Serum vitamin D levels among children aged 0–12 years in the First Affiliated Hospital of Harbin Medical University, China

Serum vitamin D levels among children aged 0–12 years in the First Affiliated Hospital of... Abstract Background Vitamin D deficiency (VDD) and vitamin D insufficiency (VDI) are highly prevalent in the world, but the vitamin D status of children in northeast China is seldom investigated. The aim of this study was to clarify the prevalence of VDD and VDI among children in the First Affiliated Hospital of Harbin Medical University in Heilongjiang province in China. Methods We collected data from 9795 children who were outpatients aged 0–12 years who visited the First Affiliated Hospital of Harbin Medical University from September 2014 to August 2016. Serum 25-hydroxy vitamin D [25(OH)D] levels were determined by chemiluminescent immunoassay and categorized as <20, 20–30 and >30 ng/mL. Results The highest mean level of serum 25(OH)D was found at the 1–3 years stage (31.14 ng/mL) and the lowest at 6–12 years stage (18.58 ng/mL). The mean serum 25(OH)D level among school girls (17.86 ng/mL) was lower than that of boys (19.12 ng/mL). The prevalence of vitamin D sufficiency during 2014 was only 17.2%, but increased to ~45% in 2016. Conclusions The prevalence of VDD and insufficiency among children in the First Affiliated Hospital of Harbin Medical University is high, especially among children aged 6–12 years. Introduction Vitamin D is a prohormone that is essential for normal absorption of calcium from the gut, and deficiency of vitamin D is associated with rickets in growing children and osteomalacia in adults.1 The major source of vitamin D for humans is exposure to sunlight.2 Unfortified foods naturally containing vitamin D are limited. The best food sources are animal products, particularly fatty fish and liver extracts like salmon or sardines and cod liver oil.3 For infants, breast milk is the best source of vitamin D.1 Vitamin D deficiency (VDD) and vitamin D insufficiency (VDI) are highly prevalent in the world.4 VDD is defined as a 25-hydroxy vitamin D [25(OH)D] serum concentration <20 ng/mL (50 nmol/L), while VDI is diagnosed when serum 25(OH)D levels are 20–30 ng/mL (50–75 nmol/L). A level of >30 ng/mL (75 nmol/L) can be considered to indicate vitamin D sufficiency.5 According to such definitions, the prevalence of VDI was the highest among American children.6 In studies of Australia, Turkey, India and Lebanon, 30–50% of children and adults had 25-hydroxy vitamin D [25(OH)D] levels under 20 ng/mL.7–9 In southeast China (Hangzhou), more than 20% of preschoolers and over 40% of school children and adolescents had 25(OH)D levels <20 ng/mL.10 However, the vitamin D status of children in northeast China is seldom investigated. Inadequate vitamin D synthesis and nutritional intake is the main cause of VDD and VDI. VDD and VDI are associated with physical agents blocking ultraviolet radiation exposure, such as clothing, sunscreen and shade, as well as factors such as latitude and season.1 VDD and VDI are associated with many acute and chronic illnesses including disorders of calcium metabolism, autoimmune diseases, cancers, type 2 and type 1 diabetes mellitus, cardiovascular diseases and infectious diseases.11 The aim of this study was to clarify the prevalence of VDD and VDI among children in the First Affiliated Hospital of Harbin Medical University. Moreover, we discuss if strategies of vitamin D supplementation should be localized. Materials and methods Ethical statement Written informed consent was obtained in the local language from all participants. All subjects included in this study provided written informed consent, and the protocol of this study was approved by the First Affiliated Hospital of Harbin Medical University Ethics Review Committee. Data collection and methods Data from all children who were outpatient accepted routine 25(OH)D testing from September 2014 to August 2016 throughout the year were included during spring (March through May), summer (June through August), autumn (September through November) and winter (December through February). The clinical information including name, age, sex, patient registration number and blood collection date were collected from all subjects involved. According to their age, children were divided into four groups: infancy (0–1 years), toddlers (1–3 years), preschool (3–6 years) and school age (6–12 years). Serum 25(OH)D levels were measured by chemiluminescent immunoassay (DiaSorin Inc., Shanghai, Italian). DiaSorin has provided laboratories with assays that accurately measure total 25(OH)D levels, thanks to antibodies that are co-specific for 25(OH)D2 and 25(OH)D3. According to their serum 25(OH)D levels, children were also divided into three groups as deficiency (25(OH)D < 20 ng/mL), insufficiency (25(OH)D = 20–30 ng/mL) and sufficiency (25(OH)D > 30 ng/mL). Statistical analysis SPSS version 17.0 was used for all statistical analysis. Continuous variables were expressed using the mean value. Mean levels of serum 25(OH)D were computed and compared between sex group using the two-sample t-test. Mean levels of serum 25(OH)D were computed and compared between other groups using the q test. In terms of categorical values, a chi-square test was used to compare differences between the three groups. In all statistical analyses, P-values below 0.05 were considered statistically significant. Results Prevalence of VDD and VDI insufficiency by age group In this cross-sectional study of a large cohort of children of ages 0–12 years, the overall prevalence of combined VDD and VDI was 70% and that of vitamin D sufficiency only 30%. The mean serum 25(OH)D level was 24.82 ng/mL among all children in this study. The mean serum 25(OH)D level was highest (31.14 ng/mL) among toddlers and decreased among infants (29.55 ng/mL) and preschoolers (22.25 ng/mL), and was the lowest among school children (18.58 ng/mL). About 50% of infants and toddlers (51.2 and 49.6%, respectively) and over 80% of preschoolers and school children (80.2 and 89.6%, respectively) had 25(OH)D levels of <30 ng/mL. Significant differences were found between the mean serum 25(OH)D level and the prevalence of VDD and VDI among the four age groups (Table 