Vitamin D has a range of biological effects of public health relevance (1). Besides its well-known role in mineralization of bone and teeth, vitamin D may also play important roles in metabolic functions, the pathogenesis of certain diseases, for example, type 1 diabetes mellitus, celiac disease, asthma, and allergies, as well as in the prevention of cancer (2).
Vitamin D status is assessed in plasma or serum levels by its metabolite 25-hydroxyvitamin D (25[OH] D) because it reflects the sum of vitamin D converted in the skin through sunlight exposure and from dietary sources. Several reports advocate that levels <37 nmol/L denote severe vitamin D deficiency, levels <50 nmol/L insufficient values, 50 to 75 nmol/L suboptimal levels, and ≥75 nmol/L optimal levels (3–5). In children, most suggested cutoff values for adequate levels of 25(OH) D are based on absence of rickets, increased measures of bone mineralization, and maximal suppression of serum parathyroid hormone (S-PTH) levels (6); this approach has been debated (7).
Sunlight exposure is the most important source of vitamin D3, yielding its most metabolically active form. Populations living in areas with limited hours of sunlight are at increased risk for vitamin D deficiency, and in such areas, the contribution of vitamin D from foods and supplements becomes more important. Foods in general contain relatively minor amounts of vitamin D, the major sources being oily fish, egg, and vitamin D–fortified foods. In Sweden low-fat, but not full-fat, milk and margarines are fortified with vitamin D3(8). It has been argued that the recommended daily intakes in all age groups including children should be higher with more fortification and supplementation (9–11).
Children with dark-skinned complexion need 5 to 10 times more sun exposure to generate the same amount of vitamin D3 compared with fair-skinned children, and therefore are at increased risk for vitamin D deficiency when exposure to sun is limited (12). Recently, the strong recommendations on protecting the skin from sunshine to reduce the risk of skin cancer later in life have been debated because it may increase the risk of vitamin D deficiency (13). Obesity in children may be another risk factor for vitamin D deficiency because an increased proportion of available vitamin D may be stored in adipose tissue, thus lowering 25(OH) D (14).
Despite studies indicating that the vitamin D intake among Swedish children (3.8–6.6 μg/day) (15–17) is significantly below the recommended 7.5 μg/day, little is known of their vitamin D status. The objective of the present study was to prospectively examine vitamin D status in preschool-age children living in northern Sweden, where sun exposure is limited during the winter, taking vitamin D intake, season, body mass index (BMI), and skin color into consideration.
Preschool-age children (4–6 years old) living within the northern Swedish county of Västerbotten (latitude 63° north) were recruited from well-baby clinics. We based the sample size on the assumption that 35 children in 2 groups, that is, light and dark skinned, and 2 seasons (2 × 2) would be needed to detect a mean (SD) difference of 4.1 (8.9) nmol/L between seasons with a power of 80% and α = 0.05. Assuming a dropout rate of 20%, 45 children in each group would be needed (18,19). The study was approved by the regional ethical review board at Umeå University, Sweden.
The participating children underwent 2 examinations and blood samplings at the clinical research unit at Pediatrics, Department of Clinical Sciences, Umeå University. The baseline measurements took place during August–September 2010, that is, right after the sunnier part of the year in northern Sweden. The follow-up measurements took place in the winter period, the following January–February. Parents not fluent in Swedish were assisted by an interpreter at study visits.
At the first visit, each child's skin color was classified by a research nurse together with the parents as “fair skinned” or “dark skinned" according to Fitzpatrick, who classifies the response of different types of skin to ultraviolet light (20). Skin type numbers I to IV were categorized as “fair” and numbers V to VI as “dark” in the analysis.
To estimate vitamin D intake and possible sunlight exposure, a vitamin D questionnaire was developed. A short food frequency questionnaire was chosen to capture also less commonly consumed foods with respect to vitamin D intake (21). The questionnaire included 14 food items known to be important sources of vitamin D among children in Sweden (16). The Swedish Food Database (version 2011–06–21) (22) was used for estimations of vitamin D intake from the foods. Questions of supplements containing vitamin D, for example, D-drops and multivitamin supplements containing vitamin D, were also included. To assess sunlight exposure, questions on how many hours the child spends outdoors on week days and weekends during each season, and whether the child was usually protected through use of sunscreen and/or clothes during sunny days were included, as well as whether the child had been on any recent trip to sunnier areas, usually abroad. Before start of the study the questionnaire was tested in a pilot study.
