Indian J Hematol Blood Transfus

https://doi.org/10.1007/s12288-018-0949-6

REVIEW ARTICLE

Management of Iron Deficiency Anemia in Pregnancy in India

Rimpy Tandon1 • Arihant Jain2 • Pankaj Malhotra2

Received: 23 February 2018 / Accepted: 8 March 2018

Ó Indian Society of Hematology and Blood Transfusion 2018

Abstract Iron deficiency anemia (IDA) continues to be the Introduction

commonest etiology of anemia in pregnancy. The preva-
lence of iron deficiency (ID) in pregnant Indian women is Iron deficiency and its consequences continue to be
amongst the highest in the world. Untreated iron deficiency prevalent in epidemic proportions despite major health
(ID) has significant adverse feto-maternal consequences. reforms over the past century [1]. Although the adverse
Plethora of investigations are available for diagnosis of consequences on maternal and child health are well known,
IDA, each having specific advantages and disadvantages it continues to be sub-optimally managed. The causes of
when used in the pregnancy setting. Therapy for ID anemia in pregnancy may be numerous, the current article
includes dietary modification, oral iron supplementation, focuses on management of iron deficiency anemia (IDA) in
intravenous iron and blood transfusion. Newer parenteral pregnancy. Management of other etiologic causes of ane-
iron preparations are safe and there is mounting evidence to mia are beyond the scope of this review.
suggest their use in frontline settings for pregnancy asso-
ciated IDA in the second and third trimester. Through this
review, we suggest an algorithm for diagnosis and treat- Definitions
ment of IDA in pregnancy depending on the severity of
anemia and period of gestation suited for widespread use in Anemia is a condition where the red blood cell number or
resource limited settings. Also, we recommend ways for their oxygen-carrying capacity is insufficient to meet
increasing public awareness and tackling this health issue physiologic needs, and is conventionally taken as a
including the observance of ‘‘National Anemia Awareness hemoglobin (Hb) value that is less than two standard
and Treatment Day.’’ deviation (SD) below the median value for healthy mat-
ched population by age, sex, altitude, smoking, and preg-
Keywords Iron deficiency anemia  Pregnancy  India nancy status [2]. Defining anemia in pregnancy is not
straight-forward given the physiologic plasma expansion,
the ethnic variations of Hb values and the frequent use of
iron supplementation in pregnancy. Center of Disease
Control (CDC) defines anemia as pregnancy hemoglobin
Electronic supplementary material The online version of this less than 11 g/dl (Hematocrit;{Hct} \ 33%) in the first and
article (https://doi.org/10.1007/s12288-018-0949-6) contains supple-
mentary material, which is available to authorized users. third trimester and less than 10.5 g/dl (Hct \ 32%) in the
second trimester while World Health Organisation (WHO)
& Pankaj Malhotra defines anemia in pregnancy as Hb values less than 11gm/
[email protected]
dl [3, 4]. Anemia in postpartum females is defined as Hb
1
Department of Obstetrics and Gynaecology, Government less than 10 g/dl by WHO. Table 1 shows WHO classifi-
Medical College and Hospital-32, Chandigarh, India cation of severity of anemia in adult females [5].
2
Department of Internal Medicine (Clinical Hematology
Division), PGIMER, Chandigarh, India

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Table 1 Hemoglobin levels to diagnose anemia at sea level [5]

Non Anemia (g/dl) Anemia (g/dl)
Mild Moderate Severe

Non pregnant women(age [ 15 years or above) [ = 12 or higher 11–11.9 8–10.9 Lower than 8
Pregnant women [ = 11 or higher 10–10.9 7–9.9 \7

