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Journal of Pregnanc(
)olume *+,* -*+,*./ Article I0 12+3,4/ ,+ pages
http566dx7doi7org6,+7,,336*+,*612+3,4&e'ie" ArticleIron 0e8cienc( Anaemia in
Pregnanc( and Postpartum5 Pathoph(siolog( and E9ect of %ral 'ersus Intra'enous
Iron $herap( Alhossain A7 :halafallah,/* and Amanda E7 0ennis*/2,0epartment of
;aematolog(/ <aunceston General ;ospital/ <aunceston/ $asmania =*3+/ Australia
*School of ;uman <ife Sciences/ >ni'ersit( of $asmania/ Australia
20epartment of %bstetrics and G(naecolog(/ <aunceston General ;ospital/
$asmania =*3+/ Australia&ecei'ed 2 #ebruar( *+,*? &e'ised @ April *+,*? Accepted
,A April *+,*Academic Editor5 Bils Milman Cop(right C *+,* Alhossain A7
:halafallah and Amanda E7 0ennis7 $his is an open access article distributed under
the Creati'e Commons Attribution <icense/ "hich permits unrestricted use/
distribution/ and reproduction in an( medium/ pro'ided the original "or is properl(
cited7AbstractButritional ironDde8cienc( anaemia -I0A. is the most common disorder
in the "orld/ a9ecting more than t"o billion people7 $he World ;ealth %rganiEationFs
global database on anaemia has estimated a pre'alence of ,@G based on a
regressionDbased anal(sis7 &ecent data sho" that the pre'alence of I0A in pregnant
"omen in industrialiEed countries is ,=7@G "hile the incidence of I0A in de'eloping
countries increases signi8cantl( up to 31G7 Although oral iron supplementation is
"idel( used for the treatment of I0A/ not all patients respond adeHuatel( to oral iron
therap(7 $his is due to se'eral factors including the side e9ects of oral iron "hich
lead to poor compliance and lac of eIcac(7 $he side e9ects/ predominantl(
gastrointestinal discomfort/ occur in a large cohort of patients taing oral iron
preparations7 Pre'iousl(/ the use of intra'enous iron had been associated "ith
undesirable and sometimes serious side e9ects and therefore "as underutilised7
;o"e'er/ in recent (ears/ ne" t(pe II and III iron complexes ha'e been de'eloped/
"hich o9er better compliance and toleration as "ell as high eIcac( "ith a good
safet( pro8le7 In summar(/ intra'enous iron can be used safel( for a rapid repletion
of iron stores and correction of anaemia during and after pregnanc(7,7 Iron
0e8cienc( in Women Butritional iron de8cienc( is the most common de8cienc(
disorder in the "orld/ a9ecting more than t"o billion people "orld"ide/ "ith
pregnant "omen at particular ris J,K2L7 World ;ealth %rganiEation -W;%. data
sho" that iron de8cienc( anaemia -I0A. in pregnanc( is a signi8cant problem
throughout the "orld "ith a pre'alence ranging from an a'erage of ,@G of
pregnant "omen in industrialiEed countries to an a'erage of 31G -range 23K=3G. in
de'eloping countries J*/ 2L7#urthermore/ I0A not onl( a9ects a large number of
"omen and children in the de'eloping "orld/ but is also considered the onl(
nutrient de8cienc( that is signi8cantl( pre'alent in the de'eloped "orld also7 $he
number of patients "ith I0 and I0A is o'er"helming as more than * billion people/
approximatel( 2+G of the "orldFs population/ are iron de8cient "ith 'ariable
pre'alence/ distribution/ and contributing factors in di9erent parts of the "orld J,K
2L7Iron de8cienc( a9ects more "omen than an( other condition/ constituting an
epidemic public health crisis7 It is usuall( present "ith subtle manifestations and
should be considered as a chronic slo"l( progressing disease that is often
underestimated and untreated "orld"ide despite se'eral "arnings and a"areness
campaigned b( the W;% J,K2L7$he high pre'alence of I0A in "omen has substantial
health conseHuences "ith subseHuent socioeconomic haEards/ including poor
pregnanc( outcome/ impaired educational performance/ and decreased "or
capacit( and producti'it( J,/ @L7Because of the magnitude and conseHuences of iron
de8cienc( anaemia in the "orld/ especiall( in "omen in their childbearing period/
se'eral international conferences on nutrition ha'e addressed this issue in order to
reduce the pre'alence of iron de8cienc( in "omen of childbearing age "ithout
