age of children was 16 months (95% CI, 15.0, 17.0). Out of 413 children with SAM, 231 (55.9%) recovered, 24 (5.8%) died and 16.3% were defaulted from TFCs. The mean weight gain (in gram per weight of kilogram per day) for recovered children was 15.61 g/kg/day (95% CI, 14.15, 17.07). The overall median recovery time for these children was 12 days (95% CI, 11.22, 12.78). Moreover, most (77.5%) of children admitted with SAM were marasmic followed by Kwash (16%). Pneumonia (54.8%), diarrhea (41.8%) and rickets (21.4%) were co-morbidities which affected SAM children. A child being admitted at Mehal Meda Hospital (Adjusted Hazard Ratio (AHR) = 2.01; 95% CI: 1.34, 2.91), edematous form of malnutrition (AHR = 0.59; 95% CI: 0.39, 0.90) and being a child infected with pneumonia (AHR = 0.71; 95% CI: 0.51, 0.98) were predictors of nutritional recovery rate., Conclusion: Under five pneumonia, diarrhea and rickets were co-morbidities that should be prevented. Recovery rate was poor when compared to SPHERE project reference value (which is > 75%). Predictors, namely presence of pneumonia and edematous form of malnutrition reduced nutritional recovery rate. Whereas, being admitted at Mehal Meda Hospital improved recovery rate. Therefore, hospitals should work in collaboration with health extension workers to prevent co-morbidities and strengthen screening and referral of malnutrition cases at community level. Moreover, Zonal Health Department and District Health Offices should facilitate experience sharing among health facilities.

This article considers the nature of written sources on the epidemiology of rickets in the post-Mediaeval period, and examines the value of these sources for palaeopathologists. There is a progression from 17th-18th century sources, which generally make ex cathedra, qualitative statements on rickets frequency to, in the 19th century, semi-quantitative geographical surveys of its occurrence, through to reports of percentage prevalence in various groups. Of course, even these latter cannot be directly compared with prevalences calculated from excavated skeletal remains, but there are also considerable difficulties in comparing them with one another, and this effectively precludes synthesis to provide reliable information on geographic and temporal trends at anything more than a very broad-brush level. Their problematic nature mandates a cautious approach when using written sources to shed light on the epidemiology of rickets. For palaeopathologists, a useful way of incorporating these sources into a biocultural approach may be to use them in order to formulate hypotheses that can then be evaluated using skeletal evidence., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Growing evidence suggests that vitamin D supports immune responses to infections, autoimmune conditions and cancers, although evidence from large-scale studies is limited. There is scope to better understand how vitamin D deficiency interacted with other diseases to affect health in past groups. This study investigated paleopathological evidence and documentary records of individual cause of death to examine disease co-occurrence in a group of mid-19th century child burials from London, UK. Twenty-one percent of children had vitamin D deficiency rickets (138/642) and 36 children with rickets had an identified cause of death. Cyclical episodes of metabolic and nutritional deficiencies (rickets and scurvy) had occurred during childhood. Active rickets co-occurred with respiratory and gastrointestinal infections in a small number of children, likely reflecting vitamin D's role in supporting immune function. Consideration of the stage of the vitamin D deficiency showed that the majority of children were affected by chronic disease loads indicative of multiple episodes of illness. Reconstructions of the wider health consequences of vitamin D deficiency in past groups are dependent on recognising whether the deficiency was active or healed. The variability of diseases identified illustrates the high disease burden that affected children in this socially disadvantaged group., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: There's abundant sunshine in the tropics but severe rickets is still observed. Nutritional rickets is associated with an increased risk of acute lower respiratory infections. Pneumonia is the leading cause of death in the under 5 -year old children with the highest burden in developing countries. Both Pneumonia and rickets are common in the developing countries and may affect clinical presentation and outcome. This study aimed to determine the prevalence and associated factors of nutritional rickets in children admitted with severe pneumonia., Methods: This was a cross-sectional study of children aged 2-59 months presenting with severe pneumonia at an emergency unit. We enrolled 221 children between February and June 2012 after consent. A pre-coded questionnaire was used to collect data on socio-demographic, nutritional and past medical history. Physical exam was done for signs of rickets and anthropometric measurements. Serum calcium, phosphorus, and alkaline phosphatase (ALP) were assessed. Children with any physical signs of rickets or biochemical rickets (ALP > 400 IU); had a wrist x-ray done. Nutritional rickets was defined as the presence of radiological changes of cupping or fraying and/ or metaphyseal thickening. Severe pneumonia was defined using the WHO criteria. Statistical analysis was performed using the Stata 10 statistical package. P- value < 0.05 was significant., Results: The prevalence of nutritional rickets among children with severe pneumonia is 9.5%. However, 14.5% had raised ALP (biochemical rickets). The factors independently associated with rickets was an elevated alkaline phosphatase; p-value < 0.001, or 32.95 95% CI (10.54-102.93). Other factors like breastfeeding, big family size, birth order were not significantly associated with rickets. Low serum calcium was detected in 22 (9.9%) of the 221 participants. Overall few children with rickets had typical clinical features of rickets on physical examination., Conclusion: Rickets is a common problem in our setting despite ample sunshine. Clinicians should actively assess children for rickets in this setting and screen for rickets in those children at high risk even without clinical features.

