1College of Pharmacy, Prince Norah Bin Abdulrahman University, Kingdom of Saudi Arabia
2King Abdullah University Hospital, Prince Norah Bin Abdulrahman University, Saudi Arabia
3Health Sciences Research Center, Prince Norah Bin Abdulrahman University, Kingdom of Saudi Arabia
Submission: August 26, 2019 ;Published: September 04, 2019
*Corresponding author: Salem Alsuwaidan, Health Sciences Research Center, Prince Norah Bin Abdulrahman University, Kingdom of Saudi Arabia
How to cite this article: Alyami A, Almohaya A, Alburaih D, Alsuwaidan S, et al. The Effectiveness of Ferric Carboxymaltose in Childbearing Age with Iron
002 Deficiency Anemia. J Gynecol Women’s Health. 2019: 16(3): 555937. DOI: 10.19080/JGWH.2019.16.555937
Iron deficiency is the most common minerals deficiency worldwide. Iron has a major role in producing hemoglobin in red blood cells, which is responsible for carrying oxygen to the body’s tissues. Treatment for an iron inadequacy depends on the cause and severity of the condition. Intravenous iron preparations are highly recommended when anemic pregnant women unable to tolerate, respond accordingly with better adherence to the regimen.
Aim of the research: This study is conducted to evaluate the possibility of using ferric carboxymaltose (FCM) as a first line treatment in pregnant women with IDA; and the effect of other contributor factors such as age, education, occupation, number of pregnancies and most importantly is the time of receiving FCM in term of first, second and third trimesters.
Methodology: Participants were gone through out personal interview answering some questions about their gestational situation and habits to achieve the study outcomes. All participants were pregnant women with abnormal hemoglobin whose either already received their first dose of FCM or those who are scheduled to take their first dose.
Result: Eighty-eight (88) pregnant women were participated in this study and their ages were divided into groups. The average of post FCM hemoglobin (10.99) after injection was significantly higher compared to the baseline hemoglobin (9.06). A shift to healthy and better response was shown after the FCM were shown in all participants.
Conclusion: A single intravenous injection of FCM improves the hemoglobin level in a significant consideration in anemic pregnant women. It showed also that the respond of sever anemic cases were more positive in improving the level of hemoglobin than mild and/or moderate cases. Blood transfusion could be avoided by using FCM injection to optimize the iron stores rapidly and effectively. Intravenous injection of FCM could be used as trend in the first and second trimester during pregnancy with or without IDA if the hemoglobin level is low.
Keywords: Ferric carboxymaltose; Iron deficiency; Iron deficiency; Hemoglobin
Anemia is a blood disorder in which hemoglobin (Hgb) concentration is less than the normal Hgb level. It is affected by age, sex, physiological condition(s) and altitude above the sea level of that person . It is a global public health problem with major consequences affecting both developing and developed countries . The most common type of anemia is Iron deficiency anemia (IDA), which is defined as anemia because of insufficient iron . Iron deficiency is the most common minerals deficiency worldwide. Women are at higher risk compared with men [4,5]. Iron has a major role in producing hemoglobin in red blood cells which is responsible for carrying oxygen to the body’s tissues . Iron is a mineral naturally found in food and supplements, and it is available in two dietary forms: heme like in (meat, poultry, and seafood) and non-heme in (iron-fortified foods, plants- beans, nuts and vegetables). Essentially, meat and seafood are the richest sources of iron. However, some vegetables such as spinach, broccoli, and beetroot are considered as a good source for iron too. Although this disagrees with previous review concludes that “Vegetarians have a higher risk for developing low iron stores, iron depletion, and associated iron deficiency anemia, compared to non-vegetarians” .
According to world health organization (WHO) data, the prevalence of IDA in Saudi Arabia is 32.0% of pregnant women and 32.3% of women of reproductive age with anemia, which presents a moderate public health risk. Hemoglobin estimation is the most common and classical hematological screening test used for iron deficiency. According to (WHO), anemia is defined
as low hemoglobin status; the cut off value for the pregnant
women is Hgb<12g/dl, mild anemia (10.0-11.9g/dl), moderate
(8.0-9.9g/dl) and severe (≤ 7.9g/dl). However, bone marrow
aspiration is the definitive test to assess iron stores and diagnose
its deficiency. Serum ferritin is an alternative to the bone marrow
aspiration, and it is the best test to distinguishing those with IDA
from those who are not iron deficient [2,8,9].
