‘A 36-year-old woman presents at 28 weeks gestation in her second pregnancy with fatigue and shortness of breath. Her haemoglobin is 95g/L and her ferritin is 5µg/L. She is taking a pregnancy multivitamin. She has an 18-month-old child who was delivered as an emergency caesarean section (CS) for fetal distress at a gestation of 40 weeks and three days. This was complicated by a 1000ml blood loss. Postpartum, she was treated for iron deficiency anaemia with oral iron tablets that caused constipation and exacerbated her haemorrhoids. It is planned that she will have a repeat CS at 39+ weeks. Does she need an iron infusion?’

Iron deficiency anaemia (IDA) affects nearly a quarter of all pregnancies in the Western world, due to the increasing iron demands of each subsequent trimester. By the third trimester, iron demands are three-times greater than in the non-pregnant menstruating woman, owing to increases in red cell mass to enable adequate fetal oxygenation.¹ Iron demands continue to be elevated if women breastfeed. Symptoms of IDA in pregnancy include fatigue, light-headedness, palpitations and shortness of breath. Extreme anaemia can present with chest pain. It is unknown at what haemoglobin level maternal mortality increases; however, maternal morbidity from untreated IDA includes susceptibility to infection and postpartum disturbances to cognition and emotions.^{2 3} The recently published National Blood Authority (NBA) ‘Patient Blood Management (PBM) Guidelines: Module 5 – Obstetrics and Maternity’ provides guidance and recommendations to clinicians for prevention and management of iron deficiency anaemia in pregnancy.

There is no nationally agreed definition for IDA in pregnancy; however, most maternity hospital laboratories have established haemoglobin reference ranges for each trimester. The World Health Organization (WHO) defines anaemia in pregnancy as Hb <110g/L in the first trimester and <105g/L in the second and third trimesters.⁴ While haemoglobin is the best measurement of anaemia, inadequate iron stores are confirmed by measuring ferritin, as it is depleted before a fall in haemoglobin is seen. A ferritin level of <15µg/L is diagnostic of iron deficiency while a level of 15–30µg/L is highly suggestive. Women noted to have a ferritin level of 80µg/L or above in the first trimester are likely to have adequate iron stores for their pregnancy.⁵

An investigation for IDA should consist of a full blood examination (FBE) and blood film looking for microcytic hypochromic anaemia at booking. If IDA is suspected, a confirmatory ferritin level should then be performed. Simultaneous testing of an FBE with ferritin should only be performed in women considered at risk of IDA so that early treatment can occur.⁶ This group includes indigenous Australian and New Zealand women, teenagers, vegetarians, women with inflammatory bowel disease or previous bariatric/bowel surgery, a past history of postpartum haemorrhage and when there has been less than 12 months duration between pregnancies. Ferritin can be spuriously elevated in infective and inflammatory states. If this is the case, complete iron studies can be done to diagnose iron deficiency. Determining the aetiology of IDA is important. The majority of maternity patients will have IDA owing to inadequate dietary iron intake in the face of the increasing physiological iron demands of pregnancy. However, other aetiology – such as previous heavy menstrual loss or gastrointestinal blood loss – should be considered in women presenting with IDA in early pregnancy or beyond six weeks postpartum.

The majority of pregnant women will have adequate iron stores to deal with the physiological demands of pregnancy and, for this reason, in the PBM Module 5 guidelines, the routine use of iron supplementation in pregnancy is not recommended.⁷ In women who require iron supplementation for IDA, first-line treatment requires an oral iron preparation containing at least 100mg of elemental iron.⁸ Given iron supplements do not require prescription, clinicians can recommend iron preparations and encourage women to check the iron content of the pregnancy supplement they purchase, as many preparations contain inadequate elemental iron to sufficiently treat IDA. Ideally, preparations will also contain vitamin C or women can be counselled to take a source of vitamin C, such as orange juice, with their iron supplement to aid iron absorption. Oral iron is cheap (one month costs less than $20) and readily available; however, unfortunately, oral iron can exacerbate adverse gastrointestinal effects of pregnancy, especially constipation, haemorrhoids and nausea. Trialling a lower dose of iron, such as 80mg daily, may help reduce these side effects.⁹ Relief of symptoms and an increase in haemoglobin by approximately 20g/L should occur after three to four weeks of compliant therapy.¹⁰