1). Table 1 Prevalence of vitamin D deficiency and vitamin D insufficiency group by sex, age group and season Mean (ng/mL) P1 Vitamin D deficiency Vitamin D insufficiency Vitamin D sufficiency P2 n = 4169 n = 2685 n = 2941 n % n % n % Sex  Boy 25.18 2336 41.3 1561 27.6 1753 31.1  Girl 24.34 0.002 1833 44.2 1124 27.1 1188 28.7 0.009 Age group, years  0–1 29.55 293 28.1 240 23.1 508 48.8  1–3 31.14 639 20.1 937 29.5 1602 50.4  3–6 22.25 1328 49.7 817 30.6 528 19.7  6–12 18.58 <0.001 1909 65.8 691 23.8 303 10.4 <0.001 Season  Spring# 23.80 1292 49.2 592 22.5 742 28.3  Summer* 29.70 698 23.1 1065 35.4 1253 41.5  Autumn## 23.82 759 43.0 563 31.9 444 25.1  Winter** 20.53 <0.001 1420 59.5 465 19.5 502 21.0 <0.001 Mean (ng/mL) P1 Vitamin D deficiency Vitamin D insufficiency Vitamin D sufficiency P2 n = 4169 n = 2685 n = 2941 n % n % n % Sex  Boy 25.18 2336 41.3 1561 27.6 1753 31.1  Girl 24.34 0.002 1833 44.2 1124 27.1 1188 28.7 0.009 Age group, years  0–1 29.55 293 28.1 240 23.1 508 48.8  1–3 31.14 639 20.1 937 29.5 1602 50.4  3–6 22.25 1328 49.7 817 30.6 528 19.7  6–12 18.58 <0.001 1909 65.8 691 23.8 303 10.4 <0.001 Season  Spring# 23.80 1292 49.2 592 22.5 742 28.3  Summer* 29.70 698 23.1 1065 35.4 1253 41.5  Autumn## 23.82 759 43.0 563 31.9 444 25.1  Winter** 20.53 <0.001 1420 59.5 465 19.5 502 21.0 <0.001 P1, two-sample t-test (sex group) q test (other groups); P2, Chi-square test. *q Test, P < 0.05, P-value is significant for summer to the other three seasons; **q test, P < 0.05, P-value is significant for winner to the other three seasons. #q Test, P < 0.05, P-value is significant for spring to the summer and winter. ##q Test, P < 0.05, P-value is significant for autumn to the summer and winter. Table 1 Prevalence of vitamin D deficiency and vitamin D insufficiency group by sex, age group and season Mean (ng/mL) P1 Vitamin D deficiency Vitamin D insufficiency Vitamin D sufficiency P2 n = 4169 n = 2685 n = 2941 n % n % n % Sex  Boy 25.18 2336 41.3 1561 27.6 1753 31.1  Girl 24.34 0.002 1833 44.2 1124 27.1 1188 28.7 0.009 Age group, years  0–1 29.55 293 28.1 240 23.1 508 48.8  1–3 31.14 639 20.1 937 29.5 1602 50.4  3–6 22.25 1328 49.7 817 30.6 528 19.7  6–12 18.58 <0.001 1909 65.8 691 23.8 303 10.4 <0.001 Season  Spring# 23.80 1292 49.2 592 22.5 742 28.3  Summer* 29.70 698 23.1 1065 35.4 1253 41.5  Autumn## 23.82 759 43.0 563 31.9 444 25.1  Winter** 20.53 <0.001 1420 59.5 465 19.5 502 21.0 <0.001 Mean (ng/mL) P1 Vitamin D deficiency Vitamin D insufficiency Vitamin D sufficiency P2 n = 4169 n = 2685 n = 2941 n % n % n % Sex  Boy 25.18 2336 41.3 1561 27.6 1753 31.1  Girl 24.34 0.002 1833 44.2 1124 27.1 1188 28.7 0.009 Age group, years  0–1 29.55 293 28.1 240 23.1 508 48.8  1–3 31.14 639 20.1 937 29.5 1602 50.4  3–6 22.25 1328 49.7 817 30.6 528 19.7  6–12 18.58 <0.001 1909 65.8 691 23.8 303 10.4 <0.001 Season  Spring# 23.80 1292 49.2 592 22.5 742 28.3  Summer* 29.70 698 23.1 1065 35.4 1253 41.5  Autumn## 23.82 759 43.0 563 31.9 444 25.1  Winter** 20.53 <0.001 1420 59.5 465 19.5 502 21.0 <0.001 P1, two-sample t-test (sex group) q test (other groups); P2, Chi-square test. *q Test, P < 0.05, P-value is significant for summer to the other three seasons; **q test, P < 0.05, P-value is significant for winner to the other three seasons. #q Test, P < 0.05, P-value is significant for spring to the summer and winter. ##q Test, P < 0.05, P-value is significant for autumn to the summer and winter. Prevalence of vitamin D deficiency and vitamin D insufficiency by sex There were 4145 girls (42.3%) and 5650 boys (57.7%) in this study. Mean serum 25(OH)D levels in boys and girls were 25.18 and 24.34 ng/mL, respectively. VDD was more prevalent in girls (44.2%) than in boys (41.3%) (Table 1). The mean serum 25(OH)D level among school girls was lower than that of boys (P = 0.001). Among school age children, the prevalence of VDD was less among girls (63.2%) than boys (69.2%), while the prevalence of VDI was higher in boys (25.9%) than in girls (21.0%) (Fig. 1). Among the other three stages, there were no significant differences between the prevalence of VDD and VDI and the mean serum 25(OH)D level between boys and girls. Fig. 1 View largeDownload slide The percents of vitamin D sufficiency, insufficiency and deficiency in different sex among 6–12 years old children. Fig. 1 View largeDownload slide The percents of vitamin D sufficiency, insufficiency and deficiency in different sex among 6–12 years old children. Prevalence of vitamin D deficiency and vitamin D insufficiency by season The mean levels of serum 25(OH)D changed according to season. The levels of 25(OH)D gradually increased in the order of winter, spring, autumn and summer (from 29.70 to 20.53 ng/mL). The mean level of serum 25(OH)D in spring was similar to that of autumn (23.80 and 23.82 ng/mL, respectively). There were no significant differences between the mean serum 25(OH)D levels in the two groups above. The prevalence of vitamin D sufficiency during the four seasons was 28.3, 41.5, 25.1 and 21.0% (Table 1). Prevalence of vitamin D deficiency and vitamin D insufficiency by year A total of 9795 children serum collected in 2014–16 in this cross-sectional study. Mean serum 25(OH)D levels increased over the course of the collection period. The mean serum 25(OH)D level was lowest (19.73 ng/mL) during 2014 and increased during 2015 (23.62 ng/mL), then reached the highest during 2016 (29.41 ng/mL) (Fig. 2). The prevalence of vitamin D sufficiency during 2014 was only 17.2%, but increased to ~45% in 2016. Fig. 2 View largeDownload slide The means of serum 25(OH)D level in different years. Fig. 2 View largeDownload slide The means of serum 25(OH)D level in different years. Discussion Main finding of this study The present study is the first one to investigate vitamin D status among the pediatric population in Heilongjiang province in the northeast of China. Our study main found that the prevalence of VDD and VDI among children in the First Affiliated Hospital of Harbin Medical University in Heilongjiang province is high, especially among children aged 6–12 years. We suggest that nutritional education information regarding vitamin D supplements in school children should be increased. We hope China will provide us with the amount of vitamin D content