ArticlePDF AvailableLiterature Review

Iron and pregnancy - A delicate balance

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  • Næatved Hospital. University College Zealand

Abstract and Figures

The review focuses on iron balance during pregnancy and postpartum in the Western affluent societies. Iron status and body iron can be monitored using serum ferritin, haemoglobin, serum soluble transferrin receptors (sTfR) and the sTfR/ferritin ratio. Requirements for absorbed iron increase during pregnancy from 0.8 mg/day in the first trimester to 7.5 mg/day in the third trimester. Average requirement during the entire gestation is approximately 4.4 mg/day. Intestinal iron absorption increases during pregnancy, but women with ample body iron reserves have lower absorption than those with depleted reserves, so increased absorption is, in part, due to progressive iron depletion. Apparently, women do not change dietary habits when they become pregnant. Non-pregnant Scandinavian women have a median dietary iron intake of approximately 9 mg/day, i.e. more than 90% of the women have an intake below the recommended approximately 18 mg/day. Non-pregnant women have a low iron status, 42% have serum ferritin levels <or=30 microg/l, i.e. small or depleted iron reserves and 2-4% have iron deficiency anaemia; only 14-20% have ferritin levels >70 microg/l corresponding to body iron of >or=500 mg. The association between high haemoglobin during gestation and a low birth weight of the newborns is caused by inappropriate haemodilution. In placebo-controlled studies on healthy pregnant women, there is no relationship between the women's haemoglobin and birth weight of the newborns and no increased frequency of preeclampsia in women taking iron supplements.
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Ann Hematol (2006) 85: 559565
DOI 10.1007/s00277-006-0108-2
REVIEW ARTICLE
Nils Milman
Iron and pregnancya delicate balance
Received: 13 February 2006 / Accepted: 23 February 2006 / Published online: 12 May 2006
# Springer-Verlag 2006
Abstract The review focuses on iron balance during
pregnancy and postpartum in the Western affluent
societies. Iron status and body iron can be monitored
using serum ferritin, haemoglobin, serum soluble transfer-
rin receptors (sTfR) and the sTfR/ferritin ratio. Require-
ments for absorbed iron increase during pregnancy from
0.8 mg/day in the first trimester to 7.5 mg/day in the third
trimester. Average requirement during the entire gestation
is 4.4 mg/day. Intestinal iron absorption increases during
pregnancy, but women with ample body iron reserves have
lower absorption than those with depleted reserves, so
increased absorption is, in part, due to progressive iron
depletion. Apparently, women do not change dietary habits
when they become pregnant. Non-pregnant Scandinavian
women have a median dietary iron intake of 9 mg/day, i.e.
more than 90% of the women have an intake below the
recommended 18 mg/day. Non-pregnant women have a
low iron status, 42% have serum ferritin levels 30 μg/l,
i.e. small or depleted iron reserves and 24% have iron
deficiency anaemia; only 1420% have ferritin levels
>70 μg/l corresponding to body iron of 500 mg. The
association between high haemoglobin during gestation
and a low birth weight of the newborns is caused by
inappropriate haemodilution. In placebo-controlled studies
on healthy pregnant women, there is no relationship
between the women s haemoglobin and birth weight of
the newborns and no increased frequency of preeclampsia
in women taking iron supplements.
Keywords Anemia
.
Iron deficiency
.
Ferritin
.
Hemoglobins
.
Iron
.
Pregnancy
.
Transferrin receptor
Iron is one of the most prevalent metals in the earth crust
and in our environment. Since the dawn of life, all living
forms have been obliged to include iron in their metabolism
and homeostasis in one way or another. Iron is essential to
man. It is vital for the synthesis of haemoglobin and
myoglobin as well as for the function of a wide range of
important iron-dependent enzymes. An adequate body iron
balance is crucial. Iron deficiency is the most prevalent
nutritional deficiency disorder on a global scale. There are
major differences in iron nutrition and iron status in
developing and developed countries. This review shall
focus on iron status during pregnancy and postpartum in
the affluent Western societies.
Assessment of iron status
Body iron stores are predominantly located in the reticu-
loendothelial cells in the bone marrow, liver and spleen, as
well as in the hepatocytes. Intracellular iron is stored inside
the spherical ferritin molecules, thereby protecting the cell
from the toxicity of free iron. At small body reserves, the
iron is present in ferritin. At larger iron reserves, ferritin is
condensed into haemosiderin, which can be visualised in
biopsy specimens from bone marrow and liver after
histochemical staining with Prussian blue.
The haemoglobin concentration is still widely used as a
pseudomarker for iron deficiency, mainly due to the
simplicity and low cost of the analysis. However,
haemoglobin is not suitable to assess iron status
especially not in pregnancy. There exists a broad overlap
between the distribution of haemoglobin in subjects with
and without iron deficiency.
Mobilizable body iron reserves can be estimated by the
serum ferritin concentration, which, in healthy subjects, is a
good biomarker for iron status [1, 2]. In non-pregnant
women, a serum ferritin concentration of 1 μg/l corre-
sponds to approximately 78 mg of mobilizable iron [1].
