**4. Discussion**

There is a high prevalence of hypovitaminosis D in the pediatric population in our environment, which potentially represents a serious public health problem. The criteria from the US Endocrine Society have been used for the comparison of the results with the previous published data. According to these criteria, calcidiol has a long half-life (2 to 3 weeks) and is the best indicator of body vitamin D content; they consider normal serum levels when they reach 30 ng/mL or higher and hypovitaminosis D below this level. In this way, hypovitaminosis is classified into insufficiency (between 21 and 29 ng/mL) and deficiency (lower than 20 ng/mL) [4, 21, 22].

The blood sample analysis shows the following prevalence: vitamin D sufficiency in 39.6% of the individuals, insufficiency 44.6% and deficiency 15.8%, respectively. These results might seem to show a high prevalence of hypovitaminosis for a healthy population, but are indeed relatively moderate in comparison to other studies published in different areas or latitudes of our planet (**Table 5**); this may

**23**

highlighted [17, 19].

**Table 5.**

*Vitamin D Deficiency in Children*

*DOI: http://dx.doi.org/10.5772/intechopen.89208*

*Prevalence of hypovitaminosis D according to different authors.*

be due to the fact that in this study their participants were exclusively of Caucasian origin, since, as is well known, the difference in skin pigmentation in different ethnic groups implies a higher risk of hypovitaminosis D [14, 17, 18, 28, 32, 34–37]. Calcidiol measurements—even though they were not significant—were higher in males, whereas PTH levels were significantly higher in females, but there were no significant differences in the prevalence of hypovitaminosis D among sexes. Previously published data are inconsistent [9, 34, 38, 39]. Nevertheless, the logistic regression analysis revealed that hypovitaminosis D, and more specifically the level of insufficiency, was significantly associated with females. Adolescents (pubertal group) had significantly lower calcidiol levels than school children, but the mean values for PTH and the prevalence of hypovitaminosis D were significantly higher in that group, and these results match those provided by other authors [17, 40]. Furthermore, the logistic regression analysis showed that hypovitaminosis D, as insufficiency and deficiency, was significantly associated to the older group. These findings could be somehow disturbing, since adolescence is a key period for growing, development, and bone formation, when vitamin D requirements are increased and deficiency may affect normal bone mass acquisition. Individuals living in urban areas had calcidiol values significantly lower than those living in rural areas, whereas PTH values and prevalence of vitamin D deficiency were significantly higher in those individuals from urban areas. These findings might be related to the different lifestyles inherent to the different environment, since residents in rural areas are likely to experience longer periods of sun exposure, as several authors have

**Authors Deficiency Insufficiency Sufficiency** Cheng et al., 2003 (Jyväskylä, Finland) [23] 32% 46% 22% Weng et al., 2007 (Philadelphia, USA) [14] 26% 29% 45% Gordon et al., 2008 (Boston, USA) [24] 12% 40% 48% Kelly et al., 2011 (Filadelfia, USA) [25] 47% 27% 26% Andiran et al., 2012 (Ankara, Turkey) [26] 40% — — Tolppanen et al., 2012 (England, UK) [27] 29% 46% 25% González-Cross et al., 2012 (Europe) [28] 19% 39% 42% Vierucci et al., 2013 (Toscana, Italy) [17] 46% 34% 20% Karagüzel et al., 2014 (Trabzon, Turkey) [29] 71% 23% 6% Durá-Travé et al., 2015 (Navarra, Spain) [30] 13% 45% 42% Kaddam et al., 2017 (Saudi Arabia) [31] 49% 46% 5% Fernández-Bustillo et al., 2018 (Galicia, Spain) [32] 5.9% 60.1% 34% Guo et al., 2018 (China) [33] 10.8% 39% 50.2%

The characteristics of sun exposure depend considerably on the location. In this way, it has been found how the axial tilt (obliquity) of our planet in the northern hemisphere (beyond 37th parallel—north), mainly in the colder months of the year, causes a change in the density of incident rays and, therefore, the ultraviolet radiation (type B) decreases up to 80–100%. That is the reason why sun radiation is not able to lead to efficient vitamin D synthesis [14, 17, 29, 41]. Hence the main reasons of vitamin D deficiency are usually in direct relation either to any physical agents that obstruct sun radiation (cutaneous pigmentation, sunscreens, etc.) or to


