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Low Vitamin D

  • Background

    Vitamin D is essential for bone and muscle health, and there is evidence it is important in other aspects of health. Vitamin D refers to both D3 (cholecalciferol) and D2 (ergocalciferol) - D3 is produced in the skin through the action of UVB in sunlight, it is the most common form in food and the form available in supplements. Mushrooms contain small amounts of D2.

    Sunlight is the most important source of vitamin D, and is estimated to provide 90% of vitamin D in humans.1

    • The amount of UVB available for skin synthesis varies with latitude, season, time of day, shade, and skin exposure (e.g. clothing). Window glass blocks UVB. There may not be enough UVB during winter months in the Southern states to maintain adequate vitamin D levels.
    • Adults with dark skin require 2-7 times the amount of UVB compared to people with light skin to produce similar vitamin D levels.2 There are no data on skin synthesis in children. Sunscreens do not result in low vitamin D with normal use in adults. See: Cancer Council Australia Position statement on sun exposure and vitamin D.

    Diet is usually a poor source of vitamin D most Australians only get around 10% of their vitamin D from dietary sources.3

    • Vitamin D is found naturally in few foods (some fatty fish, liver, small amount in eggs). Some dairy products are fortified with Vitamin D (some milk, all margarine).
    • Breastmilk contains almost no vitamin D (25 IU/L). Infant formula is fortified with D3 (360-520 IU/L).

    25(OH)D is used to measure vitamin D status. The recommended 25(OH)D level is >= 50 nmol/L at all ages and during pregnancy/lactation.

    • RCH uses a chemiluminescence assay with ~10% variation. Around 1 mL blood (200 mcL serum) is required for analysis.
    • To convert nmol/L to ng/mL divide by 2.5.

    Definitions of vitamin D status
    Severe deficiency <12.5 nmol/L
    Moderate deficiency 12.5-29 nmol/L
    Mild deficiency 30-49 nmol/L
    Sufficient >=50 nmol/L
    Elevated >250 nmol/L

    In the absence of sun exposure, recommended intakes are:4

    • 12 months - adequate intake (AI) 400 IU daily.
    • 1-18 years - estimated average requirement (EAR) 400 IU daily and recommended dietary allowance (RDA) 600 IU daily.
    EAR reflects estimated median requirements, RDA is the average daily intake that meets/exceeds the needs of 97.5% of the population. AI is used where no EAR/RDA is available. Vitamin D 1 mcg = 40 IU.

    Risk factors for low vitamin D

    • Lack of skin exposure to UVB in sunlight (time inside, chronic illness/hospitalisation, complex disability, covering clothing, southerly latitude).
    • Dark skin ( Fitzpatrick types V and VI).
    • Medical conditions/medications affecting vitamin D metabolism (obesity, liver failure, renal failure, malabsorption, medications e.g. isoniazid, rifampicin, anticonvulsants).
    • In infants: maternal vitamin D deficiency (cord levels ~65% maternal levels)5 and exclusive breastfeeding combined with at least one other risk factor.

    Prevalence

    Refugee-background communities may have multiple risk factors for low vitamin D, e.g. dark skin, covering clothing and limited time outside.

    • 61–100% of refugee background African Australians in Melbourne, Adelaide and Sydney have low vitamin D ( <50 nmol/L).6–11
    • Australian Health Survey data (2011-2013) found 36% of African Australians have low vitamin D ( <50 nmol/L) - noting <17% were from Victoria/Tasmania.12
    • Two large Australian case series of rickets found almost all children had ethnocultural risk factors (dark skin, maternal covering clothing).13,14
    • Low vitamin D is also seen commonly in other refugee cohorts wearing covering clothing (Afghani, Iraqi), and has been found in 33% of Karen refugees.15

    Assessment

    • Time outside, covering clothing, sunscreen use
    • Dietary history - dairy intake, breast/milk/formula in infants
    • Previous vitamin D levels, previous/current treatment – see  photoboard
    • Family understanding
    • Non-specific bony and/or muscular pain; fatigue with exercise
    • Poor growth, irritability, delayed motor milestones (young children)
    • Symptoms of low calcium (muscle cramps). Hypocalcaemic seizures are rare beyond 6-12 months of age.         

