Micronutrient deficiency

Key Points

Consider micronutrient deficiencies in all children with diets which are highly restricted in variety and balanced nutritional content due to neurodevelopmental conditions eg ASD, cognitive impairment
Normal growth parameters do not exclude possible micronutrient deficiency
Micronutrient deficiencies can be associated with permanent physical disabilities (eg blindness) or death
Clinical features of micronutrient deficiency may be subtle, consider in children with highly restricted diets presenting with non-specific symptoms

Background

Micronutrient deficiency may occur in children who have sufficient caloric intake for acceptable growth, but a diet significantly restricted in food variety. This can occur in the absence of an underlying medical condition or eating disorder, and differs from ‘fussy eating’, which is common in early childhood and generally resolves over time

These patterns of eating behaviour are often seen in children with:

Neurodevelopmental conditions including autism spectrum disorder
Avoidant restrictive food intake disorder (ARFID)
Multiple food allergies
Elective dietary restrictions due to cultural, religious, or environmental reasons

Children with underlying medical conditions impacting the absorption or utilisation of micronutrients should undergo management in consultation with relevant specialist services

Assessment

History

Diet highly limited in variety eg missing food groups, less than 10 foods/food types regularly consumed, minimal meal to meal variability
Dietary patterns predisposing to vitamin and mineral deficiencies eg veganism
Consider reviewing diet in context of Australian Healthy Eating Guidelines
Clinical features suggestive of specific micronutrient deficiency (see below)
History of previous micronutrient deficiency
Use of vitamin and mineral supplements
Suspected or actual diagnosis of neurodevelopmental disorder eg ASD, cognitive impairment

Examination

General assessment for micronutrient deficiency should be performed including checking for skin changes (including pallor), dry eyes, oral mucosa and gum changes, goitre, bony deformity, neuropathy, hair or nail changes
Growth measurements should be routinely performed, but noting that child may have normal growth for age and sex or even be overweight
Consideration should be given to the following clinical features associated with specific micronutrient deficiencies

Micronutrient	Clinical features of deficiency	Risks for deficiency
Vitamin A (Retinol)	Xerophthalmia: night blindness, dry conjunctiva, corneal ulceration, blindness Dry skin and pruritis Increased susceptibility to infection Poor growth	Malabsorption eg exocrine pancreatic insufficiency, chronic liver disease, short bowel syndrome, inflammatory bowel disease Maternal deficiency Some refugee populations
Vitamin B1 (Thiamine)	Fatigue, irritability, apathy, nausea, abdominal discomfort Dry beriberi (symmetric peripheral neuropathy) Wet beriberi (cardiac failure) Wernicke encephalopathy: confusion, reduced consciousness, ataxia, ophthalmoplegia Korsakoff syndrome: confusion, amnesia	White rice-based diets Malabsorption Some refugee populations
Vitamin B3 (Niacin)	Anorexia, vomiting, abdominal pain Glossitis, cheilitis Pellagra: triad of dermatitis, diarrhoea and confusion Late symptoms include apathy, weakness, headache, confusion, irritability, anxiety, tremor, depression	Corn based diets Malabsorption
Vitamin B9 (Folate)	Clinical signs of anaemia Macrocytic anaemia and hyper-segmented neutrophils on full blood count Glossitis, oral ulcers Fatigue, slow growth	Lack of fresh food in diet Malabsorption, Medications eg phenytoin, phenobarbital, methotrexate, long-term NSAID use
Vitamin B12 (Cobalamin)	Clinical skins of anaemia Macrocytic anaemia and hyper-segmented neutrophils on full blood count Irritability, developmental delay, developmental regression, involuntary movements, peripheral neuropathy Glossitis, oral ulcers Skin changes eg hyperpigmentation, vitiligo	Vegan and vegetarian diet Some refugee populations Gastrointestinal disease Exclusively breastfed infants of mothers with Vitamin B12 deficiency
Vitamin C (Ascorbic acid)	Scurvy: skeletal fractures and joint pain, poor wound healing, fatigue, weight loss, gingival inflammation with gum bleeding, petechiae, ecchymosis, purpura, dry eyes and mouth, corkscrew hair	Diets without fruit and vegetables
Vitamin D (Calciferol)	Rickets: lower limb deformities, enlargement of wrists and ankles, protruding abdomen, delayed gross motor development, generalised musculoskeletal pain Hypocalcaemia: may present with seizures and tetany	Lack of skin exposure to sun Dark skin Obesity Liver/renal failure Gastrointestinal disease Exclusively breastfed infants of mothers with vitamin D deficiency
Vitamin E (Alpha-tocopherol)	Decreased muscle mass Weakness, unsteady gait	Malabsorption
Vitamin K (Phytomenadione)	Excessive bleeding/bruising	Malabsorption
Copper	Anaemia Peripheral neuropathy	Prolonged total parenteral nutrition Malabsorption
Iodine	Goitre Other signs and symptoms of hypothyroidism	Extremely rare unless immigrated from high-risk areas eg inland Asia or Africa
Iron	Clinical signs of anaemia: pallor, irritability, anorexia, fatigue Microcytic anaemia on full blood count Behavioural disturbance, impaired cognitive function, decreased memory, impaired learning and concentration Pica (eating non-food items)	Vegetarian or vegan diet High milk intake Gastrointestinal disease Heavy menstrual loss Maternal iron deficiency Prematurity Low birth weight
Selenium	Cardiomyopathy Myositis Shortened fingers and toes	Prolonged total parenteral nutrition
Zinc	Acrodermatitis enteropathica: Periacral, periorificial dermatitis, diarrhoea, alopecia Depressed mood, apathy, and emotional disturbances in older children	Malabsorption Total parenteral nutrition Vegetarian diet