Prevalence of IDA in Pregnancy Report 2016, India ranked miserably at 170th in terms of
anemia prevalence in women [9] (Figure 1).
Globally, the commonest cause for anemia in pregnancy is
IDA. The Nutrition Impact Model Study, a systematic
analysis of 257 population-representative data sources from Consequences of IDA in Pregnancy
107 countries, estimated the global prevalence of anemia in
pregnancy as 43% in 1995 and 38% in 2011 with the range It is estimated that maternal anemia contributes to 18% of
varying from 17% in developed and 56.4% in developing perinatal mortality and 20% of maternal mortality in South
countries. Etiology of anemia was attributed to ID in 50% Asian countries including India as per a recent meta-anal-
of cases in this study [1]. The prevalence of occult ID in the ysis [10]. The exact level of maternal hemoglobin that is
absence of anemia is estimated to be between 30 and 60% critical with respect to maternal mortality is not known.
in pregnant women [6]. In a population based study from According to CHERG, the risk of maternal mortality sig-
rural Haryana in 1994–1995,we had found 50% prevalence nificantly decreases for every 1 g/dl rise in Hb, however,
of anemia among non-pregnant women in the age group of the association becomes less clear at Hb levels above
16–70 years [7]. Twenty years later, the prevalence of 8–9 g/dl [11]. With respect to neonatal birth weight, both
anemia still continues to be 53% in non-pregnant women hemoglobin level [ 11 g/dl and \ 9 g/dl are associated
and 50% in pregnant women as per population based sur- with 2–3 times increased risk of small for gestational age
veys of 2016 in our country [8]. As per the Global Nutrition neonates. The ideal Hb values with respect to prevention of
prematurity and LBW lies between 9 to 11.5 g/dl [12].
Table 2 summarizes the consequences of IDA in
pregnancy.

Physiology of Iron Balance During Pregnancy

Table 3 depicts the net iron balance during a normal

pregnancy and delivery. As shown, pregnancy costs an
approximate 630 mg of extra iron to the mother. In the
hierarchy of iron usage the fetus takes the priority, fol-
lowed by maternal hematocrit while the maternal iron
stores are the poor last and are often depleted during the
course of pregnancy. The mother indeed requires iron
stores for lactation and future pregnancies. To prevent a
negative iron balance during pregnancy a mother requires
at least 300 mg of iron stores at the time of start of preg-
nancy if she consumes a diet rich in bioavailable iron, and
would require obligatory supplementation if she consumes
a suboptimal diet [22]. Majority of iron transfer to the fetus
occurs during the second and third trimester. The average
daily requirement of iron has been calculated as 0.8 mg/d
in the first trimester and increases to 7.5 mg/day in the
third trimester. The average daily absorption form a
Fig. 1 Global and national trends in IDA in women of reproductive
age group [9] western diet is 1–5 mg/day and average daily absorption

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Table 2 Consequences of IDA in pregnancy [12–21]

Antepartum complications Intrapartum complications Postpartum complications Fetal outcome

Increased risk of preterm Prolonged labor Postpartum hemorrhage Low birth weight
delivery
Premature rupture of Increased rates of operative delivery and induced Purperal sepsis Prematurity
membranes labor
Preecclampsia Fetal distress Lactation failure Infections
Intrauterine Death Abruption Pulmonary Congenital malformation
thromboembolism
Intercurrent infection Subinvolution of uterus Neonatal Anemia
Antepartum hemorrhage Postpartum depression Abnormal cognitive
development
Congestive Heart Failure Increased risk of
Schizophrenia