maMor success J,K1L7 $he conseHuences of I0A ha'e been "idel( studied J=K,+L7
;o"e'er/ there remains a lac of data about its e9ects on patientFs
"ellbeing7$argeted iron supplementation/ an ironDrich diet/ or both/ can impro'e iron
de8cienc(7 ;o"e'er/ the 'ariabilit( of bioa'ailable iron compounds limits its 'alue
against nutritional iron de8cienc(7 $herefore/ laborator( measures of iron stores
should be utilised to determine iron de8cienc( and monitor therap( J2K1L7$his
re'ie" highlights the importance of I0A in pregnanc( and discusses appropriate
treatment in order to a'oid serious complications of anaemia7*7 Iron Metabolism $he
balance of iron metabolism in health( indi'iduals predominantl( re!ects three
'ariables5 nutritional intae/ iron loss/ and current demand7 $he nutritional iron
intae relates to the amount of digested iron in food and the abilit( to absorb iron
from the digesti'e tract J@L7 $he amount of iron absorbed depends largel( on the
presence or absence of patholog( of the gastrointestinal tract or a comorbidit(
-such as chronic in!ammator( diseases. that ma( result in expression of the iron
regulator( proteins and a peptide called hepcidin/ "hich ultimatel( blocs iron
absorption J,,K,2L7$he main source of iron in humans comes from the destruction
of er(throc(tes b( macrophages of the reticuloendothelial s(stem including the
spleen or in other "ords/ a rec(cled internal iron suppl(7 &ecent studies ha'e sho"n
ho" the human bod( upD and do"nregulates iron absorption in response to
changing iron status 'ia intestinal and hepatic proteins J,*K,3L7*7,7 Iron Metabolism
in Pregnanc(0uring pregnanc(/ fetal hepcidin controls the placental transfer of iron
from maternal plasma to the fetal circulation7 When hepcidin concentrations are
lo"/ iron enters blood plasma at a high rate7 When hepcidin concentrations are high/
ferroportin is internaliEed/ and iron is trapped in enteroc(tes/ macrophages/ and
hepatoc(tes J,,/ ,3L7 $he dail( reHuirement of external iron remains as little as
bet"een , to Amg dail( J,1L7 ;o"e'er/ more external iron is reHuired to balance
increased demand for iron especiall( "ith ph(siological reHuirements during gro"th/
pregnanc(/ and lactation J,1/ ,=L7 $his signi8cant increased demand for iron is
reHuired to de'elop the fetus and placenta in addition to support motherFs blood
'olume7 #urthermore/ pregnant "omen are subMect to iron loss during and after
deli'er( J,1K,AL7$he total iron loss associated "ith pregnanc( and lactation is
approximatel( ,+++mg J,1/ ,=L7 $herefore the recommended dail( dietar(
allo"ance for iron in pregnanc( is *=mg instead of Amg in the adult nonpregnant
population7 <actation reHuires a dail( dietar( allo"ance of ,+mg7 J,1K,AL727
<aborator( Marers for Iron Status27,7 0e8nition of Anaemia in I0A in Pregnant and
Bonpregnant WomenAnaemia of pregnanc( is generall( de8ned as ;b O,,+g6< or
O,,3g6< in some clinical practice guidelines "ith a slight 'ariation according to the
trimester of pregnanc(7 ;o"e'er/ a haemoglobin le'el O,++g6< indicates anaemia
at an( stage during pregnanc( that should initiate in'estigations and treatment
because of potentiall( serious conseHuences for the mother and her bab(/ "ith an
increased ris of intrauterine gro"th retardation and premature birth7 In the
meantime/ anaemia in "omen of reproducti'e age is de8ned as ;b O,*+g6< or in
some studies O,,3g6< as this is laborator( and population speci8c J=K,+L727*7
0e8nition of Iron 0e8cienc( -I0.Iron de8cienc( can be classi8ed as se'ere I0 "hen
the serum ferritin le'el is belo" *+K2+Pg6< and mildDmoderate I0 if the serum
ferritin le'el is belo" =+K,++Pg6<7 #erritin le'el is considered the surrogate marer
for I07 ;o"e'er/ serum ferritin is an acute phase reactant and ma( be raised in
cases of in!ammation or infection/ therefore a concurrent test for in!ammator(
marers is ad'isable in cases of anaemia "ith raised ferritin to exclude reacti'e
causes7 I0 is most liel( not present if the ferritin le'el is abo'e ,++Pg6<
J,+L7Although a stud( of bone marro" iron stores is generall( regarded as the