Management

Children at risk based on history should be strongly considered for investigations
Consider investigations even in asymptomatic children as some complications of micronutrient deficiency are irreversible
Symptomatic children should be prioritised for urgent assessment and initiation of treatment or even empirical supplementation
Dietician referral to assist in assessment and management (eg dietary change, supplementation) is recommended
Any patients with identified micronutrient deficiency should have other possible diagnoses considered in addition to dietary causes

Investigations

Given the challenges and distress caused by blood collection in many children at risk for micronutrient deficiency, consider performing all first line laboratory investigations with one blood collection unless only a specific deficiency is suspected based on history or examination
Opportunistic testing during sedation or anaesthesia should also be considered to minimise distress and trauma
Tests may also need to be prioritised based on sample volume available
Estimated blood volume required for first line investigations is 10-15 mL whole blood, with specific collection details to be confirmed with local laboratory

First line investigations

Blood

FBE
UEC, LFT, calcium, magnesium, phosphate
Iron studies
Vitamin A (light sensitive, cover tube with foil)
Thiamine
Folate
Vitamin B12
Vitamin C
Vitamin D (see flowchart for criteria)
Zinc

Second line investigations to consider if specific risks for deficiency or clinical features identified

Blood

Coagulation Profile (as marker of Vitamin K deficiency)
Thyroid function test (as marker of iodine deficiency)
Vitamin E
Selenium
Copper

Urine

Vitamin B3

Treatment

Specific micronutrient deficiencies should be managed with supplementation
Dosing suggestions and practical advice are provided below for more common deficiencies but consultation with local guidelines or pharmacist should be considered, particularly if multiple micronutrient deficiencies are identified