Severe vitamin D deficiency can be defined as the dose of vitamin D or serum 25OHD concentrations needed to prevent nutritional rickets or osteomalacia. There is large international consensus that these diseases can be prevented by 400 IU of vitamin D/d and 25OHD above 30 nmol/l (12 ng/ml). Vitamin D deficiency can also accelerate the risk of fractures and probably also of falls in elderly subjects but there is no consensus on the required daily doses or minimal 25OHD threshold for these endpoints. The majority of experts consider 800 IU/d and serum 25OHD above 50 nmol/l (20 ng/ml) as sufficient, with a minority opinion aiming for 75 nmol/l or even higher. For other extra-skeletal endpoints, no hard evidence is available to define whether or not this is causally related to vitamin D status. Therefore, for these endpoints no minimal dosage or 25OHD threshold can be defined., (Copyright © 2018. Published by Elsevier Ltd.)

The consequences of vitamin D and dietary calcium deficiency have become a huge public health concern in the UK. The burden of disease from these deficiencies includes rickets, and hypocalcaemic seizures, dilated cardiomyopathy and mostly occult myopathy and osteomalacia. The increasing burden of the disease is intrinsically linked to ethnicity and the population demographic changes in the UK. Three facts have led to the resurfacing of the English disease: (1) the UK has no ultraviolet sunlight for at least 6 months of the year, (2) dark skin produces far less vitamin D than white skin per unit ultraviolet light exposure, and (3) non-European Union immigration over the last century. To date, the UK government demonstrates incomplete understanding of these three facts, and its failure to adjust its prevention programmes to changing demographics is endangering the health and life of UK residents with dark skin, of whom infants are the most vulnerable. Establishing accountability through the implementation of monitored antenatal and infantile supplementation programmes and mandatory food fortification is overdue., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

There is concern that vitamin D deficiency is prevalent among children in Japan as well as worldwide. We conducted a nationwide epidemiologic survey of symptomatic vitamin D deficiency to observe its incidence rate among Japanese children. A questionnaire inquiring the number of new patients with vitamin D deficiency rickets and/or hypocalcemia for 3 years was sent to 855 randomly selected hospitals with a pediatrics department in Japan. In this survey, we found that 250 children were diagnosed with symptomatic vitamin D deficiency. The estimated number of patients with symptomatic vitamin D deficiency per year was 183 (95% confidence interval (CI): 145-222). The overall annual incidence rate among children under 15 years of age was 1.1 per 100,000 population (95% CI: 0.9-1.4). The second survey has provided detailed information on 89 patients with symptomatic vitamin D deficiency under 5 years of age in hospitals in the current research group. The nationwide and second surveys estimated the overall annual incidence rate of symptomatic vitamin D deficiency in children under 5 years of age to be 3.5 (2.7-4.2) per 100,000 population. The second survey revealed 83% had bowed legs, 88% had exclusive breastfeeding, 49% had a restricted and/or unbalanced diet and 31% had insufficient sun exposure among the 89 patients. This is the first nationwide survey on definitive clinical vitamin D deficiency in children in Japan. Elucidating the frequency and characteristics of symptomatic vitamin D deficiency among children is useful to develop preventative public health strategies.

We explored the association between maternal nutrition knowledge, attitude, and practice (KAP) and 25-hydroxyvitamin D (25(OH)D) values in children with rickets in Xinjiang, People's Republic of China. We recruited 514 mothers with children (<2 years) from pediatric outpatient departments. We determined general status of families, maternal nutrition KAP, and 25(OH)D values in 212 children with rickets, with doctors using "Prevention and Treatment Program for Infant and Young Children Rickets" and "Application Guideline for Vitamin D and Bone Health in Adult Chinese (2014 Standard Edition)" to identify. We then assessed the associations between nutrition KAP and 25(OH)D values. The 25(OH)D values were positively correlated with maternal nutrition KAP scores. Factors influencing rickets included per-capita monthly dietary expenditure and spousal education level. Factors associated with nutrition practice included maternal education level, gestational vitamin D level, and nutrition knowledge. Augmented maternal nutrition KAP may improve 25(OH)D levels in children with rickets to a normal range.