Table 3 Approximate iron demands during a normal pregnancy and History and Clinical Examination
delivery [22]
Gross iron demands Although known to be less sensitive than laboratory
assessment, a history for fatigue, alopecia, pica, restless leg
Obligatory Iron Loss (0.8mg 9 290 days) 230 mg syndrome, pagophagia and a brief examination for pallor,
Increase in red cell mass 450 mg koilonychia, atrophic tongue papillae, glossitis and stom-
Newborn baby (birth weight 3.5 kg) 270 mg atitis should be undertaken for all pregnant women. Severe
Placenta and umbilical cord 90 mg cases may manifest with evidence of congestive cardiac
Blood loss at delivery 200 mg failure such as orthopnea, edema, raised Jugular Venous
Total gross 1240 mg Pulse and pulmonary crepts and would merit urgent treat-
Net Iron demands ment [26].
Absence of menstruation in pregnancy - 160 mg
Post partum decrease in red cell mass - 450 mg The RBC Traits
Total net iron demands 630 mg
RBC indices and morphology characteristics are readily
available and are recommended as the first step in the
evaluation of pregnancy associated anemia.
form Indian diet varies from 0.8 mg/d to 4.5 mg/d
depending on the type of staple used [23]. Mean Corpuscular Volume (MCV) and Red Cell
Distribution Width (RDW)
Diagnosing Iron Deficiency and Iron Deficiency
Anemia in Pregnancy IDA is characterized by microcytosis, (lowMCV \ 80 fl)
and hypochromia (Mean Corpuscular Hemoglobin
Most guidelines recommend screening for anemia during {MCH} \ 27 pg) and blood film may confirm character-
pregnancy in the first trimester (or at booking) followed by istic microcytic cells or pencil cells [27].
24–28 weeks and at 36 weeks of gestation [24]. The cut off While IDA is the commonest cause for decreased MCV,
values defined by WHO/CDC for anemia in pregnancy low MCV is insensitive and up to 40% of pregnant women
along with peripheral smear showing normal morphology with true IDA have normocytic indices. Stimulation of
of RBC with central pallor have often been taken as criteria erythropoiesis in pregnancy masks the microcytosis of iron
for defining the physiologic anemia of pregnancy. A deficiency. Moreover, a low MCV, is not specific, for IDA
deviation from the above parameters should often be [28–30].
treated as pathologic and warrant further testing for the In settings where detailed biochemical evaluation for
etiology and appropriate management of anemia during iron profile is not feasible, a combination of low MCV
pregnancy [25]. accompanied by elevated RDW can be used as a sufficient
evidence to start iron therapy. A subsequent marked RDW
increase occurring early after the initiation of therapy can

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be used as a surrogate for confirmation of IDA [30]. Sen- diagnose ID, a cut off of \ 30lg/dl is 92% specific and
sitivity and specificity of RDW in the diagnosis of IDA in 98% specific in diagnosing ID [40]. As non anemic iron
pregnancy has been reported to be between 72–97 and deficiency (NAID) is also known to affect feto-maternal
82–83% respectively [29, 31]. outcome, most obstetricians and hematologists recommend
a cut off 30 lg/dl to diagnose and treat ID in pregnancy
Newer RBC Parameters [41, 42]. However, this higher threshold is bound to
increase the socio-economic burden of policy makers in
Advanced red blood cell and reticulocyte indices such as resource limited countries like India.
percentage hypochromic reticulocytes (%HYPOr), Retic-
ulocyte Hemoglobin content (CHr), and percentage circu- Diagnosing ID in the Setting of Inflammation
lating microcytes (%HYPOm) are established markers of
iron deficient erythropoiesis and are measurable with In the setting of inflammation (e.g. post-operative state) or
modern automated analysers. They have also been proven infection during pregnancy, serum ferritin may be falsely
as earlier markers of response to iron therapy as compared elevated concomitant with CRP levels [43]. Serum ferritin
to MCV and can be easily incorporated for diagnosing and levels also exhibit a post-partum rise consequent to
monitoring therapy in IDA in pregnancy [32]. Further inflammation and are no longer representative of iron status
studies are required for validating the use of these param- [44]. There is no gold standard test that diagnoses ID in the
eters in pregnancy [33]. setting of inflammation. A low Tsat \ 16% in the setting of
Table 4 gives the utility and the normal reference ranges low ferritin (empirically set at \ 100lg/dl) or the ratio
for the newer RBC parameters and Table 5 summarizes the between soluble transferrin receptor (sTFR) and log ferritin
interpretation of various iron parameters. levels, may be used in this setting [26, 45]. As the sTFR
levels are not influenced by the post partum inflammatory
Serum Ferritin state, they can be used in diagnosing IDA in early puer-
peral phase or when there is unexplained anemia with high
While bone marrow stainable iron stores is the gold stan- CRP levels [46].
dard for diagnosing IDA, the test is invasive and imprac-
tical to use during pregnancy [35]. Serum ferritin is a more Indications of Serum Ferritin Testing
sensitive and specific marker for ID than serum iron,
transferrin saturation (Tsat), and erythrocyte protopor- Routine screening with serum ferritin in patients with
phyrin values [36]. Currently low serum ferritin values are pregnancy associated anemia is not yet proven to be a cost-
regarded as the best test for confirmation of iron deficiency effective strategy to diagnose IDA [47]. Table 6 summa-
in pregnancy [37]. During pregnancy, in women with rizes indications of serum ferritin testing for pregnancy
adequate iron stores, serum ferritin initially rises and later associated anemia in resource constraint settings.
gradually falls to about 50% of pre pregnancy levels by
32 weeks (due to hemodilution), followed by a slight rise Other Iron Parameters
in the third trimester [38]. There is considerable debate in
serum ferritin thresholds used to define ID in pregnancy. Serum iron shows diurnal variation and is affected by
One of the studies suggested a pre pregnancy cut off \ dietary influences [48]. Pregnancy itself increases total iron
70lg/dl to be predicative of development of IDA in binding capacity (TIBC) even in the absence of IDA. Thus
pregnancy [39]. When compared to bone marrow iron serum iron and TIBC are unreliable markers to be used in
stores a threshold of \ 12lg/dl is only 25% sensitive to pregnancy [30]. Tsat values also fluctuate with diurnal

