Vitamin D Deficiency in Children:

a call for a network approach

Colin Michie

No commercial interestsNo conflicts of interest

Ealing Hospital ICO

Outline

• Why children?

• Perspectives

• What initiated my interest in vitamin D?• Patters of variation • Implications for presentation, diagnosis, treatment

(including a brief look at vitamin D toxicity)• Problems identified relating to vitamin D in west London• Gap analysis: precautions, monitoring: a networked

approach

Some biology and paediatrics

• Biological view of infant mortality

• Nutrition in pregnancy, infancy, breast-feeding• Adolescents and the next generation• Social evolution • Imprinting or late effects

The infant is the crucible of our species (we must strive to get infancy right!)

A series of hypocalcemic

seizures

• January 2007 three hypocalcemic seizures presented over a weekend in Ealing Hospital

• Case series: 18 cases (M 8, age 2.5-6 weeks)• Corrected calcium levels at presentation (1.19-1.46 mmol/l normal

2.15-1.55)• Vitamin D levels at presentation (2.3-15 nmol/l)• Alkaline phosphatase (350-2300 IU/l, normal up to 300)• Ethnicity (15 Asian or Afro-Caribbean, 7 Somalian)

The biology of vitamin D deficiency is variable

4 years later

• 13 well and asymptomatic, normal growth patterns (others lost to follow-up)

• 4/13 achieved 1,25 OHD > 80 nmol/l, 3/13 never > 50 nmol/l• 4/13 showed gross motor delays• 2/13 have damage to tooth enamel• Follow-up continues

The outcome of severe deficiency varies; moderate to mild deficiency is common

Serum Vitamin DOctober 2009 to December 2009

65

1231

1105

790

312 292240 226 205

159127 109 85

59 8149

22 37

0

200

400

600

800

1000

1200

1400

10 20 30 40 45 50 55 60 65 70 75 80 85 90 100 110 120 >120

Serum Vitamin D nmol/L

Fre

qu

ency

Homo sapiens

• We are the same species!

Variation…

Variation

• ‘Hapmap 3’: http://hapmap.ncbi.nlm.nih.gov/publications.html.en

• Binding to sites on genome• Binding to sites with known disease associations• Clinical associations

Just how wide is the variation in our species in the responses/biology of vitamin D?

The complex system

Variations

• Rates at which system functions • Metabolic activity of components (vitamers)• Binding proteins for individual metabolites• Role of other metabolites e.g. calcium,

phosphate, magnesium, vitamin A

A helpful cloud?

Return to biology

• The complex system has at least two rate limiting points:

• Skin (homeostatic system)• Renal hydroxylation (Type 1)• ? Intranuclear (Type 2)

What is the outcome of abnormalities at these points? Studies of rare disorders have value

The complex system

Some unpopular points

• Normal curves – what about the top 5%?• Crucial to define in order to proceed with clear risk

definitions• The vitamin OTC market has proved recession resistant:

how can we find out about self-medication?• Prescriptions for vitamin D are soaring

A problem at the zoo…

Vitamin D Toxicity

• What biological system should one test?• What are the variations within populations?• What level of vitamin D is dangerous, what level is

‘toxic’?• Hypercalcemia and hypercalcuria, with fatigue, muscle

pain or weakness, polyuria and polydipsia, high blood pressure [blood tests… 24 hour urine tests…!]

• BPSU study planned

Returning to Ealing…

• In 2011/2012: known 4 cases of hypercalcemia, one symptomatic, related to vitamin D overdose. All caused by over-supplementation by parents. • Corrected serum calcium: 2.7-3.0, urinary calcium > 350 mg/day

in all cases

• Others have observed unexpected levels of hypercalcemia

• No good epidemiology relating to this problem: what is the system whereby overdose is managed and preferably avoided?

Problems identified

• Lack of knowledge relating to vitamin D in antenatal clinics, both among mothers and staff. No concept of requirement or risk Identified in adolescents in ward school

• Lack of compliance with national recommendation for vitamin supplements and antenatal care; Healthy Start vitamins not available, licence debates

• Lack of appreciation of the importance of obesity• Maps…

Geography of hypocalcemic

seizure

Geography: blood tests for

vitamin D

Geography: Top 10 prescribing

practices for vitamin D supplements

Mapping observations

• There is variation in clinical symptoms and care provision at the level of the street

• The distribution of cases corresponds with socioeconomic factors

• There is no more/very little new funding to change this• (High levels of vitamin D were in W5 and W13)

Gaps

• Deficiency in this nutrient, related to geography and lifestyle, particularly for lower socioeconomic groups

• Distances between scientific knowledge and clinicians are growing

• Sources of messages or information relating to vitamin D are diversifying and multiplying

• UK studies show varied understanding, poor compliance with existing guidelines, incomplete guidelines and problems with reasonably priced, licensed medications

• There will be no more funding

Systems analysis: educate the public and professionals, develop a network, manage that network

Stratgies for the future

• Introduce yourself to your neighbours: network• Clinical networks (www.rcpch.ac.uk/networks)

• Create, participate, identify goals, publish• Guidelines needed: concordance and publication

• Maps (www.rightcare.nhs.uk)• Standards• Peer review

Conclusions

• Vitamin D deficiency is a public health problem, treatment of which will require a robust approach including careful monitoring

• Accurate and informed education of the public and professionals is required

• Meetings of this nature are critical in establishing a network to promote responsible management

RCPCH Nutrition CommitteeColin.Michie@eht.nhs.ukColinmichie@nhs.net

Acknowledgements and Thanks

• The organisers of this meeting

• Patients and colleagues who have helped collect details and perform audits (school teachers and junior mayor)

• Patients and colleagues who have, and I hope will continue to point out my significant areas of ignorance