    • Growth parameters, exclusion of. other musculoskeletal pathology
    • Skin colour
    • Delayed fontanel closure (normally closed by 2 years)
    • Delayed dentition (no teeth by 9 months, no molars by 14 months), enamel hypoplasia.
    • Rickets – deformity in growing bones due to failure of mineralisation of osteoid. Peak incidence during infancy, although deformity reflects age/growth (and can be in any direction). Consider other causes if asymmetrical. Look for long bone deformity, splaying (wrists, ankles), bossing, delayed fontanel closure (normally closed by 18 months, 100% by 23-26 months), rosary.         

    Screening

    • Screen children/adolescents with one or more risk factors for low vitamin D
      • Measure vitamin D, Ca, PO4 and ALP
      • Also measure PTH in those with low calcium intake, symptoms/signs or multiple risk factors
      • In exclusively breastfed infants with at least one other risk factor it is usually more practical to start supplements without screening. Consider checking levels (or adding daily supplements) in babies with risk factors for low vitamin D with mixed feeds or who have appropriately reduced their formula intake after starting solids.
    • Children with rickets: check vitamin D, Ca, PO4, ALP, PTH, Mg, UEC, urine Ca/PO4/Creatinine, X-ray wrist

    • In recent arrivals: if the initial vitamin D level is normal, repeat at the end of the first winter in Australia
    • Levels at the start and end of winter can be useful to make a clinical judgment on dosing
    • Clinical photography is useful to monitor bony deformity (nutritional rickets usually corrects after treatment of low vitamin D provided the child has adequate calcium and phosphate intake).

    Management – initial

    • Admission symptomatic rickets/hypocalcaemia (including tetany, stridor, seizures) – these children may require intravenous calcium infusion and cardiac monitoring alongside management of low vitamin D (and exclusion of other causes) – do not give Vitamin D in the outpatient setting to this group.
    • Urgent specialist assessment - children with clinical rickets or abnormal serum calcium.

    • Children with low vitamin D should be treated to restore their levels to the normal range with either daily dosing or high dose therapy.
      • See dosing tables - there is limited evidence to support high dose therapy in children age <3 months.
      • RCH uses 100,000 IU/ml D3 in olive oil. This solution is light and temperature sensitive and degrades to inactive vitamin D. The shelf life is 3 months if not kept in the fridge (with reduced potency at this time). It should be 90% potent at 3 months if stored <4 degrees C. 
    • Ensure adequate calcium intake, and consider calcium supplements if dietary intake is poor (<2 serves dairy daily).
      • Cheese, yoghurt and fortified soy dairy are alternatives for children who dislike milk.
      • 1 cup cow milk contains ~300 mg calcium. One CaltrateTM tablet contains 600 mg calcium.  RDI for calcium by age
    • Treatment should be paired with health education and advice about sun protection/sun exposure – encouraging outside play/activity. Children/young people with dark skin can tolerate intermittent sun exposure without sunscreen, although hats/sunglasses are still recommended. See Sunsmart handouts.
    • Follow-up bloods at 3 months (earlier - at 1 month - in infants with moderate-severe deficiency) - 25(OH)D, Ca, PO4 and ALP; also PTH if elevated initially

    Self-management long-term

    • Breastfed babies with at least one other risk factor for low vitamin D should be given 400 IU daily for at least the first 12 months of life.
      • Babies on full formula feeds should receive adequate vitamin D from this source. 
      • Consider adding 400 IU daily in babies with risk factors for low vitamin D with mixed feeds or who have appropriately reduced their formula intake after starting solids.
    • Children/young people with ongoing risk factors for low vitamin D need to understand this is a long-term issue – they require ongoing monitoring and a plan to maintain vitamin D and calcium status through behavioural change and self-management where possible, and supplementation where this is inadequate.
    • Provide education and a plan for self-management: e.g. 400-600 IU daily OR 3000-4000 IU once weekly over the cooler months (May–September). This provides the EAR/RDA and should avoid blood testing and the need for high dose therapy.
    • Translated handouts are available.