Table 4 Newer RBC parameters for IDA

Normal range Clinical utility

%HypoM [32] \ 3.4% Indicator of IDA

%HypoR [32] \ 3.7% Indicator of IDA
CHr [32] \ 25 pg Measures functional iron available over 3–4 days, early indicator of IDA and response to iron therapy
M/H [34] \ 3.7 Differentiating IDA from Beta Thalassemia trait
%HypoM %Hypochromic microcytes; %HypoR %Hypochromic reticulocytes; CHr reticulocyte hemoglobin content; M/H Microcytic RBC%/
Hypochromic RBC%

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Table 5 Laboratory parameters

ID IDA AOCD ID and AOCD Normal value (adult female)
to diagnose iron status [27]
Serum Iron ; ; ; ; 10–30 lM/L
Tsat% [ 16 \ 16 N/; N/; [ 16 to \ 45
Ferritin (lg/dl) \ 30 \ 12 [ 100 \100 20–200
sTFR : : N/: Variable :
sTFR/log ferritin NA [2 \1 [2
ZPP N : : : :
Serum hepcidin ; ; : N/: :
ID iron deficiency; IDA iron deficiency anemia; AOCD anemia of chronic disease; N indicates normal; T sat
transferrin saturation; sTFR soluble transferrin receptor ZPP, Zn Protoporphyrin

Table 6 Indications of testing serum ferritin in pregnancy [35, 40]

1. Prior to starting iron therapy in therapeutic doses in patients with known hemoglobinopathy
2. When an alternative etiology of microcytic anemia is being considered (chronic inflammation, lead toxicity, sideroblastic anemia)
3. Suboptimal response to oral iron when compliance is doubtful
4. In non-anemic women at increased risk of iron depletion, such as those with previous anaemia, multiple pregnancy, teenage pregnancy,
pregnancy with high risk of bleeding, consecutive pregnancies with less than a year’s interval
5. After 8 weeks of therapeutic iron therapy when non anemia iron deficiency is being treated (i.e. serum ferritin \ 30 ug/dl without anemia)
6. Preferably prior to parenteral iron therapy to confirm iron deficiency

