How Vitamin D Levels of Children Changed During COVID-19 Pandemic: A Comparison of Pre-pandemic and Pandemic Periods

Objective: The synthesis of vitamin D is related to sun exposure, thus the restrictions during the Coronavirus disease-2019 (COVID-19) pandemic may have affected the levels of vitamin D in all age groups. The aim of this study was to evaluate vitamin D levels of healthy children and adolescents during the first year of the pandemic. Methods: The study group included healthy children and adolescents who were admitted for general check-ups and evaluated with 25(OH)D levels. Then, it was divided into two groups: Group 1 "pre-pandemic", and Group 2 "pandemic". Vitamin D levels were recorded from the hospital database and were compared according to age groups, gender, and the season, retrospectively. Results: The study group [mean age=90.29±59.45 median age=79 interquartile range (IQR): 102 months, male/female: 1409/1624] included 3033 children and adolescents (Group 1/Group 2 n=1864/1169). Although the mean 25(OH)D levels among preschool children did not differ between groups, the vitamin D levels of school-aged children and adolescents were significantly lower in the pandemic period than in the pre-pandemic period [Group 1 median=16.50 (IQR: 10.5) vs Group 2 median=15.9 (IQR: 11.3) in 6-12 age group (p=0.026); Group 1 median=13.30 (IQR: 10.2) vs Group 2 median=11.20 (IQR: 9.7) in 12-18 age group (p=0.003)]. Moreover, the 25(OH)D levels of adolescents showed seasonal variance with lower levels in winter, and unexpectedly, in summer. Conclusion: Pandemic-related restrictions have caused significant decreases in vitamin D levels of school-aged children and adolescents. We suggest that children and adolescents should be given vitamin D supplementation in order to maintain sufficient levels of vitamin D during the pandemic.

Investigating the Efficiency of Vitamin D Administration with Buccal Spray in the Treatment of Vitamin D Deficiency in Children and Adolescents

Objective: The aim of this study was to evaluate the efficiency of a buccal spray form of vitamin D compared to single oral dose (stoss therapy) and oral drops therapy in the treatment of vitamin D deficiency. Methods: Ninety healthy children and adolescents (3-18 years) with vitamin D deficiency [serum level of 25-hydroxyvitamin D (25(OH) D) <12 ng/mL] were randomized to receive vitamin D3 buccal spray (2000 U, n=30, group 1) for six weeks, oral drops (2000 U, n=30, group 2) for six weeks and a single oral dose (300 000 U) vitamin D3 (n=30, group 3). Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone and 25(OH)D levels of the patients were measured at baseline and after the treatment on the 42nd day. Results: All three groups had a significant increase in serum 25(OH)D concentrations (p<0.001). In group 1, baseline mean 25(OH)D was 8.0±0.41 ng/mL, which rose to 22.1 (17.8-28.2) ng/mL after treatment with a mean increase of 15.6±1.3 ng/mL. Similarly in group 2, baseline, post-treatment and mean increase in 25(OH)D concentrations were 7.9±0.45 ng/mL, 24.4 (20.6-29.6) ng/mL and 17.3±1.1 ng/mL while for group 3 these values were 7.6±0.47 ng/mL, 40.3 (29.4-58.4) ng/mL and 34.3±3.2 ng/mL, respectively. Conclusion: We conclude that vitamin D3 supplementation with buccal spray and oral drops is equally effective in terms of raising vitamin D concentrations in short-term treatment of vitamin D deficiency.

Comparison of Treatment Regimens in Management of Severe Hypercalcemia Due to Vitamin D Intoxication in Children