The effects of rickets on children recovery from severe acute malnutrition (SAM) are unknown. Rickets may affect both growth and susceptibility to infectious diseases. We investigated the associations of clinically diagnosed rickets with life-threatening events and anthropometric recovery during 1 year following inpatient treatment for complicated SAM. This was a secondary analysis of clinical trial data among non-human immunodeficiency virus-infected Kenyan children with complicated SAM (2-59 months) followed for 1 year posthospital discharge (ClinicalTrials.gov ID NCT00934492). The outcomes were mortality, hospital readmissions, and growth during 12 months. The main exposure was clinically diagnosed rickets at baseline. Of 1,778 children recruited, 230 (12.9%, 95% CI [11.4, 14 .6]) had clinical signs of rickets at baseline. Enrolment at an urban site, height-for-age and head circumference-for-age z scores were associated with rickets. Rickets at study enrolment was associated with increased mortality (adjusted Hazard Ratio [aHR] 1.61, 95% CI [1.14, 2.27]), any readmission (aHR 1.37, 95% CI [1.09, 1.72]), readmission for severe pneumonia (aHR 1.37, 95% CI [1.05, 1.79]), but not readmission with diarrhoea (aHR 1.05, 95% CI [0.73, 1.51]). Rickets was associated with increased height gain (centimetres), adjusted regression coefficient 0.19 (95% CI [0.10, 0.28]), but not changes in head circumference, mid-upper arm circumference, or weight. Rickets was common among children with SAM at urban sites and associated with increased risks of severe pneumonia and death. Increased height gain may have resulted from vitamin D and calcium treatment. Future work should explore possibility of other concurrent micronutrient deficiencies and optimal treatment of rickets in this high-risk population., (© 2017 The Authors. Maternal and Child Nutrition Published by John Wiley & Sons, Ltd.)

Children who receive inadequate exposure to sunlight have reduced levels of vitamin D, resulting in rickets, a disease that is characterized by bone deformity, stunted growth, and long term pronounced disability. The United Kingdom rickets incidence rates declined from the early 1960's to mid-1990's, after which there was a dramatic increase. The reason for this change is not well understood. Here we show that an important low frequency mode of climate variability, the Atlantic Multidecadal Oscillation (AMO), with a period of ~60-80 years, has an impact on rickets incidence rates in the United Kingdom through changes in sea level pressure, cloud cover and sunshine duration. This research highlights the important role that multidecadal climate variability can play in human morbidity and suggests that future changes in the AMO may modulate rickets incidence rates throughout the United Kingdom.

Objectives: Poor vitamin D status has been reported to be highly prevalent in many non-western immigrant groups living in Norway and other western countries. However, data on rickets are scarce, and the aim of the current study was to identify new cases of nutritional rickets in Norway in the period 2008-2012 among children under the age of 5 years., Design: Register-based cohort study., Setting: The Norwegian population from 2008 to 2012., Participants: Children with nutritional rickets under the age of 5 years., Main Outcome Measure: Nutritional rickets. Patients with ICD10 (International Statistical Classification of Diseases and Related Health Problems, 10th revision) diagnosis code E55.0 (active rickets) treated at all Norwegian hospitals were identified in the Norwegian Patient Registry. We were able to review 85% of the medical records for diagnosis confirmation. In addition, we identified patients with the diagnoses E55.9, E64.3 and E83.3 to identify individuals with rickets who had been given other diagnoses., Results: Nutritional rickets was confirmed in 39 children aged 0-4 years with the diagnosis of E55.0. In addition, three patients with the diagnosis of unspecified vitamin D deficiency (E55.9) were classified as having nutritional rickets, giving a total of 42 patients. Mean age at diagnosis was 1.40 years (range 0.1-3.5 years), and 93% had a non-western immigrant background. The incidence rate of rickets was estimated to be 0.3 per 10 000 person-years in the total Norwegian child population under the age of 5 years and 3.1 per 10 000 person-years in those with an immigrant background from Asia or Africa., Conclusion: The number of children with nutritional rickets in Norway remained low in the period 2008-2012. Nearly all children had a non-western immigrant background., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Worldwide, nutritional rickets continues to be an evolving problem with several causes. This paper provides an updated literature review characterising the prevalence, aetiology, pathophysiology and treatment of nutritional rickets worldwide. A systematic review of articles on nutritional rickets from various geographical regions was undertaken. For each region, key information was extracted, including prevalence, cause of rickets specific to the region, methods of confirming the diagnosis and current treatment and preventive measures. Calcium deficiency continues to be a major cause of rickets in Africa and Asia. Vitamin D deficiency rickets is perhaps increasing in the Americas, Europe and parts of the Middle East. There continues to be a distinct presentation of calcium-predominant versus vitamin D predominant rickets, although there are overlapping features. More careful diagnosis of rickets and reporting of 25-OHD concentrations has improved accurate knowledge of rickets prevalence and better delineated the cause. Nutritional rickets continues to be an evolving and multi-factorial problem worldwide. It is on a spectrum, ranging from isolated vitamin D deficiency to isolated calcium deficiency. Specific areas which require emphasis include a consistent community approach to screening and diagnosis, vitamin D supplementation of infants and at-risk children, prevention of maternal vitamin D deficiency and the provision of calcium in areas with low calcium diets.