variation and nutritional status and are therefore unreliable pregnancy. However, as the extra demand of iron is often
[49]. It is recommended that samples for measurement of unmet by a routine diet, regular iron supplementation is
serum iron, Tsat and TIBC be drawn after an overnight fast recommended by most experts during pregnancy. Recom-
which may be frequently impracticable in pregnancy. The mendations for supplementation of iron vary from region to
role of serum hepcidin for diagnosing pregnancy associated region, the CDC recommends that all pregnant women
ID is an area of active research [50]. Serum Zinc Proto- begin a 30 mg per day iron supplement at the first prenatal
porphyrin (ZPP) increases with ID. Its levels are not visit [53]. WHO suggests 30–60 mg per day of elemental
influenced by the pregnancy associated plasma dilution and iron for all pregnant women whereas British guidelines do
are less affected by inflammation and infection. However not recommend any routine iron supplementation in preg-
the test is rarely available at most centers [51]. Table 5 nancy [35, 54]. In populations with an anemia prevalence
describes the differential diagnosis of IDA and other among pregnant women of less than 20% WHO recom-
microcytic anemias in pregnancy. mends, intermittent oral iron and folic acid supplementa-
tion with 120 mg of elemental iron and 2.8 mg of folic acid
Diagnosing the Etiology of IDA in Pregnancy once weekly for pregnant women to improve maternal and
neonatal outcomes [35, 54]. The equivalent of 60 mg of
A history of pre-pregnancy menorrhagia, pre-pregnancy elemental iron is 300 mg ferrous sulfate heptahydrate,
Hb, frequent child births, passage of worms and gastroin- 180 mg ferrous fumarate or 500 mg of ferrous gluconate
testinal blood loss should be taken in pregnant patients [55]. In a recent Cochrane review that analysed feto-ma-
presenting with anemia. As the etiology of IDA in preg- ternal outcome in women receiving intermittent versus
nancy often reflects a mismatch between the supply and daily iron supplementation, authors concluded that women
demand of iron, we do not recommend stool testing for receiving intermittent iron (80–300 mg of elemental iron
occult blood, worm infestation, GI endoscopies or screen- per week) had similar risk of anemia at term, premature
ing for celiac disease unless specifically indicated [52]. delivery, low birth weight with fewer side effects and lesser
risk of high Hb concentration at term, although the quality
Preventing IDA in Pregnancy of evidence was graded as low to very low [56]. Accord-
ingly, WHO added a context specific recommendation for
Iron Prophylaxis and Controversies once weekly intermittent oral iron supplementation when
daily iron is not acceptable due to gastrointestinal side
Effective communication to all pregnant women about diet effects [54]. Before commencing the intermittent regime,
and nutrition is an integral part of preventing anemia in accurate measurements of maternal Hb are required to

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Table 7 Indications and contraindications of using IV iron in pregnancy [26, 35, 37, 52]
Indications Contraindications

1. Failure to oral iron therapy 1. Lack of facilities for resuscitation

2. Non-compliance or intolerance to oral iron 2. Known history of anaphylaxis or reactions to
parenteral iron
3. Late second or third trimester with moderate to severe IDA 3. Gestation period \ 12 weeks
4. Malabsorption (e.g. Bowerl-resection/Celiac disease) 4. Known state of iron overload
5. Bleeding diathesis when hemorrhage is likely to continue
6. In combination with recombinant erythropoietin patients with pregnancy and chronic
disease
7. Moderate to severe post partum anemia when compliance to oral iron and follow up to
health care facility is doubtful
IDA iron deficiency anemia

confirm the absence of anemia and if a woman is diagnosed pregnant patients after first trimester in areas where both
with anemia she should receive 120 mg of elemental iron (1) baseline prevalence of hookworm/Trichuris Trichura
and 0.4 mg of folic daily till anemia is corrected. There- infection is [ 20% and (2) prevalence of anemia in preg-
after she can continue with standard daily regime or nant women is [ 40% and is therefore applicable to India.
intermittent regime as per tolerability [54]. National iron Infected women in non endemic areas should receive anti-
plus initiative recommends iron folic acid [IFA] supple- helmenthic treatment on a case to case basis. The safety of
mentation of 100 mg elemental iron and 500 lg of folic anti-helmenthic agents in pregnancy have not been
acid every day for at least 100 days starting after the first unequivocally established however deworming is advo-
trimester at 14–16 weeks of gestation for all non-anemic cated in regions where benefits outweigh the risks [54].
pregnant women followed by the same dose for 100 days
postpartum [57]. Treatment of Anemia

Dietary Recommendations A recent Cochrane review failed to show clear benefit of

treating IDA in pregnancy despite concrete evidence of ID
The Recommended Dietary Allowance (RDA) of iron in on adverse fetomaternal outcome [18]. In concordance with
third trimester is 30 mg/day. The average iron density in an most international guidelines we recommend treating IDA
average Indian diet is 8.5 mg/1000 KCal and the average in pregnancy [35, 54].
iron absorption from a rice based and wheat based Indian
diet in pregnancy is 13.3 and 5.3% respectively [22, 23]. Management as per the Trimester/Postpartum State
Elaborate recommendations on increasing iron intake in
diet during pregnancy are available [35, 54]. Dietary The mode of repletion of iron stores in IDA of pregnancy is
modifications are cheap and culturally acceptable. How- guided by the severity of anemia, the stage of pregnancy,
ever, considering the Indian food practices, dietary modi- obstetric risks of hemorrhage (e.g. premature labor, pla-
fications are likely to be inadequate and most pregnant centa praevia) and non-obstetric maternal comorbidities
women require supplementary iron. Supplement 1 gives the (hemoglobinopathy, chronic disease etc.). The
list of drugs and dietary products that interfere with iron flowchart depicts our approach to managing IDA in preg-
absorption. Smart phone applications can guide women on nancy depending on the stage and response (Figure 2).
their day to day iron needs, iron content of various foods
and help them monitor their dietary iron intake. We Oral Iron
encourage the development and use of such applications
adapted for Indian settings. Dependent on the type of preparation only 1–8% of iron is
absorbed from the available oral iron preparations. There
Role of Deworming are considerable controversies regarding the optimal fre-
quency, dose and type of oral iron preparation to be used.
WHO recommends routine deworming using single dose The absorption of oral iron increases with increasing doses
Albendazole (400 mg) or mebendazole (500 mg) in all of oral iron only up to 160 mg/day [37]. Accordingly,