in foods and fortified vitamin D foods and preparations. What is already known on this topic Vitamin D is a prohormone that is essential for normal absorption of calcium from the gut, and deficiency of vitamin D is associated with rickets in growing children and osteomalacia in adults.1 VDD and VDI are highly prevalent in the world.4 Some data demonstrated that the serum 25(OH)D levels among pediatric population decreased when the children became older, and the prevalence of VDD increased at the same time. The mean level of 25(OH) D among infants was much higher than that of any other stages.10 Girls had a higher prevalence of VDD compared with boys. The mean levels of 25(OH)D among girls were also lower than boys,4,6,12 especially at school age. Children of all ages are more susceptible to low vitamin D levels during the winter compared with the summer months.1 However, the vitamin D status of children in northeast China is seldom investigated. What this study adds Our data demonstrated that the mean level of 25(OH)D among toddlers was much higher than that of any other stages. The prevalence of vitamin D sufficiency among toddlers and infancy was ~50%. The prevalence of VDD and VDI among the preschool group was ~80%. But the prevalence of VDD and VDI reached ~90% among school children and the mean level of 25(OH)D was the lowest in all age groups. According to the recommendations from the Chinese Society of Nutrition, all individuals should receive 400 IU/d of vitamin D from birth until age 50.13 The parents of infants and toddlers provide breast milk and many kinds of oral supplementation agents containing vitamins D and A in water or oil drops can be purchased in pharmacies in Heilongjiang for children;10 however, the usage rate of supplementation agents containing vitamin D among school children is lower than preschool children.14 Some investigators considered the reasons of this condition is that as children age and begin playing outdoors more often, the relative effects of skin pigmentation may become more evident.6 Other researchers have thought that parents provided breast milk and supplementation agents containing vitamin D for their children as infants and toddlers; however, when children reach preschool and school age, parents devote less attention to supplementation of vitamin D because they thought the growth of children has slowed.15 Currently, China does not have a compulsory requirement for school children to intake vitamin D. We found the mean level of 25(OH)D among toddlers is higher than among infants in this study, which is different from other research results. This fully reflects the benefits of the vitamin D supplementation for infants and toddlers by national regimens. Furthermore, the Institute of Medicine suggests a recommended dietary allowance (RDA) for vitamin D of 600 IU/d from ages 1 to 70 years, corresponding to a serum 25(OH)D levels of at least 20 ng/mL (50 nmol/L) and meeting the requirements of at least 97.5% of the population.16 Hence, whether China should adjust the RDAs of vitamin D warrants further detailed study. In our study and in some studies in other countries, girls had a higher prevalence of VDD compared with boys. The mean levels of 25(OH)D among girls were also lower than boys,4,6,12 especially at school age. However, in China, many studies showed that there were no significant differences between mean serum 25(OH)D levels of boys and girls.17–19 It is noteworthy that some studies among adults in China revealed the mean of 25(OH)D among males was higher than females. This finding may be because women engage in less outdoor activity, use sunscreen and wear long sleeved clothing in order to skin lighter because women consider whiter skin to be a beauty aesthetic in China.20 Yan Xiaoning hypothesized that the subcutaneous fat content of females higher than males; thus, the fat soluble properties of vitamin D might result in women’s subcutaneous fat containing more vitamin D3 molecules in the skin, decreasing the effective molecules in the blood.21 We considered the two points above may be reasons for the mean levels of serum 25(OH)D among girls being lower than those of boys. We did not collect data related to body mass index (BMI), the amount of physical activity, or the habits of children, so the precise reasons cannot be determined. More research in this field in the future is warranted. When compared with children who lived in Hangzhou, Zhejiang province in southeast China, our children had a much higher prevalence of vitamin D levels at <20 ng/mL in all stages.10 Meanwhile, the mean levels of 25(OH)D of our children were lower in most stages. This is mainly because of the different duration and temperature of the seasons and different dietary habits. In terms of seasons, we found that mean levels of serum 25(OH)D among children changed according to season. Levels were very low during the winter, increased gradually during spring and autumn, and reached a peak during summer. The first reason is that Heilongjiang is located in the northeast of China at a northern latitude of 43–53°. Incident ultraviolet radiation decreases with increasing latitude.22 Above 37° north latitude, the number of ultraviolet-B (UV-B) photons reaching the earth’s atmosphere is decreased by 80–100% in the winter months and, as a consequence, little vitamin D3 is produced in the skin.23 A minimum amount of UV-B is necessary for vitamin D production and this may not be reached at a latitude of above 40° in winter even with prolonged sun exposure.24 Hence, there are 3 months in winter when vitamin D cannot be produced from UV-B in Heilongjiang province (43–53° north). The other reason is that the outdoor activity of children is limited. In winter, the temperature in Heilongjiang is very low and children have to stay indoors most of the time. Increased time spent indoors at work may lead to decreased time spent outdoors and, therefore, decreased vitamin D synthesis. Additionally, children who stay indoors may not receive a summertime boost in vitamin D levels.25 In regard to diet, foods naturally containing vitamin D are limited and there was no vitamin D content is listed in the Chinese Food Composition List.26 In eight areas of China, according to the Japanese