Iron is necessary for human health.
Iron deficiency in pregnant women is not conducive to the brain development of the fetus. One study confirmed [1]: from infancy follow-up to age 19 years, there was ≥ 3 months of iron deficiency in infancy with cognitive decline compared with infancy iron deficiency. Another study confirmed [2]: Iron deficiency during pregnancy is associated with future cognitive deficits in children.
Iron deficiency in pregnant women also directly harms the mother herself; anemia due to iron deficiency brings more serious complications and even the risk of death [3-4].
Iron supplementation is important in pregnant women
Iron supplementation can improve cognitive function, mood and so on in adolescents. A randomized controlled study of adolescent girls with "anemia-free" iron deficiency (serum ferritin ≤ 12 μg/L and normal haemoglobin concentrations) confirmed [5]: Iron supplementation resulted in significantly better test results for speech learning and memory. Another controlled study confirmed [6]: Iron supplementation provides a 5- to 7-fold improvement in cognitive function.
People who are not yet anemic but iron deficient may have symptoms such as fatigue or decreased exercise tolerance. Iron supplementation for such "non-anemic people" can improve symptoms.
One trial included 90 hypothermic but anaemic premenopausal women with serum ferritin ≤50 ng/mL and haemoglobin greater than ≥120 g/L. Randomized to intravenous iron supplementation and no iron supplementation; iron supplementation has been shown to improve symptoms of fatigue [7].
Trials of runners and blood donors have shown that iron supplementation can improve athletic performance, sleep disturbances, and nail breaks [8-10].
Iron deficiency in adolescents can affect academic performance, and iron supplementation can improve
Iron supplementation can also improve the prognosis of patients with heart failure. A randomized controlled study of 1132 patients with heart failure and iron deficiency (ferritin <100 ng/mL or transferrin saturation <20 percent) confirmed [11]: intravenous iron supplementation resulted in lower hospitalization rates, although cardiovascular mortality was similar.
If iron deficiency causes anemia, it also increases surgical-related mortality. A study analyzing 949,445 patients confirmed that anaemia increased perioperative case fatality, acute renal impairment, and infection [12]; moreover, the more severe the anaemia, the higher the complication rate: patients with mild anaemia increased their relative risk of complications within 30 days of surgery by approximately 35 percent, while the relative risk of complications of moderate to severe anaemia increased by approximately 56 percent [13].
Many patients have iron deficiency, but they are often missed
So, how do we judge iron deficiency?
At present, the commonly used tests are:
Ferritin: The body's most important carrier for storing iron; the lower the ferritin value, the more likely it is to be iron deficient. However, inflammation, liver disease, heart failure, and malignancies can increase ferritin values and obscure the truth about iron deficiency.
Transferrin saturation: Calculated based on serum iron ÷ total iron binding force. When iron is deficient, it goes down. However, factors such as iron supplementation and hemolysis are falsely high.
In fact, it is often wrong to judge whether iron deficiency is based solely on a certain test result.
For example, a 10-year-old child does not have any discomfort and does not have anemia. His ferritin value is 30 ng/mL, and he is likely not deficient in iron.
A 68-year-old man with various chronic diseases has a ferritin value of 40 ng/mL, but he has small cell hypopigmentemia, at which time he is likely to be iron deficient.
If according to some people's attachment to the test results, we see that 40ng/mL is higher than 30ng/mL, since 30ng/mL is not deficient in iron, then 40ng/mL will not be deficient in iron.
But, is that right?
Judging whether there is iron deficiency is a very test of professional standards
When judging iron deficiency using ferritin values, we need a tangent value. Ferritin values below the tangent point are considered iron deficiency, and above the tangent point it is considered iron deficiency.
But there are many cut points for ferritin values.
For example, some guides put the cut point at 12-15ng/mL, while some guides put it at 30ng/mL, and there are 50ng/mL and so on.
Regardless of the patient's state, if you simply look at this numerical cut point, it is easy to make mistakes.
For example, if chronic anemia (non-nephrotic) is suspected, it is customary to place the incision point of ferritin values at 100 ng/mL (see Guidelines for Anemia in Chronic Diseases); rather than the same as the average person.
If the patient is on hemodialysis (not peritoneal dialysis), the ferritin numerical tangent point for absolute iron deficiency is placed at 200 ng/mL, and the relative iron deficiency is placed at 500 ng/mL. Of course, the specific need to refer to hemoglobin, serum iron, transferrin saturation and so on to judge.
According to the detection principle of ferritin, we know that the lower the ferritin value, the more certainty of iron deficiency.
However, due to factors such as physical condition, ferritin may be falsely elevated. For example, there is wound inflammation, chronic left heart failure, chronic kidney failure and so on.
For example, a 2018 test of patients with left heart failure who were iron deficient found that their ferritin values ranged from 44 to 162 ng/mL [14]. Their iron deficiency is based on a bone marrow examination.
If the point is cut according to the general ferritin value, these left-sided heart failure patients with iron deficiency may refuse iron supplementation. But they all need iron supplementation to improve prognosis.
Iron deficiency in patients with heart failure is easy to be missed!
So how do we judge whether iron is deficient or not?
1, according to the patient's state to choose a reasonable ferritin, transferrin saturation of the numerical cut point. Healthy adolescents and elderly people with chronic diseases have very different entry points for ferritin values. People with suspected iron deficiency symptoms are not the same as those without symptoms.
2, to synthesize ferritin, transferrin saturation to judge. If necessary, other tests should be consulted, such as: percentage of low-pigmented erythrocytes, reticulocyte hemoglobin content, etc. In rare cases, reference to bone marrow iron staining is required.
3, many times, experimental iron supplementation therapy can also help us determine whether the patient is iron deficiency. For example, after intravenous iron supplementation in hemodialysis patients, if anemia can be improved, it indicates that there is a relative iron deficiency (oral iron supplementation is not enough). After all, human erythropoietin is a false increase in the value of high-iron protein.
4, many patients should not take iron supplementation orally. Because chronic diseases lead to disorders of iron metabolism regulation, the effect of oral iron supplementation is almost zero; at this time intravenous iron supplementation is required. Typical of these are hemodialysis patients and patients with chronic heart failure.
Resources:
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11，Ponikowski P, Kirwan BA, Anker SD, et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet 2020; 396:1895.
12，Fowler AJ, Ahmad T, Phull MK, et al. Meta⁃analysis of the association between preoperative anaemia and mortality after surgery[J]. Br J Surg, 2015, 102(11): 1314⁃1324. DOI: 10.1002 /bjs.9861.
13，Musallam KM, Tamim HM, Richards T, et al. Preoperative anaemia and postoperative outcomes in non⁃cardiac surgery:a retrospective cohort study[J]. Lancet, 2011, 378(9800):1396⁃1407. DOI: 10.1016/S0140⁃6736(11)61381⁃0.
14，Grote Beverborg N, Klip IT, Meijers WC, et al. Definition of Iron Deficiency Based on the Gold Standard of Bone Marrow Iron Staining in Heart Failure Patients. Circ Heart Fail 2018; 11:e004519.