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Keywords:

  • endocrinology;
  • general paediatrics;
  • infectious diseases

Abstract

  1. Top of page
  2. Abstract
  3. What is already known
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. Acknowledgements
  9. References

Aims

The primary aim of this study was to determine the frequency of vitD deficiency/insufficiency in an opportunistic sample of Northern Territory (NT) children. The secondary aim was to evaluate whether: (i) 25(OH)vitD (25(OH)D) levels differ between Indigenous/non-Indigenous children; and (ii) VitD insufficiency is associated with increased acute/infective hospitalisations.

Methods

Twenty-five (OH)D levels were measured in 98 children <16 years between August 2011 and January 2012 (children hospitalised acutely/non-acutely and well children from other studies based in Darwin). VitD deficiency was defined as 25(OH)D < 50 nmol/L, and insufficiency was postulated to be <75 nmol/L. Demographic data were collected, and computer records were reviewed.

Results

Median age was 59 months (range 2–161); 3.1% were vitD deficient, 19.4% insufficient. There was no significant difference in mean 25(OH)D level between Indigenous (93.2, standard deviation (SD) 21.9, n = 42) and non-Indigenous (97.3, SD 27.9, n = 56) children (P = 0.32). Median number of hospitalisations/year were similar (P = 0.319) between vitD sufficient (0.34, range 0–12, n = 76) and insufficient (0.22, 0–6, n = 22) children. There was no significant difference between number of infective admissions per year between vitD sufficient/insufficient groups (P = 0.119).

Conclusions

Compared with US data (19% deficient, 65% insufficient) fewer NT children are vitD deficient/insufficient. In our limited sample, being vitD insufficient was not associated with increased acute/infective hospitalisations, but a larger unbiased sample of NT children is needed. More information is needed about the optimum level of vitD for non-bone-related health in children.


What is already known

  1. Top of page
  2. Abstract
  3. What is already known
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. Acknowledgements
  9. References
  1. VitD deficiency has been associated with an increased risk of infection.
  2. VitD deficiency is widespread, but there is limited data on prevalence in children and in Indigenous children specifically.
  3. There is a high burden of infectious disease in Northern Territory (NT) children.
  4. There is controversy about the optimum vitD level for non-calcium homeostasis-related health.

What this paper adds

  1. Top of page
  2. Abstract
  3. What is already known
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. Acknowledgements
  9. References
  1. VitD deficiency is less of a problem in children in the Northern Territory than those in the USA/UK.
  2. There was no significant difference in mean VitD level between Indigenous and non-Indigenous children.
  3. We found no correlation between VitD deficiency/insufficiency and increased number of infective hospitalisations.

Vitamin D (VitD) deficiency and insufficiency have been recognised as a public health issue in many countries.[1] VitD deficiency is increasingly becoming associated with the presence and/or severity of non-bone-related diseases such as asthma, cardiac disease and certain malignancies.[2, 3] VitD has an immune-modulatory role and its deficiency has also been implicated in both viral and bacterial infections.[3]

Indigenous Australian children have a high prevalence and burden of infectious disease.[4] Those living in the Northern Territory (NT) have some of the highest reported rates of hospitalised pneumonia worldwide.[5] Data about the vitD status of NT children would therefore be useful to inform policy and possible intervention. There is currently no published data on vitD status in NT children. The limited Australian data available have reported prevalence rates of vitD insufficiency (25(OH)D< or = 50 nmol/L) 40.5%, 37.4% and 67.3% in adults living in South East Queensland, Geelong and Tasmania, respectively.[6] The prevalence of vitD deficiency in adults in Townsville was 9%.[7] In refugee children in Sydney rates of 58.8% were recently reported.[8] The sole study on vitD deficiency (defined as levels <60 nmol/L) in an Indigenous Australian population reported a prevalence of 65%.[9]

The definition of vitD sufficiency and insufficiency in both children and adults is controversial as the optimal level of 25(OH)D for its non-bone physiological actions is unknown.[10] The definition of vitD deficiency has traditionally been based on its role in calcium metabolism. The American Academy of Paediatrics defined vitD deficiency as ≤50 nmol/L but has postulated that levels of <75 nmol/L may be insufficient.[1] Carmango et al. (2011) reported decreased respiratory infections in the first 3 months of life in infants with a cord vitD level of >75 nmol/L compared with those with levels of 25–75 nmol/L.[11] The Australian Paediatric Endocrine Group (APEG) define normal 25(OH)D levels in children as being >50 nmol/L, and deficiency as ≤50 nmol/L but have not defined vitD insufficiency.[10] For the purposes of this study we have defined vitD deficiency as <50 nmol/L and have postulated that insufficiency may be <75 nmol/L.

