The importance of iron for overall health in humans cannot be overstated and its extremely widespread biological functions include electron transfer, intercellular signalling, catalysis, and oxygen binding and transport. Iron is found in all cells and is required for the synthesis of iron-sulphur clusters and heme proteins like cytochromes c, b5, and P450, myoglobin, neuroglobin and heme-based sensor proteins.1 It is also an enzyme cofactor that is essential for many important biological processes, and studies have shown that up to 6.5% of all human enzymes are iron-dependant.https://www.obstetricsandgynaecologyforum.comam2023Obstetrics and Gynaecolog

Dreyer, Greta

Zondagh, Jake

UPSpace at the University of Pretoria

OBSTETRICS & GYNAECOLOGY FORUM 2022 | ISSUE 1 | 1Iron Defi ciency in Women’s Health: An understated burden with serious health consequencesGreta Dreyer1, Jake Zondagh2 1Department of Obstetrics and Gynaecology, University of Pretoria, Pretoria, South Africa2Aspen, Medical Science Liaison, South AfricaImportance of iron e importance of iron for overall health in humans cannot be overstated and its extremely widespread biological functions include electron transfer, intercellular signalling, catalysis, and oxygen binding and transport. Iron is found in all cells and is required for the synthesis of iron-sulphur clusters and heme proteins like cytochromes c, b5, and P450, myoglobin, neuroglobin and heme-based sensor proteins.1 It is also an enzyme cofactor that is essential for many important biological processes, and studies have shown that up to 6.5% of all human enzymes are iron-dependant.2 e most widely known and appreciated function of iron is, however, that this seemingly unassuming element is a key component of the heme protein named haemoglobin (Hb), and responsible for binding oxygen and transporting it between the lungs and the rest of the body.2,3 In each haemoglobin molecule, four heme groups, each with one iron atom attached to a porphyrin, surrounds a globin group consisting of two linked pairs of polypeptide chains.1 Each healthy haemoglobin molecule can accordingly bind four oxygen molecules.  e majority of iron in circulation is used for erythropoiesis in the bone marrow, where up to three million red blood cells are produced every second. Any disruption in erythropoiesis due to the depletion of iron, will result is iron de ciency anaemia (IDA).4Considering the extensive physiological role of iron, it is easily understood how iron de ciency (ID) and even iron de ciency without anaemia (IDWA) can lead to many vague and general symptoms like fatigue (most common), poor attention and other cognitive symptoms, poor work and physical performance, poor condition and healing of skin, nails and hair, hair loss and restless legs. In children problems like growth and developmental delay, poor appetite, and frequent infections are o en reported.5 It remains, however, di  cult to separate the direct tissue e ects of iron de ciency from the e ects of iron de ciency anaemia via impaired oxygen delivery to all tissues and cardiovascular strain.3Iron de ciency in women’s healthConsidering iron de ciency in women’s health, there are several key considerations. IDA is the most common form of anaemia and research has shown that regardless of socio-economic background, women of reproductive age are particularly vulnerable to this nutritional de ciency.6 Non-pregnant women with one or more of the following are speci cally at high risk to have ID or IDA: heavy menstrual bleeding or abnormal uterine bleeding, heavy physical activity, frequently blood donation, and a history of gastrointestinal lesions.6 Among women with gynaecologic cancer, anaemia is particularly common. At diagnosis of several cancers associated with severe bleeding such as uterine body or cervical cancer, simple and severe IDA is the most common, but in many patients and later in the disease process anaemia is o en multifactorial. Factors that play an important role include blood loss, para-neoplastic e ects, kidney function impairment and reduced erythropoietin, nutritional and feeding di  culties, and bone marrow toxicity related to radiation and chemotherapy. Anaemia delays and interrupts treatment and has a direct and measurable negative e ect on quality of life as well as general and cancer speci c outcomes.7During pregnancy and in the postpartum period, iron demand o en exceeds either the nutritional supply, or the capacity of the gut enterocytes to upregulate iron absorption or both.5 Even during this high risk period, ID and IDA remain largely underdiagnosed and undertreated, resulting in potentially serious clinical consequences.6 In addition to the usual symptoms of ID, maternal e ects of ID and IDA also include an increased risk of blood transfusion, puerperal pyrexia and wound infection, heart failure and possibly risk for signi cant post-partum haemorrhage and death.6 Obstetrical outcomes that may be adversely in uenced include birth weight, preterm delivery rate, and perinatal death. E ects on the o spring can include detrimental cognitive and physical e ects and impaired mother-child relationships.8,9Burden of disease and diagnosisA lack of epidemiological data from South Africa likely masks the gravity of the local burden of disease. Phathane et al. reported that the overall prevalence of anaemia in the South African population was 12.6%, and that ID is found in almost 80% of all anaemic patients.10 ID was particularly high in females and O&G Forum 2022; 32: 01-02EDITORIALOBSTETRICS & GYNAECOLOGY FORUM 2022 | ISSUE 1 | 2black Africans, at 56.7% and 50.7%, respectively. A study by Symington et al. who looked at maternal ID in an urban South African setting, found prevalences of anaemia, ID and IDA were 29%, 15% and 15%, respectively, showing the necessity of addressing ID in southern Africa.11 More comprehensive and therapeutic-area speci c studies are needed to assess the full extent of ID and IDA in South Africa.Epidemiological data can assist to identify those patients most at risk for IDA who should at least be screened for anaemia with a haemoglobin test.  is includes at least all pregnant women, everyone suspected to have gynaecologic cancer and women reporting signi cant abnormal uterine bleeding. Full investigation is also essential if more severe anaemia is suspected in patients who present with pallor, tachycardia, ankle oedema, and even heart failure.7,12  e diagnosis of IDA requires laboratory-con rmed evidence of low Hb and microcytic red cell status or low iron stores. General symptoms of ID and IDWA are non-speci c, and diagnosis remains a challenge as there is no simple screening test for iron de ciency.  