Serum ferritin of 30 μg/l indicates iron reserves of 210
240 mg. Serum ferritin of 1530 μg/l indicates small iron
reserves; a level of <15 μg/l indicates body iron depletion
N. Milman (*)
Department of Medicine B, Rigshospitalet,
University of Copenhagen,
Copenhagen, Denmark
e-mail: milman@rh.dk
Fax: +45-35-452648
and values <12 μg/l are associated with iron deficiency [3,
4]. As a general guideline, serum ferritin levels of 30 μg/l
indicate small iron reserves and the absence of bone
marrow haemosiderin [3].
Transferrin receptors (TfR) are located on the surface of
the young erythrocytes, and their number increases during
iron deficiency [5]. The detached receptors circulate in the
blood and can be analysed in serum as soluble receptors
(sTfR). The serum sTfR level is supposed to be related to
the number of receptors on the young erythrocytes, i.e. at
iron deficiency serum sTfR rises [5]. Serum sTfR yields
information about iron deficiency on the cellular level,
whereas, serum ferritin yields information about the
capacity of body iron reserves.
In iron-replete subjects, serum sTfR is quite stable, being
independent of the size of body iron reserves [5]. Non-
pregnant and pregnant women with replete iron stores have
similar serum sTfR levels [6]. Only when the supply of iron
to the erythrocytes fails due to exhausted iron reserves does
serum sTfR begin to rise [5]. Serum sTfR can, therefore,
identify women with low serum ferritin, who, in addition,
have pronounced iron deficiency [6, 7]. Serum sTfR
appears to be a sensitive marker of iron deficiency in
pregnancy, and by combining measurements of serum
ferritin and serum sTfR, the entire spectrum of iron
deficiency is covered [6, 7].
Physiologic fluctuations in serum ferritin may be
compensated for, by calculating body iron using the
sTfR/ferritin ratio according to Cook et al. [8] and Milman
et al. 2006, submitted for publication. However, the ratio
has not been validated in a population of pregnant women.
Iron requirements in pregnancy
The requirements for absorbed iron increase gradually
through gestation from 0.8 mg/day in the first trimester to
7.5 mg/day in the third trimester (Fig. 1). The average
requirement in the entire gestation period is 4.4 mg/day
[911].
The absorbed iron is predominantly used to: 1. Expand
the womans erythrocyte mass. 2. Fulfill the foetuss iron
requirements. 3. Compensate for iron losses (i.e. blood
losses) at delivery. The newborns body iron content
depends to a large extent on their birth weight. At a low
birth weight of 2,500 g, the iron content of the newborn is
200 mg and at a normal birth weight of 3,500 g, the
iron content is 270 mg [12].
Total iron requirements in normal pregnancy have been
estimated to 1,240 mg (Table 1). A considerable amount
of iron is recycled to the body iron reserves, when the
mothers erythrocyte mass postpartum declines to the pre-
pregnancy level. Due to menostasia, the woman saves
median 160 mg iron during pregnancy. The net iron loss,
which is related to pregnancy itself, is 630 mg [10, 11].
Iron absorption increases during gestation
Iron is absorbed predominantly in the proximal part of the
small intestine by a complex process involving specific
receptors and iron-associated proteins [13]. Only ferrous
iron and haem iron is available for absorption. Iron
absorption is tightly regulated according to body iron
reserves and the intensity of erythropoiesis. Absorption is
promoted by exhausted body iron, by the increased
erythropoiesis during gestation, by blood losses at delivery,
and by postpartum treatment with erythropoietin (EPO).
Iron absorption in pregnant women has been studied
using two different methods. 1. After ingestion of radio-
active ferrous iron (
59
Fe) and subsequent measurement of
the
59
Fe retention in a whole body counter [9, 14]. 2. After
ingestion of stable, non-radioactive iron isotopes [15, 16].
The results cannot be directly compared, as the methods
rely on separate principles and use different carrier doses of
iron.
A Swedish study [9] used
59
Fe with a carrier dose of
100 mg ferrous iron and found a mean iron absorption of 7,
9 and 14% in gestational week 12, 24 and 36, respectively.
A German study [14] used
59
Fe with a carrier dose of
0.56 mg ferrous iron and found a mean iron absorption of
50, 80 and 90% in gestational week 18, 26 and 34,
respectively.
Fig. 1 Iron requirements during pregnancy and in the lactation
period (reproduced with permission from [10])
Table 1 Iron losses and iron requirements in normal pregnancy and
delivery
Iron losses in normal pregnancy Iron (mg)
Obligate loss (0.8 mg×290 days) 230
Increase in erythrocyte mass 450
Newborn (weight 3,500 g) 270
Placenta and umbilical cord 90
Blood loss at delivery 200
Gross total 1,240
Iron losses net
Reduced erythrocyte mass postpartum 450
Menostasia 160
Total net 630
560
An English study [15] of 12 women used stable iron
isotopes and a carrier dose of 6 mg ferrous iron, taken with
a breakfast meal. The mean iron absorption was 7, 36 and
66% in gestational week 12, 24 and 36, respectively. There
was a significant inverse correlation between serum ferritin
and absorption in gestational week 12 and 24. According to
the criteria chosen by the authors, iron deficiency was
infrequent. However, at 36 weeks gestation, all women had
serum ferritin <12 μg/l and 11 had ferritin <8 μg/l. Twenty
weeks after delivery absorption had declined to 11%,
which is the normal level in non-pregnant women.
