Hypovitaminosis D in adolescent females – an analytical cohort study in the United Arab Emirates Hassib Narchi1, Jose Kochiyil1, Sania Al Hamad1, Javed Yasin2, Louis Laleye3, Aisha Al Dhaheri4 1
Department of Paediatrics and 2Internal Medicine, College of Medicine and Health Sciences, 3Department of Food Sciences and 4Department of Nutrition and Health, College of Food and Agriculture, United Arab Emirates University, Al Ain, United Arab Emirates Background: Despite living in a sunny country, hypovitaminosis D is common in women of reproductive age in Al Ain, United Arab Emirates (UAE). Aims and objectives: To establish the prevalence of hypovitaminosis D in adolescent female Emirati nationals and its risk factors. Methods: This was an analytical prospective cohort study of 350 female Emirati nationals aged 11–18 years attending public schools in Al Ain. Socio-economic status, diet and amount of sun exposure were evaluated by face-to-face interviews. Serum total 25 (OH) vitamin D (D2 z D3) levels were measured by electrochemiluminescence assay. The prevalence of hypovitaminosis D was calculated and the association with risk factors analysed. Results: Data were complete for 293 girls. Only one girl [prevalence 0.3%, 95% confidence interval (CI) 0.01–1.9] had vitamin D sufficiency (serum vitamin D levels .75 nmol/L). Three girls (1.0%, 95% CI 0.2–2.9) had vitamin D insufficiency (50–75 nmol/L), 58 (19.8%, 95% CI 15.0–25.5) were deficient (27.5–50 nmol/L) and 231 (78.8%, 95% CI 68.9–89.6) had severe deficiency (,27.5 nmol/L). Serum vitamin D levels declined between the ages of 11 and 13 years before progressively rising until the age of 18 years but without regaining the levels they were at the age of 11. There was no statistically significant difference between the vitamin D status groups in age, body mass index, accommodation type, family income, percentage of surface area unexposed to the sun when outdoors, consumption of oily fish or total vitamin D intake. Conclusion: The finding of a high prevalence of hypovitaminosis D in adolescent females in UAE is of serious concern for their health and that of their infants during their reproductive lives. Adolescent girls with a similar social and cultural background currently living in less sunny, industrialised countries might also be at risk.
Keywords: Vitamin D, Diet, Sunlight, Middle East, Epidemiology
Introduction Hypovitaminosis D plays a major role in human calcium metabolism. Vitamin D deficiency in neonates and infants may lead to hypocalcaemic seizures, to rickets or cardiomyopathy in children, to tetany, seizures and bone pains in adolescents and to osteomalacia and osteoporosis in adults and the elderly. As neonatal vitamin D serum levels are directly proportional to the mother’s, maternal hypovitaminosis D can directly affect their offspring.1,2 In addition to its established role in bone health, vitamin
Correspondence to: H Narchi, Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, PO Box 17666, United Arab Emirates. Fax: z971 3767 2022; Email: [email protected]
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ß W. S. Maney & Son Ltd 2015 DOI 10.1179/2046905514Y.0000000144
D also plays physiological roles in, amongst others, cardiovascular health, diabetes and immunity.3–8 In western industrialised countries, hypovitaminosis D is caused by inadequate exposure to the sun (related to cold climate, latitude and season), life-style (inadequate diet, dress code, limited outdoor exposure to the sun) and increased skin pigmentation. It is, therefore, found commonly in immigrants who often share many of these risk factors.9–11 It has also been reported in sun-rich countries owing to the same risk factors.12–14 Hypovitaminosis D, defined as a serum vitamin D level ,50 nmol/L, is prevalent in the Al Ain district of UAE.2,15–17 It is particularly common in women in their reproductive years, as well as in their offspring. It occurs in 69–78% of pregnant mothers, has a prevalence of 50–77% in the post-partum
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period and 83% 6 months after delivery.2 It affects 70% of neonates, 22–82% of infants and 22% of children.2,15–17 To prevent its occurrence during childbearing years, it is essential to know when females start developing hypovitaminosis D in order to enable timely intervention. Adolescence is a candidate period to study as hypovitaminosis D has also been reported in this group in other countries.11,18–21 Only one study has been reported from UAE but it included adolescents of both genders and of multiple ethnicities.22 As the proportion of foreign nationals in UAE is approximately four-fold that of national Emiratis, ascertainment of the prevalence of hypovitaminosis D in adolescent female Emiratis is required. This study aimed to estimate its prevalence in adolescent female Emirati nationals and its risk factors.
Methods This study was a cross-sectional, analytical investigation of a cohort of unselected adolescent female Emirati nationals attending public schools in the Al Ain district of UAE.
Participants Between 1 September 2011 and 31 May 2012, adolescent females (aged 11–18 years) attending public schools in Al Ain were recruited. They were randomly selected by a two-stage sampling method. The first stage comprised five schools randomly selected using computer-generated random numbers from amongst all twelve public schools in the city, as all public schools have approximately the same number of students. The second stage was the schoolgirls, stratified in three agebands of 23 girls each (11–14, 14–16 and 16–18 years) and selected randomly in each age-band by computergenerated random numbers from within these randomly selected schools.
Inclusion and exclusion criteria All subjects consenting to participate were included in the absence of exclusion criteria. Exclusion criteria included children and/or families who did not consent to participate, the presence of symptoms suggestive of hypovitaminosis D (rickets or osteomalacia, carpopedal spasms, chronic liver or renal impairment, known malabsorption), and patients on anticonvulsants or with osteoporosis.
Data collection and measurement Anthropometric data (height, weight) were measured in a standardised way by a trained research assistant using a Seca 700 series scale with a height-measuring rod (Seca GmbH & Co. KG, Hamburg, Germany). Each participant was made to stand straight with the shoes off and the head erect so that the external auditory meatus and the lower border of the eye were in the same horizontal plane (Frankfurt plane). With
Hypovitaminosis D in adolescent females
the knees and legs together and the arms hanging by the side, the buttocks, shoulder blades and heels touched the scale. The moveable measuring rod was brought against the crown of the head and the height measurement read at maximum inspiration to the nearest 0.1 cm. With the participant standing, shoes off and wearing light clothes, weight was measured to the nearest 0.1 kg. The scale was checked for zero adjustment before each measurement. Body mass index (BMI) was calculated as weight (kg)/height2 (m2) and was expressed as kg/m2. Face-to-face interviews of the children was conducted by an Arabic-speaking research assistant. The data were entered on a standardised questionnaire form used in previous publications.2,15 The information collected comprised: (i) socio-economic status, (ii) type of accommodation – flat or villa (with tinted glass windows that block ultraviolet light) or traditional house (where women are not required to wear traditional public dress while in open courtyards in their homes), and (iii) dress code and amount of exposure to the sun of uncovered body parts (separately estimated for the face, forearms or hands) exposed to the sun without sunscreen. The percentage of sun-exposed surface area was calculated using the burns rule of nines.23 Average daily and weekly sun exposure was calculated as well as the sun exposure index (percentage exposed surface area multiplied by the weekly number of hours spent in the sun).24 In addition, the girls and their families were requested to complete a food diary validated in previous nutritional studies.25 Daily dietary vitamin D intake was estimated by standard methods.26,27
Laboratory investigations A fasting blood sample (5 ml) was drawn at school from each participant, just before lunch. The sample was then centrifuged and the serum stored at 270uC until analysis. Serum total 25-hydroxy [25 (OH)] vitamin D (vitamin D2 z D3), the best indicator of vitamin D status because of its long half-life), was measured by electro-chemiluminescence assay ‘ECL IA’ (ROCHE Cobas e411 analyser). Participants were classified into four vitamin D status groups, according to international guidelines: severe deficiency, ,27.5 nmol/L; deficiency, 27.5–50.0 nmol/L; insufficiency, 50–75 nmol/L; and sufficiency, §75 nmol/ L.26,28–32 Serum calcium, phosphorus and alkaline phosphatase were measured spectrophotometrically (ROCHE Cobas INTEGRA plus analyser) with the following reference ranges: calcium 2.1–2.8 mmol/L, phosphorus 1.0–1.5 mmol/L and alkaline phosphatase 32–125 U/L.