de8niti'e marer of iron de8cienc(/ it remains an impractical and in'asi'e
procedure to appl( for most patients7 Measurement of both soluble transferrin
receptor and serum ferritin pro'ides a tool for accurate diagnosis of I0A J,4K*,L7
;o"e'er/ transferrin receptor is not a "ellDstandardiEed test that can be reliabl(
reproduced "ith high precision in most laboratories "orld"ide J*,L7In the
meantime/ ferritin estimation is an eas( automated test to perform in most
laboratories in the "orld? ho"e'er/ its use is limited in cases of in!ammation or
infection as it is considered to be in!uenced b( acute phase responses and hence
negati'el( in!uences its 'alue in clinical interpretation of the test results J,4/ *+L7
$he commonl( a'ailable laborator( tests that determine iron status/ namel(/ serum
iron/ transferrin/ total ironDbinding capacit( -$IBC./ transferrin saturation/ and
ferritin are "idel( used in "orld"ide clinical practice J,4/ *+L7Soluble $f& -s$f&. is
present in human plasma and is considered as a truncated form of the tissue
receptor that exists as a transferrinDreceptor complex and therefore it re!ects tissue
iron de8cienc( J*,L7 Another protein that pla(s a crucial role in iron metabolism is
hepcidin/ "hich is primaril( made b( hepatoc(tes and secreted into the blood
circulation7 ;epcidin is a smallDsiEed molecule composed of *3Damino acid peptide/
"hich is renall( excreted and therefore can be detected and measured in urine J,@/
,3L7 #urthermore/ hepcidins rapid excretion suggests that it is regulation triggered
at the le'el of production sites7 ;epcidin circulates in the ferroportins plasma and
responds to 'arious stimuli that regulate iron stores and serum iron J,3L7&ecent
studies demonstrate that hepcidin le'els are reduced in iron de8cienc( J,@/ ,3L7
Measurement of blood or urine hepcidin le'els can be achie'ed b( mass
spectrometr( and immunoassa(s in serum/ plasma/ and urine J**L7 ;o"e'er/ the
diagnostic utilit( of serum hepcidin in iron de8cienc( has not (et been de8ned in
clinical application J*2L7 Be'ertheless/ hepcidin estimation seems a potentiall(
accurate test that re!ects the actual iron status "ith less limitations7Altogether/ ne"
technolog( such as h(pochromic reticuloc(tes and reticuloc(te haemoglobin testing/
s$f&/ and hepcidin ha'e reportedl( been de'eloped "ith higher sensiti'it(/
speci8cit(/ reproducibilit(/ and cost e9ecti'eness J,4K*@L7 $his ma( o9er a reliable
screening tool for iron de8cienc( in the future7 It is "orth noting that there are no
speci8c data addressing the di9erence of these marers in the pregnant 'ersus
nonpregnant population7 ;o"e'er/ in principle/ no essential change should occur in
iron metabolism in the pregnant 'ersus nonDpregnant population except for the
increased iron demand as discussed before72727 Current Strateg( to Assess Iron
0e8cienc( during Pregnanc(#ull blood count and MC) 'alue allo"ing the diagnosis
of microc(tic anaemia is considered a good screening tool for I0A7 ;o"e'er/ in
areas of the "orld "here haemoglobinopathies are pre'alent and these ma( be
associated "ith microc(tosis/ iron studies/ in particular ferritin le'el remains the
surrogate marer for I0A7 According to the ferritin le'el/ iron de8cienc( can be
classified as se'ere I0 "hen the ferritin le'el is O2+Pg6< or mildDmoderate I0 if
ferritin O,++Pg6< and Q2+Pg6< -there is a "ide normal range bet"een *+ and @1@
and is laborator( and method specific. JAL7 In cases of ele'ated ferritin Q,++Pg6<
"ith a concurrent anaemia/ a reacti'e common cause such as infection should be
excluded and other causes of anaemia should be examined accordingl(7 %ther
complementar( tests in iron studies such as serum iron/ iron binding capacit(/ and
transferrin saturation are helpful in con8rming the diagnosis of I0A7@7 %ral 'ersus
Intra'enous Iron for $reatment of Iron 0e8cienc( in Women of &eproducti'e Age and
Pregnanc(%ral iron therap( is the most "idel( prescribed treatment for iron
de8cienc( anaemia/ ho"e'er/ there are man( issues that ma( pre'ent oral iron
supplementation from successfull( managing I0A7 #or instance/ man( patients do
