Abstract.
Vitamin D deficiency and rickets are important pediatric health concerns, particularly in high-latitude regions. This study investigated the incidence and clinical characteristics of pediatric vitamin D deficiency in Hokkaido, Japan, between 2015 and 2019. A cross-sectional survey was distributed to the pediatric departments of 88 major hospitals across the region, achieving a response rate of 97.7%. Clinical data were collected from 262 children with vitamin D deficiency (25(OH)D < 20 ng/mL), including 153 with rickets. In 2019, the incidence of vitamin D deficiency rickets was 25.4 per 100,000 live births, approximately threefold higher than 15 yr earlier and eightfold greater than the national average. Most cases (median age 1.4–1.5 yr) occurred in children younger than four years. Patients with rickets exhibited considerably lower Ca/P and higher ALP/iPTH levels than those without rickets, despite having similar 25(OH)D levels. Exclusive breastfeeding was significantly more common in the rickets group. Approximately 90% of patients received alfacalcidol. The incidence of pediatric vitamin D deficiency and rickets in Hokkaido has increased. These findings underscore the need for continued public health education on vitamin D intake, expanded access to native vitamin D supplementation, and attention to maternal vitamin D status.
Keywords: characteristics, incidence, Japan, vitamin D deficiency, rickets
Highlights
● A survey of vitamin D deficiency was conducted in Hokkaido from 2015 to 2019.
● Incidence of vitamin D deficiency rickets has tripled over the past 15 yr.
● Exclusive breastfeeding was more common in children with rickets despite similar 25(OH)D levels.
Introduction
Vitamin D is a key regulator of bone formation and maintenance and functions as an essential nutrient for calcium and phosphorus absorption and homeostasis. Vitamin D deficiency impairs bone mineralization during growth, resulting in rickets and hypocalcemia (1). In addition to skeletal health, vitamin D is involved in multiple biological processes, including immune and cognitive function (2). Therefore, maintaining appropriate vitamin D levels is crucial.
Vitamin D is primarily produced through endogenous synthesis in the skin following exposure to ultraviolet B (UVB) radiation, in addition to dietary intake. Once synthesized or ingested, it is hydroxylated in the liver to 25-hydroxyvitamin D [25(OH)D], which is subsequently converted in the kidneys to the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)2D], by 1α-hydroxylase under the regulation of parathyroid hormone (PTH) (3). The risk factors for vitamin D deficiency are broadly categorized into dietary and UVB exposure-related factors (4). In infancy, exclusive breastfeeding is a major dietary risk factor, as breast milk contains only limited amounts of vitamin D. Inadequate maternal vitamin D status further increases the risk of deficiency in infants (5). Additionally, food allergies requiring avoidance of vitamin D-rich foods, such as fish and eggs, can exacerbate this risk (4).
Regarding UVB exposure, the recommendations in Japan’s Maternal and Child Health Handbook were revised, replacing the term “sunbathing” with “fresh air bathing” to mitigate concerns regarding UV-related adverse effects. Combined with increased indoor lifestyle patterns in modern society, these changes may contribute to insufficient vitamin D synthesis (4). In addition, high-latitude regions receive less UVB radiation. Hokkaido, the northernmost and coldest region of Japan (approximately 43° N latitude), is particularly vulnerable due to limited UVB availability and reduced outdoor activity during the prolonged winter season (6).
A survey of 84 hospitals in Hokkaido reported that the incidence of vitamin D deficiency rickets was approximately 3.5 times higher than the national average between 1999 and 2004 (7, 8). Since then, preventive and diagnostic approaches have advanced in Japan. Infant vitamin D supplements (BabyD®) became commercially available in 2014 (9), and measurement of 25(OH)D was incorporated into the national health insurance system in August 2016 (10). These developments may have influenced the epidemiology and clinical profile of vitamin D-deficient rickets.
Therefore, this study aimed to assess the incidence and clinical characteristics of vitamin D deficiency and vitamin D deficiency rickets in Hokkaido between 2015 and 2019.