An anesthetic cream (EMLA, AstraZeneca, Sweden) was used before blood sampling. Venous blood samples were taken immediately, centrifuged, and serum collected. S-PTH was analyzed on the same day at the Department of Clinical Chemistry, Umeå University Hospital. Serum was stored at −80°C until S-25(OH) D2 and D3 were analyzed by HPLC-APCI-MS (Vitas, Oslo, Norway) (23). All S-25(OH) D-samples were analyzed in 1 batch (23). S-25(OH) D values <50 nmol/L are defined as insufficient, 50 to 75 nmol/L as suboptimal, and ≥75 nmol/L as optimal levels.
Height to the nearest millimeter was measured using a CMS stadiometer (CMS Weighing Equipment, London UK) and weight to the nearest 0.1 kg using a Seca 835 digital adult scale (Seca, Hamburg, Germany). Waist circumference was measured to nearest millimeter with a measuring tape.
Calculations and Statistical Analyses
Statistical analyses were performed using PASW 18.0 (SPSS, Chicago, IL). BMI and BMI z scores were calculated and age and sex cutoff levels for overweight and obesity in children were set separately for girls and boys using the definition by the World Health Organization (24,25). S-PTH levels and total vitamin D intake were not normally distributed and were log10 transformed in the calculations. Pearson correlation coefficients were used to analyze the association between S-25(OH) D and log S-PTH. Time spent outdoors was calculated as the mean number of hours per day ([week−days × 5 + weekends × 2]/7), for each season.
Data are presented as means (SD) or proportions (%) as appropriate. For continuous outcomes, differences between independent groups, that is, sex or group with different skin color, were analyzed with t test, whereas changes from baseline to the follow-up examination within the same individuals were analyzed with paired-sample t test. For categorical data, the Fisher exact test was used. Multivariate linear regression, adjusted for sex, was used to analyze the associations among S-25(OH) D, and skin type, BMI, total vitamin D intake, seasons, sun protection, and time spent outdoors.
Of the 90 children (47 boys and 43 girls), 48 were allocated to the fair-skinned and 42 to the dark-skinned groups, respectively. At the baseline examination, 2 children in the dark-skinned group did not have blood samples drawn, and at the follow-up, 4 children from the fair-skinned group had dropped out, leaving 88 children with at least 1 blood sample and 84 children with 2 blood samples. All but 1 child was reported to be in day care.
Anthropometric and Dietary Data
At both the baseline and follow-up examination, 22% of the children were overweight or obese (Table 1). The major source of vitamin D was milk products, contributing to 31% of the dietary vitamin D intake with no difference between girls and boys, or between fair- and dark-skinned groups. In total, 96.7% of the children reported some consumption of fortified milk and 64% never consumed full-fat milk, which is not fortified with vitamin D.
At baseline, 7 children consumed vitamin D supplements at least occasionally, all belonging to the dark-skinned group. At follow-up, 10 dark- and 2 fair-skinned children consumed vitamin D supplements. Adding the dietary intake (6.6 and 7.0 μg in summer and winter, respectively) and consumption of supplements, the total mean (SD) daily intakes of vitamin D after summer and during winter were 7.8 μg/day (4.2) and 8.2 μg/day (5.0), respectively. The total vitamin D intake was significantly higher in dark-skinned children (9.0 μg/day [5.2] and 9.5 μg/day [6.1]) compared with fair-skinned children (6.8 μg/day [2.7] and 6.9 μg/day [3.2]) in the summer (P = 0.011) and winter (P = 0.015), respectively.