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Hb<11g/dl in Pregnancy

Get CBC with

indices

Normocytic to
microcytic,
normal smear

No Isolated IDA
unlikely, Rule out
other causes
If Hb<4g/dl ,signiicant
bleeding or evidence of Urgent transfusion
hemodynamic compromise
No
Screen for
hemoglobinopathy
wherever feasible

1st Trimester 2nd Trimester 3rd trimester

Hb>7g/dl Hb<7g/dl Hb<7g/dl

Hb>7g/dl

100-200 mg
elemental oral <36 weeks
Check serum Check POG
iron ferritin

Ferritin
Check for Ferritin <30ug/dl >36
Hb rise>1g/dl at >30ug/dl weeks
2 weeks
No Response
Response
+ Urgent
Check compliance, transfusion
supplement
B12,folate I V Iron
Check CRP,
T sat

No Response
Ferritin Ferritin 30-100 with
Continue iron >100with high CRP and
till 3 months Rule out T Sat>15% T Sat<15%
post partum other causes

Fig. 2 Approach to IDA in pregnancy. Hb hemoglobin; IDA iron deficiency anemia; CRP C reactive protein; POG period of gestation; TSat
transferrin saturation; IV intravenous

recommended dose of elemental iron for treating IDA in Increasing dose beyond this dose leads to increased gas-
pregnancy is between 100 and 200 mg/day in the British trointestinal side effects without improving the efficacy.
guidelines and 120 mg/d in the WHO guidelines [35, 54]. Recent data on hepcidin kinetics comparing once daily