Materials and Methods
Study design and participants
A two-stage survey was conducted targeting the pediatric departments of 88 major hospitals in Hokkaido, Japan. The first survey asked whether patients diagnosed with vitamin D deficiency or vitamin D deficiency rickets had been treated between January 2015 and December 2019. Facilities reporting relevant cases were invited to complete a secondary survey providing detailed clinical information. Vitamin D deficiency was defined as serum 25(OH)D level < 20 ng/mL (10). Vitamin D deficiency rickets was defined as vitamin D deficiency accompanied by radiological evidence of rickets.
Data collected in the secondary survey included age, sex, residential area, feeding method, ‘picky eating’ or dietary restrictions, biochemical parameters [calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), 25(OH)D, 1,25(OH)2D, intact PTH (iPTH)], X-ray findings of rickets, and treatment details. ALP values were standardized according to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) method using the following formula: ALP (IFCC) = ALP (JSCC-measured value) / 2.84 (11). Serum 25(OH)D levels were measured using either chemiluminescent immunoassay or chemiluminescence enzyme immunoassay, which are the standard diagnostic methods used in Japan during the study period. Because the specific assay for each case was not recorded, the data were standardized for analysis. Results below the assay-specific lower detection limits (< 4.0 or < 5.0 ng/mL) were uniformly treated as 3.9 ng/mL.
Exclusion criteria included hypophosphatemic rickets, hypophosphatasia, vitamin D dependence, metaphyseal dysplasia, hypoparathyroidism, pseudohypoparathyroidism, cholestasis, transient hyperphosphatasemia, and metabolic bone disease of prematurity (8).
In 2019, the incidence of vitamin D deficiency rickets among children aged < 4 yr was estimated per 100,000 live births. This was calculated by dividing the number of cases diagnosed in 2019 among children aged 0–3 yr by the total number of live births in Hokkaido during their birth years (12). Clinical characteristics were compared between patients with and without rickets.
Statistical analysis
Continuous variables are expressed as mean ± standard deviation (SD) when normally distributed and as median (interquartile range) when not normally distributed. Categorical variables were compared using the Chi-square test. Continuous variables were analyzed using Student’s t-test or the Mann–Whitney U test, as appropriate. All analyses were performed using R software (version 4.0.2; R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was set at p < 0.05.
Ethics statement
This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Asahikawa Medical University (Approval No.20006).
Results
Incidence of vitamin D deficiency and vitamin D deficiency rickets
The primary survey achieved a response rate of 97.7% (86 of 88 facilities). Among these, 41 facilities reported relevant cases, and all completed the secondary survey (100% response rate). The secondary survey yielded 333 cases; after excluding 21 cases outside the study period, 43 without 25(OH)D measurements, and 7 with 25(OH)D ≥ 20 ng/mL, a total of 262 cases met the criteria for vitamin D deficiency. Of these, 153 patients were classified as having vitamin D deficiency rickets (Fig. 1). No duplicate cases were identified. Both vitamin D deficiency and vitamin D deficiency rickets increased between 2015 and 2017, and subsequently plateaued (Fig. 2A).
Fig. 1.
Flowchart of study participant selection.
Fig. 2.
Distribution of cases with vitamin D deficiency and vitamin D deficiency rickets. (A) Distribution by year of diagnosis. (B) Distribution by age at onset. (C) Distribution by month of onset.
The median age at diagnosis was 1.4 yr (0.9–1.8) for all vitamin D deficiency cases and 1.5 yr (1.0–1.9) for rickets cases, with the vast majority occurring in children under four years of age (Fig. 2B). Three patients presented with hypocalcemia without radiological evidence of rickets. A seasonal trend was observed, with a higher incidence between February and April (Fig. 2C).
In 2019, the incidence rates per 100,000 live births were 51.6 for vitamin D deficiency and 25.4 for vitamin D deficiency rickets (Table 1). When stratified by regional UVB radiation, both conditions were more frequent in northeastern Hokkaido (71.6 and 37.9 per 100,000 live births, respectively) than in the southwestern region (38.7 and 17.6, respectively) (Fig. 3 and Table 1).