Biochemical Measurements and Sunlight Exposure
Mean S-25(OH) D was higher after summer than during winter (P < 0.001) (Table 1). After the summer and during the winter, 15% and 10% had S-25(OH) D ≥75 nmol/L, 25% and 40% had S-25(OH) D <50 nmol/L, and 9% and 16% had S-25(OH) D <37 nmol/L, respectively. Both at baseline and follow-up, dark-skinned children had significantly lower S-25(OH) D compared with fair-skinned children (P ≤ 0.001) (Table 2). In children with 2 examinations (n = 84), the mean (SD) seasonal S-25(OH) D difference was 4.9 (10.4) nmol/L (P ≤ 0.001). There was no difference in S-25(OH) D between boys and girls. The S-25(OH) D levels were inversely associated with S-PTH (r = −0.267, P ≤ 0.001) with elevated levels (≥6.9 mmol/L) in 4 children (5%).
Mean number of hours per day spent outdoors were 4 during the sunnier part of the year and 2 in the winter with no differences between boys and girls or between fair-skinned and dark-skinned children.
Associations Among S-25(OH) D, Vitamin D Intake, Season, Anthropometrics, and Skin Type
Associations among S-25(OH) D and skin type, BMI z score, waist circumference, total vitamin D intake, use of sunscreen, and time spent outdoors were assessed, first in univariate regression analysis, and then all variables with P < 0.3 were entered into a multivariate model. In the final multivariate linear regression analysis, skin type, BMI z score, sunscreen, vitamin D intake, and season were included in a model, adjusted for sex. Mean S-25(OH) D was negatively associated with darker skin type and winter season and positively associated with total vitamin D intake and with BMI z score (Table 3, Fig. 1).
In the present study, we prospectively investigated vitamin D status in preschool-age children living at latitude 63° north. After the summer season and during the winter season, 25% and 40% of the studied children had insufficient vitamin D status defined as S-25(OH) D <50 nmol/L. These numbers are higher than reported from studies in Finland, northern Europe, and Canada (4,10,26). We report an even higher proportion of insufficient S-25(OH) D among children with darker complexions, and considerably higher than expected given the present national recommendations on vitamin D supplements stating that children with darker skin should continue until 5 years of age and the widespread use of vitamin D–fortified foods (27). It is noteworthy that only 15% of the children had optimal vitamin D status, that is, S-25(OH) D >75 nmol/L, after the summer when we expected them to have had the greatest sun exposure and thus the best vitamin D status.
It is not known what intake of vitamin D children living in northern latitudes with restricted sun exposure need to reach optimal S-25(OH) D status. Despite the fact that the mean intake of vitamin D was in line with present national recommendations of 7.5 μg/day (28), a large proportion of the children's S-25(OH) D was insufficient and only a few children reached optimal S-25(OH) D. Furthermore, the total intake of vitamin D was higher in the dark-skinned group, and there were no differences in time spent outdoors between groups. Notwithstanding this, vitamin D status was less satisfactory among dark-skinned compared with fair-skinned children during both seasons.
The mean seasonal difference of 4.9 nmol/L in S-25(OH) D between late summer and winter among the children living in northern Sweden was similar to that reported from a Canadian group (6 nmol/L) of children ages 6 to 11 years (10) but smaller than reported from New Zealand (15 nmol/L) (29). A possible explanation for the lower seasonal differences in our groups may be the relatively higher vitamin D intake, particularly in dark-skinned children.
In Sweden, the prevalence of type 1 diabetes mellitus (30), celiac disease (31), asthma, and allergies (32) in children, and osteoporosis in adults (33) is high. All these conditions, as well as cardiometabolic risk factors, regardless of obesity (9), have been reported to be inversely associated with vitamin D status (34). Poor vitamin D status may have detrimental consequences for the future health of these children, and optimal vitamin D status is a crucial public health goal to achieve. In the present study, we found a positive correlation between BMI and S-25(OH) D, whereas others have reported an inverse relation in infants, children, and adults (5,34–37). It is not clear whether the associations between BMI and S-25(OH) D are dependent on difference in dietary quality, extent of outdoor activities, or fat tissue metabolism (14).
