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ORIGINAL ARTICLE
Ecacy and safety of oral iron(III) polymaltose complex versus ferrous
sulfate in pregnant women with iron-deciency anemia: a multicenter,
randomized, controlled study
Ricardo Ortiz
1
, Jorge Eduardo Toblli
2
, Juan Diego Romero
3
, Beatriz Monterrosa
3
, Cristina Frer
2
,
Eugenia Macagno
2
& Christian Breymann
4
1
Hospital Local del Norte, Bucaramanga, Colombia,
2
Hospital Alemn, Buenos Aires, Argentina,
3
Centro de Atencin Medica Inmediata
Vista Hermosa, Bogot, Colombia, and
4
UniversittsSpital Zrich, Klinik fr Geburtshilfe, Feto Maternal Research Group, Obstetric
Research, Zurich, Switzerland
Te Journal of Maternal-Fetal and Neonatal Medicine
2011
00
00
000
000
2011 Informa UK, Ltd.
10.3109/14767058.2011.599080
1476-7058
1476-4954
The Journal of Maternal-Fetal and Neonatal Medicine, 2011, 1-6, Early Online
Copyright 2011 Informa UK, Ltd.
ISSN 1476-7058 print/ISSN 1476-4954 online
DOI: 10.3109/14767058.2011.599080
Correspondence: Dr. Ricardo Ortiz, Hospital Local del Norte Cra 9 Calle 12 Norte, Bucaramanga, Colombia. Tel: +577-6405757. E-mail: rortiz@unab.edu.co
Objective: To evaluate the ecacy and safety of iron(III)
polymaltose complex (Maltofer

) versus ferrous sulfate in


iron-decient pregnant women using recommended doses.
Methods: An exploratory, open-label, randomized, controlled,
multicenter study was undertaken in 80 pregnant women with
iron-deciency anemia (hemoglobin 10.5 g/dL, serum ferritin
15 ng/mL and mean corpuscular volume < 80 fL). Patients
were randomized 1:1 to oral iron(III) polymaltose complex
or ferrous sulfate (each 100 mg iron twice daily) for 90 days.
Results: The primary endpoint, change in hemoglobin from
baseline to days 60 and 90, did not dier signicantly between
treatment groups. The mean (SD) change to day 90 was 2.16
(0.67) g/dL in the iron(III) polymaltose complex group and
1.93 (0.97) g/dL in the ferrous sulfate group (n.s). Mean serum
ferritin at day 90 was 179 (38) ng/mL and 157 (34) ng/mL with
iron(III) polymaltose complex and ferrous sulfate, respectively
(p = 0.014). Adverse events were signicantly less frequent
in the iron(III) polymaltose group, occurring in 12/41 (29.3%)
patients, than in the ferrous sulfate group (22/39 [56.4%])
(p = 0.015). Conclusions: Oral iron(III) polymaltose complex
oers at least equivalent ecacy and a superior safety prole
compared to ferrous sulfate for the treatment of iron-deciency
anemia during pregnancy.
Keywords: anemia, deciency, ferrous, IPC, polymaltose,
pregnancy, pregnant, iron, sulfate
Introduction
Iron defciency is the most common nutritional disorder in the
world [1] and is prevalent among pregnant women. Using anemia
as an indirect indicator of iron defciency, it can be estimated that
most pregnant women in non-industrialized countries, and at
least 3040% in industrialized countries, are iron defcient [1]. As
many as 50% of pregnant women may have anemia [1], and it has
been suggested that approximately 75% of all diagnosed cases of
anemia are due to iron defciency [1]. Iron defciency has a signif-
cant impact on both maternal and neonatal health, increasing
maternal mortality, prenatal and perinatal infant loss, and prema-
turity [13]. Favorable pregnancy outcomes occur 3045% less
frequently in anemic mothers, and their infants have less than
one-half of normal iron reserves [1]. WHO, United Nations
Childrens Fund (formerly United Nations International Childrens
Emergency Fund; UNICEF) and International Nutritional Anemia
Consultative Group (INACG) guidelines on the prevention and
treatment of iron-defciency anemia all recommend that preg-
nant women should routinely receive iron supplements [1]. Iron
salts (such as ferrous sulfate) and polynuclear ferric hydroxide
complexesnotably iron(III) polymaltose complexare the most
frequently prescribed oral iron preparations in this setting.