These studies consistently show that iron absorption
increases with increasing length of gestation. The increase
is most pronounced after 20 weeks gestation. However, the
question is whether the increase in iron absorption in part is
due to progressive iron depletion? Do women with pre-
pregnancy ample iron reserves display the same increase in
iron absorption as women with small or depleted iron
reserves? Two studies suggest that the answer is no. Firstly,
the English study [15] reported an inverse correlation
between serum ferritin and iron absorption. Secondly, a
Peruvian study [16] has examined iron absorption in the
third trimester using stable iron isotopes and a carrier dose
of 60 mg ferrous iron. Women who had taken 60 mg
ferrous iron daily during pregnancy had a mean iron
absorption of 12%, which is similar to non-pregnant
women. There was an inverse correlation between serum
ferritin and iron absorption. Women with serum ferritin
30 μg/l had a mean absorption of 12.2%, those with
ferritin >30 μg/l had a mean absorption of 6.8% and the
woman with the highest ferritin of 61 μg/l had an
absorption of 1.5%. The results definitely suggest that the
increase in iron absorption during gestation to a major part
is elicited by low iron status.
Dietary iron intake is inadequate in pregnant women
There are few valid nutrition surveys in pregnancy.
Apparently, women do not significantly change dietary
habits when they become pregnant [17], so we have to rely
on nutrition surveys in non-pregnant women. Danish
fertile, non-pregnant women have a median dietary iron
intake of 9 mg/day [18], which means that more than 90%
of the women have an intake below the recommended 12
18 mg/day [19].
A survey comprising 821 Scandinavian women found
similar energy intake and composition of the diet before
pregnancy as well as at 17 and 33 weeks gestation [17].
Mean energy intake was 8.9 MJ/day [17], i.e. the same as in
non-pregnant women [18]. Mean energy distribution from
protein, fat and carbohydrate was 14, 36 and 50% [17].
Cigarette smokers had a lower intake of protein, vitamin C
and iron compared with non-smokers; 96% of the women
had an iron intake below 18 mg/day.
Iron status is influenced both by the iron content in the
diet as well as the bioavailability of dietary iron. Dietary
iron intake is proportional with energy intake. The majority
of fertile women in the Western countries have a dietary
iron intake, which is inadequate to fulfil the demands in the
second and third trimester [1922]. The small iron intake is
predominantly due to a low-energy intake, which in turn is
a consequence of the sedentary lifestyle prevailing in the
Western societies.
From a nutritional point of view, it is essential to
discriminate between haem- and non-haem iron. The major
fraction of dietary iron consists of non-haem iron; however,
haem iron still plays an important role as iron source due to
its higher bioavailability [23]. The consumption of
nutrients having high iron content with high bioavailability
such as beef, pork, poultry and fish tend to increase iron
absorption [24 ]. In addition to haem iron, meat contains
organic compounds, the so-called meat factors, which
promote the absorption of non-haem iron [23].
Iron absorption is inhibited by: 1. Calcium in milk and
milk-derived products, e.g. cheese. 2. Polyphenols in
coffee and tea. 3. Phytate in whole-grain breads and
cereals. 4. Oxalic acid found in spinach and beet root [23].
Even under favourable conditions, at the most 30% of
dietary iron can be absorbed, corresponding to 3 mg iron/
day from a dietary iron intake of 9 mg/day, i.e. considerably
less than the daily iron requirements during pregnancy. In
the average Scandinavian diet, the bioavailability of iron is
only 1520%. Estimates from USA suggest that dietary
iron intake should be 27 mg/day with a bioavailability of
at least 25% to fulfill the needs during pregnancy.
However, a higher dietary iron intake with a higher
bioavailability would imply profound changes in dietary
habits, which appear to be unrealistic. As dietary iron is
insufficient to fulfill iron requirements during pregnancy in
the majority of women, the Nordic Nutrition Recommen-
dations have refrained from giving figures for recom-
mended dietary iron intake [19].
Fertile women have a fragile iron status
Epidemiologic studies in Scandinavia have disclosed that
fertile, non-pregnant women, in general, have a low iron
status. Their median serum ferritin is 3840 μg/l; 10% of
non-blood-donors and 21% of blood donors have iron
depletion, i.e. serum ferritin <15 μg/l, and 24% have iron
deficiency anaemia. In total, 42% have small iron reserves,
i.e. serum ferritin 30 μg/l. Only 1420% have ample iron
reserves of 500 mg, as indicated by ferritin levels >70 μg/l
[25, 26].
Measured by quantitative phlebotomy [1, 27] and
estimated by serum ferritin [25, 26] fertile women have
median body iron reserves of 200300 mg. Approximately
40% have no haemosiderin in the bone marrow and when
they become pregnant they will enter gestation with an
unfavourably low iron status. Only 18% have iron
reserves of 500 mg, which balances the net iron loss in
pregnancy [10, 11]; these women have sufficiently large
iron reserves to go through pregnancy without iron
supplements and without developing iron deficiency after
delivery. This estimation has been sustained in a study of
Scandinavian women [28].
561
Certain subgroups within the European societies are
likely to be of higher risk for iron deficiency than the
general population. These include multipara, those with
multiple pregnancies, blood donors, vegetarians, women of
low socio-economic status, immigrants and adolescents.