Table 1. Incidence of cases according to residential area in 2019.
Fig. 3.
Map of Hokkaido, Japan, and distribution of UVB Radiation. The numerical values represent the annual average of daily integrated UVB radiation (kJ/m2). The dashed lines indicate geographic boundaries. Hokkaido is divided into Northeast and Southwest regions based on a boundary of 11 kJ/m2 ref. (7, 13).
Comparison of clinical characteristics with and without rickets
(Table 2)
Table 2. Characteristics of patients with vitamin D deficiency.
The age at diagnosis was significantly higher in the rickets group compared with the non-rickets group (1.5 [1.0–1.9] yr vs. 1.2 [0.7–1.6] yr, p = 0.007). The sex distribution did not differ significantly, although boys were more frequent in both groups. Exclusive breastfeeding was common overall but was significantly more prevalent among children with rickets (83.0% vs. 65.2%, p < 0.001). ‘Picky eating’ or dietary restrictions were reported in 28.8% and 25.7% of the rickets and non-rickets groups, respectively, with no significant difference.
The chief presenting complaint in the rickets group was bow legs (56.7% vs. 29.4%, p < 0.001). Convulsions occurred in approximately 5% of patients in both groups. Among these, 78.6% (11/14) demonstrated hypocalcemia. Initial presentations among the 44 vitamin D-deficient patients included incidental blood test findings (n = 24), short stature (n = 11), poor weight gain (n = 3), genu valgum (n = 2), and one case each of tetany, developmental delay, gait difficulty, and kyphosis.
Pharmacological therapy was administered more frequently in the rickets group (94.1% vs. 79.0%, p < 0.001). Alfacalcidol was the most common treatment in both groups, used in 84.9% and 69.7% of the rickets and non-rickets groups, respectively. Natural vitamin D preparations (administered as Baby D® drops) were used in 4.6% and 5.5% of cases, respectively.
Comparison of biochemical findings with and without rickets
Table 3. Comparison of biochemical parameters in patients with vitamin D deficiency with and without rickets.
Table 4. Comparison of biochemical parameters in patiens with vitamin D deficiency with and without rickets among exclusive breastfed infants.
Table 5. Comparison of biochemical parameters in patiens with vitamin D deficiency with and without rickets among non-exclusive breastfed infants.
Median 25(OH)D levels did not differ significantly between the rickets (6.0 ng/mL) and non-rickets (6.9 ng/mL) groups. However, Ca (9.4 vs. 9.8 mg/dL) and P (4.0 vs. 5.1 mg/dL) levels were significantly lower in the rickets group (p < 0.001 for both). In contrast, ALP (733.4 vs. 469.1 IU/L) and iPTH (230.1 vs. 112.1 pg/mL) levels were markedly higher in the rickets group (p < 0.001 for both).
To further evaluate the influence of nutrition on rickets development, a subgroup analysis was conducted based on feeding type (exclusive vs. non-exclusive breastfeeding). The findings in the exclusively breastfed subgroup were consistent with those in the overall cohort. Specifically, there was no significant difference in serum 25(OH)D levels, whereas infants with rickets exhibited significantly lower serum Ca and P levels and significantly higher ALP and iPTH levels than those without rickets (Table 4). A similar trend in biochemical markers was observed in the non-exclusively breastfed group (Table 5); however, the differences were not statistically significant, likely due to the limited sample size of this subgroup.