Iron(III) polymaltose complex has consistently shown equivalent
efcacy to ferrous sulfate in terms of increasing hemoglobin (Hb)
levels, as confrmed by a recent meta-analysis [4]. Although the
bioavailability of iron from either preparation is similar [5,6], the
stable structure of iron(III) polymaltose complex confers an absorp-
tion behavior diferent to that of ferrous salts [7]. As a result, the
non-transferrin bound iron that can occur in the serum afer intake
of ferrous salts is not observed afer administration of an equiva-
lent iron dose in the form of iron(III) polymaltose complex [8,9].
Non-transferrin bound iron induces oxidative stress, leading to
local gut reactions and symptoms such as vomiting, dyspepsia, diar-
rhea and heartburn [10], and to systemic adverse events including
nausea, abdominal and lower back pain and a metallic taste [11].
Gastrointestinal tolerability has been shown to be superior with
iron(III) polymaltose complex compared to ferrous sulfate [4,12].
To date, however, comparative data regarding the use of iron(III)
polymaltose complex versus ferrous sulfate in pregnant women
are limited [6,1315], and previous comparative studies have used
relatively low maintenance dosing (100 mg iron/day). No random-
ized study has used the current recommended dose of iron(III)
polymaltose complex in pregnant women with iron-defciency
anemia (200300 mg iron/day [16]). Te current study aimed to
evaluate the efcacy and safety of iron(III) polymaltose complex
and ferrous sulfate in the treatment of anemia in iron-defcient
pregnant women based on recommended dosing regimens. Te
study was investigator-initiated and designed as an exploratory,
open-label, controlled and randomized multicenter study.
Methods
Recruitment took place at three centers in Colombia and
two centers in Argentina during the period December 2005
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2 R. Ortiza et al.
Te Journal of Maternal-Fetal and Neonatal Medicine
and July 2006. To be included in the study, women had to be
16 years or older, between 18 and 26 weeks of gestation, and
have iron-defciency anemia defned as Hb 10.5 g/dL, serum
ferritin 15 ng/mL and mean corpuscular volume (MCV)
<80 fL. Te Hb threshold was selected according to recom-
mendations by the Centers of Disease Control, which are based
on the presence of nadir Hb value and defne anemia as Hb <
11.0 g/dL during gestational weeks 112 and 2940, or < 10.5 g/
dL during weeks 1328 [1]. Women with iron overload, distur-
bances in iron utilization, anemia due to causes other than iron
defciency, or other signifcant clinical disease (including preec-
lampsia, infectious disease and severe organ or psychological
disease) were ineligible.
All patients stopped taking iron-containing preparations
(including multivitamin preparations containing iron) 14 days
prior to the frst dosing day. Eligible women were randomized
equally to each treatment group using sealed randomization
envelopes, stratifed according to their gestational age at inclusion
(1820 weeks, 2123 weeks and 2426 weeks). Women received
twice daily iron dosing taken during or afer a meal for 90 days
with either iron(III) polymaltose complex (Maltofer

, Vifor
International Inc., St. Gallen, Switzerland) provided as single-
dose containers (sites in Colombia, lot number 418000) or flm
tablets (sites in Argentina, lot number 227200) each containing
100 mg iron, or generic ferrous sulfate tablets (commercially
available, containing 100 mg iron). Assessments were performed
on days 30, 60, 90 and postpartum.
Te primary endpoint was the change in Hb from baseline to
days 60 and 90. Secondary efcacy endpoints were the change in
Hb from baseline to day 30, and changes from baseline to days 30,
60 and 90 in serum ferritin, transferrin saturation (TSAT), serum
iron, hematocrit, MCV, mean corpuscular hemoglobin (MCH),
and mean corpuscular hemoglobin concentration (MCHC).