not respond adeHuatel( to oral iron therap( due to diIculties associated "ith
ingestion of the tablets and their side e9ects7 Side e9ects ma( pla( a signi8cant
role in rates of compliance J*3/ *1L7 #urthermore/ the presence of bo"el disease
ma( a9ect the absorption of iron and thereb( minimiEe the bene8t recei'ed from
oral iron therap( J*=K*4L7$he side e9ects of oral iron therap( include
gastrointestinal disturbances characteriEed b( colic( pain/ nausea/ 'omiting/
diarrhoea/ and6or constipation/ and occur in about 3+G of patients taing iron
preparations J,2/ *=K*4L7#urthermore/ the most "idel( prescribed oral iron is mainl(
composed of ferrous salts J*3K*=L7 #errous salt is characteriEed b( lo" and 'ariable
absorption rates7 Its absorption can be limited b( ingestion of certain foods as "ell
as mucosal luminal damage J*=K*4L7 $herefore/ ferric compounds "ere introduced
to a'oid such obstacles7 ;o"e'er/ these compounds are generall( less soluble and
ha'e poor bioa'ailabilit( J*4L7$he usual recommended oral iron sulphate dose for
the treatment of iron de8cienc( is at least A+mg dail( of elemental iron/ "hich is
eHui'alent to *3+mg of oral iron sulphate tablets -Abbott/ Australasia Pt( <td7.7Iron
absorption reHuires an acidic medium/ therefore its absorption ma( be decreased b(
intae of antacids or proton pump inhibitors and histamine receptor antagonists7
Interference of iron absorption ma( occur "ith the intae of certain medications/
"hich thereb( minimises the bene8t recei'ed from oral iron treatment J*4L7$he
maMor challenges in the management of I0A are related to the tolerabilit( and side
e9ects of iron therap( in its di9erent forms7 $herefore/ it is crucial to determine the
most appropriate form and dose of iron as "ell as duration of treatment in order to
successfull( replenish iron stores7 Although oral iron is "idel( used "orld"ide/ the
e9ecti'eness of oral iron is largel( compromised b( lac of absorption/ poor
compliance/ increased ad'erse e9ects -up to 31G./ and discontinuation of
treatment -up to *+G. J@/ *1/ *4L7$herefore/ parenteral iron is seen to be an
attracti'e option in the treatment of I0A and is liel( to be more popular due to the
introduction of ne" intra'enous iron preparations/ "hich allo" high doses of iron to
be administered rapidl( in a single treatment J2+K2*L7@7,7 Side E9ects of I) IronIn
the past/ intra'enous iron had been associated "ith undesirable and sometimes
serious side e9ects and "as therefore limited in use J22/ 2@L7 ;o"e'er/ in recent
(ears/ ne" t(pe II and III iron complexes ha'e been de'eloped "hich are better
tolerated and can be used for rapid repletion of iron stores J2@/ 23L7 0espite the
increasing e'idence of the safet( of the ne"er preparations/ both in pregnant and
general populations/ intra'enous iron continues to be underutilised because of
pre'ious concerns "ith tolerabilit( of older intra'enous iron preparations J=/ A/
2+L7&e'ie" of infusions of iron dextran among @A, patients of both sexes re'ealed
that about *3G of patients had mild side e9ects/ "hich "ere selfDlimiting7 ;o"e'er/
about *G experienced se'ere allergic reactions and about +71G "ere considered as
anaph(lactic reactions7 Most of these reactions occurred immediatel( during the
infusion of the test dose J21L7Iron gluconate is considered to ha'e a lo"er reaction
rate and therefore a test dose is not recommended "ith onl( 272 allergic e'ents per
million doses per (ear "ith iron gluconate reported J2=L7 $here "ere no lifeD
threatening reactions recorded as a result of iron gluconate infusion7 %n the other
hand/ there "ere 2, fatalities among ,41 allergic6anaph(lactic reactions/ "hich
"ere reported for iron dextran J2=L7$he high incidence of ad'erse reactions to iron
dextran/ including serious ad'erse e'ents ha'e limited its application in pregnanc(
J2AK@+/ @2L7 Whilst the application of iron gluconate is considered safe/ it remains
impractical in theor( as it reHuires multiple infusions "ith huge implications on the
often limited health s(stem resources as "ell as on patientsF compliance7More
