Background

Vitamin B12 (cobalamin) is a water soluble vitamin. Dietary intake is predominantly from animal products (meat, organ meat, fish, seafood, dairy and eggs), although some packaged cereals and soy milk are fortified with B12. B12 is also synthesised and utilised by microorganisms in the gut microbiome. 

• B12 is important in haematopoiesis (red cell formation) and the central nervous system, it is essential for DNA synthesis, methylation and folate metabolism, and it is an enzyme cofactor (see background).
• B12 metabolism is complex. B12 in food is enzyme bound, and released in the stomach through the action of the low pH and pepsin, forming a stable complex with R binder. Intrinsic factor (IF) is released in the stomach, and binds with B12 in the upper small intestine. There is some enterohepatic circulation, and B12-IF is absorbed in the terminal ileum via a specific receptor.
• Recommended daily intakes range from 0.4 mcg (adequate intake (AI) in infants) to 2.4 mcg (recommended daily intake (RDI) in >14 years age).
• Most diets including animal products contain a much higher B12 intake than the AI/RDI. B12 is safe in doses up to 1000 times the RDI. See B12 content of common foods.

Causes of low vitamin B12

• Exclusive breastfeeding in infants of mothers with B12 deficiency - these infants may develop deficiency and typically present from 4-6 months of age.
• Vegan/vegetarian diet - due to low intake.
  
• Malabsorption - causes include: ileal resection, inflammatory bowel disease, parasites (including Giardia duodenalis), bacterial overgrowth, tropical sprue, possibly H. pylori, and medication (e.g. proton pump inhibitors (PPI), metformin)
  
• Pernicious anaemia - autoimmune atrophic gastritis causes loss of IF
• Rare metabolic disorders - including transcobalamin II (TCII) deficiency, cobalamin C/D defects.

Causes by age

• Birth - 6 months - severe maternal deficiency, consider metabolic causes, especially if severe metabolic disturbance (acidosis/vomiting) and neurological features.
• 6 months - mid-childhood - dietary deficiency, maternal deficiency (causing deficiency in breast fed infants), malabsorption. 
• Mid-childhood onwards - low intake, juvenile pernicious anaemia, gastritis, malabsorption, medications.

In refugee populations the most common cause is low intake, typically a diet low in animal products due to chronic food insecurity in countries of origin/transit. Helicobacter pylori infection also seems to be important clinically.

Prevalence of B12 deficiency in refugee background populations

• A 2013 study of 916 refugees in Australia found prevalence of B12 deficiency was 17% overall, including 12% of children aged under 14 yrs (defined as total serum B12 <150 pmol/L). Only 4.6% of those with low B12 had macrocytosis, and none had folate deficiency. The highest prevalence was in people from Bhutan, Iran, Iraq and Afghanistan (up to 20-30%). Lower prevalence was found in refugees from Africa (4-11%) and Burma (2%)
  
• Data from our service have found the prevalence of B12 deficiency is:
  • 1.5% in Karen refugees (Paxton et al, 2012).
  • 2% in asylum seeker children (Tosif et al, 2023).
  • 10.5% in Syrian refugee children with risk factors (only a small subset tested) (Heenan et al, 2018).
  • 44.7% in Afghan refugee children (Williamson et al, 2025, submitted for publication).
• A 2025 study of Ezidi refugees in Armidale NSW found prevalence of 50.7% in a community clinic and 58% in a hospital service.
• There are no data for the Australian population prevalence of B12 deficiency.
• Globally, B12 deficiency is reported in 42.8% new arrival pregnant refugee women in Canada (2015-2020) and 32% of Bhutanese refugees in the US (2008-2011). 

Assessment

B12 deficiency can cause life threatening disease due to megaloblastic anaemia with cytopaenias, or neurological abnormalities (regression/seizures). Clinical presentation of low B12 can be subtle. Consider B12 deficiency in children with poor growth or feeding difficulties, developmental delay or regression, low tone, irritability, parasthesias, ataxia and seizures. Neurological sequelae may be permanent. Patients may also be asymptomatic or diagnosed incidentally. There are associations with decreased cognitive function, mental health and long-term cardiovascular outcomes.