Efcacy endpoints in patients receiving iron(III) polymaltose
complex as single-dose containers or flm tablets were compared
descriptively. Laboratory tests were performed by a central labo-
ratory in each country. Safety was assessed by means of adverse
event monitoring, vital signs (axillary temperature, blood pressure
and heart rate), body weight and physical examinations. Te post-
partum assessment included gestational age, number of neonates,
delivery method, outcome, neonate characteristics (gender, birth
weight, head circumference, length), estimated blood loss and
duration of hospitalization.
No formal sample size calculation was performed for this
exploratory study. Te planned sample size of 40 women in each
treatment group (20 per treatment group in each country) was
chosen on the basis of clinical and practical criteria. Statistical
analyses were based on descriptive and exploratory methods. All
efcacy parameters were analyzed using the intention to treat
(ITT) population, summarized by visit using descriptive statistics,
and using the last observation carried forward (LOCF) method
for missing values. Statistical tests were performed as two-sided
t-tests with a signifcance level of 5% (0.05), assuming normality
and equal variances. Treatment group diferences in treatment
compliance and adverse events were tested at each visit and
overall using a
2
-test, collapsing the number of tablets/containers
returned into the following categories: 0, 15, 610, >10. Data are
presented as means (standard deviation, SD).
Te fnal protocol and informed consent form were approved by
the Research and Ethics Committee of the principal investigator at
each study site. Te study was performed in accordance with the
protocol, the Declaration of Helsinki, Good Clinical Practice, and
applicable regulatory requirements. All patients provided written
informed consent for their participation in the study (women
aged younger than 18 years in Colombia and aged younger than
21 years in Argentina also provided parental consent).
Results
Patient population
A total of 80 women were randomized into the study and included
in the safety and ITT sets (Figure 1). Tere were no major devia-
tions from the protocol. Tree women (two in the iron(III) poly-
maltose complex group and one in the ferrous sulfate group)
withdrew prematurely from the study between days 60 and 90 due
to premature labor. One further woman (ferrous sulfate group)
withdrew due to an adverse event (severe vomiting).
Te treatment groups were similar with regards to base-
line characteristics, including age (mean 26.8 (6.2) years in the
iron(III) polymaltose complex group and 27.2 (5.8) years in the
ferrous sulfate group) and weight (60.4 (8.8) kg in the iron(III)
polymaltose complex group and 60.1 (9.0) kg in the ferrous sulfate
group). Mean gestational age at study entry was 20.1 (2.7) weeks
in the iron(III) polymaltose complex group and 19.6 (2.3) weeks
in the ferrous sulfate group (p = 0.06). Gestational age was in the
range 1318 weeks, 1921 weeks and 2225 weeks in 11 (26.8%),
Figure 1. Patient disposition.
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Oral IPC versus ferrous sulfate in pregnant women 3
Copyright 2011 Informa UK, Ltd.
11 (26.8%) and 19 (46.3%) of women in the iron(III) polymaltose
complex group, respectively, compared to 13 (33.3%), 17 (43.6%)
and 9 (23.1%) of women in the ferrous sulfate group (p < 0.001).
Treatment
In the iron(III) polymaltose complex group, 6673% of women at
each visit returned zero tablets/containers. In the ferrous sulfate
group, 4146% of women at each visit returned zero tablets. Te
distribution of non-compliance was signifcantly in favor of the
iron(III) polymaltose group at days 30, 60 and 90 (Table I). At
day 90, the mean number of tablets/containers returned in the
iron(III) polymaltose complex group was signifcantly lower than
mean number of tablets returned in the ferrous sulfate group
(1.53 versus 2.97, respectively, p = 0.015).
Hb and hematocrit
Hb level was similar in both treatment arms at baseline, with
no signifcant diferences between groups in change from base-
line Hb to either day 60 or 90. Te mean change from baseline
to day 90 was 2.16 (0.67) g/dL in the iron(III) polymaltose
complex group and 1.93 (0.97) g/dL in the ferrous sulfate group
(Table II). At day 90, women in both treatment groups had achieved
mean Hb levels close to the normal range (mean 11.89 g/dL in the
iron(III) polymaltose complex group and 11.70 g/dL in the ferrous
sulfate group; p = 0.056). Similarly, baseline hematocrit values and
changes from baseline to days 30, 60 and 90 were comparable
between treatment groups other than a signifcantly higher hemat-
ocrit in the iron(III) polymaltose group at day 90 (Table II).