    Dosing table: Management of low vitamin D

    Age Level Treatment (oral doses D3) Maintenance/prevention in children with ongoing risk factors
    Preterm Mild deficiency 30-49 nmol/L 200 IU/kg/d, maximum 400 IU/d 200 IU/kg/d, maximum 400 IU/d
    Moderate or severe deficiency  <30 nmol/L 800 IU/d, review after 1 month 200 IU/kg/d, maximum 400 IU/d
    <3 months (term) Mild deficiency 30-49 nmol/L 400 IU daily for 3 months


    400 IU daily 

    Moderate or severe deficiency <30 nmol/L 1000 IU daily for 3 months
    3-12 months Mild deficiency 30-49 nmol/L 400 IU daily for 3 months


    400 IU daily 

    Moderate or severe deficiency  <30 nmol/L 1000 IU daily for 3 months, OR 50,000 IU and review after 1 month, consider repeating dose
    1-18 years Mild deficiency 30–49 nmol/L 1000-2000 IU daily for 3 months, OR 150,000 IU stat


    400-600 IU daily, OR 3000-4000 IU once weekly, OR 150,000 IU at the start of Autumn

    Moderate or severe deficiency  <30 nmol/L 1000-2000 IU daily for 6 months, OR 3000-4000 IU daily for 3 months, OR 150,000 IU stat and repeat at 6 weeks

    Calcium

    Age Adequate intake (AI) Estimated average requirement (EAR) Recommended dietary intake (RDI)
    0-6 months 200 mg
    7-12 months 270 mg
    1-3 years 360 mg 500 mg
    4-8 years 520 mg 700 mg
    9-11 years 800 mg 1000 mg
    12-18 years 1050 mg 1300 mg

    Sun exposure

    Skin colour Light to olive skin, Fitzpatrick type I–IV Naturally dark skin, Fitzpatrick type V–VI
    Infants, children, adolescents Summer or UV index >=3 Avoid sunburn, full sun protection with sunscreen/hat/clothing/shade and sunglasses recommended Avoid sunburn, able to tolerate intermittent sun exposure without sunscreen, hat and sunglasses still recommended
    Encourage active outside play or physical activity during and after school/preschool
    Winter Sun protection recommendations vary with latitude/UV index. If UV index <3, sun protection not required unless in alpine regions, outside for extended periods or near highly reflective surfaces such as snow/water Sunscreen not needed in Southern states/New Zealand unless near highly reflective surfaces such as snow or water. It may not be possible to maintain vitamin D levels through sun exposure alone in southern states of Australia/New Zealand
    Encourage active outside play or physical activity during and after school/preschool
    Pregnancy, adults Summer or UV index >=3 6-7 minutes with arms (or equivalent area) exposed mid-morning or mid-afternoon most days of the week, avoid sunburn, full sun protection with sunscreen/hat/clothing/shade and sunglasses recommended 15-50 minutes with arms (or equivalent area) exposed mid-morning or mid-afternoon most days of the week, avoid sunburn, intermittent sun exposure without sunscreen can be tolerated but hat and sunglasses still recommended
    Winter 7-40 minutes exposure (depending on latitude) with face arms, and hands exposed at lunchtime most days of the week. If UV index <3, sunscreen not required unless in alpine regions, outside for extended periods or near highly reflective surfaces such as snow/water Depends on latitude. Sunscreen not needed in Southern states/New Zealand unless near highly reflective surfaces such as snow or water. It may not be possible to maintain vitamin D levels through sun exposure alone in southern states of Australia/New Zealand

    References

    Immigrant health clinic protocols. Author: Georgie Paxton, reviewed April 2020. Contact georgia.paxton@rch.org.au