recentl( ne" forms of intra'enous iron that ha'e been de'eloped and are a'ailable/
are permitting treating ph(sicians to safel( administer relati'el( high doses of iron
in a single dose treatment7@7*7 Intra'enous 'ersus %ral Iron $herap( in
Pregnanc(Intra'enous iron/ including iron sucrose/ "as emplo(ed in randomised
controlled trials "ith impro'ed e9ecti'eness of intra'enous iron onl( or in
combination "ith oral iron/ compared to oral iron onl(/ based on ;b le'els J@,K@2L7A
single I) iron sucrose dose has been reported to be associated "ith an increased
incidence of thrombosis -46@,/ **G. J@2L7 In contrast/ 1 small doses of intra'enous
iron sucrose administered o'er a threeD"ee period "ere "ithout infusionD
associated thrombosis/ "ith intra'enous iron sucrose administered in 3 dail( doses
to @3 pregnant "omen/ also "ell tolerated J@,L7 In the 8rst stud( utilising
intra'enous iron sucrose/ there "as no signi8cant di9erence in ;b le'els at an( time
measured at da(s A/ ,3/ *,/ and 2+ and at deli'er( J@*L bet"een intra'enous iron
sucrose or oral iron sulphate7 In contrast/ in another trial/ "ith 1 small doses of iron
sucrose/ there "as a signi8cant di9erence in ;b le'els in fa'our of the intra'enous
iron sucrose group as measured at * and @ "ees after administration of I) iron and
at deli'er( J@,L7 ;o"e'er/ both trials administered I) iron sucrose at the expense of
a 'astl( greater e9ort from the patients to present to the hospital for 1 infusions in
a short period of time as "ell as the extra demands on hospital resources J@,/
@*L7#urthermore/ relati'el( older and established iron preparations such as
intra'enous iron pol(maltose -#errosig/ Sigma Pharmaceuticals/ Australia.
demonstrated a high safet( pro8le in the treatment of I0A in both obstetric and
general populations "ithout a maximum dose of treatment J2+L7 $he total dose of I)
iron pol(maltose is calculated according to the patientFs bod( "eight and entr( ;b
le'el "ith reference to the product guidelines as follo"s5 iron dose inmg -3+mg per
,m<. R bod( "eight in g -maximum 4+. S target ;b -,*+g6<. T actual ;b in g6<
S constant factor -+7*@. U iron depot -3++.7 Iron pol(maltose infusion sho"ed high
eIcac( and safet( pro8le during pregnanc( in the largest/ recentl( published trial
J2+L7In this stud(/ t"o hundred Caucasian pregnant "omen aged ,A (ears or abo'e
"ere identi8ed "ith moderate I0A/ de8ned as ;b V,,3g6< -reference range -&&.
,*+K,1+g6<. and lo" iron stores based on a serum ferritin le'el O2+Pg6< -&& 2+K
@@+Pg6<.7 $he I) arm reHuired a single intra'enous infusion of iron pol(maltose
-#errosig/ Sigma Pharmaceuticals/ Australia. "ithin , "ee after antennal clinic
booing/ usuall( after ,* "ees of gestation/ follo"ed b( oral maintenance therap(7
I) iron "as commenced during the *nd and 2rd trimesters onl(7 $he oral treatment
arm comprised iron sulphate *3+mg tablets -elemental iron A+mg/ Abbott/
Australasia Pt( <td7. to be taen dail( "ithin t"o da(s after booing until deli'er(
J2+L7 At preenrolment/ there "ere no signi8cant di9erences in the dietar( iron
intae or supplement intae bet"een the t"o groups based on a speciall( designed
Huestionnaire addressing these issues7 $he participants "ere follo"ed up during the
pregnanc( and at a postdeli'er( median follo"Dup period of 2* months -range *1K
@*.7 Iron status and haemoglobin "ere determined at time of entr( in the stud( as a
baseline/ then prior to deli'er( and thereafter @ "ees after deli'er( J2+L7As
reported in the original stud(/ at deli'er( the proportion of "omen "ith lo"er than
normal ferritin le'els "as =4G for "omen "ho "ere treated "ith oral iron as
compared to @73G for "omen "ho recei'ed I) iron -

O
+
7
+
+
,
. J2+L7 $he percentage of "omen at deli'er( "ith ;b le'el O,,1g6< "as *4G in the
oral iron group 'ersus ,1G in the I) iron group -

R
+
7
+
@
. J2+L7As a common practice at our institution/ "e ha'e performed more than ,+++
I) iron pol(maltose infusions for the treatment of I0A in pregnanc( during the last 3
(ears7 Most of the "omen tolerated the I) iron pol(maltose "ell "ithout maMor side