Although it remains an area of some uncertainty, there is
evidence that iron deficiency, even in the absence of
anaemia, can have deleterious consequences for non-
pregnant women (and most likely also for pregnant
women), for example, in relation to cognitive ability and
physical performance [29, 30].
Iron status during pregnancy
During gestation, characteristic changes are observed in
both haemoglobin and serum ferritin concentrations. The
physiologic increase in plasma volume of 50% is only
partly compensated by an increase in the erythrocyte mass
of 25%. This results in haemodilution, where the nadir
haemoglobin concentration is reached at 2432 weeks
gestation. Subsequently, haemoglobin rises towards the
end of the third trimester (Fig. 2)[31, 32]. There is
considerable variation in the degree of haemodilution, i.e.
women with identical erythrocyte mass can present with
different haemoglobin concentrations, which may vary up
to 35 g/l. Therefore, haemoglobin as a single parameter is
not valid as a biomarker to estimate iron status or body iron
reserves in pregnancy. In iron-replete women, mean
erythrocyte volume (MCV) is stable from the beginning
of the second trimester until term; however, in women
taking placebo, there is a significant decrease in MCV in
the third trimester indicating some degree of iron deficien-
cy (Fig. 2).
At the initial visit in the antenatal clinic in 1418 weeks
gestation, only 18% of the women have serum ferritin
>70 μg/l, i.e. iron reserves of 500 mg [33, 34]. During
gestation, there is a gradual decline in serum ferritin, and
the nadir concentrations are reached at 3538 weeks
gestation, followed by a moderate increase towards
delivery (Fig. 3)[33]. The fluctuations in serum ferritin
are, in part, physiological, being independent of iron
balance. However, is spite of these physiologic changes, a
clinically relevant association between serum ferritin and
iron status still exists, as assessed by the amount of
haemosiderin in the bone marrow. Serum ferritin is still the
best biomarker for iron status during pregnancy [ 35, 36].
As a consequence of the physiologic decline in serum
ferritin [33], the cut-off level for iron deficiency in
pregnancy should be lower than in non-pregnant women,
i.e. <12 μg/l.
The golden standard in the definition of iron-deficiency
anaemia is an increase in haemoglobin concentration
during iron therapy. This strict criterion is often not
applicable in the clinical situation. Instead, an arbitrarily
chosen haemoglobin concentration is used as cut-off value
in the definition of anaemia. The World Health Organiza-
tion has suggested a cut-off value of <110 g/l (6.8 mmol/l)
in the definition of anaemia in pregnancy [37]. In a study of
healthy pregnant women, we found that the haemoglobin
cut-off value for anaemia varied according to the period in
pregnancy (Table 2)[32]. Over the entire period of
pregnancy, a common haemoglobin cut-off value for
anaemia would be <105 g/l (6.5 mmol/l) [32]. Table 2
shows the frequency of iron deficiency in pregnant women
randomised to treatment with either placebo or iron
Fig. 2 Haemoglobin concentration and mean erythrocyte volume
(mean±SD) during pregnancy and postpartum in women taking
placebo or iron supplement, 66 mg ferrous iron/day from 14
18 weeks gestation to 8 weeks postpartum (reproduced with
permission from [33])
Fig. 3 Serum ferritin concentration (geometric mean±SEM) during
pregnancy and postpartum in women taking placebo or iron
supplement, 66 mg ferrous iron/day from 1418 weeks gestation
to 8 weeks postpartum (reproduced with permission from [33])
562
supplement. In the third trimester, 50% of women taking
placebo have serum ferritin levels <12 μg/l, i.e. iron
depletion or probable iron deficiency; 21% have serum
ferritin <12 μg/l and a low haemoglobin, compatible with
iron-deficiency anaemia. The relationship between haemo-
globin (Hb) in gram/litre and in millimole/litre is expressed
in the following formulas: Hb in g/l×0.062054=Hb in
mmol/l; Hb in mmol/l×16.115=Hb in g/l.
EPO stimulates erythropoiesis and causes the haemo-
globin concentration to rise. During normal pregnancy, the
serum EPO concentration displays a steady increase,
reaching a maximum at the end of the third trimester
(Fig. 4)[3840]. The increase in serum EPO is inversely
associated with haemoglobin and iron status [3840], being
markedly higher in pregnant women taking placebo than in
those taking iron supplement [38, 40]. These findings
could be interpreted as follows: low haemoglobin in
women taking placebo, which is due to iron deficiency, is
recognized by the bodys homeostatic mechanisms as
being inappropriately low. This, in turn, induces an EPO
release, to increase the haemoglobin concentration. As the
rise in EPO levels is blunted by iron supplements [38, 39]
we conclude that the body is providing an erythropoietic
drive as a result of lack of iron.
Iron status after delivery
Postpartum, when the redistribution of the erythrocyte
mass and plasma volume has reached a steady state, there is
an increase in serum ferritin and haemoglobin, which is
most pronounced in women taking iron supplement
(Figs. 2 and 3 ). Concomitantly, there is a decrease in
MCV, which is significantly lower in mothers taking
placebo than in mothers taking iron supplement (Fig. 2).