S-PTH is a secondary outcome measure in the assessment of vitamin D status. Insufficient 25(OH) D may result in calcium malabsorption, and the accompanying secondary hyperparathyroidism may negatively affect bone mineralization (18). The inverse association between S-25(OH) D and S-PTH in the present study suggests that the insufficient S-25(OH) D in some of the children may have been sufficient to negatively affect bone health (6,38,39). Associations among 25(OH) D, PTH, and bone mineral density (BMD) have rarely been studied in young children and the 5% of children with elevated PTH (>6.9 mmol/L) were not further investigated in the present study with BMD; however, in a recent study, adolescent girls, but not boys, with high vitamin D status (≥74.1 nmol/L) had significantly greater forearm BMD and lower S-PTH levels compared with adolescent girls with low 25(OH) D (≤46.3 nmol/L) as well as moderate (46.4–74.0 nmol/L) 25(OH) D (40).
Contrary to other studies, we found no association between vitamin D status and outdoor activities (10,41). One possible explanation may be that nearly all of the children in the present study were in day care and reported similar hours of time spent outdoors (42), limiting the variability. A second explanation is that sun exposure at latitude 63° simply is insufficient to contribute enough to the vitamin D status in preschool children. More studies on different intakes of vitamin D, sun exposure, associations between health factors, and concentrations of S-25 (OH) D are warranted.
In conclusion, the present study shows that vitamin D status is inadequate in children living in northern Sweden, although the dietary intake in the group studied was in accordance with the Nordic Nutrition Recommendations (28). The suboptimal mean levels of S-25(OH) D after the summer diminished further during the winter. Darker skin type and winter seasons negatively affected vitamin D status, whereas vitamin D intake and higher BMI were positively associated with the children's levels of S-25 (OH) D. These findings call for revised recommendations and strategies to improve the intake of vitamin D in children living in northern areas with limited sun exposure.
The authors are most grateful to the participating children and their parents; to research nurses Birgitta Isaksson, Åsa Sundstöm, Margareta Bäckman, and Camilla Steinvall; and to dietician Ann-Kristine Sandström. We received invaluable help with the blood samples from the biomedical technicians Carina Lagerqvist and Yvonne Andersson at the pediatric research laboratory.
1. Prentice A, Goldberg GR, Schoenmakers I. Vitamin D
across the lifecycle: physiology and biomarkers. Am J Clin Nutr
2. Holick MF. The vitamin D
deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med
3. Dawson-Hughes B, Heaney RP, Holick MF, et al. Estimates of optimal vitamin D
status. Osteoporos Int
4. Huh SY, Gordon CM. Vitamin D
deficiency in children and adolescents: epidemiology, impact and treatment. Rev Endocr Metab Disord
5. Yetley EA. Assessing the vitamin D
status of the US population. Am J Clin Nutr
6. Greer FR. Defining vitamin D
deficiency in children: beyond 25-OH vitamin D
serum concentrations. Pediatrics
7. Pettifor JM, Prentice A. The role of vitamin D
in paediatric bone health. Best Pract Res Clin Endocrinol Metab
9. Ganji V, Zhang X, Shaikh N, et al. Serum 25-hydroxyvitamin D
concentrations are associated with prevalence of metabolic syndrome and various cardiometabolic risk factors in US children and adolescents based on assay-adjusted serum 25-hydroxyvitamin D
data from NHANES 2001–2006. Am J Clin Nutr
10. Whiting SJ, Langlois KA, Vatanparast H, et al. The vitamin D
status of Canadians relative to the 2011 Dietary Reference Intakes: an examination in children and adults with and without supplement use. Am J Clin Nutr
11. Calvo MS, Whiting SJ. Public health strategies to overcome barriers to optimal vitamin D
status in populations with special needs. J Nutr
12. Holick MF. The vitamin D
epidemic and its health consequences. J Nutr
13. Stechschulte SA, Kirsner RS, Federman DG. Sunscreens for non-dermatologists: what you should know when counseling patients. Postgrad Med
14. Prentice A. Vitamin D
deficiency: a global perspective. Nutr Rev
15. Garemo M, Lenner RA, Strandvik B. Swedish pre-school children eat too much junk food and sucrose. Acta Paediatr
16. Enghardt B, Pearson M, Becker W. Dietary Habits and Nutrient Intake in Swedish Children 4 Years Old and School Children in Grade 2 and 5 (Riksmaten-barn 2003). Uppsala, Sweden:National Food Administration; 2006.