e9ects7 $here "as no recorded anaph(laxis or mortalit( secondar( to I) iron in this
cohort of patients7In unpublished data collected as a follo"Dup stud( of the original
trial J2+L/ there "as a signi8cant impro'ement in the general health of "omen "ho
recei'ed I) iron pol(maltose 'ersus oral iron -

O
+
7
+
+
,
.7 $he duration of breast feeding "as longer -

R
+
7
+
@
. in those "omen "ho had recei'ed I) iron pol(maltose 'ersus oral iron7 Women
"ith better iron status "ere less do"nhearted -

R
+
7
+
+
3
. and less liel( to de'elop postnatal clinical depression -

R
+
7
+
+
2
.7$his "ould indicate that it is "orth"hile considering the ;b and iron status as a
surrogate marer for assessment of "omenFs "ellbeing/ not onl( during pregnanc(
but also during the postnatal period7 ;o"e'er/ further studies are "arranted to
con8rm and extend these 8ndings7#urthermore/ recent reports demonstrate the
feasibilit( of rapid iron pol(maltose infusion o'er * hours J2+/ @@/ @3L7 ;o"e'er/ a
test dose of iron pol(maltose -,++mg. should be 8rst administered o'er 2+
minutes/ and premedication "ith antihistamine and6or lo"Ddose steroids is
recommended prior to iron treatment for better toleration J@@/ @3L7A recent
comprehensi'e metaDanal(sis and re'ie" b( &e'eiE et al7 J=L of the literature
bet"een ,4=+ till present on di9erent treatments for I0A of pregnanc( sho"ed
paucit( of good Hualit( trials assessing clinical maternal and neonatal e9ects of iron
administration in "omen "ith I0A in spite of the high incidence and burden of
disease associated "ith I0A7 0uring this period/ there "as onl( one prospecti'e
randomiEed trial of the e9ect of I) iron 'ersus oral iron in the treatment of I0A
during pregnanc( that ful8ls the stringent independent re'ie"er Hualit( criteria J=/
2+L737 &ecent 0ata on $reatment of I0A in the Postpartum Period$he ne"
preparations of intra'enous iron -$able ,. are seeing appro'al for use during
pregnanc( in phase II and III clinical trials from the authorised organisational bodies
in Europe and the >SA7 Be'ertheless/ the( can be potentiall( used currentl( in the
nonDpregnant female population for the treatment of postpartum/ preDfurther/ and
postmenopausal iron de8cienc( anaemia according to the regional health authorit(
appro'al7tab,$able ,5 &ecentl( a'ailable intra'enous -I). iron preparations7In a
randomised trial to assess safet( and eIcac( of intra'enous ferric carbox(maltose
in the treatment of postpartum I0A/ **= "omen "ere assigned to I) ferric
carbox(maltose "ith ,+++mg maximum dose -up to 2 "eel( doses. 'ersus ,,=
"omen "ho recei'ed oral ferrous sulphate ,++mg t"ice dail( J3*L7 Intra'enous iron
carbox(maltose "as as e9ecti'e as oral ferrous sulfate "ith no statisticall(
signi8cant di9erences bet"een groups at an( time point despite the shorter
treatment period and a lo"er total dose of iron -mean ,72g I) iron 'ersus ,17Ag
oral iron.7 #urthermore/ in the I) iron carbox(maltose group/ the increases in ferritin
le'els "ere signi8cantl( greater than in the ferrous sulphate -

O
+
7
+
+
+
,
. indicating a successful repletion of iron stores and accessibilit( for er(thropoiesis
J3*L7In a multicenter randomiEed/ controlled stud(/ *4, "omen directl( after
deli'er( "ith haemoglobin V,++g6< "ere randomiEed to recei'e ,+++mg I) iron
carbox(maltose -,@2 "omen./ repeated "eel( to a calculated replacement dose
-maximum dose *73g./ or ferrous sulfate -,@A "omen. 2*3mg orall( three times
dail( for 1 "ees -total dose @+74g. J32L7 #erric carbox(maltoseDtreated "omen
achie'ed a haemoglobin Q,*+g6< in a shorter period of time "ith a sustained
haemoglobin Q,*+g6< at da( @*7 #urthermore/ the achie'ed haemoglobin rise of
W2+g6< "as signi8cantl( more rapid in the I) iron group than the oral group in
achie'ing higher serum ferritin le'els7 0rugDrelated ad'erse e'ents occurred less
freHuentl( "ith ferric carbox(maltose J32L7In a phase 2 randomised trial ,=@ "omen
"ho recei'ed I) ferric carbox(maltose "ith a mean total dose of ,7@g 'ersus ,=A
"omen "ho recei'ed 2*3mg ferrous sulfate three times dail( for 1 "ees -total
dose @+74g. "ere assessed J3@L7 Patients assigned to I) ferric carbox(maltose