Objective: No large study has been conducted to date to compare the effectiveness of prednisolone, alendronate and pamidronate as first-line treatment in children with hypercalcemia due to vitamin D intoxication. The aim was to perform a multicenter, retrospective study assessing clinical characteristics and treatment results. Methods: A standard questionnaire was uploaded to an online national database system to collect data on children with hypercalcemia (serum calcium level >10.5 mg/dL) due to vitamin D intoxication [serum 25-hydroxyvitamin D (25(OH)D) level >150 ng/mL] who were treated in pediatric endocrinology clinics. Results: Seventy-four children [median (range) age 1.06 (0.65-1.60) years, 45 males (61%) from 11 centers] were included. High-dose vitamin D intake was evident in 77% of the cases. At diagnosis, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D and parathyroid hormone concentrations were 15±3.2 mg/dL, 5.2±1.2 mg/dL, 268±132 IU/L, 322 (236-454) ng/mL, and 5.5 (3-10.5) pg/mL, respectively. Calcium levels showed moderate correlation with 25(OH)D levels (rs=0.402, p<0.001). Patients were designated into five groups according to the initial specific treatment regimens (hydration-only, prednisolone, alendronate, pamidronate, and combination). Need for another type of specific drug treatment was higher in children who initially received prednisolone (p<0.001). Recurrence rate of hypercalcemia was significantly lower in children who were treated with pamidronate (p=0.02). Conclusion: Prednisolone is less effective in the treatment of children with severe hypercalcaemia secondary to vitamin D intoxication and timely implementation of other treatment regimens should be considered.

Factors Influencing Serum Vitamin D Concentration in Turkish Children Residing in Izmir: A Single-Center Experience.

OBJECTIVE: The aim of this study was to examine the vitamin D status of children and to determine the factors influencing serum 25-hydroxyvitamin D [25(OH)D] concentration in Turkish infants living in Izmir. METHODS: In this study, we examined the serum 25(OH)D levels of 100 infants aged 1 to 24 months and of 22 mothers from Izmir, Turkey. The study also included a questionnaire given to the mothers to acquire data on the demographic characteristics of the infants and their mothers as well as information on vitamin D supplementation, clothing habits, and sunlight exposure. RESULTS: Vitamin D deficiency was present in 31% of infants and 81.8% of mothers. Twenty-four male (42.9%) and 7 female (15.9%) infants were found to be vitamin D deficient (<20 mg/dL); 9 male (16.1%) and 17 female (38.6%) infants to be vitamin D insufficient (20-30 mg/dL); and 23 male (41.1%) and 20 female (45.5%) infants were vitamin D sufficient (>30 mg/dL). Only 63% of the infants were receiving vitamin D supplementation and 52% were said to be having regular exposure to sunlight. Mean serum vitamin D levels were lower in infants whose mothers were dressed according to the culture of traditional covered clothing (44%) compared to those infants whose mothers' dressing style provided more exposure to sunlight. CONCLUSION: We conclude that low exposure to sunlight, inadequate use of vitamin D supplementation, and large family size are factors influencing the vitamin D status of Turkish children living in the inner city of Izmir.

Serum vitamin D levels in children with recurrent otitis media.

The aims of this study were to evaluate serum vitamin D levels in cases of recurrent otitis media and investigate the effect of vitamin D therapy on the risk of re-occurrence of the disease. This prospective study was performed by comparing serum vitamin D levels in children with recurrent otitis media and healthy children. Eighty-four children between 1 and 5 years of age and diagnosed with recurrent otitis media were enrolled as the study group. One hundred-and-eight healthy children with similar demographic characteristics were enrolled as the control group. Patients were divided into groups according to their serum 25(OH) vitamin D levels. In patients with low initial serum vitamin D levels, vitamin D therapy was administered in addition to conventional treatment for otitis media. Mean serum 25(OH) vitamin D level in the study group was 11.4 ± 9.8 ng/mL Serum 25(OH) vitamin D levels were below 20 ng/mL in 69 % (n = 58) of cases in this group. In the control group, mean serum 25(OH) vitamin D level was 29.2 ± 13.9 ng/mL and was below 20 ng/mL in 30 % (n = 32) of cases. Comparison of serum 25(OH) vitamin D levels and PTH in the study and control groups revealed a statistically significant difference (p < 0.05). Treatment was initiated in cases diagnosed with vitamin D deficiency, and patients were followed up in due course. The only episodes detected over the course of 1-year follow-up were one attack in five patients and two attacks in two. We believe that co-administration of supplementary vitamin D together with conventional treatments is appropriate in the management of upper respiratory infections such as otitis media.