Iron status parameters
Mean serum ferritin level at baseline was 113 (26) ng/mL in the
iron(III) polymaltose complex group and 112 (29) ng/mL in the
ferrous sulfate group. Tere was a small increase to 179 (38) ng/
mL in the iron(III) polymaltose complex arm and 157 (34) ng/mL
in the ferrous sulfate arm (p = 0.014); the diference in the change
from baseline was statistically signifcant (p = 0.004) (Table III).
Tere were also small increases in TSAT during the study, which
did not difer signifcantly between treatment groups (Table
III). Serum iron level was signifcantly greater in the iron(III)
polymaltose group at both day 60 and at day 90, with mean values
at day 90 of 11.4 (3.5) mol/L and 9.8 (2.9) mol/L in the iron(III)
polymaltose complex and ferrous sulfate groups, respectively
(p = 0.022).
Red cell indices
MCH, MCHC and MCV showed no statistically signifcant difer-
ences between treatment groups at baseline or at any subsequent
Table I. Distribution of non-compliance.
Tablets/containers
returned
Iron(III) polymaltose
complex (n = 41)
Ferrous
sulfate (n=39) P value
Day 30
0 30 (73.2) 16 (41) <0.001
15 7 (17.1) 16 (41)
610 2 (4.9) 3 (7.7)
1120 1 (2.4) 3 (7.7)
>20 1 (2.4) 1 (2.6)
Day 60
0 27 (65.9) 16 (41) <0.001
15 9 (22) 17 (43.6)
610 4 (9.8) 4 (10.3)
1120 1 (2.4) 2 (5.1)
>20 0 0
Day 90
0 27 (65.9) 18 (46.2) <0.001
15 7 (17.1) 13 (33.3)
610 4 (9.8) 4 (10.3)
1120 0 2 (5.1)
>20 1 (2.4) 1 (2.6)
Values are shown as absolute frequencies (percentages). Signifcant p values are shown
in bold.
Table II. Hb and hematocrit values and change from baseline at days 30,
60 and 90.

Iron(III)
polymaltose
complex (n = 41)
Ferrous
sulfate
(n = 39) P value
Hemoglobin (g/dL)
Baseline 9.64 (0.89) 9.79 (0.64) 0.35
Day 30 10.30 (0.70) 10.45 (0.58) 0.72
Change from baseline 0.66 (0.43) 0.66 (0.48) 0.88
Day 60 11.05 (0.75) 11.06 (0.70) 0.40
Change from baseline 1.41 (0.38) 1.27 (0.73) 0.41
Day 90 11.89 (0.53) 11.70 (0.76) 0.056
Change from baseline 2.16 (0.67) 1.93 (0.97) 0.25
Hematocrit (%)
Baseline 29.08 (2.36) 29.26 (2.29) 0.71
Day 30 31.03 (2.26) 31.34 (2.49) 0.88
Change from baseline 1.95 (1.41) 2.08 (1.51) 0.66
Day 60 33.50 (2.38) 33.04 (2.42) 0.14
Change from baseline 4.42 (1.85) 3.77 (1.84) 0.08
Day 90 35.83 (2.05) 35.03 (2.38) 0.009
Change from baseline 6.62 (2.04) 5.81 (2.4) 0.07
Values are shown as mean (SD).
Table III. Iron indices.