#### **Table 5.**

*Vitamin D Deficiency*

Sex

Age group

Season

Residence

Nutritional status

**Items Deficiency OR (IC 95%)**

Females 1.1 (0.9–1.8)

Adolescent 2.0 (1.2–3.4)

Autumn 3.8 (1.3–11.5)

Winter 5.8 (1.9–17.4)

Spring 3.1 (0.9–9.9)

Urban 2.4 (1.4–4.0)

Overweight 1.3 (0.7–1.8)

Obesity 1.3 (0.7–2.8)

Severe obesity 4.4 (2.2–8.6)

**p**

Males 1 (reference) 1 (reference)

0.676

School 1 (reference) 1 (reference)

0.005

Summer 1 (reference) 1 (reference)

0.018

0.002

0.058

Rural 1 (reference) 1 (reference)

0.020

Normal 1 (reference) 1 (reference)

0.442

0.443

<0.001

*Multiple logistic regression analysis for the presumed risk factor for hypovitaminosis (deficiency and* 

**Insufficiency OR (CI 95%) p**

> 1.6 (1.1–2.3) 0.011

> 1.8 (1.2–2.6) 0.003

9.5 (4.8–18.7) <0.001

8.8 (4.5–17.5) <0.001

13.2 (6.4–27.5) <0.001

1.6 (1.1–2.2) 0.01

0.8 (0.5–1.4) 0.476

1.2 (0.7–2.2) 0.498

4.4 (1.9–10.3) <0.001

**22**

**4. Discussion**

**Table 4.**

*insufficiency).*

There is a high prevalence of hypovitaminosis D in the pediatric population in our environment, which potentially represents a serious public health problem. The criteria from the US Endocrine Society have been used for the comparison of the results with the previous published data. According to these criteria, calcidiol has a long half-life (2 to 3 weeks) and is the best indicator of body vitamin D content; they consider normal serum levels when they reach 30 ng/mL or higher and hypovitaminosis D below this level. In this way, hypovitaminosis is classified into insufficiency (between 21 and 29 ng/mL) and deficiency (lower than 20 ng/mL) [4, 21, 22]. The blood sample analysis shows the following prevalence: vitamin D sufficiency in 39.6% of the individuals, insufficiency 44.6% and deficiency 15.8%, respectively. These results might seem to show a high prevalence of hypovitaminosis for a healthy population, but are indeed relatively moderate in comparison to other studies published in different areas or latitudes of our planet (**Table 5**); this may

*Prevalence of hypovitaminosis D according to different authors.*

be due to the fact that in this study their participants were exclusively of Caucasian origin, since, as is well known, the difference in skin pigmentation in different ethnic groups implies a higher risk of hypovitaminosis D [14, 17, 18, 28, 32, 34–37].

Calcidiol measurements—even though they were not significant—were higher in males, whereas PTH levels were significantly higher in females, but there were no significant differences in the prevalence of hypovitaminosis D among sexes. Previously published data are inconsistent [9, 34, 38, 39]. Nevertheless, the logistic regression analysis revealed that hypovitaminosis D, and more specifically the level of insufficiency, was significantly associated with females. Adolescents (pubertal group) had significantly lower calcidiol levels than school children, but the mean values for PTH and the prevalence of hypovitaminosis D were significantly higher in that group, and these results match those provided by other authors [17, 40]. Furthermore, the logistic regression analysis showed that hypovitaminosis D, as insufficiency and deficiency, was significantly associated to the older group. These findings could be somehow disturbing, since adolescence is a key period for growing, development, and bone formation, when vitamin D requirements are increased and deficiency may affect normal bone mass acquisition. Individuals living in urban areas had calcidiol values significantly lower than those living in rural areas, whereas PTH values and prevalence of vitamin D deficiency were significantly higher in those individuals from urban areas. These findings might be related to the different lifestyles inherent to the different environment, since residents in rural areas are likely to experience longer periods of sun exposure, as several authors have highlighted [17, 19].