Several studies have shown that iron supplements during
pregnancy result in higher iron status in the mothers
postpartum [32, 33, 4143]. Eight weeks after normal
delivery, 16% of mothers taking placebo display iron
deficiency and 12% iron-deficiency anaemia. Among iron-
supplemented mothers, 3% display iron deficiency and
1.6% iron-deficiency anaemia (Table 2)[32, 33], i.e. a
slightly lower frequency of iron-deficiency anaemia than in
fertile non-pregnant women [25, 26].
Considering the physical and psychological demands
being posed to the new mother, it would be unfortunate if
she is not in good shape due to iron deficiency anaemia. At
510% of deliveries blood losses are so substantial that the
mother develops anaemia [44, 45]. This will of course
stimulate erythropoiesis, which implies the presence of
mobilizable iron reserves. A limiting factor for correction
of the anaemia caused by bleeding is, therefore, absent iron
reserves in late pregnancy [33, 44, 45]. To avoid blood
transfusion, some obstetricians have suggested treatment of
anaemia with intravenous iron in combination with EPO
[44, 45]. From a physiologic point of view, it would be
more convenient if the mother s own iron reserves at the
end of pregnancy were adequate to compensate for the
blood losses associated with delivery.
It is thought-provoking that one pregnancy leaves
fingerprints on iron status for many years. Nullipara have
Table 2 Iron deficiency (ID), low haemoglobin (Hb) and iron deficiency anaemia (IDA) during pregnancy and postpartum in women taking
placebo or iron supplement from 1418 weeks gestation to 8 weeks postpartum (from [32, 33])
Gestation (week) Postpartum (week)
1418 1922 2326 2730 3134 3538 3943 8
PLACEBO n= 46575656575724 58
ID (% of women) 4.4 5.3 19.6 32.1 47.4 49.1 50.0 15.5
Low Hb
a
(%) 19.6 14.0 5.4 16.1 19.3 29.8 41.7 25.7
IDA (%) 0 0 0 5.4 10.5 17.5 20.8 12.1
Ferrous iron 66 mg/day n= 47616261625929 62
ID (% women) 2.1 1.6 3.2 9.8 8.1 5.1 3.5 3.2
Low Hb
a
(%) 8.5 4.9 1.6 3.3 4.8 8.5 10.3 6.5
IDA (%) 0 0 0 0 0 0 0 1.6
Hb cut-off level for anaemia (g/l) 110 106 103 106 106 110 114 123
Iron deficiency: serum ferritin <12 μg/l during pregnancy, <15 μg/l postpartum. Iron deficiency anaemia: serum ferritin <12 μg/l during
pregnancy, <15 μg/l postpartum and haemoglobin below cut-off level for anaemia [26]
a
Hb below cut-off level for anaemia
Fig. 4 Serum erythropoietin (EPO) (geometric mean±SEM) during
pregnancy and postpartum in women taking placebo or iron
supplement, 66 mg ferrous iron/day from 1418 weeks gestation
to 8 weeks postpartum (reproduced with permission from [33])
563
higher serum ferritin than uniparawho in turn have higher
serum ferritin than multipara [46]. These birth-related
differences in iron status persist even after menopause.
Association between pregnant womens haemoglobin
and newborns birth weight
Pregnant women taking iron supplements have higher
haemoglobin concentrations than women taking placebo.
In this context, it is important to discriminate between the
effect of iron supplements and the problems related to
inappropriate haemodilution of pregnancy. In a population
of unselected pregnant women, comprising women with
both normal and complicated pregnancies, there exists an
inverse association between the womens haemoglobin
concentration and the newborns birth weight, which
means that high haemoglobin levels are associated with
low birth weight [4749]. This association is statistically
significant from the second trimester, i.e. before the
haemoglobin concentration has reached its nadir. High
haemoglobin concentrations of >145 g/l (9 mmol/l)
increase blood viscosity, which may reduce placental
perfusion and, thereby, the nutrition of the foetus, resulting
in low birth weight [48].
However, birth weight is also reduced at low haemoglo-
bin concentrations of <85 g/l (5.3 mmol/l) [4749], i.e. at
pronounced iron-deficiency anaemia. Welsh women, who
in 1324 weeks gestation had haemoglobin levels of
<105 g/l (6.5 mmol/l), displayed a 1.6-fold higher risk for
preterm birth and low birth weight of their newborns than
non-anaemic women [49].
The association between a high haemoglobin concen-
tration and a low birth weight is primarily caused by an
inappropriate haemodilution of pregnancy. Preeclampsia
and eclampsia are characterised by inadequate hæmodilu-
tion, and these disorders are associated with low birth
weight of the newborns. In placebo-controlled studies on
healthy pregnant women, there is no relationship between
the womens haemoglobin and the birth weight of the
newborns, and there is no increased frequency of pre-
eclampsia in the women taking iron supplements [33, 34].
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... Both dietary iron absorption and iron mobilization from storage are enhanced during pregnancy to meet increasing needs. This concerns both heme and non-heme iron [53][54][55]. The hepcidin concentration decreases throughout normal pregnancy and its nadir is usually reached during the third trimester, as the iron needs are maximal [41,56]. ...