History

• Dietary intake - current and previous, ask about breastfeeding duration and solids in infants, vegetarian/vegan diets and food insecurity. Consumption of animal products more often than weekly should be protective – consider malabsorption in children with clinical symptoms and apparent adequate intake. Check maternal dietary history in breast fed infants.
  
• Symptoms of anaemia or cytopaenias - fatigue, lethargy, pallor, jaundice, infections.
• Developmental and neurological symptoms - regression, seizures, floppiness/low tone, dystonia/involuntary movements.
• Underlying disorders including Helicobacter pylori, malabsorption (diarrhoea, failure to thrive, bowel surgery/short bowel syndrome, coeliac disease, inflammatory bowel disease), other (autoimmune conditions such as pernicious anaemia, metabolic conditions).
• Medications such as metformin and PPI.

Examination

• Pallor, jaundice, bruising.
• Neurological – reduced tone in infants, defects in vibration sense/proprioception, cutaneous sensation, ataxia, weakness, reduced reflexes, choreoathetoid movements, gait abnormalities, cognitive changes, developmental delays.
• Microcephaly and growth pattern.
• Skin pigmentation changes and oedema in infants.

Screening

• Screen all: Afghan, Palestinian, Rohingyan and Bhutanese cohorts, mothers of infants with deficiency, and breastfed babies where there has been poor maternal food access or where deficiency is suspected.
• Consider B12 screening in other cohorts, especially where there is a history of poor food access or where Helicobacter pylori is identified. Screening is generally not required for asymptomatic individuals with an adequate dietary intake, or those who have been in Australia for >6 months and consume animal products.
  
• An FBE (and ferritin) is part of initial refugee health screening, although this is not adequate screening for B12 deficiency.

Screening tests

Where B12 deficiency is suspected:

• Active B12 (holotranscobalamin) is more sensitive and the appropriate initial investigation (used at RCH). Active B12 is a measure of available stores. Results are reported as low, indeterminate, or normal range, check reference ranges as these vary. 
  • Total serum B12 is not sensitive or specific for clinical deficiency (this test is not available at RCH). Total B12 includes the protein bound fraction, and should be interpreted with serum homocysteine (HC) and urine methylmalonic acid (MMA) - both are elevated in B12 deficiency. Total serum B12 <150 pmol/L is usually consistent with significant clinical deficiency, however results at the lower end of the normal range may be deficient (false negative).
    
• Red cell folate to determine concurrent folate deficiency. Always treat low B12 first before treating low folate, to avoid precipitating subacute combined degeneration of the cord. 
• Full blood examination and film - macrocytic red cells, hypersegmented neutrophils. Macrocytosis can be masked by concomitant iron deficiency and thalassemia, and is not a useful screening test, we have not seen macrocytosis in practice over the last 20 years in refugee health. Leukopaenia, thrombocytopenia, pancytopaenia are all possible associations.
  

If B12 deficiency is confirmed:

• Serum HC and urine MMA are useful to confirm tissue deficiency. One or both are elevated in almost all patients with clinical deficiency, but decrease immediately after treatment. It is sensible to order HC and MMA at the same time as B12 levels where there is a high suspicion or clinical features of deficiency, especially in infants <2 years. 
  • HC may also be elevated in folate deficiency.
  • Testing for MMA (urine organic acids) will incur a cost (~$170) if completed outside the hospital.
• Haemolysis screen - Increased LDH (often very high), bilirubin and AST, decreased haptoglobin.
• Iron studies for coexisting deficiency if not already completed.
• Bone marrow aspirate is not usually necessary.
• If history does not suggestive dietary deficiency, consider other causes and investigate as appropriate.

Management

Seek urgent specialist advice for all infants <2 years with B12 deficiency and all patients with symptomatic B12 deficiency. At RCH management is usually in consultation with the Haematology and/or Metabolic units. 

