Iron homeostasis

• Iron levels in the body are balanced through the absorption of dietary iron, iron recycling, utilization and loss. As humans are unable to excrete iron, iron homeostasis must be maintained by regulating the amount of iron that is absorbed from the diet by the absorptive intestinal cells (enterocytes) and the amount of iron that may be utilized or stored by extraintestinal tissues (73). Iron requirements in the general population with SCD
• People with SCD often receive blood transfusions, either for treatment or prophylaxis. Repeated blood transfusions are associated with a risk of iron overload, as transfusions are a much more efficient form of iron uptake than dietary absorption. In addition, chronic haemolysis in SCD increases serum iron, which also contributes to iron overload (74). Iron overload can have serious consequences including organ damage, particularly in the liver and heart (75). Therefore, iron supplementation is not a consideration in the management of SCD, unless iron-deficiency anaemia is identified. Increased iron requirements during pregnancy
• During pregnancy there is increased need for iron due to the needs of the fetus and placenta, and expansion of the maternal red blood cell mass (76). The duodenum increases iron absorption in pregnancy but increased dietary intake is typically also needed (76). Pregnant women frequently suffer from irondeficiency anaemia as a result (76).
• Iron-deficiency anaemia in pregnancy is associated with increased rates of adverse maternal outcomes (e.g. pre-eclampsia, placenta previa, caesarean delivery, longer hospitalization, increased antenatal admission, and increased requirement for red blood cell transfusion) and adverse neonatal outcomes (e.g. preterm birth, small for gestational age, a low 5-min Apgar score, and neonatal and perinatal death) (77, 78).
• For women in the general pregnant population, WHO recommends daily supplementation with 30 to 60 mg elemental iron or, in contexts when daily iron is not acceptable to the woman due to side-effects or in areas where prevalence of anaemia is low (e.g. <20%), weekly supplements of 120 mg of elemental iron (14, 35). Iron supplementation during pregnancy for women with SCD
• The systematic review conducted to inform this guideline found that the effect of iron supplementation compared to placebo on the risk of sickle-cell crisis, maternal postnatal haemoglobin and birthweight is uncertain (one trial; 14 women; very low certainty) (45). No other priority maternal or newborn outcomes were reported.
• The GDG noted that, due to the potential for iron overload in women with SCD receiving blood transfusions, confirmation of iron deficiency (rather than other causes of anaemia) is needed before anaemia is treated with iron supplementation. Prenatal vitamins often contain iron and may also contribute to iron overload in women who do not have confirmed iron deficiency.
• WHO recommends the use of ferritin concentrations to assess iron stores in healthy individuals. Because ferritin is an acute phase protein that rises due to the inflammatory process, use of a higher threshold (i.e. 70 µg/L) is recommended under conditions of infection and inflammation to diagnose iron deficiency (79). Additionally, under these conditions a ferritin concentration exceeding 500 µg/L may indicate the risk of iron overload and further clinical and laboratory evaluation is recommended. Although WHO recommends a ferritin cutoff of <15 µg/L for diagnosing iron deficiency in healthy women in their first trimester of pregnancy (79), there is no guidance on thresholds for defining iron deficiency or overload specifically for pregnant women with infection or inflammation. There are several changes occurring in pregnancy that may affect plasma or serum ferritin concentrations when assessing iron status, including the physiological rise in acute phase proteins in pregnancy and the expansion of plasma volume in the second trimester (80).