Risk factors for anaemia during pregnancy

Iron deficiency (or lack of iron) can create a low haemoglobin (or low red blood cell count). This is usually referred to as 'anaemia'. Iron deficiency is very common in developing countries, especially in children and childbearing women. However, it is estimated that less than !" of childbearing women are iron deficient in countries like #ustralia, $ew %ealand, the &nited 'tates, (anada and the &nited )ingdom. 'igns of being iron deficient (whether pregnant or not) can include e*cessive tiredness, lethargy, lack of motivation and feeling irritable and weak than would normally be e*pected. +ou may also e*perience headaches or have a poor resistance to minor illnesses and possibly 'feel the cold' more. ,air skinned women will tend to look very pale, but women with dark skin need to look on the underside of their eyelids to notice whether the mucous lining looks pale, rather than more pink or red (this is a classic sign of anaemia for fair and dark skinned people). #n unusual side effect of iron deficiency can be 'pica'. This is a desire or 'craving' to eat nonfood substances such as dirt, clay, ice or toothpaste. These do not contain iron, and in the case of clay or dirt, can actually inhibit the absorption of iron from normal foods.

Risk factors for anaemia during pregnancy

.hile pregnant women are at increased risk of becoming iron deficient, not all pregnant women become significantly anaemic and only a few will truly re/uire iron supplements. #naemia may be evident very early in the pregnancy, or something that does not become obvious until the last few months (after 01 weeks). 2lood tests for iron levels and3or haemoglobin are routinely performed at the first pregnancy visit and once (or more) later in the pregnancy. This is discussed later in this section in blood tests for iron. 4ccasionally, caregivers may recommend iron supplements, particularly if your blood levels are not within the normal range. However, care should be taken not to take iron supplements unless necessary. This is covered later in iron supplements.

Management of IDA

# recommended approach to assessment and management of I5# is outlined in 2o* 0. The underlying cause must be established in all patients. Importantly, in men and postmenopausal women with I5#, and also in some premenopausal women, evaluation for benign or malignant 6I lesions, inflammatory conditions (such as inflammatory bowel disease) and peptic ulceration is indicated. 'creening for coeliac disease should be performed.7,08
Dietary therapy

Increasing dietary iron intake alone is inade/uate to treat frank I5# and higher supplemental doses of iron are re/uired (2o* 7). However, increasing iron consumption and optimising absorption by minimising inhibitors and ma*imising enhancers may be valuable for secondary prevention of iron deficiency. 9ecommended daily dietary intake of iron at different ages is presented in 2o* .
Oral therapies

#lthough more than !! preparations containing iron are available over the counter in #ustralia, few contain sufficient elemental iron to treat I5# effectively. The usual recommended dose of oral iron for the treatment of I5# in adults is !!:0!! mg of elemental iron daily or in 0 to ; divided doses<;! recommended doses for children are ;:= mg3kg3day of elemental iron.0!,; #ppropriate formulations are presented in 2o* 7. >ultivitamin-mineral supplements should not be used to treat I5# as iron content is low and absorption may be reduced. 'tudies in women and children have shown lower doses of oral iron may be effective and associated with fewer 6I side effects.;0 In adults, lower doses can be administered through either intermediate-dose tablets (containing around ;!:=! mg of elemental iron) or intermittent dosing (eg, second daily to weekly)< the latter approach has been recommended by the .H4 for some developing countries. ?ither approach may be useful in patients with mild I5# who e*perience 6I upset with standard doses of iron, but rapid Hb rise is not essential< however, appropriate intermediate-dose iron tablets are not available in #ustralia. 6I upset may also be reduced by taking the dose with food or at night. .hen given at e/uivalent elemental iron doses, different oral iron salts have similar efficacy and tolerability. 2ased on limited available data, controlled-release iron formulations appear to have fewer 6I side effects, but similar discontinuation rates and comparable efficacy<;; release of iron distal to the site of ma*imal intestinal absorption may theoretically limit response in some patients. #fter therapeutic doses of oral iron, reticulocytosis should occur within @0 hours, and Hb levels should rise by about 0! g3A every ; weeks. It is reasonable to replenish iron stores by continuing treatment for ;:= months (0:; months in children0!) beyond normalisation of Hb. (auses of failure to respond to oral iron are listed in 2o* B. If I5# recurs following repletion of iron stores, a bleeding source must be vigorously sought.