The level of serum ferritin, hemoglobin and hematocrit, and
transferrin or total iron-binding capacity could evaluate iron
inadequacy. The symptoms of iron deficiency vary, depending
on its severity. Iron deficiency anemia can cause chronic fatigue,
hair loss, cold hands and feet, shortness of breath and many
other symptoms in addition to several physical signs. One of the
characteristics symptoms is pagophagia, which is known by a
craving to eat substance without nutritional value such as ice,
dust or paint due to iron deficiency [10,11].
The reasons behind iron deficiency anemia during pregnancy
can be classified into three causes. First, it can be as a result of
the decrease in the hemoglobin level due to an increase in the
maternal plasma volume. Second, begin the pregnancy with
inadequate iron storage, which can lead to an inability to meet
the requirements throughout the pregnancy. Last, an increase
in the maternal demand for iron . The body requirements
for iron in pregnant woman nearly increases to 1000mg,
which can be divided by, 350mg for placental and fetal growth,
250mg for blood loss at the delivery and the biggest part will
be for the dilation in the red blood cell mass that will consume
approximately 500mg iron . Iron deficiency anemia lead to
health problems such as rapid or irregular heartbeat, premature
births and low birth weight babies and delayed growth and
Treatment for an iron inadequacy depends on the cause and
severity of the condition. Iron deficiency anemia could be treated
either orally or by intravenous (IV) injection. In spite of the fact
that oral iron supplementations are considered as the first line
option for the majority of pregnant women with IDA due to
their effectiveness, safety, and lower cost; yet an intolerable side
effects (gastrointestinal side effects), non-compliance and/or
predisposing pathology such as malabsorption (celiac disease)
may limit the use of oral ferrous supplements .
On the other hand, intravenous iron preparations are highly
recommended when anemic pregnant women unable to tolerate,
respond accordingly with better adherence to the regimen.
Ferric carboxymaltose (FCM) is a new type of iron III complex,
dextran free, which makes it possible to be administered without
a test dose for hypersensitivity, has a neutral PH (5.0-7.0) and
physiological osmolality. Therefore, up to 1000 mg as single dose
can be infused over 15-30 minutes, with lower side effects than
oral iron supplement thus the patients are more compliant with
injectable dosage form. If the patient did not respond adequately
after a single dose of FCM, another dose can be administered one
week later [10,16-18].
Ferrous as an element is a trend use for all pregnant women
in most if not all gynecological clinics, usually the practitioners
start with ferrous sulfate (FS) 325mg orally or ferrous gluconate
(FG) 300mg orally. However, the starting point to prescribe
ferrous is crucial to decide whether if the first, second or third
trimester; moreover, what is the most appropriate and effective
way to initiate FCM injection during pregnancy; and what is the
most cost-effective treatment specifically if the pregnant women
with IDA .
This study was conducted with a sample of eighty-eight (88)
pregnant women aged between (20) and (44) years old; whom
participated through out personal interview answering some
questions about their gestational situation and habits to achieve
the study outcomes. All participants were pregnant women with
abnormal hemoglobin whose either already received their first
dose of ferric carboxymaltose or those who are scheduled to
take their first dose. Women who are post-delivery or pregnant
women with normal hemoglobin are excluded from the study
Data were analyzed using SPSS 21.0 version statistical
software. Descriptive statistics (mean, standard deviation,
frequencies and percentages) were used to describe the
quantitative and categorical variables. Student’s paired t test was
used to compare the mean values of quantitative variables (Hgb)
between the baseline and post ferric carboxymaltose (FCM).
One-way analysis of variance was used to compare the mean
difference of Hgb values in relation to the categorical variables,
which has more than two categories. A p-value of ≤0.05 was used
to report the statistical significance of findings to report the
precision of results.