Discussion
In this study, the incidence and clinical features of vitamin D deficiency were investigated. Vitamin D deficiency rickets in Hokkaido, a high-latitude region in northern Japan, are known to be associated with an elevated risk of vitamin D deficiency. The incidence of vitamin D deficiency rickets increased approximately threefold to 25.4 cases per 100,000 live births, compared with a survey conducted 15 yr earlier in this region (7). In contrast, the seasonal variation and differences in the incidence rates between the northeastern and southwestern regions were consistent with those reported previously (7), supporting the role of varying UVB radiation exposure in Hokkaido. The higher incidence observed between February and April may be attributed to reduced UVB exposure during the preceding winter months (November to January). Although recent epidemiological data on vitamin D deficiency rickets from regions at latitudes similar to the study period are unavailable, a study from New Zealand conducted between 2010 and 2013 provides a relevant comparison (14). This report documented an overall annual incidence of 2.2 per 100,000 in children aged < 15 yr, with a peak of 6.8 per 100,000 in the southern region of the country. The incidence was higher among children aged < 5 yr (6.6 per 100,000 individuals). The incidence rate observed in the present study exceeded that reported in New Zealand. Furthermore, this rate was remarkably higher, approximately eight-fold, than the annual incidence of symptomatic vitamin D deficiency (including hypocalcemia or rickets) in Japanese children under five years of age from 2013 to 2016, reported as 3.5 per 100,000 individuals (8).
One factor contributing to the increased incidence may be the inclusion of 25(OH)D measurements under national medical insurance coverage in Japan since 2016. Indeed, the number of vitamin D deficiency rickets cases approximately tripled from 2015 (before 25(OH)D measurement became insurance-covered) to 2017 (after coverage) and then plateaued (Fig. 2A). However, the incidence rate has not declined despite the commercial availability of infant vitamin D supplements in Japan since 2014 (9). This trend is not confined to Hokkaido but appears to reflect broader societal shifts in Japan (15). Several factors, such as increased sun avoidance, reduced outdoor activity among children, and dietary changes including decreased consumption of oily fish, have contributed to this increase. In addition, the lack of widespread vitamin D food fortification in Japan, combined with practices such as prolonged exclusive breastfeeding without supplementation, further exacerbates this public health issue (15). While it remains difficult to compare recent trends with those in other developed countries owing to the lack of current, large-scale data (16), these findings highlight a significant and growing concern within our region.
In the present study, 41.6% of patients diagnosed with vitamin D deficiency did not present with rickets. Although the diagnosis of genu varum was based on clinical judgment rather than on a pre-specified objective criterion, this finding was observed in at least 29.4% of these patients. This finding is consistent with a previous report indicating that vitamin D deficiency can cause genu varum even in the absence of overt rickets (17). Therefore, infants and toddlers presenting with genu varum should undergo 25(OH)D testing even if ALP, Ca, and P levels are within the normal ranges. Recent reports have indicated a high prevalence of vitamin D deficiency in Hokkaido (6), suggesting the need for continued public health education regarding vitamin D intake.
In this study, biochemical parameters were compared between vitamin D deficiency patients with and without rickets. The median 25(OH)D level was markedly low in both groups, with no significant difference observed. However, Ca and P levels were significantly lower in the rickets group, whereas ALP and iPTH levels were significantly higher in both the entire cohort and exclusively breastfed subgroup. These findings support the notion that a reduced calcium-phosphorus product level is crucial for the development of rickets. Notably, rickets can be ameliorated in vitamin D receptor knockout mice when normal calcium-phosphorus product levels are maintained, even in the complete absence of vitamin D activity (18). This underscores the importance of both vitamin D and adequate calcium intake in preventing rickets (19). Similarly, Sempos et al. demonstrated that the serum 25(OH)D concentration required to prevent nutritional rickets is inversely dependent on calcium intake (20). Although dietary calcium intake was not directly evaluated in this study, the significantly lower serum calcium levels observed in the rickets group suggest insufficient calcium intake. Additionally, prolonged vitamin D deficiency is thought to contribute to the development and progression of rickets through sustained reductions in intestinal calcium and phosphorus absorption and altered bone mineralization (21). However, the time-dependent influence of vitamin D deficiency on the development and progression of rickets was not investigated in this study. In contrast, breastfeeding was more frequent in the rickets group, suggesting an association between breastfeeding and ricket development despite similar 25(OH)D concentrations.
