Infant-Child Vitamin D recommendations from NZ (many are wrong) – Feb 2017

Vitamin D deficiency - investigation and management

Produced by Starship Children Organization (charity?) in NZ, Feb 2017

About half of the document is below – see entire document online or   Download the PDF from VitaminDWiki

Table of Contents

Guideline exclusions

• Identification of 'at risk' groups
• Classification of vitamin D status
• Target vitamin D level
• Clinical features of vitamin D deficiency
• Principles of treatment
• Management of children at risk of vitamin D deficiency
• Management of children with clinical vitamin D deficiency
• Treatment monitoring
• Available forms of vitamin D in New Zealand
• Symptomatic vitamin D deficiency with hypocalcaemia, hypophosphataemia and elevated PTH (parathyroid hormone)
• Symptomatic hypocalcaemia
• Vitamin D toxicity
• Primary prevention
• Prevalence
• Vitamin D and sun exposure
• Vitamin D and diet
• Information for Families

Supplementation for pregnant women or lactating mothers - please refer to the Ministry of Health Companion Statement on vitamin D and Sun Exposure in Pregnancy and Infancy in New Zealand 5

Vitamin D is important across all age groups for bone health and metabolism. There is increasing evidence for its role in immune modulation and its anti-inflammatory properties.

Many individuals have multiple risk factors for vitamin D deficiency, including:

• Winter and Spring seasons (exacerbated by more southern latitude)
• Darker skin pigmentation
• Prolonged exclusive breastfeeding
• Being born to a vitamin D deficient mother (more common in dark-skinned, veiled, recent migrant mothers)
• Reduced sun exposure
• Veiled or modest clothing
• Active avoidance of sun exposure
• Chronic illness or disability that prevents regular sun exposure
• Malabsorption syndromes (e.g. Coeliac disease, pancreatic insufficiency)
• Chronic liver or renal disease
• Use of drugs that affect vitamin D synthesis or degradation (eg. Rifampicin, some anticonvulsants)

Classification of vitamin D status (very conservative__
Sufficiency: > 50 nmol/L
Biochemical insufficiency: 30 - 50 nmol/L
Deficiency: < 30 nmol/L

Target vitamin D level
The current recommended lower limit for serum 25(OH)D = 50nmol/L. This defines normal vitamin D status and is the level required for optimal calcium metabolism.6,7 Emerging data from studies in adults examining the relationship between vitamin D status and other health outcomes suggest that 25(OH)D levels of >75nmol/L may be optimal (Nowson CA Med J Aust 2012; 196: 686-687.)

Clinical features of vitamin D deficiency

Vitamin D deficiency is most commonly asymptomatic. However, severe vitamin D deficiency may manifest as rickets with the below clinical features:
Bony Signs
- Swelling of wrists and ankles
- Leg deformities (genu varum or valgum)
- Rachitic rosary in the chest wall ( enlarged costochondral joints)
- Delayed tooth eruption (no incisors by aged 10 months, no molars by age 18 months)
- Craniotabes (softening of skull bones)
- Delayed closure of anterior fontanelle
- Frontal bossing
- Minimal trauma fractures
Non-Bony Signs
- Delayed gross motor development
- Poor linear growth
- Raised intracranial pressure
- Dilated cardiomyopathy
- Symptoms of hypocalcaemia - tetany, stridor, seizure
Radiological features
- Splaying, fraying and cupping of metaphyses
- Osteopenia
Principles of treatment
Treatment choice should be balanced by the following considerations:

• safety of treatment
• adherence considerations, i.e. infrequent higher ("STOSS") dosing or daily lower dosing
• medications that are available and funded in New Zealand
• Management of children at risk of vitamin D deficiency
• Children at risk of vitamin D deficiency but without symptoms or signs generally do not need blood tests and can just commence supplementation.

Age Recommended treatment Stoss is good, but once a year is too infrequent)
< 12 months 400 IU daily (Vitadol C 0.3ml = 10 drops daily)
Advise breastfeeding mother to be checked by her GP for low vitamin D and treated as well
1-2 years Consider annual high dose treatment in Autumn (eg April)
150,000 IU as single dose (3 x 1.25mg capsules* - caps can be opened and mixed with oil or food)
2-5 years Consider annual high dose treatment in Autumn (eg April)
300,000 IU as single dose (6 x 1.25mg capsules* - caps can be opened and mixed with oil or food)
> 5 years Consider annual high dose treatment in Autumn (eg April)
600,000 IU as single dose (12 x 1.25mg capsules* - caps can be opened and mixed with oil or food)

• 1.25mg capsule = Vitamin D3 brand capsule, contains soya oil

Management of children with clinical vitamin D deficiency
150,000 IU as single dose (3 x 1.25mg capsules* - caps can be opened and mixed with oil or food) 2000 IU daily (1.25mg capsule* - mix contents of one capsule* with 10ml soya oil and give 0.4ml daily)
2-5 years 25(OH)D <50 nmol/L
Normal serum Calcium
Normal serum Phosphate High dose treatment
300,000 IU as single dose (6 x 1.25mg capsules* - caps can be opened and mixed with oil or food) 2000 IU daily (1.25mg capsule* - mix contents of one capsule* with 10ml soya oil and give 0.4ml daily)
> 5 years 25(OH)D <50 nmol/L