All the participants involved in this study provided written
informed consent acknowledging the investigation’s purpose and
were assured of the confidentiality of the results. Institutional
review board approval for the research was obtained from Health
Sciences Research Center at Princess Noura bint Abdulrahman
University, with IRB Log Number: 18-1098.
Eighty-eight (88) pregnant women were participated in this
study and their ages were divided into groups, from 20-25 years were 13 participants (14.8%), from 26-30 years 28(31.8%),
from 31 to 35 years 27 (30.7%), and for 36 years and older were
20(22.7%). Their educational level was distributed as following:
under high school 2(2.3%), high school 32(36.4%), bachelor’s
degree 41 (46.6%), and master’s degree or above 13(14.8%).
Their occupational status was assigned as employed 48 (54.5%)
and un-employed 40(45.5%). More detail for the timing of FCM injection during the gestational trimester whether if it is first,
second or third trimester, were shown in (Table 1), together with
information related to the number of deliveries. The average of
post ferric carboxymaltose hemoglobin (10.99) after injection
was significantly higher compared to the baseline hemoglobin
(9.06) (P<0.0001; 95% CI: 1.65-2.21).
In regard to age groups and its efficient in absorbing Hgb
before FCM injection as a baseline and after FCM injection,
compared to the whole group as shown in (Figure1). The range of
hemoglobin level between baseline and after FCM injection was
(9.06-10.99), showing the response of the participants after FCM injection with a difference of 1.93 for the whole group, where the
maximum difference was 2.16 found with the group of 25 years
and lower with no significant difference (p>0.05) compared with
any of other age group including the minimal difference for the
age group of 30-35 years with 1.7.
Another comparison for level of hemoglobin was found when
FCM was injected within the gestational trimester, first, second
and third trimester. It was found that although the third trimester
with the highest hemoglobin level compare to the others, yet
the first trimester showed the best response with a difference between the baseline and post FCM injection with 2.15. None
of these differences were calculated as significantly different.
Figure 2 showed relative differences between gestational
trimesters first, second and third trimester compared with the
total group before and after receiving one full dose of FCM.
Participants (at the baseline) were classified in accordance
with WHO classification to mild, moderate and sever anemia. A
shift to healthy and better response was shown after the FCM
with 14 participants were shown within healthy hemoglobin
level, compared with none at the baseline. Then a big shift 8,
70 and 10 out of the total participants as baseline before FCM
injection for severe, moderate and mild anemia correspondingly.
The improvement had shown after the FCM injection with only
one participant with severe anemia or low hemoglobin level, 15
participants for moderate, and 58 participants become with mild
anemia. It is also shown that 14 participants were getting full
improvement and considered as health or non-anemic women.
Table 2 showed full detail for all the data of this study mainly
the shift of hemoglobin level during sever, moderate and mild to
moderate, mild and healthy hemoglobin level before and after
This is the first prospective study for ferric carboxymaltose
in Saudi Arabia among pregnant women presenting with IDA. An
intravenous ferric carboxymaltose was remarkably increased
hemoglobin levels without serious side effects were recorded.
Only one case in this study had experienced dizziness, which
were reported at the emergency department after FCM injection.
FCM shown to be effective in childbearing age women with IDA,
this phenomenon had been shown noticeable with those who
aged with 25 or younger, where they have remarkably better
response compared with other groups of age due to the ability to
quickly absorb of iron as shown in (Figure 1). This difference is
numerically deferent but not statistically deferent. Age as a factor
in pregnant women with IDA had not been studied elsewhere;
whereas in this study, age was divided into 4 age groups to study
the associated differences of Hgb levels post FCM injection.
Results from this FCM analysis of pregnant women with IDA
during first, second and third trimester of pregnancy showed
that Hgb levels increased after FCM treatment with full safety
parameters; therefore, intravenous FCM could be considered as
a first line treatment for IDA pregnant women in case of severe
cases. This is in contrast to CDC , WHO  and Society of
Obstetricians and Gynecologists of Canada , where all these
authorities recommended oral iron supplementation in pregnant
women as first line therapy. Intravenous iron is recommended when oral iron is poorly tolerated, absorption is likely to be
impaired, the response to oral iron is inadequate, or when rapid
restoration of Hgb and iron stores is required .
