In 2019, the global prevalence of anaemia was 36.5% among pregnant women, 29.6% in non-pregnant women, and 39.8% in children aged six- to 59-months. The highest prevalence of anaemia (56%) was found among pregnant women in LMICs. Africa has the highest prevalence of anaemia in pregnancy (57%), followed by South-East Asia (48%).² 

In women of childbearing age, anaemia is associated with the increased risk of adverse maternal (eg ante-partum and post-partum haemorrhage) and perinatal health outcomes (eg intrauterine foetal growth retardation, preterm birth, stillbirth), impaired physical health and cognitive development, and stunting in children.²  

Definition of anaemia

Iron is an essential element for blood production. About 70% of the body's iron is found in haemoglobin (HB) and in muscle cells. The WHO defines anaemia as ‘a condition in which the number of red blood cells or the HB concentration within them is lower than normal’.¹

IDA is characterised by low serum iron, low serum ferritin, decreased transferrin saturation, increased total iron-binding capacity, elevated soluble serum transferrin receptors, elevated serum zinc protoporphyrin and low serum hepcidin-25, the active form of hepcidin.¹

What causes IDA?

Generally, anaemia is classified according to its cause. Nutritional anaemia often results from inadequate intake of micronutrients, such as iron, folate, riboflavin, vitamins A, B12, and C required for blood formation.²

Other causes of anaemia include heavy menstruation, increased iron requirements during pregnancy and in growing children, chronic infections (such as tuberculosis, HIV, hookworm, and malaria), and poor iron absorption, transport, and storage, including haemoglobinopathies. Nutritional ID is results from low dietary iron intake, increased iron demand and/or iron loss, as well as low bioavailability of iron from staple foods.²

Symptoms and clinical implications

Patients with IDA can present with symptoms such as pallor of the skin, conjunctivae, and nail beds. Other symptoms and signs include fatigue, exertional dyspnoea progressing to breathlessness at rest, vertigo, syncope, headache, tachycardia, cardiac systolic flow murmur result from hypoxic functioning, dryness and roughness of the skin, dry and damaged hair, diffuse and moderate alopecia, and koilonychia (spoon-shaped fingernails).^3,4

Loss of tongue papillae may occur in patients with mild-to-moderate ID. Furthermore, ID  has also been associated with restless legs syndrome, febrile seizures, breath-holding spells, and cold intolerance.^3,4

Risk factors for IDA

IDA is the ultimate result of untreated ID. Infrequent consumption of meat, inadequate vitamin C intake, and diets rich in inhibitors of iron absorption are important risk factors for IDA in developing countries.⁴

Causes of anaemia in LMICs low-income include other nutritional deficiencies (vitamin B12, folic acid, riboflavin), chronic diseases, parasitic infections like malaria, hemoglobinopathies, and lead poisoning.⁴

Treatment

Regardless of the presence of symptoms, patients with IDA should be treated as early as possible because they are at risk for organ ischaemia and further worsening of the anaemia unless the underlying cause is relieved, and the bone marrow iron stores refilled.⁴

Likewise, children with iron deficiency alone should be treated because sideropaenia (an abnormally low level of iron in the blood serum) is associated with long-lasting neurocognitive impairments, decreased learning ability, and altered motor function.⁴

The WHO recommends screening before treatment is initiated. Regardless of the presence of symptoms, patients with IDA should be treated as early as possible because they are at risk for organ ischaemia and further worsening of the anaemia unless the underlying cause is relieved, and the bone marrow iron stores refilled.¹

Iron supplementation is the most commonly prescribed treatment for anaemia. As a micronutrient, iron has a relatively narrow range of safety - whether given as a supplement or fortificant.^1,5

Treatment of IDA with iron supplements can be divided into two phases: first the HB levels are restored and then the iron stores are replenished. To fully restore this mineral reserve, supplementation should continue for about three months after the normalisation of HB levels.⁶

First-line treatment is oral therapy with ferrous iron (Fe) salt. However, Fe is associated with low patient adherence to treatment as a result of adverse gastrointestinal (GI) side effects including nausea, flatulence, abdominal pain, diarrhoea, constipation, and black or tarry stools. A source of iron which has been shown to be highly bioavailable and associated with fewer side-effects is iron chelated with amino acids.^5,7

Ferrous bis-glycine chelate (FeBC) is the most studied and used form. Supplementation trials have demonstrated that FeBC is efficacious in treating IDA in pregnant women and infants.^7,8

Abbas et al (2019) compared the efficacy and tolerability of oral FeBC versus Fe in the treatment of IDA in with pregnant participants (14-18 weeks of gestation with mild to moderate IDA).⁷

Patients (n=187) were randomised into two groups: (Group I) received oral FeBC once daily for eight consecutive weeks and (Group II) received oral Fe capsules in the same dose and duration. The primary outcome of the study was the rate of increase of HB level after eight weeks of iron treatment.⁷

The mean increase in HB level after eight weeks of treatment in the FeBC group was 2.48 ± 0.12 g/dL versus 1.32 ± 0.18 g/dL in the Fe group. The percentage of women with HB level more than 11 g/dL after eight weeks of treatment was 89.2% in FeBC group versus 71.3% in Fe group. More women in the Fe group experienced significant side effects.⁷