... The intracellular iron storage pool correlates with the circulating ferritin concentration [92]. Without iron supplementation, the ferritin concentration decreases throughout pregnancy, with a nadir between 35 and 38 WG, and then slowly increases afterward [54]. Serum ferritin < 30 µg/L is the main criterion for iron deficiency for pregnant women if no chronic inflammation is suspected. ...
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Iron is required for energy production, DNA synthesis, and cell proliferation, mainly as a component of the prosthetic group in hemoproteins and as part of iron-sulfur clusters. Iron is also a critical component of hemoglobin and plays an important role in oxygen delivery. Imbalances in iron metabolism negatively affect these vital functions. As the crucial barrier between the fetus and the mother, the placenta plays a pivotal role in iron metabolism during pregnancy. Iron deficiency affects 1.2 billion individuals worldwide. Pregnant women are at high risk of developing or worsening iron deficiency. On the contrary, in frequent hemoglobin diseases, such as sickle-cell disease and thalassemia, iron overload is observed. Both iron deficiency and iron overload can affect neonatal development. This review aims to provide an update on our current knowledge on iron and heme metabolism in normal and pathological pregnancies. The main molecular actors in human placental iron metabolism are described, focusing on the impact of iron deficiency and hemoglobin diseases on the placenta, together with normal metabolism. Then, we discuss data concerning iron metabolism in frequent pathological pregnancies to complete the picture, focusing on the most frequent diseases.
... In this study anemia were 4.48 (AOR) and 2.66 (AOR) more prevalent in pregnant woman with third and second trimesters respectively compared to those in the first trimesters. Because the requirements for absorbed iron increase from 0.8 mg/day in the first trimester to 7.5 mg/day in the third trimester [34,35]. This finding was in line with WHO report [36]. ...
... The result of this study shown that anemia was 2.266 more prevalent in pregnant women who did not take iron supplements during pregnancy than those who had (AOR = 2.166; 95% CI: 1.410-3.327). this is because Requirements for absorbed iron increase in an average of ~ 4.4 mg/day in the entire gestation period [34,35]. In the current study, tea intake immediately after meal had been associated with increased risk of 3.4 times to be anaemic (AOR: 3.430; 95% CI: 2.004-5.873). ...
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Background: Anemia in pregnancy is a serious global public health problem in most developing countries and a major cause of maternal morbidity and mortality. Somalia which already had very high maternal mortality ratio of 829 per 100,000 live births, pregnant women in internally displaced camps (IDPs) remain at most exposed. The aim of the study was to determine the prevalence, severity and associated risk factors of anemia among pregnant women in internally displaced camps in Mogadishu, Somalia. Methods: A community based cross-sectional study was conducted among 383 households in the most IDP settled districts in Mogadishu. Every pregnant mother in these sampled households who was voluntarily consented was targeted. A sample of blood was also taken by pricking the fingertip and inserted into hemoglobin meter. Those with Hb < 11 g/dl from hemoglobin meter had been taken another sample of 3 cc blood and put into EDTA tube for CBC analysis to identify the type of anemia. Data on risk factors were collected using structured pretested questionnaire via an interview. Collected data was coded and entered in SPSS- Version 22 for analysis. Descriptive analysis, bivariate chi-square and multivariate logistic regression were done. Results: The overall prevalence of anemia among study participants was 44.4% (95%CI: 39.5-49.3%), where severe and moderate anemia were 11.8 and 47.0% respectively. In addition all anaemic cases were microcytic hypochromic anemia. Young maternal age, low Family income, fewer/zero parity, being at third or second trimesters, lack of ANC attendance during pregnancy, lack of iron supplementation during pregnancy, taking tea immediately after meal during pregnancy, lower/zero frequency of daily meat and vegetables consumption during pregnancy were associated risk factors of anemia. Conclusion: The anemia prevalence from this study was severe public health problem. Several factors were found to be associated with anemia during pregnancy. Measures has to be taken to curb the problem by including them mass iron supplementation and health education towards identified risk factors.
... Although iron deficiency is common among the general population, a preponderance of pregnant women is affected by this condition, due in part to an expansion in blood volume and increased erythropoiesis, as well as increased iron demands from the fetal-placental unit [23]. Routine iron supplementation is recommended in the second and third trimesters because most women cannot meet their increased iron requirements from dietary sources alone [24]. ...
... Iron deficiency during pregnancy is a preventable cause of several health problems in both the mother and infant, including an increased risk of anemia, premature birth, low birth-weight, developmental abnormalities, and postpartum depression [1,2]. Physiologically, pregnant women have a higher iron demand, which starts shortly after conception and increases gradually during gestation [3]. Iron is essential to support the increases in maternal erythropoiesis and to meet the requirements of the fetal organogenesis, notably the development of the central nervous system and hematopoietic tissues [4]. ...
