Vitamin D plays a crucial role in calcium and phosphorus metabolism and the mineralization of bone. In addition to this widely known function, research conducted in recent years has demonstrated its influence on various genes involved in cellular proliferation and differentiation and on the immune system.1,2 These new findings reinforce the importance of maintaining optimal vitamin D levels in adults as well as children.2–4

The main source of vitamin D is sun exposure of the skin, so vitamin D deficiency is not an expected problem in cities located in the Mediterranean basin, where there are many hours of sunlight (region of Valencia, 2789h of sunlight in 2013).5 However, cases of rickets and severe deficiency continue to be reported in these areas, albeit only in high-risk populations.6–8 Despite the recommendations made by the Spanish Association of Pediatrics (Asociación Española de Pediatría [AEP]),9 the American Academy of Pediatrics (AAP)10 and the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN),11 this continues to be a global health challenge, and it seems that preventive measures are not being implemented correctly.12

This could be due to other factors that reduce sun exposure, such as cultural habits, racial differences in skin pigmentation, and a reduction in the time spent outdoors, as well as the excessive use of sunscreen.

To gain a better understanding of these factors, it would be convenient to determine the vitamin D levels of the healthy population for all age groups. Substantial research has been conducted in areas where vitamin D deficiency should not be expected a priori, especially on adolescents and school-aged children; however, infants have only been studied in countries with fewer hours of sunlight per year.13,14

The main objective of this study was to assess vitamin D levels in children aged less than 2 years admitted to a tertiary care hospital in Valencia with mild acute diseases. The secondary objective of this study was to determine the presence of vitamin D deficiency, describing the variables associated with it and its clinical manifestations.

Out of the total of 213 children that met the inclusion criteria, only 169 ended up participating in the study. In one case, the parents did not sign the informed consent form; in thirty-three, not enough blood was collected to determine the concentration of vitamin D; and in ten cases, either the history taking or the physical examination could not be completed due to early discharge of the patient.

The different diseases of the participants fell into the following categories: 26% (44) urinary tract infection; 20.1% (34) bronchiolitis; 17.2% (29) bacteraemia; 14.2% (24) pneumonia; 5.3% (9) acute gastroenteritis; 4.7% (8) upper respiratory tract infection; 3.6% (6) disease requiring surgical treatment; 3.6% (6) seizures; 1.8% (3) skin infection; and there was one case each of hypoglycaemia, drug intoxication, erythema multiforme, Kawasaki disease, meningitis and varicella.

The mean age of the 169 children was 9.02±7.69 months, with a predominance of children less than 1 year of age (79.3%; 134/169); 56.2% (95/169) were male and 43.8% (74/169) female. Their anthropometric measurements were within normal ranges.

The distribution by ethnicity or national origin was the following: 75.7% Caucasian (128/169), 7.7% Latin American (13/169), 7.7% Roma (13/169), 4.1% Maghrebi (7/169), 2.3% Sub-Saharan African (4/169), 1.7% Indo-Pakistani (3/169), 0.6% Chinese (1/169).

Of all children, 24.3% (41/169) had vitamin D levels below30ng/mL, with 16% (27/169) having values between 30 and 20ng/mL, and 8.3% (14/169) values below 20ng/mL (Fig. 1). Thus, group 1 was comprised of 41 children (M/F, 26/15) and group 2 of 128 children (M/F, 69/59).

Figure 1.

Distribution of vitamin D levels.

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Table 1 summarizes the associations of the different variables under study for groups 1 and 2.

The most salient findings involved the median month of admission, with a higher proportion of admissions in the winter and spring for the group with low vitamin D levels (median, May) compared to a higher proportion of admissions in the summer and autumn in the group with normal levels (median, July).

We found a greater frequency of previous infections in group 1 (P=0.08) along with a predominance of skin phototypes higher in the Fitzpatrick scale (P<0.01). The frequency of clinical signs of rickets (anterior fontanelle with soft edges, mild frontal bossing, deformation of lower limbs) was higher in these children than in the control group.

Group 2 membership was significantly associated with administration of vitamin D prophylaxis and its duration, mothers of Caucasian descent, and mothers that did not wear a hijab regularly. We did not find statistically significant differences in the vitamin D levels of patients whose mothers wore a hijab based on the type of feeding (human milk vs formula). On the other hand, we did not find significant differences between groups based on the number of hours of sun exposure and the type of feeding, even for breastfed children that did not receive supplementation (P=0.65) (Table 1).

Due to the abundance of sunlight in locations of the Mediterranean region such as Valencia (which had 2789h of sunlight in 2013),5 there is a widespread belief, in the general population as well as among healthcare professionals, that vitamin D levels are adequate. Contrary to this belief, our study found that 24.3% of children aged less than 2 years admitted to our hospital for mild acute diseases had levels below 30ng/mL.

We should also mention that another study conducted in the city of Valencia in 2007 found levels below 10ng/mL in 8.3% of infants aged less than 6 months.22 These studies prove that vitamin D deficiency continues to be a problem in Valencia.