Iron(III)
polymaltose
complex (n = 41)
Ferrous
sulfate
(n = 39) P value
Serum ferritin (ng/mL)
Baseline 113 (26) 112 (29) 0.98
Day 30 121 (23) 122 (28) 0.61
Change from baseline 9 (12) 9 (17) 0.63
Day 60 145 (31) 133 (38) 0.11
Change from baseline 32 (26) 20 (31) 0.04
Day 90 179 (39) 157 (34) 0.014
Change from baseline 64 (40) 41 (28) 0.004
Transferrin saturation (%)
Baseline 15.4 (4.7) 15.6 (5.1) 0.88
Day 30 17.1 (4.7) 16.3 (4.0) 0.22
Change from baseline 1.8 (3.6) 0.7 (2.7) 0.21
Day 60 18.7 (4.2) 18.1 (4.7) 0.08
Change from baseline 3.3 (3.9) 2.5 (3.9) 0.31
Day 90 21.3 (4.6) 19.4 (6.4) 0.01
Change from baseline 6.1 (5.5) 3.9 (6.8) 0.21
Serum iron (mol/L)
Baseline 5.8 (1.3) 5.7 (2.0) 0.52
Day 30 7.4 (1.2) 7.0 (2.3) 0.66
Change from baseline 1.6 (1.6) 1.6 (1.2) 0.28
Day 60 9.6 (3.2) 8.2 (2.4) 0.04
Change from baseline 3.8 (3.3) 2.5 (1.9) 0.15
Day 90 11.4 (3.5) 9.8 (2.9) 0.022
Change from baseline 5.6 (3.9) 4.3 (2.3) 0.10
Values are shown as mean (SD). Signifcant p values are shown in bold.
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4 R. Ortiza et al.
Te Journal of Maternal-Fetal and Neonatal Medicine
time point during the study. Mean values for MCH, MCHC and
MCV in patients randomized to iron(III) polymaltose complex
were 26.1 (8.8) pg, 31.6 (2.9) g/dL and 75.0 (8.5) fL at baseline and
27.7 (1.5) pg, 33.0 (1.0) g/dL and 82.2 (3.2) fL at day 90. For the
ferrous sulfate arm, baseline values were 25.1 (2.3) pg, 31.5 (2.7)
g/dL and 75.9 (3.4) fL, and day 90 values were 27.6 (2.1) pg, 32.6
(1.7) g/dL and 80.9 (3.5) fL, respectively.
Safety
Adverse events were reported by 34 women; 12/41 (29.3%) in the
iron(III) polymaltose complex group and 22/39 (56.4%) in the
ferrous sulfate group (p = 0.015).Te most commonly reported
adverse events were nausea, vomiting and constipation, all of
which occurred signifcantly more frequently in the ferrous
sulfate group (Figure 2). All events in the iron(III) polymaltose
complex arm were of mild intensity. Moderately severe cases
of nausea, vomiting and constipation occurred in the ferrous
sulfate group. One woman in the ferrous sulfate group experi-
enced vomiting that was graded severe, which led to permanent
withdrawal from the study. No serious adverse events occurred
in either treatment group.
In all cases, nausea, vomiting and constipation were considered
possibly or probably related to study medication. Te episode of
moderate pruritus in the ferrous sulfate group was considered
certainly related to study medication. All episodes of cephalea,
back pain, and bronchospasm were considered unlikely or unre-
lated to study medication. In almost all the cases, adverse events
resolved without concomitant medication, with symptomatic
treatment, or with temporary suspension of treatment, and every
adverse event resolved without sequelae.
Mean values for blood pressure, heart rate and body
temperature were in the expected range and were similar
between treatment groups at baseline across the total study
population: overall mean systolic blood pressure 106 mmHg,
diastolic blood pressure 66 mmHg, heart rate 84 bpm, and
temperature 36.8C (0.4). Blood pressure increased slightly in
both treatment groups during the study, with the total study
population at day 90 having mean systolic blood pressure of
115 mmHg and diastolic blood pressure 73 mmHg. Mean heart
rate and temperature remained stable (overall 84 bpm and
36.7C, respectively, at day 90). Sporadic instances of statis-
tically significant differences between treatment groups for
temperature and heart rate during the study were not consid-
ered clinically relevant.