Sample size and statistical analysis The required sample size was based on a 50% prevalence rate of hypovitaminosis D in adolescents
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in Al Ain.22 A sample size of 350 participants was required to ensure a 95% confidence level, a precision of 5% and an alpha risk of 5% (EpiInfo statistical package, CDC and WHO). Statistical analysis was performed with Stata version 11 (StataCorp, College Station, Texas, USA). Descriptive statistics of continuous variables with a normal distribution included means and standard deviations. The percentiles of serum vitamin D levels by age were calculated on the basis of observed data (not transformed) and were not calculated from specific distributional assumption. The resulting percentile charts by age were plotted by constructing LOWESS smooth curves using the weighted quadratic least squares regression method. Comparisons of the continuous explanatory variables in the four vitamin D status groups were analysed by one-way analysis of variance (ANOVA) if they had a normal distribution, or by non-parametric methods otherwise. Calculations included the prevalence of hypovitaminosis D with 95% CIs. Its univariate association with each of the relevant explanatory variables was analysed with the Pearson x2 test or Fisher’s Exact test (when any expected frequency was ,5). For all tests, statistical significance was defined by P , 0.05.
Figure 1 Vitamin D status classification in 293 female adolescents
or a traditional house (130, 44.3%) and only eight girls lived in a flat (2.7%). No girl with a serum vitamin D level .50 nmol/L lived in a flat or a traditional house. Only 40 girls (14%) were from a low-income family (,US$2500/month). The only girl with vitamin D sufficiency came from a high-income family (.US$5000/month). When outdoors, 238 girls (81.2%) always covered their forearms, 53 (18.1%) also covered their face and, in addition, 23 (7.8%) covered their hands. No girls with serum vitamin D levels .50 nmol/L covered either their face or hands. The mean (SD) percentage of exposed surface area while outdoors was 13.6% (6.3) for all participants. Daily sun exposure and the sun exposure index were not available for four girls (1.3%) who all had serum vitamin D levels .50 nmol/L. Twenty-seven girls (9%) were prescribed regular vitamin D supplementation of 400 IU but only 12 (44.4%) were taking it regularly. At least once a week, all participants drank vitamin D-fortified milk (median 5 times, range 1–20 times a week) and consumed oily fish (median 5, range 1–8 times a week). For all participants, the mean (SD) daily vitamin D intake from consumption of milk was 70.9 (43.6) IU and of oily fish was 251.5 (162.9) IU, with a mean (SD) total daily vitamin D intake of 338.8 (198.3) IU. There was no statistically significant difference amongst the four vitamin D status groups in age, body mass index, accommodation type, family income, percentage of exposed surface area when outdoors, consumption of oily fish or total vitamin D intake. However, daily vitamin D intake from fortified milk was significantly higher in those with serum vitamin D levels .50 nmol/L than in those with lower concentrations (P 5 0.002).
Ethical approval Approval for the study was granted by the Al Ain Medical District Human Research Ethics Committee (07/144). Signed, informed consent was obtained from all the participants and their guardians, in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Results Of the 350 enrolled participants, 57 (16%) declined blood sampling and were excluded from further analysis. The remaining 293 girls (84%) with complete data were included in the final analysis. The demographic characteristics and risk factors such as sun exposure and dietary vitamin D intake were not significantly different between these two groups.
Vitamin D status classification Based on serum vitamin D levels, only one girl (0.3%, 95% CI 0.01–1.9) was vitamin D-sufficient (serum vitamin D level 87.5 nmol/L). Vitamin D insufficiency (serum levels 50–75 nmol/L) occurred in three girls (prevalence 1.0%, 95% CI 0.2–2.9), deficiency (27.5–50 nmol/L) in 58 girls (19.8%, 95% CI 15.0– 25.5) and severe deficiency (,27.5 nmol/L) in 231 (78.8%, 95% CI 68.9–89.6) (Fig. 1).
Descriptive analysis (Table 1) The descriptive characteristics of the four groups are described in Table 1. The mean (SD) age of participants was 15.2 (2.0) years. Approximately equal numbers of girls lived in a villa (155, 52.9%)
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Laboratory investigations The results of the biochemical investigations are summarised in Table 2. Mean (SD) serum concentration
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was not seen in those with higher vitamin D levels, the difference was not statistically significant. Fiftyfour girls (18.4%) had hyperphosphoraemia (serum phosphorus .1.5 mmol/L), all of whom had serum vitamin D levels ,75 nmol/L. Serum alkaline phosphatase levels were elevated (.125 U/L) in 72 girls (25%): 53 (24%) had severe vitamin D deficiency, 17 (29%) were deficient and two (67%) had insufficiency. The level was normal in the only participant with sufficient serum vitamin D levels (.75 nmol/L), but the difference between the groups was not statistically significant.
of 25 (OH) vitamin D for all participants was 21.5 (10.0) nmol/L. The percentiles of serum vitamin D concentration by age are shown in Table 3. These levels declined steadily between the ages of 11 and 13 years before progressively rising until the age of 18 years, but without regaining the levels at 11 years (Fig. 2). Mean (SD) serum calcium level for all participants was 2.5 (0.2) mmol/L (normal range 2.1–2.8 mmol/L) and there was no statistically significant difference between the four groups (Table 2). Ten girls (3.4%) had asymptomatic low serum calcium levels (,2.1 mmol/ L) with serum vitamin D levels ,50 nmol/L. Low serum calcium levels occurred more commonly in those with severe vitamin D deficiency (9, 3.9%) than in those with insufficiency (1, 1.7%). The difference, however, was not statistically significant. There was no hypocalcaemia when serum vitamin D levels were .50 nmol/L (Table 2). Mean (SD) serum phosphorus level was 1.3 (0.2) mmol/L (normal range 1.0–1.5 mmol/L) and there was no statistically significant difference between the four groups (Table 2). Although five girls (1.8%) had hypophosphoraemia (serum phosphorus ,1 mmol/ L) with serum vitamin D levels ,50 nmol/L which
Discussion The prevalence of hypovitaminosis D in adolescent girls in Al Ain was much higher than expected and was found in more than 99% of them. It is, therefore, higher in adolescence than in childhood or women of childbearing age. It also exceeds the prevalence in 315 adolescents between the ages of 15 and 18 years in another recent study in Al Ain in which 65.1% of the participants were either vitamin D-deficient or insufficient.22 One reason for the difference is that only 198 of the adolescents in that study were Emiratis and, in addition, gender was not reported, resulting,
Table 1 Descriptive characteristics of 293 female adolescents Severe deficiency Vitamin D status, serum vitamin ,27.5 D2 z D3, nmol/L Participants, n (%) Age, yrs, mean (SD) Body mass index, kg/m2, mean (SD) Housing Flat, n (%) Villa, n (%) Traditional house, n (%) Family income Low, n (%) Medium, n (%) High, n (%) Face covered, n (%) Forearms covered, n (%) Hands covered, n (%) Percentage exposed surface area, mean (SD) Daily sun exposure, hrs, mean (SD) Sun exposure index,{ mean (SD) Daily vitamin D intake from oily fish, IU, mean (SD) Daily vitamin D intake from fortified milk, IU, mean (SD) Regularly taken vitamin D supplementation, n (%) Total daily vitamin D intake in IU,1 mean (SD)
Deficiency
Insufficiency
Sufficiency
27.5–50
50–75
.75
All participants P–value
231 (78.8) 15.2 (1.9) 21.9 (4.6)
58 (19.8) 15.2 (2.3) 22.7 (5.9)
3 (1) 13.6 (3.0) 21.8 (1.5)
1 (0.3) 16.0 (0) 19.2 (0)
293 (100) 15.3 (2.0) 22.1 (4.9)
7 (3.0) 125 (54.0) 99 (43.0)
1 (1.8) 26 (44.8) 31 (53.4)
0 3 (100) 0
0 1 (100) 0
8 (2.7) 155 (52.9) 130 (44.3)
32 (13.9) 86 (37.4) 112 (48.7) 41 (17.5) 189 (81.8) 18 (7.8) 13.6 (6.4)
8 (13.8) 25 (43.1) 25 (43.1) 12 (20.7) 45 (77.6) 5 (8.6) 13.6 (6.3)
0 0 1 (100) 0 1 (100) 9 (0) 9.5 (0)
40 (13.6) 113 (38.5) 140 (47.9) 53 (18.1) 238 (81.2) 23 (7.8) 13.6 (6.3)
0.8{ 0.7{ 0.8{ 0.8*
1.76 (0.6)