The characteristics of sun exposure depend considerably on the location. In this way, it has been found how the axial tilt (obliquity) of our planet in the northern hemisphere (beyond 37th parallel—north), mainly in the colder months of the year, causes a change in the density of incident rays and, therefore, the ultraviolet radiation (type B) decreases up to 80–100%. That is the reason why sun radiation is not able to lead to efficient vitamin D synthesis [14, 17, 29, 41]. Hence the main reasons of vitamin D deficiency are usually in direct relation either to any physical agents that obstruct sun radiation (cutaneous pigmentation, sunscreens, etc.) or to

geographical features, such as sunlight exposure, atmospheric pollution, altitude, latitude, and the season of the year [1, 3].

The negative correlation between calcidiol and parathyroid hormone plasma levels has been previously described by different authors [14, 17, 33, 42]; nonetheless, the discussion about the combined oscillations existing among both hormones along a natural year has not been that intense [43, 44]. The analysis of our data has shown simultaneous and asynchronous changes in parathyroid hormone levels with respect to calcidiol, simultaneously with monthly and/or seasonal modifications in calcidiol levels. These adjustments presumably would take place in order to maintain constant calcium levels along the year, as we have noticed in this study. In point of fact, the highest body vitamin D levels are detected in the summer months—there is a more intense sunlight exposure. The levels decrease gradually in the autumn and winter months—except for some biological variability—and they reach the lowest point in springtime. By comparison to the findings of other authors [3, 17, 29], only 18.2% of the 602 individuals classified in the status of vitamin D insufficiency of deficiency presented with PTH levels within the range of hyperparathyroidism; since no diagnosis of hypercalcemia or hypocalcaemia or any bone semiology was previously described, a potential conclusion is that seasonal changes in calcidiol and parathyroid hormone levels would be related to a physiological phenomenon of adaptation to the geographical and climatic conditions endemic to this region. Navarre is a Spanish region located on a high latitude (between 41°55″22 N and 43°16″42 N) with frequent cloudy and rainy days, and this characteristic is important enough to take into consideration that cyclical variation in calcidiol levels in relation to the season of the year could be explained by a possible inefficient vitamin synthesis induced by sun radiation, as several authors have noted [14, 17, 24, 29, 42, 45–47]. Admittedly, the results confirm that vitamin D levels in the summer months were sufficient in 80% of the individuals. They moderately decrease in the months of autumn and winter (the percentage of individual in a situation of hypovitaminosis D gets to 66.6 and 62.7% in autumn and winter, respectively) and fall to the lowest point in spring months, when the prevalence of hypovitaminosis gets to 72.7%.

Because geographical and climatic conditions significantly influence body vitamin D content and, secondarily, PTH plasma levels, a comparison of the different results obtained in the published works from different countries and/or climatic conditions would be unwise and faulty, since the place of residence, latitude, and especially the month of the year when the blood sample is collected always have to be considered. In other words, it is not possible to establish a vitamin D status in a concrete population without considering the seasonal variations because, as this work has shown, a potential condition of hypovitaminosis D is related to the season of the year in which the determination has been made [48, 49].

As BMI (Z-score) increases, calcidiol values decrease and PTH significantly rises, in a way that individuals with severe obesity showed minimum values of calcidiol and maximum values of PTH with respect to the individuals of the remaining nutritional situations. This means, there seems to be a noticeable tendency to present with vitamin D deficiency in the individuals with severe obesity [9, 20, 40, 50]; this eventuality has been outlined as a cardiovascular and/or metabolic risk factor [4, 8–10, 15, 19]. Even though there is not a conclusive explanation in this respect, it has been suggested that this circumstance in obese individuals may be related to environmental factors (decreased sun exposure as a consequence of a sedentary lifestyle, inadequate diet, etc.), although, at present, some authors postulate a hypothetical "sequestration" or excessive accretion of vitamin D in the adipose tissue [2, 4, 7, 8, 16, 18, 21, 42]. Previous reports did not distinguish between obesity and severe obesity, as we did in this work, and this special feature could be of practical relevance, since the logistic regression analysis has verified that hypovitaminosis

**25**

**5. Conclusion**

*Vitamin D Deficiency in Children*

*DOI: http://dx.doi.org/10.5772/intechopen.89208*

nutritional situation of severe obesity.