Currently, no prescription of native vitamin D preparations are available for the treatment of symptomatic vitamin D deficiencies in Japan. In the present study, approximately 90% of patients were treated with alfacalcidol. However, alfacalcidol administration does not increase 25(OH)D levels and is associated with side effects such as nephrolithiasis and hypercalcemia (22). The concomitant use of native vitamin D preparations was observed in only 5% of cases, most likely reflecting co-administration of the BabyD® supplement. Therefore, improving access to prescription native vitamin D preparations in Japan is warranted.
As vitamin D deficiency rickets is preventable, the importance of vitamin D supplementation during infancy is emphasized (19). National guidelines in the United States, Canada, and the United Kingdom recommend providing 400 IU/d of vitamin D to all infants from birth (23,24,25). In Japan, although the Japan Pediatric Society has issued recommendations for preventing infant vitamin D deficiency, the universal administration of native vitamin D to newborns and infants remains controversial (26). However, when lifestyle or dietary risk factors for vitamin D deficiency are difficult to modify, native vitamin D supplementation should be considered for infants (26). The findings of this study support active recommendation of vitamin D supplementation in high-latitude regions such as Hokkaido. Furthermore, fetal vitamin D concentrations are proportional to maternal vitamin D concentrations (27), making maternal vitamin D deficiency a risk factor for vitamin D deficiency in offspring. In Hokkaido, vitamin D deficiency is evident at birth (28), likely reflecting maternal vitamin D insufficiency (29). Therefore, in Hokkaido, promoting adequate vitamin D intake through lifestyle and dietary habits is essential not only for infants, but also for women before conception and during pregnancy.
A limitation of this study is its reliance on hospital-based cases and the absence of a standardized assay for 25(OH)D, which prevents a comprehensive understanding of vitamin D status across the entire pediatric population. However, the findings related to rickets are highly reliable, given the high response rate (97.7%) from major pediatric departments across Hokkaido. Second, this study did not include data on vitamin D supplement use, dietary habits, or UVB exposure. Therefore, it does not fully capture overall vitamin D status in children in Hokkaido. Future research should investigate whether public health education regarding vitamin D administration contribute to a reduction in the incidence of vitamin D deficiency and rickets.
Conclusion
The findings revealed that the incidence of vitamin D deficiency and vitamin D deficiency rickets has increased and is significantly higher than the Japanese average. This study also highlights the potential for symptomatic vitamin D deficiency even in the absence of overt rickets. Therefore, continued public health awareness and preventive strategies against vitamin D deficiency are warranted.
Conflict of interests
None of the authors have any potential conflicts of interest associated with this study. No public or commercial funding was received for the conduct of this work.
Acknowledgements
The authors thank Drs. M. Takase, K. Murono, E. Nakamura, H. Kajino, H. Kamasaki, A. Ishii, M. Nagao, S. Sai, M. Shirai, G. Taketazu, A. Nakamura, S. Shida, Y. Odagawa, K. Uetake, T. Yamaguchi, M. Nakanishi, H. Sano, K. Okuhara, N. Kobayashi, M. Takahashi, R.Takeuchi, K. Ishii, I. Kobayashi, K. Matsuo, F. Kakuya, T. Ishioka, Y. Tachibana, M. Saito, Y. Sakai, T. Ohara, M. Kihara, T. Mori, T. Hotsubo, M. Nakajima, H. Aoyagi, T. Tajima, T. Sato, Y. Ito, J. Tsubaki, H. Naito, M Kikuchi, M. Yokozawa, Y. Okada, M. Segawa, M. Tatsumi, and Y. Okada for providing patient information, as well as the other physicians at the participating hospitals in Hokkaido, Japan.