Food Standard Components List, tremella is the most important dietary source of vitamin D in children, followed by yogurt, mushrooms, eggs, duck and fish, while the contribution of supplement preparations of vitamin D was only 0.01%.27 It indicated parents rarely provide children with vitamin D supplements, fish and other foods that contain large amounts of vitamin D. Furthermore, there are no vitamin D fortified foods in China.20 Many countries already have vitamin D fortified dairy products or juices, such as the United Kingdom and Canada28 and vitamin D fortified foods can improve vitamin D status.29 Black et al.30 showed that vitamin D fortified foods, especially milk, could effectively increase levels of vitamin D by systematic analysis. Thus, China should provide vitamin D content in foods and fortified vitamin D foods and preparations. In addition, we analyzed variations in the mean of 25(OH)D and the prevalence of VDD in different years (2014–16). We found that the mean of 25(OH)D increased over the period of data collection, while the prevalence of VDD decreased. This may indicate greater recognition by parents of the importance of supplementation with vitamin D and more active dietary management in this respect. Limitations of this study There are still some limitations in the present study. Data from subjects related to possible factors and elements of vitamin D status including intake of supplements, children’s BMI, the amount of physical activity, and levels of intact parathyroid hormone, calcium, inorganic phosphate and alkaline phosphatase were not collected. A further study based on subjects investigating the possible related factors and elements of vitamin D status is warranted. Furthermore, the optimal vitamin D level among children should to be established by more studies given that an adequate amount of vitamin D in all human populations for sustaining both innate and acquired immunity against infection is very important.31 Acknowledgements We thank the participants and staff of the Department of Laboratory Diagnosis of the First Affiliated Hospital of Harbin Medical University, without whose generosity none of this work would have been possible. We also thank Joel G. Anderson, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this article. Funding Source Natural Science Foundation of Heilongjiang Province (Grant no. H201455). Financial Disclosure The authors have no financial relationships relevant to this article to disclose. Conflicts of Interest The authors have no conflicts of interest relevant to this article to disclose. Contributors’ Statements FW drafted the initial manuscript, and reviewed and revised the article. WZ conceptualized and designed the study, and reviewed and revised the article. JW collected data, and reviewed and revised the article. HX carried out the initial analyses, and reviewed and revised the article. HZ coordinated and supervised data collection, and critically reviewed the article. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. References 1 Misra M , Pacaud D , Petryk A , Collett-Solberg PF , Kappy M . Vitamin D deficiency in children and its management: review of current knowledge and recommendations . Pediatrics 2008 ; 122 ( 2 ): 398 – 417 . Google Scholar CrossRef Search ADS PubMed 2 Holick MF , Chen TC . Vitamin D deficiency: a worldwide problem with health consequences . Am J Clin Nutr 2008 ; 87 ( 4 ): 1080S – 6S . Google Scholar CrossRef Search ADS PubMed 3 Norman AW , Bouillon R . Vitamin D nutritional policy needs a vision for the future . Exp Biol Med 2010 ; 235 ( 9 ): 1034 – 45 . Google Scholar CrossRef Search ADS 4 Al Shaikh AM , Abaalkhail B , Soliman A et al. . Prevalence of vitamin D deficiency and calcium homeostasis in Saudi children . J Clin Res Pediatr Endocrinol 2016 ; 8 ( 4 ): 461 . Google Scholar CrossRef Search ADS PubMed 5 Holick MF . Vitamin D deficiency . N Engl J Med 2007 ; 357 ( 3 ): 266 – 81 . Google Scholar CrossRef Search ADS PubMed 6 Mansbach JM , Ginde AA , Camargo CA Jr . Serum 25-hydroxyvitamin D levels among US children aged 1 to 11 years: do children need more vitamin D? Pediatrics 2009 ; 124 ( 5 ): 1404 – 10 . Google Scholar CrossRef Search ADS PubMed 7 Marwaha RK , Tandon N , Reddy DR et al. . Vitamin D and bone mineral density status of healthy schoolchildren in northern India . Am J Clin Nutr 2005 ; 82 ( 2 ): 477 – 82 . Google Scholar CrossRef Search ADS PubMed 8 El-Hajj FG , Nabulsi M , Choucair M et al. . Hypovitaminosis D in healthy schoolchildren . Pediatrics 2001 ; 107 ( 4 ): 53 . Google Scholar CrossRef Search ADS 9 McGrath JJ , Kimlin MG , Saha S et al. . Vitamin D insufficiency in south-east Queensland . Med J Aust 2001 ; 174 ( 3 ): 150 – 1 . Google Scholar PubMed 10 Zhu Z , Zhan J , Shao J et al. . High prevalence of vitamin D deficiency among children aged 1 month to 16 years in Hangzhou, China . BMC Public Health 2012 ; 12 ( 1 ): 126 . Google Scholar CrossRef Search ADS PubMed 11 Roh YE , Kim BR , Choi WB et al. . Vitamin D deficiency in children aged 6 to 12 years: single center’s experience in Busan . Ann Pediatr Endocrinol Metab 2016 ; 21 ( 3 ): 149 – 54 . Google Scholar CrossRef Search ADS PubMed 12 Saintonge S , Bang H , Gerber LM . Implications of a new definition of vitamin D deficiency in a multiracial us adolescent population: the National Health and Nutrition Examination Survey III . Pediatrics 2009 ; 123 ( 3 ): 797 – 803 . Google Scholar CrossRef Search ADS PubMed 13 Chinese Society of Nutrition . Reference Intake of Nutrients in Dietary for Chinese People (Chinese DRIs) Handbook . Beijing : Science press , 2014 . (in Chinese). 14 Wang J , Zhang Y , Xue Y et al. . Intake of supplement vitamin and mineral of Chinese children aged 3–12 years old . Chin J Child Health Care 2015 ; 23 ( 06 ): 584 – 91 . (in Chinese). 15 Wang H , Wen H , Wang L et al. . Investigation and analysis of vitamin D nutritional status in 6651 children at 0–16 years old . Chin J Child Health Care 2016 ; 253 ( 09 ): 1325 – 7 . (in Chinese). 16 Ross AC , Manson JAE , Abrams SA et al. . The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know . J Clin Endocrinol Metab 2011 ; 96 ( 1 ): 53 – 8 . Google Scholar CrossRef Search ADS PubMed 17 Ma Y , Wang Y , Li Z . Investigation of serum 25-hydroxyvitamin D in children and teenagers . J Prev Med Inf 2016 ; 32 ( 02 ): 156 – 8 . (in Chinese). 