If oral iron has been inadequate, not tolerated or patients are noncompliant, then using intravenous iron may be appropriate. Other indications to use intravenous iron upfront include women diagnosed with IDA in late pregnancy (more than 38 weeks gestation); women with IDA with a high risk of antepartum blood loss, for example, women with placenta percreta; or symptomatic postpartum women that have suffered moderate blood loss (Hb <80g/L).¹¹ The total iron deficit must be calculated before the administration of intravenous iron. In most cases, 1000mg of iron replacement is adequate. Iron carboxymaltose is now superseding both iron polymaltose and iron sucrose as the preparation of choice for infusion. Mainly because an equivalent dose of 1000mg of iron can be given over 15 minutes, rates of anaphylaxis during infusion are lower and incorporation into red cells with symptomatic relief occurs in a short timeframe (48–72 hours). Iron carboxymaltose has also been used in randomised controlled trials in pregnant and postpartum women with maternal and fetal comorbidity equivalent to oral iron.¹² The main drawback is cost: upfront iron carboxymaltose is approximately ten-times more expensive than iron polymaltose. However, the cost of the drug is offset by a cheaper inpatient stay, as beds and staffing are required for much shorter periods of time. Iron carboxymaltose is very easy to use to treat IDA intravenously and hospitals need to have robust clinical practice guidelines and auditing tools in place to ensure that its administration is not misused and that quality assurance processes are met.

The patient in this scenario meets the definition of IDA. Her risk factors include less than 12 months between pregnancies and a previous postpartum haemorrhage. She has had gastrointestinal side effects from oral iron in the past, which may make her reluctant to take oral iron again. She requires definitive treatment, given her iron stores will continue to fall as she enters the final trimester of pregnancy. In accordance to the PBM Module 5 guidelines, it is important to treat her anaemia and optimise her red cell mass before her repeat CS to reduce the transfusion risk in the setting of potential blood loss. In this woman an iron infusion is reasonable, but when is administration appropriate? If she is amenable, there is time to trial a reduced dose of oral iron for four weeks with a clinical review and follow-up. However, if she is already suffering from constipation and haemorrhoids she is unlikely to submit to an oral iron trial. In this setting, it is reasonable to offer an iron infusion with iron carboxymaltose upfront.

Iron infusions should be offered to women who have IDA, not iron deficiency alone. While untreated iron deficiency will result in anaemia with time, there is no evidence that treating iron deficiency without the presence of anaemia (in other words, treating a low ferritin level <30µg/L and normal Hb level >110g/L), reduces maternal or fetal morbidity. These patients, who are unlikely to be symptomatic, should be monitored and offered a trial of oral iron.

The PBM Module 5 guidelines indicate that in an obstetric and maternity setting, blood transfusion is usually appropriate if a patient’s haemoglobin is less than 70g/L. With intravenous iron so easy to administer, clinical trials are needed in the maternity setting to determine at what haemoglobin level intravenous iron is ineffective and blood transfusion more appropriate.

1. Pasricha SR, Flecknoe-Brown SC, Allen KJ et al. Diagnosis and managemaent of iron deficiency anaemia: a clinical update. Med J Aust. 2010; 193(9):525-32.
2. Ekiz C, Agaoglu L, Gurel N et al. Hematol J. 2005; 5(7):579-83.
3. Beard JL, Hendricks MK, Perez EM et al. Maternal iron deficiency affects postpartum emotions and cognition. Journal of Nutrition. 2005; 135(2):267-72.
4. WHO. Iron deficiency anaemia: assessment, prevention and control. 2001. WHO/NHD/01.3, Geneva.
5. Hallberg L, Bengtsson C, Lapidus L et al. Screening for iron deficiency: an analysis based on bone marrow examinations and serum ferritin determinations in a population sample of women. Br J Haematol. 1993; 47(120):875-9.
6. Pavord S, Myers B, Robinson S et al for the British Committee for Standards in Haematology. UK guidelines on the management of iron deficiency in pregnancy. BCSH: July 2011.
7. National Blood Authority. Patient blood management guidelines: Module 5 Obstetric and Maternity. National Blood Authority, Canberra, Australia. 2015. Available from: www.blood.gov.au/pbm-module-5.
8. National Blood Authority. Patient blood management guidelines: Module 5 Obstetric and Maternity. National Blood Authority, Canberra, Australia. 2015. Available from: www.blood.gov.au/pbm-module-5
9. National Blood Authority. Patient blood management guidelines: Module 5 Obstetric and Maternity. National Blood Authority, Canberra, Australia. 2015. Available from: www.blood.gov.au/pbm-module-5.
10. Pavord S, Myers B, Robinson S et al for the British Committee for Standards in Haematology. UK guidelines on the management of iron deficiency in pregnancy. BCSH: July 2011.
11. National Blood Authority. Patient blood management guidelines: Module 5 Obstetric and Maternity. National Blood Authority, Canberra, Australia. 2015. Available from: www.blood.gov.au/pbm-module-5.
12. Seid MH, Derman RJ, Baker JB et al. Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anaemia: a randomised controlled trial. Am J Obstet Gynecol. 2008; 199(4):435.e1-7.