References
- 1.Holick MF. Vitamin D deficiency. N Engl J Med 2007;357: 266–81. doi: 10.1056/NEJMra070553 [DOI] [PubMed] [Google Scholar]
- 2.Rebelos E, Tentolouris N, Jude E. The Role of vitamin D in health and disease: a narrative review on the mechanisms linking vitamin D with disease and the effects of supplementation. Drugs 2023;83: 665–85. doi: 10.1007/s40265-023-01875-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Giustina A, Bilezikian JP, Adler RA, Banfi G, Bikle DD, Binkley NC, et al. Consensus statement on Vitamin D status assessment and supplementation: whys, whens, and hows. Endocr Rev 2024;45: 625–54. doi: 10.1210/endrev/bnae009 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96: 1911–30. doi: 10.1210/jc.2011-0385 [DOI] [PubMed] [Google Scholar]
- 5.Dawodu A, Tsang RC. Maternal vitamin D status: effect on milk vitamin D content and vitamin D status of breastfeeding infants. Adv Nutr 2012;3: 353–61. doi: 10.3945/an.111.000950 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Yang L, Sato M, Saito-Abe M, Irahara M, Nishizato M, Sasaki H, et al. Japan Environment and Children’s Study (JECS) Group). 25-Hydroxyvitamin D levels among 2-year-old children: findings from the Japan environment and Children’s study (JECS). BMC Pediatr 2021;21: 539. doi: 10.1186/s12887-021-03005-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Matsuo K, Mukai T, Suzuki S, Fujieda K. Prevalence and risk factors of vitamin D deficiency rickets in Hokkaido, Japan. Pediatr Int 2009;51: 559–62. doi: 10.1111/j.1442-200X.2009.02834.x [DOI] [PubMed] [Google Scholar]
- 8.Kubota T, Nakayama H, Kitaoka T, Nakamura Y, Fukumoto S, Fujiwara I, et al. Incidence rate and characteristics of symptomatic vitamin D deficiency in children: a nationwide survey in Japan. Endocr J 2018;65: 593–9. doi: 10.1507/endocrj.EJ18-0008 [DOI] [PubMed] [Google Scholar]
- 9.https://babyd.jintan.jp/what.html (last accessed August 18, 2025).
- 10.Okazaki R, Ozono K, Fukumoto S, Inoue D, Yamauchi M, Minagawa M, et al. Assessment criteria for vitamin D deficiency/insufficiency in Japan - proposal by an expert panel supported by Research Program of Intractable Diseases, Ministry of Health, Labour and Welfare, Japan, The Japanese Society for Bone and Mineral Research and The Japan Endocrine Society [Opinion] [Opinion]. Endocr J 2017;64: 1–6. doi: 10.1507/endocrj.EJ16-0548 [DOI] [PubMed] [Google Scholar]
- 11.Hanaoka S, Motokura K, Tomotaki S, Akita M, Araki R, Tomobe Y, et al. Comparison of two methods measuring serum alkaline phosphatase in neonates. Pediatr Int 2022;64: e15108. doi: 10.1111/ped.15108 [DOI] [PubMed] [Google Scholar]
- 12.https://www.pref.hokkaido.lg.jp/ss/tuk/900brr/index2.html#1 (last accessed August 18, 2025).
- 13.https://www.env.go.jp/chemi/uv/uv_manual.html (last accessed August 18, 2025).