Vitamin D intoxication.

Vitamin D intoxication (VDI) may result from supplementation rarely, but it has been reported more frequently in recent years. This may be attributable to an increase in vitamin D supplement intake due to an understanding of the role of vitamin D (25OHD) in the pathogenesis of several diseases. The symptoms and findings associated with VDI are closely related to serum calcium concentration and duration of hypercalcemia. In patients with VDI, hypercalcemia, normal or high serum phosphorus levels, normal or low levels of alkaline phosphatase (ALP), high levels of serum 25OHD, low serum parathyroid hormone (PTH), and high urine calcium/creatinine are usually present. Serum 25OHD levels above 150 ng/ml are considered as VDI. The main goal of treatment for VDI is correction of the hypercalcemia. When the calcium concentration exceeds 14 mg/dl, emergency intervention is necessary because of the adverse effects of hypercalcemia on cardiac, central nervous system, renal, and gastrointestinal functions. However, since vitamin D is stored in fat tissues, effects of toxicity may last for months despite the removal of the exogenous source of vitamin D. Treatment for VDI includes: discontinuation of intake, a diet with low calcium and phosphorus content, intravenous hydration with saline, loop diuretics, glucocorticoids, calcitonin, and bisphosphonates. In conclusion, the diagnosis of vitamin D deficiency rickets (VDDR) without checking serum 25OHD level may cause redundant treatment that leads to VDI. All patients who are clinically suspected of VDDR should be checked for serum vitamin D status and questioned for previous vitamin D administration before starting vitamin D therapy. On the other hand, parents of all infants should be asked whether they are using dietary or oral supplements, and serial questioning may be required during supplementation to avoid excessive intake.

Nutritional rickets in Turkey.

Nutritional rickets (NR) remains the most common form of developmental bone disease, in spite of the efforts of clinicians and health care providers to reduce the incidence of the disease in Turkey. Today, it is well known that the etiology of NR exists along a spectrum ranging from isolated vitamin D deficiency to isolated calcium deficiency. In Turkey, almost all NR results from vita-min D deficiency that may have temporary but profound effects on short- and long-term skeletal development. Recent evidence suggests that vitamin D deficiency during infancy may predispose a patient to diseases such as diabetes mellitus, cancer, multiple sclerosis, etc. The factors responsible for the high prevalence of vitamin D deficiency in developing countries and its resurgence in developed countries include the following: limited sunshine exposure as individuals spend more time indoors watching television and working on computers or intentional sunshine avoidance for skin cancer prevention. Traditional clothing (covered dress) further limits the exposure to sunshine and thus decreases the endogenous synthesis of vitamin D. In Turkey, maternal vitamin D deficiency and breast feeding without supplementation are the most prominent reasons. The diagnosis of NR is established with a thorough history and physical examination and confirmed by laboratory evaluation. In conclusion, recent literature has drawn attention to the supplemental doses of vitamin D required to achieve a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/l), the serum concentration that is needed to optimize absorption of dietary calcium, suppress excess secretion of parathyroid hormone, and reduce fracture risk as well as prevent long-term negative effects.

Nutritional rickets.

Nutritional rickets (NR) is still the most common form of growing bone disease despite the efforts of health care providers to reduce the incidence of the disease. Today, it is well known that the etiology of NR ranges from isolated vitamin D deficiency (VDD) to isolated calcium deficiency. In Turkey, almost all NR cases result from VDD. Recent evidence suggests that in addition to its short- or long-term effects on skeletal development, VDD during infancy may predispose the patient to diseases such as diabetes mellitus, cancer and multiple sclerosis. Among the factors responsible for the high prevalence of VDD in developing countries and its resurgence in developed countries is limited sunshine exposure due to individuals' spending more time indoors (watching television and working on computer) or avoiding sun exposure intentionally for fear of skin cancer. Traditional clothing (covering the entire body except the face and hands) further limits the exposure time to sunlight and, thus, decreases the endogenous synthesis of vitamin D. In Turkey, maternal VDD and exclusive breastfeeding without supplementation were reported to be the most prominent reasons leading to NR. The diagnosis of NR is established by a thorough history and physical examination and confirmed by laboratory evaluation. Recent reports draw attention to the supplemental doses of vitamin D required to achieve a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/l) - the serum concentration that is needed to optimize absorption of dietary calcium and to suppress excessive secretion of parathyroid hormone. This type of prevention will also reduce fracture risk as well as prevent long-term negative effect of vitamin D insufficiency.