1.7 (0.5)
NA
NA
1.75 (0.6)
0.7*
25.3 (14.7)
23.9 (13.6)
NA
NA
25.0 (14.5)
0.5*
263.2 (160.4)
206.9 (165.3)
166.6 (202.0)
400 (0)
251.5 (162.9)
0.06*
70.4 (41.6)
67.2 (43.4)
161.9 (107.2)
114.3 (0)
70.9 (43.6)
0.002*
0.5* 0.9* 0.3{
0.9{
6 (2.6) 344.0 (189.1)
6 (10.3) 315.5 (234.2)
0 2 2 0 3 0 10.8
(50.0) (50.0) (100) (2.3)
0 328.5 (175.1)
0 514.3 (0)
12 (4.1)
0.07{
338.8 (198.3)
0.6*
SD, standard deviation; IU, international units; * analysis of variance (ANOVA); { 2 x or Fisher’s Exact test for small values; { % exposed body surface area multiplied by the weekly number of hours spent in the sun; 1 recommended dietary allowance 600 IU vitamin D/day27
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therefore, in a smaller sample size of adolescent female Emiratis than in this study. Furthermore, the report also included private schools with students of diverse ethnicities and to which only Emirati families with a high income would send their daughters. The results therefore are not representative of the adolescent female Emirati population. In addition, the authors did not report specifically whether they measured total vitamin D2 and D3 levels and thus the radio-immunoassay method used might not have yielded results comparable to this study. Another difference is that this study was undertaken between September and May whereas the other study was performed during March and April when serum vitamin D levels are at their highest.33 The prevalence of hypovitaminosis D in female adolescents in Al Ain also exceeds that which has been described in reports from developed and developing countries.19–21 Various factors might explain this difference, such as lifestyle, climate, sun exposure, degree of skin pigmentation, diet and vitamin D supplementation. In this study, serum vitamin D levels declined between the ages of 11 and 13 years before progressively rising until the age of 18 years, but without regaining the levels at 11 years of age. While some reports confirm these findings,20,34, others have found either a reduction in serum vitamin D concentrations with increasing age during adolescence35 or no change at all.36 Population differences in age at menarche might explain these differences as the higher oestrogen levels associated with the menarche are known to induce an increase in the binding protein of vitamin D with a resulting decrease of the unbound bio-available fraction of the vitamin which acts on target cells. In this study, apart from a higher daily vitamin D intake from fortified milk in participants with serum vitamin D levels .50 nmol/L than in those with lower levels, no other risk factors for hypovitaminosis D were identified. One possible reason may be that the overwhelming majority of girls were deficient, resulting in the absence of ‘controls’ with adequate serum levels with whom to compare. There might be other explanations for the unexpected lack of a significant association between daily vitamin D intake and hypovitaminosis D. Although a
daily dietary intake (RDA) of 600 IU of vitamin D is advised,27 diet is generally a poor source of vitamin D and regular vitamin D supplementation is advised. A vitamin D supplementation programme has already been in place in the UAE for several years, in which all infants, including those exclusively breastfed, receive a daily minimum 200 IU vitamin D from the age of 2 months and throughout childhood.29 Unfortunately, although this is also indicated for adolescents, it has not been regularly implemented. This is mainly because, for cultural reasons, after the age of 13 years, adolescents in the UAE are no longer cared for by paediatricians but by general practitioners who might not always be aware of their need for vitamin D supplementation.29,37 Although 27 girls were taking a daily supplement of 400 IU vitamin D, 26 of them still had unexpectedly low levels of serum vitamin D. One possible reason might be that a significantly increased vitamin D requirement during the adolescent growth spurt might require a higher dosage than currently recommended.38,39 Another possible explanation might be recall bias or some inaccuracy in the food diary. Surprisingly, insufficient sun exposure was not found to be associated with hypovitaminosis D. The Al Ain district (latitude 24uN, longitude 55uE) has daily sunlight hours of 8–10 hours from November to April (average maximum temperature 27.7uC) and 10–12 hours from May to October (average maximum temperature 41uC). During the study period (September–May), average temperature is 17–33uC and mean (SD) daily duration of sunlight hours ranges from 9 (1.0) to 11 (1.0). As this is the time of year when temperatures are not at their highest, there is an increase in outdoor activity and, therefore, exposure to the sun is at its maximum and is associated with the highest vitamin D stores.33 It has been proposed that an hour of sun a day prevents hypovitaminosis D, and therefore the daily mean exposure time of 1.75 hours in our participants with a very high prevalence of hypovitaminosis D is surprising.40 A possible reason might be that those with increased skin pigmentation, as in our population, require a far higher dose of ultraviolet B to maximize cutaneous vitamin D production than, for example, those with lighter or no pigmentation.40 In addition, the negligible
Table 2 Laboratory results of 293 female adolescents
Vitamin D status, serum vitamin D2 z D3 (nmol/L)
Severe deficiency
Deficiency
Insufficiency
Sufficiency
,27.5
27.5–50
50–75
.75
Total
2.6 (0.2) 1.4 (0.2) 34.4 (5.4)
2.7 (0.1) 1.4 (0.2) 52.1 (0.6)
2.6 (0) 1.4 (0) 97.5 (0)
2.5 (0.2) 0.2* 1.3 (0.2) 0.3* 21.5 (10.0) NA
Serum calcium, mmol/L, mean (SD) 2.5 (0.2) Serum phosphorus, mmol/L, mean (SD) 1.3 (0.2) Serum 25 OH vitamin D, nmol/L, mean (SD) 17.6 (5.5)
SD, standard deviation; NA, not applicable; * analysis of variance (ANOVA); normal serum values: calcium 2.1–2.8 mmol/L, phosphorus 1.0–1.5 mmol/L
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skin surface area exposed to the sun in the majority of this cohort is probably insufficient for adequate cutaneous vitamin D production. Furthermore, even adequate sun exposure may not always ensure vitamin D sufficiency because of racial differences, the skin’s intrinsic ability to limit vitamin D synthesis, decreased cutaneous synthesis by sun-induced increased melanin production, enhanced cutaneous destruction, or transport abnormalities from the skin to the circulation.41 No association between BMI and hypovitaminosis D was found. Although obesity is associated with decreased bio-availability of vitamin D because of its sequestration into a larger pool of adipose tissue,26 the relationship between BMI and hypovitaminosis D is still debated. Several reports have observed a relationship between BMI and vitamin D concentrations,42 with some reporting either an inverse relationship20,43,44 or a positive association.45,46 The categorisation of obesity on the basis of BMI and the variations associated with growth and development in different populations might explain these differences. Although secondary hypoparathyroidism caused by hypovitaminosis D explains the expected hypophosphoraemia found in many participants, the hyperphosphoraemia in others was unexpected. Hyperphosphoraemia in the context of hypovitaminosis may mimic pseudohypoparathyroidism type 2 and is a transient condition caused by renal tubular cell receptor desensitisation/resistance to chronically elevated serum parathormone levels.47–49 The strength of this study was the large sample size of a representative group of subjects. The methods of estimating vitamin D dietary intake and sun exposure have been validated in many studies. The laboratory assay measured total 25(OH) vitamin levels (D2 and D3) which accurately reflects both dietary intake and skin synthesis of vitamin D during sun exposure. As the study was undertaken during the season of maximum sunlight which is associated with the highest vitamin D stores in this region, the findings are likely to represent the ‘best-case scenario’. The study has some limitations. As dietary history and sun exposure were self-reported, the data could be
Hypovitaminosis D in adolescent females
Figure 2 Smoothed serum vitamin D levels percentile curves (P 5 5th, 25th, 50th, 75th and 95th percentiles) in 293 female adolescents