In the Iberian Peninsula, at a latitude of 43° North and 36° South, exposure of 30% of the total body surface area to ultraviolet B radiation (UBV) for 10–15min between the hours of 10 am and 3 pm during non-winter months is enough to produce 1000IU of vitamin D.23 Our data seem to support that season is related to vitamin D levels, as inadequate levels were more common in the winter and spring. This finding could be explained by the decrease in sunlight that occurs in the winter, which would prevent the synthesis of optimal amounts of vitamin D and result in hypovitaminosis during the spring.

Consistent with the literature, the vitamin D levels were negatively correlated to the skin phototype of the child, with the risk of hypovitaminosis seemingly increasing with the phototype.24 When this factor is associated with specific maternal cultural habits involving clothing that restricts sun exposure or a diet rich in phytates, low levels of vitamin D in the mother pose an evident risk to the child. There is evidence that maternal vitamin D levels are directly correlated to neonatal levels and child growth and development.24–26 Unlike other authors, we did not find statistically significant differences between the groups in the weekly number of hours of direct sun exposure (P=0.24).

Human milk contains approximately 2IU/100mL of vitamin D, compared to concentrations of 40–56IU/100mL in infant formulas and 68–72IU/100mL in follow-on formulas.27 Based on these data, we would assume that breastfeeding without vitamin supplementation carries a higher risk of vitamin D deficiency, but we did not find a higher prevalence of deficiency in breastfed children, grouped on the basis of receiving or not receiving vitamin D prophylaxis, compared to formula-fed children.

Other factors under study, such as sex, age, weight, length, head circumference and BMI, were not affected by vitamin D levels. However, several studies have found an association between obesity (BMI) and the prevalence of hypovitaminosis D due to the accumulation of the vitamin in fatty tissues and the resulting reduction in its bioavailability.28,29

We found that signs of rickets were more frequent in children with concentrations below 30ng/mL (P<0.01), but the physical examination does not seem to suffice to suspect deficiency in the early stages, as the abnormalities that we found (mild frontal bossing, wide anterior fontanelle with soft edges, minimal deformation of lower limbs with or without proximal muscle weakness) are difficult to identify because they are nonspecific and highly subjective, and may be overlooked in routine health checkups.

Given the importance of maintaining optimal vitamin D levels in the pediatric age group and the high prevalence of vitamin D deficiency, health institutions recommend the routine administration 400IU of vitamin D a day to all infants aged less than 1 year, either through diet with an oral preparation, or through the parenteral route.9–11,30–33

A 2007 Cochrane review provided strong evidence in support of daily supplementation with 400IU of vitamin D in the first 12 months of life for the prevention of rickets,34 while the evidence currently available does not suffice to recommend supplementation in older children.

Contrary to what we expected, we could not precisely define the at-risk population based on the factors under study, but we were able to corroborate that the administration of prophylaxis correlated to higher vitamin D levels, which supports its recommendation.

At present, the definition of the normal levels of vitamin D is the subject of heated debate. Due to the use of different laboratory methods to measure the concentration of 25(OH)D and the difficulties involved in establishing the limits for reference levels in every age group, there is no consensus on the serum concentrations that define vitamin D insufficiency in infants and children.34,35 Some authors and scientific institutions consider that vitamin D levels are insufficient when the serum concentration of 25(OH)D is less than 20ng/mL, and that they are deficient when the concentration is less than 12ng/mL.36,37

However, some studies have found data that contradict this definition, such as the presence of bone changes in radiographs of dark-skinned infants with levels ranging between 16 and 18ng/mL, or a decrease in bone density in adolescents with values below 16ng/mL in Sweden,38,39 leading other recognized authors to define optimal levels of 25(OH)D as a range of 30–90ng/mL, insufficient levels as a range of 20–30ng/mL, and deficiency as levels below 20ng/mL.16–19,23,30

These definitions have been extrapolated from studies in the adult population that associated the serum concentrations of vitamin D, parathyroid hormone, and calcium and bone resorption, and were based on the levels at which the production of parathyroid hormone, the intestinal reabsorption of calcium and bone calcium resorption were lowest.40

The objectives, population and methods of our study do not allow for it to make a relevant contribution to this interesting debate, and further studies with better resources, a higher level of standardization and homogeneous and reproducible laboratory methods are needed to improve the current level of evidence on the optimal vitamin D levels for infants and older children.

Even though there is enough sunlight in Valencia to guarantee adequate vitamin D synthesis, approximately 25% of the children in the study had levels below30ng/mL and clinical manifestations that could be overlooked in routine health checkups. Adherence to current recommendations for vitamin D prophylaxis was only found in 50% of the infants. Our results should make pediatricians more aware of the need of routine vitamin D supplementation in the first year of life, even in sunny cities in the Mediterranean region.

The authors have no conflicts of interest to declare.