For all infants and all patients with neurological involvement, standard replacement is intramuscular B12 (hydroxocobalamin). Although oral doses (cyanocobalamin in tablets, mecobalamin in melts/sublingual sprays) are less well absorbed (0.5-4% absorbed), high doses can be effective for lower-risk cases - i.e. older children/adolescents without evidence of tissue deficiency (i.e. no clinical features and normal HC/MMA), and no malabsorption. In general we treat both confirmed low levels and indeterminate levels - check laboratory reference ranges, as these vary. Treatment regimens also vary, a suggested approach is outlined below:

• Infants <2y with clinical deficiency (low/indeterminate B12 and any of: anaemia, neurological involvement, raised MMA/HC):
  
  • Admit to hospital* - 1000 mcg intramuscular B12 daily for 3 doses. Check levels after the third dose (+/- further doses). Continue 250 mcg B12 weekly for 6 weeks. Check levels at 6 weeks (+/- ongoing dosing). 
  • Short term parenteral therapy is often sufficient, especially if maternal deficiency is proven. Screen and treat maternal B12 deficiency.
  • Only switch to oral supplements once child is well, no diarrhoea, feeding improved, and maternal stores are replaced. 
  • If diagnosis is unclear, where a metabolic cause is possible, or there are ongoing symptoms, seek ongoing specialist advice. 
• Older children/adolescents with clinical deficiency (low/indeterminate B12 and any of: anaemia, neurological involvement, raised MMA/HC):
  • 1000 mcg intramuscular B12 for 1 dose, then 1000 mcg B12 melts for 6 days. Check levels after 1 week (+/- further doses). Continue 1000 mcg B12 weekly for 6 weeks.  Check levels at 6 weeks (+/- ongoing dosing). 
    
• Infants <2y with normal clinical status and low/indeterminate levels:
  • 1000 mcg intramuscular B12 for one dose, then 1000 mcg B12 melts daily for 2 days and check levels after the third dose. Continue 250 mcg B12 weekly for 6 weeks. Check levels at 6 weeks. 
    
• Older children/adolescents with normal clinical status and low levels: 
  • 1000 mcg B12 melts oral daily for 1 week and then check levels. Continue 1000 mcg B12 melts weekly for 6 weeks. Check levels at 6 weeks (+/- ongoing dosing).
• Older children/adolescents with normal clinical status and indeterminate levels:
  • 1000mcg B12 melts oral weekly for 3-6 months, check levels at 6 weeks, OR 
  • 100-200 mcg B12 tablets oral daily for 3-6 months, check levels at 6 weeks. 
    
• Supplement (not deficient, no dietary intake):
  • 50-100 mcg B12 daily or alternate daily, or 1000 mcg B12 melts weekly - fortnightly. Check levels annually if ongoing risk factors (e.g. vegan diet). 
    

*Hospital in the home services may be appropriate. 

At all ages: increase dietary intake of B12 containing foods and assess for contributors as above. 

Medications - notes

• B12 injections (hydroxocobalamin - preferred) are given IM. Never give IV. Cyanocobalamin IM (or deep subcutaneous) injections are also available. 
  
• B12 melts (mecobalamin) 1000mcg.
• B12 tablets (cyanocobalamin) are generally 100 mcg, which can be crushed
• B12 is also available as sublingual sprays (mecobalamin) doses vary and may have high ethanol content - up to 10%. May not be suitable for infants or Muslim populations. 
  

Follow-up

• In infants and children with severe deficiency, repeat HC and MMA levels 1-2 weeks after commencement of treatment (levels should normalise quickly).
• Repeat B12 levels at 6 weeks as above (seek advice if still low) and then repeat after 3 months then 6 months. 
• Patients with deficiency due to metabolic causes require individual and specialised management.
  

Rapid clinical improvement is usually seen with replacement, but neurological impairment may persist if there has been prolonged deficiency. Long term developmental follow-up may be required if presentation included neurological features (seizures and neurocognitive deficits are common). 

_{Immigrant health resources Author: Daniel Engelman. Initial - November 2013, reviewed and updated Georgie Paxton Feb 2026. Contact: georgia.paxton@rch.org.au}