inaccurate and recall bias is possible. Self-reporting of dietary intake, vitamin D supplementation and degree of sun exposure could mean that some data were biased or inaccurate. Skin pigmentation was not evaluated as it was assumed to be uniform in girls from the same ethnicity. The prevalence of hypovitaminosis D is very high in female adolescent Emiratis. Its prevention during that time would therefore improve the vitamin D status of women of procreation age and their offspring. For cultural reasons which include the conservative dress code and the limitation of outdoor activity for women, realistically, vitamin D supplementation is probably the only preventive option in this part of the world. Supplementation guidelines should be implemented by all physicians taking care of adolescents.29,37 As some girls were vitamin D-deficient despite standard vitamin D supplementation, it is possible that the current recommended doses might not be adequate in this population. A randomised controlled trial is therefore being planned using different doses of vitamin D supplementation. The finding of a very high prevalence of hypovitaminosis D in adolescent females in this area, although primarily of regional interest, is very likely to also affect adolescent girls with a similar social and
Table 3 Serum vitamin D percentiles (p2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th and 97.5th) by age in female adolescents (n5293). Serum vitamin D (nmol/L) Age yrs
Participants n (%)
p2.5
p5
p10
p25
p50
p75
p90
p95
p97.5
11 12 13 14 15 16 17 18
10 27 38 25 28 71 67 27
14.9 5.0 5.0 7.6 5.0 7.5 8.9 5.0
14.9 5.0 5.0 7.9 8.4 10.0 11.8 9.7
17.5 5.0 8.2 9.4 11.4 12.3 12.1 12.8
23.2 13.7 11.6 12.9 15.6 16.3 13.7 17.0
29.3 20.7 16.6 17.2 20.2 20.9 19.8 20.6
30.9 29.3 20.7 24.7 25.1 25.4 26.7 26.8
47.3 36.5 28.5 29.3 39.5 31.4 35.0 35.4
51.5 42.2 39.6 29.6 44.7 34.6 38.2 42.6
51.5 42.9 52.7 46.7 45.5 52.0 45.8 46.3
(3.4) (9.2) (13.0) (8.5) (9.6) (24.2) (22.9) (9.2)
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12 Siddiqui AM, Kamfar HZ. Prevalence of vitamin D deficiency rickets in adolescent school girls in Western region, Saudi Arabia. Saudi Med J. 2007;28:441–4. 13 El-Hajj FG, Nabulsi M, Choucair M, Salamoun M, Hajj SC, Kizirian A, et al. Hypovitaminosis D in healthy schoolchildren. Pediatrics. 2001;107:E53. 14 Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. Regional variation and determinants of vitamin D status in sunshine-abundant Thailand. BMC Public Health. 2011;11:853. 15 Narchi H, Kochiyil J, Zayed R, Abdulrazzak W, Agarwal M. Maternal vitamin D status throughout and after pregnancy. J Obstet Gynaecol. 2010;30:137–42. 16 Dawodu A, Dawson KP, Amirlak I, Kochiyil J, Agarwal M, Badrinath P. Diet, clothing, sunshine exposure and micronutrient status of Arab infants and young children. Ann Trop Paediatr. 2001;21:39–44. 17 Dawodu A, Agarwal M, Hossain M, Kochiyil J, Zayed R. Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breast-feeding infants. J Pediatr. 2003;142:169–73. 18 Narchi H, El Jamil M, Kulaylat N. Symptomatic rickets in adolescence. Arch Dis Child. 2001;84:501–3. 19 Andiran N, Celik N, Akca H, Dogan G. Vitamin D deficiency in children and adolescents. J Clin Res Pediatr Endocrinol. 2012;4:25–9. 20 Gonzalez-Gross M, Valtuena J, Breidenassel C, Moreno LA, Ferrari M, Kersting M, et al. Vitamin D status among adolescents in Europe: the Healthy Lifestyle in Europe by Nutrition in Adolescence study. Br J Nutr. 2012;107:755–64. 21 Shin YH, Kim KE, Lee C, Shin HJ, Kang MS, Lee HR, et al. High prevalence of vitamin D insufficiency or deficiency in young adolescents in Korea. Eur J Pediatr. 2012;171:1475–80. 22 Muhairi SJ, Mehairi AE, Khouri AA, Naqbi MM, Maskari FA, Kaabi J, et al. Vitamin D deficiency among healthy adolescents in Al Ain, United Arab Emirates. BMC Public Health. 2013;13:33. 23 Knaysi GA, Crikelair GF, Cosman B. The role of nines: its history and accuracy. Plast Reconstr Surg. 1968;41:560–3. 24 Barger-Lux MJ, Heaney RP. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption. J Clin Endocrinol Metab. 2002;87:4952–6. 25 Cheikh Ismail LI, Al-Hourani H, Lightowler HJ, Aldhaheri AS, Henry CJ. Energy and nutrient intakes during different phases of the menstrual cycle in females in the United Arab Emirates. Ann Nutr Metab. 2009;54:124–8. 26 Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266–81. 27 Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010. 28 The National Academies Collection. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Institutes of Health, 1997. 29 Gartner LM, Greer FR. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics. 2003;111:908–10. 30 Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–16. 31 Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080–6S. 32 Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86:50–60. 33 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, et al. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone. 2006;39:1136–43. 34 Koenig J, Elmadfa I. Status of calcium and vitamin D of different population groups in Austria. Int J Vitam Nutr Res. 2000;70:214–20. 35 Gregory JR, Lowe S, Bates CJ, Prentice A, Jackson L, Smithers G, et al. National Diet and Nutrition Survey: Young People Aged 4 to 18 years. Report of the Diet and Nutrition Survey. London: HMSO, 2000. 36 Dong Y, Pollock N, Stallmann-Jorgensen IS, Gutin B, Lan L, Chen TC, et al. Low 25-hydroxyvitamin D levels in adolescents: race, season, adiposity, physical activity, and fitness. Pediatrics. 2010;125:1104–11.
cultural background who are currently living in less sunny, industrialised countries.9,10
Disclaimer statements Contributors None. Funding Research grant from the College of Medicine and Health Sciences, United Arab Emirates University (NP-10-11/104). Conflicts of interest None. Ethics approval Approval was granted by the Al Ain Medical District Human Research Ethics Committee (07/144).
Acknowledgments We thank the staff of the participating schools, the Department of Al Ain Educational Zone, Abu Dhabi Education Council and all the girls who participated and their families. The study was funded exclusively by a research grant from the College of Medicine and Health Sciences, United Arab Emirates University (NP-10-11/104), but they had no role in the study design, collection, analysis and interpretation of data, writing of the manuscript or in the decision to submit the manuscript for publication. There was no external funding.
References 1 Dawodu A, Agarwal M, Sankarankutty M, Hardy D, Kochiyil J, Badrinath P. Higher prevalence of vitamin D deficiency in mothers of rachitic than nonrachitic children. J Pediatr. 2005;147:109–11. 2 Narchi H, Kochiyil J, Zayed R, Abdulrazzak W, Agarwal M. Longitudinal study of vitamin D status in the 1st 6 months of life. Ann Trop Paediatr. 2011;31:225–30. 3 Buyukinan M, Ozen S, Kokkun S, Saz EU. The relation of vitamin D deficiency with puberty and insulin resistance in obese children and adolescents. J Pediatr Endocrinol Metab. 2012;25:83–7. 4 Williams DM, Fraser A, Lawlor DA. Associations of vitamin D, parathyroid hormone and calcium with cardiovascular risk factors in US adolescents. Heart. 2011;97:315–20. 5 Mutlu A, Mutlu GY, Ozsu E, Cizmecioglu FM, Hatun S. Vitamin D deficiency in children and adolescents with type 1 diabetes. J Clin Res Pediatr Endocrinol. 2011;3:179–83. 6 Muldowney S, Lucey AJ, Paschos G, Martinez JA, Bandarra N, Thorsdottir I, et al. Relationships between vitamin D status and cardio-metabolic risk factors in young European adults. Ann Nutr Metab. 2011;58:85–93. 7 Walker VP, Modlin RL. The vitamin D connection to pediatric infections and immune function. Pediatr Res. 2009;65:106–13R. 8 Reis JP, von Muhlen D, Miller ER 3rd, Michos ED, Appel LJ. Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics. 2009;124:e371–9. 9 Hintzpeter B, Scheidt-Nave C, Muller MJ, Schenk L, Mensink GB. Higher prevalence of vitamin D deficiency is associated with immigrant background among children and adolescents in Germany. J Nutr. 2008;138:1482–90. 10 McGillivray G, Skull SA, Davie G, Kofoed SE, Frydenberg A, Rice J, et al. High prevalence of asymptomatic vitamin D and iron deficiency in East African immigrant children and adolescents living in a temperate climate. Arch Dis Child. 2007;92:1088–93. 11 Das G, Crocombe S, McGrath M, Berry JL, Mughal MZ. Hypovitaminosis D among healthy adolescent girls attending an inner city school. Arch Dis Child. 2006;91:569–72.