18 Mo L , Huang C , Deng Y et al. . Analysis on nutritional status of vitamin D in children and adolescents in Hunan province . Matern Child Health Care China 2012 ; 27 ( 03 ): 4926 – 8 . (in Chinese). 19 Lin T , Chen H , Chen Y et al. . Study on vitamin D nutritional status among 25295 children in Guangzhou area in 2012 . Chin J Child Health Care 2013 ; 21 ( 08 ): 836 – 9 . (in Chinese). 20 Song S , Jia H , Liu J et al. . Vitamin D status in different age and gender groups . Clin J Med Officer 2015 ; 43 ( 06 ): 551 – 3 . (in Chinese). 21 Yan X . Differences of vitamin D contents of residents of different gender in Taiyuan city . J Shanxi Coll Traditional Chin Med 2015 ; 16 ( 02 ): 57 – 9 . (in Chinese). 22 Diamond J . Evolutionary biology: geography and skin colour . Nature 2005 ; 435 ( 7040 ): 283 – 4 . Google Scholar CrossRef Search ADS PubMed 23 Holick MF . Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease . Am J Clin Nutr 2004 ; 80 ( 6 suppl ): 1678S – 88S . Google Scholar CrossRef Search ADS PubMed 24 Matsuoka LY , Wortsman J , Haddad JG et al. . In vivo threshold for cutaneous synthesis of vitamin D3 . J Lab Clin Med 1989 ; 114 ( 3 ): 301 – 5 . Google Scholar PubMed 25 Del Arco C , Riancho JA , Luzuriaga C et al. . Vitamin D status in children with Down’s syndrome . J Intellect Disabil Res 1992 ; 36 ( pt 3 ): 251 – 7 . Google Scholar PubMed 26 Yang Y , Wang G , Pan X . Chinese Food Composition List . Beijing : Peking University Press , 2009 . (in Chinese). 27 Liu Y , Pan Z , Wang M et al. . Investigation on vitamin D intake among preschoolers from eight areas in China . Acta Nutrimenta Sinica 2016 ; 38 ( 06 ): 541 – 5 . (in Chinese). 28 O’donnell S , Cranney A , Horsley T et al. . Efficacy of food fortification on serum 25-hydroxyvitamin D concentrations: systematic review . Am J Clin Nutr 2008 ; 88 ( 6 ): 1528 – 34 . Google Scholar CrossRef Search ADS PubMed 29 Hower J , Knoll A , Ritzenthaler KL et al. . Vitamin D fortification of growing up milk prevents decrease of serum 25-hydroxyvitamin D concentrations during winter: a clinical intervention study in Germany . Eur J Pediatr 2013 ; 172 ( 12 ): 1597 – 605 . Google Scholar CrossRef Search ADS PubMed 30 Black LJ , Seamans KM , Cashman KD et al. . An updated systematic review and meta-analysis of the efficacy of vitamin D food fortification . J Nutr 2012 ; 142 ( 6 ): 1102 – 8 . Google Scholar CrossRef Search ADS PubMed 31 Fabri M , Stenger S , Shin DM et al. . Vitamin D is required for IFN-{gamma}-mediated antimicrobial activity of human macrophages . Sci Transl Med 2011 ; 3 ( 104 ): 104ra102 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Public Health Oxford University Press

Serum vitamin D levels among children aged 0–12 years in the First Affiliated Hospital of Harbin Medical University, China

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Abstract

Abstract Background Vitamin D deficiency (VDD) and vitamin D insufficiency (VDI) are highly prevalent in the world, but the vitamin D status of children in northeast China is seldom investigated. The aim of this study was to clarify the prevalence of VDD and VDI among children in the First Affiliated Hospital of Harbin Medical University in Heilongjiang province in China. Methods We collected data from 9795 children who were outpatients aged 0–12 years who visited the First Affiliated Hospital of Harbin Medical University from September 2014 to August 2016. Serum 25-hydroxy vitamin D [25(OH)D] levels were determined by chemiluminescent immunoassay and categorized as <20, 20–30 and >30 ng/mL. Results The highest mean level of serum 25(OH)D was found at the 1–3 years stage (31.14 ng/mL) and the lowest at 6–12 years stage (18.58 ng/mL). The mean serum 25(OH)D level among school girls (17.86 ng/mL) was lower than that of boys (19.12 ng/mL). The prevalence of vitamin D sufficiency during 2014 was only 17.2%, but increased to ~45% in 2016. Conclusions The prevalence of VDD and insufficiency among children in the First Affiliated Hospital of Harbin Medical University is high, especially among children aged 6–12 years. Introduction Vitamin D is a prohormone that is essential for normal absorption of calcium from the gut, and deficiency of vitamin D is associated with rickets in growing children and osteomalacia in adults.1 The major source of vitamin D for humans is exposure to sunlight.2 Unfortified foods naturally containing vitamin D are limited. The best food sources are animal products, particularly fatty fish and liver extracts like salmon or sardines and cod liver oil.3 For infants, breast milk is the best source of vitamin D.1 Vitamin D deficiency (VDD) and vitamin D insufficiency (VDI) are highly prevalent in the world.4 VDD is defined as a 25-hydroxy vitamin D [25(OH)D] serum concentration <20 ng/mL (50 nmol/L), while VDI is diagnosed when serum 25(OH)D levels are 20–30 ng/mL (50–75 nmol/L). A level of >30 ng/mL (75 nmol/L) can be considered to indicate vitamin D sufficiency.5 According to such definitions, the prevalence of VDI was the highest among American children.6 In studies of Australia, Turkey, India and Lebanon, 30–50% of children and adults had 25-hydroxy vitamin D [25(OH)D] levels under 20 ng/mL.7–9 In southeast China (Hangzhou), more than 20% of preschoolers and over 40% of school children and adolescents had 25(OH)D levels <20 ng/mL.10 However, the vitamin D status of children in northeast China is seldom investigated. Inadequate vitamin D synthesis and nutritional intake is the main cause of VDD and VDI. VDD and VDI are associated with physical agents blocking ultraviolet radiation exposure, such as clothing, sunscreen and shade, as well as factors such as latitude and season.1 VDD and VDI are associated with many acute and chronic illnesses including disorders of calcium metabolism, autoimmune diseases, cancers, type 2 and type 1 diabetes mellitus, cardiovascular diseases and infectious diseases.11 The aim of this study was to clarify the prevalence of VDD and VDI among children in the First Affiliated Hospital of Harbin Medical University. Moreover, we discuss if strategies of vitamin D supplementation should be localized. Materials