Nutrient	Dosing advice	Formulations	Practice advice	Common food Sources
Vitamin A (Retinol)	Level 0.35-0.7 micromol/L (or low for age) <6 months: 50,000 IU oral stat 6-12 months: 100,000 IU oral stat >12 months: 200,000 IU oral stat Repeat dose at 6 months if risk factors persist Level <0.35 micromol/L or Xerophthalmia Dose on day 1, 2 and 14 <6 months: 50,000 IU oral 6-12 months: 100,000 IU oral >12 months: 200,000 IU oral	Oral Capsules (5,000 IU and 10,000 IU) Drops (5000 IU/0.2 mL) Intramuscular 100,000 IU per dose, requires Special Access Scheme (SAS) Approval	Toxicity occurs at chronic daily intakes >6,000 microg Repeat levels after treatment	Liver, oily fish, dairy products, eggs, orange fruits and vegetables, green leafy vegetables
Vitamin B1 (Thiamine)	Subclinical deficiency 2mg/kg (rounded to nearest 25 mg, max 100 mg) oral once daily for 6 weeks If symptomatic, discuss parenteral treatment with local paediatric team	Oral Tablet (100 mg) Intravenous/ Intramuscular Seek local pharmacist advice	Low toxicity risk Repeat levels after treatment	Red meats, poultry, fish, shellfish, eggs, nuts and seeds, fortified breads and cereals
Vitamin B9 (Folate)	Treatment of folate deficiency anaemia 1-12 months: 0.5 mg/kg (maximum 5 mg) once daily for 4 months >12 months: 5 mg oral once daily for 4 months, then 5 mg every 1-7 days Prevention of folate deficiency if ongoing risk factors 1 month: 12 years, oral 2.5-10 mg once daily 12-18 years: 5-10 mg oral once daily	Oral Tablets (5 mg) Injectable forms available. Seek local pharmacist advice	Low toxicity risk Repeat levels after treatment Exclude Vitamin B12 deficiency prior to dosing Supplementation can reduce serum levels of some antiepileptics (Phenytoin, Carbamazepine, Valproate)	Offal, oily fish, fortified cereals, breads and pasta, lentils and legumes, green vegetables, root vegetables
Vitamin B12 (Cobalamin)	Subclinical deficiency 100 microg oral once daily If symptomatic or unable to tolerate oral treatment, discuss parenteral treatment with local paediatric team	Oral (Cyanocobalamin) Tablet (100 microg and 1000 microg) Sublingual wafer (1,000 microg) Sublingual spray (500 microg, limited evidence for use) Intramuscular (Hydroxocobalamin) 1,000 microg	Low toxicity risk Repeat levels after treatment High dose oral replacement may be considered in place of intramuscular if no features of malabsorption	Shellfish, fish, red meats, poultry, eggs, dairy, fortified breads and cereals
Vitamin C (Ascorbic acid)	Subclinical/symptomatic 100 mg tds (oral, IV, IM) for one week, then 100mg oral once daily for several weeks until patient is fully recovered or repeat levels normalised	Oral Tablet (100 mg) Liquid Intravenous/ Intramuscular Seek local pharmacist advice	Low toxicity risk Repeat levels after treatment	Fruit, raw or steamed vegetables, fruit juice
Vitamin D	See vitamin D deficiency			Oily fish, eggs, offal, fortified dairy products, fortified cereal
Iron	See iron deficiency			Red meats, poultry, fish, shellfish, offal, fortified cereals and breads, legumes, tofu, eggs, nuts, green leafy vegetables
Zinc	Subclinical deficiency 1 mg/kg/day oral in 1-3 doses, repeat levels after 1 month Acrodermatitis enteropathica 3 mg/kg/day oral	Oral Tablets (25 mg, 40 mg) Capsules (can be opened and dispersed) Liquid	Toxicity can lead to copper deficiency, otherwise low toxicity risk	Meats, shellfish, oily fish, eggs, dairy products, nuts and seeds, wholegrain breads and cereals

Consider the use of a multivitamin in all children at risk of micronutrient deficiency. Seek advice from dietician on choice and dosage of multivitamins meeting recommended vitamin and mineral daily intake for age, while considering tolerability of different formulations eg liquid, tablet, powder
Occupational or speech therapy services can assist with administration strategies and addressing underlying food aversions. Specialised feeding services or feeding therapists may be available in some regions or via telehealth from larger centres
Children with identified micronutrient deficiency who have completed initial replacement should have management put in place to maintain sufficient nutrient intake (maintenance dosing). This should continue until such a time that the dietary risk factors have been addressed or resolved

Consider consultation with local paediatric team when

Child has symptomatic micronutrient deficiency
Cause of micronutrient deficiency is not clear
Oral supplementation not successful
Consideration of feeding support through nasogastric tube or gastrostomy is required

Consider transfer when

Care required is beyond the capability of the local hospital

Consider discharge when

Micronutrient deficiency successfully treated, and risk factors have been addressed

Parent information

Healthy Eating for Children
Nutrition – babies and toddlers
Nutrition – school age to adolescence
Iron
Vitamin D

Additional notes

Australian Government Eat for Health Resources and Nutritional Guidelines
Nutrient reference values for age
RCH Food and Nutrition resources
Nutrition Education Materials Online (NEMO) | Queensland Health

Last updated September 2023

Reference List

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AMH Children’s Dosing Companion (online). Vitamin B12. Adelaide: Australian Medicines Handbook Pty Ltd; 2020 July. Available from: https://childrens.amh.net.au/

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The Royal Children's Hospital Melbourne

Clinical Practice Guidelines