Pregnancy outcomes
Data on pregnancy outcome were available for 43 women (22
iron(III) polymaltose complex, 21 ferrous sulfate), all of whom
had live births. Mean gestational age at time of birth was 37.6
(1.6) weeks in the iron(III) polymaltose complex group and
37.9 (1.3) weeks in the ferrous sulfate arm. Tere were no difer-
ences between treatment groups in mean gestational age at birth
(overall 37.8 weeks) or delivery method (overall 70% had a
vaginal delivery, 30% had Caesarean section). Te overall mean
duration of hospital stay was 2.3 days. No patient required blood
transfusion. Tere were no diferences between treatment groups
in terms of neonatal characteristics, with a similar distribution of
sex (overall 56% males), mean weight and height at birth (overall
3038 g and 49 cm) and mean head circumference (overall 35 cm).
Iron(III) polymaltose complex formulation
Demographic and clinical characteristics at baseline were similar
in patients receiving iron(III) polymaltose complex as single-dose
container (n = 20, Colombia) or flm tablets (n=21, Argentina)
other than slightly lower mean Hb levels in women receiving the
single-dose container formulation (9.3 [1.0] g/dL) compared to
those receiving flm tablets (9.9 [0.5] g/dL). Treatment compliance
was higher in Colombia, where patients randomized to iron(III)
polymaltose complex received the single-dose container formula-
tion, compared to Argentina where flm tablets were provided.
At days 30, 60 and 90, the mean number of tablets/containers
returned was 0.5 (1.1), 0.6 (1.7) and 3.3 (11.4) in Colombia
compared to 4.8 (7.0), 3.9 (4.1) and 3.2 (3.9) in Argentina, respec-
tively (data are not available separately for iron(III) polymaltose
complex and ferrous sulfate). Te mean change in Hb from
baseline to day 90 was 2.7 (0.9) g/dL among women receiving the
single-dose container formulation compared to 1.9 (0.5) g/dL for
the flm tablets. Te mean change in serum ferritin from baseline
to day 90 was 30 (42) ng/mL and 83 (31) ng/mL with the single-
dose container and flm tablets, respectively; the mean change in
TSAT was 10.3% (4.8) and 2.7% (3.4), respectively. Tese difer-
ences were considered likely to have been due to the variation in
treatment compliance and possibly the lower Hb level at baseline
in women receiving iron(III) polymaltose complex in single-dose
Figure 2. Incidence of adverse events. No patient reported the same adverse event more than once.
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Oral IPC versus ferrous sulfate in pregnant women 5
Copyright 2011 Informa UK, Ltd.
containers. No clinically relevant diferences in safety profle were
observed between the two iron(III) polymaltose formulations.
Discussion
Both oral iron(III) polymaltose complex and oral ferrous sulfate
demonstrated good efcacy in the treatment of iron-defciency
anemia during pregnancy, with clinically meaningful increases in
Hb during the 90-day treatment period. Although some studies
have indicated that therapeutic response to iron(III) polymaltose
complex is slightly slower than to ferrous sulfate [17,18], there was
no diference between treatment groups in the speed of response
in terms of Hb levels in the current study. Tis may be due to the
fact that study medication was taken with or afer food, which has
been shown to improve uptake of iron(III) polymaltose complex
[19]. Tere was no clear indication of a diference in efcacy
between the two single-dose container or flm tablet formulations
of iron(III) polymaltose complex.
Tese results are in accordance with previous experience
showing equivalent efcacy of iron(III) polymaltose complex
and ferrous sulfate across a spectrum of patient types [4]. Two
comparative studies have previously assessed the relative efcacy
of the two preparations in pregnant women [7,13]. Each of these
demonstrated similar efcacy in terms of Hb response at a daily
dose of 100 mg iron/day for iron(III) polymaltose complex and
100120 mg iron/day for ferrous sulfate. However, Jacobs et al.