D, in levels of insufficiency as well as deficiency, is significantly associated to the

The development of this study unveiled several limitations. The main weaknesses are the cross-sectional nature of the study and the absence of data on exercise, sun exposure, and the use of sunscreens. There have been some difficulties to get adequate and accurate data, and it restrained us from completing the registration. A nutritional survey (including dietary vitamin D intake, daily supplementation, etc.) was not incorporated in the study. Our experience reflects that dairy product intake in our social context is below the recommended amount and particularly fish intake is quite low in the pediatric population [51]; in this way, only the dietary supplementation of vitamin D could condition the results achieved,

Given the difficulties in maintaining a sufficient body vitamin D content in the pediatric age group throughout the year, the prevention, detection, and, when required, treatment and follow-up of hypovitaminosis should be fully integrated in the programs of health promotion and disease prevention in child and adolescent population corresponding to primary health care. In other words, primary care teams and, more specifically, pediatricians should include a series of preventive measures in addition to the mandatory vitamin D daily supplementation during the first year of life, 400 UI per day [4, 52, 53], such as promoting adequate sun exposure, in the service portfolio. Around 10–15 minutes of midday sun exposure (between 10 in the morning and 3 in the afternoon) on at least 20% of total body surface (uncovered head and extremities) during spring, summer, and autumn is considered enough to get an adequate vitamin D synthesis [2]. In addition, in case any of the hypovitaminosis D-associated factors is present, especially in those individuals at risk of limited sun exposure (disabled and/or undergoing long stay in the hospital, etc.), the need for additional vitamin D supplementation should be considered, either as pharmacological supplements (600 IU per day), an increase of the ingestion of higher amounts from its natural dietary sources (herring, salmon, sardines, tuna, etc.), or vitamin D fortified foods (dairy products, cereals, etc.) during the months of winter and spring,

but, at present, it is not a widespread practice in our society.

as several authors have suggested [6, 12, 14, 15, 18, 21, 28, 34, 54].

There is a high prevalence of hypovitaminosis D in the pediatric population in our environment, being female sex, pubertal age, the seasons of autumn, winter and spring, living in urban area, and severe obesity considered as associated factors in hypovitaminosis D. Consideration should be given to the administration of vitamin supplements and/or the increase in the ingestion of natural vitamin D dietary sources.

#### *Vitamin D Deficiency in Children DOI: http://dx.doi.org/10.5772/intechopen.89208*

*Vitamin D Deficiency*

latitude, and the season of the year [1, 3].

geographical features, such as sunlight exposure, atmospheric pollution, altitude,

The negative correlation between calcidiol and parathyroid hormone plasma levels has been previously described by different authors [14, 17, 33, 42]; nonetheless, the discussion about the combined oscillations existing among both hormones along a natural year has not been that intense [43, 44]. The analysis of our data has shown simultaneous and asynchronous changes in parathyroid hormone levels with respect to calcidiol, simultaneously with monthly and/or seasonal modifications in calcidiol levels. These adjustments presumably would take place in order to maintain constant calcium levels along the year, as we have noticed in this study. In point of fact, the highest body vitamin D levels are detected in the summer months—there is a more intense sunlight exposure. The levels decrease gradually in the autumn and winter months—except for some biological variability—and they reach the lowest point in springtime. By comparison to the findings of other authors [3, 17, 29], only 18.2% of the 602 individuals classified in the status of vitamin D insufficiency of deficiency presented with PTH levels within the range of hyperparathyroidism; since no diagnosis of hypercalcemia or hypocalcaemia or any bone semiology was previously described, a potential conclusion is that seasonal changes in calcidiol and parathyroid hormone levels would be related to a physiological phenomenon of adaptation to the geographical and climatic conditions endemic to this region. Navarre is a Spanish region located on a high latitude (between 41°55″22 N and 43°16″42 N) with frequent cloudy and rainy days, and this characteristic is important enough to take into consideration that cyclical variation in calcidiol levels in relation to the season of the year could be explained by a possible inefficient vitamin synthesis induced by sun radiation, as several authors have noted [14, 17, 24, 29, 42, 45–47]. Admittedly, the results confirm that vitamin D levels in the summer months were sufficient in 80% of the individuals. They moderately decrease in the months of autumn and winter (the percentage of individual in a situation of hypovitaminosis D gets to 66.6 and 62.7% in autumn and winter, respectively) and fall to the lowest point in spring

months, when the prevalence of hypovitaminosis gets to 72.7%.