achie'ed a haemoglobin rise Q*+g6< faster than the oral iron group -= da(s
compared "ith ,@ da(s in the oral iron group/

O
+
7
+
+
,
.7 $he I) iron group signi8cantl( achie'ed a haemoglobin rise Q2+g6< at an( time
-A172G compared "ith 1+7@G in the oral iron group/

O
+
7
+
+
,
./ and "ere more liel( to achie'e a haemoglobin Q,*+g6< -4+73G compared "ith
1A71G/

O
+
7
+
+
,
.7 In the meantime/ there "ere no serious ad'erse drug reactions in both groups
J3@L7In a large randomiEed/ controlled phase 2 multicentre trial/ @== "omen "ith
I0A and hea'( uterine bleeding "ere assigned to recei'e either I) ferric
carbox(maltose -*2+ "omen. "ith a maximum dose of ,+++mg repeated "eel( to
achie'e a total calculated replacement dose/ or 2*3mg of oral ferrous sulphate -13
mg elemental iron. three times dail( for 1 "ees "ith a total dose of @+74g in **1
"omen J33L7 $"ent(Done patients did not recei'e the assigned treatment in this
stud(7About A*G of the I) iron arm achie'ed haemoglobin rise W*+g6< 'ersus 1*G
in the oral iron

O
+
7
+
+
,
7 Women "ho achie'ed a haemoglobin rise W2+g6< "ere 32G in the I) iron group
'ersus 21G in the oral iron group -

O
+
7
+
+
,
.7 Also/ more "omen -=2G. achie'ed normal haemoglobin Q,*+g6< in the I) iron
group compared to 3+G in the oral iron group -

O
+
7
+
+
,
.7 $here "ere no serious ad'erse drug e'ents7 $his trial demonstrated that patients
"ith I0A due to hea'( uterine bleeding "ho recei'ed I) iron carbox(maltose/ are
more liel( to ha'e normal haemoglobin "ith replenished iron stores
J33L7Altogether/ the ne" intra'enous iron preparations represent a medical
re'olution in e9ecti'e/ rapid/ and safe iron repletion in the management of iron
de8cienc( anaemia J@1K33L7 $his "ill positi'el( re!ect on the treatment of I0A in
di9erent populations b( application of a single highDdose intra'enous iron treatment
"ith e9ecti'e subseHuent repletion of iron stores and hence impro'ement of
subMecti'e and obMecti'e outcomes of the I0A7 Although iron de8cienc( is a
precursor of I0A/ man( clinical studies treat it similarl( to I0A717 Cost E9ecti'eness
$he cost of one iron sulphate tablet is approximatel( >S0 X+72/ so the a'erage cost
throughout one pregnanc( is calculated to be bet"een X3@ and XA47 $he cost of
iron pol(maltose containing 3++mg is X3+/ so the a'erage treatment cost is X,++7
In Australia/ the cost of the outpatient hospital 'isit and nursing time for the I) iron
adds approximatel( X1+KX,++ to the drug cost subMect to 'ariations according to
di9erent health s(stems7 $he cost of the ne" iron preparation ferric carbox(maltose
is approximatel( X*=* per a'erage ,+++mg total dose compared to X*A+ for ,+++
mg of iron sucrose -$able *.7 $his cost anal(sis is subMect to change according to
di9erent health s(stems and countries7tab*$able *5 Comparison of costs of di9erent
oral and I) iron preparations7=7 A'oiding Blood $ransfusionIn the case of se'ere I0A/
a blood transfusion has been the traditional eIcient approach to correct anaemia/
especiall( if patients did not respond to oral iron therap( or "hen a rapid correction
of anaemia is clinicall( reHuired7 Although there is a lac of data regarding the
a'oidance of blood transfusion during pregnanc(/ a recent trial in'estigating
treatment of I0A "ith oral 'ersus I) iron in pregnanc( demonstrated that none of
both treatment arm participants recei'ed blood transfusion for correction of
anaemia during pregnanc(7 ;o"e'er t"o patients -+74G. in the oral iron arm
recei'ed blood transfusion in the postpartum period J2+L7Currentl(/ the
de'elopment of ne" intra'enous iron formulations that o9er higher doses in a
single administration has pro'ided the treating ph(sicians "ith the opportunit( to
emplo( intra'enous iron as an e9ecti'e/ rapid/ and safe treatment for I0A J@1K33L/
a'oiding the use of blood transfusion "ith its no"n haEards J31L7 $here is
increasing e'idenceDbased research that supports the safet( and eIcac( of I) iron
in I0A7 $here is also increasing e'idence for inadeHuac( of oral iron in terms of