Oral iron supplementation could increase hemoglobin
and ferritin levels in pregnancy, with or without IDA. This
study demonstrated safe and effective use of FCM infusion in
pregnant women during the first, second, and third trimesters of
pregnancy. Safety profile for intravenous FCM had been shown,
having the practical advantage of allowing a higher iron dose in
one time of administration (minimizing repeated administration
times and increasing patient comfort) . Another study
showed Hgb levels significantly increased above baseline levels
with 66% of women reported an improvement of their wellbeing
with mostly minor and self-limiting side effects . The cases
described in this study was also in line with the retrospective
case-control study from the Netherlands reporting similar
significant increases in maternal Hgb levels above baseline and
low rates of adverse outcomes . Third trimester cases in
this study had improvement with 21.3% with a single dose of
intravenous injection of FCM (Figure 2).
It was noticed from this study that Ferric Carboxymaltose
(FCM) was significantly increased hemoglobin levels, this
increment in Hgb had been noticed started at 3 to 4 weeks
interval post FCM dose; this achievement also had been
previously studied . The responses of severe anemic cases are more positive in improving the level of hemoglobin than
mild and/or moderate cases after a single dose (1000mg) FCM.
All cases related to severity of IDA had been shifted from sever,
moderate, mild to moderate, mild, healthy respectively. Only one
case with severe IDA remained severe after using FCM, therefore
another dose maybe warranted.
Treatment of IDA will never lead to iron toxicity, however,
incase of injection of higher dose above the requirements, it
needs further monitoring although teratogenicity is with limited
possibility, specifically if the treatment within the first trimester.
If iron accumulation has been noticed, intravenous deferoxamine
should be administered as chelation therapy . Excessive Hgb
levels were not observed in this study, all participants on FCM
injection had elevated levels that fell within normal ranges.
Traditionally, blood transfusion is considered as an option
in severe anemic cases; especially when oral replacement is not
effectively and rapidly replenished the iron stores. The newly
developed iron formulation such as FCM is offering the benefit
of administrating a single higher dose with rapid, effective and
safe repletion of iron, which can employ to avoid the risk of
blood transfusion in severe anemia. This study could not find
any correlation between Hgb levels and education, job, number
of pregnancies, the consumed iron from food (vegetarian or not),
A side issue related to the cost of treatment in comparison
between FCM and oral ferrous treatment considering that the
cost of FCM is 200$ per injection of 1000mg single dose with
almost absolute treatment for more than 6 months and only one
visit comparing with multiple visits, cost more than 200$ USD
per each visit, and irregular treatment subjecting premature
births and low birth weight babies and delayed growth and
This study approved that one intravenous injection of FCM
improves the hemoglobin level in a significant consideration in
anemic pregnant women. Also, it showed that the respond of
sever anemic cases were more positive in improving the level
of hemoglobin than mild and/or moderate cases. Only one case
remained severe despite receiving one dose of FCM. Dizziness
was experienced and reported by only one pregnant woman at
the emergency department post FCM injection, which indicated
its effectiveness and safety. Blood transfusion could be avoided
by using FCM injection to optimize the iron stores rapidly and
effectively. The proposed recommendation is that intravenous
injection of FCM could be used as trend in the first and
second trimester during pregnancy with or without IDA if the
hemoglobin level is low. Moreover, Intravenous iron can be given
late in pregnancy in the third trimester when rapid restoration
of the iron stores and hemoglobin is required to avoid blood
transfusion at delivery, it is also often needed after delivery
when there is excessive bleeding in labor.
We would like to express our deepest appreciation to
the health sciences research center. A special gratitude to all
coworkers in the gynecology clinics at King Abdullah University
Hospital and those who gave us the permission to use all the
required access to complete the study. Furthermore, we are
indebted to all pregnant women involved in this study.
Alem Meseret (2013) Prevalence of anemia and associated risk factors among pregnant women attending antenatal care in Azezo Health Center Gondar town, Northwest Ethiopia. J Interdiscipl Histopathol 1(3): 137-144.