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with twice daily and thrice daily iron administration show Intravenous iron
little added benefit of twice or thrice daily dosing and
suggest an equivalent iron absorption even with alternate Intravenous (IV) iron combines the advantages of complete
day iron dosing [58, 59]. Considering the increased fre- bioavailability with fewer GI side effects and faster
quency of GI side effects in pregnancy [60] these data recovery of Hb than oral iron. However the increased risk
become relevant and require further investigation in preg- of oxidant damage, increased cost and small but finite risk
nancy setting. Multiple studies comparing various oral of hypersensitivity reaction limit the widespread use of IV
preparations do not show conclusive evidence of superi- iron [67]. The odds ratio/overall risk (OR) of reported total
ority of one iron preparation over the other. We recom- absolute rates of adverse life-threatening events with par-
mend avoiding the use of enteric coated and delayed enteral iron is 38 per million doses, predominantly with
release preparations as they have proven poor bioavail- high molecular weight iron dextran [68]. Thus, while the
ability [61]. All pregnant women should be instructed to use of high-molecular iron dextran is no longer justified,
take oral iron empty stomach or 1 h after meals for better numerous other iron preparations have been proven to be
absorption preferably with vitamin C rich product such as safe in pregnancy. One of the previous disadvantage of IV
orange juice or guava [62]. Supplement 2 enlists the iron was the requirement of multiple infusions. This has
available oral iron preparations for use in pregnancy. been circumvented by the newer preparations like iron-
isomaltoside and iron carboxymaltose which allow larger
Management of Gastrointestinal (GI) Side Effects of Oral infusion doses of elemental iron to be administered over a
Iron short period of time [37, 70]. Supplement 3 summarizes the
various IV iron preparations available in Indian market,
In general Ferric salts (III) have a superior GI tolerability with their infusion time and dose (Table 7).
than Ferrous (II) salts at the cost of reduced iron absorption We recommend that parenteral iron should always be
[63]. Gastrointestinal side effects (nausea, constipation, administered once ID is confirmed using serum ferritin or
diarrhea, indigestion, and metallic taste) are reported in other specific investigations, after an informed consent at a
70% of pregnant patients owing to the progesterone center where resuscitation facilities are available. Vitals
induced decreased GI motility and effect of gravid uterus. should be checked periodically during and at the end of
Twenty percent of women stop iron irrespective of iron infusion by a physician, nurse or trained mid wife. A test
preparation. Few patients adhere to the prescribed duration dose is required only for LMW Iron dextran while other
of 3–6 months [64, 65]. Measures such as reducing the parenteral iron preparations do not require test dosing.
frequency, content of oral iron and changing it to an Patient should be explained about the transient side effects
alternative preparation or taking the iron with meals may of IV iron supplementation include nausea, vomiting,
be employed to reduce GI side effects [35]. pruritus, headache, and flushing; myalgia, arthralgia, and
back and chest pain that usually resolve within 48 h of
infusion [27].
Parenteral Iron Therapy Ganzoni’s equation is the standard formula used for
calculating the dose of par enteral iron in pregnancy is [69]:
Intramuscular (IM) Iron Required iron dose ½mg
¼ ½2:4  ½target Hb  actual Hb
The Ministry of Health and Family Welfare (MoHFW)
guidelines for treatment of IDA in pregnancy continue to  pre - pregnancy weight½kg
recommend IM iron following a test dose as a cost-effective þ 1000 mg for replenishment of stores
treatment for moderate anemia in pregnancy [57]. However
In practice the dose can be titrated according to the
the intramuscular route has essentially been replaced by
available iron stores, history of ongoing blood loss and
intravenous route because of the inconvenience of painful
hemoglobin response.
injection, dark discoloration of the skin, and the risk of
myalgias, arthritis, hypersensitivity, lymphadenopathy at
Assessing Response to iron
most centers [66]. Moreover, there is increased risk of
development of sarcoma at the site of injection in treated
Increase in reticulocyte Hb content (CHr) is the earliest
animals [27]. Low molecular weight iron dextran is the only
marker of response as early as 3 days.It requires validation in
preparation which can be recommended for intra muscular
pregnancy and is not widely available currently [33]. A rise
use in primary care settings with a Z technique if resuscita-
in hemoglobin by 1 g/dl is expected at the end of 2 weeks
tion facilities are available [57].
and by 2 g/dl by the end of 4 weeks in the absence of other

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Table 8 Indications of blood transfusion in pregnancy with IDA [74, 75, 77, 78]
Antepartum period Intrapartum period Post partum period

1. Pregnancy \ 36 weeks a. Hb \ 7 g/dL[in labor] [Decision of blood a. Anemia with signs of shock/acute
a. Hb \ 4 g/dL with or without signs of cardiac transfusion depends on medical history or hemorrhage with signs of hemodynamic
failure or hypoxia symptoms] instability
b. 5–7 g/dL with presence of impending heart b. Severe anemia with decompensation or acute b. Hb \ 7gm %:Decision of transfusion
failure,hemodynamic instability or acute hemorrhage with decompensation depends on medical history or symptoms
hemorrhage
2. Pregnancy [ 36 weeks
a. Hb \ 7 g/dL even without signs of cardiac
failure or hypoxia
b. Severe anemia with decompensation or acute
hemorrhage with decompensation
c. Hemoglobinopathy/Bone marrow failure
syndromes or malignancy