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Iron deficiency in pregnancy is a major public health problem that causes maternal compli- cations. The objective of this randomized, controlled trial was to examine the bioavailability, efficacy, and safety of oral ferrous bisglycinate plus folinic acid supplementation in pregnant women with iron deficiency. Subjects (12–16 weeks of gestation, n = 120) were randomly allocated to receive oral iron as ferrous bisglycinate (equiv. iron 24 mg) in supplement form with folinic acid and multivitamins (test group, n = 60) or as ferrous fumarate (equiv. iron 66 mg iron, control group, n = 60) after breakfast daily. Iron absorption was assessed by measuring fasted serum iron levels at 1 and 2 h immediately after supplementation. Hematological biomarkers and iron status were assessed before intervention, and at 3 and 6 months. Side effects were monitored throughout the intervention. A significant increase in serum iron was seen in both groups (p < 0.001) during the bioavailability assessment; however, the test group increases were comparatively higher than the control values at each timepoint (p < 0.001). Similarly, both test and control groups demonstrated a statistically significant increases in hemoglobin (Hb) (p < 0.001), erythrocytes (p < 0.001), reticulocytes (p < 0.001), mean corpuscular volume (MCV) (p < 0.001), mean corpuscular hemoglobin (MCH) (p < 0.001), mean corpuscular hemoglobin concentration (MCHC) (p < 0.001), % transferrin saturation (p < 0.001), and ferritin (p < 0.001) at 3 and 6 months after supplementation. However, in all cases, the test group increases were numerically larger than the control group increases at each timepoint. The test intervention was also associated with significantly fewer reports of nausea, abdominal pain, bloating, constipation, or metallic taste (p < 0.001). In conclusion, ferrous bisglycinate with folinic acid as a multivitamin nutraceutical format is comparable to standard ferrous fumarate for the clinical management of iron deficiency during pregnancy, with comparatively better absorption, tolerability, and efficacy and with a lower elemental iron dosage.
... However, this is not without risk, particularly in iron-replete women where the indiscriminate use of supplementary iron can lead to maternal organ damage and impaired fetal development (7,19). IHAT has shown promise as a potential replacement for currently available supplements based on ferrous iron salts, with published data indicating that it is as efficacious as ferrous sulfate, but with fewer side effects (20). Results from our current study also suggest that IHAT may be an effective supplement for treating iron deficiency during pregnancy, with an efficacy similar to that of ferrous sulfate. ...
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Background Many women enter pregnancy with iron stores that are insufficient to maintain maternal iron balance and support fetal development and, consequently, often require iron supplements. However, the side effects associated with many currently available iron supplements can limit compliance. Objective This study aimed to test the safety and efficacy of a novel nanoparticulate iron supplement, a dietary ferritin analogue termed iron hydroxide adipate tartrate (IHAT), in pregnant mice. Methods Female C57BL/6 mice were maintained on either an iron deficient or a control diet for two weeks prior to timed mating to develop iron deficient or iron sufficient pregnancy models respectively. Mice from each model were then gavaged daily with 10 mg iron/kg body weight as either IHAT or ferrous sulfate, or with water only, beginning on embryonic day (E) 4.5. Mice were euthanized on E18.5 and maternal iron and hematological parameters were measured. The expression of genes encoding iron transporters and oxidative stress markers in the duodenum and placenta were determined, along with hepatic expression of the gene encoding the iron regulatory hormone hepcidin and fetal iron. Results Oral IHAT and ferrous sulfate were equally effective at increasing maternal hemoglobin (20.2% and 16.9% respectively) and hepatic iron (30.2% and 29.3% respectively), as well as total fetal iron (99.7% and 83.8% respectively), in iron deficient pregnant mice compared to those gavaged with water only, with no change in oxidative stress markers seen with either treatment. However, there was a significant increase in the placental expression of the oxidative stress marker heme oxygenase 1 in iron replete pregnant mice treated with ferrous sulfate when compared to iron replete pregnant mice gavaged with IHAT (96.9%, P < 0.05). Conclusions IHAT has proved a safe and effective alternative to oral ferrous sulfate in mice, and it has potential for treating iron deficiency in human pregnancy.
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Chapter
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Background: Iron deficiency affects thyroid hormones synthesis by impairing the activity of the heme-dependent thyroid peroxidase. The prevalence of iron deficiency is elevated particularly in pregnant women. This study aimed to investigate the effects of iron status on thyroid function in a nationally representative sample of mildly iodine-deficient pregnant women. Methods: The study population comprised a sample of pregnant women in Belgium during the first and third trimesters of pregnancy (n= 1241). Women were selected according to a multistage proportional- to-size stratified and clustered sampling design. Urine and blood samples were collected, and a questionnaire was completed face to face with the study nurse. Concentrations of FT4, total T4, FT3, TSH, thyroglobulin (Tg), thyroid peroxidase antibodies, thyroglobulin anti-bodies, hemoglobin, serum ferritin (SF), soluble transferrin receptor, urinary iodine concentrations (UIC) were measured and body iron stores (BIS) were calculated. Results: Median UIC were 117 and 132 μg/L in the first and third trimester of pregnancy respectively (p<0.05). The frequency of SF < 15 μg/L was 6.2 % in the first trimester and 39.6 % in the third trimester of pregnancy (p<0.05). Urinary iodine concentration was a significant predictor of serum Tg concentrations (p<0.01) but not of thyroid hormones or TSH concentrations. The frequency of FT4 < percentile 10th in the third trimester of pregnancy was 24% and 14% in pregnant women with negative BIS and positive BIS respectively (P<0.05). Serum ferritin and BIS were significant predictors of FT4 and T4 in the first trimester of pregnancy (p<0.05). Hemoglobin was a significant predictor of FT4 in both trimesters (p<0.01) and for T4 in the third trimester (p=0.015). Conclusion: Iron deficiency, but not mild iodine deficiency, is a determinant of serum FT4 and T4 in pregnant women. Correcting iron deficiency may help to maintain optimal thyroid function, in addition to preventing anemia during pregnancy.