17. Öhlund K, Olsson C, Hernell O, et al. Dietary shortcomings in children on a gluten-free diet. J Hum Nutr Diet
18. Gordon CM, Feldman HA, Sinclair L, et al. Prevalence of vitamin D
deficiency among healthy infants and toddlers. Arch Pediatr Adolesc Med
19. Thieden E, Philipsen PA, Heydenreich J, et al. Vitamin D
level in summer and winter related to measured UVR exposure and behavior. Photochem Photobiol
20. Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol
21. Millen AE, Bodnar LM. Vitamin D
assessment in population-based studies: a review of the issues. Am J Clin Nutr
23. Snellman G, Melhus H, Gedeborg R, et al. Determining vitamin D
status: a comparison between commercially available assays. PLoS One
24. Cole TJ, Bellizzi MC, Flegal KM, et al. Establishing a standard definition for child
overweight and obesity worldwide: international survey. BMJ
26. Piirainen T, Laitinen K, Isolauri E. Impact of national fortification of fluid milks and margarines with vitamin D
on dietary intake and serum 25-hydroxyvitamin D
concentration in 4-year-old children. Eur J Clin Nutr
27. Axelsson I, Gebre-Medhin M, Hernell O, et al. [The AD-drops can be replaced by D-drops]. Lakartidningen
28. Nordic Nutrition Recommendations 2004
. 4th ed. Copenhagen: Nordic Council of Ministers; 2004.
29. Rockell JE, Green TJ, Skeaff CM, et al. Season
and ethnicity are determinants of serum 25-hydroxyvitamin D
concentrations in New Zealand children aged 5–14 y. J Nutr
30. Berhan Y, Waernbaum I, Lind T, et al. Thirty years of prospective nationwide incidence of childhood type 1 diabetes: the accelerating increase by time tends to level off in Sweden. Diabetes
31. Myleus A, Ivarsson A, Webb C, et al. Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic. J Pediatr Gastroenterol Nutr
32. Rönmark E, Bjerg A, Perzanowski M, et al. Major increase in allergic sensitization in schoolchildren from 1996 to 2006 in northern Sweden. J Allergy Clin Immunol
33. Landfeldt E, Lundkvist J, Strom O. The societal burden of poor persistence to treatment of osteoporosis in Sweden. Bone
34. Mark SG-D, Delvin K, O’Loughlin EE, et al. Low vitamin D
status in a representative sample of youth from Quebec, Canada. Clin Chem
35. Ostergard M, Arnberg K, Michaelsen KF, et al. Vitamin D
status in infants: relation to nutrition and season
. Eur J Clin Nutr
36. Eriksson S, Strandvik B. [Vitamin D
status in healthy children in Sweden still satisfactory. Changed supplementation and new knowledge motivation for further studies]. Läkartidningen
37. Arnberg K, Ostergard M, Madsen AL, et al. Associations between vitamin D
status in infants and blood lipids, body mass index and waist circumference. Acta Paediatr
38. Houghton LA, Szymlek-Gay EA, Gray AR, et al. Predictors of vitamin D
status and its association with parathyroid hormone in young New Zealand children. Am J Clin Nutr
39. Hill TR, Cotter AA, Mitchell S, et al. Vitamin D
status and parathyroid hormone relationship in adolescents and its association with bone health parameters: analysis of the Northern Ireland Young Heart's Project. Osteoporos Int
40. Cashman KD, FitzGerald AP, Viljakainen HT, et al. Estimation of the dietary requirement for vitamin D
in healthy adolescent white girls. Am J Clin Nutr
41. Farrar MD, Kift R, Felton SJ, et al. Recommended summer sunlight exposure amounts fail to produce sufficient vitamin D
status in UK adults of South Asian origin. Am J Clin Nutr
42. Boldemann C, Blennow M, Dal H, et al. Impact of preschool environment upon children's physical activity and sun exposure. Prev Med
Keywords:© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
child; latitude; season; serum 25-hydroxyvitamin D; vitamin D