Given the lack of vitD data in NT children who have a high burden of infectious disease, we undertook an opportunistic study in 100 children.[4] We related their serum 25(OH)D levels to their ethnicity and number of acute/infective hospitalisations.

Methods

  1. Top of page
  2. Abstract
  3. What is already known
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. Acknowledgements
  9. References

Study population

One hundred children aged <16 (median 56 months) who presented to Royal Darwin Hospital, NT, Australia, over a 6-month period between August and December 2011 and required venepuncture or intravenous cannulation for another reason were recruited prospectively following informed consent from the parent/guardian. Children previously known to be vitD deficient or those children already on vitD supplementation were excluded from the study. Patients were recruited from the day surgery unit, inpatient wards/emergency department and from concurrently running studies in Royal Darwin Hospital. The study was approved by the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (#2011-1633 and #07-63).

Clinical and socio-demographic data were collected using standardised data collection forms. Hospitalisation for infection was defined as overnight stay in hospital for treatment of an acute infectious disease. As the children varied in age, hospitalisations were calculated as hospitalisations per year.

VitD analysis

Venous blood was collected in heparinised tubes and the plasma collected and stored at −80°C within 24 h. The samples were transported frozen to Queensland Health Pathology, Brisbane, Queensland, for quantification of 25(OH)D (nmol/L) by chromatography/mass spectrometry. VitD deficiency was defined as 25(OH)D < 50 nmol/L and insufficiency postulated to be <75 nmol/L.

Statistical analyses

The results were analysed using Microsoft Excel (Microsoft Corp., Redmond, WA, USA) and SPSS 18.0 (PASW Statistics 18; SPSS Inc., Chicago, IL, USA). Data conforming to a normal distribution was assessed for significance using a t-test; other data were analysed using a Kruskal–Wallis test, two-tailed P-value of <0.05 were considered significant.

Results

  1. Top of page
  2. Abstract
  3. What is already known
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. Acknowledgements
  9. References

Patient characteristics

Over the 6-month period, 100 children were recruited, and sufficient blood for vitD analysis was obtained in 98 children. No children were excluded as none had previously been diagnosed with vitD deficiency or were on vitD supplements. The median age of the cohort was 56 months (range 2–161). Other demographics of the children are outlined in Table 1.

Table 1. Socio-demographics of the children (n = 100)
  1. a

    Data missing in 34 children. HRCT, high resolution computed tomography.

EthnicityNon-Indigenous57%
Indigenous43%
SexMale65%
Female35%
Age groupInfant8%
1–5 years43%
5–16 years48%
GestationTerm76%
Preterm7%
Unknown17%
Living environmentRural31%
Urban67%
Unknown2%
Place of recruitmentWards/ED38%
Daycase procedure unit33%
HRCT/bronchoscopy list16%
Healthy blood drive13%
Mean weight z-scores (n = 66a)Indigenous−0.6
Non-Indigenous0.2
Overall−0.3

Of the 98 children in whom sufficient blood was collected for analysis, three children (3.1%) were found to be vitD deficient. Of these, two were mildly deficient (25–50 nmol/L), and one severely deficient (<12.5 nmol/L). Two of the three children identified as being deficient had risk factors for vitD deficiency; the severely vitD deficient child was a 10-year-old boy admitted with nephrotic syndrome. Of the mildly vitD deficient children, one was an Indigenous child hospitalised with sepsis requiring an intensive care unit admission, and the second child had no known risk factors for vitD deficiency and had a normal level on repeat testing.

Nineteen children (19.4%) were vitD ‘insufficient’ (50–75 nmol/L), and the rest (n = 76, 77.6%) were deemed ‘sufficient’. Of the 19 children who were vitD insufficient, 48% were Indigenous and 52% non-Indigenous.

There was no significant difference (P = 0.33) in the mean 25(OH)D (nmol/L) between Indigenous children (n = 42, mean 92.2) and non-Indigenous children (n = 64, mean 97.3).