and methods Ethical statement Written informed consent was obtained in the local language from all participants. All subjects included in this study provided written informed consent, and the protocol of this study was approved by the First Affiliated Hospital of Harbin Medical University Ethics Review Committee. Data collection and methods Data from all children who were outpatient accepted routine 25(OH)D testing from September 2014 to August 2016 throughout the year were included during spring (March through May), summer (June through August), autumn (September through November) and winter (December through February). The clinical information including name, age, sex, patient registration number and blood collection date were collected from all subjects involved. According to their age, children were divided into four groups: infancy (0–1 years), toddlers (1–3 years), preschool (3–6 years) and school age (6–12 years). Serum 25(OH)D levels were measured by chemiluminescent immunoassay (DiaSorin Inc., Shanghai, Italian). DiaSorin has provided laboratories with assays that accurately measure total 25(OH)D levels, thanks to antibodies that are co-specific for 25(OH)D2 and 25(OH)D3. According to their serum 25(OH)D levels, children were also divided into three groups as deficiency (25(OH)D < 20 ng/mL), insufficiency (25(OH)D = 20–30 ng/mL) and sufficiency (25(OH)D > 30 ng/mL). Statistical analysis SPSS version 17.0 was used for all statistical analysis. Continuous variables were expressed using the mean value. Mean levels of serum 25(OH)D were computed and compared between sex group using the two-sample t-test. Mean levels of serum 25(OH)D were computed and compared between other groups using the q test. In terms of categorical values, a chi-square test was used to compare differences between the three groups. In all statistical analyses, P-values below 0.05 were considered statistically significant. Results Prevalence of VDD and VDI insufficiency by age group In this cross-sectional study of a large cohort of children of ages 0–12 years, the overall prevalence of combined VDD and VDI was 70% and that of vitamin D sufficiency only 30%. The mean serum 25(OH)D level was 24.82 ng/mL among all children in this study. The mean serum 25(OH)D level was highest (31.14 ng/mL) among toddlers and decreased among infants (29.55 ng/mL) and preschoolers (22.25 ng/mL), and was the lowest among school children (18.58 ng/mL). About 50% of infants and toddlers (51.2 and 49.6%, respectively) and over 80% of preschoolers and school children (80.2 and 89.6%, respectively) had 25(OH)D levels of <30 ng/mL. Significant differences were found between the mean serum 25(OH)D level and the prevalence of VDD and VDI among the four age groups (Table 1). Table 1 Prevalence of vitamin D deficiency and vitamin D insufficiency group by sex, age group and season Mean (ng/mL) P1 Vitamin D deficiency Vitamin D insufficiency Vitamin D sufficiency P2 n = 4169 n = 2685 n = 2941 n % n % n % Sex  Boy 25.18 2336 41.3 1561 27.6 1753 31.1  Girl 24.34 0.002 1833 44.2 1124 27.1 1188 28.7 0.009 Age group, years  0–1 29.55 293 28.1 240 23.1 508 48.8  1–3 31.14 639 20.1 937 29.5 1602 50.4  3–6 22.25 1328 49.7 817 30.6 528 19.7  6–12 18.58 <0.001 1909 65.8 691 23.8 303 10.4 <0.001 Season  Spring# 23.80 1292 49.2 592 22.5 742 28.3  Summer* 29.70 698 23.1 1065 35.4 1253 41.5  Autumn## 23.82 759 43.0 563 31.9 444 25.1  Winter** 20.53 <0.001 1420 59.5 465 19.5 502 21.0 <0.001 Mean (ng/mL) P1 Vitamin D deficiency Vitamin D insufficiency Vitamin D sufficiency P2 n = 4169 n = 2685 n = 2941 n % n % n % Sex  Boy 25.18 2336 41.3 1561 27.6 1753 31.1  Girl 24.34 0.002 1833 44.2 1124 27.1 1188 28.7 0.009 Age group, years  0–1 29.55 293 28.1 240 23.1 508 48.8  1–3 31.14 639 20.1 937 29.5 1602 50.4  3–6 22.25 1328 49.7 817 30.6 528 19.7  6–12 18.58 <0.001 1909 65.8 691 23.8 303 10.4 <0.001 Season  Spring# 23.80 1292 49.2 592 22.5 742 28.3  Summer* 29.70 698 23.1 1065 35.4 1253 41.5  Autumn## 23.82 759 43.0 563 31.9 444 25.1  Winter** 20.53 <0.001 1420 59.5 465 19.5 502 21.0 <0.001 P1, two-sample t-test (sex group) q test (other groups); P2, Chi-square test. *q Test, P < 0.05, P-value is significant for summer to the other three seasons; **q test, P < 0.05, P-value is significant for winner to the other three seasons. #q Test, P < 0.05, P-value is significant for spring to the summer and winter. ##q Test, P < 0.05, P-value is significant for autumn to the summer and winter. Table 1 Prevalence of vitamin D deficiency and vitamin D insufficiency group by sex, age group and season Mean (ng/mL) P1 Vitamin D deficiency Vitamin D insufficiency Vitamin D sufficiency P2 n = 4169 n = 2685 n = 2941 n % n % n % Sex  Boy 25.18 2336 41.3 1561 27.6 1753 31.1  Girl 24.34 0.002 1833 44.2 1124 27.1 1188 28.7 0.009 Age group, years  0–1 29.55 293 28.1 240 23.1 508 48.8  1–3 31.14 639 20.1 937 29.5 1602 50.4  3–6 22.25 1328 49.7 817 30.6 528 19.7  6–12 18.58 <0.001 1909 65.8 691 23.8 303 10.4 <0.001 Season  Spring# 23.80 1292 49.2 592 22.5 742 28.3  Summer* 29.70 698 23.1 1065 35.4 1253 41.5  Autumn## 23.82 759 43.0 563 31.9 444 25.1  Winter** 20.53 <0.001 1420 59.5 465 19.5 502 21.0 <0.001 Mean (ng/mL) P1 Vitamin D deficiency Vitamin D insufficiency Vitamin D sufficiency P2 n = 4169 n = 2685 n = 2941 n % n % n % Sex  Boy 25.18 2336 41.3 1561 27.6 1753 31.1  Girl 24.34 0.002 1833 44.2 1124 27.1 1188 28.7 0.009 Age group, years  0–1 29.55 293 28.1 240 23.1 508 48.8  1–3 31.14 639 20.1 937 29.5 1602 50.4  3–6 22.25 1328 49.7 817 30.6 528 19.7  6–12 18.58 <0.001 1909 65.8 691 23.8 303 10.4 <0.001 Season  Spring# 23.80 1292 49.2 592 22.5 742 28.3  Summer* 29.70 698 23.1 1065 35.4 1253 41.5  Autumn## 23.82 759 43.0 563 31.9 444 25.1  Winter** 20.53 <0.001 1420 59.5 465 19.5 502 21.0 <0.001 P1, two-sample t-test (sex group) q test (other groups); P2, Chi-square test. *q Test, P < 0.05, P-value is significant for summer to the other three seasons; **q test, P < 0.05, P-value is significant for winner to the other three seasons. #q Test, P < 0.05, P-value is significant for spring to the summer and winter. ##q Test, P < 0.05, P-value is significant for autumn to the summer and winter. Prevalence of vitamin D deficiency and vitamin D insufficiency by sex There were 4145 