of the year in which the determination has been made [48, 49].

Because geographical and climatic conditions significantly influence body vitamin D content and, secondarily, PTH plasma levels, a comparison of the different results obtained in the published works from different countries and/or climatic conditions would be unwise and faulty, since the place of residence, latitude, and especially the month of the year when the blood sample is collected always have to be considered. In other words, it is not possible to establish a vitamin D status in a concrete population without considering the seasonal variations because, as this work has shown, a potential condition of hypovitaminosis D is related to the season

As BMI (Z-score) increases, calcidiol values decrease and PTH significantly rises, in a way that individuals with severe obesity showed minimum values of calcidiol and maximum values of PTH with respect to the individuals of the remaining nutritional situations. This means, there seems to be a noticeable tendency to present with vitamin D deficiency in the individuals with severe obesity [9, 20, 40, 50]; this eventuality has been outlined as a cardiovascular and/or metabolic risk factor [4, 8–10, 15, 19]. Even though there is not a conclusive explanation in this respect, it has been suggested that this circumstance in obese individuals may be related to environmental factors (decreased sun exposure as a consequence of a sedentary lifestyle, inadequate diet, etc.), although, at present, some authors postulate a hypothetical "sequestration" or excessive accretion of vitamin D in the adipose tissue [2, 4, 7, 8, 16, 18, 21, 42]. Previous reports did not distinguish between obesity and severe obesity, as we did in this work, and this special feature could be of practical relevance, since the logistic regression analysis has verified that hypovitaminosis

**24**

D, in levels of insufficiency as well as deficiency, is significantly associated to the nutritional situation of severe obesity.

The development of this study unveiled several limitations. The main weaknesses are the cross-sectional nature of the study and the absence of data on exercise, sun exposure, and the use of sunscreens. There have been some difficulties to get adequate and accurate data, and it restrained us from completing the registration. A nutritional survey (including dietary vitamin D intake, daily supplementation, etc.) was not incorporated in the study. Our experience reflects that dairy product intake in our social context is below the recommended amount and particularly fish intake is quite low in the pediatric population [51]; in this way, only the dietary supplementation of vitamin D could condition the results achieved, but, at present, it is not a widespread practice in our society.

Given the difficulties in maintaining a sufficient body vitamin D content in the pediatric age group throughout the year, the prevention, detection, and, when required, treatment and follow-up of hypovitaminosis should be fully integrated in the programs of health promotion and disease prevention in child and adolescent population corresponding to primary health care. In other words, primary care teams and, more specifically, pediatricians should include a series of preventive measures in addition to the mandatory vitamin D daily supplementation during the first year of life, 400 UI per day [4, 52, 53], such as promoting adequate sun exposure, in the service portfolio. Around 10–15 minutes of midday sun exposure (between 10 in the morning and 3 in the afternoon) on at least 20% of total body surface (uncovered head and extremities) during spring, summer, and autumn is considered enough to get an adequate vitamin D synthesis [2]. In addition, in case any of the hypovitaminosis D-associated factors is present, especially in those individuals at risk of limited sun exposure (disabled and/or undergoing long stay in the hospital, etc.), the need for additional vitamin D supplementation should be considered, either as pharmacological supplements (600 IU per day), an increase of the ingestion of higher amounts from its natural dietary sources (herring, salmon, sardines, tuna, etc.), or vitamin D fortified foods (dairy products, cereals, etc.) during the months of winter and spring, as several authors have suggested [6, 12, 14, 15, 18, 21, 28, 34, 54].