For the total cohort, the median number of hospitalisations/year was 0.3. There was no significant difference (P = 0.32) in median number of hospitalisations per year according to vitD sufficiency (n = 76, median 0.34, range 0–12) or insufficiency/deficiency (n = 22, median 0.22, range 0–6). There was no significant difference (P = 0.12) in the median number of infective hospitalisations per year between vitD sufficient (0.42, range 0–6) and insufficient (0, range 0–1.7) groups. There was no correlation between vitD and infective admissions/year (P = 0.89).

Discussion

  1. Top of page
  2. Abstract
  3. What is already known
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. Acknowledgements
  9. References

In this small opportunistic study of 98 NT children, we found relatively low levels of vitD deficiency and insufficiency. Although the number of hospitalisations for infections was high for the cohort (83 admissions, mean of 0.38 admissions/year), there was no difference between children grouped according to vitD status.

VitD deficiency/insufficiency has been recognised as a significant problem in the USA and the UK.[1, 12] A large prevalence study of children aged 1–11 years was carried out in the USA, showing that <1% of children had levels <25 nmol/L, 18% <50 nmol/L and 95% had levels <75 nmol/L.[1] A similar study in the UK found that 35.1% of children aged 4–17 years had 25(OH)D levels <50 nmol/L.[12] As the main source of vitD is sunlight, the most likely major reason for the lower prevalence of vitD deficiency/insufficiency in Darwin is its higher average number of hours per year of sunlight; in Darwin it is 8.4 h per day (approximately 3102 h per year)[13] whereas across the UK it is 1354.9 h per year.[14] Our data are also in contrast to the limited available Australian data (described in the introduction) showing a prevalence of vitD deficiency of 37–67%.[6, 8, 9]

We found no significant difference between the numbers of acute or infective hospitalisations per year depending on vitD status. There have been multiple studies documenting possible associations between clinical rickets and a predisposition to infection.[15] Muhe et al. found a probable correlation between the development of pneumonia and the presence of clinical rickets in children in Ethiopia suggesting the role of vitD in immune system.[16] The immune-modulatory actions of vitD were first demonstrated in Mycobacterium tuberculosis–infected macrophages, and there is evidence that the mechanism by which vitD impacts on the immune system includes the upregulation of cathelicidin and β-defensin, antimicrobial peptides of the innate immune system.[3]

The strengths of this study are that the sample ethnicity was representative of the NT population[17] and that is was possible to accurately record the number of hospitalisations due to the electronic health record of the NT. The limitations of the study are that due to our small numbers of vitD deficient children it is difficult to confidently say that there is no association between vitD status and acute/infectious hospitalisation. Further larger studies looking at children in the community as well as in hospital recruited over a longer time period (taking seasonal variation in sunlight exposure into account) would help to clarify this matter. As the majority of children were recruited from a hospital environment this is likely to bias our results; however, it is more likely that vitD deficiency would be overrepresented rather than underrepresented in this population.

Non-bone-related vitD deficiency causation and/or increased severity of various diseases currently has high profile in the literature, leading to increased vitD testing (and thus increased cost) worldwide. In Australia, the cost of vitD testing has increased by nearly a hundredfold since the year 2000.[18] Further, others have expressed concern over the mismatch between high quality evidence and causation.[19] Our pilot study contributes to this debate as our data do not support the routine screening of children in the NT as it is very unlikely that vitD deficiency contributes to their high burden of infectious disease in our setting. Our study does not support aiming for a vitD level of >75 nmol/L in children, we recommend continuing to follow the APEG guideline, aiming for vitD levels >50 nmol/L.[10]

Acknowledgements

  1. Top of page
  2. Abstract
  3. What is already known
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. Acknowledgements
  9. References

Without the help of the respiratory team at the Menzies School of Health Research and the support of the paediatric department at Royal Darwin Hospital this project would not have been possible. The study is supported by a NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children grant (number 1040830). AC (grant 545216) is supported by a NHMRC practitioner fellowship.

References

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  2. Abstract
  3. What is already known
  4. What this paper adds
  5. Methods
  6. Results
  7. Discussion
  8. Acknowledgements
  9. References
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    Muhe L, Lulseged S, Mason KE, Simoes EA. Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children. Lancet 1997; 349: 18011804. Elsevier.
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    Harvey NC. Vitamin D: some perspective please. BMJ 2012; 345: e4695.