An Update on Vitamin D. Professor Zulf Mughal Consultant in Paediatric Bone Disorders Royal Manchester Childrens Hospital Manchester, UK

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1 An Update on Vitamin D Professor Zulf Mughal Consultant in Paediatric Bone Disorders Royal Manchester Childrens Hospital Manchester, UK

2 Overview Sources & Metabolism of Vitamin D Consequences of Vitamin D deficiency in Children & Adolescents Prevention of Vitamin D deficiency Answers to some key questions

3 Vitamin D: Sources & Metabolism

4 Sources & Metabolism of Vitamin D Solar UVB ( nm) Endogenous Vitamin D 3 (7-dehydoxycholesterol) DBP Liver 25-hydroxylase (CYP2R1) Dietary source Vitamin D 2 & D 3 Oily fish, eggs, fortified foods DBP 25-Hydroxyvitamin D (major circulating metabolite) Kidney 24,25-dihydroxyvitamin D Calcitroic acid 24-hydroxylase (CYP24A1) 1α hydroxylase (CYP27B1) 1,25-Dihydroxyvitamin D PTH (+) P (+) FGF23 (-)

5 Factors which contribute to development of Vitamin D deficiency Residence in Northern or Southern Latitudes Pigmented skin Sun blocking creams Factor 8 Vit D synthesis by >95% Sunshine avoidance for religious or cultural reasons Cloud Cover & Atmospheric Pollution Obesity Genetic propensity An independent protective effect of meat consumption Low dietary Calcium intake

6 Vitamin D Supplementation During Pregnancy & Lactation

7 Prolonged Breast-feeding without Vitamin D supplementation in Infants born to Vitamin D deficient Mothers Infants born to vitamin D deficient mothers - infant s serum 25OHD ~75-105% maternal concentrations. Prolonged breast feeding - a litre of human breast milk ~ 40 I.U. of Vitamin D. Breast milk calcium concentration of vitamin D deficient mothers ~16% lower than that of vitamin D replete mothers (Arch Dis Child 2008;93:179). No vitamin D supplements provided to mothers or infants. Mughal, Salama, Greenaway, Laing & Mawer. Florid rickets associated with prolonged breast-feeding without vitamin D supplementation. BMJ 1999;318(7175):39-40

8 The Nutritional Vitamin D & Rickets Global Consensus Group May 2014 Societies ESPE PES SLEP JSPE ASPAE ISPAE CSPEM APPES APEG ESPGHAN Craig F. Munns, Nick Shaw, Mairead Kiely, Bonny L. Specker, Thomas D. Thacher, Keiichi Ozono, Tochimi Michigami, Dov Tiosano, M Zulf Mughal, Outi Mäkitie, Lorna Ramos-Abad, Leanne Ward, Linda Dimeglio, Navoda Atapattu, Hamilton Cassinelli, Christian Braegger, John M. Pettifor, Anju Seth, Hafsatu Wasagi-Idris, Vivajalakshmi Bhathia, Junfen Fu, Gail Goldberg, Lars Sävendahl, Rajesh Khadgawat, Pawel Pludowski, Jane Maddock, Elina Hypponen, Abiola Oduwole, Emma Frew, Magda Aguiar, Ted Tulchinsky, Gary Butler, Wolfgang Högler Munns et al The Journal of Clinical Endocrinology & Metabolism :2,

9 Influence of Vitamin D Supplementation in Pregnancy on Breast Milk Vitamin D. Munns et al The Journal of Clinical Endocrinology & Metabolism :2,

10 Risk of Maternal Vitamin D Excess Munns et al The Journal of Clinical Endocrinology & Metabolism :2,

11 Vitamin D Supplementation in Pregnancy & Lactation Recommendations: Pregnant & lactating women should ensure they meet the dietary recommendations for vitamin D (600 IU/day) for their own needs, but not for the needs of their infant. Lactating women should not take high amounts of vitamin D as a means of supplementing their infant. Munns et al The Journal of Clinical Endocrinology & Metabolism :2,

12 Vitamin D deficiency in Infancy & Childhood

13 Vitamin D deficiency in the Neonatal Period & Early Infancy Infants born to vitamin D deficient mothers: Tetany Stridor Seizures Dilated Cardiomyopathy & heart failure