ad'erse e9ects/ lac of compliance as "ell as lac of absorption and slo" and often
Huestionable e9ect in I0A patients J2@/ 23/ @*L7A common reHuirement across the
range of clinical situations is the need for safe/ e9ecti'e/ higher/ and less freHuent
doses to achie'e optimal clinical outcomes7 $he maMor goals of such strategies
include o'erall cost reduction/ relief to o'erstretched health s(stem-s./ impro'ed
patient con'enience/ impro'ed compliance/ preser'ation of 'enous access/ and
reduced blood transfusion J2@/ 31/ 3=L7 $his "ill ultimatel( reduce the demand for
blood transfusions/ especiall( in the case of short suppl(7 #urthermore/ some of the
ne" iron preparations such as ferric carbox(maltose and iron isomaltoside do not
reHuire a test dose and therefore/ ease the application of intra'enous iron in a
timel( and costDe9ecti'e fashion7 $his certainl( "ill enhance the use of intra'enous
iron in clinical practice7A7 Summar( $he W;% has recognised the problem of I0A in
the general population as the most debilitating nutritional de8cienc( "orld"ide in
the t"ent(D8rst centur(/ noting "omen to be at particularl( high ris7 Such a
problem/ if ignored and not addressed properl(/ can ha'e a de'astating e9ect on
entire populations "ith serious conseHuences7 $herefore/ the use of intra'enous
iron should be considered as an e9ecti'e/ rapid/ and safe treatment option in some
clinical situations7 An algorithm for the treatment of iron de8cienc( anaemia in
pregnanc( and postpartum period based on di9erent prospecti'e randomised trials
is proposed in #igure , J=/ *3/ 2+/ @,/ @*L7 $he intra'enous iron is increasingl(
emplo(ed to a'oid or reduce the demand for blood transfusions or for e9ecti'e
rapid repletion of iron stores7 $reatment options for I0A should consider the recentl(
de'eloped intra'enous iron formulations/ "hich are considered a milestone in the
management of I0A -#igure ,.712+3,478g7++,#igure ,5 Proposed treatment for
anaemia in pregnanc( and postpartum period based on di9erent randomiEed and
nonDrandomiEed trials J=/ *3/ 2+/ @,/ @*/ 3*K33L7%'erall/ the de'eloping "orld is
most 'ulnerable/ especiall( the poorest and the least educated populations that are
disproportionatel( a9ected b( iron de8cienc(/ and therefore ha'e the most to gain
b( eradication of I0A7 #urthermore/ a"areness of the magnitude and scale of the
I0A problem during pregnanc( and also in the nonDpregnant female population "ill
help health practitioners in recognising the most appropriate methods of diagnosis
and treatment/ "hich are crucial in o'ercoming such a de'astating health problem7
A consensus guideline set b( "orld experts in managing I0A in "omen and in the
general population/ incorporating ne" intra'enous iron therapies "ith a global
approach of the health and econom( aspects of I0A/ should be considered7 It is
"orth"hile considering a uni'ersal comprehensi'e I0A management algorithm that
o9ers di9erent e'idenceDbased treatment options and addresses local conditions7
;o"e'er/ de'eloping countries "ith pre'alent I0A often ha'e lac of resources7
$herefore/ it is crucial to adapt a 'iable programme "ith the aim of utilising the
local a'ailable resources e9ecti'el(7 Perhaps prioritising the treatment of I0A and
increasing the a"areness among the communit( of such a chronic de'astating
problem of paramount importance is the e( for success and sustainabilit( of such a
programme7 Certainl(/ successful eradication of I0A "ill result in huge bene8ts for
communit( health and producti'it( "ith a maMor health sa'ing not onl( in the
de'eloping "orld but also in de'eloped nations7Con!ict of Interests $he authors
declare no con!ict of interests in relation to this research7 $here are non8nancial
associations that ma( be rele'ant or seen as rele'ant to the submitted paper7
Acno"ledgments$he authors "ould lie to acno"ledge the enormous help of Mrs7
Mar( Sexton/ Patholog( 0epartment/ <aunceston General ;ospital/ and Mrs7 Y'onne
;ablutEel/ Pharmac( 0epartment/ <aunceston General ;ospital in preparing the
manuscript7&eferences

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