Article
Iron requirements are greater in pregnancy than in the nonpregnant state. Although iron requirements are reduced in the first trimester because of the absence of menstruation, they rise steadily thereafter; the total requirement of a 55-kg woman is ≈1000 mg. Translated into daily needs, the requirement is ≈0.8 mg Fe in the first trimester, between 4 and 5 mg in the second trimester, and >6 mg in the third trimester. Absorptive behavior changes accordingly: a reduction in iron absorption in the first trimester is followed by a progressive rise in absorption throughout the remainder of pregnancy. The amounts that can be absorbed from even an optimal diet, however, are less than the iron requirements in later pregnancy and a woman must enter pregnancy with iron stores of ≥300 mg if she is to meet her requirements fully. This is more than most women possess, especially in developing countries. Results of controlled studies indicate that the deficit can be met by supplementation, but inadequacies in health care delivery systems have limited the effectiveness of larger-scale interventions. Attempts to improve compliance include the use of a supplement of ferrous sulfate in a hydrocolloid matrix (gastric delivery system, or GDS) and the use of intermittent supplementation. Another approach is intermittent, preventive supplementation aimed at improving the iron status of all women of childbearing age. Like all supplementation strategies, however, this approach has the drawback of depending on delivery systems and good compliance. On a long-term basis, iron fortification offers the most cost-effective option for the future.
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A review of nutritional anaemia in Africa is presented above. It has been noted that nutritional anaemia, including iron-deficiency anaemia, megaloblastic anaemia due to folate deficiency or vitamin B12 deficiency, or both, and protein deficiency-anaemia, is widespread throughout Africa. It is particularly common in growing children, women of child-bearing age, pregnant women and lactating mothers. The anaemia is also especially common during the second half of the dry season and the first Half of the wet season, when food supplies are limited. In all cases the anaemia is caused either by limited dietary intake, excessive loss of nutrients or excessive utilization. The anaemia is associated with a number of sequelae including both structural changes, like mitochondrial swelling and mucosal atrophy, and functional abnormalities, such as cardiac failure, decreased work output, increased pregnancy risks and increased susceptibility to infections. The evidence in favour of increased susceptibility to infections in megaloblastic anaemia and protein-deficiency anaemia is overwhelming, but in iron-deficiency anaemia the available information argues in favour of reduced susceptibility to infections, except after initiation of iron therapy. The treatment of nutritional anaemia includes replacement of the deficient nutrients (and blood transfusion in severe cases), prevention of further nutrient losses and treatment of associated complications.
Article
In a double-blind, randomised study we treated 36 women in the puerperium with haemoglobin concentration below 9 g / dl with 400 mg Fe+++. 20 women received 20 000 IE erythropoietin (rHuEP0) i.v. in addition, 12 women received placebos. In both groups there were no differences in the haematological and iron parameters in the first 4 weeks after delivery. The results show that the additional therapy with rHuEPO in postpartum anaemia is not justified. The limiting factor in a quick correction of the postpartum anaemia is the insufficient presence of iron at the end of pregnancy. The therapy of choice for quick and safe correction of p.p. anaemia is the effective intravenous iron supplementation
Article
This article describes a study of the relationship between diet and smoking in a group of 821 Norwegian pregnant women. The study is part of a multi-centre project, examining risk factors for intrauterine growth retardation. Two 3-day dietary records were collected during the 17th and 33rd week of pregnancy. Information on smoking habits and other relevant parameters were collected through an extensive questionnaire. The results showed that the smokers consumed significantly less than the non-smokers of bread, cakes and cookies, vegetables, fruits and berries, cheese, yoghurt, low fat milk, juice and tea. The smokers also consumed significantly more meat, margarine, whole milk, soft drinks and coffee than the non-smokers on both occasions. The diet of the smokers contained significantly less protein, carbohydrate, dietary fibre, thiamin, riboflavin, vitamin C, calcium and iron as compared with the non-smokers. Fat contributed significantly more to the energy content of the diet of the smokers and it is concluded that their diet was less nutritious than that of the non-smokers throughout pregnancy.
Article
Intestinal59Fe-absorption was used as an indicator of prelatent and latent iron deficiency and was measured from the 4th to 9th month of pregnancy in 85 women with the59Fe-absorption-whole body retention test using an oral test dose of 0.558 mg59Fe++ (10µMol=0.05–0.20µC)+17.6 mg (≡100µMol)L-(+) ascorbic acid. Intestinal59Fe-Absorption was measured to be 31.7±8.1% in normal menstruating women and increased permanently during pregnancy to 74.6±17% during the 6th month, 84±13% in the 7th month and 90±4.9% in the last month. A considerably augmented59Fe-absorption, caused by a depletion of the usable iron stores, was observed in 40% of normal menstruating women, and in pregnant women with a frequency of 58% in the 5th month, 92% in the 6th month and with 100% during the 7th to 9th month. Prelatent (14–33%), latent (64–72%) and manifest (9–20%) iron deficiency states are observed during the 3rd trimester of pregnancy without exception in all women.