Parenteral iron therapy Intramuscular (IM) iron therapy

#lthough I> inCection of iron is effective, it is painful, associated with permanent skin staining and no safer than ID infusion. Its use is therefore discouraged;7 unless other approaches cannot be practically delivered (eg, when parenteral iron is indicated in remote settings).
Intravenous (IV) iron therapy

.hile oral iron remains the cornerstone of I5# therapy, some patients re/uire ID iron therapy (2o* =). &nderuse of ID iron may have stemmed in part from concerns about the risk of serious allergic reactions E for e*ample, !.=" of patients treated with high molecular weight iron de*tran (no longer available in #ustralia) had life-threatening allergic reactions.;B Iron polymaltose (,errum H F#spen GharmacareH, ,errosig F'igma GharmaceuticalsH) and iron sucrose (Denofer F#spen GharmacareH) are the parenteral iron formulations currently available in #ustralia. # Itotal-doseJ infusion (where iron stores can be repleted in a single treatment episode) can be administered only with iron polymaltose.
Iron polymaltose

#lthough iron polymaltose (iron de*trin) has been widely used in #ustralia since the 8=!s, there is limited literature concerning its safety, particularly outside the nephrology setting. #n #ustralian audit of the inhospital safety and tolerability of iron polymaltose identified no cases of anaphyla*is or other cardiorespiratory compromise in 7! infusions, and noted infre/uent minor side effects during infusion.;= This concurs with the clinical e*perience of several members of our group. 'elf-limited side effects that occur up to 0 days after infusion, including headache, fever and arthralgias, are common, affecting 0=" of patients in a recent study.;@ #n average total-dose infusion of iron polymaltose (sufficient to replenish iron stores, commonly !!! mg:0B!! mg for adults), given at the rates recommended in #ustralian approved product information, takes around B hours. # recent survey of policies at different $ew 'outh .ales health services found a broad range of infusion and premedication practices.;1 ,ew published data indicate the fastest safe rate for either total-dose infusions or smaller dose infusions given in the renal setting (B!!: !!! mg or less). 'everal #ustralian nephrology units have developed protocols and used accelerated infusion rates (9owan .alker, 5eputy 5irector of $ephrology, 9oyal >elbourne Hospital, Dictoria, and #shley Irish, 'enior 'taff $ephrologist, 9oyal Gerth Hospital, .estern #ustralia, personal communications). 5elivery of total-dose iron polymaltose infusions at accelerated rates have been safely administered by some of the authors (' ( ,-2, 9 T, G 9 6) in specialist outpatient treatment centres, with and without routine premedication. #ccounts of this e*perience should be published through prospective clinical studies in #ustralia and $ew %ealand because use of iron polymaltose outside these countries is limited. .e are not aware of accelerated administration of iron polymaltose in children.
Iron sucrose

Iron sucrose is funded by the Gharmaceutical 2enefits 'cheme for iron deficiency only in patients with chronic kidney disease who are having an erythropoietin-stimulating agent and react systemically to iron polymaltose. However, it has been licensed for treatment of I5# in ?urope for decades and has a well-documented safety profile.;8 It cannot be given as a single total-dose infusion (due to the rate of release of vasoactive iron), but is instead given as multiple smaller (commonly !!:0!! mg) ID doses. 5espite this limitation, it has the potential to provide a fle*ible alternative to iron polymaltose, being licensed for use as a Islow ID inCectionJ in many countries outside #ustralia, including the &nited )ingdom and $%. Iron sucrose may be useful to partially replace iron stores, helping to ensure more rapid increases in Hb levels when clinically important. Iron stores can then be fully replaced with oral therapy (if tolerated), with ID iron polymaltose or further doses of ID iron sucrose. 'ome hospital drug committees have approved off-label use of iron sucrose for I5#, including perioperative use.
New IV iron preparations

There are a number of new ID iron preparations. Iron carbo*ymaltose, which is available in ?urope but has not yet been granted marketing approval in #ustralia, appears to have a low risk of serious adverse effects, and infusions of !!! mg can be given over B minutes.7! 4ther preparations available internationally include low molecular weight iron de*trans, iron gluconate and ferumo*ytol.
Re cell transfusion

Transfusion of red cells remains an overused treatment for I5#.7 It is also e*pensive and potentially haKardous. In physiologically compensated patients, transfusion carries unnecessary risks and fails to replenish deficient iron stores. #de/uate doses of oral iron can improve Hb concentrations within a few weeks, and ID iron can provide more rapid and predictable increases when clinically important. Transfusion is associated with adverse outcomes, including fluid overload (around " of patients), and a range of immunological and infectious haKards. Hence, it should be reserved for immediate, targeted management in patients with severe anaemia compromising end-organ function (eg, angina pectoris or cardiac failure) or where I5# is complicated by serious, acute ongoing bleeding. Iron therapy should always follow transfusion to replenish iron stores.
!onclusion

I5# remains a common and important disorder. >easures to alleviate the burden of I5# in #ustralia should include strategies to increase awareness of the problem among clinicians and the general public, improved availability of suitable oral formulations, enhanced access to modern ID iron therapies, and prospective studies of the epidemiology, investigation and treatment of I5#, which would inform the development of best practice guidelines.