Prevalence of vitamin D deficiency rickets in the eastern part of Turkey.

Turkey, especially its eastern part, has been accepted as endemic for vitamin D deficiency rickets (VDDR). In a study performed by our team in the region in 1998, the incidence of VDDR was 6.09% in children aged between 0-3 years. In 2005, the Ministry of Health initiated a free vitamin D supplementation campaign nationwide for every infant to eradicate VDDR. In this study, we aimed to investigate the prevalence of VDDR in children aged between 0-3 years in order to evaluate the effectiveness of this campaign. Between March 2007 and February 2008, 39,133 children aged between 0-3 years who were brought to different pediatric outpatient clinics in Erzurum, Turkey, were examined for VDDR. VDDR diagnosis was made by radiological and biochemical findings in the cases who were initially suspected of having clinical VDDR. During a one-year period, 39 (0.099%) of the 39,133 patients were diagnosed with VDDR. None of the cases with rickets was taking vitamin D supplementation. The most frequent physical findings were rachitic rosary, enlargement of the wrists, and craniotabes. The laboratory findings of the cases were compatible with VDDR; serum calcium (Ca) 7.5 +/- 1.9 mg/dL, PO4 4.4 +/- 1.3 mg/dL, alkaline phosphatase (ALP) 1,341 +/- 823, 25-hydroxyvitamin D (25 (OH) D) 5.8 +/- 2.9 ng/mL, intact parathyroid hormone (iPTH) 240 +/- 106 pg/mL. It was concluded that, although VDDR has been a continuing childhood health problem, a nationwide free vitamin D supplementation campaign initiated by the government appeared to be effective in eliminating VDDR.

Vitamin D deficiency in early infancy.

We analyzed the characteristics of young infants diagnosed with vitamin D deficiency in early infancy at 2 medical centers in Turkey. In this retrospective, cross-sectional study, the clinical, biochemical, and radiographic findings of infants who were diagnosed with vitamin D deficiency at <3 mo of age between May 2001 and May 2003 were reviewed. A total of 42 infants (27 boys and 15 girls) were diagnosed with vitamin D deficiency in the first 3 mo of life during this 2-y period. The age of infants at diagnosis was 60 +/- 19 d (range 32-112 d). The majority (78.7%) presented with seizures. No skeletal deformities were detected clinically, and radiological findings were subtle. All infants had low serum calcium levels but serum phosphorous levels varied. Eight infants (19.0%) had low, 19 (45.3%) had normal, and 15 (35.7%) had elevated serum phosphorous levels. Serum 25-hydroxyvitamin D levels in those measured (29 infants and 15 mothers) were <37.5 nmol/L. Most infants (83%) were exclusively breast-fed without supplemental vitamin D, and none of the mothers were supplemented with vitamin D during pregnancy. All mothers had limited sunlight exposure and 33 of 42 mothers (78.6%) wore concealing clothing. The majority of young infants diagnosed with vitamin D deficiency present with seizures, have low dietary vitamin D intake, and mothers with poor vitamin D reserves. Evaluation of vitamin D status should be included into the workup of hypocalcemia in early infancy. Prevention of deficiency by supplementing pregnant women and infants who are exclusively breast-fed is essential.

A case of dilated cardiomyopathy due to nutritional vitamin D deficiency rickets.

Vitamin D deficiency rickets was detected as the cause in a nine-month-old girl with dilated cardiomyopathy and signs of congestive heart failure. The patient responded to calcium and vitamin D supplementation promptly and left ventricular systolic functions normalized at the 3rd month of treatment. Nutritional rickets must be remembered in etiological assessment of dilated cardiomyopathy among infants living in regions in which nutritional rickets is still common.