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37 Canadian Paediatric Society. Vitamin D supplementation: Recommendations for Canadian mothers and infants. Paediatr Child Health. 2007;12:583–98. 38 Cashman KD, FitzGerald AP, Viljakainen HT, Jakobsen J, Michaelsen KF, Lamberg-Allardt C, et al. Estimation of the dietary requirement for vitamin D in healthy adolescent white girls. Am J Clin Nutr. 2011;93:549–55. 39 Abrams SA. Vitamin D requirements in adolescents: what is the target? Am J Clin Nutr. 2011;93:483–4. 40 Holick MF. Environmental factors that influence the cutaneous production of vitamin D. Am J Clin Nutr. 1995;61:638–45S. 41 Binkley N, Novotny R, Krueger D, Kawahara T, Daida YG, Lensmeyer G, et al. Low vitamin D status despite abundant sun exposure. J Clin Endocrinol Metab. 2007;92:2130–5. 42 Souberbielle JC, Friedlander G, Kahan A, Cormier C. Evaluating vitamin D status. Implications for preventing and managing osteoporosis and other chronic diseases. Joint Bone Spine. 2006;73:249–53. 43 Smotkin-Tangorra M, Purushothaman R, Gupta A, Nejati G, Anhalt H, Ten S. Prevalence of vitamin D insufficiency in obese children and adolescents. J Pediatr Endocrinol Metab. 2007;20:817–23. 44 Lenders CM, Feldman HA, Von Scheven E, Merewood A, Sweeney C, Wilson DM, et al. Relation of body fat indexes to
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vitamin D status and deficiency among obese adolescents. Am J Clin Nutr. 2009;90:459–67. Jago R, Harrell JS, McMurray RG, Edelstein S, El Ghormli L, Bassin S. Prevalence of abnormal lipid and blood pressure values among an ethnically diverse population of eighth-grade adolescents and screening implications. Pediatrics. 2006;117:2065– 73. Weng FL, Shults J, Leonard MB, Stallings VA, Zemel BS. Risk factors for low serum 25-hydroxyvitamin D concentrations in otherwise healthy children and adolescents. Am J Clin Nutr. 2007;86:150–8. Rao DS, Parfitt AM, Kleerekoper M, Pumo BS, Frame B. Dissociation between the effects of endogenous parathyroid hormone on adenosine 39,59-monophosphate generation and phosphate reabsorption in hypocalcemia due to vitamin D depletion: an acquired disorder resembling pseudohypoparathyroidism type II. J Clin Endocrinol Metab. 1985;61:285– 90. Shriraam M, Bhansali A, Velayutham P. Vitamin D deficiency masquerading as pseudohypoparathyroidism type 2. J Assoc Physicians India. 2003;51:619–20. Levine BS, Kleeman CR, Felsenfeld AJ. The journey from vitamin D-resistant rickets to the regulation of renal phosphate transport. Clin J Am Soc Nephrol. 2009;4:1866–77.
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Department of Paediatrics and 2Internal Medicine, College of Medicine and Health Sciences, 3Department of Food Sciences and 4Department of Nutrition and Health, College of Food and Agriculture, United Arab Emirates University, Al Ain, United Arab Emirates Background: Despite living in a sunny country, hypovitaminosis D is common in women of reproductive age in Al Ain, United Arab Emirates (UAE). Aims and objectives: To establish the prevalence of hypovitaminosis D in adolescent female Emirati nationals and its risk factors. Methods: This was an analytical prospective cohort study of 350 female Emirati nationals aged 11–18 years attending public schools in Al Ain. Socio-economic status, diet and amount of sun exposure were evaluated by face-to-face interviews. Serum total 25 (OH) vitamin D (D2 z D3) levels were measured by electrochemiluminescence assay. The prevalence of hypovitaminosis D was calculated and the association with risk factors analysed. Results: Data were complete for 293 girls. Only one girl [prevalence 0.3%, 95% confidence interval (CI) 0.01–1.9] had vitamin D sufficiency (serum vitamin D levels .75 nmol/L). Three girls (1.0%, 95% CI 0.2–2.9) had vitamin D insufficiency (50–75 nmol/L), 58 (19.8%, 95% CI 15.0–25.5) were deficient (27.5–50 nmol/L) and 231 (78.8%, 95% CI 68.9–89.6) had severe deficiency (,27.5 nmol/L). Serum vitamin D levels declined between the ages of 11 and 13 years before progressively rising until the age of 18 years but without regaining the levels they were at the age of 11. There was no statistically significant difference between the vitamin D status groups in age, body mass index, accommodation type, family income, percentage of surface area unexposed to the sun when outdoors, consumption of oily fish or total vitamin D intake. Conclusion: The finding of a high prevalence of hypovitaminosis D in adolescent females in UAE is of serious concern for their health and that of their infants during their reproductive lives. Adolescent girls with a similar social and cultural background currently living in less sunny, industrialised countries might also be at risk.
Keywords: Vitamin D, Diet, Sunlight, Middle East, Epidemiology
Introduction Hypovitaminosis D plays a major role in human calcium metabolism. Vitamin D deficiency in neonates and infants may lead to hypocalcaemic seizures, to rickets or cardiomyopathy in children, to tetany, seizures and bone pains in adolescents and to osteomalacia and osteoporosis in adults and the elderly. As neonatal vitamin D serum levels are directly proportional to the mother’s, maternal hypovitaminosis D can directly affect their offspring.1,2 In addition to its established role in bone health, vitamin
Correspondence to: H Narchi, Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, PO Box 17666, United Arab Emirates. Fax: z971 3767 2022; Email: [email protected]
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ß W. S. Maney & Son Ltd 2015 DOI 10.1179/2046905514Y.0000000144
D also plays physiological roles in, amongst others, cardiovascular health, diabetes and immunity.3–8 In western industrialised countries, hypovitaminosis D is caused by inadequate exposure to the sun (related to cold climate, latitude and season), life-style (inadequate diet, dress code, limited outdoor exposure to the sun) and increased skin pigmentation. It is, therefore, found commonly in immigrants who often share many of these risk factors.9–11 It has also been reported in sun-rich countries owing to the same risk factors.12–14 Hypovitaminosis D, defined as a serum vitamin D level ,50 nmol/L, is prevalent in the Al Ain district of UAE.2,15–17 It is particularly common in women in their reproductive years, as well as in their offspring. It occurs in 69–78% of pregnant mothers, has a prevalence of 50–77% in the post-partum
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period and 83% 6 months after delivery.2 It affects 70% of neonates, 22–82% of infants and 22% of children.2,15–17 To prevent its occurrence during childbearing years, it is essential to know when females start developing hypovitaminosis D in order to enable timely intervention. Adolescence is a candidate period to study as hypovitaminosis D has also been reported in this group in other countries.11,18–21 Only one study has been reported from UAE but it included adolescents of both genders and of multiple ethnicities.22 As the proportion of foreign nationals in UAE is approximately four-fold that of national Emiratis, ascertainment of the prevalence of hypovitaminosis D in adolescent female Emiratis is required. This study aimed to estimate its prevalence in adolescent female Emirati nationals and its risk factors.
Methods This study was a cross-sectional, analytical investigation of a cohort of unselected adolescent female Emirati nationals attending public schools in the Al Ain district of UAE.
Participants Between 1 September 2011 and 31 May 2012, adolescent females (aged 11–18 years) attending public schools in Al Ain were recruited. They were randomly selected by a two-stage sampling method. The first stage comprised five schools randomly selected using computer-generated random numbers from amongst all twelve public schools in the city, as all public schools have approximately the same number of students. The second stage was the schoolgirls, stratified in three agebands of 23 girls each (11–14, 14–16 and 16–18 years) and selected randomly in each age-band by computergenerated random numbers from within these randomly selected schools.
Inclusion and exclusion criteria All subjects consenting to participate were included in the absence of exclusion criteria. Exclusion criteria included children and/or families who did not consent to participate, the presence of symptoms suggestive of hypovitaminosis D (rickets or osteomalacia, carpopedal spasms, chronic liver or renal impairment, known malabsorption), and patients on anticonvulsants or with osteoporosis.