girls (42.3%) and 5650 boys (57.7%) in this study. Mean serum 25(OH)D levels in boys and girls were 25.18 and 24.34 ng/mL, respectively. VDD was more prevalent in girls (44.2%) than in boys (41.3%) (Table 1). The mean serum 25(OH)D level among school girls was lower than that of boys (P = 0.001). Among school age children, the prevalence of VDD was less among girls (63.2%) than boys (69.2%), while the prevalence of VDI was higher in boys (25.9%) than in girls (21.0%) (Fig. 1). Among the other three stages, there were no significant differences between the prevalence of VDD and VDI and the mean serum 25(OH)D level between boys and girls. Fig. 1 View largeDownload slide The percents of vitamin D sufficiency, insufficiency and deficiency in different sex among 6–12 years old children. Fig. 1 View largeDownload slide The percents of vitamin D sufficiency, insufficiency and deficiency in different sex among 6–12 years old children. Prevalence of vitamin D deficiency and vitamin D insufficiency by season The mean levels of serum 25(OH)D changed according to season. The levels of 25(OH)D gradually increased in the order of winter, spring, autumn and summer (from 29.70 to 20.53 ng/mL). The mean level of serum 25(OH)D in spring was similar to that of autumn (23.80 and 23.82 ng/mL, respectively). There were no significant differences between the mean serum 25(OH)D levels in the two groups above. The prevalence of vitamin D sufficiency during the four seasons was 28.3, 41.5, 25.1 and 21.0% (Table 1). Prevalence of vitamin D deficiency and vitamin D insufficiency by year A total of 9795 children serum collected in 2014–16 in this cross-sectional study. Mean serum 25(OH)D levels increased over the course of the collection period. The mean serum 25(OH)D level was lowest (19.73 ng/mL) during 2014 and increased during 2015 (23.62 ng/mL), then reached the highest during 2016 (29.41 ng/mL) (Fig. 2). The prevalence of vitamin D sufficiency during 2014 was only 17.2%, but increased to ~45% in 2016. Fig. 2 View largeDownload slide The means of serum 25(OH)D level in different years. Fig. 2 View largeDownload slide The means of serum 25(OH)D level in different years. Discussion Main finding of this study The present study is the first one to investigate vitamin D status among the pediatric population in Heilongjiang province in the northeast of China. Our study main found that the prevalence of VDD and VDI among children in the First Affiliated Hospital of Harbin Medical University in Heilongjiang province is high, especially among children aged 6–12 years. We suggest that nutritional education information regarding vitamin D supplements in school children should be increased. We hope China will provide us with the amount of vitamin D content in foods and fortified vitamin D foods and preparations. What is already known on this topic Vitamin D is a prohormone that is essential for normal absorption of calcium from the gut, and deficiency of vitamin D is associated with rickets in growing children and osteomalacia in adults.1 VDD and VDI are highly prevalent in the world.4 Some data demonstrated that the serum 25(OH)D levels among pediatric population decreased when the children became older, and the prevalence of VDD increased at the same time. The mean level of 25(OH) D among infants was much higher than that of any other stages.10 Girls had a higher prevalence of VDD compared with boys. The mean levels of 25(OH)D among girls were also lower than boys,4,6,12 especially at school age. Children of all ages are more susceptible to low vitamin D levels during the winter compared with the summer months.1 However, the vitamin D status of children in northeast China is seldom investigated. What this study adds Our data demonstrated that the mean level of 25(OH)D among toddlers was much higher than that of any other stages. The prevalence of vitamin D sufficiency among toddlers and infancy was ~50%. The prevalence of VDD and VDI among the preschool group was ~80%. But the prevalence of VDD and VDI reached ~90% among school children and the mean level of 25(OH)D was the lowest in all age groups. According to the recommendations from the Chinese Society of Nutrition, all individuals should receive 400 IU/d of vitamin D from birth until age 50.13 The parents of infants and toddlers provide breast milk and many kinds of oral supplementation agents containing vitamins D and A in water or oil drops can be purchased in pharmacies in Heilongjiang for children;10 however, the usage rate of supplementation agents containing vitamin D among school children is lower than preschool children.14 Some investigators considered the reasons of this condition is that as children age and begin playing outdoors more often, the relative effects of skin pigmentation may become more evident.6 Other researchers have thought that parents provided breast milk and supplementation agents containing vitamin D for their children as infants and toddlers; however, when children reach preschool and school age, parents devote less attention to supplementation of vitamin D because they thought the growth of children has slowed.15 Currently, China does not have a compulsory requirement for school children to intake vitamin D. We found the mean level of 25(OH)D among toddlers is higher than among infants in this study, which is different from other research results. This fully reflects the benefits of the vitamin D supplementation for infants and toddlers by national regimens. Furthermore, the Institute of Medicine suggests a recommended dietary allowance (RDA) for vitamin D of 600 IU/d from ages 1 to 70 years, corresponding to a serum 25(OH)D levels of at least 20 ng/mL (50 nmol/L) and meeting the requirements of at least 97.5% of the population.16 Hence, whether China should adjust the RDAs of vitamin D warrants further detailed study. In our study and in some studies in other countries, girls had a higher prevalence of VDD compared with boys. The mean levels of 25(OH)D among girls were also lower than boys,4,6,12 especially at school age. However, in China, many studies showed that there were no significant differences between mean serum 25(OH)D levels of boys and girls.17–19 It is noteworthy that some studies among adults in China revealed