Normal serum Calcium
Normal serum Phosphate High dose treatment
600,000 IU as single dose (12 x 1.25mg capsules* - caps can be opened and mixed with oil or food) 2000 IU daily (1.25mg capsule* - mix contents of one capsule* with 10ml soya oil and give 0.4ml daily)
† Recommended treatment is based on a combination of international consensus recommendations combined with local experience with use of high dose regimes
†† Alternative treatment can be considered as an alternative to high dose regime. This is based on international consensus and relies on good adherence to daily dosing

• 1.25mg capsule = Vitamin D3 brand capsule, contains soya oil

Treatment monitoring
3 months after STOSS therapy recheck the following to ensure adequate response:

Annual testing of at risk children or those previously treated for Vitamin D deficiency is controversial. Biochemical testing is more expensive than empiric treatment regimes.8

Empiric treatment options include:

Annual STOSS therapy at the start of each autumn season (simple dosing used locally over long term increases vitamin D levels over winter when sun exposure is lowest)
Monthly STOSS therapy
Daily dosing (follows international guidance, however concerns about long term adherence)
Available forms of vitamin D in New Zealand
There are a number of over the counter vitamin D preparations available as either capsules, drops, oral sprays or sublingual preparations. These come predominantly as either as 1000 IU capsules/sprays or 200 IU/0.5ml solutions, or 400IU/drop. None are funded but offer smaller dosages without other Vitamins. Adherence can be a problem with daily lower dose vitamin D supplementation. A larger loading dose of cholecalciferol improves adherence and is funded.

Intermittent high dose therapy is known as STOSS therapy. Starship Endocrinology recommends this for children with symptomatic deficiency. STOSS therapy will provide a 'supraphysiologic' dose that is redistributed into fat and will provide 2-3 month stores of vitamin D. Timing of initiation of STOSS therapy will depend on initial serum calcium and phosphate levels as per table above.

Daily dosing may be considered for either the prevention of vitamin D deficiency or in asymptomatic vitamin D deficiency in a child where compliance with daily therapy can be assured. Note the recommended dietary allowance of Vitamin D is 600 IU from 1 to 18 years of age including pregnancy. From birth to 12 months adequate vitamin D intake is 400 IU daily.

Fully funded formulations
Vitadol C (0.3ml = 400IU Vitamin D)
Preparation contains Vitamin A,C and D
0.3ml is the maximum prescribed dose, higher doses will exceed the maximum safe dose for the accompanying vitamin A in the preparation.
Cholecalciferol capsule 1 tab/capsule = 50,000 IU Vitamin D3 = 1.25mg
Note: these capsules contain soya oil. They must not be prescribed for children known to have a peanut or soya allergy unless under the supervision of the Paediatric Endocrinology Service
Alfacalcidol Drops 2mcg/ml - 1 drop contains approximately 0.1mcg Vit D3 analogue
Note: 1 mcg of vitamin D = 40 IU of vitamin D
Symptomatic vitamin D deficiency with hypocalcaemia, hypophosphataemia and elevated PTH (parathyroid hormone)
Intermittent high dose vitamin D therapy (STOSS therapy) while serum PTH is elevated may cause hypervitaminosis D and severe hypercalcaemia.

Vitamin D toxicity
Vitamin D toxicity is uncommon but can occur due to excessive supplementation and has been seen in doses between 40,000-560,000 IU/kg. 9 It may also occur if an individual has prescribed vitamin D supplements and then also obtains over the counter supplements with high levels of Vitamin D such as cod liver oil.

The main effects of vitamin D toxicity are due to the hypercalcaemia it produces.

Signs and symptoms of hypercalcaemia
Constipation
Abdominal pain and vomiting
Bony pain
Renal calculi +/- renal impairment
Fatigue/behaviour changes
Headaches
Growth restriction in children
Polydipsia
Cardiac arrhythmias (rare)

Other opportunities to prescribe:

At risk infants discharged from paediatric wards after admission with other acute presentations
Through communication to GP in any routine correspondence from clinics/wards etc
Infant formula is fortified with vitamin D at 5mcg/L (200IU/L). Therefore routine supplementation of formula-fed babies is not recommended until they are consuming less than 500ml formula per day.

A recent Otago study has demonstrated that giving mothers 100,000 IU of cholecalciferol will result in a significant rise in infant Vitamin D levels with breastfeeding. This may prove to be another method of preventing vitamin D deficiency in at risk groups during pregnancy (Wheeler et al. J Nutr. 2016 Aug 24. pii: jn236679.)