Data collection and measurement Anthropometric data (height, weight) were measured in a standardised way by a trained research assistant using a Seca 700 series scale with a height-measuring rod (Seca GmbH & Co. KG, Hamburg, Germany). Each participant was made to stand straight with the shoes off and the head erect so that the external auditory meatus and the lower border of the eye were in the same horizontal plane (Frankfurt plane). With
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the knees and legs together and the arms hanging by the side, the buttocks, shoulder blades and heels touched the scale. The moveable measuring rod was brought against the crown of the head and the height measurement read at maximum inspiration to the nearest 0.1 cm. With the participant standing, shoes off and wearing light clothes, weight was measured to the nearest 0.1 kg. The scale was checked for zero adjustment before each measurement. Body mass index (BMI) was calculated as weight (kg)/height2 (m2) and was expressed as kg/m2. Face-to-face interviews of the children was conducted by an Arabic-speaking research assistant. The data were entered on a standardised questionnaire form used in previous publications.2,15 The information collected comprised: (i) socio-economic status, (ii) type of accommodation – flat or villa (with tinted glass windows that block ultraviolet light) or traditional house (where women are not required to wear traditional public dress while in open courtyards in their homes), and (iii) dress code and amount of exposure to the sun of uncovered body parts (separately estimated for the face, forearms or hands) exposed to the sun without sunscreen. The percentage of sun-exposed surface area was calculated using the burns rule of nines.23 Average daily and weekly sun exposure was calculated as well as the sun exposure index (percentage exposed surface area multiplied by the weekly number of hours spent in the sun).24 In addition, the girls and their families were requested to complete a food diary validated in previous nutritional studies.25 Daily dietary vitamin D intake was estimated by standard methods.26,27
Laboratory investigations A fasting blood sample (5 ml) was drawn at school from each participant, just before lunch. The sample was then centrifuged and the serum stored at 270uC until analysis. Serum total 25-hydroxy [25 (OH)] vitamin D (vitamin D2 z D3), the best indicator of vitamin D status because of its long half-life), was measured by electro-chemiluminescence assay ‘ECL IA’ (ROCHE Cobas e411 analyser). Participants were classified into four vitamin D status groups, according to international guidelines: severe deficiency, ,27.5 nmol/L; deficiency, 27.5–50.0 nmol/L; insufficiency, 50–75 nmol/L; and sufficiency, §75 nmol/ L.26,28–32 Serum calcium, phosphorus and alkaline phosphatase were measured spectrophotometrically (ROCHE Cobas INTEGRA plus analyser) with the following reference ranges: calcium 2.1–2.8 mmol/L, phosphorus 1.0–1.5 mmol/L and alkaline phosphatase 32–125 U/L.
Sample size and statistical analysis The required sample size was based on a 50% prevalence rate of hypovitaminosis D in adolescents
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in Al Ain.22 A sample size of 350 participants was required to ensure a 95% confidence level, a precision of 5% and an alpha risk of 5% (EpiInfo statistical package, CDC and WHO). Statistical analysis was performed with Stata version 11 (StataCorp, College Station, Texas, USA). Descriptive statistics of continuous variables with a normal distribution included means and standard deviations. The percentiles of serum vitamin D levels by age were calculated on the basis of observed data (not transformed) and were not calculated from specific distributional assumption. The resulting percentile charts by age were plotted by constructing LOWESS smooth curves using the weighted quadratic least squares regression method. Comparisons of the continuous explanatory variables in the four vitamin D status groups were analysed by one-way analysis of variance (ANOVA) if they had a normal distribution, or by non-parametric methods otherwise. Calculations included the prevalence of hypovitaminosis D with 95% CIs. Its univariate association with each of the relevant explanatory variables was analysed with the Pearson x2 test or Fisher’s Exact test (when any expected frequency was ,5). For all tests, statistical significance was defined by P , 0.05.
Figure 1 Vitamin D status classification in 293 female adolescents
or a traditional house (130, 44.3%) and only eight girls lived in a flat (2.7%). No girl with a serum vitamin D level .50 nmol/L lived in a flat or a traditional house. Only 40 girls (14%) were from a low-income family (,US$2500/month). The only girl with vitamin D sufficiency came from a high-income family (.US$5000/month). When outdoors, 238 girls (81.2%) always covered their forearms, 53 (18.1%) also covered their face and, in addition, 23 (7.8%) covered their hands. No girls with serum vitamin D levels .50 nmol/L covered either their face or hands. The mean (SD) percentage of exposed surface area while outdoors was 13.6% (6.3) for all participants. Daily sun exposure and the sun exposure index were not available for four girls (1.3%) who all had serum vitamin D levels .50 nmol/L. Twenty-seven girls (9%) were prescribed regular vitamin D supplementation of 400 IU but only 12 (44.4%) were taking it regularly. At least once a week, all participants drank vitamin D-fortified milk (median 5 times, range 1–20 times a week) and consumed oily fish (median 5, range 1–8 times a week). For all participants, the mean (SD) daily vitamin D intake from consumption of milk was 70.9 (43.6) IU and of oily fish was 251.5 (162.9) IU, with a mean (SD) total daily vitamin D intake of 338.8 (198.3) IU. There was no statistically significant difference amongst the four vitamin D status groups in age, body mass index, accommodation type, family income, percentage of exposed surface area when outdoors, consumption of oily fish or total vitamin D intake. However, daily vitamin D intake from fortified milk was significantly higher in those with serum vitamin D levels .50 nmol/L than in those with lower concentrations (P 5 0.002).
Ethical approval Approval for the study was granted by the Al Ain Medical District Human Research Ethics Committee (07/144). Signed, informed consent was obtained from all the participants and their guardians, in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Results Of the 350 enrolled participants, 57 (16%) declined blood sampling and were excluded from further analysis. The remaining 293 girls (84%) with complete data were included in the final analysis. The demographic characteristics and risk factors such as sun exposure and dietary vitamin D intake were not significantly different between these two groups.
Vitamin D status classification Based on serum vitamin D levels, only one girl (0.3%, 95% CI 0.01–1.9) was vitamin D-sufficient (serum vitamin D level 87.5 nmol/L). Vitamin D insufficiency (serum levels 50–75 nmol/L) occurred in three girls (prevalence 1.0%, 95% CI 0.2–2.9), deficiency (27.5–50 nmol/L) in 58 girls (19.8%, 95% CI 15.0– 25.5) and severe deficiency (,27.5 nmol/L) in 231 (78.8%, 95% CI 68.9–89.6) (Fig. 1).
Descriptive analysis (Table 1) The descriptive characteristics of the four groups are described in Table 1. The mean (SD) age of participants was 15.2 (2.0) years. Approximately equal numbers of girls lived in a villa (155, 52.9%)
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Laboratory investigations The results of the biochemical investigations are summarised in Table 2. Mean (SD) serum concentration
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was not seen in those with higher vitamin D levels, the difference was not statistically significant. Fiftyfour girls (18.4%) had hyperphosphoraemia (serum phosphorus .1.5 mmol/L), all of whom had serum vitamin D levels ,75 nmol/L. Serum alkaline phosphatase levels were elevated (.125 U/L) in 72 girls (25%): 53 (24%) had severe vitamin D deficiency, 17 (29%) were deficient and two (67%) had insufficiency. The level was normal in the only participant with sufficient serum vitamin D levels (.75 nmol/L), but the difference between the groups was not statistically significant.