micronutrient deficiencies and ongoing blood loss for severe peripartum anemia in conjunction with IV iron,
patients on oral iron [35, 37]. A suboptimal rise is an indi- particularly in cases with antepartum and postpartum
cation for checking compliance, reconfirmation of diagnosis hemorrhage and patients with rare blood groups. However
and consideration for parenteral iron therapy. Once the Hb is currently there is insufficient evidence for routine use of
in normal range, 100–200 mg/day of iron should continue EPO in pregnancy except in cases with renal disease [73].
for at least 3 months and at least 6 weeks postpartum to
replenish the stores and 60–100 mg/d oral iron should con- Role of Transfusion
tinue for at least 3–6 months postpartum [26].
Transfusion in pregnancy carries additional risks of RBC
Postpartum Anemia allo-immunization, volume overload and fetal hemolytic
disease. The current AABB and the RCOG guidelines
Postpartum anemia is associated with poor quality of life suggest a threshold of Hb \ 7 g/dl for transfusion and a
(QOL) and increased rates of depression in women [70]. threshold of \ 8 g/dl in patients with pre-existing cardio-
Routine postpartum prophylaxis by WHO recommended vascular disease [74, 75]. However in obstetrics, the deci-
doses of 60 mg/d for three months or MoHFW doses of sion of transfusion should be individualized depending on
100 mg/d to non-anemic women for 6 months has been available alternatives of oral and parenteral iron, present
shown to be cost effective in decreasing the rates of anemia and future risk of hemorrhage, comorbidities like DIC,
in our country. It should be reinforced at the time of dis- thrombocytopenia, acuteness of fall in Hb and cardiovas-
charge from health care facility to the lactating mother cular status. Partial exchange transfusion has not been
[57]. Hemoglobin should be checked in all women where shown to be superior to transfusion under diuretic cover for
estimated blood loss is [ 500 ml within 48 h of delivery or patients who present with severe anemia and congestive
in women known to have antepartum anemia or having cardiac failure at term [76]. We do not recommend the
symptoms of anemia [71]. While mildly symptomatic routine use of exchange transfusion except for patients with
women can be treated with therapeutic oral iron at the dose sickle cell disease. Table 8 summarizes the indications for
of 100–200 mg/d for next 3 months, IV iron can be con- transfusion in case of ID.
sidered in moderate anemia [72]. In case of severe anemia
or evidence of hemodynamic comprise patients should Management of Labor in Patients with Anemia
receive transfusion prior to discharge from health facility.
Wherever feasible, a follow up CBC with serum ferritin Increasing use of regional anaesthesia, use of upright
should be considered before discontinuation of iron therapy position during delivery, manual removal of placenta and
at 3 to 6 months. episiotomy lead to heavier blood loss even in modern
obstetrics [12]. All patients with anemia should preferably
Role of Erythropoietin undergo delivery where facility of blood transfusion and
intra venous access are available. Cross matched blood
Recombinant human erythropoietin (RhuEPO) has been units should be kept reserved in patients with moderate to
shown to be safe and effective for the rapid correction of severe anemia undergoing delivery. In all anemic patients

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with pregnancy active management of third stage of labor Mineral Nutrition Information System, WHO, Geneva, World
with the use of syntocin or misoprostol is effective in Health Organisation, Switerzerland
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and oxygen carrying capacity in pregnancy. Acta Obstet Gynecol
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Conclusions and Future Vision 7. Malhotra P, Kumari S, Kumar R et al (2004) Prevalence of
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IDA in pregnancy is readily manageable yet an unmet 8. Ministry of Health and Family Welfare (2015–2016) Govt. of
health demand. The management strategy is dependent India, National Family Health Survey (NFHS-4), State Fact
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9. Haddad L, Hawkes C, Udomkesmalee E et al (2016) Global
Widespread implementation of preventive and therapeutic Nutrition Report 2016: From Promise to Impact: Ending Mal-
strategies is still lacking in our country. Organization of nutrition by 2030. International Food Policy Research Institute,
awareness camps, patient group meetings and the use of Washington
social media can spread awareness of this public health 10. Rahman MM, Abe SK, Rahman MS et al (2016) Maternal anemia
and risk of adverse birth and health outcomes in low- and middle-
issue. We strongly advocate observation of ‘‘National income countries: systematic review and meta-analysis. Am J
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Conflict of interest All authors declare that they have no conflict of anemia, cigarette smoking and risk of abruptio placentae. J Ob-
interest. stetr Gynaecol Res 35(3):446–452
18. Reveiz L, Gyte GM, Cuervo LG et al (2011) Treatments for iron-
Ethical Approval This article does not involve any study with par- deficiency anaemia in pregnancy. The Cochrane database of
ticipation with human participants or animals by the authors. systematic reviews. 2(10):3094
19. Goshtasebi A, Alizadeh M, Gandevani SB (2013) Association
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