1. Vitamin D Supplementation in Healthy Children and Adolescents SCH Journal Club Rachel Harrison 20 th September 2012

2. Background Vit D plays an essential role in maintaining good health: –calcium and phosphate regulation –may regulate cell growth, neuromuscular and immune function, and reduction of inflammation. Sunshine! Vitamin D supplementation agenda since 1990’s An independent advisory committee is reviewing current recommendations on vit D (expected 2014)

4. Background Vitamin D deficiency serum 25(OH)D level ≤25nmol/l Insufficiency serum 25(OH)D level between 26 and 50nmol/l

5. DOH DOH says the following people may be at risk of vit D deficiency: –all pregnant and breastfeeding women –all children aged under five years old –all people aged 65 or over –people who are not exposed to much sun –people who have darker skin (because their bodies are less able to produce as much vit D)

6. Current Guidelines http://www.sheffield.nhs.uk/professionals/resources/Vita min_D_guidelines_children_Final_March%202012[1].pdfhttp://www.sheffield.nhs.uk/professionals/resources/Vita min_D_guidelines_children_Final_March%202012[1].pdf Advice – obtain Vit D from safe sun exposure and diet. Improving availability and uptake of Vit D supplements for children in multiethnic populations is essential to the strategy of rickets prevention. During treatment of deficiency consider referral to secondary care at any stage if new symptoms cause parental or professional concern.

7. Trust Policy

8. Available multivitamin preparations ProductVitamin D contentDoseOther considerations Healthy Start Drops (10ml). Multivitamin preparation Colecalciferol – 300IU per 5 drops 300IU / dose (5 drops)Free from soya and peanut residues Dalivit (25ml or 50ml bottles). Multivitamin preparation Licensed product. Ergocalciferol 400 IU per 0.6 mL 6 weeks- 1year –200IU - 0.3ml (7drops) daily ≥ 1 year 400IU = 0.6ml = 14 drops daily Can be added to squash, juice, milk or jam for ease of administration. Does not contain peanut oil or soya Abidec (25ml) Multivitamin preparation Licensed product Ergocalciferol 400 IU per 0.6 mL, Birth -1year -200units – 0.3ml (7drops) daily ≥ 1 year 400iu = 0.6ml = 14 drops daily Contains peanut oil. Contraindicated in patients with a peanut allergy. Also avoid in patients with a soya allergy. Adcal D3 chewable tablets / caplets Contains calcium and Vitamin D Chewable tablets - Colecalciferol 400IU /tablet (and 600mg Calcium) Caplets –colecalciferol 200IU/caplet (and 300mg Calcium) Chewable tablets – One daily (only licensed in children above 12 years) Caplets – Two daily (only licensed in children above 12 years) Please note the difference strengths between the chewable tablets and the caplets Contains soya oil in the chewable tablets. Refer to SPC for full list of excipients.

9. The Clinical Question PopulationHealthy children and adolescents InterventionVitamin D supplementation ComparisonPlacebo OutcomeBone Density Study DesignSystematic Review

10. Effects of Vitamin D supplementation on bone density in healthy children: a systematic review Winzenberg,T. Powell, S. Shaw, K A. Jones, G. BMJ. 2011;342:c7254.

11. Objectives To determine effectiveness of Vitamin D supplementation for improving BMD in children and adolescents To determine if effects of supplementation vary with factors such as vitamin D dose and status

12. Methods Systematic review and meta-analysis RCT’s of vitamin D supplementation including a placebo control Children and adolescents aged 1 month to <20 years Identification of papers –Databases –Conference abstracts –Cited references

13. Methods Extracted data by 2 reviewers Percent change in baseline of bone outcomes Standardised mean difference Hetrogeneity Fixed effects model

14. Outcomes BMD – spine, radius, hip BMC – total body Subgroup analysis –Age –Gender –Pubertal stage –Vitamin D dose –Vitamin D status

15. Results – Papers Reviewed 1653 papers identified 1599 excluded 54 disagreements 6 German papers 23 full text review 4 not RCTs 3 children not 1/12 to <20 yr 2 not bone outcomes 1 not Vit D intervention 1 not placebo controlled 6 studies included in meta analysis 1 no variance measured reported 12 papers for 7 studies

16. Results – Baseline Characteristics Event Title If Required (Change Text in Footer)

17. Results – Main Effects Event Title If Required (Change Text in Footer)

18. Results – Forrest Plot Event Title If Required (Change Text in Footer)

19. Results – Vit D Status

20. Are the results of the review valid? Did the review address a clearly focused question? Yes – Clear population, intervention, and outcome Did the authors look for the appropriate sort of papers? Yes – RCT’s placebo controlled

21. Is it worth continuing? Do you think the important, relevant studies were included? Yes – appropriate databases searched, no language restrictions, reference lists of cited studies searched, conference abstracts Did the review’s authors do enough to assess the quality of the included studies? Yes – independently assessed by 2 reviewers If the results of the review have been combined, was it reasonable to do so? Yes – Similar studies, similar outcomes

22. What are the results? What are the overall results of the reviews? LS BMD 0.15 (-0.01 to 0.31; p=0.07) standardised mean difference Supplementation not beneficial in children and adolescents with normal Vit D levels In deficient children may be useful, but needs confirmation How precise are the results? Not sure – Confidence intervals reported, standardised mean difference

23. Will the results help locally? Can the results be applied to the local population? Yes - children 8-17 yrs Were all important outcomes considered? Not sure – main outcome covered Are the benefits worth the harms and costs? No

24. Summary and Conclusions Overall a good paper Publication of negative results Clear bottom line reported For clinicians and other health professionals: No action to be take. What this space.