of 25 (OH) vitamin D for all participants was 21.5 (10.0) nmol/L. The percentiles of serum vitamin D concentration by age are shown in Table 3. These levels declined steadily between the ages of 11 and 13 years before progressively rising until the age of 18 years, but without regaining the levels at 11 years (Fig. 2). Mean (SD) serum calcium level for all participants was 2.5 (0.2) mmol/L (normal range 2.1–2.8 mmol/L) and there was no statistically significant difference between the four groups (Table 2). Ten girls (3.4%) had asymptomatic low serum calcium levels (,2.1 mmol/ L) with serum vitamin D levels ,50 nmol/L. Low serum calcium levels occurred more commonly in those with severe vitamin D deficiency (9, 3.9%) than in those with insufficiency (1, 1.7%). The difference, however, was not statistically significant. There was no hypocalcaemia when serum vitamin D levels were .50 nmol/L (Table 2). Mean (SD) serum phosphorus level was 1.3 (0.2) mmol/L (normal range 1.0–1.5 mmol/L) and there was no statistically significant difference between the four groups (Table 2). Although five girls (1.8%) had hypophosphoraemia (serum phosphorus ,1 mmol/ L) with serum vitamin D levels ,50 nmol/L which
Discussion The prevalence of hypovitaminosis D in adolescent girls in Al Ain was much higher than expected and was found in more than 99% of them. It is, therefore, higher in adolescence than in childhood or women of childbearing age. It also exceeds the prevalence in 315 adolescents between the ages of 15 and 18 years in another recent study in Al Ain in which 65.1% of the participants were either vitamin D-deficient or insufficient.22 One reason for the difference is that only 198 of the adolescents in that study were Emiratis and, in addition, gender was not reported, resulting,
Table 1 Descriptive characteristics of 293 female adolescents Severe deficiency Vitamin D status, serum vitamin ,27.5 D2 z D3, nmol/L Participants, n (%) Age, yrs, mean (SD) Body mass index, kg/m2, mean (SD) Housing Flat, n (%) Villa, n (%) Traditional house, n (%) Family income Low, n (%) Medium, n (%) High, n (%) Face covered, n (%) Forearms covered, n (%) Hands covered, n (%) Percentage exposed surface area, mean (SD) Daily sun exposure, hrs, mean (SD) Sun exposure index,{ mean (SD) Daily vitamin D intake from oily fish, IU, mean (SD) Daily vitamin D intake from fortified milk, IU, mean (SD) Regularly taken vitamin D supplementation, n (%) Total daily vitamin D intake in IU,1 mean (SD)
Deficiency
Insufficiency
Sufficiency
27.5–50
50–75
.75
All participants P–value
231 (78.8) 15.2 (1.9) 21.9 (4.6)
58 (19.8) 15.2 (2.3) 22.7 (5.9)
3 (1) 13.6 (3.0) 21.8 (1.5)
1 (0.3) 16.0 (0) 19.2 (0)
293 (100) 15.3 (2.0) 22.1 (4.9)
7 (3.0) 125 (54.0) 99 (43.0)
1 (1.8) 26 (44.8) 31 (53.4)
0 3 (100) 0
0 1 (100) 0
8 (2.7) 155 (52.9) 130 (44.3)
32 (13.9) 86 (37.4) 112 (48.7) 41 (17.5) 189 (81.8) 18 (7.8) 13.6 (6.4)
8 (13.8) 25 (43.1) 25 (43.1) 12 (20.7) 45 (77.6) 5 (8.6) 13.6 (6.3)
0 0 1 (100) 0 1 (100) 9 (0) 9.5 (0)
40 (13.6) 113 (38.5) 140 (47.9) 53 (18.1) 238 (81.2) 23 (7.8) 13.6 (6.3)
0.8{ 0.7{ 0.8{ 0.8*
1.76 (0.6)
1.7 (0.5)
NA
NA
1.75 (0.6)
0.7*
25.3 (14.7)
23.9 (13.6)
NA
NA
25.0 (14.5)
0.5*
263.2 (160.4)
206.9 (165.3)
166.6 (202.0)
400 (0)
251.5 (162.9)
0.06*
70.4 (41.6)
67.2 (43.4)
161.9 (107.2)
114.3 (0)
70.9 (43.6)
0.002*
0.5* 0.9* 0.3{
0.9{
6 (2.6) 344.0 (189.1)
6 (10.3) 315.5 (234.2)
0 2 2 0 3 0 10.8
(50.0) (50.0) (100) (2.3)
0 328.5 (175.1)
0 514.3 (0)
12 (4.1)
0.07{
338.8 (198.3)
0.6*
SD, standard deviation; IU, international units; * analysis of variance (ANOVA); { 2 x or Fisher’s Exact test for small values; { % exposed body surface area multiplied by the weekly number of hours spent in the sun; 1 recommended dietary allowance 600 IU vitamin D/day27
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therefore, in a smaller sample size of adolescent female Emiratis than in this study. Furthermore, the report also included private schools with students of diverse ethnicities and to which only Emirati families with a high income would send their daughters. The results therefore are not representative of the adolescent female Emirati population. In addition, the authors did not report specifically whether they measured total vitamin D2 and D3 levels and thus the radio-immunoassay method used might not have yielded results comparable to this study. Another difference is that this study was undertaken between September and May whereas the other study was performed during March and April when serum vitamin D levels are at their highest.33 The prevalence of hypovitaminosis D in female adolescents in Al Ain also exceeds that which has been described in reports from developed and developing countries.19–21 Various factors might explain this difference, such as lifestyle, climate, sun exposure, degree of skin pigmentation, diet and vitamin D supplementation. In this study, serum vitamin D levels declined between the ages of 11 and 13 years before progressively rising until the age of 18 years, but without regaining the levels at 11 years of age. While some reports confirm these findings,20,34, others have found either a reduction in serum vitamin D concentrations with increasing age during adolescence35 or no change at all.36 Population differences in age at menarche might explain these differences as the higher oestrogen levels associated with the menarche are known to induce an increase in the binding protein of vitamin D with a resulting decrease of the unbound bio-available fraction of the vitamin which acts on target cells. In this study, apart from a higher daily vitamin D intake from fortified milk in participants with serum vitamin D levels .50 nmol/L than in those with lower levels, no other risk factors for hypovitaminosis D were identified. One possible reason may be that the overwhelming majority of girls were deficient, resulting in the absence of ‘controls’ with adequate serum levels with whom to compare. There might be other explanations for the unexpected lack of a significant association between daily vitamin D intake and hypovitaminosis D. Although a
daily dietary intake (RDA) of 600 IU of vitamin D is advised,27 diet is generally a poor source of vitamin D and regular vitamin D supplementation is advised. A vitamin D supplementation programme has already been in place in the UAE for several years, in which all infants, including those exclusively breastfed, receive a daily minimum 200 IU vitamin D from the age of 2 months and throughout childhood.29 Unfortunately, although this is also indicated for adolescents, it has not been regularly implemented. This is mainly because, for cultural reasons, after the age of 13 years, adolescents in the UAE are no longer cared for by paediatricians but by general practitioners who might not always be aware of their need for vitamin D supplementation.29,37 Although 27 girls were taking a daily supplement of 400 IU vitamin D, 26 of them still had unexpectedly low levels of serum vitamin D. One possible reason might be that a significantly increased vitamin D requirement during the adolescent growth spurt might require a higher dosage than currently recommended.38,39 Another possible explanation might be recall bias or some inaccuracy in the food diary. Surprisingly, insufficient sun exposure was not found to be associated with hypovitaminosis D. The Al Ain district (latitude 24uN, longitude 55uE) has daily sunlight hours of 8–10 hours from November to April (average maximum temperature 27.7uC) and 10–12 hours from May to October (average maximum temperature 41uC). During the study period (September–May), average temperature is 17–33uC and mean (SD) daily duration of sunlight hours ranges from 9 (1.0) to 11 (1.0). As this is the time of year when temperatures are not at their highest, there is an increase in outdoor activity and, therefore, exposure to the sun is at its maximum and is associated with the highest vitamin D stores.33 It has been proposed that an hour of sun a day prevents hypovitaminosis D, and therefore the daily mean exposure time of 1.75 hours in our participants with a very high prevalence of hypovitaminosis D is surprising.40 A possible reason might be that those with increased skin pigmentation, as in our population, require a far higher dose of ultraviolet B to maximize cutaneous vitamin D production than, for example, those with lighter or no pigmentation.40 In addition, the negligible
Table 2 Laboratory results of 293 female adolescents
Vitamin D status, serum vitamin D2 z D3 (nmol/L)
Severe deficiency
Deficiency
Insufficiency
Sufficiency
,27.5
27.5–50
50–75
.75
Total
2.6 (0.2) 1.4 (0.2) 34.4 (5.4)
2.7 (0.1) 1.4 (0.2) 52.1 (0.6)
2.6 (0) 1.4 (0) 97.5 (0)
2.5 (0.2) 0.2* 1.3 (0.2) 0.3* 21.5 (10.0) NA
Serum calcium, mmol/L, mean (SD) 2.5 (0.2) Serum phosphorus, mmol/L, mean (SD) 1.3 (0.2) Serum 25 OH vitamin D, nmol/L, mean (SD) 17.6 (5.5)
SD, standard deviation; NA, not applicable; * analysis of variance (ANOVA); normal serum values: calcium 2.1–2.8 mmol/L, phosphorus 1.0–1.5 mmol/L