Abbas et al concluded that pregnant women with second trimester IDA could be supplied with FeBC, which is more efficient in increasing HB level. Moreover, it has tolerable adverse effects and high compliance than Fe.⁷

Pineda et al (2001) compared the efficacy and safety of FeBC versus FE salt in infants aged six- to 36-months admitted to the paediatric intensive care unit as a result of IDA.⁸

Participants (n = 40) were randomised to identically appearing syrups labelled A and B that contained equal amounts of iron per millilitres (30mg Fe/mL) or  FeBC.⁸

The standard treatment protocol of the hospital called for a daily dosage of 5mg of iron/kg and 250mg/d of folic acid. These treatments were administered to infants as a single dose of the required amount of iron based on body weight plus folic acid for 28 days.⁸

After 28 days of treatment, there were significant increases in HB levels and body iron reserves as measured by plasma ferritin levels after treatment with FeBC. The results clearly indicate that more of the iron from the chelate than from Fe was absorbed, which suggests a higher bioavailability for the FeBC.⁸

The bio availabilities of the FeBC and Fe were 90.9% and 26.7%, respectively. The ratio of apparent bioavailability’s showed that the FeBC was absorbed 3.4 times better than Fe, making it the iron of choice for treatment, concluded Pineda et al.⁸

Recommended dosing

Iron supplementation must be prescribed in a high enough dose to be appreciably absorbed, but low enough to avoid toxicity. This concern can be ameliorated by careful choice of the form of iron administered.⁵

How should iron supplements be taken?

1. Iron is best absorbed on an empty stomach. However, iron supplements can cause GI side effects in some patients. In these patients, recommend taking iron with a small meal.¹⁰

2. Milk, calcium, and antacids should not be taken at the same time as iron supplements. Wait You at least two hours after having these foods before taking an iron supplement.¹⁰

3. Foods that should not be eaten at the same time as iron supplements include:¹⁰

• • High fibre foods, such as whole grains, raw vegetables, and bran
  • Foods or drinks with caffeine.

4. Some experts suggest taking a vitamin C supplement or drinking orange juice with an iron supplement. This can help the iron absorb into the body.¹⁰

5. Before prescribing an iron supplement, ask the patients about all the medicines he/she are taking, because it may interfere with the efficacy of some medicines such as cause other tetracycline, penicillin, and ciprofloxacin and drugs used for hypothyroidism, Parkinson disease, and seizures. In addition, medicine that reduce stomach acid will impair iron absorption.¹⁰

Conclusion

IDA is a public health concern – especially in developing countries such as South Africa. It affects quality of life and increases the risk of mortality and morbidity. Pregnant women and children are at high risk of IDA.^1,2

Iron supplementation is recommended as first-line therapy for the treatment of IDA. The WHO cautions that screening and testing should be done before treatment is initiated.¹

The Lancet Series (2013) on maternal and child nutrition reported that during a trial of iron supplements in pregnant women they found a 67% reduction of IDA.¹¹

Furthermore, in non-pregnant women a review of studies showed that intermittent iron supplementation was effective in reducing the risk of anaemia by 27%. This review also indicated that daily iron supplementation reduced the incidence of low birth weight by 19%.¹¹

REFERENCES:

1. Anaemia. https://www.who.int/health-topics/anaemia#tab=tab_1
2. Turawa E, Awontiwon O, Dhansay MA, et al. Prevalence of Anaemia, Iron Deficiency, and Iron Deficiency Anaemia in Women of Reproductive Age and Children under 5 Years of Age in South Africa (1997–2021): A Systematic Review. Int. J. Environ. Res. Public Health, 2021.
3. Lopez A, Cacoub P, Macdougall IC, Peyrin‐Biroulet L, et al.Iron deficiency anaemia. Lancet, 2016.
4. Mantadakis E, Chatzmichael E, and Zikidou P. Iron Deficiency Anemia in Children Residing in High and Low-Income Countries: Risk Factors, Prevention, Diagnosis and Therapy. Mediterr J Hematol Infect Dis, 2020.
5. Jeppsen RB. Toxicology and safety of Ferrochel and other iron amino acid chelates. Archivos Latinoamericanos de Nutrición, 2001.
6. DeWayne H. The absorption and metabolism 01 iron amino acid chelate. Archivos Latinoamericanos de Nutrición, 2001.
7. Abbas AM, Abdelbadee SA, Alanwar A, et al. Efficacy of ferrous bis-glycinate versus ferrous glycine sulfate in the treatment of iron deficiency anemia with pregnancy: a randomized double-blind clinical trial. J Matern Fetal Neonatal Med, 2019.
8. Pineda O and DeWayne H. Effectiveness of Treatment of Iron-Deficiency Anemia in Infants and Young Children With Ferrous Bis-glycinate Chelate. Nutrition, 2001.
9. Office of Dietary Supplements. Iron. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/
10. National Library of Medicine. Taking iron supplements. https://medlineplus.gov/ency/article/007478.htm#:~:text=Iron%20is%20best%20absorbed%20on,food%20to%20avoid%20this%20problem.
11. Bhutta Z, Das J, Rizvi KA, et al. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? The Lancet,