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O
+
7
+
+
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. 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 -
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+
7
+
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. 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cohort of patients7In unpublished data collected as a follo"Dup stud( of the original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 $he duration of breast feeding "as longer -
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+
7
+
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. in those "omen "ho had recei'ed I) iron pol(maltose 'ersus oral iron7 Women
"ith better iron status "ere less do"nhearted -
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+
7
+
+
3
. and less liel( to de'elop postnatal clinical depression -
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+
7
+
+
2
.7$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
+
+
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,
. 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
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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
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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
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,
.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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