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skin surface area exposed to the sun in the majority of this cohort is probably insufficient for adequate cutaneous vitamin D production. Furthermore, even adequate sun exposure may not always ensure vitamin D sufficiency because of racial differences, the skin’s intrinsic ability to limit vitamin D synthesis, decreased cutaneous synthesis by sun-induced increased melanin production, enhanced cutaneous destruction, or transport abnormalities from the skin to the circulation.41 No association between BMI and hypovitaminosis D was found. Although obesity is associated with decreased bio-availability of vitamin D because of its sequestration into a larger pool of adipose tissue,26 the relationship between BMI and hypovitaminosis D is still debated. Several reports have observed a relationship between BMI and vitamin D concentrations,42 with some reporting either an inverse relationship20,43,44 or a positive association.45,46 The categorisation of obesity on the basis of BMI and the variations associated with growth and development in different populations might explain these differences. Although secondary hypoparathyroidism caused by hypovitaminosis D explains the expected hypophosphoraemia found in many participants, the hyperphosphoraemia in others was unexpected. Hyperphosphoraemia in the context of hypovitaminosis may mimic pseudohypoparathyroidism type 2 and is a transient condition caused by renal tubular cell receptor desensitisation/resistance to chronically elevated serum parathormone levels.47–49 The strength of this study was the large sample size of a representative group of subjects. The methods of estimating vitamin D dietary intake and sun exposure have been validated in many studies. The laboratory assay measured total 25(OH) vitamin levels (D2 and D3) which accurately reflects both dietary intake and skin synthesis of vitamin D during sun exposure. As the study was undertaken during the season of maximum sunlight which is associated with the highest vitamin D stores in this region, the findings are likely to represent the ‘best-case scenario’. The study has some limitations. As dietary history and sun exposure were self-reported, the data could be
Hypovitaminosis D in adolescent females
Figure 2 Smoothed serum vitamin D levels percentile curves (P 5 5th, 25th, 50th, 75th and 95th percentiles) in 293 female adolescents
inaccurate and recall bias is possible. Self-reporting of dietary intake, vitamin D supplementation and degree of sun exposure could mean that some data were biased or inaccurate. Skin pigmentation was not evaluated as it was assumed to be uniform in girls from the same ethnicity. The prevalence of hypovitaminosis D is very high in female adolescent Emiratis. Its prevention during that time would therefore improve the vitamin D status of women of procreation age and their offspring. For cultural reasons which include the conservative dress code and the limitation of outdoor activity for women, realistically, vitamin D supplementation is probably the only preventive option in this part of the world. Supplementation guidelines should be implemented by all physicians taking care of adolescents.29,37 As some girls were vitamin D-deficient despite standard vitamin D supplementation, it is possible that the current recommended doses might not be adequate in this population. A randomised controlled trial is therefore being planned using different doses of vitamin D supplementation. The finding of a very high prevalence of hypovitaminosis D in adolescent females in this area, although primarily of regional interest, is very likely to also affect adolescent girls with a similar social and
Table 3 Serum vitamin D percentiles (p2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th and 97.5th) by age in female adolescents (n5293). Serum vitamin D (nmol/L) Age yrs
Participants n (%)
p2.5
p5
p10
p25
p50
p75
p90
p95
p97.5
11 12 13 14 15 16 17 18
10 27 38 25 28 71 67 27
14.9 5.0 5.0 7.6 5.0 7.5 8.9 5.0
14.9 5.0 5.0 7.9 8.4 10.0 11.8 9.7
17.5 5.0 8.2 9.4 11.4 12.3 12.1 12.8
23.2 13.7 11.6 12.9 15.6 16.3 13.7 17.0
29.3 20.7 16.6 17.2 20.2 20.9 19.8 20.6
30.9 29.3 20.7 24.7 25.1 25.4 26.7 26.8
47.3 36.5 28.5 29.3 39.5 31.4 35.0 35.4
51.5 42.2 39.6 29.6 44.7 34.6 38.2 42.6
51.5 42.9 52.7 46.7 45.5 52.0 45.8 46.3
(3.4) (9.2) (13.0) (8.5) (9.6) (24.2) (22.9) (9.2)
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12 Siddiqui AM, Kamfar HZ. Prevalence of vitamin D deficiency rickets in adolescent school girls in Western region, Saudi Arabia. Saudi Med J. 2007;28:441–4. 13 El-Hajj FG, Nabulsi M, Choucair M, Salamoun M, Hajj SC, Kizirian A, et al. Hypovitaminosis D in healthy schoolchildren. Pediatrics. 2001;107:E53. 14 Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. Regional variation and determinants of vitamin D status in sunshine-abundant Thailand. BMC Public Health. 2011;11:853. 15 Narchi H, Kochiyil J, Zayed R, Abdulrazzak W, Agarwal M. Maternal vitamin D status throughout and after pregnancy. J Obstet Gynaecol. 2010;30:137–42. 16 Dawodu A, Dawson KP, Amirlak I, Kochiyil J, Agarwal M, Badrinath P. Diet, clothing, sunshine exposure and micronutrient status of Arab infants and young children. Ann Trop Paediatr. 2001;21:39–44. 17 Dawodu A, Agarwal M, Hossain M, Kochiyil J, Zayed R. Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breast-feeding infants. J Pediatr. 2003;142:169–73. 18 Narchi H, El Jamil M, Kulaylat N. Symptomatic rickets in adolescence. Arch Dis Child. 2001;84:501–3. 19 Andiran N, Celik N, Akca H, Dogan G. Vitamin D deficiency in children and adolescents. J Clin Res Pediatr Endocrinol. 2012;4:25–9. 20 Gonzalez-Gross M, Valtuena J, Breidenassel C, Moreno LA, Ferrari M, Kersting M, et al. Vitamin D status among adolescents in Europe: the Healthy Lifestyle in Europe by Nutrition in Adolescence study. Br J Nutr. 2012;107:755–64. 21 Shin YH, Kim KE, Lee C, Shin HJ, Kang MS, Lee HR, et al. High prevalence of vitamin D insufficiency or deficiency in young adolescents in Korea. Eur J Pediatr. 2012;171:1475–80. 22 Muhairi SJ, Mehairi AE, Khouri AA, Naqbi MM, Maskari FA, Kaabi J, et al. Vitamin D deficiency among healthy adolescents in Al Ain, United Arab Emirates. BMC Public Health. 2013;13:33. 23 Knaysi GA, Crikelair GF, Cosman B. The role of nines: its history and accuracy. Plast Reconstr Surg. 1968;41:560–3. 24 Barger-Lux MJ, Heaney RP. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption. J Clin Endocrinol Metab. 2002;87:4952–6. 25 Cheikh Ismail LI, Al-Hourani H, Lightowler HJ, Aldhaheri AS, Henry CJ. Energy and nutrient intakes during different phases of the menstrual cycle in females in the United Arab Emirates. Ann Nutr Metab. 2009;54:124–8. 26 Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266–81. 27 Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academy Press, 2010. 28 The National Academies Collection. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Institutes of Health, 1997. 29 Gartner LM, Greer FR. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics. 2003;111:908–10. 30 Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–16. 31 Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008;87:1080–6S. 32 Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011;86:50–60. 33 Saadi HF, Nagelkerke N, Benedict S, Qazaq HS, Zilahi E, Mohamadiyeh MK, et al. Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone. 2006;39:1136–43. 34 Koenig J, Elmadfa I. Status of calcium and vitamin D of different population groups in Austria. Int J Vitam Nutr Res. 2000;70:214–20. 35 Gregory JR, Lowe S, Bates CJ, Prentice A, Jackson L, Smithers G, et al. National Diet and Nutrition Survey: Young People Aged 4 to 18 years. Report of the Diet and Nutrition Survey. London: HMSO, 2000. 36 Dong Y, Pollock N, Stallmann-Jorgensen IS, Gutin B, Lan L, Chen TC, et al. Low 25-hydroxyvitamin D levels in adolescents: race, season, adiposity, physical activity, and fitness. Pediatrics. 2010;125:1104–11.
cultural background who are currently living in less sunny, industrialised countries.9,10
Disclaimer statements Contributors None. Funding Research grant from the College of Medicine and Health Sciences, United Arab Emirates University (NP-10-11/104). Conflicts of interest None. Ethics approval Approval was granted by the Al Ain Medical District Human Research Ethics Committee (07/144).
Acknowledgments We thank the staff of the participating schools, the Department of Al Ain Educational Zone, Abu Dhabi Education Council and all the girls who participated and their families. The study was funded exclusively by a research grant from the College of Medicine and Health Sciences, United Arab Emirates University (NP-10-11/104), but they had no role in the study design, collection, analysis and interpretation of data, writing of the manuscript or in the decision to submit the manuscript for publication. There was no external funding.
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