e following blood tests are usually performed to assess patients in whom IDWA is suspected: complete blood count, serum iron, serum ferritin, transferrin saturation, and reticulocyte Hb content.13,14 In these patients, assessment of anaemia alone is insu  cient, and iron stores also need to be taken into consideration when developing a treatment plan as any disruption in iron intake or metabolism could result in anaemia. Anaemia is the  nal stage of the disease and measures should be taken to prevent progression to this stage to ensure better patient outcomes.15TreatmentTreatment of ID and IDA needs to be individualised according to the cause, severity, previous treatment, co-morbidities, symptoms and laboratory-con rmed diagnosis. Importantly, the time available to correct the anaemia should also be taken into account. In many clinical situations, oral therapy remains the chosen  rst-line therapy for  ID and IDA, but indications for the use of parenteral iron are increasing with reduced cost and improved safety and e  cacy pro les.16,17,18Typical clinical scenarios with an urgency to correct IDA include pre-operative and antenatal patients and women awaiting further treatment such as radiation or chemotherapy. Where there is such urgency, intolerance or failure of previous oral treatment, suspected or proven poor absorption, ongoing blood loss or very severe anaemia or iron de ciency, parenteral options are more attractive as the response to treatment is faster and not in uenced by compliance or gastro-intestinal function and therefore more predictable.19   e e ect or the high dosage of iron has an additional bone marrow stimulating e ect similar to erythropoietin.20Newer innovative parenteral iron preparations, such as ferric carboxymaltose (FCM), have signi cant safety and e  cacy advantages over older-generation IV therapies, oral preparations and even blood transfusions.19,21,22 Its e  cacy and safety have been established in 2nd and 3rd trimester pregnancy.17,18 For women in later stages of pregnancy (>34 weeks of gestation), it is widely recommended internationally that IV iron be used as a  rst-line treatment.16 In the postpartum period, oral iron therapy should be administered for those with mild ID.19 For those with a more severe de ciency or anaemia, parenteral iron should be considered.22  e wide availability of safe intravenous iron therapy can dramatically reduce the use of allogenic blood transfusions.21 In women’s health parenteral high dose iron should typically replace blood transfusion in young patients without ongoing severe blood loss such as a er early pregnancy complications, post-partum, post-operative, pre-operative  and cancer patients awaiting therapy.21,22 For many patients it will be a safer and even a more e ective treatment with a better long term outcome. Moreover, one should consider the availability and scarcity of blood in South Africa.  ere is a blood shortage in South Africa with both the South African National Blood Services (SANBS), and the Western Cape Blood services o en at critically low levels.24 Blood should therefore be reserved for those who acutely need it for survival, as well as patients with signi cant bone marrow disease unable to produce haemoglobin from iron. ConclusionIn conclusion, there are numerous health consequences for women that are iron de cient.  ere are many aspects to this condition, and there remains an unmet need for South African epidemiological data, and clear diagnostic and treatment protocols. More widespread availability and use of parenteral therapy hold great promise to help reduce blood transfusions and the high burden of anaemia among South African women.25  ere is a general lack of awareness of, and a lack of attention to the prevention, short and long term management of iron de ciency among female patients in South Africa.  is is despite the obvious detrimental e ects on the health and well-being of the women and children of our country. Although there is a clear need to address these issues in South Africa, there is a lack of guidelines, clear recommendations and implementation thereof for the diagnosis and treatment of this condition especially for female patients. References1. Lin Y-W, Wang J.  Structure and function of heme proteins in non-mative states: a mini-review. J Inorg Biochem 2013:129;162-171. doi: 10.1016/j.jinorgbio.2013.07.023.2. Andreini, C., Putignano, V., Rosato, A. & Banci, L.  e human iron-proteome. Metallomics 10, 1223–1231 (2018).3. Philpott, C. C., Ryu, M. S., Frey, A. & Patel, S. Cytosolic iron chaperones: Proteins delivering iron cofactors in the cytosol of mammalian cells. J. Biol. Chem. 292, 12764–12771 (2017).4. Ginzburg, Y. Z. & Li, H. Crosstalk between iron metabolism and erythropoiesis. Adv. Hematol. 2010, (2010).5. Short, Matthew and Domagalski, J. Iron De ciency Anemia: Evaluation and Management - American Family Physician. Am. Fam. Physician 87, 98–104 (2013).6. Coad, J. & Pedley, K. Iron de ciency and iron-de ciency anemia in women. Scand. J. Clin. Lab. Invest. 74, 82–89 (2014).7. Mirza, F. G., Abdul-Kadir, R., Breymann, C., Fraser, I. S. & Taher, A. Impact and management of iron de ciency and iron-de ciency anemia in women’s health. Expert Rev. Hematol. 11, 727–736 (2018).8. Tran, T. D. et al. Impact on Infants’ Cognitive Development of Antenatal Exposure to Iron De ciency Disorder and O&G Forum 2022; 32: 01-02EDITORIAL

Iron deficiency in women’s health : an understated burden with serious health consequences

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Iron deficiency in women’s health : an understated burden with serious health consequences

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