- 14.Wheeler BJ, Dickson NP, Houghton LA, Ward LM, Taylor BJ. Incidence and characteristics of vitamin D deficiency rickets in New Zealand children: a New Zealand Paediatric Surveillance Unit study. Aust N Z J Public Health 2015;39: 380–3. doi: 10.1111/1753-6405.12390 [DOI] [PubMed] [Google Scholar]
- 15.Itoh M, Tomio J, Toyokawa S, Tamura M, Isojima T, Kitanaka S, et al. Vitamin D-deficient rickets in Japan. Glob Pediatr Health 2017. Jun 1;4:2333794X17711342. [DOI] [PMC free article] [PubMed]
- 16.Soliman AT, Alyafei F, Alaaraj NM, Elsiddig S, Hamed N, Ahmed S, et al. Vitamin D deficiency and infantile rickets worldwide (2000–2025): epidemiological patterns, public health gaps and interventional insights. GSC Advanced Research and Reviews 2025;24: 262–77. doi: 10.30574/gscarr.2025.24.1.0212 [DOI] [Google Scholar]
- 17.Sakamoto Y, Ishijima M, Nakano S, Suzuki M, Liu L, Tokita A, et al. Physiologic leg bowing is not a physiologic condition but instead is associated with vitamin D disorders in toddlers. Calcif Tissue Int 2020;106: 95–103. doi: 10.1007/s00223-019-00619-9 [DOI] [PubMed] [Google Scholar]
- 18.Masuyama R, Nakaya Y, Katsumata S, Kajita Y, Uehara M, Tanaka S, et al. Dietary calcium and phosphorus ratio regulates bone mineralization and turnover in vitamin D receptor knockout mice by affecting intestinal calcium and phosphorus absorption. J Bone Miner Res 2003;18: 1217–26. doi: 10.1359/jbmr.2003.18.7.1217 [DOI] [PubMed] [Google Scholar]
- 19.Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, et al. Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab 2016;101: 394–415. doi: 10.1210/jc.2015-2175 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Sempos CT, Durazo-Arvizu RA, Fischer PR, Munns CF, Pettifor JM, Thacher TD. Serum 25-hydroxyvitamin D requirements to prevent nutritional rickets in Nigerian children on a low-calcium diet-a multivariable reanalysis. Am J Clin Nutr 2021;114: 231–7. doi: 10.1093/ajcn/nqab048 [DOI] [PubMed] [Google Scholar]
- 21.Morris HA, Turner AG, Anderson PH. Vitamin-D regulation of bone mineralization and remodelling during growth. Front Biosci (Elite Ed) 2012;4: 677–89. doi: 10.2741/e409 [DOI] [PubMed] [Google Scholar]
- 22.Letavernier E, Daudon M. Vitamin D, hypercalciuria and kidney stones. Nutrients 2018;10: 366. doi: 10.3390/nu10030366 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Abrams SA. Committee on Nutrition. Calcium and vitamin d requirements of enterally fed preterm infants. Pediatrics 2013;131: e1676–83. doi: 10.1542/peds.2013-0420 [DOI] [PubMed] [Google Scholar]
- 24.Irvine J, Ward LM. Preventing symptomatic vitamin D deficiency and rickets among Indigenous infants and children in Canada. Paediatr Child Health 2022;27: 127–8. doi: 10.1093/pch/pxac003 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.NICE Public health guideline on vitamin D – Supplement use in specific population groups (2014, updated 2017) https://www.nice.org.uk/guidance/ph56.
- 26.Kawai M, Ida S, Kitanaka S, Takitani K, Tokita A, Ito S, et al. Statement on the prevention of vitamin D deficiency in infancy. J Jpn Pediatr Soc. 2025;129: 494–6 (in Japanese). [Google Scholar]
- 27.Wang X, Jiao X, Tian Y, Zhang J, Zhang Y, Li J, et al. Shanghai Birth Cohort Study. Associations between maternal vitamin D status during three trimesters and cord blood 25(OH)D concentrations in newborns: a prospective Shanghai birth cohort study. Eur J Nutr 2021;60: 3473–83. doi: 10.1007/s00394-021-02528-w [DOI] [PubMed] [Google Scholar]
- 28.Nohara F, Okamoto T, Takahashi K, Sugiyama T, Hashimoto A, Nii M, et al. Vitamin D status and the adequacy of its supplementation during the first year of life in preterm infants in northern Japan. Pediatr Neonatol 2025;66: 594–600. doi: 10.1016/j.pedneo.2025.03.003 [DOI] [PubMed] [Google Scholar]
- 29.Nakanishi K, Mutoh M, Itoh S, Kobayashi S, Yamaguchi T, Iwata H, et al. Vitamin D concentration in maternal serum during pregnancy: Assessment in Hokkaido in adjunct study of the Japan Environment and Children’s Study (JECS). PLoS One 2024;19: e0312516. doi: 10.1371/journal.pone.0312516 [DOI] [PMC free article] [PubMed] [Google Scholar]