14 Life threatening Cardiomyopathy in Early Infancy 16 infants (6 South Asian, 10 Black ethnicity) admitted to GOS with Heart Failure Median age 5.3 months (3 weeks - 8 months);12 exclusively breast-fed 12 needed inotropic support 8 ventilated & 2 needed ECMO 2 referred for cardiac transplantation 6 suffered a cardiac arrest & 3 died! Median (range) Reference range Calcium (mmol/l) 1.50 ( ) PTH (pmol/l) 34.3 ( ) OHD (nmol/l) 18.5 ( ) >50 Fractional shortening (%) 10 (5-18) Left ventricular end diastolic dimension Z score 4.1 (3.1-7) -2 < +2 Maiya S et al Hypocalcaemia and Vitamin D deficiency: an important, but preventable cause of life threatening infant heart failure. Heart (5):581-4

15 Hospitalisation for Children with Rickets in England Goldacre et al. The Lancet, Volume 383, Issue 9917, pages (2014)

16 Rickets in Toddlers Video

17 Severe Motor Developmental Delay in a 2 yr Old Secondary to Vitamin D Deficiency

18 Vitamin D Deficiency in Adolescents Tetany & Convulsions Limb pains Lower limb & pelvic deformities

19 Myopathy Secondary to Vitamin D Deficiency 8 th April 09 5 th May 09 Pre Rx Post Rx 25(OH)D (ng/ml) < PTH (ng/ml) (10-60) Calcium (mmol/l) ( ) Phosphate (mmol/l) ( ) Alk Phos (I/U) ( ) Rx: Single orally dose 180,000 IU Vitamin D mg/day Ca supplement

20 Optimum Levels of (Vitamin D) Serum 25OHD & Non-skeletal Effects of Vitamin D Deficiency

21 Definition of Vitamin D Sufficiency [serum 25(OH)D level] The Institute of Medicine (USA) recommendation: Vitamin D sufficiency defined as serum 25(OH)D level of 50 nmol/l. The Endocrine Society (USA) recommendation: Vitamin D sufficiency defined as serum 25(OH)D level of 75 nmol/l. European Society of Paediatric Gastroenterology, Hepatology & Nutrition Committee on Nutrition recommendation: Vitamin D sufficiency defined as serum a serum 25(OH)D level of 50 nmol/l & severe deficiency as serum 25(OH)D level of < 25 nmol/l.

22 The Use of Cod Liver Oil to Prevent Rickets Taken from Google Images

23 2 nd February 2012

24 Healthy Start Vitamin Tables for Pregnant & Lactating Mothers (A, C & D) 10 micrograms of vitamin D3/tablet Children s Healthy Start Vitamin drops contain (5 drops daily): 233 micrograms of vitamin A 20 milligrams of vitamin C 7.5 micrograms of vitamin D3 (

25 In 2006, free vitamin D supplements available to: Arch Dis Child 2012;97: All women from the start of pregnancy until their child was 12 months old. All children under 5 years old. Supplement uptake rate rose by 17%.

26 Sunbathing?

27 Sunbathing? A consensus vitamin D position statement by the British Association of Dermatologists, along with a number of other health organisations, advises: The time required to make sufficient vitamin D is typically short and less that the amount of time needed for the skin to redden and burn. Regularly going outside for a matter of minutes around the middle of the day without sunscreen should be enough. Reference: Sunscreen factsheet, the British Association of Dermatologists,

28 Serum 25(OH) Levels after Simulated Summer Sunlight Exposures in Whites & South Asians 109 Whites 15 South Asians Farrar et al Am J Clin Nutr. 2011;94(5):

29 Questions How to treat in pregnancy/breast feeding Supplement mother & her infant If GP suspects Vitamin D deficiency, what should they do? Refer cases of rickets to local Paediatric unit & treat osteomalacia Nutrition and the under 5's 400 i.u. vitamin D daily, especially in dark-skinned children Who is responsible for Vitamin D prescribing? Mainly GPs although Rx may be started in hospital Myth busting on Vitamin D - who needs it? We all need supplements at least during september to March

30 Thank You