have demonstrated in a population of adult blood donors receiving
iron(III) polymaltose complex that a dose of 200 mg iron/day is
associated with signifcantly greater efcacy than 100 mg iron/
day [6]. Herein, we have confrmed that the Hb response remains
comparable with iron(III) polymaltose complex or ferrous
sulfate at the higher, recommended dose of 200 mg iron/day in
each treatment group. Tere was a signifcantly greater increase
in serum ferritin levels (a marker of storage iron levels) in the
iron(III) polymaltose complex group than in the ferrous sulfate
group at day 90, as has been reported elsewhere in a population
of pregnant women [13]. In contrast, TSAT, a marker of iron
availability for erythropoeisis, did not difer between groups. In
this group of patients with severe iron defciency (serum ferritin
15 ng/mL at study entry), iron utilization by the erythrocytes
will have been high; longer-term treatment would be expected
to replenish iron levels to a greater degree. Te diference in
serum iron levels between patients receiving iron(III) poly-
maltose complex and ferrous sulfate was not anticipated based
on data in the literature [4,5,12,13]. However, serum iron is not
regarded as a relevant marker of efcacy [20] and the slow rate
of iron release from iron(III) polymaltose complex [7] prevents
formation of non-transferrin bound iron, as indicated here by
the lower rate of adverse events compared to the ferrous sulfate
group. As expected, there were no efects on red cell indices in
either treatment group.
Consistent with fndings across other patient populations [4],
iron(III) polymaltose complex was better tolerated than ferrous
sulfate. Gastrointestinal side efects in the iron(III) polymaltose
complex group were less frequent and milder, and the only
premature withdrawal due to side efects occurred in the ferrous
sulfate group. Gastrointestinal side efects (including nausea,
vomiting, constipation and diarrhea) are widespread with oral
iron (II) therapies [1], and may result in low treatment compli-
ance, a frequent issue in pregnant women prescribed iron thera-
pies [21]. Although iron (II) salts are ofen administered with
food (as in this study), which may decrease such side efects, it
also results in a decreased bioavailability. Te superior safety
profle of iron(III) polymaltose complex group was refected by a
higher rate of treatment compliance, as measured by the number
of tablets or containers that were returned. Reduced treatment
compliance with ferrous sulfate has been reported previously
[22], and is likely to be more marked under real life conditions,
i.e., outside the context of a study such as this in which compli-
ance was encouraged and monitored. Tis is of particular concern
in patients with more severe anemia, as the iron defcit could
be carried forward into any subsequent pregnancy. Further, if
the anemia is not treated efectively during pregnancy, this can
have severe impact on the outcome of the pregnancy (including
increased maternal mortality, prenatal and perinatal infant loss,
and prematurity [2325]). Te infants may also sufer iron def-
ciency, which may in turn lead to developmental impairment.
Te signifcantly improved treatment compliance with iron(III)
polymaltose complex is therefore a relevant clinical beneft.
Tere were no diferences between the treatment groups in
pregnancy outcome, indicating equivalent safety for the neonate,
although patient numbers for postpartum follow-up were limited.
It might have been interesting in this study to have followed the
womens hematological parameters postpartum to determine
whether the iron therapy during pregnancy had a long-term
protective efect from anemia.
In conclusion, in this randomized, multicenter trial both
iron(III) polymaltose complex and ferrous sulfate at a dose of
200 mg iron/day were efective for treatment of iron-defciency
anemia during pregnancy in terms of increased Hb levels. Iron
status showed a small improvement in both groups, with higher
serum ferritin in the iron(III) polymaltose complex treatment
arm. Iron(III) polymaltose complex exhibited a better safety
profle than ferrous sulfate, with a lower incidence of gastrointes-
tinal side efects and higher treatment compliance.
Acknowledgements
Iron(III) polymaltose complex (Maltofer

) was kindly provided


by Vifor (International) Inc, St Gallen, Switzerland. Te authors
would like to thank to Conrado Marsik, MD, Guillermo Lovestein,
MD and Carlos Rusconi, MD, for their collaboration in this study.
Medical writing support was provided by Caroline Dunstall with
funding from Vifor (International) Inc. JE Toblli and JD Romero
undertook data collection, data analysis and wrote the manu-
script. All other authors undertook data collection.
Declaration of interest: JE Toblli and JD Romero have received
research funding and travel grants from Vifor Pharma. All other
authors declare that they have no competing interests. Te study
was funded by Vifor (International) Inc, St Gallen, Switzerland.
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