At risk, asymptomatic children

For asymptomatic children with multiple risk factors for vitamin D deficiency, our current recommendation is to check baseline serum 25(OH)D level, serum calcium and phosphate to confirm deficiency BEFORE the initiation of intermittent high dose vitamin D therapy (STOSS therapy).

Repeated vitamin D testing is more expensive than pragmatic empiric treatment regimes in a child with ongoing multiple risk factors for vitamin D deficiency as it is most likely that the serum testing will just confirm clinical suspicion of a low vitamin D level. (see Treatment monitoring).

Some children at very high risk may need high dose vitamin D supplementation more often than annually. If suspected then serum 25(OH)D concentration should be measured to guide prescribing.

Some recently arrived migrant children with known risk factors for deficiency may have normal vitamin D status on arrival to NZ. These children should have their vitamin D level re-checked at the end of their first NZ winter.6

Prevalence
In 2002 a study of the nutritional status of a random ethnically stratified sample of 413 Auckland children aged 6-23 months found:

Vitamin D deficiency present in 10% (defined by a serum 25-hydroxy-Vitamin D concentration 25(OH)D <27.5nmol/L, the 25(OH)D concentration that defines a child as being at risk of rickets)
Risk of vitamin D deficiency 7 times higher in children whose vitamin D status was determined during winter versus summer.
Prevalence of vitamin D deficiency (in the summer?) varied with ethnicity:

• Pacific 24%,
• Maori 11%,
• European 3% and
• Other Ethnic Groups 16% .1,2

In a recently published study of vitamin D status of exclusively breastfed infants in Auckland aged 2-3 months, 24% were vitamin D deficient (25(OH)D <27.5nmol/L).3 A group at particular risk of symptomatic deficiency presenting to Starship Children's hospital are Indian children from vegan families.4 .

Vitamin D and sun exposure
Exposure of the skin to ultraviolet B (UVB) from sunlight is the main source of Vitamin D synthesis for most people. It is estimated to provide over 90% of Vitamin D in humans.11

The ability to synthesise adequate Vitamin D depends on skin colour, timing and amount of sun exposure as well as seasonal changes in UVB levels, cloud cover and the latitude of place of residence.

There are no specific paediatric data available as to the amount of sun exposure required for different skin types to synthesise adequate Vitamin D. Therefore it is not possible to make a single recommendation for amount of sun exposure required that would suit all children.
(No NZ. Aust data – but lots of data from other countries)

All prescriptions for Vitamin D therapy must be accompanied by appropriate education with regards to safe sun exposure.

References (Limited to Aust or NZ?)

• Grant C et al (2009), Vitamin D Deficiency in early childhood: prevalent in the sunny South Pacific; Public Health Nutrition: 12(10), 1893-1901
• Gartner LM, Greer F. Prevention of Rickets and Vitamin D Deficiency: New Guidelines for Vitamin D Intake. Section on Breastfeeding and Committee on Nutrition. Pediatrics 2003;111:908-10.
• Wall CR, Grant CC, Jones I (2013), Vitamin D status of exclusively breastfed infants aged 2-3 months; Arch Dis Child 98:176-179
• Blok BH, Grant CC, McNeil AR, Reid IR. Characteristics of children with florid Vitamin D deficient rickets in the Auckland region in 1998. New Zealand Medical Journal 2000;113:374-6.
• Ministry of Health ( 2013). Companion Statement on Vitamin D and Sun Exposure in Pregnancy and Infancy in New Zealand.
• Australasian Paediatric Endocrine Group ( 2013). Vitamin D and health in pregnancy, infants, children and adolescents in Australia and New Zealand : a position statement. Med J Aust 2013; 198(3):142-148
• Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and Vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011;96:53-8
• Grey A, Bolland M, Davidson J (2012). Vitamin D testing; The Lancet vol 379 p 1699
• Vogiatzi MG1, Jacobson-Dickman E, DeBoer MD; Drugs, and Therapeutics Committee of The Pediatric Endocrine Society. Vitamin D supplementation and risk of toxicity in pediatrics: a review of current literature. J Clin Endocrinol Metab. 2014 Apr;99(4):1132-41
• Dawodu A, Wagner CL. Mother-child Vitamin D deficiency: an international perspective. Archives of Disease in Childhood 2007;92:737-40.
• Ministry of Health ( 2012). Consensus Statement on Vitamin D and Sun Exposure in New Zealand
• Best Practice Advisory Centre (2011). Vitamin D Supplmentation: navigating the debate; BPJ : Issue 36 pp26-33
• Ministry of Health (2013). Vitamin D and your baby. Available at http://www.health.govt.nz/your-health/healthy-living/babies-and-toddlers/vitamin-d-and-your-baby (accessed July 2013) http://www.medsafe.govt.nz/safety/EWS/2016/AlertVitaminD.asp
• Munns et al (2015) Global Consensus Recommendations on Prevention and Management of Nutritional Rickets. J Clin Endocrinol Metabol 100:0000-0000