the mean of 25(OH)D among males was higher than females. This finding may be because women engage in less outdoor activity, use sunscreen and wear long sleeved clothing in order to skin lighter because women consider whiter skin to be a beauty aesthetic in China.20 Yan Xiaoning hypothesized that the subcutaneous fat content of females higher than males; thus, the fat soluble properties of vitamin D might result in women’s subcutaneous fat containing more vitamin D3 molecules in the skin, decreasing the effective molecules in the blood.21 We considered the two points above may be reasons for the mean levels of serum 25(OH)D among girls being lower than those of boys. We did not collect data related to body mass index (BMI), the amount of physical activity, or the habits of children, so the precise reasons cannot be determined. More research in this field in the future is warranted. When compared with children who lived in Hangzhou, Zhejiang province in southeast China, our children had a much higher prevalence of vitamin D levels at <20 ng/mL in all stages.10 Meanwhile, the mean levels of 25(OH)D of our children were lower in most stages. This is mainly because of the different duration and temperature of the seasons and different dietary habits. In terms of seasons, we found that mean levels of serum 25(OH)D among children changed according to season. Levels were very low during the winter, increased gradually during spring and autumn, and reached a peak during summer. The first reason is that Heilongjiang is located in the northeast of China at a northern latitude of 43–53°. Incident ultraviolet radiation decreases with increasing latitude.22 Above 37° north latitude, the number of ultraviolet-B (UV-B) photons reaching the earth’s atmosphere is decreased by 80–100% in the winter months and, as a consequence, little vitamin D3 is produced in the skin.23 A minimum amount of UV-B is necessary for vitamin D production and this may not be reached at a latitude of above 40° in winter even with prolonged sun exposure.24 Hence, there are 3 months in winter when vitamin D cannot be produced from UV-B in Heilongjiang province (43–53° north). The other reason is that the outdoor activity of children is limited. In winter, the temperature in Heilongjiang is very low and children have to stay indoors most of the time. Increased time spent indoors at work may lead to decreased time spent outdoors and, therefore, decreased vitamin D synthesis. Additionally, children who stay indoors may not receive a summertime boost in vitamin D levels.25 In regard to diet, foods naturally containing vitamin D are limited and there was no vitamin D content is listed in the Chinese Food Composition List.26 In eight areas of China, according to the Japanese Food Standard Components List, tremella is the most important dietary source of vitamin D in children, followed by yogurt, mushrooms, eggs, duck and fish, while the contribution of supplement preparations of vitamin D was only 0.01%.27 It indicated parents rarely provide children with vitamin D supplements, fish and other foods that contain large amounts of vitamin D. Furthermore, there are no vitamin D fortified foods in China.20 Many countries already have vitamin D fortified dairy products or juices, such as the United Kingdom and Canada28 and vitamin D fortified foods can improve vitamin D status.29 Black et al.30 showed that vitamin D fortified foods, especially milk, could effectively increase levels of vitamin D by systematic analysis. Thus, China should provide vitamin D content in foods and fortified vitamin D foods and preparations. In addition, we analyzed variations in the mean of 25(OH)D and the prevalence of VDD in different years (2014–16). We found that the mean of 25(OH)D increased over the period of data collection, while the prevalence of VDD decreased. This may indicate greater recognition by parents of the importance of supplementation with vitamin D and more active dietary management in this respect. Limitations of this study There are still some limitations in the present study. Data from subjects related to possible factors and elements of vitamin D status including intake of supplements, children’s BMI, the amount of physical activity, and levels of intact parathyroid hormone, calcium, inorganic phosphate and alkaline phosphatase were not collected. A further study based on subjects investigating the possible related factors and elements of vitamin D status is warranted. Furthermore, the optimal vitamin D level among children should to be established by more studies given that an adequate amount of vitamin D in all human populations for sustaining both innate and acquired immunity against infection is very important.31 Acknowledgements We thank the participants and staff of the Department of Laboratory Diagnosis of the First Affiliated Hospital of Harbin Medical University, without whose generosity none of this work would have been possible. We also thank Joel G. Anderson, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this article. Funding Source Natural Science Foundation of Heilongjiang Province (Grant no. H201455). Financial Disclosure The authors have no financial relationships relevant to this article to disclose. Conflicts of Interest The authors have no conflicts of interest relevant to this article to disclose. Contributors’ Statements FW drafted the initial manuscript, and reviewed and revised the article. WZ conceptualized and designed the study, and reviewed and revised the article. JW collected data, and reviewed and revised the article. HX carried out the initial analyses, and reviewed and revised the article. HZ coordinated and supervised data collection, and critically reviewed the article. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. 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Google Scholar CrossRef Search ADS PubMed 31 Fabri M , Stenger S , Shin DM et al. . Vitamin D is required for IFN-{gamma}-mediated antimicrobial activity of human macrophages . Sci Transl Med 2011 ; 3 ( 104 ): 104ra102 . Google Scholar CrossRef Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Journal of Public HealthOxford University Press

Published: Mar 26, 2018

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