Nutritional rickets continues to be a significant health problem for children worldwide with recent evidence of increasing incidence in many developed countries. It is due to vitamin D deficiency and/or inadequate dietary calcium intake with variation in the relative contributions of each of these dependant on environmental factors such a dietary intake and sunlight exposure. Key to the prevention of rickets is ensuring that pregnant women and their infants receive vitamin D supplementation with good evidence from randomised controlled trials that infants who receive 400iu daily can achieve levels of 25 hydroxyvitamin D of >50nmol/l. However, public health implementation of daily supplementation is more challenging with a need to revisit food fortification strategies to ensure optimal vitamin D status of the population. Treatment of nutritional rickets has traditionally been with vitamin D2 or D3, often given as a daily oral dose for several weeks until biochemical and radiological evidence of healing. However, other treatment regimes with single or intermittent high doses have also proved to be effective. It is now recognised that oral calcium either as dietary intake or supplements should be routinely used in conjunction with vitamin D for treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Concern has been expressed about the rising incidence of nutritional rickets with its associated long-term sequelae in children globally. In order to address the condition worldwide, it is imperative that accurate figures of its incidence are available particularly in at-risk communities. In order to obtain these figures, various screening tools and diagnostic criteria have been used with no standardization of methodologies, resulting in varying prevalences which may under- or over-estimate the prevalence depending of the techniques used. This review discusses the advantages and disadvantages of various screening tests used to diagnose rickets in communities. Clinical signs characteristic of rachitic deformities have been used extensively, but are likely to over-estimate the prevalence and are dependent on the clinical skills of the observer. Biochemical tests such as alkaline phosphatase and 25-hydroxyvitamin D have also been proposed. There is no consensus on the usefulness of alkaline phosphatase as a screening tool, while there is general agreement that the measurement of vitamin D status is unhelpful in screening for rickets. Finally, the confirmation of the presence of active rickets in suspected infants and children is dependent on radiographic findings, although these may be less helpful in adolescents whose growth plates might be closed or nearly so. In order to obtain uniformity in screening for rickets globally, the is a need for consensus among public health specialists, paediatric endocrinologists and those interested in paediatric bone disease as to the best methods to be employed to determine the prevalence of rickets, particularly in communities with limited resources., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children's Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency., Competing Interests: The authors declare that they have no conflicts of interest., (© 2015 John Wiley & Sons Ltd.)

Congenital rickets is the term given to fetus born with clinical features of rickets, but those born with biochemical evidence of rickets without obvious clinical features still can be considered occult congenital rickets. Some of the affected babies with this disease have the intrauterine rachitic environment, but a calcium trans-placental pump prevents the fetus from having clinical features of rickets. They may present with hypocalcemia few days after birth or later with more florid features of rickets. Congenital rickets cases born with florid features reported over the last 40 years are few and can be divided into two groups. The first due to severe maternal osteomalacia in which their bones were so decalcified to have enough calcium to be pumped to their fetus. Another group in which newborn babies were hypocalcemic due to other maternal diseases as malabsorption, celiac disease, pre-eclampsia, and prematurity. All inherited rickets cases per se, or as part of other syndromes can be considered congenital rickets. Most cases seen in our region are due to maternal vitamin D deficiency with symptoms becoming obvious when the infants are breastfed, or may present with hypocalcemic convulsions or craniotabes. This is a review of congenital rickets with the aim of shedding light on this potentially acute disease that needs more attention and awareness in the neonatal period to avoid rare serious complications as cardiomyopathy or myelofibrosis and the complications of hypocalcemic convulsions. Congenital rickets cases seen simulate a tip of an ice-burg and its prevention is an important issue, especially with the tremendous urbanization with tall buildings living in sun-deprived flats as the commonest type of residence leading to the increasing incidence of maternal osteomalacia and rickets.